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Sample records for damage mechanics formulation

  1. 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)

  2. Entropic formulation of relativistic continuum mechanics.

    PubMed

    Fukuma, Masafumi; Sakatani, Yuho

    2011-08-01

    An entropic formulation of relativistic continuum mechanics is developed in the Landau-Lifshitz frame. We introduce two spatial scales, one being the small scale representing the linear size of each material particle and the other the large scale representing the linear size of a large system which consists of material particles and is to linearly regress to the equilibrium. We propose a local functional which is expected to represent the total entropy of the larger system and require the entropy functional to be maximized in the process of linear regression. We show that Onsager's original idea on linear regression can then be realized explicitly as current conservations with dissipative currents in the desired form. We demonstrate the effectiveness of this formulation by showing that one can treat a wide class of relativistic continuum materials, including standard relativistic viscous fluids and relativistic viscoelastic materials.

  3. 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

  4. 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.

  5. 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.

  6. 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).

  7. A method of damage mechanics analysis for solder material

    SciTech Connect

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

    1997-06-01

    This paper presents as a method of damage mechanics analysis for solder joint material stressed to extensive plastic deformation. The material chosen for the current work is the 60Sn-40Pb eutectic alloy due to its wide use. The analysis is based on the thermodynamic theory of irreversible processes. With the introduction of a set of internal state variables, known as damage variables, and a damage effect tensor, a damage dissipative potential function is proposed to enable the formulation of the constitutive equations of elasticity and plasticity coupled with damage. The equations of damage evolution are also derived to monitor damage initiation and growth. Before a damage analysis can be performed with a finite element analysis, the mechanical properties of the chosen solder joint material and its damage variables must first be determined. A method of experimental analysis was developed and used to successfully measure the highly strain sensitive 60Sn-40Pb solder material. The measured properties are presented and various characteristics of the solder material are examined and discussed. 7 refs., 8 figs.

  8. 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.

  9. Non local damage model based on micromorphic formulation

    NASA Astrophysics Data System (ADS)

    Evangelia, Diamantopoulou; Carl, Labergere; Khemais, Saanouni

    2016-10-01

    This paper presents an experimental-numerical study based on simple tensile test of a high strength metallic sheet, including the diffuse necking stage, up to the large plastic strain and damage localization. A micromorphic approach including nonlocal damage can overcome the mesh dependency problem. The numerical implementation into ABAQUS/Explicit is made for 2D quadrangular elements thanks to the VUEL user's subroutine. Promising results are obtained which qualitatively are compatible with the experiments.

  10. [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.

  11. Subsurface damage detection and damage mechanism analysis of chemical-mechanical polished optics

    NASA Astrophysics Data System (ADS)

    Ye, Hui; Yang, Wei; Bi, Guo; Yang, Ping; Guo, Yinbiao

    2014-09-01

    Detection of the subsurface damage depth in optical elements has significance on the subsequent material removal amount and improving element surface quality. The paper focuses on the subsurface damage of chemical-mechanical polished K9 specimen, and analyses the chemical-mechanical polishing mechanism and the cause of subsurface damage. A most suitable etchant is chosen and the step-by-step etching method is applied to measure the subsurface damage depth. A microscope is used to detect the damage morphology and the variation trend at different depth. Research shows that the subsurface damage caused by chemical-mechanical polishing is Hertz scratch, and the scratch quantity below surface presents a variation of zero-more-less-disappeared. The K9 specimen is polished for 3 min under the pressure of 2.5 Kgf and the spindle speed of 43139 r/min, thus resulting in a subsurface damage depth 15.3μm.

  12. 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

  13. Volatile Emission of Mechanically Damaged Almonds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mature almonds from the Monterey variety were evaluated for their volatile composition after mechanical damage and compared to the volatile composition of the corresponding undamaged almonds. Volatiles were collected on Tenax, desorbed with diethyl ether, and identified via GC-MS analyses. Volatile ...

  14. 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.

  15. A damage mechanics based general purpose interface/contact element

    NASA Astrophysics Data System (ADS)

    Yan, Chengyong

    Most of the microelectronics packaging structures consist of layered substrates connected with bonding materials, such as solder or epoxy. Predicting the thermomechanical behavior of these multilayered structures is a challenging task in electronic packaging engineering. In a layered structure the most complex part is always the interfaces between the strates. Simulating the thermo-mechanical behavior of such interfaces, is the main theme of this dissertation. The most commonly used solder material, Pb-Sn alloy, has a very low melting temperature 180sp°C, so that the material demonstrates a highly viscous behavior. And, creep usually dominates the failure mechanism. Hence, the theory of viscoplasticity is adapted to describe the constitutive behavior. In a multilayered assembly each layer has a different coefficient of thermal expansion. Under thermal cycling, due to heat dissipated from circuits, interfaces and interconnects experience low cycle fatigue. Presently, the state-of-the art damage mechanics model used for fatigue life predictions is based on Kachanov (1986) continuum damage model. This model uses plastic strain as a damage criterion. Since plastic strain is a stress path dependent value, the criterion does not yield unique damage values for the same state of stress. In this dissertation a new damage evolution equation based on the second law of thermodynamic is proposed. The new criterion is based on the entropy of the system and it yields unique damage values for all stress paths to the final state of stress. In the electronics industry, there is a strong desire to develop fatigue free interconnections. The proposed interface/contact element can also simulate the behavior of the fatigue free Z-direction thin film interconnections as well as traditional layered interconnects. The proposed interface element can simulate behavior of a bonded interface or unbonded sliding interface, also called contact element. The proposed element was verified against

  16. 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.

  17. 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.

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

    PubMed

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

    2016-02-06

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

  19. Constitutive formulations for the mechanical investigation of colonic tissues.

    PubMed

    Carniel, Emanuele Luigi; Gramigna, Vera; Fontanella, Chiara Giulia; Stefanini, Cesare; Natali, Arturo N

    2014-05-01

    A constitutive framework is provided for the characterization of the mechanical behavior of colonic tissues, as a fundamental tool for the development of numerical models of the colonic structures. The constitutive analysis is performed by a multidisciplinary approach that requires the cooperation between experimental and computational competences. The preliminary investigation pertains to the review of the tissues histology. The complex structural configuration of the tissues and the specific distributions of fibrous elements entail the nonlinear mechanical behavior and the anisotropic response. The identification of the mechanical properties requires to perform mechanical tests according to different loading situations, as different loading directions. Because of the typical functionality of colon structures, the tissues mechanics is investigated by tensile tests, which are performed on taenia coli and haustra specimens from fresh pig colons. Accounting for the histological investigation and the results from the mechanical tests, a specific hyperelastic framework is provided within the theory of fiber-reinforced composite materials. Preliminary analytical formulations are defined to identify the constitutive parameters by the inverse analysis of the experimental tests. Finite element models of the specimens are developed accounting for the actual configuration of the colon structures to verify the quality of the results. The good agreement between experimental and numerical model results suggests the reliability of the constitutive formulations and parameters. Finally, the developed constitutive analysis makes it possible to identify the mechanical behavior and properties of the different colonic tissues.

  20. 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

  1. 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

  2. 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.

  3. Constitutive formulation and analysis of heel pad tissues mechanics.

    PubMed

    Natali, A N; Fontanella, C G; Carniel, E L

    2010-06-01

    This paper presents a visco-hyperelastic constitutive model developed to describe the biomechanical response of heel pad tissues. The model takes into account the typical features of the mechanical response such as large displacement, strain phenomena, and non-linear elasticity together with time-dependent effects. The constitutive model was formulated, starting from the analysis of the complex structural and micro-structural configuration of the tissues, to evaluate the relationship between tissue histology and mechanical properties. To define the constitutive model, experimental data from mechanical tests were analyzed. To obtain information about the mechanical response of the tissue so that the constitutive parameters could be established, data from both in vitro and in vivo tests were investigated. Specifically, the first evaluation of the constitutive parameters was performed by a coupled deterministic and stochastic optimization method, accounting for data from in vitro tests. The comparison of constitutive model results and experimental data confirmed the model's capability to describe the compression behaviour of the heel pad tissues, regarding both constant strain rate and stress relaxation tests. Based on the data from additional experimental tests, some of the constitutive parameters were modified in order to interpret the in vivo mechanical response of the heel pad tissues. This approach made it possible to interpret the actual mechanical function of the tissues.

  4. A Dynamic Damage Mechanics Source Model for Explosions in Crystalline Rock

    NASA Astrophysics Data System (ADS)

    Mihaly, J. M.; Bhat, H. S.; Sammis, C. G.; Rosakis, A.

    2011-12-01

    The micromechanical damage mechanics formulated by Ashby and Sammis [PAGEOPH, 1990] and generalized by Deshpande and Evans [J. Mech. Phys. Solids, 2008] has been extended to allow for a more generalized stress state and to incorporate an experimentally motivated 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, and thus produces strain-rate sensitivity in the constitutive response. The model is experimentally verified by predicting the failure strength of Dionysus-Pentelicon marble over strain rates ranging from to . This rate-dependent damage mechanics has been implemented in the ABAQUS dynamic finite element code and used to explore the effects of burn rate (loading rate) and lithostatic stress on the spatial extent of fracture damage and S waves generated by explosions in crystalline rock. Slower rise times and longer pressure pulses produce more damage and stronger S waves.

  5. Formulation and process strategies to minimize coat damage for compaction of coated pellets in a rotary tablet press: A mechanistic view.

    PubMed

    Xu, Min; Heng, Paul Wan Sia; Liew, Celine Valeria

    2016-02-29

    Compaction of multiple-unit pellet system (MUPS) tablets has been extensively studied in the past few decades but with marginal success. This study aims to investigate the formulation and process strategies for minimizing pellet coat damage caused by compaction and elucidate the mechanism of damage sustained during the preparation of MUPS tablets in a rotary tablet press. Blends containing ethylcellulose-coated pellets and cushioning agent (spray dried aggregates of micronized lactose and mannitol), were compacted into MUPS tablets in a rotary tablet press. The effects of compaction pressure and dwell time on the physicomechanical properties of resultant MUPS tablets and extent of pellet coat damage were systematically examined. The coated pellets from various locations at the axial and radial peripheral surfaces and core of the MUPS tablets were excavated and assessed for their coat damage individually. Interestingly, for a MUPS tablet formulation which consolidates by plastic deformation, the tablet mechanical strength could be enhanced without exacerbating pellet coat damage by extending the dwell time in the compaction cycle during rotary tableting. However, the increase in compaction pressure led to faster drug release rate. The location of the coated pellets in the MUPS tablet also contributed to the extent of their coat damage, possibly due to uneven force distribution within the compact. To ensure viability of pellet coat integrity, the formation of a continuous percolating network of cushioning agent is critical and the applied compaction pressure should be less than the pellet crushing strength.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Autonomous Indication of Mechanical Damage in Polymeric Coatings.

    PubMed

    Li, Wenle; Matthews, Christopher C; Yang, Ke; Odarczenko, Michael T; White, Scott R; Sottos, Nancy R

    2016-03-16

    High-resolution in situ autonomous visual indication of mechanical damage is achieved through a microcapsule-based polymeric material system. Upon mechanical damage, ruptured microcapsules release a liquid indicator molecule. A sharp color change from light yellow to bright red is triggered when the liberated indicator 2',7'-dichlorofluorescein reacts with the polymeric coating matrix.

  13. Surface Damage Mechanism of Monocrystalline Si Under Mechanical Loading

    NASA Astrophysics Data System (ADS)

    Zhao, Qingliang; Zhang, Quanli; To, Suet; Guo, Bing

    2017-03-01

    Single-point diamond scratching and nanoindentation on monocrystalline silicon wafer were performed to investigate the surface damage mechanism of Si under the contact loading. The results showed that three typical stages of material removal appeared during dynamic scratching, and a chemical reaction of Si with the diamond indenter and oxygen occurred under the high temperature. In addition, the Raman spectra of the various points in the scratching groove indicated that the Si-I to β-Sn structure (Si-II) and the following β-Sn structure (Si-II) to amorphous Si transformation appeared under the rapid loading/unloading condition of the diamond grit, and the volume change induced by the phase transformation resulted in a critical depth (ductile-brittle transition) of cut (˜60 nm ± 15 nm) much lower than the theoretical calculated results (˜387 nm). Moreover, it also led to abnormal load-displacement curves in the nanoindentation tests, resulting in the appearance of elbow and pop-out effects (˜270 nm at 20 s, 50 mN), which were highly dependent on the loading/unloading conditions. In summary, phase transformation of Si promoted surface deformation and fracture under both static and dynamic mechanical loading.

  14. Mechanisms for mechanical damage in the intervertebral disc annulus fibrosus.

    PubMed

    Iatridis, J C James C; ap Gwynn, Iolo

    2004-08-01

    Intervertebral disc degeneration results in disorganization of the laminate structure of the annulus that may arise from mechanical microfailure. Failure mechanisms in the annulus were investigated using composite lamination theory and other analyses to calculate stresses in annulus layers, interlaminar shear stress, and the region of stress concentration around a fiber break. Scanning electron microscopy (SEM) was used to evaluate failure patterns in the annulus and evaluate novel structural features of the disc tissue. Stress concentrations in the annulus due to an isolated fiber break were localized to approximately 5 microm away from the break, and only considered a likely cause of annulus fibrosus failure (i.e., radial tears in the annulus) under extreme loading conditions or when collagen damage occurs over a relatively large region. Interlaminar shear stresses were calculated to be relatively large, to increase with layer thickness (as reported with degeneration), and were considered to be associated with propagation of circumferential tears in the annulus. SEM analysis of intervertebral disc annulus fibrosus tissue demonstrated a clear laminate structure, delamination, matrix cracking, and fiber failure. Novel structural features noted with SEM also included the presence of small tubules that appear to run along the length of collagen fibers in the annulus and a distinct collagenous structure representative of a pericellular matrix in the nucleus region.

  15. Three-Hilbert-Space Formulation of Quantum Mechanics

    NASA Astrophysics Data System (ADS)

    Znojil, Miloslav

    2009-01-01

    In paper [Znojil M., Phys. Rev. D 78 (2008), 085003, 5 pages, arXiv:0809.2874] the two-Hilbert-space (2HS, a.k.a. cryptohermitian) formulation of Quantum Mechanics has been revisited. In the present continuation of this study (with the spaces in question denoted as H(auxiliary) and H(standard)) we spot a weak point of the 2HS formalism which lies in the double role played by H(auxiliary). As long as this confluence of roles may (and did!) lead to confusion in the literature, we propose an amended, three-Hilbert-space (3HS) reformulation of the same theory. As a byproduct of our analysis of the formalism we offer an amendment of the Dirac's bra-ket notation and we also show how its use clarifies the concept of covariance in time-dependent cases. Via an elementary example we finally explain why in certain quantum systems the generator H(gen) of the time-evolution of the wave functions may differ from their Hamiltonian H.

  16. Bohmian mechanics with complex action: A new trajectory-based formulation of quantum mechanics

    SciTech Connect

    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{sup -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.

  17. 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.

  18. 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.

  19. Formulations and computational methods for contact problems in solid mechanics

    NASA Astrophysics Data System (ADS)

    Mirar, Anand Ramchandra

    2000-11-01

    A study of existing formulations and computational methods for contact problems is conducted. The purpose is to gain insights into the solution procedures and pinpoint their limitations so that alternate procedures can be developed. Three such procedures based on the augmented Lagrangian method (ALM) are proposed. Small-scale benchmark problems are solved analytically as well as numerically to study the existing and proposed methods. The variational inequality formulation for frictionless contact is studied using the two bar truss-wall problem in a closed form. Sub-differential formulation is investigated using the spring-wall contact and the truss-wall friction problems. A two-phase analytical procedure is developed for solving the truss-wall frictional contact benchmark problem. The variational equality formulation for contact problems is studied using the penalty method along with the Newton-Raphson procedure. Limitations of such procedures, mainly due to their dependence on the user defined parameters (i.e., the penalty values and the number of time steps), are identified. Based on the study it is concluded that alternate formulations need to be developed. Frictionless contact formulation is developed using the basic concepts of ALM from optimization theory. A new frictional contact formulation (ALM1) is then developed employing ALM. Automatic penalty update procedure is used to eliminate dependence of the solution on the penalty values. Dependence of the solution on the number of time steps in the existing as well as ALM1 formulations is attributed to a flaw in the return mapping procedure for friction. Another new frictional contact formulation (ALM2) is developed to eliminate the dependence of solution on the number of time steps along with the penalty values. Effectiveness of ALM2 is demonstrated by solving the two bar and five bar truss-wall problems. The solutions are compared with the analytical and existing formulations. Design sensitivity analysis of

  20. 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.

  1. Formulation of engineered particulate systems for chemical mechanical polishing applications

    NASA Astrophysics Data System (ADS)

    Basim, Gul Bahar

    slurry formulations are developed by studying the frictional forces, which are representative of the particle-substrate interactions, while achieving stability by introducing adequate interparticle repulsion. Finally, optimal slurry particulate properties are examined by analyzing the material removal mechanisms for silica-silica polishing. Based on the reported findings, a slurry design criterion is developed to achieve optimal polishing performance.

  2. Damage progression in mechanically fastened composite structural joints

    SciTech Connect

    Minnetyan, L.; Chamis, C.C.; Murthy, P.L.N.

    1994-12-31

    Progressive damage and fracture of a bolted graphite/epoxy composite laminate is evaluated via computational simulation. The objective of this paper is to demonstrate a new methodology that scales up constituent material properties, stress and strain limits to the structure level to evaluate the overall damage and fracture propagation for mechanically fastened composite structures. An integrated computer code is used for the simulation of structural degradation under loading. Damage initiation, growth, accumulation, and propagation to fracture are included in the simulation. Results show the damage progression sequence and structural fracture resistance during different degradation stages. The effect of fastener spacing is investigated with regard to the structural durability of a bolted joint.

  3. Analyses of the cell mechanical damage during microinjection.

    PubMed

    Liu, Fei; Wu, Dan; Wu, Xiaoyong; Chen, Ken

    2015-02-04

    The microinjection is an essential technique to introduce foreign materials into biological cells. The soft cell is inevitably ruptured by the microinjector during microinjection. We discuss the way to reduce the mechanical damage by analyzing the control parameters during microinjection. The computational model is developed with the dissipative particle dynamics to simulate the soft mechanical properties of biological cells. The cell model contains the membrane networks, the internal cytoskeleton, crosslink proteins, motors and their functions. The weak power law rheology verifies our computational model. The number of ruptured bonds is used to describe the extent of the mechanical damage that the cell experiences during microinjection. Some experiments are conducted on the Zebrafish embryos. Both the simulation works and experimental results show that the size, shape of the microinjector tip, and the injection velocity have a significant influence on the cell damage. A small, sharp microinjector with a high velocity can reduce the mechanical damage.

  4. Anisotropic Damage Mechanics Modeling in Metal Matrix Composites

    DTIC Science & Technology

    1993-05-15

    conducted on a titanium aluminide SiC-reinforced metal matrix composite. Center-cracked plates with laminate layups of (0/90) and (±45). were tested...Kattan, P. I., "Finite Strain Plasticity and Damage in Constitutive Modeling of Metals with Spin Tensors," Applied Mechanics Reviews, Vol. 45, No. 3...34Contractors Meeting on Mechanics of Materials," Dayton, Ohio, October 1991. Voyiadjis, G. Z., and Kattan, P. I., "Finite Strain Plasticity and Damage in

  5. Mechanisms of Microwave Induced Damage in Biologic Materials

    DTIC Science & Technology

    1989-01-01

    Activities and Microwave Exposures Ornithine decarboxylase (ODC), an enzyme involved in the production of the polyamines putrescine and spermidine, has...f 0 0 Mechanisms of Microwave Induced N Damage in Biologic Materials I ,<DTIC .. E LECTEI I Annual Report S FEB08 1990 U January, 1989 m D EFFECTS OF...Clasufication) (U) Mechanisms of Microwave Induced Damage in Biologic Materials I 12. PERSONAL AUTHOR(S) .3a. TYPE OF REPORT 13b. TIME COVERED 14

  6. Magnetic flux leakage modeling for mechanical damage in transmission pipelines

    SciTech Connect

    Ivanov, P.A.; Zhang, Z.; Yeoh, C.H.; Udpa, L.; Sun, Y.; Udpa, S.S.; Lord, W.

    1998-09-01

    This paper presents a two stage FE model for prediction of magnetic flux leakage, resulting from mechanical damage. In the first stage the stress distribution associated with mechanical damage is obtained from a structural model. In the second stage the stress distribution is incorporated into a magnetic FE model, by mapping stress levels to permeability. MFL signals are calculated and compared with experimental gouge MFL signatures.

  7. 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.

  8. 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

  9. Viscoelastic-damage interface model formulation with friction to simulate the delamination growth in mode II shear

    NASA Astrophysics Data System (ADS)

    Goodarzi, Mohammad Saeed; Hosseini-Toudeshky, Hossein

    2017-02-01

    In this paper a formulation of a viscoelastic-damage interface model with friction in mode-II is presented. The cohesive constitutive law contains elastic and damage regimes. It has been assumed that the shear stress in the elastic regime follows the viscoelastic properties of the matrix material. The three element Voigt model has been used for the formulation of relaxation modulus of the material. Damage evolution proceeds according to the bilinear cohesive constitutive law combined with friction stress consideration. Combination of damage and friction is based on the presumption that the damaged area, related to an integration point, can be dismembered into the un-cracked area with the cohesive damage and cracked area with friction. Samples of a one element model have been presented to see the effect of parameters on the cohesive constitutive law. A comparison between the predicted results with available results of end-notched flexure specimens in the literature is also presented to verify the model. Transverse crack tension specimens are also simulated for different applied displacement velocities.

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

    PubMed

    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.

  11. 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

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

    NASA Astrophysics Data System (ADS)

    Meng, Qinghua; Wang, Zhenqing

    2016-12-01

    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.

  13. 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.

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

    PubMed

    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.

  15. 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; V. V., Subba Rao

    2017-02-01

    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.

  16. Research on Creep Damage and Life Forecast of Rod Fastening Rotor Based on Damage Mechanics

    NASA Astrophysics Data System (ADS)

    Qiang, Liu; Ai-lun, Wang

    2017-03-01

    Rod fastening rotor (RFR) is the core part of gas turbine, the degradation of RFR has great effect on gas turbine’s performance. One of the main reasons which cause the RFR performance degradation is creep damage, while few studies have been carried out in terms of it so far. In order to analyze the influence of preload on virtual material parameters, a dynamic model of RFR considering interface contact effect was built. Then equivalent stiffness of RFR and elements was analyzed as well. Furthermore, creep damage of elements under higher stress were analyzed with damage mechanics to get their influence on the total damage. Likewise, RFR were analyzed with damage mechanics to get the connection between the total damage and rupture life. The results showed that connection between the total damage and rupture life was a complicated, non-linear process. Moreover, the rods of turbine and combustion chamber were the biggest influencing factors. The results of this dissertation can be a support for structural design and life prediction of RFR.

  17. 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

  18. 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.

  19. Evolution of the passive film on mechanically damaged nitinol.

    PubMed

    Schroeder, Valeska

    2009-07-01

    The corrosion behavior of Nitinol-based medical implants is critical to their success in vivo. Contemporary Nitinol-based medical implants are typically chemically passivated or electrochemically polished to form a protective passive film. However, mechanically formed surfaces caused by handling damage, fretting, or fatigue fracture may also be present on a device in vivo. In this study, mechanically polished surfaces are used to simulate mechanically damaged surfaces such that analytical techniques, including electrochemical impedance spectroscopy, open circuit potential monitoring, X-ray photoelectron spectroscopy (XPS), and Mott-Schottky analysis may be used to monitor the evolution of the passive film on mechanically damaged Nitinol. These mechanically polished Nitinol surfaces are compared with chemically passivated and electrochemically polished Nitinol surfaces and mechanically polished titanium surfaces in phosphate buffered saline solution. The mechanically polished Nitinol exhibits lower impedance at low frequencies, empirically modeled to a thinner film with lower film resistance than chemically passivated and electrochemically polished Nitinol and mechanically polished titanium. Moreover, the passive film on mechanically polished Nitinol continues to develop over time, increasing in its thickness and film resistance. This characterization demonstrates that mechanically formed surfaces may be initially less protective than chemically passivated and electrochemically polished Nitinol surfaces, but continue to become thicker and more resistant to electrochemical reactions with exposure to saline solution.

  20. Phototoxicity mechanisms: chlorpromazine photosensitized damage to DNA and cell membranes

    SciTech Connect

    Kochevar, K.E.

    1981-07-01

    Photosensitized damage to biological molecules is the initial process in phototoxic responses. It is now recognized that many phototoxic compounds can photosensitize damage to more than one type of biological substrate. The in vitro light-initiated reactions of phototoxic compounds with DNA, soluble proteins and membrane components can be classified by their molecular mechanisms: (1) those in which an excited state of the phototoxic compound (or an unstable species derived from it) reacts directly with the biological substrate and (2) those in which a molecule derived from the phototoxic compound (a photoproduct or an activated oxygen species) reacts with the biological substrate. This paper describes the mechanisms by which chlorpromazine photosensitizes damage to membranes, protein and DNA and compares them to the mechanisms of photosensitization by psoralens, porphyrins, dyes, and other molecules.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. An anisotropic damage mechanics model for concrete with applications for fatigue loading and freeze-thaw effects

    NASA Astrophysics Data System (ADS)

    Reberg, Andrew Steven

    It is well known that the formation and propagation of microcracks within concrete is anisotropic in nature, and has a degrading effect on its mechanical performance. In this thesis an anisotropic damage mechanics model is formulated for concrete which can predict the behavior of the material subjected to monotonic loading, fatigue loading, and freeze-thaw cycles. The constitutive model is formulated using the general framework of the internal variable theory of thermodynamics. Kinetic relations are used to describe the directionality of damage accumulation and the associated softening of mechanical properties. The rate independent model is then extended to cover fatigue loading cycles and freeze-thaw cycles. Two simple softening functions are used to predict the mechanical properties of concrete as the number of cyclic loads as well as freeze-thaw cycles increases. The model is compared with experimental data for fatigue and freeze-thaw performance of plain concrete.

  7. Early mechanisms in radiation-induced biological damage

    SciTech Connect

    Powers, E.L.

    1983-01-01

    An introduction to the mechanisms of radiation action in biological systems is presented. Several questions about the nature of the radiation damage process are discussed, including recognition of the oxygen effects, dose-response relationships, and the importance of the hydroxyl radical. (ACR)

  8. Alcohol teratogenesis: mechanisms of damage and strategies for intervention.

    PubMed

    Goodlett, Charles R; Horn, Kristin H; Zhou, Feng C

    2005-06-01

    There are multiple mechanisms by which alcohol can damage the developing brain, but the type of damage induced will depend on the amount and developmental timing of exposure, along with other maternal and genetic factors. This article reviews current perspectives on how ethanol can produce neuroteratogenic effects by its interactions with molecular regulators of brain development. The current evidence suggests that alcohol produces many of its damaging effects by exerting specific actions on molecules that regulate key developmental processes (e.g., L1 cell adhesion molecule, alcohol dehydrogenase, catalase), interfering with the early development of midline serotonergic neurons and disrupting their regulatory-signaling function for other target brain structures, interfering with trophic factors that regulate neurogenesis and cell survival, or inducing excessive cell death via oxidative stress or activation of caspase-3 proteases. The current understanding of pathogenesis mechanisms suggests several strategic approaches to develop rational molecular prevention. However, the development of behavioral and biologic treatments for alcohol-affected children is crucial because it is unlikely that effective delivery of preventative interventions can realistically be achieved in ways to prevent prenatal damage in at-risk pregnancies. Toward that end, behavioral training that promotes experience-dependent neuroplasticity has been effective in a rat model of cerebellar damage induced by alcohol exposure during the period of brain development that is comparable to that of the human third trimester.

  9. 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.

  10. 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

  11. Dynamic Rate Dependent Elastoplastic Damage Modeling of Concrete Subject to Blast Loading: Formulation and Computational Aspects

    DTIC Science & Technology

    1990-10-31

    damage are observed in fibrous composite laminates, concrete and ceramics (Weitsman [1987]). Several definitions of damage are possible for...Concrete is a three-phase cementitious composite material composed of aggregate, mortar and interface zone (see, e.g., Mehta [1986]). Each of the three...example, we perform two replicate uniaxial unconfined compression tests of mortar (with f ’c = 12 ksi). The composition of mortar is as follows

  12. Damage mechanisms for ultrasound-induced cavitation in tissue

    NASA Astrophysics Data System (ADS)

    Warnez, M.; Vlaisavljevich, E.; Xu, Z.; Johnsen, E.

    2017-03-01

    In a variety of biomedical applications, cavitation occurs in soft tissue. Although significant amounts of research have been performed on cavitation in water, bubble dynamics, and related bioeffects remain poorly understood. We use numerical simulations of spherical bubble dynamics in soft tissue to assess the extent to which viscoelasticity affects "known" and introduces "new" damage mechanisms. We find that deviatoric stresses - although not an important damage mechanism in water - are significantly enhanced and could be an important bioeffect mechanism in tissue. Both the viscoelastic properties and the nonlinear, large-collapse radius contribute to stress amplification in the surroundings. In addition, temperatures in the surrounding medium increase more in the Zener tissue than in water, due to viscous heating.

  13. Mechanisms of Recovering Low Cycle Fatigue Damage in Incoloy 901.

    DTIC Science & Technology

    1979-01-01

    Quality at Less Cost," Metals Prog. 106/2, 80-82 (July 1974). 20. D. Raynor and J. M. Silcock, "Strengthening Mechanisms in Gamma -Prime Precipitating...Z AO-A107 255 AIR FORCE INST OF TLCH WRIGHT-PATTERSON AFB OH F/A Il/A MECHANISMS OF RECOVERING LOW CYCLE FATIGUE OAMAGE IN INCOLOY 90-ETC(U) 1979 R E... MECHANISMS OF RECOVERING LOW CYCLE FATIGUE DAMAGE IN INCOLOY 901 Robert E. Schafrik, Capt. USAF (Ph.D.) The Ohio State University, 1979 Professor James A

  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. 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

  16. Investigation of mechanisms leading to laser damage morphology

    NASA Astrophysics Data System (ADS)

    Lamaignère, L.; Chambonneau, M.; Diaz, R.; Grua, P.; Courchinoux, R.; Natoli, J.-Y.; Rullier, J. L.

    2016-12-01

    The original damage ring pattern at the exit surface of fused silica induced by highly modulated nanosecond infrared laser pulses demonstrates the time dependence of damage morphology. Such a damage structure is used to study the dynamics of the plasma issued from open cracks. This pattern originates from electron avalanche in this plasma, which simultaneously leads to an ionization front displacement in air and a silica ablation process. Experiments have shown that the propagation speed of the detonation wave reaches about 20 km/s and scales as the cube root of the laser intensity, in good agreement with theoretical hydrodynamics modeling. During this presentation, we present the different phases and the associated mechanisms leading to this peculiar morphology: • During an incubation phase, a precursor defect provides energy deposit that drives the near surface material into a plasma state. • Next the silica plasma provides free electrons in the surrounding air, under laser irradiation an electron avalanche is initiated and generates a breakdown wave. • Then this breakdown wave leads to an expansion of the air plasma. This latter is able to heat strongly the silica surface as well as generate free electrons in its conduction band. Hence, the silica becomes activated along the breakdown wave. • When the silica has become absorbent, an ablation mechanism of silica occurs, simultaneously with the air plasma expansion, resulting in the formation of the ring patterns in the case of these modulated laser pulses. These mechanisms are supported by experiments realized in vacuum environment. A model describing the expansion of the heated area by thermal conduction due to plasma free electrons is then presented. Next, the paper deals with the two damage formation phases that are distinguished. The first phase corresponds to the incubation of the laser flux by a subsurface defect until the damage occurrence: an incubation fluence corresponds to this phase. The

  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, 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.

  19. 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.

  20. Mechanisms of fatigue damage and crack growth in advanced materials

    NASA Astrophysics Data System (ADS)

    Ritchie, Robert O.

    2001-03-01

    In terms of in-service failures, cyclic fatigue is the most prevalent form of fracture. Despite the wealth of information on fatigue failures in traditional structural materials such as (ductile) metals and alloys, far less is understood about the susceptibility of the newer advanced materials, such as (brittle) intermetallics, ceramics and their composites. In this presentation, the mechanics and mechanisms of fatigue damage and crack propagation are examined with particular emphasis on the similarities and differences between cyclic crack growth in ductile metallic materials, and corresponding behavior in the more brittle advanced materials. This is achieved by considering the process of subcritical crack growth as a mutual competition between intrinsic mechanisms of microstructural damage ahead of the crack tip, which promote crack growth, and extrinsic mechanisms of crack-tip shielding behind the tip, which impede it. This approach is shown to be important for the understanding of the structural fatigue properties of advanced materials, such as monolithic and composite ceramics, and a range of intermetallics (e.g., TiAl, MoSi2, Nb3Al), as the mechanisms of fatigue in these brittle materials are conceptually distinct from that associated with the well known metal fatigue. Examples of the application and life-prediction methodologies for such materials in fatigue-critical situations will be given from the aerospace and bioengineering industries.

  1. Damages to optical silica glass: processes and mechanisms

    NASA Astrophysics Data System (ADS)

    Luo, Sheng-Nian; Zheng, Lianqing; An, Qi; Wu, Heng-An; Xia, Kaiwen; Ni, Sidao

    2007-01-01

    We present recent results of molecular dynamics simulations to illustrate the processes and mechanisms in damages to silica glass, including densification, cavitation, fragmentation and agglomeration via photon, electron, ion and neutron radiations and stresses. Radiation of glass creates point defects (vacancies and interstitials), and subsequent structure relaxation induces densification. Nanovoid below a certain size and rapid-quenching of silica liquid can also densify a glass. Hot spots due to photon-absorbing impurities in glass may cause local densification and cavitation as well. Densification can also be induced by compressional stress, and spall, by tensile stress. The densified glasses, regardless of the exact processes, share similar structural and vibrational properties, for example, the five-fold coordinated Si atoms. Densification is essentially a kinetic frustration during structure relaxation driven by excessive free energy, e.g., due to defects or stresses. The point-defect mechanism is dominant for densification without compression and complemented by thermal spike mechanism in thermal processes. Defects, thermal effects and stresses may interplay in a general damage process in silica glass.

  2. [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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. Application and mechanism of inhalation profile improvement of DPI formulations by mechanofusion with magnesium stearate.

    PubMed

    Kumon, Michiko; Machida, Satoshi; Suzuki, Masahiko; Kusai, Akira; Yonemochi, Etsuo; Terada, Katsuhide

    2008-05-01

    In our previous paper, we reported the inhalation properties of dry powder inhaler (DPI) formulations containing Compound A and mechanofusion-processed lactose carriers. The mechanofusion process with magnesium stearate (Mg-St) on the lactose carrier enhanced the fine particle fraction (FPF) value of the Andersen cascade impactor (ACI) study. The increase of FPF seemed to be associated with the increase of the dispersibility of drug particles. The objectives of this study were (1) to evaluate the applicability of lactose carrier mechanofusion-processed with Mg-St and (2) to examine the mechanism of FPF alteration by the mechanofusion process applied on the lactose carrier with or without additive. The inhalation profiles of DPI formulations containing four different pharmaceutical compounds were evaluated with an ACI. The dispersibility of the formulations was observed by particle size distribution measurement in the air stream and the adhesive force was measured bydirect separation method. It was found that higher FPF was obtained with lactose mechanofusion-processed with Mg-St as compared to control lactose carriers for all four compounds. This suggested that mechanofusion process with Mg-St is widely applicable in DPI formulations. The homogenization of surface adhesiveness was attributed to the increased FPF of the DPI including lactose mechanofusion-processed with Mg-St, as suggested by the combination of several physicochemical characteristics. Combination of different characterization methods would be of help to clarify the whole mechanism which defines the inhalation properties of DPI formulations.

  8. 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.

  9. 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.

  10. Protective effects of topical application of a poorly soluble antioxidant astaxanthin liposomal formulation on ultraviolet-induced skin damage.

    PubMed

    Hama, Susumu; Takahashi, Kanako; Inai, Yuko; Shiota, Kanako; Sakamoto, Ryota; Yamada, Asako; Tsuchiya, Hiroyuki; Kanamura, Kiyoshi; Yamashita, Eiji; Kogure, Kentaro

    2012-08-01

    Astaxanthin (Asx) would be expected to prevent ultraviolet (UV)-induced skin damage, as it is regarded as a potent antioxidative carotenoid in biological membranes. However, it is difficult to administer Asx topically to skin because of its poor water solubility. In this study, we attempted to solve this problem by preparing liposomes containing Asx (Asx-lipo), which were dispersible in the water phase, and therefore, suitable for topical application to the skin. Asx-lipo was shown to have potent scavenging ability against chemiluminescence-dependent singlet oxygen production in the water phase. When Asx-lipo was applied to skin before UV exposure, UV-induced skin thickening was prevented. Interestingly, collagen reduction induced by UV exposure was also prevented by preadministration of Asx-lipo. In addition, topical administration of Asx-lipo containing cationic lipid inhibited melanin production in skin exposed to UV. Consequently, we succeeded in preventing UV-induced skin damage using a topical application of a liposomal formulation containing Asx.

  11. The effects of starches on mechanical properties of paracetamol tablet formulations. I. Pregelatinization of starch binders.

    PubMed

    Alebiowu, Gbenga; Itiola, Oludele Adelanwa

    2003-09-01

    A study has been made of the effects of pregelatinization of native sorghum and plantain starches on the mechanical properties of a paracetamol tablet formulation in comparison with corn starch BP. The mechanical properties tested, viz. tensile strength (T) and brittle fracture index (BFI) of the paracetamol tablets were affected by pregelatinization of the starch. The results suggest that pregelatinized starches may be useful as binders when a particular degree of bond strength and brittleness is desired.

  12. 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.

  13. 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.

  14. Predicting weld solidification cracking using damage mechanics -- LDRD summary report

    SciTech Connect

    Dike, J.J.; Brooks, J.A.; Bammann, D.J.; Li, M.; Krafcik, J.S.; Yang, N.Y.C.

    1997-04-01

    This report summarizes the efforts to develop and validate a finite element based model to predict weld solidification cracking behavior. Such a model must capture the solidification behavior, the thermal behavior in the weld pool region, the material mechanical response, and some failure criteria to determine when solidification cracking will occur. For such a program to be successful, each aspect of the model had to be accurately modeled and verified since the output of one portion of the model served as the input to other portions of the model. A solidification model which includes dendrite tip and eutectic undercooling was developed and used in both the thermal and mechanical finite element analysis. High magnification video techniques were developed to measure strains for validation of the mechanical predictions using a strain rate and temperature dependent constitutive model. This model was coupled with a ductile void growth damage model and correlated with experimental observations to determine capabilities of predicting cracking response. A two phase (solid + liquid) material model was also developed that can be used to more accurately capture the mechanics of weld solidification cracking. In general, reasonable agreement was obtained between simulation and experiment for location of crack initiation and extent of cracking for 6061-T6 aluminum. 35 refs.

  15. 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

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

    PubMed

    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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Mechanisms of CNS invasion and damage by parasites.

    PubMed

    Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina

    2013-01-01

    Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection.

  2. Skin Damage Mechanisms Related to Airborne Particulate Matter Exposure.

    PubMed

    Magnani, Natalia D; Muresan, Ximena M; Belmonte, Giuseppe; Cervellati, Franco; Sticozzi, Claudia; Pecorelli, Alessandra; Miracco, Clelia; Marchini, Timoteo; Evelson, Pablo; Valacchi, Giuseppe

    2016-01-01

    Epidemiological studies suggest a correlation between increased airborne particulate matter (PM) and adverse health effects. The mechanisms of PM-health effects are believed to involve oxidative stress and inflammation. To evaluate the ability of PM promoting skin tissue damage, one of the main organs exposed to outdoor pollutants, we analyzed the effect of concentrated ambient particles (CAPs) in a reconstructed human epidermis (RHE) model. RHE tissues were exposed to 25 or 100 µg/ml CAPs for 24 or 48 h. Data showed that RHE seems to be more susceptible to CAPs-induced toxicity after 48 h exposure than after 24 h. We found a local reactive O(2) species (ROS) production increase generated from metals present on the particle, which contributes to lipids oxidation. Furthermore, as a consequence of altered redox status, NFkB nucleus translocation was increase upon CAPs exposure, as well as cyclooxygenase 2 and cytochrome P450 levels, which may be involved in the inflammatory response initiated by PM. CAPs also triggered an apoptotic process in skin. Surprisingly, by transition electron microscopy analysis we showed that CAPs were able to penetrate skin tissues. These findings contribute to the understanding of the cutaneous pathophysiological mechanisms initiated by CAPs exposure, where oxidative stress and inflammation may play predominant roles.

  3. Understanding the Effects of Electrode Formulation on the Mechanical Strength of Composite Electrodes for Flexible Batteries.

    PubMed

    Gaikwad, Abhinav M; Arias, Ana Claudia

    2017-02-22

    Flexible lithium-ion batteries are necessary for powering the next generation of wearable electronic devices. In most designs, the mechanical flexibility of the battery is improved by reducing the thickness of the active layers, which in turn reduces the areal capacity and energy density of the battery. The performance of a battery depends on the electrode composition, and in most flexible batteries, standard electrode formulation is used, which is not suitable for flexing. Even with considerable efforts made toward the development of flexible lithium-ion batteries, the formulation of the electrodes has received very little attention. In this study, we investigate the relation between the electrode formulation and the mechanical strength of the electrodes. Peel and drag tests are used to compare the adhesion and cohesion strength of the electrodes. The strength of an electrode is sensitive to the particle size and the choice of polymeric binder. By optimizing the electrode composition, we were able to fabricate a high areal capacity (∼2 mAh/cm(2)) flexible lithium-ion battery with conventional metal-based current collectors that shows superior electrochemical and mechanical performance in comparison to that of batteries with standard composition.

  4. Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides

    NASA Astrophysics Data System (ADS)

    Zitnay, Jared L.; Li, Yang; Qin, Zhao; San, Boi Hoa; Depalle, Baptiste; Reese, Shawn P.; Buehler, Markus J.; Yu, S. Michael; Weiss, Jeffrey A.

    2017-03-01

    Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and potentiates in pathological processes. Here, we utilize collagen hybridizing peptide (CHP), which binds unfolded collagen by triple helix formation, to detect molecular level subfailure damage to collagen in mechanically stretched rat tail tendon fascicle. Our results directly reveal that collagen triple helix unfolding occurs during tensile loading of collagenous tissues and thus is an important damage mechanism. Steered molecular dynamics simulations suggest that a likely mechanism for triple helix unfolding is intermolecular shearing of collagen α-chains. Our results elucidate a probable molecular failure mechanism associated with subfailure injuries, and demonstrate the potential of CHP targeting for diagnosis, treatment and monitoring of tissue disease and injury.

  5. Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides

    PubMed Central

    Zitnay, Jared L.; Li, Yang; Qin, Zhao; San, Boi Hoa; Depalle, Baptiste; Reese, Shawn P.; Buehler, Markus J.; Yu, S. Michael; Weiss, Jeffrey A.

    2017-01-01

    Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and potentiates in pathological processes. Here, we utilize collagen hybridizing peptide (CHP), which binds unfolded collagen by triple helix formation, to detect molecular level subfailure damage to collagen in mechanically stretched rat tail tendon fascicle. Our results directly reveal that collagen triple helix unfolding occurs during tensile loading of collagenous tissues and thus is an important damage mechanism. Steered molecular dynamics simulations suggest that a likely mechanism for triple helix unfolding is intermolecular shearing of collagen α-chains. Our results elucidate a probable molecular failure mechanism associated with subfailure injuries, and demonstrate the potential of CHP targeting for diagnosis, treatment and monitoring of tissue disease and injury. PMID:28327610

  6. Incorporating Micro-Mechanics Based Damage Models into Earthquake Rupture Simulations

    NASA Astrophysics Data System (ADS)

    Bhat, H.; Rosakis, A.; Sammis, C. G.

    2012-12-01

    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 a wide range of strain rates. Model parameters determined from quasi-static experiments were used to predict the failure strength at higher loading rates. Agreement with experimental results was excellent. After this verification step the constitutive law was incorporated into a Finite Element Code focused on simulating dynamic earthquake ruptures with specific focus on the ends of the fault (fault tip process zone) and the resulting strong ground motion radiation was studied.

  7. 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

  8. 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.

  9. A BEM formulation applied in the mechanical material modelling of viscoelastic cracked structures

    NASA Astrophysics Data System (ADS)

    Oliveira, Hugo Luiz; Leonel, Edson Denner

    2016-12-01

    The present study aims at performing a mechanical analysis of 2D viscoelastic cracked structural materials using the Boundary Element Method (BEM). The mesh dimensionality reduction provided by the BEM and its accuracy in representing high gradient fields make this numerical method robust to solve fracture mechanics problems. Viscoelastic models address phenomena that provide changes on the mechanical material properties along time. Well-established viscoelastic models such as Maxwell, Kelvin-Voigt and Boltzmann are used in this study. The numerical viscoelastic scheme, which is based on algebraic BEM equations, utilizes the Euler method for time derivative evaluation. Therefore, the unknown variables at the structural boundary and its variations along time are determined through an ordinary linear system of equations. Moreover, time-dependent boundary conditions may be considered, which represent loading phases. The dual BEM formulation is adopted for modelling the mechanical structural behaviour of cracks bodies. Three examples are considered to illustrate the robustness of the adopted formulation. The results achieved by the BEM are in good agreement with reported data and numerical stability is observed.

  10. A BEM formulation applied in the mechanical material modelling of viscoelastic cracked structures

    NASA Astrophysics Data System (ADS)

    Oliveira, Hugo Luiz; Leonel, Edson Denner

    2017-03-01

    The present study aims at performing a mechanical analysis of 2D viscoelastic cracked structural materials using the Boundary Element Method (BEM). The mesh dimensionality reduction provided by the BEM and its accuracy in representing high gradient fields make this numerical method robust to solve fracture mechanics problems. Viscoelastic models address phenomena that provide changes on the mechanical material properties along time. Well-established viscoelastic models such as Maxwell, Kelvin-Voigt and Boltzmann are used in this study. The numerical viscoelastic scheme, which is based on algebraic BEM equations, utilizes the Euler method for time derivative evaluation. Therefore, the unknown variables at the structural boundary and its variations along time are determined through an ordinary linear system of equations. Moreover, time-dependent boundary conditions may be considered, which represent loading phases. The dual BEM formulation is adopted for modelling the mechanical structural behaviour of cracks bodies. Three examples are considered to illustrate the robustness of the adopted formulation. The results achieved by the BEM are in good agreement with reported data and numerical stability is observed.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. An adhesive contact mechanics formulation based on atomistically induced surface traction

    SciTech Connect

    Fan, Houfu; Ren, Bo; Li, Shaofan

    2015-12-01

    In this work, we have developed a novel multiscale computational contact formulation based on the generalized Derjuguin approximation for continua that are characterized by atomistically enriched constitutive relations in order to study macroscopic interaction between arbitrarily shaped deformable continua. The proposed adhesive contact formulation makes use of the microscopic interaction forces between individual particles in the interacting bodies. In particular, the double-layer volume integral describing the contact interaction (energy, force vector, matrix) is converted into a double-layer surface integral through a mathematically consistent approach that employs the divergence theorem and a special partitioning technique. The proposed contact model is formulated in the nonlinear continuum mechanics framework and implemented using the standard finite element method. With no large penalty constant, the stiffness matrix of the system will in general be well-conditioned, which is of great significance for quasi-static analysis. Three numerical examples are presented to illustrate the capability of the proposed method. Results indicate that with the same mesh configuration, the finite element computation based on the surface integral approach is faster and more accurate than the volume integral based approach. In addition, the proposed approach is energy preserving even in a very long dynamic simulation.

  16. 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.

  17. 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.

  18. Mechanisms of mitochondrial damage in keratinocytes by pemphigus vulgaris antibodies.

    PubMed

    Kalantari-Dehaghi, Mina; Chen, Yumay; Deng, Wu; Chernyavsky, Alex; Marchenko, Steve; Wang, Ping H; Grando, Sergei A

    2013-06-07

    The development of nonhormonal treatment of pemphigus vulgaris (PV) has been hampered by a lack of clear understanding of the mechanisms leading to keratinocyte (KC) detachment and death in pemphigus. In this study, we sought to identify changes in the vital mitochondrial functions in KCs treated with the sera from PV patients and healthy donors. PV sera significantly increased proton leakage from KCs, suggesting that PV IgGs increase production of reactive oxygen species. Indeed, measurement of intracellular reactive oxygen species production showed a drastic increase of cell staining in response to treatment by PV sera, which was confirmed by FACS analysis. Exposure of KCs to PV sera also caused dramatic changes in the mitochondrial membrane potential detected with the JC-1 dye. These changes can trigger the mitochondria-mediated intrinsic apoptosis. Although sera from different PV patients elicited unique patterns of mitochondrial damage, the mitochondria-protecting drugs nicotinamide (also called niacinamide), minocycline, and cyclosporine A exhibited a uniform protective effect. Their therapeutic activity was validated in the passive transfer model of PV in neonatal BALB/c mice. The highest efficacy of mitochondrial protection of the combination of these drugs found in mitochondrial assay was consistent with the ability of the same drug combination to abolish acantholysis in mouse skin. These findings provide a theoretical background for clinical reports of the efficacy of mitochondria-protecting drugs in PV patients. Pharmacological protection of mitochondria and/or compensation of an altered mitochondrial function may therefore become a novel approach to development of personalized nonhormonal therapies of patients with this potentially lethal autoimmune blistering disease.

  19. Mechanisms of Mitochondrial Damage in Keratinocytes by Pemphigus Vulgaris Antibodies*

    PubMed Central

    Kalantari-Dehaghi, Mina; Chen, Yumay; Deng, Wu; Chernyavsky, Alex; Marchenko, Steve; Wang, Ping H.; Grando, Sergei A.

    2013-01-01

    The development of nonhormonal treatment of pemphigus vulgaris (PV) has been hampered by a lack of clear understanding of the mechanisms leading to keratinocyte (KC) detachment and death in pemphigus. In this study, we sought to identify changes in the vital mitochondrial functions in KCs treated with the sera from PV patients and healthy donors. PV sera significantly increased proton leakage from KCs, suggesting that PV IgGs increase production of reactive oxygen species. Indeed, measurement of intracellular reactive oxygen species production showed a drastic increase of cell staining in response to treatment by PV sera, which was confirmed by FACS analysis. Exposure of KCs to PV sera also caused dramatic changes in the mitochondrial membrane potential detected with the JC-1 dye. These changes can trigger the mitochondria-mediated intrinsic apoptosis. Although sera from different PV patients elicited unique patterns of mitochondrial damage, the mitochondria-protecting drugs nicotinamide (also called niacinamide), minocycline, and cyclosporine A exhibited a uniform protective effect. Their therapeutic activity was validated in the passive transfer model of PV in neonatal BALB/c mice. The highest efficacy of mitochondrial protection of the combination of these drugs found in mitochondrial assay was consistent with the ability of the same drug combination to abolish acantholysis in mouse skin. These findings provide a theoretical background for clinical reports of the efficacy of mitochondria-protecting drugs in PV patients. Pharmacological protection of mitochondria and/or compensation of an altered mitochondrial function may therefore become a novel approach to development of personalized nonhormonal therapies of patients with this potentially lethal autoimmune blistering disease. PMID:23599429

  20. 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

  1. Covariant formulation of the governing equations of continuum mechanics in an Eulerian description

    NASA Astrophysics Data System (ADS)

    Schöberl, Markus; Schlacher, Kurt

    2007-05-01

    We present the balance relations for a continuum in the Eulerian formulation in a pure covariant fashion. Based on the analysis of nonrelativistic particle mechanics, we adapt the covariant description to the case of a continuum. The use of the covariant Nijenhuis differential as well as the splitting of the vertical configuration bundle are the key objects that allow a coordinate-free representation. We state the balance equations such that they are valid, also when time variant transformations are applied, which leads to a nontrivial space-time connection and a metric which explicitly depends on the time.

  2. Damage mechanisms and influence of gradation for steep riprap

    SciTech Connect

    Rohan, K.; Belfadhel, M.B.; Lefebvre, G. ); Dascal, O. )

    1994-03-01

    Model tests in a laboratory flume were performed to verify certain hypotheses put forward to explain steep riprap behavior observed in the field at several embankment dam sites. The laboratory study has focused on riprap degradation under wave attack, and on the influence of fine blocks incorporated into riprap. Unlike flatter riprap, steep riprap is characterized by a low rate of damage until a point of acceleration, after which damage progresses rapidly. At that stage, damage is characterized by sliding and crumbling, which results in an upward propagation of damage toward the crest. The inclusion of a portion of small blocks into the riprap significantly reduces the stability of seep riprap. This detrimental effect is gradually reduced as the riprap slope becomes flatter.

  3. 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

  4. 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.

  5. Mitigating thermal mechanical damage potential during two-photon dermal imaging.

    PubMed

    Masters, Barry R; So, Peter T C; Buehler, Christof; Barry, Nicholas; Sutin, Jason D; Mantulin, William W; Gratton, Enrico

    2004-01-01

    Two-photon excitation fluorescence microscopy allows in vivo high-resolution imaging of human skin structure and biochemistry with a penetration depth over 100 microm. The major damage mechanism during two-photon skin imaging is associated with the formation of cavitation at the epidermal-dermal junction, which results in thermal mechanical damage of the tissue. In this report, we verify that this damage mechanism is of thermal origin and is associated with one-photon absorption of infrared excitation light by melanin granules present in the epidermal-dermal junction. The thermal mechanical damage threshold for selected Caucasian skin specimens from a skin bank as a function of laser pulse energy and repetition rate has been determined. The experimentally established thermal mechanical damage threshold is consistent with a simple heat diffusion model for skin under femtosecond pulse laser illumination. Minimizing thermal mechanical damage is vital for the potential use of two-photon imaging in noninvasive optical biopsy of human skin in vivo. We describe a technique to mitigate specimen thermal mechanical damage based on the use of a laser pulse picker that reduces the laser repetition rate by selecting a fraction of pulses from a laser pulse train. Since the laser pulse picker decreases laser average power while maintaining laser pulse peak power, thermal mechanical damage can be minimized while two-photon fluorescence excitation efficiency is maximized.

  6. Market-Based Coordination of Thermostatically Controlled Loads—Part I: A Mechanism Design Formulation

    SciTech Connect

    Li, Sen; Zhang, Wei; Lian, Jianming; Kalsi, Karanjit

    2016-03-01

    This paper focuses on the coordination of a population of Thermostatically Controlled Loads (TCLs) with unknown parameters to achieve group objectives. The problem involves designing the bidding and market clearing strategy to motivate self-interested users to realize efficient energy allocation subject to a peak power constraint. Using the mechanism design approach, we propose a market-based coordination framework, which can effectively incorporate heterogeneous load dynamics, systematically deal with user preferences, account for the unknown load model parameters, and enable the real-world implementation with limited communication resources. This paper is divided into two parts. Part I presents a mathematical formulation of the problem and develops a coordination framework using the mechanism design approach. Part II presents a learning scheme to account for the unknown load model parameters, and evaluates the proposed framework through realistic simulations.

  7. Damage mechanisms avoided or managed for NIF large optics

    SciTech Connect

    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.; Finucane, R. G.; Guss, G. M.; Henesian, M. A.; Honig, J.; Kalantar, D. H.; Kegelmeyer, L. M.; Liao, Z. M.; MacGowan, B. J.; Matthews, M. J.; Mehta, N. C.; Norton, M. A.; Nostrand, M. C.; Sacks, R. A.; Siegel, L. R.; Stolz, C. J.; Suratwala, T. I.; Trenholme, J. B.; Wegner, P. J.; Whitman, P. K.; Widmayer, C. C.; Yang, S. T.; McCandless, K. P.; Miller, P. E.; Negres, R. A.; Orth, C. D.; Cross, D. A.; Demos, S. G.

    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 them 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.

  8. Damage mechanisms avoided or managed for NIF large optics

    DOE PAGES

    Manes, K. R.; Spaeth, M. L.; Adams, J. J.; ...

    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

  9. Intercomparison of chemical mechanisms for air quality policy formulation and assessment under North American conditions.

    PubMed

    Derwent, Richard

    2017-02-22

    The intercomparison of seven chemical mechanisms for their suitability for air quality policy formulation and assessment is described. Box modelling techniques were employed using 44 sets of background environmental conditions covering North America to constrain the chemical development of the longer-lived species. The selected mechanisms were modified to enable an unbiased assessment of the adequacy of the parameterisations of photochemical ozone production from VOC oxidation in the presence of NOx. Photochemical ozone production rates responded differently to 30% NOx and VOC reductions with the different mechanisms, despite the striking similarities between the base case ozone production rates. The 30% reductions in NOx and VOCs also produced changes in OH. The responses in OH to 30% reductions in NOx and VOCs appeared to be more sensitive to mechanism choice, compared with the responses in the photochemical ozone production rates. Whereas 30% NOx reductions generally led to decreases in OH, 30% reductions in VOCs led to increases in OH, irrespective of mechanism choice and background environmental conditions. The different mechanisms therefore gave different OH responses to NOx and VOC reductions and so would give different responses in terms of changes in the fate and behaviour of air toxics, acidification and eutrophication and fine particle formation compared with others, in response to ozone control strategies. Policy-makers need to understand that there are likely to be inherent differences in the responses to ozone control strategies between different mechanisms, depending on background environmental conditions and the extents of NOx and VOC reductions under consideration. IMPLICATIONS The purpose of this paper is to compare predicted ozone responses to NOx and VOC reductions with seven chemical mechanisms under North American conditions. The good agreement found between the tested mechanisms should provide some support for their application in the air

  10. 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.

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

    PubMed

    Cui, Ganglong; Yang, Weitao

    2011-05-28

    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

  12. 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.

  13. Mechanisms of Retinal Damage from Chronic Laser Radiation.

    DTIC Science & Technology

    1981-07-01

    stopped at the corneal epithelium and at high intensity can cause damage there. The arc welders’ superficial keratitis and the "eyes open sun lamp...John Wiley & Sons Inc., New York, p. 218. 1967. 31. Osterberg, G.: Topography of the layer of rods and cones in the human retina. Acta

  14. Absorption mechanism of DHP107, an oral paclitaxel formulation that forms a hydrated lipidic sponge phase

    PubMed Central

    Jang, Yura; Chung, Hye Jin; Hong, Jung Wan; Yun, Cheol-Won; Chung, Hesson

    2017-01-01

    Paclitaxel is a most widely used anticancer drug with low oral bioavailability, thus it is currently administered via intravenous infusion. DHP107 is a lipid-based paclitaxel formulation that can be administered as an oral solution. In this study, we investigated the mechanism of paclitaxel absorption after oral administration of DHP107 in mice and rats by changing the dosing interval, and evaluated the influence of bile excretion. DHP107 was orally administered to mice at various dosing intervals (2, 4, 8, 12, 24 h) to examine how residual DHP107 affected paclitaxel absorption during subsequent administration. Studies with small-angle X-ray diffraction (SAXS) and cryo-transmission electron microscopy (cryo-TEM) showed that DHP107 formed a lipidic sponge phase after hydration. The AUC values after the second dose were smaller than those after the first dose, which was correlated to the induction of expression of P-gp and CYP in the livers and small intestines from 2 h to 7 d after the first dose. The smaller AUC value observed after the second dose was also attributed to the intestinal adhesion of residual formulation. The adhered DHP107 may have been removed by ingested food, thus resulting in a higher AUC. In ex vivo and in vivo mucoadhesion studies, the formulation adhered to the villi for up to 24 h, and the amount of DHP107 that adhered was approximately half that of monoolein. The paclitaxel absorption after administration of DHP107 was not affected by bile in the cholecystectomy mice. The dosing interval and food intake affect the oral absorption of paclitaxel from DHP107, which forms a mucoadhesive sponge phase after hydration. Bile excretion does not affect the absorption of paclitaxel from DHP107 in vivo. PMID:27867185

  15. Non-Fourier based thermal-mechanical tissue damage prediction for thermal ablation.

    PubMed

    Li, Xin; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

    2017-01-02

    Prediction of tissue damage under thermal loads plays important role for thermal ablation planning. A new methodology is presented in this paper by combing non-Fourier bio-heat transfer, constitutive elastic mechanics as well as non-rigid motion of dynamics to predict and analyze thermal distribution, thermal-induced mechanical deformation and thermal-mechanical damage of soft tissues under thermal loads. Simulations and comparison analysis demonstrate that the proposed methodology based on the non-Fourier bio-heat transfer can account for the thermal-induced mechanical behaviors of soft tissues and predict tissue thermal damage more accurately than classical Fourier bio-heat transfer based model.

  16. Mechanical Properties Studies of Components Formulation for Mixing Process Contain of Polypropylene, Polyethylene, and Aluminium Powder

    NASA Astrophysics Data System (ADS)

    Hamsi, A.; Dinzi, R.

    2017-03-01

    Certain powder and others components can induce toxic reactions if not properly handled in the mixing stage. During handling, the small particles can become airborne and be trapped in the lungs, another concern is inhomogeneities in the mixing process. Uniform quantities of the particles of the components are needed in all portions of the mixture. This paper reports the results of mechanical properties studies of mixing three components formulation for mixing process. Contain of Polyethylene (PE), Polyprophylene (PP) and Aluminium Powder. Powder mixer, Autodesk mold flow and computer based on excell method was carried out to study the influence of each formulation component on the flow %, PE 20% and Aluminium powder 2%. Macroscopic optic and macro photo was carried out to identify the homogenity of mixing, tensile test for identify the strength of component after mixing. Finally the optimal tensile test with composition PP 785,PE 20% and Aluminium powder 2% at speed 52 rpm, temperature 1500C, the tensile strength 20,92 N/mm2. At temperature 1600C, speed 100 rpm the optimum tensile strength 17,91 N/mm2. The result of simulation autodesk mold flow adviser the filling time 6 seconds. Otherwise on manual hot hidraulic press the time of filling 10 seconds.

  17. Direct Observations of Fracture and the Damage Mechanics of Ceramics

    DTIC Science & Technology

    1988-10-31

    microplasticity up to the fracture load. d. It shculd have low enough strength in tension and compression to enable strength measurements at easily accessible...15jm. SEM examination of the grains after large amounts of deformation indicated that the grains are brittle without any evidence of microplasticity . In...and microplasticity in polycrystalline alumina", J.Mater.Sci., 12(1977)791-796. 93. J Lankford, "Compressive microfracture and indentation damage in A1

  18. Electron radiation damage mechanisms in 2D MoSe2

    NASA Astrophysics Data System (ADS)

    Lehnert, T.; Lehtinen, O.; Algara-Siller, G.; Kaiser, U.

    2017-01-01

    The contributions of different damage mechanisms in single-layer MoSe2 were studied by investigating different MoSe2/graphene heterostructures by the aberration-corrected high-resolution transmission electron microscopy (AC-HRTEM) at 80 keV. The damage cross-sections were determined by direct counting of atoms in the AC-HRTEM images. The contributions of damage mechanisms such as knock-on damage or ionization effects were estimated by comparing the damage rates in different heterostructure configurations, similarly to what has been earlier done with MoS2. The behaviour of MoSe2 was found to be nearly identical to that of MoS2, which is an unexpected result, as the knock-on mechanism should be suppressed in MoSe2 due to the high mass of Se, as compared to S.

  19. A physically-based continuum damage mechanics model for numerical prediction of damage growth in laminated composite plates

    NASA Astrophysics Data System (ADS)

    Williams, Kevin Vaughan

    Rapid growth in use of composite materials in structural applications drives the need for a more detailed understanding of damage tolerant and damage resistant design. Current analytical techniques provide sufficient understanding and predictive capabilities for application in preliminary design, but current numerical models applicable to composites are few and far between and their development into well tested, rigorous material models is currently one of the most challenging fields in composite materials. The present work focuses on the development, implementation, and verification of a plane-stress continuum damage mechanics based model for composite materials. A physical treatment of damage growth based on the extensive body of experimental literature on the subject is combined with the mathematical rigour of a continuum damage mechanics description to form the foundation of the model. The model has been implemented in the LS-DYNA3D commercial finite element hydrocode and the results of the application of the model are shown to be physically meaningful and accurate. Furthermore it is demonstrated that the material characterization parameters can be extracted from the results of standard test methodologies for which a large body of published data already exists for many materials. Two case studies are undertaken to verify the model by comparison with measured experimental data. The first series of analyses demonstrate the ability of the model to predict the extent and growth of damage in T800/3900-2 carbon fibre reinforced polymer (CFRP) plates subjected to normal impacts over a range of impact energy levels. The predicted force-time and force-displacement response of the panels compare well with experimental measurements. The damage growth and stiffness reduction properties of the T800/3900-2 CFRP are derived using published data from a variety of sources without the need for parametric studies. To further demonstrate the physical nature of the model, a IM6

  20. 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…

  1. Failure Behavior Simulation for Bolted Composite Joints Based on Damage Mechanics Approach

    NASA Astrophysics Data System (ADS)

    Xiao, Yi; Ishikawa, Takashi

    This paper presents the development of an accumulative damage model based on continuum damage mechanics (CDM) to simulate the bearing failure and response in the bolted composite joints. The simulation is implemented into a general-purpose FEM code ABAQUS. The main damage mechanisms observed from experimental study are described as accumulated compressive damage that appeared by matrix compression failure and fiber compression-shear failure. The fundamental approach consists of contact problem at the pin/hole interface, progressive damage, large deformation problem and material nonlinear problem. A complex approach based on a nonlinear shear elasticity theory combined with a continuum damage mechanics approach can be also utilized to represent the material nonlinear behavior during loading. The damage accumulation criteria using the hybrid method based on Hashin and Yamada-Sun’s failure criteria are adopted, and the stress redistribution analysis using a degradation model for the damaged ply is performed. The accurate prediction results include progressive damage and strength response of the joints that agrees well with the existing experimental data.

  2. 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.

  3. Instabilities of Damage and Surface Degradation Mechanisms in Brittle Material Structural Systems

    DTIC Science & Technology

    1992-03-15

    ultrasonic measurements are obtained at various locations on the -specimens. The damage and instability distributions obtained by using a finite ele- ment...procedure and symbolic computation are related to the dissipated energy derived from ultrasonic measurements. Comparisons of theoretical predictions and... ultrasonic ) and mechanical experiments to obtain quantitative measurements of the surface damage dissipated energy and its relation to instabilities

  4. Investigation of Mechanism(s) of DNA Damage Induced by 4-Monochlorobiphenyl (PCB3) Metabolites

    PubMed Central

    Xie, Wei; Wang, Kai; Robertson, Larry W.; Ludewig, Gabriele

    2010-01-01

    4-Monochlorobiphenyl (PCB3) is readily converted by xenobiotic-metabolizing enzymes to dihydroxy-metabolites and quinones. The PCB3 hydroquinone (PCB3-HQ; 2-(4’-chlorophenyl)-1,4-hydroquinone) induces chromosome loss in Chinese Hamster V79 cells, whereas the para-quinone (PCB3-pQ; 2-(4’-chlorophenyl)-1,4-benzoquinone) very efficiently induces gene mutations and chromosome breaks. Apparently, each of these two metabolites, which are a redox pair, has a different spectrum of genotoxic effects due to different, metabolite-specific mechanisms. We hypothesized that the HQ requires enzymatic activation by peroxidases with the formation of reactive oxygen species (ROS) as the ultimate genotoxin, whereas the pQ reacts directly with nucleophilic sites in DNA and/or proteins. To examine this hypothesis, we employed two cell lines with different myeloperoxidase (MPO) activities, MPO-rich HL-60 and MPO-deficient Jurkat cells, and measured cytotoxicity, DNA damage (COMET assay), MPO activity, intracellular levels of reactive oxygen species (ROS) and intracellular free –SH groups (monochlorobimane assay, MCB) and free GSH contents (enzyme recycling method) after treatment with PCB3-HQ and PCB3-pQ. We also examined the modulation of these effects by normal/low temperature, pre-treatment with an MPO inhibitor (succinylacetone, SA), or GSH depletion. PCB3-p-Q increased intracellular ROS levels and induced DNA damage in both HL-60 and Jurkat cells at 37 °C and 6 °C, indicating a direct, MPO-independent mode of activity. It also strongly reduced intracellular free –SH groups and GSH levels in normal and GSH-depleted cells. Thus the ROS increase could be caused by reduced protection by GSH or non-enzymatic autoxidation of the resulting PCB3-HQ-GSH adduct. PCB3-HQ did not produce a significant reduction of intracellular GSH in HL-60 cells and reduced intracellular free –SH groups only at the highest concentration tested in GSH depleted cells. Moreover, PCB3-HQ induced DNA

  5. 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.

  6. AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience.

    PubMed

    Adler-Moore, Jill; Proffitt, Richard T

    2002-02-01

    Amphotericin B is the treatment of choice for life-threatening systemic fungal infections such as candidosis and aspergillosis. To improve this drug's efficacy and reduce its acute and chronic toxicities, several lipid formulations of the drug have been developed, including AmBisome, a liposomal formulation of amphotericin B. The liposome is composed of high transition temperature phospholipids and cholesterol, designed to incorporate amphotericin B securely into the liposomal bilayer. AmBisome can bind to fungal cell walls, where the liposome is disrupted. The amphotericin B, after being released from the liposomes, is thought to transfer through the cell wall and bind to ergosterol in the fungal cell membrane. This mechanism of action of AmBisome results in its potent in vitro fungicidal activity while the integrity of the liposome is maintained in the presence of mammalian cells, for which it has minimal toxicity. In animal models, AmBisome is effective in treating both intracellular (leishmaniasis and histoplasmosis) and extracellular (candidosis and aspergillosis) systemic infections. Because of its low toxicity at the organ level, intravenous AmBisome can be safely delivered at markedly high doses of amphotericin B (1-30 mg/kg) for the treatment of systemic fungal infections. AmBisome has a circulating half-life of 5-24 h in animals, and in animal models appears to localize at sites of infection in the brain (cryptococcosis, aspergillosis, coccidioidomycosis), lungs (blastomycosis, paracoccidioidomycosis, aspergillosis) and kidneys (candidosis), delivering amphotericin B that remains bioavailable in tissues for several weeks following treatment.

  7. A cellular automaton for the signed particle formulation of quantum mechanics

    NASA Astrophysics Data System (ADS)

    Sellier, J. M.; Kapanova, K. G.; Dimov, I.

    2017-02-01

    Recently, a new formulation of quantum mechanics, based on the concept of signed particles, has been suggested. In this paper, we introduce a cellular automaton which mimics the dynamics of quantum objects in the phase-space in a time-dependent fashion. This is twofold: it provides a simplified and accessible language to non-physicists who wants to simulate quantum mechanical systems, at the same time it enables a different way to explore the laws of Physics. Moreover, it opens the way towards hybrid simulations of quantum systems by combining full quantum models with cellular automata when the former fail. In order to show the validity of the suggested cellular automaton and its combination with the signed particle formalism, several numerical experiments are performed, showing very promising results. Being this article a preliminary study on quantum simulations in phase-space by means of cellular automata, some conclusions are drawn about the encouraging results obtained so far and the possible future developments.

  8. Mechanism of site-specific DNA damage induced by ozone.

    PubMed

    Ito, Kimiko; Inoue, Sumiko; Hiraku, Yusuke; Kawanishi, Shosuke

    2005-08-01

    Ozone has been shown to induce lung tumors in mice. The reactivity of ozone with DNA in an aqueous solution was investigated by a DNA sequencing technique using 32P-labeled DNA fragments. Ozone induced cleavages in the deoxyribose-phosphate backbone of double-stranded DNA, which were reduced by hydroxyl radical scavengers, suggesting the participation of hydroxyl radicals in the cleavages. The ozone-induced DNA cleavages were enhanced with piperidine treatment, which induces cleavages at sites of base modification, but the inhibitory effect of hydroxyl radical scavengers on the piperidine-induced cleavages was limited. Main piperidine-labile sites were guanine and thymine residues. Cleavages at some guanine and thymine residues after piperidine treatment became more predominant with denatured single-stranded DNA. Exposure of calf thymus DNA to ozone resulted in a dose-dependent increase of the 8-oxo-7,8-dihydro-2'-deoxyguanosine formation, which was partially inhibited by hydroxyl radical scavengers. ESR studies using 5,5-dimethylpyrroline-N-oxide (DMPO) showed that aqueous ozone produced the hydroxyl radical adduct of DMPO. In addition, the fluorescein-dependent chemiluminescence was detected during the decomposition of ozone in a buffer solution and the enhancing effect of D2O was observed, suggesting the formation of singlet oxygen. However, no or little enhancing effect of D2O on the ozone-induced DNA damage was observed. These results suggest that DNA backbone cleavages were caused by ozone via the production of hydroxyl radicals, while DNA base modifications were mainly caused by ozone itself and the participation of hydroxyl radicals and/or singlet oxygen in base modifications is small, if any. A possible link of ozone-induced DNA damage to inflammation-associated carcinogenesis as well as air pollution-related carcinogenesis is discussed.

  9. 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.

  10. 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.

  11. Navy Enhanced Sierra Mechanics (NESM): Toolbox for predicting Navy shock and damage

    DOE PAGES

    Moyer, Thomas; Stergiou, Jonathan; Reese, Garth; ...

    2016-05-25

    Here, the US Navy is developing a new suite of computational mechanics tools (Navy Enhanced Sierra Mechanics) for the prediction of ship response, damage, and shock environments transmitted to vital systems during threat weapon encounters. NESM includes fully coupled Euler-Lagrange solvers tailored to ship shock/damage predictions. NESM is optimized to support high-performance computing architectures, providing the physics-based ship response/threat weapon damage predictions needed to support the design and assessment of highly survivable ships. NESM is being employed to support current Navy ship design and acquisition programs while being further developed for future Navy fleet needs.

  12. Simplified strategies based on damage mechanics for concrete under dynamic loading.

    PubMed

    Mazars, Jacky; Grange, Stéphane

    2017-01-28

    Based on previous work, the µ damage model has been designed to figure out the various damage effects in concrete correlated with monotonic and cyclic loading, including unilateral effects. Assumptions are formulated to simplify constitutive relationships while still allowing for a correct description of the main nonlinear effects. In this context, the paper presents an enhanced simplified finite-element description including a damage description, based on the use of multifibre beam elements and including strain rate effects. Applications show that such a strategy leads to an efficient tool to simulate dynamic loading at low, medium and high velocities.This article is part of the themed issue 'Experimental testing and modelling of brittle materials at high strain rates'.

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

    NASA Astrophysics Data System (ADS)

    Fan, Linfeng; Lehmann, Peter; Or, Dani

    2014-05-01

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

  14. An in vivo mechanism for the reduced peripheral neurotoxicity of NK105: a paclitaxel-incorporating polymeric micellar nanoparticle formulation

    PubMed Central

    Nakamura, Iwao; Ichimura, Eiji; Goda, Rika; Hayashi, Hitomi; Mashiba, Hiroko; Nagai, Daichi; Yokoyama, Hirofumi; Onda, Takeshi; Masuda, Akira

    2017-01-01

    In our previous rodent studies, the paclitaxel (PTX)-incorporating polymeric micellar nanoparticle formulation NK105 had showed significantly stronger antitumor effects and reduced peripheral neurotoxicity than PTX dissolved in Cremophor® EL and ethanol (PTX/CRE). Thus, to elucidate the mechanisms underlying reduced peripheral neurotoxicity due to NK105, we performed pharmacokinetic analyses of NK105 and PTX/CRE in rats. Among neural tissues, the highest PTX concentrations were found in the dorsal root ganglion (DRG). Moreover, exposure of DRG to PTX (Cmax_PTX and AUC0-inf._PTX) in the NK105 group was almost half that in the PTX/CRE group, whereas exposure of sciatic and sural nerves was greater in the NK105 group than in the PTX/CRE group. In histopathological analyses, damage to DRG and both peripheral nerves was less in the NK105 group than in the PTX/CRE group. The consistency of these pharmacokinetic and histopathological data suggests that high levels of PTX in the DRG play an important role in the induction of peripheral neurotoxicity, and reduced distribution of PTX to the DRG of NK105-treated rats limits the ensuing peripheral neurotoxicity. In further analyses of PTX distribution to the DRG, Evans blue (Eb) was injected with BODIPY®-labeled NK105 into rats, and Eb fluorescence was observed only in the DRG. Following injection, most Eb dye bound to albumin particles of ~8 nm and had penetrated the DRG. In contrast, BODIPY®–NK105 particles of ~90 nm were not found in the DRG, suggesting differential penetration based on particle size. Because PTX also circulates as PTX–albumin particles of ~8 nm following injection of PTX/CRE, reduced peripheral neurotoxicity of NK105 may reflect exclusion from the DRG due to particle size, leading to reduced PTX levels in rat DRG (275). PMID:28243090

  15. A fully coupled Thermo-Hydro-Mechanical Double Porosity Formulation for Modeling Multiphysics Problems in Geological Media

    NASA Astrophysics Data System (ADS)

    Sanchez, M. J.; Gens, A.; Jarecki, Z.; Olivella, S.

    2012-12-01

    This work presents a coupled Thermo-Hydro-Mechanical (THM) formulation developed to handle multiphysic problems in porous media with two dominant void levels. The proposed framework assumes the presence of two porous media linked through a mass transfer term between them. In many cases, the use of a double porosity formulation is more realistic because it is possible to take explicitly into account the different physical phenomena that take place in each void level, and also their mutual interactions. The formulation is especially suitable for cases in which the material exhibits a strong coupling between the mechanical and the hydraulic problem in both media. The problem is approached using a multi-phase, multi-species formulation that expresses mathematically the main coupled thermo-hydro-mechanical phenomena in terms of: balance equations, constitutive equations and equilibrium restrictions. In its more general form, the proposed approach allows the consideration of multiphase flow in the two pore levels coupled with the mechanical problem. The formulation presented is quite open and general, and able to incorporate different constitutive laws for each basic structural level considered; for the mechanical, hydraulic and thermal problems. The double structure formulation has been implemented in the finite element program CODE_BRIGHT and it has been used to analyze a variety of engineering problems associated with the design of radioactive waste disposal in deep geological media and petroleum engineering problems. This work presents two case studies; one is related to oil production in a heterogeneous reservoir, and the other case focuses on the analysis of a repository for nuclear waste in a clayed formation. Both cases show the potential of the proposed formation to tackle coupled multiphysics problems in porous media.

  16. 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.

  17. 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.

  18. Design of a dual nanostructured lipid carrier formulation based on physicochemical, rheological, and mechanical properties

    NASA Astrophysics Data System (ADS)

    Vitorino, Carla; Alves, Luís; Antunes, Filipe E.; Sousa, João J.; Pais, Alberto A. C. C.

    2013-10-01

    The synergy between nanostructured lipid carriers (NLC) and chemical penetration enhancers provides the basis for a promising strategy to effectively deliver drugs through the skin. In the present work, focus is given to the study of the interaction of limonene, ethanol, and Carbopol Ultrez® 10NF, as the gelling agent, with a co-encapsulating NLC dispersion, containing both olanzapine and simvastatin. The analysis is based on rheological, mechanical, and physicochemical properties. The nanoparticle size ranged from 130 to 400 nm, depending on the system considered. The inclusion of carbopol resulted in a considerable increase in the NLC particle size, which was attributed to carbomer bridging nanoparticles, resulting in some particle aggregation. Rheological measurements indicated that the viscosity of the neat carbopol hydrogel was reduced by the enhancers and to a higher extent by the presence of NLC. A more apolar medium can be pointed out as a general explanation, while a polymer/nanoparticle hydrophobic interaction coupled with surfactant/polymer H-bonding provides the rationale for the NLC effect. The inclusion of enhancers and a carbomer largely contributed to the physicochemical stability of the NLC formulation, as revealed by the low transmission profiles and more negative zeta potential values.

  19. Frame functions in finite-dimensional quantum mechanics and its Hamiltonian formulation on complex projective spaces

    NASA Astrophysics Data System (ADS)

    Moretti, Valter; Pastorello, Davide

    2016-12-01

    This work concerns some issues about the interplay of standard and geometric (Hamiltonian) approaches to finite-dimensional quantum mechanics, formulated in the projective space. Our analysis relies upon the notion and the properties of so-called frame functions, introduced by Gleason to prove his celebrated theorem. In particular, the problem of associating quantum states with positive Liouville densities is tackled from an axiomatic point of view, proving a theorem classifying all possible correspondences. A similar result is established for classical-like observables (i.e. real scalar functions on the projective space) representing quantum ones. These correspondences turn out to be encoded in a one-parameter class and, in both cases, the classical-like objects representing quantum ones result to be frame functions. The requirements of U(n) covariance and (convex) linearity play a central role in the proof of those theorems. A new characterization of classical-like observables describing quantum observables is presented, together with a geometric description of the C∗-algebra structure of the set of quantum observables in terms of classical-like ones.

  20. 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.

  1. Mechanism of nitroimidazole damage to DNA: coulometric evidence

    SciTech Connect

    Knox, R.J.; Edwards, D.I.; Knight, R.C.

    1984-08-01

    A high resolution coulometric technique has been developed to measure the electron requirement for reduction of 12 nitroimidazoles, both in the presence and absence of DNA. The cytotoxic species is shown to be a light sensitive intermediate of drug reduction and a common mechanism of cytotoxicity proposed which involves electron transfer from DNA to the one-electron radical anion (R-NO/sub 2//sup -/).

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

    PubMed Central

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

    2014-01-01

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

  3. Cellular mechanisms of neurovascular damage and repair after stroke.

    PubMed

    Arai, Ken; Lok, Josephine; Guo, Shuzhen; Hayakawa, Kazuhide; Xing, Changhong; Lo, Eng H

    2011-09-01

    The biological processes underlying stroke are complex, and patients have a narrow repertoire of therapeutic opportunities. After the National Institutes of Health (NIH) convened the Stroke Progress Review Group in 2001, stroke research shifted from having a purely neurocentric focus to adopting a more integrated view wherein dynamic interactions between all cell types contribute to function and dysfunction in the brain. This so-called "neurovascular unit" provides a conceptual framework that emphasizes cell-cell interactions between neuronal, glial, and vascular elements. Under normal conditions, signaling within the neurovascular unit helps maintain homeostasis. After stroke, cell-cell signaling is disturbed, leading to pathophysiology. More recently, emerging data now suggest that these cell-cell signaling mechanisms may also mediate parallel processes of neurovascular remodeling during stroke recovery. Because plasticity is a signature feature of the young and developing brain, these concepts may have special relevance to how the pediatric brain responds after stroke.

  4. Neural network based system for damage identification and location in structural and mechanical systems

    SciTech Connect

    Farrar, C.R.; Doebling, S.W.; Prime, M.B.; Cornwell, P.; Kam, M.; Straser, E.G.; Hoerst, B.C.

    1998-11-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Recent advances in wireless, remotely monitored data acquisition systems coupled with the development of vibration-based damage detection algorithms make the possibility of self- or remotely-monitored structures and mechanical systems appear to be within the capabilities of current technology. However, before such a system can be relied upon to perform this monitoring, the variability of the vibration properties that are the basis for the damage detection algorithm must be understood and quantified. This understanding is necessary so that the artificial intelligence/expert system that is employed to discriminate when changes in modal properties are indicative of damage will not yield false indications of damage. To this end, this project has focused on developing statistical methods for quantifying variability in identified vibration proper ties of structural and mechanical systems.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Progressive damage analysis of carbon/epoxy laminates under couple laser and mechanical loading

    NASA Astrophysics Data System (ADS)

    Liu, Wanlei; Chang, Xinlong; Zhang, Xiaojun; Zhang, Youhong

    A multiscale model based bridge theory is proposed for the progressive damage analysis of carbon/epoxy laminates under couple laser and mechanical loading. The ablation model is adopted to calculate ablation temperature changing and ablation surface degradation. The polynomial strengthening model of matrix is used to improve bridging model for reducing parameter input. Stiffness degradation methods of bridging model are also improved in order to analyze the stress redistribution more accurately when the damage occurs. Thermal-mechanical analyses of the composite plate are performed using the ABAQUS/Explicit program with the developed model implemented in the VUMAT. The simulation results show that this model can be used to proclaim the mesoscale damage mechanism of composite laminates under coupled loading.

  10. Reducing Mechanical Formation Damage by Minimizing Interfacial Tension and Capillary Pressure in Tight Gas

    NASA Astrophysics Data System (ADS)

    Ahmed, Arshad; Talib Shuker, Muhannad; Rehman, Khalil; Bahrami, Hassan; Memon, Muhammad Khan

    2013-12-01

    Tight gas reservoirs incur problems and significant damage caused by low permeability during drilling, completion, stimulation and production. They require advanced improvement techniques to achieve flow gas at optimum rates. Water blocking damage (phase Trapping/retention of fluids) is a form of mechanical formation damage mechanism, which is caused by filtrate invasion in drilling operations mostly in fracturing. Water blocking has a noticeable impact on formation damage in gas reservoirs which tends to decrease relative permeability near the wellbore. Proper evaluation of damage and the factors which influence its severity is essential to optimize well productivity. Reliable data regarding interfacial tension between gas and water is required in order to minimize mechanical formation damage potential and to optimize gas production. This study was based on the laboratory experiments of interfacial tension by rising drop method between gas-brine, gas-condensate and gas-brine. The results showed gas condensate has low interfacial tension value 6 - 11 dynes/cm when compared to gas-brine and gas- diesel which were 44 - 58 dynes/cm and 14 - 19 dynes/cm respectively. In this way, the capillary pressure of brine-gas system was estimated as 0.488 psi, therefore diesel-gas system was noticed about 0.164 psi and 0.098 psi for condensate-gas system. A forecast model was used by using IFT values to predict the phase trapping which shows less severe phase trapping damage in case of condensate than diesel and brine. A reservoir simulation study was also carried out in order to better understand the effect of hysteresis on well productivity and flow efficiency affected due to water blocking damage in tight gas reservoirs.

  11. 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.

  12. Independent mechanisms recruit the cohesin loader protein NIPBL to sites of DNA damage

    PubMed Central

    Bot, Christopher; Pfeiffer, Annika; Giordano, Fosco; Dantuma, Nico P.; Ström, Lena

    2017-01-01

    ABSTRACT NIPBL is required to load the cohesin complex on to DNA. While the canonical role of cohesin is to couple replicated sister chromatids together until the onset of mitosis, it also promotes tolerance to DNA damage. Here, we show that NIPBL is recruited to DNA damage throughout the cell cycle via independent mechanisms, influenced by type of damage. First, the heterochromatin protein HP1γ (also known as CBX3) recruits NIPBL to DNA double-strand breaks (DSBs) through the corresponding HP1-binding motif within the N-terminus. By contrast, the C-terminal HEAT repeat domain is unable to recruit NIPBL to DSBs but independently targets NIPBL to laser microirradiation-induced DNA damage. Each mechanism is dependent on the RNF8 and RNF168 ubiquitylation pathway, while the recruitment of the HEAT repeat domain requires further ATM or ATR activity. Thus, NIPBL has evolved a sophisticated response to damaged DNA that is influenced by the form of damage, suggesting a highly dynamic role for NIPBL in maintaining genomic stability. PMID:28167679

  13. 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.

  14. Independent mechanisms recruit the cohesin loader protein NIPBL to sites of DNA damage.

    PubMed

    Bot, Christopher; Pfeiffer, Annika; Giordano, Fosco; Manjeera, Dharani E; Dantuma, Nico P; Ström, Lena

    2017-03-15

    NIPBL is required to load the cohesin complex on to DNA. While the canonical role of cohesin is to couple replicated sister chromatids together until the onset of mitosis, it also promotes tolerance to DNA damage. Here, we show that NIPBL is recruited to DNA damage throughout the cell cycle via independent mechanisms, influenced by type of damage. First, the heterochromatin protein HP1γ (also known as CBX3) recruits NIPBL to DNA double-strand breaks (DSBs) through the corresponding HP1-binding motif within the N-terminus. By contrast, the C-terminal HEAT repeat domain is unable to recruit NIPBL to DSBs but independently targets NIPBL to laser microirradiation-induced DNA damage. Each mechanism is dependent on the RNF8 and RNF168 ubiquitylation pathway, while the recruitment of the HEAT repeat domain requires further ATM or ATR activity. Thus, NIPBL has evolved a sophisticated response to damaged DNA that is influenced by the form of damage, suggesting a highly dynamic role for NIPBL in maintaining genomic stability.

  15. Computational Simulation of Damage Progression of Composite Thin Shells Subjected to Mechanical Loads

    NASA Technical Reports Server (NTRS)

    Gotsis, P. K.; Chamis, C. C.; Minnetyan, L.

    1996-01-01

    Defect-free and defected composite thin shells with ply orientation (90/0/+/-75) made of graphite/epoxy are simulated for damage progression and fracture due to internal pressure and axial loading. The thin shells have a cylindrical geometry with one end fixed and the other free. The applied load consists of an internal pressure in conjunction with an axial load at the free end, the cure temperature was 177 C (350 F) and the operational temperature was 21 C (70 F). The residual stresses due to the processing are taken into account. Shells with defect and without defects were examined by using CODSTRAN an integrated computer code that couples composite mechanics, finite element and account for all possible failure modes inherent in composites. CODSTRAN traces damage initiation, growth, accumulation, damage propagation and the final fracture of the structure. The results show that damage initiation started with matrix failure while damage/fracture progression occurred due to additional matrix failure and fiber fracture. The burst pressure of the (90/0/+/- 75) defected shell was 0.092% of that of the free defect. Finally the results of the damage progression of the (90/0/+/- 75), defective composite shell was compared with the (90/0/+/- theta, where theta = 45 and 60, layup configurations. It was shown that the examined laminate (90/0/+/- 75) has the least damage tolerant of the two compared defective shells with the (90/0/+/- theta), theta = 45 and 60 laminates.

  16. 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.

  17. 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.

  18. 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.

  19. Study on fatigue damage characteristics of deformable mirrors under thermal-mechanical coupling effect.

    PubMed

    Chen, Lixia; Wu, Zhen; Zhang, Bin; Sun, Nianchun

    2016-11-01

    In a wavefront correction process, both the mechanical effect and the irradiation of a high-power continuous-wave laser distort the deformable mirror (DM) surface, which inevitably speeds up the fatigue damage of the DM. By utilizing the stress analysis model for the fatigue damage of the DM, the fatigue damage effects are analyzed quantitatively on the consideration of thermal-mechanical coupling effects, and the fatigue life prediction model has further been proposed based on the S-N curve and Miner cumulative damage theory. On this basis, thermal-mechanical conditions have been analyzed, and the influence of laser parameters on the fatigue life of the DM has also been discussed in detail. The results indicate that the increasing of maximum temperature rise of the DM leads to the increasing of stress, and further brings about the decreasing of the fatigue life. Meanwhile, the position at the rear surface of the DM subjected to the maximum stress always presents the minimum fatigue life. Furthermore, the laser irradiation makes the DM more easily damaged when the DM is correcting a distorted wavefront, and the fatigue life decreases with the increasing of irradiation time and power density for a given peak and valley (PV) value of the corrected wavefront. Additionally, the fatigue life also decreases with the increasing of power density and the decreasing of spot radius for a certain total irradiation. On the other hand, for the given laser parameters, the influence of the mechanical effect on fatigue life is gradually apparent with increasing PV value of the corrected wavefront, and when the PV value is more than 2λ, the mechanical effect instead of the thermal effect becomes the key factor for fatigue damage of the DM.

  20. Mechanisms of mutagenesis: DNA replication in the presence of DNA damage

    PubMed Central

    Liu, Binyan; Xue, Qizhen; Tang, Yong; Cao, Jia; Guengerich, F. Peter; Zhang, Huidong

    2017-01-01

    Environmental mutagens cause DNA damage that disturbs replication and produces mutations, leading to cancer and other diseases. We discuss mechanisms of mutagenesis resulting from DNA damage, from the level of DNA replication by a single polymerase to the complex DNA replisome of some typical model organisms (including bacteriophage T7, T4, Sulfolobus solfataricus, E. coli, yeast and human). For a single DNA polymerase, DNA damage can affect replication in three major ways: reducing replication fidelity, causing frameshift mutations, and blocking replication. For the DNA replisome, protein interactions and the functions of accessory proteins can yield rather different results even with a single DNA polymerase. The mechanism of mutation during replication performed by the DNA replisome is a long-standing question. Using new methods and techniques, the replisomes of certain organisms and human cell extracts can now be investigated with regard to the bypass of DNA damage. In this review, we consider the molecular mechanism of mutagenesis resulting from DNA damage in replication at the levels of single DNA polymerases and complex DNA replisomes, including translesion DNA synthesis. PMID:27234563

  1. 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

  2. Nephro-protective effect of a novel formulation of unopened coconut inflorescence sap powder on gentamicin induced renal damage by modulating oxidative stress and inflammatory markers.

    PubMed

    Jose, Svenia P; S, Asha; Im, Krishnakumar; M, Ratheesh; Santhosh, Savitha; S, Sandya; B, Girish Kumar; C, Pramod

    2017-01-01

    Fresh oyster white translucent sap obtained from the tender unopened inflorescence of coconut trees (Cocos nucifera) is identified to have great health benefits. Drug induced Nephrotoxicity is one of the major causes of renal damage in present generation. As a therapeutic agent, gentamicin imparts direct toxicity to kidney, resulting in acute tubular necrosis, glomerular and tubulointerstitial injury, haemodynamically mediated damage and obstructive nephropathy.There exists an increasing demand for safe and natural agents for the treatment and/or preventionofchronic nephrotoxicity and pathogenesis of kidney diseases. Our study shows the nephro protective/curing effect of a novel powder formulation of micronutrient enriched, unfermented coconut flower sap (CSP). The study was performed on adult male Wistar rats. The animals were grouped into three and treated separately with vehicle, gentamicin and gentamicin+CSP for 16days. Initially, gentamicin treatment significantly (p<0.05)reduced thelevels of antioxidant enzymes (SOD, CAT, GPx) and GSH and increased (p<0.05) the levels of creatinine, uric acid, urea, inflammatory markers (nitrite, IL-6, TNF- α, iNOS) and lipid peroxidation. Supplementation of coconut flower sap powder showed significant (p<0.05) reversal of all these biochemical parameters indicating an effective inhibition of the pathogenesis of nephrotoxicity and kidney disease.

  3. Performance of mixed formulations for the particle finite element method in soil mechanics problems

    NASA Astrophysics Data System (ADS)

    Monforte, Lluís; Carbonell, Josep Maria; Arroyo, Marcos; Gens, Antonio

    2016-11-01

    This paper presents a computational framework for the numerical analysis of fluid-saturated porous media at large strains. The proposal relies, on one hand, on the particle finite element method (PFEM), known for its capability to tackle large deformations and rapid changing boundaries, and, on the other hand, on constitutive descriptions well established in current geotechnical analyses (Darcy's law; Modified Cam Clay; Houlsby hyperelasticity). An important feature of this kind of problem is that incompressibility may arise either from undrained conditions or as a consequence of material behaviour; incompressibility may lead to volumetric locking of the low-order elements that are typically used in PFEM. In this work, two different three-field mixed formulations for the coupled hydromechanical problem are presented, in which either the effective pressure or the Jacobian are considered as nodal variables, in addition to the solid skeleton displacement and water pressure. Additionally, several mixed formulations are described for the simplified single-phase problem due to its formal similitude to the poromechanical case and its relevance in geotechnics, since it may approximate the saturated soil behaviour under undrained conditions. In order to use equal-order interpolants in displacements and scalar fields, stabilization techniques are used in the mass conservation equation of the biphasic medium and in the rest of scalar equations. Finally, all mixed formulations are assessed in some benchmark problems and their performances are compared. It is found that mixed formulations that have the Jacobian as a nodal variable perform better.

  4. In situ observation of mechanical damage within a SiC-SiC ceramic matrix composite

    NASA Astrophysics Data System (ADS)

    Saucedo-Mora, L.; Lowe, T.; Zhao, S.; Lee, P. D.; Mummery, P. M.; Marrow, T. J.

    2016-12-01

    SiC-SiC ceramic matrix composites are candidate materials for fuel cladding in Generation IV nuclear fission reactors and as accident tolerant fuel clad in current generation plant. Experimental methods are needed that can detect and quantify the development of mechanical damage, to support modelling and qualification tests for these critical components. In situ observations of damage development have been obtained of tensile and C-ring mechanical test specimens of a braided nuclear grade SiC-SiC ceramic composite tube, using a combination of ex situ and in situ computed X-ray tomography observation and digital volume correlation analysis. The gradual development of damage by matrix cracking and also the influence of non-uniform loading are examined.

  5. Transmission electron microscopy analysis of mechanical polishing-related damage in silicon carbide wafers

    NASA Astrophysics Data System (ADS)

    Grim, J. R.; Benamara, M.; Skowronski, M.; Everson, W. J.; Heydemann, V. D.

    2006-12-01

    The subsurface damage generated by mechanical polishing of silicon carbide wafers was investigated and quantified by plan view transmission electron microscopy (TEM) and atomic force microscopy (AFM). Damage generated during polishing using diamond abrasives with 0.5 µm particle size consists of dislocation loops with length up to 400 nm from the scratches. The total dislocation density was estimated at 5 × 1010 dislocations cm-2. TEM analysis of the Burgers vectors indicates that the initial perfect dislocations have a Burgers vector of b = a/3 lang11-20rang-type with many dislocation dissociated into two partials with b = a/3 lang1-100rang. The depth of damage was estimated to be up to 50 nm. 4H-SiC homoepitaxial layers grown on mechanically polished substrates without further surface treatment exhibit threading dislocation density along scratches in the order of 105 cm-1.

  6. Effects of composite formulation on the mechanical properties of biodegradable poly(propylene fumarate)/bone fiber scaffolds

    PubMed Central

    Zhu, Xun; Liu, Nathan; Yaszemski, Michael J.; Lu, Lichun

    2010-01-01

    The objective of our study was to determine the effects of composite formulation on the compressive modulus and ultimate strength of a biodegradable, in situ polymerizable poly(propylene fumarate) (PPF) and bone fiber scaffold. The following parameters were investigated: the incorporation of bone fibers (either mineralized or demineralized), PPF molecular weight, N-vinyl pyrrolidinone (NVP) crosslinker amount, benzoyl peroxide (BP) initiator amount, and sodium chloride porogen amount. Eight formulations were chosen based on a resolution III two level fractional factorial design. The compressive modulus and ultimate strength of these formulations were measured on a materials testing machine. Absolute values for compressive modulus varied from 21.3 to 271 MPa and 2.8 to 358 MPa for dry and wet samples, respectively. The ultimate strength of the crosslinked composites varied from 2.1 to 20.3 MPa for dry samples and from 0.4 to 16.6 MPa for wet samples. Main effects of each parameter on the measured property were calculated. The incorporation of mineralized bone fibers and an increase in PPF molecular weight resulted in higher compressive modulus and ultimate strength. Both mechanical properties also increased as the amount of benzoyl peroxide increased or the NVP amount decreased in the formulation. Sodium chloride had a dominating effect on the increase of mechanical properties in dry samples but showed little effects in wet samples. Demineralization of bone fibers led to a decrease in the compressive modulus and ultimate strength. Our results suggest that bone fibers are appropriate as structural enforcement components in PPF scaffolds. The desired orthopaedic PPF scaffold might be obtained by changing a variety of composite formulation parameters. PMID:22034584

  7. Effects of composite formulation on the mechanical properties of biodegradable poly(propylene fumarate)/bone fiber scaffolds.

    PubMed

    Zhu, Xun; Liu, Nathan; Yaszemski, Michael J; Lu, Lichun

    2010-01-01

    The objective of our study was to determine the effects of composite formulation on the compressive modulus and ultimate strength of a biodegradable, in situ polymerizable poly(propylene fumarate) (PPF) and bone fiber scaffold. The following parameters were investigated: the incorporation of bone fibers (either mineralized or demineralized), PPF molecular weight, N-vinyl pyrrolidinone (NVP) crosslinker amount, benzoyl peroxide (BP) initiator amount, and sodium chloride porogen amount. Eight formulations were chosen based on a resolution III two level fractional factorial design. The compressive modulus and ultimate strength of these formulations were measured on a materials testing machine. Absolute values for compressive modulus varied from 21.3 to 271 MPa and 2.8 to 358 MPa for dry and wet samples, respectively. The ultimate strength of the crosslinked composites varied from 2.1 to 20.3 MPa for dry samples and from 0.4 to 16.6 MPa for wet samples. Main effects of each parameter on the measured property were calculated. The incorporation of mineralized bone fibers and an increase in PPF molecular weight resulted in higher compressive modulus and ultimate strength. Both mechanical properties also increased as the amount of benzoyl peroxide increased or the NVP amount decreased in the formulation. Sodium chloride had a dominating effect on the increase of mechanical properties in dry samples but showed little effects in wet samples. Demineralization of bone fibers led to a decrease in the compressive modulus and ultimate strength. Our results suggest that bone fibers are appropriate as structural enforcement components in PPF scaffolds. The desired orthopaedic PPF scaffold might be obtained by changing a variety of composite formulation parameters.

  8. 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.

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. Numerical simulation of thick sheet slitting processes: Modelling using continuum damage mechanics

    NASA Astrophysics Data System (ADS)

    Ghozzi, Y.; Labergere, C.; Saanouni, K.

    2013-05-01

    This work consists on the modelling and numerical simulation of specific cutting processes of thick sheets using advanced constitutive equations accounting for elastoplasticity with mixed hardening and ductile damage. Strong coupling between all the mechanical fields and the ductile damage is accounted for. First the complex kinematics of the slitting process is described. Then, the fully and strongly coupled constitutive equations are presented. Finally the influence of the main technological parameters of the slitting process is studied focusing in the minimization of the cutting forces.

  14. 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.

  15. A damage mechanics based method for fatigue life prediction of the metal graded materials

    NASA Astrophysics Data System (ADS)

    Tong, Yang; Hu, Weiping; Meng, Qingchun

    2017-03-01

    Based on the continuum damage mechanics theory, the fatigue life prediction for TC4-TC11 graded material was conducted. At first, the damage evolution equation was derived, then the method to calibrate material parameters for TC4-TC11 graded material was proposed, and all the material parameters were obtained. A beam model with TC4-TC11 graded material was established by using the stratified method and finite element method. Finally, the fatigue life of TC4-TC11 graded beam was predicted.

  16. Damage mechanisms and failure modes of cortical bone under components of physiological loading.

    PubMed

    George, W T; Vashishth, D

    2005-09-01

    Fatigue damage development in cortical bone was investigated in vitro under different mechanical components of physiological loading including tension, compression, and torsion. During each test, stress and strain data were collected continuously to monitor and statistically determine the occurrence of the primary, secondary, and tertiary stages associated with fatigue and/or creep failure of bone. The resultant microdamage and failure modes were identified by histological and fractographic analysis, respectively. The tensile group demonstrated Mode I cracking and the three classic stages of fatigue and creep suggesting a low crack initiation threshold, steady crack propagation and final failure by coalescence of microcracks. In contrast, the compressive group displayed Mode II cracking and a two-stage fatigue behavior with limited creep suggesting a high crack initiation threshold followed by a sudden fracture. The torsion group also displayed a two-stage fatigue profile but demonstrated extensive damage from mixed mode (Modes II and III) microcracking and predominant time-dependent damage. Thus, fatigue behavior of bone was found to be uniquely related to the individual mechanical components of physiological loading and the latter determined the specific damage mechanisms associated with fatigue fracture.

  17. Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage

    PubMed Central

    Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V.; Eddington, Natalie D.; Lee, Insong J.

    2010-01-01

    Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage. PMID:20420575

  18. Role of damage mechanics in nanoindentation of lamellar bone at multiple sizes: experiments and numerical modeling.

    PubMed

    Lucchini, Riccardo; Carnelli, Davide; Ponzoni, Matteo; Bertarelli, Emanuele; Gastaldi, Dario; Vena, Pasquale

    2011-11-01

    The aim of this paper is to show that damage mechanisms can account for the response of lamellar bone to nanoindentation tests, with particular regards to the decrease of indentation stiffness with increasing penetration depth and to the loss of contact stiffness during the unloading phase of the test. For this purpose, indentation experiments on bovine cortical bone samples along axial and transverse directions have been carried out at five penetration depths from 50 to 450 nm; furthermore, a continuum damage model has been implemented into finite element analyses, which are able to simulate indentation experiments. Experiments along the axial direction have shown a decrease of about 20% of the indentation modulus with indentation depth; a similar trend was found along the transverse direction. All unloading branches of the force-displacement indentation curves exhibited relevant stiffness loss (curve concavity). The numerical model with damage was able to correctly predict the indentation stiffness and hardness at 300 nm penetration depth along both axial and transverse directions. Furthermore, stiffness loss during unloading was simulated with both qualitative and quantitative agreement with experiments. A final validation has been provided by simulating axial indentation experiments at the remaining penetration depths using the same set of constitutive parameters as those used to simulate the experiments at 300 nm depth. These results support the hypothesis that damage plays a relevant role in the mechanics of lamellar bone and should be taken into account when studying bone mechanical properties at multiple scales.

  19. Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage.

    PubMed

    Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V; Eddington, Natalie D; Lee, Insong J

    2010-08-01

    Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage.

  20. Hot switching damage mechanisms in MEMS contacts—evidence and understanding

    NASA Astrophysics Data System (ADS)

    Basu, Anirban; Hennessy, Ryan P.; Adams, George G.; McGruer, Nicol E.

    2014-10-01

    Using an AFM-based test setup, experiments were performed on Ru microcontacts under a variety of leading and trailing edge hot switching conditions, including different voltages, different currents, different polarities (including bipolar and ac up to 20 MHz), and different approach and separation rates. It was found that hot switching damage is a complex phenomenon for microcontacts. It consists of a number of different mechanisms occurring simultaneously to different degrees depending on the hot switching conditions. It was determined through a combination of experiments and models that the mechanisms leading to contact erosion operate when the electrodes are separated by less than a few Å or are barely touching. For leading edge hot switching, i.e. hot switching when the contacts are closing, the main damage mechanism was found to be associated with currents less than 0.15 mA. Pre-contact currents were observed on uncleaned contacts and were not found to contribute to contact damage. Despite the damage caused by hot switching, it was found that unless the contact material is almost or completely eroded, hot switching does not lead to high contact resistance or high adhesion on Ru contacts. Under bipolar hot switching conditions, microcontacts with a 400 μN contact force maintained a contact resistance of less than 1 Ω and a pull-off force less than 60 μN for more than 100 million cycles.

  1. 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.

  2. Impaired Facilitatory Mechanisms of Auditory Attention After Damage of the Lateral Prefrontal Cortex

    PubMed Central

    Bidet-Caulet, Aurélie; Buchanan, Kelly G.; Viswanath, Humsini; Black, Jessica; Scabini, Donatella; Bonnet-Brilhault, Frédérique; Knight, Robert T.

    2015-01-01

    There is growing evidence that auditory selective attention operates via distinct facilitatory and inhibitory mechanisms enabling selective enhancement and suppression of sound processing, respectively. The lateral prefrontal cortex (LPFC) plays a crucial role in the top-down control of selective attention. However, whether the LPFC controls facilitatory, inhibitory, or both attentional mechanisms is unclear. Facilitatory and inhibitory mechanisms were assessed, in patients with LPFC damage, by comparing event-related potentials (ERPs) to attended and ignored sounds with ERPs to these same sounds when attention was equally distributed to all sounds. In control subjects, we observed 2 late frontally distributed ERP components: a transient facilitatory component occurring from 150 to 250 ms after sound onset; and an inhibitory component onsetting at 250 ms. Only the facilitatory component was affected in patients with LPFC damage: this component was absent when attending to sounds delivered in the ear contralateral to the lesion, with the most prominent decreases observed over the damaged brain regions. These findings have 2 important implications: (i) they provide evidence for functionally distinct facilitatory and inhibitory mechanisms supporting late auditory selective attention; (ii) they show that the LPFC is involved in the control of the facilitatory mechanisms of auditory attention. PMID:24925773

  3. Impaired Facilitatory Mechanisms of Auditory Attention After Damage of the Lateral Prefrontal Cortex.

    PubMed

    Bidet-Caulet, Aurélie; Buchanan, Kelly G; Viswanath, Humsini; Black, Jessica; Scabini, Donatella; Bonnet-Brilhault, Frédérique; Knight, Robert T

    2015-11-01

    There is growing evidence that auditory selective attention operates via distinct facilitatory and inhibitory mechanisms enabling selective enhancement and suppression of sound processing, respectively. The lateral prefrontal cortex (LPFC) plays a crucial role in the top-down control of selective attention. However, whether the LPFC controls facilitatory, inhibitory, or both attentional mechanisms is unclear. Facilitatory and inhibitory mechanisms were assessed, in patients with LPFC damage, by comparing event-related potentials (ERPs) to attended and ignored sounds with ERPs to these same sounds when attention was equally distributed to all sounds. In control subjects, we observed 2 late frontally distributed ERP components: a transient facilitatory component occurring from 150 to 250 ms after sound onset; and an inhibitory component onsetting at 250 ms. Only the facilitatory component was affected in patients with LPFC damage: this component was absent when attending to sounds delivered in the ear contralateral to the lesion, with the most prominent decreases observed over the damaged brain regions. These findings have 2 important implications: (i) they provide evidence for functionally distinct facilitatory and inhibitory mechanisms supporting late auditory selective attention; (ii) they show that the LPFC is involved in the control of the facilitatory mechanisms of auditory attention.

  4. 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

  5. Chitosan gels for the vaginal delivery of lactic acid: relevance of formulation parameters to mucoadhesion and release mechanisms.

    PubMed

    Bonferoni, Maria Cristina; Giunchedi, Paolo; Scalia, Santo; Rossi, Silvia; Sandri, Giuseppina; Caramella, Carla

    2006-01-01

    The aim of this work was to assess the effect of formulation parameters of a mucoadhesive vaginal gel based on chitosan and lactic acid, and to highlight its release mechanisms. Two molecular weight chitosans were used to prepare gels with 2 lactic acid concentrations. Both chitosan molecular weight and lactic acid concentration had a significant and mutually dependent influence on mucoadhesion, measured on pig vaginal mucosa. Similarly, the lactate release profiles were found to be dependent on lactic acid content and polymer molecular weight. One gel formulation based on the stoichiometric lactate to chitosan ratio was subjected to release test in media with 2 different counterions and increasing ionic strength. This test demonstrated that the lactate release is mainly due to ionic displacement.

  6. Effects of chondroitin and glucosamine sulfate in a dietary bar formulation on inflammation, interleukin-1beta, matrix metalloprotease-9, and cartilage damage in arthritis.

    PubMed

    Chou, May M; Vergnolle, Nathalie; McDougall, Jason J; Wallace, John L; Marty, Stephanie; Teskey, Val; Buret, Andre G

    2005-04-01

    This study examined the effects of chondroitin sulfate (CS) alone and CS plus glucosamine sulfate (GS) in a dietary bar formulation on inflammatory parameters of adjuvant-induced arthritis and on the synthesis of interleukin-1beta (IL-1beta) and matrix metalloprotease-9 (MMP-9). Following 25 days pretreatment with dietary bars containing either CS alone, CS plus GS, or neither CS nor GS, rats were either sham injected or injected with Freund's complete adjuvant into the tail vein. Rats were fed their respective bars for another 17 days after inoculation. Parameters of disease examined included clinical score (combination of joint temperature, edema, hyperalgesia, and standing and walking limb function), incidence of disease, levels of IL-1beta in the serum and paw joints, levels of MMP-9 in the paw joints, paw joint histology, and joint cartilage thickness. Treatment with CS plus GS, but not CS alone, significantly reduced clinical scores, incidences of disease, joint temperatures, and joint and serum IL-1beta levels. Treatment with CS alone and CS plus GS inhibited the production of edema and prevented raised levels of joint MMP-9 associated with arthritis. Similarly, CS alone and CS plus GS treatment also prevented the development of cartilage damage associated with arthritis. Combination CS plus GS treatment in a dietary bar formulation ameliorates clinical, inflammatory, and histologic parameters of adjuvant-induced arthritis. The benefits of CS and GS in combination are more pronounced than those of CS alone. The reduction of arthritic disease by CS plus GS is associated with a reduction of IL-1beta and MMP-9 synthesis.

  7. Forward models for extending the mechanical damage evaluation capability of resonant ultrasound spectroscopy.

    PubMed

    Goodlet, B R; Torbet, C J; Biedermann, E J; Jauriqui, L M; Aldrin, J C; Pollock, T M

    2017-02-08

    Finite element (FE) modeling has been coupled with resonant ultrasound spectroscopy (RUS) for nondestructive evaluation (NDE) of high temperature damage induced by mechanical loading. Forward FE models predict mode-specific changes in resonance frequencies (ΔfR), inform RUS measurements of mode-type, and identify diagnostic resonance modes sensitive to individual or multiple concurrent damage mechanisms. The magnitude of modeled ΔfR correlate very well with the magnitude of measured ΔfR from RUS, affording quantitative assessments of damage. This approach was employed to study creep damage in a polycrystalline Ni-based superalloy (Mar-M247) at 950°C. After iterative applications of creep strains up to 8.8%, RUS measurements recorded ΔfR that correspond to the accumulation of plastic deformation and cracks in the gauge section of a cylindrical dog-bone specimen. Of the first 50 resonance modes that occur, ranging from 3 to 220kHz, modes classified as longitudinal bending were most sensitive to creep damage while transverse bending modes were found to be largely unaffected. Measure to model comparisons of ΔfR show that the deformation experienced by the specimen during creep, specifically uniform elongation of the gauge section, is responsible for a majority of the measured ΔfR until at least 6.1% creep strain. After 8.8% strain considerable surface cracking along the gauge section of the dog-bone was observed, for which FE models indicate low-frequency longitudinal bending modes are significantly affected. Key differences between historical implementations of RUS for NDE and the FE model-based framework developed herein are discussed, with attention to general implementation of a FE model-based framework for NDE of damage.

  8. Oxidative damage and cellular defense mechanisms in sea urchin models of aging.

    PubMed

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

    2013-10-01

    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 because of 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 life span. Levels of protein carbonyls and 4-hydroxynonenal measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2'-deoxyguanosine 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.

  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. Induction of oxidative DNA damage by flavonoids of propolis: its mechanism and implication about antioxidant capacity.

    PubMed

    Tsai, Yi-Chih; Wang, Yi-Hsiang; Liou, Chih-Chiang; Lin, Yu-Cun; Huang, Haimei; Liu, Yin-Chang

    2012-01-13

    Propolis from beehives is commonly used as a home remedy for various purposes including as a topical antiseptic. Despite its antioxidant capacity, propolis induces oxidative DNA damage. In exploring the underlying mechanism, we found that the induction of oxidative DNA damage is attributed to the hydrogen peroxide (H(2)O(2)) produced by propolis. The formation of H(2)O(2) can take place without the participation of cells but requires the presence of transition metal ions such as iron. Flavonoids such as galangin, chrysin, and pinocembrin that are commonly detected in propolis have the capacity to induce oxidative DNA damage, and that capacity correlates with the production of H(2)O(2), suggesting the involvement of flavonoids in propolis in this process. On the basis of these results, we propose that the flavonoids of propolis serve as temporary carriers of electrons received from transition metal ions that are relayed to oxygen molecules to subsequently generate superoxide and H(2)O(2). In addition, propolis induces oxidative DNA damage that is subject to repair, and propolis-treated cells show a lower level of DNA damage level when challenged with another oxidative agent such as amoxicillin. This is reminiscent of an adaptive response that might contribute to the beneficial effects of propolis.

  11. Failure Mechanisms and Damage Model of Ductile Cast Iron Under Low-Cycle Fatigue Conditions

    NASA Astrophysics Data System (ADS)

    Wu, Xijia; Quan, Guangchun; MacNeil, Ryan; Zhang, Zhong; Sloss, Clayton

    2014-10-01

    Strain-controlled low-cycle fatigue (LCF) tests were conducted on ductile cast iron (DCI) at strain rates of 0.02, 0.002, and 0.0002/s in the temperature range from room temperature to 1073 K (800 °C). A constitutive-damage model was developed within the integrated creep-fatigue theory (ICFT) framework on the premise of strain decomposition into rate-independent plasticity and time-dependent creep. Four major damage mechanisms: (i) plasticity-induced fatigue, (ii) intergranular embrittlement (IE), (iii) creep, and (iv) oxidation were considered in a nonlinear creep-fatigue interaction model which represents the overall damage accumulation process consisting of oxidation-assisted fatigue crack nucleation and propagation in coalescence with internally distributed damage ( e.g., IE and creep), leading to final fracture. The model was found to agree with the experimental observations of the complex DCI-LCF phenomena, for which the linear damage summation rule would fail.

  12. 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.

  13. Simulations of pulsatile suspension flow through bileaflet mechanical heart valves to quantify platelet damage

    NASA Astrophysics Data System (ADS)

    Yun, Brian; Aidun, Cyrus; Yoganathan, Ajit

    2012-11-01

    Studies have shown that high shear stress and long exposure times on platelets have a strong impact on thromboembolic complications in bileaflet mechanical heart valves (BMHVs). This numerical study quantifies the platelet damage incurred in pulsatile flow through various BMHV designs. The lattice-Boltzmann method with external boundary force (LBM-EBF) was implemented to simulate pulsatile flow and capture the dynamics and surface shear stresses of modeled platelets with realistic geometry. The platelets are released in key regions of interest in the geometry as well as at various times of the cardiac cycle. The platelet damage is quantified using a linear shear stress-exposure time blood damage index (BDI) model. The multiscale computational method used to quantitatively measure the BDI during the pulsatile flow has been validated as being able to accurately capture bulk BMHV fluid flow and for accurately quantifying platelet damage in BMHV flows. These simulations will further knowledge of the geometric features and cardiac cycle times that most affect platelet damage. This study will ultimately lead to optimization of BMHV design in order to minimize thromboembolic complications.

  14. Laser-induced damage threshold of camera sensors and micro-opto-electro-mechanical systems

    NASA Astrophysics Data System (ADS)

    Schwarz, Bastian; Ritt, Gunnar; Körber, Michael; Eberle, Bernd

    2016-10-01

    The continuous development of laser systems towards more compact and efficient devices constitutes an increasing threat to electro-optical imaging sensors such as complementary metal-oxide-semiconductors (CMOS) and charge-coupled devices (CCD). These types of electronic sensors are used in day-to-day life but also in military or civil security applications. In camera systems dedicated to specific tasks, also micro-opto-electro-mechanical systems (MOEMS) like a digital micromirror device (DMD) are part of the optical setup. In such systems, the DMD can be located at an intermediate focal plane of the optics and it is also susceptible to laser damage. The goal of our work is to enhance the knowledge of damaging effects on such devices exposed to laser light. The experimental setup for the investigation of laser-induced damage is described in detail. As laser sources both pulsed lasers and continuous-wave (CW) lasers are used. The laser-induced damage threshold (LIDT) is determined by the single-shot method by increasing the pulse energy from pulse to pulse or in the case of CW-lasers, by increasing the laser power. Furthermore, we investigate the morphology of laser-induced damage patterns and the dependence of the number of destructed device elements on the laser pulse energy or laser power. In addition to the destruction of single pixels, we observe aftereffects like persisting dead columns or rows of pixels in the sensor image.

  15. Damage and failure mechanisms of continuous glass fiber reinforced polyphenylene sulfide

    NASA Technical Reports Server (NTRS)

    Chen, F.; Hiltner, A.; Baer, E.

    1992-01-01

    The damage that accompanies flexural deformation of a unidirectional glass fiber composite of polyphenylene sulfide was examined by AE and SEM. These complementary techniques were used to identify damage mechanisms at the microscale and correlate them with the macroscopic stress state in four-point bending. The flexural stress-strain curve was nominally linear to about 1.0 percent strain, but the onset of damage detectable by AE occurred at 0.3 percent strain. Two peaks in the AE amplitude distribution were observed at 35 dB and 60 dB. Low-amplitude events were detected along the entire length of the specimen, and correlation with direct observations of damage made by deforming the composite on the SEM stage suggested that these events arose from matrix cracking and fiber debonding concentrated at flaws on the composite. High amplitude events occurred primarily in the region of highest flexural stress between the inner loading points. They were attributed to fracture of glass fibers on the tension side and surface damage on the compressive side.

  16. Passive and active thermography for in situ damage monitoring in woven composites during mechanical testing

    NASA Astrophysics Data System (ADS)

    Roche, J.-M.; Balageas, D.; Lamboul, B.; Bai, G.; Passilly, F.; Mavel, A.; Grail, G.

    2013-01-01

    The aim of the present paper is to highlight the contribution of both passive and active infrared thermography for in situ damage detection and monitoring in a 2D woven composite, during a mechanical testing constituted of multiple sequences of loadings and intermediate pauses. During the monotonic tensile loadings, damages such as matrix cracking and fiber-matrix debondings are monitored by passive thermography. Their thermal signatures are analyzed and the released heat, which is assumed to be a relevant index of their severity, is evaluated and correlated to the associated acoustic energies, simultaneously recorded. Finally, the contribution of the TSR (Thermographic Signal Reconstruction) advanced processing technique to provide a qualitative overview of the detected damages is underlined. As for the constant stress plateau levels, a nondestructive damage inspection of the tested specimen is carried out by pulsed thermography. The difficulties, due to the woven structure of the composite, in detecting any damage are put into relief. Once more, it is shown that the TSR technique can be useful.

  17. 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.

  18. 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.

  19. Dual wavelength laser damage mechanisms in the ultra-short pulse regime

    NASA Astrophysics Data System (ADS)

    Gyamfi, Mark; Costella, Marion; Willemsen, Thomas; Jürgens, Peter; Mende, Mathias; Jensen, Lars; Ristau, Detlev

    2016-12-01

    New ultrashort pulse laser systems exhibit an ever increasing performance which includes shorter pulses and higher pulse energies. Optical components used in these systems are facing increasing requirements regarding their durability, and therefore understanding of the damage mechanism is crucial. In the ultra-short pulse regime electron ionization processes control the damage mechanisms. For the single wavelength, single pulse regime the Keldysh [1] and the Drude model [2] allow a quantitative description of these ionization processes. However, in this model, the electrical field is restricted to a single wavelength, and therefore it cannot be applied in the case of irradiation with two pulses at different wavelengths. As frequency conversion is becoming more common in ultra-short pulse applications, further research is needed in this field to predict the damage resistance of optical components. We investigate the damage behavior of high reflective mirrors made of different metal oxide materials under simultaneous exposure to ultra-short pulses at the wavelengths 387.5 nm and 775 nm, respectively.

  20. 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}.

  1. Bromination of deoxycytidine by eosinophil peroxidase: A mechanism for mutagenesis by oxidative damage of nucleotide precursors

    PubMed Central

    Henderson, Jeffrey P.; Byun, Jaeman; Williams, Michelle V.; McCormick, Michael L.; Parks, William C.; Ridnour, Lisa A.; Heinecke, Jay W.

    2001-01-01

    Oxidants generated by eosinophils during chronic inflammation may lead to mutagenesis in adjacent epithelial cells. Eosinophil peroxidase, a heme enzyme released by eosinophils, generates hypobromous acid that damages tissue in inflammatory conditions. We show that human eosinophils use eosinophil peroxidase to produce 5-bromodeoxycytidine. Flow cytometric, immunohistochemical, and mass spectrometric analyses all demonstrated that 5-bromodeoxycytidine generated by eosinophil peroxidase was taken up by cultured cells and incorporated into genomic DNA as 5-bromodeoxyuridine. Although previous studies have focused on oxidation of chromosomal DNA, our observations suggest another mechanism for oxidative damage of DNA. In this scenario, peroxidase-catalyzed halogenation of nucleotide precursors yields products that subsequently can be incorporated into DNA. Because the thymine analog 5-BrUra mispairs with guanine in DNA, generation of brominated pyrimidines by eosinophils might constitute a mechanism for cytotoxicity and mutagenesis at sites of inflammation. PMID:11172002

  2. Fracture-Based Mesh Size Requirements for Matrix Cracks in Continuum Damage Mechanics Models

    NASA Technical Reports Server (NTRS)

    Leone, Frank A.; Davila, Carlos G.; Mabson, Gerald E.; Ramnath, Madhavadas; Hyder, Imran

    2017-01-01

    This paper evaluates the ability of progressive damage analysis (PDA) finite element (FE) models to predict transverse matrix cracks in unidirectional composites. The results of the analyses are compared to closed-form linear elastic fracture mechanics (LEFM) solutions. Matrix cracks in fiber-reinforced composite materials subjected to mode I and mode II loading are studied using continuum damage mechanics and zero-thickness cohesive zone modeling approaches. The FE models used in this study are built parametrically so as to investigate several model input variables and the limits associated with matching the upper-bound LEFM solutions. Specifically, the sensitivity of the PDA FE model results to changes in strength and element size are investigated.

  3. 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.

  4. Continuum Mechanics Based Bi-linear Shear Deformable Shell Element Using Absolute Nodal Coordinate Formulation

    DTIC Science & Technology

    2014-03-07

    the convergent solution in the case of the continuum mechanics based bi- linear shear deformable ANCF shell element. 5.3 Slit Annular Plate Subjected...UNCLASSIFIED: Distribution Statement A. Approved for public release. #24515 CONTINUUM MECHANICS BASED BI- LINEAR SHEAR DEFORMABLE SHELL ELEMENT...MAR 2014 2. REPORT TYPE Technical Report 3. DATES COVERED 07-01-2014 to 04-03-2014 4. TITLE AND SUBTITLE CONTINUUM MECHANICS BASED BI- LINEAR

  5. Cavitation Damage Mechanisms: Experimental Study of Cavitation in a Spool Valve.

    DTIC Science & Technology

    1980-02-01

    oscillating conditions. SECURITY CLASSIFICATION OF T-1 PAGrWhon Date Enteted) 6 L PREFACE This final report is the result of a two -year contract...School of Civil Engineering, Georgia Institute of Technology. The two co-principal investigators were Dr. C. S. Martin, Professor of Civil Engineering...mechanisms in a hydraulic flow system. This report is the culminatioan of the experimental phase of the program. A companion study entitled "Cavitation Damage

  6. Comparison of Phases Formation Process in Initial and Mechanically Activated Ceramic Batches with Pyrochlore Formulations

    SciTech Connect

    Stefanovsky, S. V.; Chizhevskaya, S. V.; Yudintsev, S. V.

    2002-02-25

    Formation of two pyrochlore ceramics with formulations CaZr0.25U0.75Ti2O7 and CaUTi2O7 within the temperature range 1000-1500 C from batches prepared by grinding of oxide powders in a mortar and an activator with hydrostatic yokes AGO-2U as well as soaking of a Ca, Zr, and Ti oxide mixture with uranylnitrate solution was studied. The pyrochlore ceramics are produced through intermediate calcium uranate formation. Phase formation reactions in the batch pre-treated in the AGO-2U unit were completed within the temperature range 1000-1100 C that is lower than in the batches prepared by two other methods.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. A detailed fluid mechanics study of tilting disk mechanical heart valve closure and the implications to blood damage.

    PubMed

    Manning, Keefe B; Herbertson, Luke H; Fontaine, Arnold A; Deutsch, Steven

    2008-08-01

    Hemolysis and thrombosis are among the most detrimental effects associated with mechanical heart valves. The strength and structure of the flows generated by the closure of mechanical heart valves can be correlated with the extent of blood damage. In this in vitro study, a tilting disk mechanical heart valve has been modified to measure the flow created within the valve housing during the closing phase. This is the first study to focus on the region just upstream of the mitral valve occluder during this part of the cardiac cycle, where cavitation is known to occur and blood damage is most severe. Closure of the tilting disk valve was studied in a "single shot" chamber driven by a pneumatic pump. Laser Doppler velocimetry was used to measure all three velocity components over a 30 ms period encompassing the initial valve impact and rebound. An acrylic window placed in the housing enabled us to make flow measurements as close as 200 microm away from the closed occluder. Velocity profiles reveal the development of an atrial vortex on the major orifice side of the valve shed off the tip of the leaflet. The vortex strength makes this region susceptible to cavitation. Mean and maximum axial velocities as high as 7 ms and 20 ms were recorded, respectively. At closure, peak wall shear rates of 80,000 s(-1) were calculated close to the valve tip. The region of the flow examined here has been identified as a likely location of hemolysis and thrombosis in tilting disk valves. The results of this first comprehensive study measuring the flow within the housing of a tilting disk valve may be helpful in minimizing the extent of blood damage through the combined efforts of experimental and computational fluid dynamics to improve mechanical heart valve designs.

  12. 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

  13. 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.

  14. A comprehensive monitoring system for damage identification and location in large structural and mechanical systems

    SciTech Connect

    Farrar, C.R.; Doebling, S.W.; Prime, M.B.

    1998-11-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project conducted at the Los Alamos National Laboratory (LANL). This project has focused on developing and experimentally verifying a suite of analytical tools for identifying the onset of damage in structural and mechanical systems from changes in their vibration characteristics. A MATLAB-based computer code referred to as Damage Identification And Modal Analysis of Data (DIAMOND) was developed. The code was then extensively exercised on data obtained from a variety of test structures. The most notable structure was an in situ bridge located ten mile north of Truth or Consequences, New Mexico. The suite of tools contained in DIAMOND is now being applied to the nuclear weapons enhanced surveillance program and an industrial partner has asked to enter into a partnership so that they can implement routines from DIAMOND into their commercial damage assessment hardware for large civil engineering structures. Because of the large volume of requests from around the world for DIAMOND, it can now be downloaded from the web site: http://esaea-www.esa.lanl.gov/damage{_}id.

  15. 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.

  16. Analysis of the Damage Mechanism Related to CO2 Laser Cochleostomy on Guinea Pig Cochlea

    PubMed Central

    Liu, Xiang; Qian, Xiao-qing; Ma, Rui

    2016-01-01

    Different types of lasers have been used in inner ear surgery. Therefore, it is of the utmost importance to avoid damage to the inner ear (e.g., hyperthermia and acoustic effects) caused by the use of such lasers. The aim of this study was to use a high powered fibre-enabled CO2 laser (10 W, 606 J/cm2) to perform cochleostomies on guinea pig cochlea and to investigate the possible laser-induced damage mechanisms. The temperature changes in the round window membrane, auditory evoked brainstem response, and morphological of the hair cells were measured and recorded before and after laser application. All of the outcomes differed in comparison with the control group. A rise in temperature and subsequent increased hearing loss were observed in animals that underwent surgery with a 10 W CO2 laser. These findings correlated with increased injury to the cochlear ultrastructure and a higher positive expression of E-cadherin and β-catenin in the damaged organ of Corti. We assume that enhanced cell-cell adhesion and the activated β-catenin-related canonical Wnt-signalling pathway may play a role in the protection of the cochlea to prevent further damage. PMID:28070426

  17. Mechanisms of DNA Damage Response to Targeted Irradiation in Organotypic 3D Skin Cultures

    PubMed Central

    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

  18. 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.

  19. 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.

  20. Programmatic features of aging originating in development: aging mechanisms beyond molecular damage?

    PubMed Central

    de Magalhães, João Pedro

    2012-01-01

    The idea that aging follows a predetermined sequence of events, a program, has been discredited by most contemporary authors. Instead, aging is largely thought to occur due to the accumulation of various forms of molecular damage. Recent work employing functional genomics now suggests that, indeed, certain facets of mammalian aging may follow predetermined patterns encoded in the genome as part of developmental processes. It appears that genetic programs coordinating some aspects of growth and development persist into adulthood and may become detrimental. This link between development and aging may occur due to regulated processes, including through the action of microRNAs and epigenetic mechanisms. Taken together with other results, in particular from worms, these findings provide evidence that some aging changes are not primarily a result of a build-up of stochastic damage but are rather a product of regulated processes. These processes are interpreted as forms of antagonistic pleiotropy, the product of a “shortsighted watchmaker,” and thus do not assume aging evolved for a purpose. Overall, it appears that the genome does, indeed, contain specific instructions that drive aging in animals, a radical shift in our perception of the aging process.—de Magalhães, J. P. Programmatic features of aging originating in development: aging mechanisms beyond molecular damage? PMID:22964300

  1. 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.

  2. 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).

  3. Mutational strand asymmetries in cancer genomes reveal mechanisms of DNA damage and repair

    PubMed Central

    Haradhvala, Nicholas J.; Polak, Paz; Stojanov, Petar; Covington, Kyle R.; Shinbrot, Eve; Hess, Julian; Rheinbay, Esther; Kim, Jaegil; Maruvka, Yosef; Braunstein, Lior Z.; Kamburov, Atanas; Hanawalt, Philip C.; Wheeler, David A.; Koren, Amnon; Lawrence, Michael S.; Getz, Gad

    2016-01-01

    Mutational processes constantly shape the somatic genome, leading to immunity, aging, and other diseases. When cancer is the outcome, we are afforded a glimpse into these processes by the clonal expansion of the malignant cell. Here, we characterize a less explored layer of the mutational landscape of cancer: mutational asymmetries between the two DNA strands. Analyzing whole genome sequences of 590 tumors from 14 different cancer types, we reveal widespread asymmetries across mutagenic processes, with transcriptional (“T-class”) asymmetry dominating UV-, smoking-, and liver-cancer-associated mutations, and replicative (“R-class”) asymmetry dominating POLE-, APOBEC-, and MSI-associated mutations. We report a striking phenomenon of Transcription-Coupled Damage (TCD) on the non-transcribed DNA strand, and provide evidence that APOBEC mutagenesis occurs on the lagging-strand template during DNA replication. As more genomes are sequenced, studying and classifying their asymmetries will illuminate the underlying biological mechanisms of DNA damage and repair. PMID:26806129

  4. 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…

  5. A possible mechanism for combined arsenic and fluoride induced cellular and DNA damage in mice.

    PubMed

    Flora, Swaran J S; Mittal, Megha; Pachauri, Vidhu; Dwivedi, Nidhi

    2012-01-01

    Arsenic and fluoride are major contaminants of drinking water. Mechanisms of toxicity following individual exposure to arsenic or fluoride are well known. However, it is not explicit how combined exposure to arsenic and fluoride leads to cellular and/or DNA damage. The present study was planned to assess (i) oxidative stress during combined chronic exposure to arsenic and fluoride in drinking water, (ii) correlation of oxidative stress with cellular and DNA damage and (iii) mechanism of cellular damage using IR spectroscopy. Mice were exposed to arsenic and fluoride (50 ppm) either individually or in combination for 28 weeks. Arsenic or fluoride exposure individually led to a significant increase in reactive oxygen species (ROS) generation and associated oxidative stress in blood, liver and brain. Individual exposure to the two toxicants showed significant depletion of blood glutathione (GSH) and glucose 6-phosphate dehydrogenase (G6PD) activity, and single-stranded DNA damage using a comet assay in lymphocytes. We also observed an increase in the activity of ATPase, thiobarbituric acid reactive substance (TBARS) and a decreased, reduced and oxidized glutathione (GSH : GSSG) ratio in the liver and brain. Antioxidant enzymes like superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were decreased and increased in liver and brain respectively. The changes were more pronounced in liver compared to brain suggesting liver to be more susceptible to the toxic effects of arsenic and fluoride. Interestingly, combined exposure to arsenic and fluoride resulted in less pronounced toxic effects compared to their individual effects based on biochemical variables, IR spectra, DNA damage (TUNEL and comet assays) and histopathological observations. IR spectra suggested that arsenic or fluoride perturbs the strength of protein and amide groups; however, the shifts in peaks were not pronounced during combined exposure. These results thus highlight the role of

  6. 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

  7. 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

  8. 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

    2016-08-31

    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.

  9. 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.

  10. 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.

  11. Effect of heat treatments on mechanical properties and damage evolution of thixoformed aluminium alloys

    SciTech Connect

    Cavaliere, P. . E-mail: pasquale.cavaliere@unile.it; Cerri, E.; Leo, P.

    2005-07-15

    In the present work, the effects of heat treatments on mechanical properties, microstructure evolution and damage resulting from plastic deformation of thixoformed A319 and A356 aluminium alloys, are studied. The thixoforming process can lead to the production of components that are characterized by very good mechanical properties and low porosity with a globular microstructure which is fine and uniform. The mechanical properties can be further improved through heat treatments such as T5 and T6. The prime factor influencing the damage in the alloys belonging to the Al-Si system is represented by decohesion of silicon particles resulting from the stress concentration at the particle-matrix interfaces. A statistical analysis of fractured particles after tensile tests in the as-cast and as-treated condition has been carried out in the present work; optical and scanning electron microscopy techniques have been used to characterize the microstructure and fracture surfaces of the specimens and the results are fully presented.

  12. 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

  13. Molecular mechanisms for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

    PubMed

    Watanabe, Hiroshi

    2013-01-01

    Chronic kidney disease (CKD), marked by a progressive loss in renal function, is a leading cause of hemodialysis initiation and cardiovascular disease (CVD). There are currently 13.3 million patients with CKD and 300 thousand patients are currently undergoing hemodialysis in Japan. Therefore, preventing the initiation of dialysis and reducing the risk of cardiovascular death are high-priority issues from the viewpoint of public health and economic implications. Understanding the molecular mechanism responsible for the progression of CKD and cardiovascular damage regarding crosstalk between the kidney and cardiovascular system is an important issue in controlling the pathogenesis of CKD-CVD. However, the mechanisms involved in CKD-CVD are not well understood. This hinders the development of new treatment strategies. We have been investigating the role of protein bound uremic toxins, that are difficult to remove by hemodialysis, on the onset and progression of CKD and CVD. The relationship between their redox properties and the pathogenesis of CKD-CVD was examined. In this review, we focus on two sulfate conjugated uremic toxins, namely, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and summarize recent studies that provide new insights on the molecular mechanisms responsible for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

  14. 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.

  15. Mechanisms of radiation damage to Sc/Si multilayer mirrors under EUV laser irradiation

    NASA Astrophysics Data System (ADS)

    Pershyn, Y. P.; Zubarev, E. N.; Voronov, D. L.; Sevryukova, V. A.; Kondratenko, V. V.; Vaschenko, G.; Grisham, M.; Menoni, C. S.; Rocca, J. J.; Artioukov, I. A.; Uspenskii, Y. A.; Vinogradov, A. V.

    2009-06-01

    Specific structural changes in Sc/Si multilayer mirrors irradiated with extreme ultraviolet (EUV) laser single pulses (λ = 46.9 nm) at near damage threshold fluences (0.04-0.23 J cm-2) are analysed. We have identified melting of surface layers as the basic degradation mechanism for the mirrors. Both heat generation during silicide formation and low heat conduction of the layered system significantly decreases the degradation threshold of Sc/Si multilayer mirrors compared with bulk materials. The results are relevant to the use of the multilayer mirrors for shaping and directing the intense beams produced by the new generation of coherent EUV sources.

  16. Mechanism and Site of Attack for Direct Damage to DNA by Low-Energy Electrons

    SciTech Connect

    Pan, X.; Sanche, L.

    2005-05-20

    We report results on the desorption of OH{sup -} induced by 0-19 eV electrons incident on self-assembled monolayer films made of single and double DNA strands of different orientations with respect to a gold substrate. Such measurements make it possible to deduce the mechanism and site of OH{sup -} formation within a biomolecule as complex as DNA. This type of damage is attributed to dissociative electron attachment to the phosphate group of DNA, when it contains the counterion H{sup +}.

  17. A Possible Cumulative Shear Mechanism For Tissue Damage Initiation In SWL

    NASA Astrophysics Data System (ADS)

    Freund, Jonathan B.

    2007-04-01

    In shock-wave lithotripsy, inertial cavitation is observed in kidney tissue after hundreds of shocks are delivered, which seems to correspond with the onset of wide-spread injury. However, it is unclear what initiates the process. It is possible, and has been suggested before, that hemorrhage is a prelude to cavitation damage. We investigate the possibility that the net shear of multiple shocks can accumulate to cause this initial hemorrhage. A mathematical model is used to show that the larger interstitial volume fraction in the medulla toward the papilla tip would make it particularly sensitive there to this mechanism. This is consistent with observations.

  18. Failure mechanism analysis of electromigration dominated damage in TiSi2 nanowires

    NASA Astrophysics Data System (ADS)

    Zou, Chen-Xia; Xu, Jun; Zhang, Xin-Zheng; Song, Xue-Feng; Yu, Da-Peng

    2009-06-01

    Electromigration-induced damage has been an important concern in very large scale integrated circuit design for a long time and will be a major road block in the pursuit of nanoelectronics devices and next generation power electronics. In this letter, the failure mechanism analysis on two-terminal TiSi2 nanowire devices was reported. Electromigration dominant mass migration is observed and verified by energy dispersive spectroscopy. The contribution of thermomigration is discussed based on temperature simulation. This work provides useful reference for future devices and the failure analysis on nanostructures.

  19. 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

  20. 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

  1. Micro-mechanical modelling of mechanical and electrical properties in homogeneous piezoelectric ceramic by using boundary integral formulations

    NASA Astrophysics Data System (ADS)

    Biglar, M.; Stachowicz, F.; Trzepiecinski, T.; Gromada, M.

    2017-02-01

    Recent experiments on polycrystalline materials show that microcrystalline materials have a strong dependency ona grain size. In this study, mechanical and electrical properties of polycrystalline materials in micro level were studied by using averaging theorems. To completely understand the size-dependency of polycrystalline materials, an integral non-local approach that can predict the stress-strain relations for these materials was presented. In microcrystalline materials, crystalline and grain-boundary were considered as two separate phases. Mechanical properties of the crystalline phase were modelled using crystalline brittle material and is composed of randomly distributed and orientated single crystal anisotropic elastic grains. For microcrystalline materials, the surface-to-volume ratio of the grain boundaries is low enough to ignore its contribution to the elastic deformation. Therefore, the grain boundary phase was not considered in microcrystalline materials and mechanical properties of the crystalline phase were modelled using appropriate integral non-local approach. Finally, the constitutive equations for polycrystalline materials were implemented into a boundary integral equation and the results and some examples are provided for piezoelectric ceramic.

  2. Formulation of the information capacity of the optical-mechanical line-scan imaging process

    NASA Technical Reports Server (NTRS)

    Huck, F. O.; Park, S. K.

    1975-01-01

    An expression for the information capacity of the optical-mechanical line-scan imaging process is derived which includes the effects of blurring of spatial, photosensor noise, aliasing, and quantization. Both the information capacity for a fixed data density and the information efficiency (the ratio of information capacity to data density) exhibit a distinct single maximum when displayed as a function of sampling rate, and the location of this maximum was determined by the system frequency-response shape, signal-to-noise ratio, and quantization interval.

  3. 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

  4. 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

  5. Recurrent Initiation: A Mechanism for Triggering p53 Pulses in Response to DNA Damage

    PubMed Central

    Batchelor, Eric; Mock, Caroline; Bhan, Irun; Loewer, Alexander; Lahav, Galit

    2008-01-01

    SUMMARY DNA damage initiates a series of p53 pulses. Although much is known about the interactions surrounding p53, little is known about which interactions contribute to p53’s dynamical behavior. The simplest explanation is that these pulses are oscillations intrinsic to the p53/Mdm2 negative feedback loop. Here we present evidence that this simple mechanism is insufficient to explain p53 pulses; we show that p53 pulses are externally driven by pulses in the upstream signaling kinases, ATM and Chk2, and that the negative feedback between p53 and ATM, via Wip1, is essential for maintaining the uniform shape of p53 pulses. We propose that p53 pulses result from repeated initiation by ATM which is re-activated by persistent DNA damage. Our study emphasizes the importance of collecting quantitative dynamic information at high temporal resolution for understanding the regulation of signaling pathways and opens new ways to manipulate p53 pulses to ask questions about their function in response to DNA damage. PMID:18471974

  6. 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.

  7. Mechanics and mechanisms of surface damage in Al-Si alloys under ultra-mild wear conditions

    NASA Astrophysics Data System (ADS)

    Chen, Ming

    Al-Si alloys intended for use in engine components must operate under ultra-mild wear (UMW) conditions to fit an acceptable amount of wear during a typical vehicle life. This study simulated surface damage in a UMW regime on five chemically etched Al-Si alloy surfaces using a pin-on-disc tribometer at low loads (0.5-2.0 N) under boundary lubricated conditions. The five alloys contained 11 to 25 wt.% Si and differed in matrix hardness, silicon particle morphology, and size. The mechanisms leading to the UMW damage and the role that the matrix hardness and microstructure play on said mechanisms were studied. Quantitative measurement methods based on statistical analysis of particle height changes and material loss from elevated aluminum using a profilometer technique were developed and used to assess UMW. The Greenwood and Tripp's numerical model was adapted to analyze the contact that occurred between Al-Si alloys with silicon particles protruding above the aluminum and steel balls. The estimation of the real contact pressure applied to the silicon particles was used to rationalize the damage mechanisms. The UMW mechanisms consisted of (i) abrasive wear on the top of the silicon particle surfaces; (ii) sinking-in of the silicon particles; (iii) piling-up of the aluminium around sunken-in particles and (vi) wear of the aluminium by the counterface, which eventually led to the initiation of UMW-II. Increasing the size or areal density of silicon particles with small aspect ratios delayed the onset of UMW-II by providing resistance against the silicon particles sinking-in and the aluminum piling-up. The UMW wear rates, however, began to decrease after long sliding cycles once an oil residue layer supported by hardened ultra-fine subsurface grains formed on the deformed aluminium matrix. The layer formation depended on the microstructure and applied load. Overall experimental observations suggested that Al-11% Si with small silicon particles exhibited optimal long

  8. 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.

  9. Mechanisms of neurotoxicity induced in the developing brain of mice and rats by DNA-damaging chemicals.

    PubMed

    Doi, Kunio

    2011-01-01

    It is not widely known how the developing brain responds to extrinsic damage, although the developing brain is considered to be sensitive to diverse environmental factors including DNA-damaging agents. This paper reviews the mechanisms of neurotoxicity induced in the developing brain of mice and rats by six chemicals (ethylnitrosourea, hydroxyurea, 5-azacytidine, cytosine arabinoside, 6-mercaptopurine and etoposide), which cause DNA damage in different ways, especially from the viewpoints of apoptosis and cell cycle arrest in neural progenitor cells. In addition, this paper also reviews the repair process following damage in the developing brain.

  10. 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

  11. Edible films and coatings from whey proteins: a review on formulation, and on mechanical and bioactive properties.

    PubMed

    Ramos, Oscar L; Fernandes, João C; Silva, Sara I; Pintado, Manuela E; Malcata, F Xavier

    2012-01-01

    The latest decade has witnessed joint efforts by the packaging and the food industries to reduce the amount of residues and wastes associated with food consumption. The recent increase in environmental awareness has also contributed toward development of edible packaging materials. Viable edible films and coatings have been successfully produced from whey proteins; their ability to serve other functions, viz. carrier of antimicrobials, antioxidants, or other nutraceuticals, without significantly compromising the desirable primary barrier and mechanical properties as packaging films, will add value for eventual commercial applications. These points are tackled in this review, in a critical manner. The supply of whey protein-based films and coatings, formulated to specifically address end-user needs, is also considered.

  12. Mechanisms underpinning protection against eccentric exercise-induced muscle damage by ischemic preconditioning.

    PubMed

    Franz, Alexander; Behringer, Michael; Nosaka, Kazunori; Buhren, Bettina Alexandra; Schrumpf, Holger; Mayer, Constantin; Zilkens, Christoph; Schumann, Moritz

    2017-01-01

    Eccentric exercise training is effective for increasing muscle mass and strength, and improving insulin sensitivity and blood lipid profiles. However, potential muscle damage symptoms such as prolonged loss of muscle function and delayed onset of muscle soreness may restrict the use of eccentric exercise, especially in clinical populations. Therefore, strategies to reduce eccentric exercise-induced muscle damage (EIMD) are necessary, and an extensive number of scientific studies have tried to identify potential intervention modalities to perform eccentric exercises without adverse effects. The present paper is based on a narrative review of current literature, and provides a novel hypothesis by which an ischemic preconditioning (IPC) of the extremities may reduce EIMD. IPC consists of an intermittent application of short-time non-lethal ischemia to an extremity (e.g. using a tourniquet) followed by reperfusion and was discovered in clinical settings in an attempt to minimize inflammatory responses induced by ischemia and ischemia-reperfusion-injury (I/R-Injury) during surgery. The present hypothesis is based on morphological and biochemical similarities in the pathophysiology of skeletal muscle damage during clinical surgery and EIMD. Even though the primary origin of stress differs between I/R-Injury and EIMD, subsequent cellular alterations characterized by an intracellular accumulation of Ca(2+), an increased production of reactive oxygen species or increased apoptotic signaling are essential elements for both. Moreover, the incipient immune response appears to be similar in I/R-Injury and EIMD, which is indicated by an infiltration of leukocytes into the damaged soft-tissue. Thus far, IPC is considered as a potential intervention strategy in the area of cardiovascular or orthopedic surgery and provides significant impact on soft-tissue protection and downregulation of undesired excessive inflammation induced by I/R-Injury. Based on the known major impact of IPC

  13. Quantum-mechanical formulation of light propagation: A multiple-scattering approach

    SciTech Connect

    Guo Wei

    2007-08-15

    Since in quantum optics light is represented in terms of photons, light propagation through a linear medium is discussed quantum mechanically in this paper by following the multiple-scattering process of one incident photon from the medium. To treat the photon and the medium on the same quantum footing, the medium is assumed to be an ensemble of uniformly distributed identical two-level atoms. It is found that inside the medium the incident photon follows the same propagation rules as a plane wave does in the classical domain, and has a possibility to become entangled with the atoms. It is also found that when interacting with a two-level test atom outside the medium, the output photon appears to be formally in a single mode identical to that of the incident photon.

  14. Characterization of HTPB-based solid fuel formulations: Performance, mechanical properties, and pollution

    NASA Astrophysics Data System (ADS)

    DeLuca, L. T.; Galfetti, L.; Maggi, F.; Colombo, G.; Merotto, L.; Boiocchi, M.; Paravan, C.; Reina, A.; Tadini, P.; Fanton, L.

    2013-12-01

    Features such as safety, low-cost, and throttleability make hybrid rocket engines an attractive option for suborbital flights and space exploration missions in general. While the domain of possible liquid oxidizers is well characterized, the choice of a suitable solid fuel is still a matter of investigation. Space Propulsion Laboratory (SPLab) at Politecnico di Milano has developed a series of proprietary techniques to evaluate, on a relative grading, the quality of innovative solid fuels while visualizing at the same time their flame structure. But a serious alert was recently notified that soot emission from hydrocarbon fuels has the potential to contribute to global climate change. In this paper, HTPB polymer has been taken as baseline and characterized at laboratory level in terms of ballistic properties, mechanical testing, and thermochemical calculations.

  15. 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

  16. 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

  17. Causes of excitation-induced muscle cell damage in isometric contractions: mechanical stress or calcium overload?

    PubMed

    Fredsted, Anne; Gissel, Hanne; Madsen, Klavs; Clausen, Torben

    2007-06-01

    Prolonged or unaccustomed exercise leads to muscle cell membrane damage, detectable as release of the intracellular enzyme lactic acid dehydrogenase (LDH). This is correlated to excitation-induced influx of Ca2+, but it cannot be excluded that mechanical stress contributes to the damage. We here explore this question using N-benzyl-p-toluene sulfonamide (BTS), which specifically blocks muscle contraction. Extensor digitorum longus muscles were prepared from 4-wk-old rats and mounted on holders for isometric contractions. Muscles were stimulated intermittently at 40 Hz for 15-60 min or exposed to the Ca2+ ionophore A23187. Electrical stimulation increased 45Ca influx 3-5 fold. This was followed by a progressive release of LDH, which was correlated to the influx of Ca2+. BTS (50 microM) caused a 90% inhibition of contractile force but had no effect on the excitation-induced 45Ca influx. After stimulation, ATP and creatine phosphate levels were higher in BTS-treated muscles, most likely due to the cessation of ATP-utilization for cross-bridge cycling, indicating a better energy status of these muscles. No release of LDH was observed in BTS-treated muscles. However, when exposed to anoxia, electrical stimulation caused a marked increase in LDH release that was not suppressed by BTS but associated with a decrease in the content of ATP. Dynamic passive stretching caused no increase in muscle Ca2+ content and only a minor release of LDH, whereas treatment with A23187 markedly increased LDH release both in control and BTS-treated muscles. In conclusion, after isometric contractions, muscle cell membrane damage depends on Ca2+ influx and energy status and not on mechanical stress.

  18. Mechanisms of Damage to DNA Labeled with Electrophilic Nucleobases Induced by Ionizing or UV Radiation.

    PubMed

    Rak, Janusz; Chomicz, Lidia; Wiczk, Justyna; Westphal, Kinga; Zdrowowicz, Magdalena; Wityk, Paweł; Żyndul, Michał; Makurat, Samanta; Golon, Łukasz

    2015-07-02

    Hypoxia--a hallmark of solid tumors--makes hypoxic cells radioresistant. On the other hand, DNA, the main target of anticancer therapy, is not sensitive to the near UV photons and hydrated electrons, one of the major products of water radiolysis under hypoxic conditions. A possible way to overcome these obstacles to the efficient radio- and photodynamic therapy of cancer is to sensitize the cellular DNA to electrons and/or ultraviolet radiation. While incorporated into genomic DNA, modified nucleosides, 5-bromo-2'-deoxyuridine in particular, sensitize cells to both near-ultraviolet photons and γ rays. It is believed that, in both sensitization modes, the reactive nucleobase radical is formed as a primary product which swiftly stabilizes, leading to serious DNA damage, like strand breaks or cross-links. However, despite the apparent similarity, such radio- and photosensitization of DNA seems to be ruled by fundamentally different mechanisms. In this review, we demonstrate that the most important factors deciding on radiodamage to the labeled DNA are (i) the electron affinity (EA) of modified nucleoside (mNZ), (ii) the local surroundings of the label that significantly influences the EA of mNZ, and (iii) the strength of the chemical bond holding together the substituent and a nucleobase. On the other hand, we show that the UV damage to sensitized DNA is governed by long-range photoinduced electron transfer, the efficiency of which is controlled by local DNA sequences. A critical review of the literature mechanisms concerning both types of damage to the labeled biopolymer is presented. Ultimately, the perspectives of studies on DNA sensitization in the context of cancer therapy are discussed.

  19. 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.

  20. Pathway of a damaging mechanism - Analyzing chloride attack by synchrotron based X-ray diffraction

    NASA Astrophysics Data System (ADS)

    Schlegel, M. C.; Stroh, J.; Malaga, K.; Meng, B.; Panne, U.; Emmerling, F.

    2015-06-01

    Typically, the changes of the phase compositions due to the chemical attack are studied in-situ only by chemical analysis or microscopy. In this study, the chloride transport and binding in the cement matrix in different cementitious materials was analyzed by synchrotron based X-ray diffraction (SyXRD) and energy dispersive X-ray spectroscopy (EDX). Sample materials consisting of cement paste were embedded in high concentrated sodium chloride solution over different time spans. Afterwards, the phase and chemical compositions were determined. The high spatial resolution and the information about the chloride distribution offer a detailed view of chloride binding in the cement matrix and allow the conclusions about the degradation mechanisms. The results are discussed related to the influence of different supplementary cementitious materials on the damaging mechanism.

  1. Damage mechanisms of MoN/SiN multilayer optics for next-generation pulsed XUV light sources.

    PubMed

    Sobierajski, R; Bruijn, S; Khorsand, A R; Louis, E; van de Kruijs, R W E; Burian, T; Chalupsky, J; Cihelka, J; Gleeson, A; Grzonka, J; Gullikson, E M; Hajkova, V; Hau-Riege, S; Juha, L; Jurek, M; Klinger, D; Krzywinski, J; London, R; Pelka, J B; Płociński, T; Rasiński, M; Tiedtke, K; Toleikis, S; Vysin, L; Wabnitz, H; Bijkerk, F

    2011-01-03

    We investigated the damage mechanism of MoN/SiN multilayer XUV optics under two extreme conditions: thermal annealing and irradiation with single shot intense XUV pulses from the free-electron laser facility in Hamburg - FLASH. The damage was studied "post-mortem" by means of X-ray diffraction, interference-polarizing optical microscopy, atomic force microscopy, and scanning transmission electron microscopy. Although the timescale of the damage processes and the damage threshold temperatures were different (in the case of annealing it was the dissociation temperature of Mo2N and in the case of XUV irradiation it was the melting temperature of MoN) the main damage mechanism is very similar: molecular dissociation and the formation of N2, leading to bubbles inside the multilayer structure.

  2. Thermodynamic damage mechanism of Ni/Cr film on neutral density filter by 1064-nm pulsed laser

    NASA Astrophysics Data System (ADS)

    Han, Jinghua; Li, Yaguo; Han, Wei; Feng, Guoying; Zhang, Qiuhui; Hu, Ruifeng; Liu, Yanyan

    2017-01-01

    We investigate the damage characteristics and mechanism of neutral density filters consisting of metal film on K9 glass substrate by 1064-nm pulsed laser. The damage morphologies present marked differences with different laser pulse energies. Specifically, with the increase of laser fluence, the damage pits density increase as well, and at the same time, the cracks appear around the pits and interconnect, which lead to the abscission of film. The damage mechanism has been studied from the viewpoint of embedded impurities in the film. The theoretical results show that the difference between the thermodynamic properties of impurities and film can lead to thermos-elastic stress, which plays important roles in deformation of film, nucleation and propagation of cracks. Last, methods have been proposed to improve the laser damage resistance by controlling the size distribution of impurity particles and increasing the film tensile strength.

  3. Mechanical Properties and Elastic Constants Due to Damage Accumulation and Amorphization in SiC

    SciTech Connect

    Gao, Fei; Weber, William J.

    2004-06-28

    Damage accumulation due to cascade overlap, which was simulated previously, has been used to study the changes of elastic constants, bulk and elastic moduli as a function of dose. These mechanical properties generally decrease with increasing dose, and the rapid decrease at low-dose level indicates that point defects and small clusters play an important role in the changes of elastic constants rather than topological disorder. The internal strain relaxation has no effect on the elastic constants, C11 and C12, in perfect SiC, but it has a significant influence on all elastic constants calculated in damaged SiC. The elastic constants in the cascade-amorphized (CA) SiC decrease about 19%, 29% and 46% for C11, C12 and C44, respectively. The bulk modulus decrease 23% and the elastic modulus decreases 29%, which is consistent with experimental measurements. The stability of both the perfect SiC and CA-SiC under hydrostatic tension has been also investigated. All mechanical properties in the CA-SiC exhibit behavior similar to that in perfect SiC, but the critical stress at which the CA-SiC becomes structurally unstable is one order of magnitude smaller than that for perfect SiC.

  4. 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

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

    2009-07-01

    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.

  5. 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

  6. 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

  7. 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.

  8. Effects of Biowastes Released by Mechanically Damaged Muscle Cells on the Propagation of Deep Tissue Injury: A Multiphysics Study.

    PubMed

    Yao, Yifei; Da Ong, Lucas Xian; Li, Xiaotong; Wan, Kinlun; Mak, Arthur F T

    2017-03-01

    Deep tissue injuries occur in muscle tissues around bony prominences under mechanical loading leading to severe pressure ulcers. Tissue compression can potentially compromise lymphatic transport and cause accumulation of metabolic biowastes, which may cause further cell damage under continuous mechanical loading. In this study, we hypothesized that biowastes released by mechanically damaged muscle cells could be toxic to the surrounding muscle cells and could compromise the capability of the surrounding muscle cells to withstand further mechanical loadings. In vitro, we applied prolonged low compressive stress (PLCS) and short-term high compressive stress to myoblasts to cause cell damage and collected the biowastes released by the damaged cells under the respective loading scenarios. In silico, we used COMSOL to simulate the compressive stress distribution and the diffusion of biowastes in a semi-3D buttock finite element model. In vitro results showed that biowastes collected from cells damaged under PLCS were more toxic and could compromise the capability of normal myoblasts to resist compressive damage. In silico results showed that higher biowastes diffusion coefficient, higher biowastes release rate, lower biowastes tolerance threshold and earlier timeline of releasing biowastes would cause faster propagation of tissue damage. This study highlighted the importance of biowastes in the development of deep tissue injury to clinical pressure ulcers under prolonged skeletal compression.

  9. 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

    2015-04-06

    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.

  10. 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

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

    DOE PAGES

    Beirau, Tobias; Nix, William D.; Bismayer, Ulrich; ...

    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

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

    SciTech Connect

    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 of 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.

  13. A cumulative shear mechanism for tissue damage initiation in shock-wave lithotripsy

    PubMed Central

    Freund, Jonathan B.; Colonius, Tim; Evan, Andrew P.

    2007-01-01

    Evidence suggests that inertial cavitation plays an important role in the renal injury incurred during shock-wave lithotripsy. However, it is unclear how tissue damage is initiated, and significant injury typically occurs only after a sufficient dose of shock waves. While it has been suggested that shock-induced shearing might initiate injury, estimates indicate that individual shocks do not produce sufficient shear to do so. In this paper, we hypothesize that the cumulative shear of the many shocks is damaging. This mechanism depends upon whether there is sufficient time between shocks for tissue to relax to its unstrained state. We investigate the mechanism with a physics-based simulation model wherein the the basement membranes that define the tubules and vessels in the inner medulla are represented as elastic shells surrounded by viscous fluid. Material properties are estimated from in vitro tests of renal basement membranes and documented mechanical properties of cells and extracellular gels. Estimates for the net shear deformation from a typical lithotripter shock (~ 0.1%) are found from a separate dynamic shock simulation. The results suggest that the larger interstitial volume (~ 40%) near the papilla tip gives the tissue there a relaxation time comparable to clinical shock delivery rates (~ 1Hz), thus allowing shear to accumulate. Away from the papilla tip, where the interstitial volume is smaller (≲ 20%), the model tissue relaxes completely before the next shock would be delivered. Implications of the model are that slower delivery rates and broader focal zones should both decrease injury, consistent with some recent observations. PMID:17507147

  14. 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

  15. 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.

  16. 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.

  17. Mechanism investigation of dioscin against CCl4-induced acute liver damage in mice.

    PubMed

    Lu, Binan; Xu, Yousong; Xu, Lina; Cong, Xiaonan; Yin, Lianhong; Li, Hua; Peng, Jinyong

    2012-09-01

    The mechanisms of the ameliorating effects of dioscin against CCl(4) induced acute liver damage are investigated in this study. Dioscin significantly inhibited (p<0.01) the increases of serum ALT and AST activities compared with the CCl(4)-treated animals. The hepatic lipid peroxidation formation and, concentrations of TNF-α and IL-6 were also decreased. Liver histopathologic studies and a DNA laddering assay indicated that dioscin protected hepatocytes against CCl(4)-induced apoptosis and necrosis. Furthermore, dioscin decreased the protein expressions of Fas/FasL, increased Bcl-2/Bax ratio, inhibited the release of cytochrome c from mitochondrion to cytosol and attenuated CCl(4)-induced caspase-3 and -8 activities. The expressions of ICAM-1, vimentin, prohibitin, HGF, c-MET and GSTA1 were also regulated by dioscin and iNOS was also involved in the effects of this agent. These protective effects against CCl(4) induced acute liver damage might be through inhibiting lipid peroxidation, inflammatory cytokines, necrosis and apoptosis, and dioscin shows promise for development toward the treatment of acute chemically mediated liver injury.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. [Occupational therapy for work-related damage induced by mechanical vibration].

    PubMed

    Foti, C; Ciocchetti, E; Antignani, E; Pitruzzella, M; Laurini, A

    2010-01-01

    Vibrations are defined as repeated oscillatory movements of a body; they can be transmitted by contact to humans. From the point of view of physics, vibrations can be differentiated on the basis of frequency, wavelength, amplitude of the oscillation, velocity and acceleration. As far as concerns occupational hazards, two risk factors have been identified: the first involves low frequency vibrations (vehicle drivers), while the second involves high frequency vibrations (manual percussion tools). The transmission of vibration energy can be localized or generalized. Tertiary prevention of exposure to vibrations is based on the use of anti-vibration gloves (for vibrations of the hand and arm) and on anti-vibration shoes (for vibrations of the whole body). The damage caused by vibrations is due to reduced blood circulation and mechanical stimulation in the joints exposed.

  4. Genome damage in induced pluripotent stem cells: assessing the mechanisms and their consequences.

    PubMed

    Hussein, Samer M I; Elbaz, Judith; Nagy, Andras A

    2013-03-01

    In 2006, Shinya Yamanaka and colleagues discovered how to reprogram terminally differentiated somatic cells to a pluripotent stem cell state. The resulting induced pluripotent stem cells (iPSCs) made a paradigm shift in the field, further nailing down the disproval of the long-held dogma that differentiation is unidirectional. The prospect of using iPSCs for patient-specific cell-based therapies has been enticing. This promise, however, has been questioned in the last two years as several studies demonstrated intrinsic epigenetic and genomic anomalies in these cells. Here, we not only review the recent critical studies addressing the genome integrity during the reprogramming process, but speculate about the underlying mechanisms that could create de novo genome damage in iPSCs. Finally, we discuss how much an elevated mutation load really matters considering the safety of future therapies with cells heavily cultured in vitro.

  5. Multi scale analysis by acoustic emission of damage mechanisms in natural fibre woven fabrics/epoxy composites.

    NASA Astrophysics Data System (ADS)

    Bonnafous, C.; Touchard, F.; Chocinski-Arnault, L.

    2010-06-01

    This paper proposes to develop an experimental program to characterize the type and the development of damage in composite with complex microstructure. A multi-scale analysis by acoustic emission has been developed and applied to hemp fibre woven fabrics/epoxy composite. The experimental program consists of tensile tests performed on single yarn, neat epoxy resin and composite materials to identify their AE amplitude signatures. A statistical analysis of AE amplitude signals has been realised and correlated with microscopic observations. Results have enabled to identify three types of damage in composites and their associated AE amplitudes: matrix cracking, interfacial debonding and reinforcement damage and fracture. Tracking of these damage mechanisms in hemp/epoxy composites has been performed to show the process of damage development in natural fibre reinforced composites.

  6. 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.

  7. 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).

  8. 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.

  9. Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms

    PubMed Central

    Gammella, Elena; Recalcati, Stefania; Rybinska, Ilona; Buratti, Paolo; Cairo, Gaetano

    2015-01-01

    The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies. PMID:25878762

  10. 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

  11. Analysis of composite repair methods for pipeline mechanical damages subjected to cyclic loading

    SciTech Connect

    Alexander, C.R.; Fowler, J.R.; Leewis, K.

    1997-05-01

    In service mechanical damage occurring on operating transmission pipelines can induce leakage and eventual failure. Considering that there are approximately 250,000 miles of domestic gas pipelines, repair of these anomalies results in significant costs to the industry. This paper describes a research project sponsored by the Gas Research Institute to determine the capabilities of a composite based assembly designed as an alternative to steel sleeves. This system was evaluated as a repair for mechanical dents and gouges on line pipe with D/t ratios of 51, 68 and 96. The composite wraps were placed over mechanical defects consisting of dents 15% of the diameter and gouge depths of 15, 30, and 50% of the wall thickness. Internal pressures were cycled from 0--50% MAOP and 50--100% MAOP. Results indicate that sharp axial defects in the pipe can be successfully reinforced if they are first blunted by grinding to remove the stress concentrators. The repair system increases fatigue life by 2 to 5 times over those dents with gouges that were not ground.

  12. Update of cell damage mechanisms in thiamine deficiency: focus on oxidative stress, excitotoxicity and inflammation.

    PubMed

    Hazell, Alan S; Butterworth, Roger F

    2009-01-01

    Thiamine deficiency (TD) is a well-established model of Wernicke's encephalopathy. Although the neurologic dysfunction and brain damage resulting from the biochemical consequences of TD is well characterized, the mechanism(s) that lead to the selective histological lesions characteristic of this disorder remain a mystery. Over the course of many years, various structural and functional changes have been identified that could lead to cell death in this disorder. However, despite a concerted effort to explain the consequences of TD in terms of these changes, our understanding of the pathophysiology of this disorder remains unclear. This review will focus on three of these processes, i.e. oxidative stress, glutamate-mediated excitotoxicity and inflammation and their role in selective vulnerability in TD. Since TD inhibits oxidative metabolism, a feature of many neurodegenerative disease states, it represents a model system with which to explore pathological mechanisms inherent in such maladies, with the potential to yield new insights into their possible treatment and prevention.

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

    DOE PAGES

    Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; ...

    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

  14. Towards mechanism-based simulation of impact damage using exascale computing

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

    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 at the macroscale with cellular automata at 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.

  15. Nitric oxide-mediated mitochondrial damage in the brain: mechanisms and implications for neurodegenerative diseases.

    PubMed

    Bolaños, J P; Almeida, A; Stewart, V; Peuchen, S; Land, J M; Clark, J B; Heales, S J

    1997-06-01

    Within the CNS and under normal conditions, nitric oxide (.NO) appears to be an important physiological signalling molecule. Its ability to increase cyclic GMP concentration suggests that .NO is implicated in the regulation of important metabolic pathways in the brain. Under certain circumstances .NO synthesis may be excessive and .NO may become neurotoxic. Excessive glutamate-receptor stimulation may lead to neuronal death through a mechanism implicating synthesis of both .NO and superoxide (O2.-) and hence peroxynitrite (ONOO-) formation. In response to lipopolysaccharide and cytokines, glial cells may also be induced to synthesize large amounts of .NO, which may be deleterious to the neighbouring neurones and oligodendrocytes. The precise mechanism of .NO neurotoxicity is not fully understood. One possibility is that it may involve neuronal energy deficiency. This may occur by ONOO- interfering with key enzymes of the tricarboxylic acid cycle, the mitochondrial respiratory chain, mitochondrial calcium metabolism, or DNA damage with subsequent activation of the energy-consuming pathway involving poly(ADP-ribose) synthetase. Possible mechanisms whereby ONOO- impairs the mitochondrial respiratory chain and the relevance for neurotoxicity are discussed. The intracellular content of reduced glutathione also appears important in determining the sensitivity of cells to ONOO- production. It is concluded that neurotoxicity elicited by excessive .NO production may be mediated by mitochondrial dysfunction leading to an energy deficiency state.

  16. 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.

  17. 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.

  18. Mechanism of Pole-mounted Transformer Damage by Backflow Lightning and Measures against the Damage on Low-voltage Distribution Line

    NASA Astrophysics Data System (ADS)

    Honda, Hideki; Hongo, Yasuji; Kado, Hiroyuki; Yokoyama, Shigeu

    Pole-mounted transformer is one of the equipment that is easier to receive lightning damage. As our information society advances, the needs for supply reliability of electric power become higher, and the decreasing of lightning damages of pole-mounted transformers becomes necessary. In recent years, lightning protective devices (surge arresters) have been installed around the primary bushing of the transformers. Therefore, the number of disconnections around the primary bushing caused by lightning has been decreasing. However, the surge arrester that installed at the primary side of transformer cannot protect the transformer against backflow lightning that invades to the secondary side of transformer. The characteristic of the transformer damage by the backflow lightning is that electro-magnetic force occurring by the current flowing into the secondary side of transformer deforms the windings of the transformer. In this paper, the mechanism of transformer damage by the current flowing into the secondary side is clarified by the comparison between actual lightning damage case and the results of verification test using short-circuit generator. Effective counter measures against the damage of transformer by the backflow lightning are examined by EMTP calculations. From the calculation results, neutral grounding on low-voltage distribution line is the most effective measures in the point of decreasing of the amount of current flowing into the transformer. The less the grounding resistance, the less the amount of current flowing into the transformer. Moreover, decreasing the voltage of the secondary-side of the transformer is important to protect the bushing of the secondary-side. By the calculation result, it is clarified that the surge arresters installed around the secondary side of the transformer are effective for decreasing the voltage of the secondary side of the transformer.

  19. 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.

  20. Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing.

    PubMed

    Rossiello, Francesca; Herbig, Utz; Longhese, Maria Pia; Fumagalli, Marzia; d'Adda di Fagagna, Fabrizio

    2014-06-01

    The DNA damage response (DDR) orchestrates DNA repair and halts cell cycle. If damage is not resolved, cells can enter into an irreversible state of proliferative arrest called cellular senescence. Organismal ageing in mammals is associated with accumulation of markers of cellular senescence and DDR persistence at telomeres. Since the vast majority of the cells in mammals are non-proliferating, how do they age? Are telomeres involved? Also oncogene activation causes cellular senescence due to altered DNA replication and DDR activation in particular at the telomeres. Is there a common mechanism shared among apparently distinct types of cellular senescence? And what is the role of telomeric DNA damage?

  1. 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

  2. Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans

    DOE PAGES

    Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; ...

    2015-10-08

    Here, evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. 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 inmore » 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. 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. 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 reaction. In response to DNA damage, elephant lymphocytes

  3. Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans

    SciTech Connect

    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.

    2015-10-08

    Here, evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. 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. 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. 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 reaction. In response to DNA damage, elephant lymphocytes

  4. 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.

  5. Repair of radiation-induced damage to the cell division mechanism of Escherichia coli.

    PubMed

    Adler, H I; Fisher, W D; Hardigree, A A; Stapleton, G E

    1966-02-01

    Adler, Howard I. (Oak Ridge National Laboratory, Oak Ridge, Tenn.), William D. Fisher, Alice A. Hardigree, and George E. Stapleton. Repair of radiation-induced damage to the cell division mechanism of Escherichia coli. J. Bacteriol. 91:737-742. 1966.-Microscopic observations of irradiated populations of filamentous Escherichia coli cells indicated that filaments can be induced to divide by a substance donated by neighboring cells. We have made this observation the basis for a quantitative technique in which filaments are incubated in the presence of nongrowing donor cells. The presence of "donor" organisms promotes division and subsequent colony formation in filaments. "Donor" bacteria do not affect nonfilamentous cells. An extract of "donor" cells retains the division-promoting activity. The extract has been partially fractionated, and consists of a heat-stable and a heat-labile component. The heat-stable component is inactive in promoting cell division, but enhances the activity of the heat-labile component. The division-promoting system is discussed as a radiation repair mechanism and as a normal component of the cell division system in E. coli.

  6. Mechanical problem-solving strategies in left-brain damaged patients and apraxia of tool use.

    PubMed

    Osiurak, François; Jarry, Christophe; Lesourd, Mathieu; Baumard, Josselin; Le Gall, Didier

    2013-08-01

    Left brain damage (LBD) can impair the ability to use familiar tools (apraxia of tool use) as well as novel tools to solve mechanical problems. Thus far, the emphasis has been placed on quantitative analyses of patients' performance. Nevertheless, the question still to be answered is, what are the strategies employed by those patients when confronted with tool use situations? To answer it, we asked 16 LBD patients and 43 healthy controls to solve mechanical problems by means of several potential tools. To specify the strategies, we recorded the time spent in performing four kinds of action (no manipulation, tool manipulation, box manipulation, and tool-box manipulation) as well as the number of relevant and irrelevant tools grasped. We compared LBD patients' performance with that of controls who encountered difficulties with the task (controls-) or not (controls+). Our results indicated that LBD patients grasped a higher number of irrelevant tools than controls+ and controls-. Concerning time allocation, controls+ and controls- spent significantly more time in performing tool-box manipulation than LBD patients. These results are inconsistent with the possibility that LBD patients could engage in trial-and-error strategies and, rather, suggest that they tend to be perplexed. These findings seem to indicate that the inability to reason about the objects' physical properties might prevent LBD patients from following any problem-solving strategy.

  7. Revisiting the Molecular Mechanism of Neurological Manifestations in Antiphospholipid Syndrome: Beyond Vascular Damage

    PubMed Central

    Carecchio, M.; Cantello, R.; Comi, C.

    2014-01-01

    Antiphospholipid syndrome (APS) is a multiorgan disease often affecting the central nervous system (CNS). Typically, neurological manifestations of APS include thrombosis of cerebral vessels leading to stroke and requiring prompt initiation of treatment with antiplatelet drugs or anticoagulant therapy. In these cases, alterations of the coagulation system at various levels caused by multiple effects of antiphospholipid antibodies (aPL) have been postulated to explain the vascular damage to the CNS in APS. However, several nonvascular neurological manifestations of APS have progressively emerged over the past years. Nonthrombotic, immune-mediated mechanisms altering physiological basal ganglia function have been recently suggested to play a central role in the pathogenesis of these manifestations that include, among others, movement disorders such as chorea and behavioral and cognitive alterations. Similar clinical manifestations have been described in other autoimmune CNS diseases such as anti-NMDAR and anti-VGCK encephalitis, suggesting that the spectrum of immune-mediated basal ganglia disorders is expanding, possibly sharing some pathophysiological mechanisms. In this review, we will focus on thrombotic and nonthrombotic neurological manifestations of APS with particular attention to immune-mediated actions of aPL on the vascular system and the basal ganglia. PMID:24741580

  8. 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.

  9. Damage mechanics approach to remove the constraint dependence of elastic-plastic fracture toughness

    NASA Astrophysics Data System (ADS)

    Wang, T.-J.; Kuang, Z.-B.

    1995-02-01

    It is now generally agreed that the applicability of a one-parameter J-based ductile fracture approach is limited to so-called high constraint crack geometries, and that the elastic-plastic fracture toughness J(Ic) is not a material constant but strongly specimen geometry constraint-dependent. In this paper, the constraint effect on elastic-plastic fracture toughness is investigated by use of a continuum damage mechanics approach. Based on a new local damage theory for ductile fracture (proposed by the author) which has a clear physical meaning and can describe both deformation and constraint effects on ductile fracture, a relationship is described between the conventional elastic-plastic fracture toughness, J(Ic), and crack tip constraint, characterized by crack tip stress triaxiality T. Then, a new parameter J(dc) (and associated criterion, J(d) = J(dc)) for ductile fracture is proposed. Experiments show that toughness variation with specimen geometry constraint changes can effectively be removed by use of the constraint correction procedure proposed in this paper, and that the new parameter J(dc) is a material constant independent of specimen geometry (constraint). This parameter can serve as a new parameter to differentiate the elastic-plastic fracture toughness of engineering materials, which provides a new approach for fracture assessments of structures. It is not necessary to determine which laboratory specimen matches the structural constraint; rather, any specimen geometry can be tested to measure the size-independent fracture toughness J(dc). The potential advantage is clear and the results are very encouraging.

  10. 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

  11. Mechanisms of larval midgut damage following exposure to phoxim and repair of phoxim-induced damage by cerium in Bombyx mori.

    PubMed

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

    2015-04-01

    Bombyx mori is an important economic animal for silk production. However, it is liable to be infected by organophosphorus pesticide that can contaminate its food and growing environment. It has been known that organophosphorus pesticide including phoxim exposure may damage the digestive systems, produce oxidative stress and neurotoxicity in silkworm B. mori, whereas cerium treatment has been demonstrated to relieve phoxim-induced toxicity in B. mori. However, very little is known about the molecular mechanisms of midgut injury due to phoxim exposure and B. mori protection after cerium pretreatment. The aim of this study was to evaluate the midgut damage and its molecular mechanisms, and the protective role of cerium in B. mori following exposure to phoxim. The results showed that phoxim exposure led to severe midgut damages and oxidative stress; whereas cerium relieved midgut damage and oxidative stress caused by phoxim in B. mori. Furthermore, digital gene expression suggested that phoxim exposure led to significant up-regulation of 94 genes and down-regulation of 52 genes. Of these genes, 52 genes were related with digestion and absorption, specifically, the significant alterations of esterase, lysozyme, amylase 48, and lipase expressions. Cerium pretreatment resulted in up-regulation of 116 genes, and down-regulation of 29 genes, importantly, esterase 48, lipase, lysozyme, and α-amylase were up-regulated. Treatment with Phoxim + CeCl3 resulted in 66 genes up-regulation and 39 genes down-regulation; specifically, levels of esterase 48, lipase, lysozyme, and α-amylase expression in the midgut of silkworms were significantly increased. Therefore, esterase 48, lipase, lysozyme, and α-amylase may be potential biomarkers of midgut toxicity caused by phoxim exposure. These findings may expand the application of rare earths in sericulture.

  12. 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

  13. A phenomenological model for mechanically mediated growth, remodeling, damage, and plasticity of gel-derived tissue engineered blood vessels.

    PubMed

    Raykin, Julia; Rachev, Alexander I; Gleason, Rudolph L

    2009-10-01

    Mechanical stimulation has been shown to dramatically improve mechanical and functional properties of gel-derived tissue engineered blood vessels (TEBVs). Adjusting factors such as cell source, type of extracellular matrix, cross-linking, magnitude, frequency, and time course of mechanical stimuli (among many other factors) make interpretation of experimental results challenging. Interpretation of data from such multifactor experiments requires modeling. We present a modeling framework and simulations for mechanically mediated growth, remodeling, plasticity, and damage of gel-derived TEBVs that merge ideas from classical plasticity, volumetric growth, and continuum damage mechanics. Our results are compared with published data and suggest that this model framework can predict the evolution of geometry and material behavior under common experimental loading scenarios.

  14. Simple and exact approach to the electronic polarization effect on the solvation free energy: formulation for quantum-mechanical/molecular-mechanical system and its applications to aqueous solutions.

    PubMed

    Takahashi, Hideaki; Omi, Atsushi; Morita, Akihiro; Matubayasi, Nobuyuki

    2012-06-07

    We present a simple and exact numerical approach to compute the free energy contribution δμ in solvation due to the electron density polarization and fluctuation of a quantum-mechanical solute in the quantum-mechanical/molecular-mechanical (QM/MM) simulation combined with the theory of the energy representation (QM/MM-ER). Since the electron density fluctuation is responsible for the many-body QM-MM interactions, the standard version of the energy representation method cannot be applied directly. Instead of decomposing the QM-MM polarization energy into the pairwise additive and non-additive contributions, we take sum of the polarization energies in the QM-MM interaction and adopt it as a new energy coordinate for the method of energy representation. Then, it is demonstrated that the free energy δμ can be exactly formulated in terms of the energy distribution functions for the solution and reference systems with respect to this energy coordinate. The benchmark tests were performed to examine the numerical efficiency of the method with respect to the changes in the individual properties of the solvent and the solute. Explicitly, we computed the solvation free energy of a QM water molecule in ambient and supercritical water, and also the free-energy change associated with the isomerization reaction of glycine from neutral to zwitterionic structure in aqueous solution. In all the systems examined, it was demonstrated that the computed free energy δμ agrees with the experimental value, irrespective of the choice of the reference electron density of the QM solute. The present method was also applied to a prototype reaction of adenosine 5'-triphosphate hydrolysis where the effect of the electron density fluctuation is substantial due to the excess charge. It was demonstrated that the experimental free energy of the reaction has been accurately reproduced with the present approach.

  15. A smart sensor using a mechanical memory for structural health monitoring of a damage-controlled building

    NASA Astrophysics Data System (ADS)

    Mita, Akira; Takhira, Shinpei

    2003-04-01

    A smart sensor using a mechanical memory that can monitor peak strain or displacement was developed. The mechanism of the mechanical memory relies on the pure plastic extension of the sensing section that is realized by elastic buckling of a thin wire. The change in length of the sensing section is detected via a change in resistance, inductance or capacitance. In addition, by introducing an LC-circuit into the sensor we can add a capability for wireless retrieval of the measured data. Basically, the sensor does not need any power supply for measurements. A small power supply is required only when the data retrieval becomes necessary. Theoretical and experimental studies show the feasibility of using the sensor developed for structural health monitoring of damage-controlled structures. Though the sensor is designed to memorize the peak strain or displacement only, it can be easily modified to measure other damage indices that are physical values well correlated with the critical damage in a structure. Typical damage indices include peak strain, peak displacement, peak acceleration, absorbed energy and accumulated plastic deformation. Simple and inexpensive passive sensors that can monitor such damage indices are particularly useful for quantifying the performance of a damage-controlled building, as most damaging energy due to a large earthquake is taken care of by structural control devices. The devices are usually covered by a wall or a fire-protection material, so a simple inspection by eye is not possible without removing cover materials. We believe the installation of the sensors developed will ensure the safety of such a building with minimal cost.

  16. Laser-matter coupling mechanisms governing particulate-induced damage on optical surfaces

    NASA Astrophysics Data System (ADS)

    Matthews, M. J.; Feigenbaum, E.; Demos, S. G.; Raman, R. N.; Qiu, S. R.; Shen, N.; Harris, C.; Negres, R. A.; Norton, M.; Cross, D.; Rubenchik, A. M.

    2016-12-01

    A comprehensive study of laser-induced damage associated with particulate damage on optical surfaces is presented. Contaminant-driven damage on silica windows and multilayer dielectrics is observed to range from shallow pitting to more classical fracture-type damage, depending on particle-substrate material combination, as well as laser pulse characteristics. Ejection dynamics is studied in terms of plasma emission spectroscopy and pump-probe shadowgraphy. Our data is used to assess the momentum coupling between incident energy and the ejected plasma, which dominates the laser-particle-substrate interaction. Beam propagation analysis is also presented to characterize the impact of contaminant-driven surface pitting on optical performance.

  17. Sperm Chromatin Integrity: Etiologies and Mechanisms of Abnormality, Assays, Clinical Importance, Preventing and Repairing Damage

    PubMed Central

    Hekmatdoost, Azita; Lakpour, Niknam; Sadeghi, Mohammad Reza

    2009-01-01

    The standard semen analysis is the first line and the most popular laboratory test in the diagnosis of male fertility. It evaluates sperm concentration, motility, morphology and their vitality. However, it is well-known that normal results of semen analysis can not exclude men from the causes of couples′ infertility. One of the most important parameters of sperm in its fertilizing potential is “Sperm chromatin integrity” that has direct positive correlation with Assisted Reproductive Techniques (ART) outcomes including; fertilization rate, embryo quality, pregnancy and successful delivery rate. It seems that sperm DNA chromatin integrity provides better diagnostic and prognostic approaches than standard semen parameters. For these reasons under-standing the sperm chromatin structure, etiology of sperm chromatin abnormality, identification factors that disturbs sperm chromatin integrity and the mechanism of their action can help in recognizing the causes of couples′ infertility. Various methods of its evaluation, its importance in male fertility, clinical relevance in the outcomes of ART and application of laboratory and medical protocols to improve this integrity have valuable position in diagnosis and treatment of male infertility. There has recently been interest in the subject and its application in the field of andrology. Therefore, with regard to the above mentioned importance of sperm chromatin integrity, this review article describes details of the useful information pertaining to sperm DNA damage including the origins, assessments, etiologies, clinical aspects, and prevention of it. PMID:23408441

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

    PubMed

    Meier, Bettina; Gartner, Anton

    2014-11-15

    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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Mechanisms of pheromone communication disruption in Choristoneura rosaceana exposed to microencapsulated (Z)-11-tetradecenyl acetate formulated with and without horticultural oil.

    PubMed

    Wins-Purdy, Andreas H; Judd, Gary J R; Evenden, Maya L

    2008-08-01

    Flight tunnel and electrophysiological assays with male Choristoneura rosaceana Harris (Lepidoptera: Tortricidae) were conducted to investigate the non-competitive mechanisms of communication disruption caused by microencapsulated (MEC) (Z)-11-tetradecenyl acetate (3M MEC-LR) formulated with and without horticultural oil (Purespray Green). Male C. rosaceana were exposed for 1 h by resting on metal surfaces sprayed with either water, 2% oil in water, MEC-LR in water, or MEC-LR + 2% oil in water. In one experiment, sprayed surfaces were allowed to age up to 47 days in a laboratory fume hood prior to moth exposure to examine the effect of ageing on the disruptive efficacy of the formulations. In flight tunnel assays with calling females, males exposed to MEC or MEC + oil treatments for 1 h were significantly disrupted up to 1 h after exposure, and both treatments were effective for 47 days. Electroantennograms revealed no reduction in antennal sensitivity when measured 75 s after a 1-h exposure. Collectively, these results support habituation as a key mechanism of communication disruption for C. rosaceana exposed to the MEC formulations tested here. Male proximity to the pheromone-treated surfaces appears to be important in maintaining a disruptive effect as MEC treatments age and pheromone release rates decline. The addition of 2% oil increased the number of microcapsules deposited on sprayed surfaces and caused a moderate but significant increase in the disruptive effect of the MEC formulation. A better understanding of the mechanisms that underlie disruption by MEC formulations, and how an adjuvant like horticultural oil may enhance these mechanisms, may lead to improvements in this technology.

  5. 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.

  6. 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(...

  7. Variational and perturbative formulations of quantum mechanical/molecular mechanical free energy with mean-field embedding and its analytical gradients

    NASA Astrophysics Data System (ADS)

    Yamamoto, Takeshi

    2008-12-01

    Conventional quantum chemical solvation theories are based on the mean-field embedding approximation. That is, the electronic wavefunction is calculated in the presence of the mean field of the environment. In this paper a direct quantum mechanical/molecular mechanical (QM/MM) analog of such a mean-field theory is formulated based on variational and perturbative frameworks. In the variational framework, an appropriate QM/MM free energy functional is defined and is minimized in terms of the trial wavefunction that best approximates the true QM wavefunction in a statistically averaged sense. Analytical free energy gradient is obtained, which takes the form of the gradient of effective QM energy calculated in the averaged MM potential. In the perturbative framework, the above variational procedure is shown to be equivalent to the first-order expansion of the QM energy (in the exact free energy expression) about the self-consistent reference field. This helps understand the relation between the variational procedure and the exact QM/MM free energy as well as existing QM/MM theories. Based on this, several ways are discussed for evaluating non-mean-field effects (i.e., statistical fluctuations of the QM wavefunction) that are neglected in the mean-field calculation. As an illustration, the method is applied to an SN2 Menshutkin reaction in water, NH3+CH3Cl→NH3CH3++Cl-, for which free energy profiles are obtained at the Hartree-Fock, MP2, B3LYP, and BHHLYP levels by integrating the free energy gradient. Non-mean-field effects are evaluated to be <0.5 kcal/mol using a Gaussian fluctuation model for the environment, which suggests that those effects are rather small for the present reaction in water.

  8. 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.

  9. 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...

  10. 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

  11. 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

  12. 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.

  13. A statistical mechanics model to predict electromigration induced damage and void growth in solder interconnects

    NASA Astrophysics Data System (ADS)

    Wang, Yuexing; Yao, Yao; Keer, Leon M.

    2017-02-01

    Electromigration is an irreversible mass diffusion process with damage accumulation in microelectronic materials and components under high current density. Based on experimental observations, cotton type voids dominate the electromigration damage accumulation prior to cracking in the solder interconnect. To clarify the damage evolution process corresponding to cotton type void growth, a statistical model is proposed to predict the stochastic characteristic of void growth under high current density. An analytical solution of the cotton type void volume growth over time is obtained. The synchronous electromigration induced damage accumulation is predicted by combining the statistical void growth and the entropy increment. The electromigration induced damage evolution in solder joints is developed and applied to verify the tensile strength deterioration of solder joints due to electromigration. The predictions agree well with the experimental results.

  14. 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.

  15. 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

  16. Studying the effect of a hydrostatic stress/strain reduction factor on damage mechanics of concrete materials

    NASA Astrophysics Data System (ADS)

    Taqieddin, Ziad N.; Voyiadjis, George Z.

    2013-12-01

    In the non-linear finite element analysis (NFEA) of concrete materials, continuum damage mechanics (CDM) provides a powerful framework for the derivation of constitutive models capable of describing the mechanical behavior of such materials. The internal state variables of CDM can be introduced to the elastic analysis of concrete to form elastic-damage models (no inelastic strains), or to the elastic-plastic analysis in order to form coupled/uncoupled elastic-plastic-damage models. Experimental evidence that is well documented in literature shows that the susceptibility of concrete to damage and failure is distinguished under deviatoric loading from that corresponding to hydrostatic loading. A reduction factor is usually introduced into a CDM model to reduce the susceptibility of concrete to hydrostatic stresses/strains. In this work, the effect of a hydrostatic stress/strain reduction factor on the performances of two NFEA concrete models will be studied. These two (independently published) models did not provide any results showing such effect. One of these two models is an elastic-damage model, whereas the other is an uncoupled elastic-plastic-damage model. Simulations and comparisons are carried out between the performances of the two models under uniaxial tensile and compressive loading conditions. Simulations are also provided for the uncoupled elastic-plastic-damage model under the following additional loading conditions: biaxial tension and biaxial compression, uniaxial cyclic loading, and varying ratios of triaxial compressive loadings. These simulations clearly show the effect of the reduction factor on the numerically depicted behaviors of concrete materials. To have rational comparisons, the hydrostatic stress reduction factor applied to each model is chosen to be a function of the internal state variables common to both models. Therefore, once the two models are calibrated to simulate the experimental behaviors, their corresponding reduction factors

  17. 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

  18. Fatigue Damage Mechanical Model of the Envelope Material for Stratospheric Airships

    NASA Astrophysics Data System (ADS)

    Meng, Junhui; Qu, Zhipeng; Zhu, Weiyu; Lv, Mingyun

    2016-11-01

    As a major part of the stratospheric airship structure, the envelope material is used to contain lifting gas and keep the aerodynamic configuration. The main force on the envelope material comes from differential pressure between inside and outside the structure, which is cyclic stress because of the alternative temperature. Three different damage modes of the envelope material, including fracture damage of fabric yarns, cracking damage of resin matrix and functional membrane are investigated in this paper. A theoretical model to predict fatigue life of the envelope material under cycle load is developed base on the damage evolution properties of the material. The results indicates that the theoretical model can well predict the fatigue life. In addition, it can be seen from the results that the fracture of fabric yarns is the main damage modes for the material with off-axial angle of 0°and 90°, while the cracking damage of resin and functional membrane is the main damage modes for the material with other off-axial angles.

  19. Cavitation distribution within large phantom vessel and mechanical damage formed on surrounding vessel wall.

    PubMed

    Qiao, Yangzi; Yin, Hui; Li, Zhaopeng; Wan, Mingxi

    2013-11-01

    Blood vessel is one of the most important targets encountered during focused ultrasound (FU) therapy. The lasting high temperature caused by continuous FU can result in structural modification of small vessel. For the vessel with a diameter larger than 2mm, convective cooling can significantly weaken the thermal effect of FU. Meanwhile, the continued presence of ultrasound will cause repetitive cavitation and acoustic microstreaming, making comprehension of continuous wave induced cavitation effect in large vessels necessary. The Sonoluminescence (SL) method, mechanical damage observation and high-speed camera were used in this study to investigate the combination effect of ultrasound contrast agents (UCAs) and continuous FU in large phantom vessels with a diameter of 10mm without consideration of thermal effect. When the focus was positioned at the proximal wall, cylindrical hole along the acoustic axis opposite the ultrasound wave propagation direction was observed at the input power equal to or greater than 50 W. When the focus was located at the distal wall, only small tunnels can be found. The place where the cylindrical hole formed was corresponding to where bubbles gathered and emitted brilliant light near the wall. Without UCAs neither such bright SL nor cylindrical hole can be found. However, the UCAs concentration had little influence on the SL distribution and the length of cylindrical hole. The SL intensity near the proximal vessel wall and the length of the cylindrical hole both increased with the input power. It is suggested that these findings need to be considered in the large vessel therapy and UCAs usage.

  20. Protective role and related mechanism of Gnaq in neural cells damaged by oxidative stress.

    PubMed

    Jia, Nannan; Li, Guoping; Huang, Pu; Guo, Jiazhi; Wei, Lugang; Lu, Di; Chen, Shaochun

    2017-03-22

    Gnaq is a member of G protein family and is rich in brain tissue. It has attracted the attention of many researchers in melanoma due to its high ratio of mutation. We have previously reported that the expression level of Gnaq in the mouse forebrain cortex was significantly decreased with age. Oxidative stress (OS) is the main cause leading to brain aging and related diseases. The roles and mechanisms of Gnaq in antioxidation in the brain have not been fully explored. In the present study, gene recombinant technique and lentivirus transfection technique were used to generate a Gnaq-overexpression cell model (Gnaq-SY5Y) coupled with H2O2 to build an OS model. The viability of cells, concentration of reactive oxygen species (ROS), apoptosis-related proteins (Bcl-2 and Bax), and signal pathways (NF-κB and Erk1/2) were compared between model cells and control cells. Results showed that the antioxidative ability of Gnaq-SY5Y cells was significantly improved. Concomitantly, the ROS level in Gnaq-SY5Y cells was significantly decreased whether the cells were subject to or not to H2O2 treatment. Anti-apoptotic protein Bcl-2 was up-regulated and apoptosis-promoting protein Bax was down-regulated in Gnaq-SY5Y cells after treatment with H2O2. NF-κB and phosphorylated Erk1/2 (p-Erk1/2) was significantly down-regulated in Gnaq-SY5Y cells. H2O2 treatment decreased Gnaq expression but increased NF-κB and p-Erk1/2 expressions in Gnaq-SY5Y cells. It is therefore concluded that Gnaq plays a pivotal role in antioxidation in neural cells. A possible mechanism for this would be that the overexpressed Gnaq inhibits the cellular damaging effect mediated by NF-κB and Erk1/2 signal pathways.

  1. Insights into the epigenetic mechanisms involving histone lysine methylation and demethylation in ischemia induced damage and repair has therapeutic implication.

    PubMed

    Chakravarty, Sumana; Jhelum, Priya; Bhat, Unis Ahmad; Rajan, Wenson D; Maitra, Swati; Pathak, Salil S; Patel, Anant B; Kumar, Arvind

    2017-01-01

    Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. Therapeutic interventions to minimize ischemia-induced neural damage are limited due to poor understanding of molecular mechanisms mediating complex pathophysiology in stroke. Recently, epigenetic mechanisms mostly histone lysine (K) acetylation and deacetylation have been implicated in ischemic brain damage and have expanded the dimensions of potential therapeutic intervention to the systemic/local administration of histone deacetylase inhibitors. However, the role of other epigenetic mechanisms such as histone lysine methylation and demethylation in stroke-induced damage and subsequent recovery process is elusive. Here, we established an Internal Carotid Artery Occlusion (ICAO) model in CD1 mouse that resulted in mild to moderate level of ischemic damage to the striatum, as suggested by magnetic resonance imaging (MRI), TUNEL and histopathological staining along with an evaluation of neurological deficit score (NDS), grip strength and rotarod performance. The molecular investigations show dysregulation of a number of histone lysine methylases (KMTs) and few of histone lysine demethylases (KDMs) post-ICAO with significant global attenuation in the transcriptionally repressive epigenetic mark H3K9me2 in the striatum. Administration of Dimethyloxalylglycine (DMOG), an inhibitor of KDM4 or JMJD2 class of histone lysine demethylases, significantly ameliorated stroke-induced NDS by restoring perturbed H3K9me2 levels in the ischemia-affected striatum. Overall, these results highlight the novel role of epigenetic regulatory mechanisms controlling the epigenetic mark H3K9me2 in mediating the stroke-induced striatal damage and subsequent repair following mild to moderate cerebral ischemia.

  2. Overview of Low Plasticity Burnishing for Mitigation of Fatigue Damage Mechanisms

    DTIC Science & Technology

    2005-09-01

    cycle fatigue strength for electropolished base-line Ti- 6 - 4 is nominally 538 MPa (78 ksi), which decreased drastically to 172 MPa (25 ksi) with...in IN718, improved damage tolerance in Ti- 6 - 4 fan blades, mitigation of fretting fatigue damage in Ti- 6 - 4 , and improved corrosion fatigue in 17...of LE of 17-4PH compressor blade with caliper tool. Figure 3 Single point tool LPB processing of the dovetail of Ti - 6 - 4 compressor blade

  3. 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

  4. Efficacy of electrolyzed water and an acidic formulation compared with regularly used chemical sanitizers for tableware sanitization during mechanical and manual ware-washing protocols.

    PubMed

    Handojo, Aldo; Lee, Jaesung; Hipp, Joel; Pascall, Melvin A

    2009-06-01

    This study investigated residual bacteria and different food types left on tableware items after various washing and sanitization protocols. Escherichia coli K-12 and Staphylococcus epidermidis were inoculated into whole milk and soft cream cheese. The milk was used to contaminate regular drinking glasses and the cheese was used to contaminate plates and silverware. These tableware items were washed in manual (43 degrees C) and mechanical (49 degrees C) washers and sanitized with different sanitizers (24 degrees C) for 5 s. Quaternary ammonium compound, sodium hypochlorite, peroxyacetic acid, neutral electrolyzed water (NEW), and a combination of citric acid with sodium dodecylbenzene sulfonate (acidic formulation) were used as the chemical sanitizers. Tap water was used as a control. Results showed that at least 5-log reductions in both bacterial numbers were achieved for all sanitizers in both types of washers, except for the control. With mechanical dishwashing, the NEW and acidic formulation treatments reduced bacterial populations by >6.9 and >6.0 log CFU per tableware item, respectively. With the manual operation, bacterial numbers were reduced by >5.4 and >6.0 log CFU per tableware item, respectively. This study revealed that NEW and the acidic formulation are as effective as the other chemical sanitizers for food contact surface sanitization in manual and mechanical ware washing.

  5. 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.

  6. 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

  7. 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

  8. Damage monitoring using fiber optic sensors and by analysing electro-mechanical admittance signatures obtained from piezo sensor

    NASA Astrophysics Data System (ADS)

    Maheshwari, Muneesh; Annamdas, Venu Gopal M.; Pang, John Hock Lye; Tjin, Swee C.; Asundi, Anand

    2015-12-01

    Damage monitoring is the need of the hour in this age of infrastructure. Many methods are being used for damage monitoring in different mechanical and civil structures. Some of them are strain based methods in which abruptly increased strain signifies the presence of damage in the structure. This article focuses on crack monitoring of a fixedfixed beam using fiber optic sensors which can measure strain locally or globally. The two types of fiber optic sensors used in this research are fiber Bragg grating (FBG) and fiber optic polarimetric sensors (FOPS). FBG and FOPS are used for local strain monitoring (at one point only) and global strain monitoring (in the entire specimen) respectively. At the centre of the specimen, a piezoelectric wafer active sensor (PWAS) is also attached. PWAS is used to obtain electromechanical admittance (EMA) signatures. Further, these EMA signatures are analysed to access the damage state in the beam. These multiple smart materials together provide improved information on damages in the specimen which is very valuable for the structural health monitoring (SHM) of the specimen.

  9. 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.

  10. Mechanisms compensating for visual field restriction in adolescents with damage to the retro-geniculate visual system

    PubMed Central

    Jacobson, L; Lennartsson, F; Pansell, T; Öqvist Seimyr, G; Martin, L

    2012-01-01

    Background To describe visual field (VF) outcome in three adolescents with damage to the optic radiation and to focus on mechanisms that may compensate the practical functional limitations of VF defects. Design Descriptive, prospective multi-case study in a hospital setting. Participants Three teenagers with cerebral visual dysfunction because of damage to the retro-geniculate visual pathways. Methods Best-corrected visual acuity and eye alignment were assessed. Visual field function was tested with Goldmann perimetry, and with Rarebit, Humphrey Visual Field Analyzer and Esterman computerized techniques. Fixation was registered with video oculography during Rarebit examination. Magnetic resonance imaging of the brain illustrated brain damage and its relation to the posterior visual system. Results One of the three subjects had bilateral asymmetric white matter damage of immaturity, early-onset exotropia, and a relative homonymous VF defect, but normal binocular VF. The second subject also had bilateral asymmetric white matter damage of immaturity and showed an inferior right quadrantanopia, confirmed by the binocular field. Registration of fixation revealed automatic scanning during perimetry. The third subject had an almost total left homonymous hemianopia after resection of a brain tumour in the right temporal lobe. The hemianopia could be compensated for by fast voluntary scanning. Conclusion Congenital and later-acquired homonymous VF defects may, at least in young subjects, be compensated for by scanning. Exotropia may compensate VF defects and, therefore, the VF should be tested before strabismus surgery. PMID:22995940

  11. Delamination identification of laminated composite plates using a continuum damage mechanics model and subset selection technique

    NASA Astrophysics Data System (ADS)

    Shang, Shen; Yun, Gun Jin; Qiao, Pizhong

    2010-05-01

    In this paper, a new model-based delamination detection methodology is presented for laminated composite plates and its performance is studied both numerically and experimentally. This methodology consists of two main parts: (1) modal analysis of an undamaged baseline finite element (FE) model and experimental modal testing of panels with delamination damage at single or multiple locations and (2) a sensitivity based subset selection technique for single or multiple delamination damage localizations. As an identification model, a higher-order finite element model is combined with a rational micromechanics-based CDM model which defines the delamination damage parameter as a ratio of delaminated area to entire area. The subset selection technique based on sensitivity of the dynamic residual force has been known to be capable of detecting multiple damage locations. However, there has been no experimental study specifically for the applications in laminated composite structures. To implement the methodology, a sensitivity matrix for the laminated composite plate model has been derived. Applications of the proposed methodology to an E-glass/epoxy symmetric composite panel composed of 16 plies [CSM/UM1208/3 layers of C1800]s = [CSM/0/(90/0)3]s with delamination damage are demonstrated both numerically and experimentally. A non-contact scanning laser vibrometer (SLV), a lead zirconate titanate (PZT) actuator and a polyvinylidene fluoride (PVDF) sensor are used to conduct experimental modal testing. From the experimental example, capabilities of the proposed methodology for damage identification are successfully demonstrated for a 2D laminated composite panel. Furthermore, various damage scenarios are considered to show its performance and detailed results are discussed for future improvements.

  12. 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.

  13. Pulsed-CO2-laser-induced damage mechanisms in semiconductors

    NASA Astrophysics Data System (ADS)

    Lefranc, Sebastian; Autric, Michel L.

    1998-09-01

    Laser irradiation induced damage to several materials of interest for use as 10.6 micrometer laser system windows and lenses is investigated in this paper. The irradiation source in these single shot experiments was a pulsed TEA CO2 laser (lambda equals 10.6 micrometer, (tau) pulse equals 3.5 microsecond, I equals 1 - 100 MW/cm2 onto the sample). A time resolved study of the damage process in semiconductors (Ge, ZnSe, ZnS) has been carried out during the interaction by measuring the variation of the transmitted and reflected intensity of a CO2 cw laser through the samples. An analysis of the pulse shape dependence on the damage parameters has been investigated. Results show that damages are initiated by the high power peak of the laser pulse on both surfaces and in the bulk of the materials. The damaged materials have been characterized for various incident fluences by means of optical microscopy and scanning electron microscopy in terms of morphology.

  14. Autonomous Repair Mechanism of Creep Damage in Fe-Au and Fe-Au-B-N Alloys

    NASA Astrophysics Data System (ADS)

    Zhang, S.; Kwakernaak, C.; Tichelaar, F. D.; Sloof, W. G.; Kuzmina, M.; Herbig, M.; Raabe, D.; Brück, E.; van der Zwaag, S.; van Dijk, N. H.

    2015-12-01

    The autonomous repair mechanism of creep cavitation during high-temperature deformation has been investigated in Fe-Au and Fe-Au-B-N alloys. Combined electron-microscopy techniques and atom probe tomography reveal how the improved creep properties result from Au precipitation within the creep cavities, preferentially formed on grain boundaries oriented perpendicular to the applied stress. The selective precipitation of Au atoms at the free creep cavity surface results in pore filling, and thereby, autonomous repair of the creep damage. The large difference in atomic size between the Au and Fe strongly hampers the nucleation of precipitates in the matrix. As a result, the matrix acts as a reservoir for the supersaturated solute until damage occurs. Grain boundaries and dislocations are found to act as fast transport routes for solute gold from the matrix to the creep cavities. The mechanism responsible for the self-healing can be characterized by a simple model for cavity growth and cavity filling.

  15. Mechanism initiated by nanoabsorber for UV nanosecond-pulse-driven damage of dielectric coatings.

    PubMed

    Wei, Chaoyang; Shao, Jianda; He, Hongbo; Yi, Kui; Fan, Zhengxiu

    2008-03-03

    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.

  16. Role of Buffers in Protein Formulations.

    PubMed

    Zbacnik, Teddy J; Holcomb, Ryan E; Katayama, Derrick S; Murphy, Brian M; Payne, Robert W; Coccaro, Richard C; Evans, Gabriel J; Matsuura, James E; Henry, Charles S; Manning, Mark Cornell

    2017-03-01

    Buffers comprise an integral component of protein formulations. Not only do they function to regulate shifts in pH, they also can stabilize proteins by a variety of mechanisms. The ability of buffers to stabilize therapeutic proteins whether in liquid formulations, frozen solutions, or the solid state is highlighted in this review. Addition of buffers can result in increased conformational stability of proteins, whether by ligand binding or by an excluded solute mechanism. In addition, they can alter the colloidal stability of proteins and modulate interfacial damage. Buffers can also lead to destabilization of proteins, and the stability of buffers themselves is presented. Furthermore, the potential safety and toxicity issues of buffers are discussed, with a special emphasis on the influence of buffers on the perceived pain upon injection. Finally, the interaction of buffers with other excipients is examined.

  17. 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.

  18. 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; K.E. Brown

    2003-02-01

    There are four primary goals of contract DE-FG26-99FT40703: (1) We seek to better understand how and why two damage mechanisms--(1) inorganic precipitants, and (2) hydrocarbons and organic residues, occur at the reservoir/wellbore interface in gas storage wells. (2) We plan on testing potential prevention and remediation strategies related to these two damage mechanisms in the laboratory. (3) We expect to demonstrate in the field, cost-effective prevention and remediation strategies that laboratory testing deems viable. (4) We will investigate new technology for the gas storage industry that will provide operators with a cost effective method to reduce non-darcy turbulent flow effects on flow rate. For the above damage mechanisms, our research efforts will demonstrate the diagnostic technique for determining the damage mechanisms associated with lost deliverability as well as demonstrate and evaluate the remedial techniques in the laboratory setting and in actual gas storage reservoirs. We plan on accomplishing the above goals by performing extensive lab analyses of rotary sidewall cores taken from at least two wells, testing potential remediation strategies in the lab, and demonstrating in the field the applicability of the proposed remediation treatments. The benefits from this work will be quantified from this study and extrapolated to the entire storage industry. The technology and project results will be transferred to the industry through DOE dissemination and through the industry service companies that work on gas storage wells. Achieving these goals will enable the underground gas storage industry to more cost-effectively mitigate declining deliverability in their storage fields. Work completed to date includes the following: (1) Solicited potential participants from the gas storage industry; (2) Selected one participant experiencing damage from inorganic precipitates; (3) Developed laboratory testing procedures; (4) Collected cores from National Fuel Gas

  19. 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 ...

  20. 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.

  1. 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

  2. A novel experimental design method to optimize hydrophilic matrix formulations with drug release profiles and mechanical properties.

    PubMed

    Choi, Du Hyung; Lim, Jun Yeul; Shin, Sangmun; Choi, Won Jun; Jeong, Seong Hoon; Lee, Sangkil

    2014-10-01

    To investigate the effects of hydrophilic polymers on the matrix system, an experimental design method was developed to integrate response surface methodology and the time series modeling. Moreover, the relationships among polymers on the matrix system were studied with the evaluation of physical properties including water uptake, mass loss, diffusion, and gelling index. A mixture simplex lattice design was proposed while considering eight input control factors: Polyethylene glycol 6000 (x1 ), polyethylene oxide (PEO) N-10 (x2 ), PEO 301 (x3 ), PEO coagulant (x4 ), PEO 303 (x5 ), hydroxypropyl methylcellulose (HPMC) 100SR (x6 ), HPMC 4000SR (x7 ), and HPMC 10(5) SR (x8 ). With the modeling, optimal formulations were obtained depending on the four types of targets. The optimal formulations showed the four significant factors (x1 , x2 , x3 , and x8 ) and other four input factors (x4 , x5 , x6 , and x7 ) were not significant based on drug release profiles. Moreover, the optimization results were analyzed with estimated values, targets values, absolute biases, and relative biases based on observed times for the drug release rates with four different targets. The result showed that optimal solutions and target values had consistent patterns with small biases. On the basis of the physical properties of the optimal solutions, the type and ratio of the hydrophilic polymer and the relationships between polymers significantly influenced the physical properties of the system and drug release. This experimental design method is very useful in formulating a matrix system with optimal drug release. Moreover, it can distinctly confirm the relationships between excipients and the effects on the system with extensive and intensive evaluations.

  3. Effects of starches on the mechanical properties of paracetamol tablet formulations. II. Sorghum and plantain starches as disintegrants.

    PubMed

    Alebiowu, Gbenga; Itiola, Oludele Adelanwa

    2003-12-01

    This study evaluates the disintegrant properties--tablet disintegration time (DT) and crushing strength--friability/disintegration time (CSFR/DT) ratio of a paracetamol tablet formulation prepared with sorghum and plantain starches in comparison with corn starch BP. The effects of disintegrant concentration, relative density of tablets and the mode of disintegrants addition were studied. The study revealed that the rank order of effectiveness of the starches as disintegrants was corn > plantain > sorghum. The mode of addition of disintegrants, disintegrant concentration and relative density had a significant impact on the disintegrant properties. The tested starches, namely, sorghum and plantain, showed promising results.

  4. 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).

  5. Gradation of mechanical properties in gas-diffusion electrode. Part 2: Heterogeneous carbon fiber and damage evolution in cell layers

    NASA Astrophysics Data System (ADS)

    Poornesh, K. K.; Cho, C. D.; Lee, G. B.; Tak, Y. S.

    In PEM fuel cell, gas-diffusion electrode (GDE) plays very significant role in force transmission from bipolar plate to the membrane. This paper investigates the effects of geometrical heterogeneities of gas-diffusion electrode layer (gas-diffusion layer (GDL) and catalyst layer (CL)) on mechanical damage evolution and propagation. We present a structural integrity principle of membrane electrode assembly (MEA) based on the interlayer stress transfer capacity and corresponding cell layer material response. Commonly observable damages such as rupture of hydrophobic coating and breakage of carbon fiber in gas-diffusion layer are attributed to the ductile to brittle phase transition within a single carbon fiber. Effect of material inhomogeneity on change in modulus, hardness, contact stiffness, and electrical contact resistance is also discussed. Fracture statistics of carbon fiber and variations in flexural strength of GDL are studied. The damage propagation in CL is perceived to be influenced by the type of gradation and the vicinity from which crack originates. Cohesive zone model has been proposed based on the traction-separation law to investigate the damage propagation throughout the two interfaces (carbon fiber/CL and CL/membrane).

  6. 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.

  7. 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

    2015-11-02

    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.

  8. Sunscreen product formulation.

    PubMed

    Tanner, Paul R

    2006-01-01

    On the surface, sunscreen products are pretty simple. They consist of a delivery vehicle containing one or more sunscreen active ingredients. When applied to the skin, these sunscreen actives intercept solar ultraviolet (UV) rays before they can damage the underlying skin. However, while conceptually simple, a detailed analysis reveals that sunscreen formulations are quite complex, requiring careful selection of sunscreen active and vehicle components to control multiple performance and in-use parameters.Thus, to enable a better understanding and appreciation of sunscreen products, the typical steps in formulating a sunscreen product are described. Throughout this process, the key is to apply scientific principles together with a bit of formulation art to holistically create the best sunscreen product that meets the design targets--a sunscreen product that people will use regularly and properly.

  9. Replication of chromosomal and episomal DNA in X-ray-damaged human cells: A cis- or trans-acting mechanism

    SciTech Connect

    Cleaver, J.E.; Rose, R.; Mitchell, D.L. )

    1990-12-01

    Episomal plasmids and viruses in mammalian cells present small targets for X-ray-induced DNA damage. At doses up to 100 Gy, DNA strand breaks or endonuclease III-sensitive sites were not discernible in 10.3-kb Epstein-Barr virus-based plasmid DNA or in 4.9-kb defective simian virus 40 DNA. DNA replication in these small molecules, however, was inhibited strongly by X-ray doses of greater than or equal to 20 Gy, decreasing to only 20 to 40% of control values. Inhibition was relieved slightly by growth in caffeine but was increased by growth in 3-aminobenzamide. Inhibition of DNA replication in episomal DNA molecules that are too small to sustain significant damage directly to their DNA may be due to either (a) a trans-acting diffusible factor that transfers the consequences of DNA breakage to episomes and to other replicating molecules, (b) a cis-acting mechanism in which episomes are structurally linked to genomic chromatin, and replication of both episomal and chromosomal replicons is under common control, or (c) radiation damage on other cellular structures unrelated to DNA. The resolution of these cellular mechanisms may shed light on the X-ray-resistant replication in ataxia-telangiectasia and may suggest strategies for molecular characterization of potential trans- or cis-acting factors.

  10. 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

  11. [Investigations concerning the mechanism of contrast damage. The significance lipophilia (author's transl)].

    PubMed

    Gottlob, R; Knapp, G; Porschinski, K; Saghir, F

    1980-02-01

    The damaging action on vascular endothelia of meglumin iothalamate and of meglumin ioxitalamate was tested on the rat aorta. Ioxitalamate was significantly better tolerated than iothalamate. The octanol-water-partition coefficient of various contrast media was evaluated by assessing the iodine content of the octanol phase after mixing. The coefficients found were about 100 fold lower than the coefficients computed by Levitan and Rapoport. The significance of the octanol-water-partition coefficient for endothelial injuries caused by contrast media is disputed.

  12. Damage control mechanisms in articular cartilage: the role of the insulin-like growth factor I axis.

    PubMed

    Martin, J A; Scherb, M B; Lembke, L A; Buckwalter, J A

    2000-01-01

    Articular chondrocytes maintain cartilage throughout life by replacing lost or damaged matrix with freshly synthesized material. Synthesis activity is regulated, rapidly increasing to well above basal levels in response to cartilage injury. Such responses suggest that synthesis activity is linked to the rate of matrix loss by endogenous "damage control" mechanisms. As a major stimulator of matrix synthesis in cartilage, insulin-like growth factor I (IGF-I) is likely to play a role in such mechanisms. Although IGF-I is nearly ubiquitous, its bioavailability in cartilage is controlled by IGF-I binding proteins (IGFBPs) secreted by chondrocytes. IGFBPs are part of a complex system, termed the IGF-I axis, that tightly regulates IGF-I activities. For the most part, IGFBPs block IGF-I activity by sequestering IGF-I from its cell surface receptor. We recently found that the expression of one binding protein, IGFBP-3, increases with chondrocyte age, paralleling an age-related decline in synthesis activity. In addition, IGFBP-3 is overexpressed in osteoarthritic cartilage, leading to metabolic disturbances that contribute to cartilage degeneration. These observations indicate that IGFBP-3 plays a crucial role in regulating matrix synthesis in cartilage, and suggest that cartilage damage control mechanisms may fail due to age-related changes in IGFBP-3 expression or distribution. Our investigation of this hypothesis began with immunolocalization studies to determine the tissue distribution of IGFBP-3 in human cartilage. We found that IGFBP-3 accumulated around chondrocytes in the pericellular/territorial matrix, where it co-localized with fibronectin, but not with the other matrix proteins tenascin-C and type VI collagen. This result suggested that the IGFBP-3 distribution is determined by binding to fibronectin. Binding studies using purified proteins demonstrated that IGFBP-3 does in fact bind to fibronectin, but not to tenascin-C or type VI collagen. Finally, we

  13. 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.

  14. Heat-processed Panax ginseng and diabetic renal damage: active components and action mechanism

    PubMed Central

    Kang, Ki Sung; Ham, Jungyeob; Kim, Young-Joo; Park, Jeong Hill; Cho, Eun-Ju; Yamabe, Noriko

    2013-01-01

    Diabetic nephropathy is one of the serious complications in patients with either type 1 or 2 diabetes mellitus but current treatments remain unsatisfactory. Results of clinical research studies demonstrate that Panax ginseng can help adjust blood pressure and reduce blood sugar and may be advantageous in the treatment of tuberculosis and kidney damage in people with diabetes. The heat-processing method to strengthen the efficacy of P. ginseng has been well-defined based on a long history of ethnopharmacological evidence. The protective effects of P. ginseng on pathological conditions and renal damage associated with diabetic nephropathy in the animal models were markedly improved by heat-processing. The concentrations of less-polar ginsenosides (20(S)-Rg3, 20(R)-Rg3, Rg5, and Rk1) and maltol in P. ginseng were significantly increased in a heat-processing temperature-dependent manner. Based on researches in animal models of diabetes, ginsenoside 20(S)-Rg3 and maltol were evaluated to have therapeutic potential against diabetic renal damage. These effects were achieved through the inhibition of inflammatory pathway activated by oxidative stress and advanced glycation endproducts. These findings indicate that ginsenoside 20(S)-Rg3 and maltol are important bioactive constituents of heat-processed ginseng in the control of pathological conditions associated with diabetic nephropathy. PMID:24233065

  15. The Mechanisms of Deformation and Damage of Mudstones: A Micro-scale Study Combining ESEM and DIC

    NASA Astrophysics Data System (ADS)

    Wang, L. L.; Bornert, M.; Héripré, E.; Chanchole, S.; Pouya, A.; Halphen, B.

    2015-09-01

    Combining environmental scanning electron microscopy (ESEM) and digital image correlation techniques, the mechanical behaviour of mudstones is studied at the scale of their composite microstructure (that is, grains of carbonate and quartz embedded in a clay matrix). A specially designed apparatus is developed to allow in-situ uniaxial compression tests on samples with controlled humidity states in the ESEM chamber. As the mechanical behavior of mudstones is sensitive to water content, two tests on samples with contrasting water contents (3.8 and 7.4 %) are performed to identify the unified mechanisms of deformation and damage. We illustrate heterogeneous local strain fields that well correlate with the microstructure of mudstones. Three types of deformation bands involving different mechanisms have been classified: orthogonal (compaction of macro-pores and closure of pre-existing cracks), parallel (micro-cracking) and inclined (shear deformation) to the uniaxial compression direction. These deformation modes are activated at different stress levels, and they strongly interact: for instance, a high-strained shear band may result in tensile micro-cracks at its tip. We also illustrate damage phenomena, particularly at the inclusion-matrix interface, which is found to be a hazardous position for nucleation of micro-cracks.

  16. Efficient repairing effect of PEG based tri-block copolymer on mechanically damaged PC12 cells and isolated spinal cord.

    PubMed

    Rad, Iman; Mobasheri, Hamid; Najafi, Farhood; Rezaei, Maryam

    2014-06-01

    Membrane sealing effects of polymersomes made of tri-block copolymer, PEG-co-FA/SC-co-PEG, (PFSP) were studied on isolated spinal cord strips, PC12 cell lines and artificial bilayer following mechanical impact implemented by aneurism clip, sonication and electric shock, respectively. The homogeneity and size of PFSP, membrane permeability and cell viability were assessed by dynamic light scattering, LDH release and MTT assays. According to the results, the biocompatible, physico-chemical, size, surface charge and amphipathic nature of PFSP polymersome makes it an ideal macromolecule to rapidly reseal damaged membranes of cells in injured spinal cord as well as in culture medium. Compound action potentials recorded from intentionally damaged spinal cord strips incubated with PFSP showed restoration of neural excitability by 82.24 % and conduction velocity by 96.72 % after 5 min that monitored in real time. Thus, they triggered efficient instant and sustained sealing of membrane and reactivation of temporarily inactivated axons. Treatment of ultrasonically damaged PC12 cells by PFSP caused efficient cell membrane repair and led to their increased viability. The optimum effects of PFSP on stabilization and impermeabilizing of the lipid bilayer occurred at the same concentrations applied to the damaged cells and spinal cord fibers and was approved by restoration of membrane conductance and calcein release manifested by NanoDrop technique. The unique physico-chemical characteristics of novel polymersomes introduced here, make them capable to reorganize membrane lipid molecules, reseal the breaches and restore the hydrophobic insulation in spinal cord damaged cells. Thus, they might be considered in the clinical treatment of SCI at early stages.

  17. A systems pharmacology perspective to decipher the mechanism of action of Parangichakkai chooranam, a Siddha formulation for the treatment of psoriasis.

    PubMed

    Sundarrajan, Sudharsana; Arumugam, Mohanapriya

    2017-04-01

    Psoriasis is a chronic relapsing immune mediated disorder of the skin. The disease presents itself with well featured clinical and histological characteristics however the aetiology of the disease still remains obscure. The current systemic therapies aim to eliminate the symptoms of disease rather than offering a complete cure. Parangichakkai chooranam (PC), a Siddha oral herbal formulation has been widely prescribed for the treatment of psoriasis. Though the medication is highly prescribed by the Siddha healers the mechanism of PC for the treatment of psoriasis remains to be elucidated. The current study utilizes an integrated systems pharmacology approach to decipher the mechanism of action of PC. The comprehensive network pharmacological approach resulted in the construction of a Compound-Target network which encloses 155 compounds and 583 protein targets. A Disease-Target network was constructed by assembling disease proteins and their partners. When the compound targets were mapped to the network their involvement as controllers of the disease and triggers of disease associated comorbidities were identified. A Target-Pathway network raised from the pathway enrichment analysis not only identified disease specific pathways but also the pathways mediating secondary complications such as skin hemostasis, wound healing, desquamation and itch. The present work sheds light on the mechanism of action of PC in treating psoriasis. This work not only highlights the pharmacological action of the formulation but also emphasis on safe herbal remedies offered by the Siddha medicinal system.

  18. Eigenproperties of suspension bridges with damage

    NASA Astrophysics Data System (ADS)

    Materazzi, Annibale Luigi; Ubertini, Filippo

    2011-12-01

    The vertical vibration of suspension bridges with a damage in the main cables is studied using a continuum formulation. Starting from a model for damaged suspended cables recently proposed in the literature, an improved expression for the dynamic increment of cable tension is derived. The nonlinear equation of motion of the damaged bridge is obtained by extending this model to include the stiffening girder. The linear undamped modal eigenproperties are then extracted, in closed-form, from the linearized equation of motion, thus generalizing to the presence of an arbitrary damage the expressions known from the literature for undamaged suspension bridges. The linear dynamics of the damaged bridge reveals to be completely described by means of the same two non-dimensional parameters that govern the linear dynamics of undamaged bridges and which account for the mechanical characteristics of both the main cable and the girder, with the addition of three non-dimensional parameters characterizing damage intensity, position and extent. After presenting the mathematical formulation, a parametric analysis is conducted with the purpose of investigating the sensitivity of natural frequencies and mode shapes to damage, which, in fact, is a crucial point concerning damage detection applications using inverse methods. All through the paper, systematic comparisons with finite element simulations are presented for the purpose of model validation.

  19. Formulations and nebulizer performance.

    PubMed

    O'Riordan, Thomas G

    2002-11-01

    To deliver a drug by nebulization, the drug must first be dispersed in a liquid (usually aqueous) medium. After application of a dispersing force (either a jet of gas or ultrasonic waves), the drug particles are contained within the aerosol droplets, which are then inhaled. Some drugs readily dissolve in water, whereas others need a cosolvent such as ethanol or propylene glycol. Some drugs are delivered as suspensions, and the efficiency of nebulizers can be different for solutions and suspensions. Solutions are delivered more efficiently with most devices. In general, conventional ultrasonic nebulizers should not be used to aerosolize suspensions, because of low efficiency. Newer strategies to improve the delivery of non-water-soluble drugs include the use of liposomes and the milling of the drug into very small "nanoparticles." In addition to the active therapeutic ingredient and solvents, drug formulations may include buffers (the solubility of some medications is influenced by pH), stabilizers, and, in the case of multi-dose preparations, antibacterial agents. Though formulations are designed to optimize drug solubility and stability, changes in formulation can also affect inhaled mass, particle size, and treatment time, though the differences between nebulizer brands probably have a greater impact than differences in formulation. Ultrasonic and jet nebulizers may damage protein and other complex agents through heat or shear stress. Additives to multi-dose formulations, especially antimicrobial and chelating agents, may cause adverse events, so there is a trend towards single-use, preservative-free vials.

  20. 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.

  1. Cellular and molecular mechanisms of bone damage and repair in inflammatory arthritis.

    PubMed

    Swales, Catherine; Sabokbar, Afsie

    2014-08-01

    Bone remodelling relies on tightly controlled cycles of bone resorption and formation, mediated by osteoclasts and osteoblasts, respectively. The past two decades have seen a huge increase in our understanding of immune modulation and disruption of bone homeostasis in rheumatic diseases; identification of the molecular pathways responsible for accelerated bone loss in such conditions has given rise to potential novel therapeutic targets. Most recently, the role of microRNAs in inflammatory and noninflammatory bone loss raises the intriguing possibility that modification of cellular protein translation could also be a treatment strategy for bone damage.

  2. 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.

  3. 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

  4. A numerical investigation of crevasse propagation and stability of calving glaciers using nonlocal continuum damage mechanics

    NASA Astrophysics Data System (ADS)

    Duddu, R.; Bassis, J. N.; Waisman, H.

    2012-12-01

    We investigate iceberg calving from grounded tidewater and outlet glaciers using a novel creep continuum damage model for polycrystalline ice, which is valid for low stresses or strain rates. The proposed three-dimensional model is based on a thermo-viscoelastic constitutive law for ice creep and a nonlocal damage accumulation law for tension, compression and shear loadings. The model has been validated by published experimental data and is implemented in the commercially available finite element code ABAQUS by adopting a strain-based algorithm using a Lagrangian description. The model is then used to investigate conditions that enable surface crevasse propagation resulting from different boundary conditions applied to an idealized rectangular slab of ice in contact with the ocean. The basal boundary condition of the ice slab is varied from free slip to fixed (no slip) to study its effect on surface crack (crevasse) growth. The depth varying ice flow velocities lead to tensile stresses in the top region of the ice slab that leads to surface crevasse propagation. The simulation results suggest that if the ice slab is thick enough and the water depth small enough, surface crevasses will penetrate the entire ice thickness. On the other hand, if the ice slab is thin and water depth sufficiently large, crevasses will not penetrate the ice thickness.

  5. 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.

  6. Recent progresses on insights of laser damage mechanisms and influence of contamination in optics

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

    In high power laser system, laser-induced damage threshold (LIDT) in optical coating is very important for obtaining high performances. The dependence of LIDT on the pulse duration and the repetition rate are well known phenomena. But recently, LIDT was found to have strong temperature dependences in the bulk, surface of substrates, and in coatings. This temperature dependence of LIDT was carefully measured, and the damage formation model was constructed regarding to this temperature dependence. This paper introduces LFEX laser system for First Ignition scheme in the laser fusion. A large-scale pulse compression chamber was designed and constructed, and segmented grating system has been employed for large-scale pulse compressor. This compressor provided good pulse compression performances, but we observed a heavy oil-contamination of optics in this chamber. We have analyzed contaminants and evaluated the effects of the contamination. We also developed new cleaning methods to remove contamination from the coating, and the quantitative analysis of contamination on LIDT was made. We have investigated the characteristics of LIDT in dielectric coatings under the controlled contamination. LIDT of coating drops to 1/2 in the saturated toluene vapor at room temperature.

  7. The interplay among chromatin dynamics, cell cycle checkpoints and repair mechanisms modulates the cellular response to DNA damage.

    PubMed

    Lazzaro, Federico; Giannattasio, Michele; Muzi-Falconi, Marco; Plevani, Paolo

    2007-06-01

    Cells are continuously under the assault of endogenous and exogenous genotoxic stress that challenges the integrity of DNA. To cope with such a formidable task cells have evolved surveillance mechanisms, known as checkpoints, and a variety of DNA repair systems responding to different types of DNA lesions. These lesions occur in the context of the chromatin structure and, as expected for all DNA transactions, the cellular response to DNA damage is going to be influenced by the chromatin enviroment. In this review, we will discuss recent studies implicating chromatin remodelling factors and histone modifications in the response to DNA double-strand breaks (DSBs) and in checkpoint activation in response to UV lesions.

  8. Proposal of a new degradation mechanism of enalapril maleate and improvement of enalapril maleate stability in tablet formulation with different stabilizers.

    PubMed

    Chen, J; Zhang, L H; Xu, R J; Bu, N J; Zhang, L

    2014-04-01

    Enalapril maleate (EM) is unstable in poorly designed tablet formulations. To improve the stability of EM, the degradation mechanism should be elucidated. In this study, we found that several commonly used excipients promoted the degradants of EM, particularly a diketopiperazine derivative (DKP). We propose two degradation pathways in which both acid and alkali can promote the formation of DKP, although previous reports suggested that DKP is produced mainly in acidic media. Based on the degradation pathways, we believe that subtle control of the microenvironmental pH can inhibit the formation of DKP. This was confirmed by the observation that the degradation rate became slower when certain organic acids were added to the binary mixtures of EM and excipient. The data showed that the stability of EM in the ternary mixtures was much higher than that in binary mixtures. It was further proved that tablets containing these organic acids produced less DKP after the accelerated test. We also found that the formation of DKP in tablets varied with different ratios of tartaric acid, which was used as a model organic acid. This illustrated that an optimum ratio of tartaric acid is required. These results indicated that the stability of EM in tablet formulation is closely associated with microenvironmental pH and the addition of a suitable organic acid based on the reaction mechanism is an effective strategy for improving the stability of EM.

  9. Interaction and oxidative damage of DVDMS to BSA: a study on the mechanism of photodynamic therapy-induced cell death.

    PubMed

    Li, Li; Wang, Huiyu; Wang, Haiping; Li, Lijun; Wang, Pan; Wang, Xiaobing; Liu, Quanhong

    2017-03-02

    Photodynamic therapy (PDT) is a promising method for neoplastic and nonneoplastic diseases. In this study, we utilized sinoporphyrin sodium (DVDMS) as a sensitizer combined with light to investigate its cytotoxic effect on different cell lines. For this purpose, we chose bovine serum albumin (BSA) as a model to explore the mechanism of PDT-induced cell death at a molecular level. Our findings indicated that the combined treatment significantly suppressed cell survival. Fluorescence spectroscopy revealed a strong interaction between DVDMS and BSA molecules in aqueous solution, affecting DVDMS' targeting distribution and metabolism. Spectroscopic analysis and carbonyl content detection indicated that DVDMS-PDT significantly enhanced the damage of BSA at a higher extent than Photofrin II-PDT under similar experimental conditions. Our observations were consistent with the cytotoxicity results. Excessive reactive oxygen species (ROS) were induced by the synergy effect of the sensitizer and light, which played an important role in damaging BSA and tumor cells. These results suggested that the interaction and oxidative damage of protein molecules by DVDMS were the main reasons to cell death and constitute a valuable reference for future DVDMS-PDT investigations.

  10. 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.

  11. Mutagenicity associated with O6-methylguanine-DNA damage and mechanism of nucleotide flipping by AGT during repair

    NASA Astrophysics Data System (ADS)

    Jena, N. R.; Bansal, Manju

    2011-08-01

    Methylated guanine damage at O6 position (i.e. O6MG) is dangerous due to its mutagenic and carcinogenic character that often gives rise to G:C-A:T mutation. However, the reason for this mutagenicity is not known precisely and has been a matter of controversy. Further, although it is known that O6-alkylguanine-DNA alkyltransferase (AGT) repairs O6MG paired with cytosine in DNA, the complete mechanism of target recognition and repair is not known completely. All these aspects of DNA damage and repair have been addressed here by employing high level density functional theory in gas phase and aqueous medium. It is found that the actual cause of O6MG mediated mutation may arise due to the fact that DNA polymerases incorporate thymine opposite to O6MG, misreading the resulting O6MG:T complex as an A:T base pair due to their analogous binding energies and structural alignments. It is further revealed that AGT mediated nucleotide flipping occurs in two successive steps. The intercalation of the finger residue Arg128 into the DNA double helix and its interaction with the O6MG:C base pair followed by rotation of the O6MG nucleotide are found to be crucial for the damage recognition and nucleotide flipping.

  12. Interaction and oxidative damage of DVDMS to BSA: a study on the mechanism of photodynamic therapy-induced cell death

    PubMed Central

    Li, Li; Wang, Huiyu; Wang, Haiping; Li, Lijun; Wang, Pan; Wang, Xiaobing; Liu, Quanhong

    2017-01-01

    Photodynamic therapy (PDT) is a promising method for neoplastic and nonneoplastic diseases. In this study, we utilized sinoporphyrin sodium (DVDMS) as a sensitizer combined with light to investigate its cytotoxic effect on different cell lines. For this purpose, we chose bovine serum albumin (BSA) as a model to explore the mechanism of PDT-induced cell death at a molecular level. Our findings indicated that the combined treatment significantly suppressed cell survival. Fluorescence spectroscopy revealed a strong interaction between DVDMS and BSA molecules in aqueous solution, affecting DVDMS’ targeting distribution and metabolism. Spectroscopic analysis and carbonyl content detection indicated that DVDMS-PDT significantly enhanced the damage of BSA at a higher extent than Photofrin II-PDT under similar experimental conditions. Our observations were consistent with the cytotoxicity results. Excessive reactive oxygen species (ROS) were induced by the synergy effect of the sensitizer and light, which played an important role in damaging BSA and tumor cells. These results suggested that the interaction and oxidative damage of protein molecules by DVDMS were the main reasons to cell death and constitute a valuable reference for future DVDMS-PDT investigations. PMID:28252029

  13. Neonatal tissue damage facilitates nociceptive synaptic input to the developing superficial dorsal horn via NGF-dependent mechanisms

    PubMed Central

    Li, Jie; Baccei, Mark L.

    2011-01-01

    Tissue injury during a critical period of early life can facilitate spontaneous glutamatergic transmission within developing pain circuits in the superficial dorsal horn (SDH) of the spinal cord. However, the extent to which neonatal tissue damage strengthens nociceptive synaptic input to specific subpopulations of SDH neurons, as well as the mechanisms underlying this distinct form of synaptic plasticity, remains unclear. Here we use in vitro whole-cell patch clamp recordings from rodent spinal cord slices to demonstrate that neonatal surgical injury selectively potentiates high-threshold primary afferent input to immature lamina II neurons. In addition, the increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs) after hindpaw incision was prevented by neonatal capsaicin treatment, suggesting that early tissue injury enhances glutamate release from nociceptive synapses. This occurs in a widespread manner within the developing SDH, as incision elevated mEPSC frequency in both GABAergic and presumed glutamatergic lamina II neurons of Gad-GFP transgenic mice. The administration of exogenous nerve growth factor (NGF) into the rat hindpaw mimicked the effects of early tissue damage on excitatory synaptic function, while blocking trkA receptors in vivo abolished the changes in both spontaneous and primary afferent-evoked glutamatergic transmission following incision. These findings illustrate that neonatal tissue damage can alter the gain of developing pain pathways by activating NGF-dependent signaling cascades which modify synaptic efficacy at the first site of nociceptive processing within the CNS. PMID:21550171

  14. 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.

  15. 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

  16. An approach for generating trajectory-based dynamics which conserves the canonical distribution in the phase space formulation of quantum mechanics. II. Thermal correlation functions

    SciTech Connect

    Liu Jian; Miller, William H.

    2011-03-14

    We show the exact expression of the quantum mechanical time correlation function in the phase space formulation of quantum mechanics. The trajectory-based dynamics that conserves the quantum canonical distribution-equilibrium Liouville dynamics (ELD) proposed in Paper I is then used to approximately evaluate the exact expression. It gives exact thermal correlation functions (of even nonlinear operators, i.e., nonlinear functions of position or momentum operators) in the classical, high temperature, and harmonic limits. Various methods have been presented for the implementation of ELD. Numerical tests of the ELD approach in the Wigner or Husimi phase space have been made for a harmonic oscillator and two strongly anharmonic model problems, for each potential autocorrelation functions of both linear and nonlinear operators have been calculated. It suggests ELD can be a potentially useful approach for describing quantum effects for complex systems in condense phase.

  17. An approach for generating trajectory-based dynamics which conserves the canonical distribution in the phase space formulation of quantum mechanics. I. Theories.

    PubMed

    Liu, Jian; Miller, William H

    2011-03-14

    We have reformulated and generalized our recent work [J. Liu and W. H. Miller, J. Chem. Phys. 126, 234110 (2007)] into an approach for generating a family of trajectory-based dynamics methods in the phase space formulation of quantum mechanics. The approach (equilibrium Liouville dynamics) is in the spirit of Liouville's theorem in classical mechanics. The trajectory-based dynamics is able to conserve the quantum canonical distribution for the thermal equilibrium system and approaches classical dynamics in the classical (ℏ → 0), high temperature (β → 0), and harmonic limits. Equilibrium Liouville dynamics provides the framework for the development of novel theoretical∕computational tools for studying quantum dynamical effects in large∕complex molecular systems.

  18. An approach for generating trajectory-based dynamics which conserves the canonical distribution in the phase space formulation of quantum mechanics. I. Theories

    NASA Astrophysics Data System (ADS)

    Liu, Jian; Miller, William H.

    2011-03-01

    We have reformulated and generalized our recent work [J. Liu and W. H. Miller, J. Chem. Phys. 126, 234110 (2007)] into an approach for generating a family of trajectory-based dynamics methods in the phase space formulation of quantum mechanics. The approach (equilibrium Liouville dynamics) is in the spirit of Liouville's theorem in classical mechanics. The trajectory-based dynamics is able to conserve the quantum canonical distribution for the thermal equilibrium system and approaches classical dynamics in the classical (ℏ → 0), high temperature (β → 0), and harmonic limits. Equilibrium Liouville dynamics provides the framework for the development of novel theoretical/computational tools for studying quantum dynamical effects in large/complex molecular systems.

  19. An approach for generating trajectory-based dynamics which conserves the canonical distribution in the phase space formulation of quantum mechanics. II. Thermal correlation functions

    NASA Astrophysics Data System (ADS)

    Liu, Jian; Miller, William H.

    2011-03-01

    We show the exact expression of the quantum mechanical time correlation function in the phase space formulation of quantum mechanics. The trajectory-based dynamics that conserves the quantum canonical distribution-equilibrium Liouville dynamics (ELD) proposed in Paper I is then used to approximately evaluate the exact expression. It gives exact thermal correlation functions (of even nonlinear operators, i.e., nonlinear functions of position or momentum operators) in the classical, high temperature, and harmonic limits. Various methods have been presented for the implementation of ELD. Numerical tests of the ELD approach in the Wigner or Husimi phase space have been made for a harmonic oscillator and two strongly anharmonic model problems, for each potential autocorrelation functions of both linear and nonlinear operators have been calculated. It suggests ELD can be a potentially useful approach for describing quantum effects for complex systems in condense phase.

  20. Atomic level observations of mechanical damage in shot peened TiAl

    NASA Astrophysics Data System (ADS)

    Appel, Fritz

    2013-01-01

    High-resolution transmission microscopy has been used to reveal the defect processes occurring during shot peening of a high-strength titanium aluminide alloy with a nearly lamellar microstructure. Deformation is characterised by intensive dislocation glide and mechanical twinning, involving all potential slip systems available in the α2(Ti3Al) and γ(TiAl) phases. The outermost surface layer consists of extremely fine crystals that are probably a contaminant titanium nitride phase, embedded into an amorphous phase. The mechanisms involved in this mechanically driven solid state transformation will be elucidated. Particular emphasis is paid on the thermodynamic and kinetic factors involved in the amorphisation reaction.

  1. 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.

  2. Shock-induced damage to mitochondrial function and some cellular antioxidant mechanisms in humans.

    PubMed

    Corbucci, G G; Gasparetto, A; Candiani, A; Crimi, G; Antonelli, M; Bufi, M; De Blasi, R A; Cooper, M B; Gohil, K

    1985-01-01

    The effects of circulatory shock on skeletal muscle mitochondrial oxidative activity in various substrates and cytochrome oxidase activity have been investigated using samples of muscle obtained by the needle biopsy technique from human subjects. The effect of shock on superoxide dismutase activity and glutathione content of skeletal muscle was also examined. The results show that there is a large decrease in cytochrome oxidase activity during shock and also in the capacity of the mitochondria to oxidize either succinate, or pyruvate, or palmitoyl carnitine. There is a fall in the tissue content of superoxide dismutase and in the total glutathione present. Furthermore, an increased oxidized glutathione content causes a decrease in the molar ratio of reduced to oxidized glutathione present in the muscle. These findings suggest that mitochondrial electron transport chain (ETC) oxidative damage can play a relevant role in the pathogenesis of circulatory shock and support the hypothesis of oxygen-free radical involvement in the cellular injury.

  3. Theoretical analyses on a flipping mechanism of UV-induced DNA damage

    PubMed Central

    Sato, Ryuma; Harada, Ryuhei; Shigeta, Yasuteru

    2016-01-01

    As for UV-induced DNA damage, which may induce skin cancer in animals and growth inhibition in plants, there are two types of photoproducts, namely cis-sin cyclobutane pyrimidine dimers (CPD) and pyrimidine-pyrimidone (6-4) photoproducts. When they are to be repaired, base-flipping occurs, and they bind to enzymes. However, this process remains relatively unknown at a molecular level. We analyze conformation and interaction energy changes upon base-flipping using classical molecular dynamics (CMD) simulations and ab initio electronic structure calculations. CMD simulations starting with a CPD in the flipped-in and flipped-out states showed that both states were unchanged for 500 ns, indicating the flipped-in and flipped-out processes do not occur spontaneously (without any help of the enzyme) after photo-damage. To deeply understand the reasons, we investigated interaction energy changes among bases upon structure changes during the flipped-in and flipped-out processes using Parallel Cascade Selection-MD (PaCS-MD) simulations at 400 K, followed by a fragment molecular orbital (FMO) method. The total inter-fragment interaction energy (IFIE) between CPD and other bases at the flipped-in state is estimated to be −60.08 kcal/mol. In particular, four bases strongly interact with CPD with interaction energies being −10.96, −13.70, −21.52, and −14.46 kcal/mol each. On the other hand, the total IFIE at the obtained flipped-out state increased to −10.40 kcal/mol by partly losing hydrogen bonds and π-π stacking interactions, respectively. These results clearly indicate that the base-flipping process of DNA lesions occurs with the help of external forces like interactions with appropriate enzymes such as photolyases.

  4. 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

  5. Oxidative damage: the biochemical mechanism of cellular injury and necrosis in choline deficiency.

    PubMed

    Repetto, Marisa G; Ossani, Georgina; Monserrat, Alberto J; Boveris, Alberto

    2010-02-01

    Oxidative stress and damage are characterized by decreased tissue antioxidant levels, consumption of tissue alpha-tocopherol, and increased lipid peroxidation. These processes occur earlier than necrosis in the liver, heart, kidney, and brain of weanling rats fed a choline deficient (CD) diet. In tissues, water-soluble antioxidants were analyzed as total reactive antioxidant potential (TRAP), alpha-tocopherol content was estimated from homogenate chemiluminescence (homogenate-CL), and lipid peroxidation was evaluated by thiobarbituric acid reactive substances (TBARS). Histopathology showed hepatic steatosis at days 1-7, tubular and glomerular necrosis in kidney at days 6 and 7, and inflammation and necrosis in heart at days 6 and 7. TRAP levels decreased by 18%, 48%, 56%, and 66% at day 7, with t(1/2) (times for half maximal change) of 2.0, 1.8, 2.5, and 3.0 days in liver, kidney, heart, and brain, respectively. Homogenate-CL increased by 97%, 113%, 18%, and 297% at day 7, with t(1/2) of 2.5, 2.6, 2.8, and 3.2 days in the four organs, respectively. TBARS contents increased by 98%, 157%, 104%, and 347% at day 7, with t(1/2) of 2.6, 2.8, 3.0, and 5.0 days in the four organs, respectively. Plasma showed a 33% decrease in TRAP and a 5-fold increase in TBARS at day 5. Oxidative stress and damage are processes occurring earlier than necrosis in the kidney and heart. In case of steatosis prior to antioxidant consumption and increased lipid peroxidation, no necrosis is observed in the liver.

  6. Damage Tolerance Assessment Handbook. Volume 1. Introduction Fracture Mechanics Fatigue Crack Propagation

    DTIC Science & Technology

    1993-10-01

    Volume ,: Introduction NJ 08405 Fracture Mechanics Fatigue Crack Propagation Research and Special Programs Administration John A. Volpe National...Load-displacement plot [Adapted from John M. Barson/Stanley T. Rolfe, Fracture and Fatigue Control in Structures. Applications of Fracture Mechanics...Methods ASTM STP 527, American Society for Testing and Materials, Philadelphia, PA, 1973. 2-19. Ratwani, M.M. and Wilhem , DP. Develonment and EvaluAtion of

  7. Oxidative damage to human parametrial ligament fibroblasts induced by mechanical stress.

    PubMed

    Hong, Shasha; Li, Hong; Wu, Debin; Li, Bingshu; Liu, Cheng; Guo, Wenjun; Min, Jie; Hu, Ming; Zhao, Yang; Yang, Qing

    2015-10-01

    The aim of the present study was to explore the underlying mechanisms of the roles of mechanical factors in the pathogenesis of pelvic organ prolapse (POP). The experiments were performed on fibroblasts derived from uterosacral ligaments and cardinal ligaments of patients who received total hysterectomy due to benign disease excluding POP. Fibroblasts were cultured after collagenase digestion and identified by morphological observation and immunocytochemical methods. A four‑point bending device was used to subject fibroblasts at passage 4‑6 to strains of 0, 1,333 µ (1 mm), 2,666 µ (2 mm) or 5,333 µ (4 mm) at a frequency of 0.1 Hz for 4 h. Intracellular reactive oxygen species (ROS) were quantified using the fluorescent probe 2',7'‑dichlorodihydrofluorescein diacetate. Changes in the mitochondrial membrane potential were verified using the fluorescent dye JC‑1, and apoptosis was detected using Annexin V/propidium iodide staining and flow cytometric analysis. Mechanical strain changed the morphology and adherence ability of parametrial ligament fibroblasts. Furthermore, the production of ROS was significantly increased and the mitochondrial membrane potential obviously declined with the enhancement of mechanical stress loading. In addition, the apoptotic rate of fibroblasts subjected to high mechanical strain was significantly increased compared with that in fibroblast under low‑intensity strain. In conclusion, the present study showed that mechanical strain enhanced intracellular ROS levels, decreased the mitochondrial membrane potential and increased the apoptotic rate in human parametrial ligament fibroblasts, which may contribute to POP.

  8. Nanomicelle formulation for topical delivery of cyclosporine A into the cornea: in vitro mechanism and in vivo permeation evaluation

    PubMed Central

    Guo, Chuanlong; Zhang, Yan; Yang, Zhao; Li, Mengshuang; Li, Fengjie; Cui, Fenghua; Liu, Ting; Shi, Weiyun; Wu, Xianggen

    2015-01-01

    A stable topical ophthalmic cyclosporine A (CsA) formulation with good tolerance and high efficacy is still a desire in pharmaceutics and clinics. This article describes the preparation of CsA containing nanomicelles using a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCL-PVA-PEG) graft copolymer. Both the polymer itself and the CsA nanomicelles were evaluated for cytotoxicity and ocular irritation. The in vitro uptake and intracellular fate of nanomicelles were characterized. In vivo cornea permeation test performed with 0.5 mg/mL CsA containing nanomicelles, and compared with a commercially available CsA (10 mg/mL) oil-based ophthalmic solution. The CsA nanomicelle ophthalmic solution was simple to prepare and remained storage stable. PVCL-PVA-PEG had no cytotoxicity as its monomer solution, and as its micelle solution (IC50(48 h) = 14.02 mg/mL). CsA nanomicelles also had excellent ocular tolerance in rabbits. The use of nanomicelles significantly improved in vitro cellular uptake, apparently by an energy dependent intracellular endocytosis pathway that involved early endosomes, late endosomes, lysosomes, and ER. In vivo permeation showed that 0.5 mg/mL CsA nanomicelles delivered high levels of CsA into the cornea, when compared to the oil-based 10 mg/mL CsA ophthalmic solution. These findings indicated PVCL-PVA-PEG nanomicelles could be a promising topical delivery system for ocular administration of CsA.

  9. 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...

  10. Oxidative stress as a damage mechanism in porcine cumulus-oocyte complexes exposed to malathion during in vitro maturation.

    PubMed

    Flores, Diana; Souza, Verónica; Betancourt, Miguel; Teteltitla, Mario; González-Márquez, Humberto; Casas, Eduardo; Bonilla, Edmundo; Ramírez-Noguera, Patricia; Gutiérrez-Ruíz, María Concepción; Ducolomb, Yvonne

    2017-02-10

    Malathion is one of the most commonly used insecticides. Recent findings have demonstrated that it induces oxidative stress in somatic cells, but there are not enough studies that have demonstrated this effect in germ cells. Malathion impairs porcine oocyte viability and maturation, but studies have not shown how oxidative stress damages maturation and which biochemical mechanisms are affected in this process in cumulus-oocyte complexes (COCs). The aims of the present study were to determine the amount of oxidative stress produced by malathion in porcine COCs matured in vitro, to define how biochemical mechanisms affect this process, and determine whether trolox can attenuate oxidative damage. Sublethal concentrations 0, 750, and 1000 µM were used to evaluate antioxidant enzyme expressions, reactive oxygen species (ROS production), protein oxidation, and lipid peroxidation, among other oxidation products. COCs viability and oocyte maturation decreased in a concentration-dependent manner. Malathion increased Cu, Zn superoxide dismutase (SOD1), glutathione-S-transferase (GST), and glucose 6 phosphate dehydrogenase (G6PD) protein level and decreased glutathione peroxidase (GSH-Px) and catalase (CAT) protein level. Species reactives of oxygen (ROS), protein oxidation and Thiobarbituric acid reactive substances (TBARS) levels increased in COCs exposed to the insecticide, but when COCs were pre-treated with the trolox (50 µM) 30 min before and during malathion exposure, these parameters decreased down to control levels. This study showed that malathion has a detrimental effect on COCs during in vitro maturation, inducing oxidative stress, while trolox attenuated malathion toxicity by decreasing oxidative damage.

  11. 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.

  12. 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.

  13. 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.

  14. Molecular ageing of alpha- and Beta-synucleins: protein damage and repair mechanisms.

    PubMed

    Vigneswara, Vasanthy; Cass, Simon; Wayne, Declan; Bolt, Edward L; Ray, David E; Carter, Wayne G

    2013-01-01

    Abnormal α-synuclein aggregates are hallmarks of a number of neurodegenerative diseases. Alpha synuclein and β-synucleins are susceptible to post-translational modification as isoaspartate protein damage, which is regulated in vivo by the action of the repair enzyme protein L-isoaspartyl O-methyltransferase (PIMT). We aged in vitro native α-synuclein, the α-synuclein familial mutants A30P and A53T that give rise to Parkinsonian phenotypes, and β-synuclein, at physiological pH and temperature for a time course of up to 20 days. Resolution of native α-synuclein and β-synuclein by two dimensional techniques showed the accumulation of a number of post-translationally modified forms of both proteins. The levels of isoaspartate formed over the 20 day time course were quantified by exogenous methylation with PIMT using S-Adenosyl-L-[(3)H-methyl]methionine as a methyl donor, and liquid scintillation counting of liberated (3)H-methanol. All α-synuclein proteins accumulated isoaspartate at ∼1% of molecules/day, ∼20 times faster than for β-synuclein. This disparity between rates of isoaspartate was confirmed by exogenous methylation of synucleins by PIMT, protein resolution by one-dimensional denaturing gel electrophoresis, and visualisation of (3)H-methyl esters by autoradiography. Protein silver staining and autoradiography also revealed that α-synucleins accumulated stable oligomers that were resistant to denaturing conditions, and which also contained isoaspartate. Co-incubation of approximately equimolar β-synuclein with α-synuclein resulted in a significant reduction of isoaspartate formed in all α-synucleins after 20 days of ageing. Co-incubated α- and β-synucleins, or α, or β synucleins alone, were resolved by non-denaturing size exclusion chromatography and all formed oligomers of ∼57.5 kDa; consistent with tetramerization. Direct association of α-synuclein with β-synuclein in column fractions or from in vitro ageing co-incubations was

  15. A servo-mechanical load frame for in situ, non-invasive, imaging of damage development

    SciTech Connect

    Breunig, T.M.; Nichols, M.C.; Gruver, J.S.; Kinney, J.H.; Haupt, D.L.

    1993-12-31

    The X-ray tomographic microscope (XTM) is a non-invasive X-ray imaging instrument for characterizing a material`s structure three-dimensionally with microscopic spatial resolution. The authors have designed a servomechanical load frame for use with the XTM which will allow imaging of samples under load. The load frame is capable of generating tensile or compressive forces up to 15.6 kN with a design system stiffness of 8.76 {times} 10{sup 8} N/m. The test specimen can be rotated through 360{degree}, without induced bending or torque. Torqueless motion is accomplished by synchronously rotating the grips on precision bearings with an accuracy of 0.01{degree}. With this load frame it will be possible, for the first time, to image the initiation and accumulation of internal damage (0.5 {mu}m detectability) formed in a 6 mm diameter specimen during the application of a monotonic or low frequency cyclic load. This is accomplished by interrupting the test and maintaining a fixed load (or displacement) during the non-invasive XTM data collection procedure. This paper describes the in situ load frame design and experimental capabilities. This system can be used to enhance the understanding of failure in composite materials.

  16. Discovery of photochemical damage mechanisms using in vitro and in silico models

    NASA Astrophysics Data System (ADS)

    Fink, Pamela K.; Denton, Michael L.; Castellanos, Cherry C.; Tijerina, Amanda J.; Schuster, Kurt J.; Oliver, Jeffrey W.

    2013-02-01

    A computer-based model has been built that simulates the response of the retinal pigmented epithelial (RPE) cell to laser exposure in the photochemical (non-thermal) damage exposure range (>= 100 s exposures). The modeling approach used is knowledge-based, modular, and hierarchical, allowing the explicit modeling of the cascades of intracellular events in response to laser application. Thus, the model can be used to both analyze existing in vitro data sets, as well as efficiently direct sampling strategies for future in vitro and in vivo studies. This model has been validated using laboratory data from several studies reported in the literature using blue light (413 nm and 458 nm) lasers with 100 s, 200 s, and 3600 s exposure durations. The model was able to predict the in vitro ED50 response curve from these studies, as well as the results for which we have no in vitro data (extrapolated based on irradiance reciprocity), within 1-6% for the shorter duration exposures. Based on exploration of this computer model using lethal vs. non-lethal laser exposure scenarios, the RPE cell's oxidative stress response differs quantitatively very little with respect to typical oxidative stress sources such as superoxide and hydrogen peroxide. However, in the lethal exposure scenarios the model points to a potential tipping point in the oxidative stress response of the mitochondrial-based cellular energetics. Further studies are underway to explore issues related to the levels of ATP/ADP and GSH/GSSG that are predicted by the model in these lethal vs. non-lethal exposure scenarios.

  17. Mechanisms of Oxidative Damage in Multiple Sclerosis and Neurodegenerative Diseases: Therapeutic Modulation via Fumaric Acid Esters

    PubMed Central

    Lee, De-Hyung; Gold, Ralf; Linker, Ralf A.

    2012-01-01

    Oxidative stress plays a crucial role in many neurodegenerative conditions such as Alzheimer’s disease, amyotrophic lateral sclerosis and Parkinson’s as well as Huntington’s disease. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis (MS). Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic-progressive MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Here, fumaric acid esters (FAE) are a new, orally available treatment option which had already been tested in phase II/III MS trials demonstrating beneficial effects on relapse rates and magnetic resonance imaging markers. In vitro, application of dimethylfumarate (DMF) leads to stabilization of Nrf2, activation of Nrf2-dependent transcriptional activity and abundant synthesis of detoxifying proteins. Furthermore, application of FAE involves direct modification of the inhibitor of Nrf2, Kelch-like ECH-associated protein 1. On cellular levels, the application of FAE enhances neuronal survival and protects astrocytes against oxidative stress. Increased levels of Nrf2 are detected in the central nervous system of DMF treated mice suffering from experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In EAE, DMF ameliorates the disease course and improves preservation of myelin, axons and neurons. Finally, Nrf2 is also up-regulated in the spinal cord of autopsy specimens from untreated patients with MS, probably as part of a naturally occurring anti-oxidative response. In summary, oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapies like FAE. PMID:23109883

  18. 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.

  19. 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.

  20. Camptothecin resistance in cancer: insights into the molecular mechanisms of a DNA-damaging drug.

    PubMed

    Beretta, G L; Gatti, L; Perego, P; Zaffaroni, N

    2013-01-01

    Poisoning of DNA topoisomerase I is the mechanism by which camptothecins interfere with tumor growth. Although the clinical use of camptothecins has had a significant impact on cancer therapy, de novo or acquired clinical resistance to these drugs is common. Clinical resistance to camptothecins is still a poorly understood phenomenon, likely involving pharmacological and tumor-related factors. Experimental models including yeast and mammalian cell cultures suggest three general mechanisms of camptothecin resistance: i) reduced cellular accumulation of drugs, ii) alteration in the structure/expression of topoisomerase I, and iii) alterations in the cellular response to camptothecin-DNA-ternary complex formation. Some lines of evidence have also suggested links between cellular camptothecin resistance, the existence of a subset of tumor-initiating cells and miRNA deregulation. In this regard, a better definition of the molecular events clarifying the regulation of tumorigenesis and gene expression might contribute to gain insight into the molecular mechanisms on the basis of camptothecin resistance of tumors and to identify new molecular tools for targeting cancer cells. The relevance of these mechanisms to clinical drug resistance has not yet been completely defined, but their evaluation in clinical specimens should help to define personalized treatments including camptothecins as single agents or in combination with other cytotoxic and target-specific anticancer agents. The present review focuses on the cellular/ molecular aspects involved in resistance of tumor cells to camptothecins, including the potential role of cancer stem cells and deregulated miRNAs, and on the approaches proposed for overcoming resistance.

  1. 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.

  2. 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.

  3. Influence of dietary carbohydrate on zinc-deficiency-induced changes in oxidative defense mechanisms and tissue oxidative damage in rats.

    PubMed

    Kim, S H; Keen, C L

    1999-10-01

    The aim of this study was to determine the effect of dietary carbohydrate type on the expression of zinc (Zn) deficiency in rats with respect to tissue oxidative damage and defense mechanisms. Rats were fed diets containing adequate (+Zn) or low concentrations (-Zn) of Zn. Both fructose- and glucose-based diets were tested. Pair-fed controls were also studied to evaluate changes in the oxidative defense system which are secondary to Zn-deficiency-induced anorexia. Plasma and liver Zn concentrations and CuZn superoxide dismutase activities were lower in the -Zn rats than in the +Zn rats. Liver glutathione (GSH) and disulfide glutathione concentrations were higher in the -Zn rats than in the +Zn rats; this difference was most pronounced in the fructose groups. Liver and heart selenium glutathione peroxidase (Se-GSH-Px) activities were lower in the -Zn-fructose group than in the +Zn-fructose group. Liver Se-GSH-Px activity was higher in the fructose groups than in the glucose groups. Liver GSH reductase (GSH-Red) activity was lower in the -Zn-fructose group than in its control group. Liver glutamine synthetase activity was lower in the -Zn-glucose group and in the fructose groups than in the glucose control group. Liver thiobarbituric acid reactive substance (TBARS) production was similar among the groups. Collectively, these results support the concept that Zn deficiency can result in an impaired oxidant defense system. Based on the observation that pair-fed control animals also showed evidence of oxidative damage, we suggest that one factor that contributes to the effect of Zn deficiency is the reduction in caloric intake that occurs in these animals. Fructose feeding resulted in increased activities of several of the oxidant defense enzymes. Protein oxidative damage assessed by glutamine synthetase activity was increased by both Zn deficiency and fructose feeding.

  4. Wavelength dependence of ultraviolet-induced DNA damage distribution: involvement of direct or indirect mechanisms and possible artefacts.

    PubMed

    Kuluncsics, Z; Perdiz, D; Brulay, E; Muel, B; Sage, E

    1999-03-01

    DNA damage profiles have been established in plasmid DNA using purified DNA repair enzymes and a plasmid relaxation assay, following exposure to UVC, UVB, UVA or simulated sunlight (SSL). Cyclobutane pyrimidine dimers (CPDs) are revealed as T4 endonuclease V-sensitive sites, oxidation products at purine and pyrimidine as Fpg- and Nth-sensitive sites, and abasic sites are detected by Nfo protein from Escherichia coli. CPDs are readily detected after UVA exposure, though produced 10(3) and 10(5) times less efficiently than by UVB or UVC, respectively. We demonstrate that CPDs are induced by UVA radiation and not by contaminating UVB wavelengths. Furthermore, they are produced at doses compatible with human exposure and are likely to contribute to the mutagenic specificity of UVA [E. Sage et al., Proc. Natl. Acad. Sci. USA 93 (1996) 176-180]. Oxidative damage is induced with a linear dose dependence, for each region of the solar spectrum, with the exception of oxidized pyrimidine and abasic sites, which are not detectable after UVB irradiation. The distribution of the different classes of photolesions varies markedly, depending on wavelengths. However, the unexpectedly high yield of oxidative lesions, as compared to CPDs, by UVA and SSL led us to investigate their production mechanism. An artificial formation of hydroxyl radicals is observed, which depends on the material of the sample holder used for UVA irradiation and is specific for long UV wavelengths. Our study sheds light on a possible artefact in the production of oxidative damage by UVA radiation. Meanwhile, after eliminating some potential sources of the artefact ratios of CPDs to oxidized purine of three and five upon irradiation with UVA and SSL, respectively, are still observed, whereas these ratios are about 140 and 200 after UVC and UVB irradiation.

  5. A FFT-based formulation for efficient mechanical fields computation in isotropic and anisotropic periodic discrete dislocation dynamics

    NASA Astrophysics Data System (ADS)

    Bertin, N.; Upadhyay, M. V.; Pradalier, C.; Capolungo, L.

    2015-09-01

    In this paper, we propose a novel full-field approach based on the fast Fourier transform (FFT) technique to compute mechanical fields in periodic discrete dislocation dynamics (DDD) simulations for anisotropic materials: the DDD-FFT approach. By coupling the FFT-based approach to the discrete continuous model, the present approach benefits from the high computational efficiency of the FFT algorithm, while allowing for a discrete representation of dislocation lines. It is demonstrated that the computational time associated with the new DDD-FFT approach is significantly lower than that of current DDD approaches when large number of dislocation segments are involved for isotropic and anisotropic elasticity, respectively. Furthermore, for fine Fourier grids, the treatment of anisotropic elasticity comes at a similar computational cost to that of isotropic simulation. Thus, the proposed approach paves the way towards achieving scale transition from DDD to mesoscale plasticity, especially due to the method’s ability to incorporate inhomogeneous elasticity.

  6. Mechanisms of hepatoprotection of Terminalia catappa L. extract on D-Galactosamine-induced liver damage.

    PubMed

    Tang, Xin-Hui; Gao, Ling; Gao, Jing; Fan, Yi-Mei; Xu, Li-Zhi; Zhao, Xiao-Ning; Xu, Qiang

    2004-01-01

    The hepatoprotective effects of the extract of Terminalia catappa L. leaves (TCE) against D-Galactosamine (D-GalN)-induced liver injury and the mechanisms underlying its protection were studied. In acute hepatic injury test, it was found that serum ALT activity was remarkably increased (3.35-fold) after injection of D-GalN in mice. But with oral pretreatment of TCE (20, 50 and 100 mg/kg/d) for 7days, change in serum ALT was notably reversed. In primary cultured hepatocytes from fetal mice, it was found that cell viability was decreased by 45.0% after addition of D-GalN, while incubation with TCE (0.1, 0.5 and 1.0 mg/ml) for 36 hours could prevent the decrease in a dose-dependent manner. Meanwhile, D-GalN-induced both the increase of AST level (1.9-fold) and the decrease of SOD activity (48.0%) in supernatant of primary cultured hepatocytes could also be inhibited by pretreatment with TCE. In order to study the possible mechanisms underlying its hepatoprotective effects, one effective component separated from TCE, 2alpha, 3beta, 23-trihydroxyursane-12-en-28-oic acid (DHUA), was used to determine anti-mitochondrial swelling activity and superoxide radicals scavenging activity in vitro. It was found that at the concentration range of 50-500 micromol/L DHUA, Ca2+ -induced mitochondrial swelling was dose-dependently inhibited, and superoxide radicals scavenging activity was also shown in a dose-dependent manner. It was concluded that TCE has hepatoprotective activity and the mechanisms underlying its protective effects may be related to the direct mitochondrion protection and strong scavenging activity on reactive oxygen species (ROS).

  7. Mechanisms of direct radiation damage to DNA: the effect of base sequence on base end products.

    PubMed

    Sharma, Kiran K K; Swarts, Steven G; Bernhard, William A

    2011-04-28

    It has been generally assumed that product formation in DNA damaged by ionizing radiation is relatively independent of base sequence, i.e., that the yield of a given product depends primarily on the chemical properties of each DNA constituent and not on its base sequence context. We examined this assumption by comparing direct-type end products produced in films of d(CTCTCGAGAG)(2) with those produced in films of d(GCACGCGTGC)(2). Here we report the product yields in d(CTCTCGAGAG)(2) hydrated to Γ = 2.5 and 15, where Γ is the hydration level given in moles of H(2)O/mole of nucleotide. Of the 17 products monitored by GC/MS, seven exhibited statistically significant yields: 8-oxoGua, 8-oxoAde, 5-OHMeUra, 5,6-diHUra, 5,6-diHThy, 5-OHCyt, and 5-OHUra. These yields at Γ = 2.5 are compared with the yields from our previously reported study of d(GCACGCGTGC)(2) (after projecting the yields to a CG/AT ratio of 1). The ratio of projected yields, d(CTCTCGAGAG)(2) divided by d(GCACGCGTGC)(2), are 1.3 ± 0.9, 1.8 ± 0.3, 1.6 ± 0.6, 11.4 ± 4.7, 0.2 ± 0.1, >28, and 0.8 ± 1.1, respectively. Considering just d(CTCTCGAGAG)(2), the ratios of yields at Γ = 2.5 divided by yields at Γ = 15 are 0.7 ± 0.2, 0.5 ± 0.1, 2.3 ± 4.0, 3.4 ± 1.2, 3.5 ± 3.3, 1.2 ± 0.2, and 0.4 ± 0.2, respectively. The effects of sequence and hydration on base product yields are explained by a working model emphasizing the difference between two distinctly different types of reaction: (i) radical reactions that progress to nonradical intermediates and product prior to dissolution and (ii) reactions that stem from radicals trapped in the solid state at room temperature that go on to yield nonradical product after sample dissolution. Based on these findings, insights into rates of hole and excess electron-transfer relative to rates of proton transfer are discussed.

  8. Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy.

    PubMed

    Elahy, Mina; Baindur-Hudson, Swati; Cruzat, Vinicius F; Newsholme, Philip; Dass, Crispin R

    2014-09-01

    Pigment epithelium-derived factor (PEDF) is a pluripotent glycoprotein belonging to the serpin family. PEDF can stimulate several physiological processes such as angiogenesis, cell proliferation, and survival. Oxidative stress plays an important role in the occurrence of diabetic retinopathy (DR), which is the major cause of blindness in young diabetic adults. PEDF plays a protective role in DR and there is accumulating evidence of the neuroprotective effect of PEDF. In this paper, we review the role of PEDF and the mechanisms involved in its antioxidative, anti-inflammatory, and neuroprotective properties.

  9. 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.

  10. Ultraviolet-B-induced DNA damage and ultraviolet-B tolerance mechanisms in species with different functional groups coexisting in subalpine moorlands.

    PubMed

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

    2016-08-01

    High doses of ultraviolet-B (UV-B; 280-315 nm) radiation can have detrimental effects on plants, and especially damage their DNA. Plants have DNA repair and protection mechanisms to prevent UV-B damage. However, it remains unclear how DNA damage and tolerance mechanisms vary among field species. We studied DNA damage and tolerance mechanisms in 26 species with different functional groups coexisting in two moorlands at two elevations. We collected current-year leaves in July and August, and determined accumulation of cyclobutane pyrimidine dimer (CPD) as UV-B damage and photorepair activity (PRA) and concentrations of UV-absorbing compounds (UACs) and carotenoids (CARs) as UV-B tolerance mechanisms. DNA damage was greater in dicot than in monocot species, and higher in herbaceous than in woody species. Evergreen species accumulated more CPDs than deciduous species. PRA was higher in Poaceae than in species of other families. UACs were significantly higher in woody than in herbaceous species. The CPD level was not explained by the mechanisms across species, but was significantly related to PRA and UACs when we ignored species with low CPD, PRA and UACs, implying the presence of another effective tolerance mechanism. UACs were correlated negatively with PRA and positively with CARs. Our results revealed that UV-induced DNA damage significantly varies among native species, and this variation is related to functional groups. DNA repair, rather than UV-B protection, dominates in UV-B tolerance in the field. Our findings also suggest that UV-B tolerance mechanisms vary among species under evolutionary trade-off and synergism.

  11. Photo-induced oxidative damage to dissolved free amino acids by the photosensitizer polycyclic musk tonalide: Transformation kinetics and mechanisms.

    PubMed

    Fang, Hansun; Gao, Yanpeng; Wang, Honghong; Yin, Hongliang; Li, Guiying; An, Taicheng

    2017-05-15

    Residue from the polycyclic musks (PCMs) in household and personal care products may harm human beings through skin exposure. To understand the health effects of PCMs when exposed to sunlight at molecular level, both experimental and computational methods were employed to investigate the photosensitized oxidation performance of 19 natural amino acids, the most basic unit of life. Results showed that a typical PCM, tonalide, acts as a photosensitizer to significantly increase photo-induced oxidative damage to amino acids. Both common and exceptional transformation pathways occurred during the photosensitization damage of amino acids. Experimental tests further identified the different mechanisms involved. The common transformation pathway occurred through the electron transfer from α amino-group of amino acids, accompanying with the formation of O2(•-). This pathway was controlled by the electronic density of N atom in α amino-group. The exceptional transformation pathway was identified only for five amino acids, mainly due to the reactions with reactive oxygen species, e.g. (1)O2 and excited triplet state molecules. Additionally, tonalide photo-induced transformation products could further accelerate the photosensitization of all amino acids with the common pathway. This study may support the protection of human health, and suggests the possible need to further restrict polycyclic musks use.

  12. Effect of acetaminophen exposure in Oncorhynchus mykiss gills and liver: detoxification mechanisms, oxidative defence system and peroxidative damage.

    PubMed

    Ramos, A S; Correia, A T; Antunes, S C; Gonçalves, F; Nunes, B

    2014-05-01

    The increasing presence of pharmaceutical drugs in nature is cause of concern due to the occurrence of oxidative stress in non-target species. Acetaminophen is widely used in human medicine as an analgesic and antipyretic drug, and it is one of the most sold non-prescription drugs. The present study aimed to assess the toxic effects of acetaminophen (APAP) in Oncorhynchus mykiss following acute and chronic exposures in realistic levels. In order to evaluate the APAP effects in the rainbow trout, gills and liver were analyzed with biochemical biomarkers, such as catalase (CAT), total and selenium-dependent glutathione peroxidase (GPx), glutathione reductase (GRed) and glutathione-S-transferases (GSTs) activity and also lipid peroxidation levels (TBARS). The results obtained in all tests indicate that a significant response of oxidative stress was established, along with the increase of APAP concentrations. The establishment of an oxidative stress scenario occurred with the involvement of all tested biomarkers, sustaining a generalized set of pro-oxidative effects elicited by APAP. Additionally, the occurrence of oxidative damage strongly suggests the impairment of the antioxidant defense mechanism of O. mykiss. It is important to note that the occurrence of oxidative deleterious effects and peroxidative damages occurred for concentrations similar to those already reported for several freshwater ecosystems. The importance of these assumptions is further discussed under the scope of ecological relevance of the assessment of effects caused by pharmaceuticals in non-target organisms.

  13. 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.

  14. Nanomechanical mechanism for lipid bilayer damage induced by carbon nanotubes confined in intracellular vesicles

    PubMed Central

    von dem Bussche, Annette; Yi, Xin; Qiu, Yang; Wang, Zhongying; Weston, Paula; Hurt, Robert H.; Kane, Agnes B.; Gao, Huajian

    2016-01-01

    Understanding the behavior of low-dimensional nanomaterials confined in intracellular vesicles has been limited by the resolution of bioimaging techniques and the complex nature of the problem. Recent studies report that long, stiff carbon nanotubes are more cytotoxic than flexible varieties, but the mechanistic link between stiffness and cytotoxicity is not understood. Here we combine analytical modeling, molecular dynamics simulations, and in vitro intracellular imaging methods to reveal 1D carbon nanotube behavior within intracellular vesicles. We show that stiff nanotubes beyond a critical length are compressed by lysosomal membranes causing persistent tip contact with the inner membrane leaflet, leading to lipid extraction, lysosomal permeabilization, release of cathepsin B (a lysosomal protease) into the cytoplasm, and cell death. The precise material parameters needed to activate this unique mechanical pathway of nanomaterials interaction with intracellular vesicles were identified through coupled modeling, simulation, and experimental studies on carbon nanomaterials with wide variation in size, shape, and stiffness, leading to a generalized classification diagram for 1D nanocarbons that distinguishes pathogenic from biocompatible varieties based on a nanomechanical buckling criterion. For a wide variety of other 1D material classes (metal, oxide, polymer), this generalized classification diagram shows a critical threshold in length/width space that represents a transition from biologically soft to stiff, and thus identifies the important subset of all 1D materials with the potential to induce lysosomal permeability by the nanomechanical mechanism under investigation. PMID:27791073

  15. Leishmania infections damage the feeding mechanism of the sandfly vector and implement parasite transmission by bite.

    PubMed Central

    Schlein, Y; Jacobson, R L; Messer, G

    1992-01-01

    Leishmania parasites are transmitted by the bites of infected female sandflies by a mechanism that has not been clarified. Leishmania infections in the vector develop only in the gut, and the parasites' exit is through the food channel in the proboscis. The problem is how during the bite, when blood flows in, parasites are emitted through the same channel in the opposite direction. It is well documented that infected sandflies maintained on sugar diets are potent vectors, whereas transmission fails after constant feeding on blood. Hence to study the mechanism of transmission, we fed these diets to Phlebotomus papatasi infected with L. major. Histological examination demonstrated that only in the sugar-fed flies did the cuticle lining of the cardiac valve detach and other valve tissues degenerate gradually. The injury of the main valve of the food pumps hindered gorging of most flies when force-fed from capillaries, and they regurgitated the gut contents with fluids from the capillaries. We suggest that infections are caused by parasites regurgitated from the stomach that are deposited in the host tissue. We found that secretion of chitinolytic enzymes by cultured L. major parasites is inhibited by blood or hemoglobin, and hence these enzymes are apparently absent from the blood-fed infected flies, where the cardiac valve appears undamaged. We therefore presume that lysis of the chitin in the cuticle lining of the valve leads to exposure and degeneration of the underlying tissues. Images PMID:1409724

  16. 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.

  17. 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

  18. Two more approaches for generating trajectory-based dynamics which conserves the canonical distribution in the phase space formulation of quantum mechanics.

    PubMed

    Liu, Jian

    2011-05-21

    We show two more approaches for generating trajectory-based dynamics in the phase space formulation of quantum mechanics: "equilibrium continuity dynamics" (ECD) in the spirit of the phase space continuity equation in classical mechanics, and "equilibrium Hamiltonian dynamics" (EHD) in the spirit of the Hamilton equations of motion in classical mechanics. Both ECD and EHD can recover exact thermal correlation functions (of even nonlinear operators, i.e., nonlinear functions of position or momentum operators) in the classical, high temperature, and harmonic limits. Both ECD and EHD conserve the quasi-probability within the infinitesimal volume dx(t)dp(t) around the phase point (x(t), p(t)) along the trajectory. Numerical tests of both approaches in the Wigner phase space have been made for two strongly anharmonic model problems and a double well system, for each potential auto-correlation functions of both linear and nonlinear operators have been calculated. The results suggest EHD and ECD are two additional potential useful approaches for describing quantum effects for complex systems in condense phase.

  19. Mechanical properties of some pigmented and unpigmented aqueous-based film coating formulations applied to aspirin tablets.

    PubMed

    Okhamafe, A O; York, P

    1986-06-01

    The Brinell hardness and Young's modulus of pigmented and unpigmented films of hydroxypropyl methylcellulose alone, and in combination with either polyethylene glycol 400 (plasticizer) or polyvinyl alcohol, which were applied to aspirin tablets, have been measured. Generally hardness and modulus data showed similar trends. The hardness and modulus of hydroxypropyl methylcellulose fell in the presence of polyethylene glycol 400 as a result of its plasticizing action. On the other hand, the hardness and modulus of the film former rose slightly when polyvinyl alcohol was initially incorporated, probably due to the crystalline phase of the additive, and then decreased when the level of the additive was further raised. Hardness and modulus were higher in films pigmented with talc than in those containing titanium dioxide because of the plate-like shape of talc and its greater interaction with the polymer systems. Some correlation was found between the Young's moduli of the applied films and those of the corresponding free films, with the moduli of the latter two 2-5 times greater. Ageing at 37 degrees C and 75% r.h. was found to cause a decrease in the mechanical properties of the unplasticized film coating systems probably as a result of decreased molecular order and enhanced polymer chain mobility.

  20. 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

  1. 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

  2. Micro-mechanical analysis of damage growth and fracture in discontinuous fiber reinforced metal matrix composites

    NASA Technical Reports Server (NTRS)

    Goree, James G.; Richardson, David E.

    1991-01-01

    An experimental verification is presented for a new two parameter fracture model based on the equivalent remote biaxial stresses (ERBS). A detailed comparison is made between the new theory and the constant K(sub IC) approach of linear elastic fracture mechanics (LEFM). Fracture is predicted through a failure curve representing the change in a variable fracture toughness K(sub IC) with the ERBS ratio B(sub E). The nonsingular term (T) in the series expansion of the near crack-tip transverse stress is included in the model. Experimental results for polymethyl methacrylate (PPMA) show that the theory can account for the effects of geometry on fracture toughness as well as indicate the initiation of crack branching. It is shown that the new criterion predicts failure for PMMA with a 95 percent confidence zone which is nearly three times smaller than that of the LEFM K(sub IC) approach.

  3. 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.

  4. 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.

  5. Evolutionary malignant resistance of cells to damaging factors as common biological defence mechanism in neoplastic development. Review of conception.

    PubMed

    Monceviciute-Eringiene, E

    2000-09-01

    Cells have some inborn resistance to harmful factors, which could be called physiological or natural resistance. The mechanisms of multixenobiotic resistance (MXR) and multidrug resistance (MDR) have common features in the formation of acquired resistance in microorganisms, carcinogenesis, tumour metastases and chemotherapy or irradiation. ATP-dependent membrane P-glycoprotein, as an MDR efflux pump, glutathione S-transferases and other products of evolutionary resistance-related genes arised for exportation and detoxification of cytotoxic xenobiotics and drugs are transmitted from bacteria to man. On the one hand, this evolutionary MXR as a common biological defence mechanism is a "driving" power to conserve homeostasis of cells, tissues and organs. On the other hand, mutation, selection and simplification of properties are the causes of functional and morphological changes in tumour cells which regress to a more primitive mode of existence (atavism) for adaptation to survival. In the present work are presented data on the forms of E. coli resistant to antibiotics and of sarcoma 45 resistant to alkylic preparations. They may be helpful in revealing the causes of resistance and acquired accelerated growth of cells. The development of tumours as fibromas 14-15 years following injection of a vital dye trypan blue into human skin supports our conception that neoplastic growth is a particular case of the evolutionary resistance of cells adapted to the damaging factors. So, tumour cells adopting the enhancement mechanisms of general biological persistent resistance, i. e. undergoing repeated cycles of malignancy enhancement, adapt themselves to survive under the changed unfavourable conditions.

  6. Repair of oxidatively induced DNA damage by DNA glycosylases: Mechanisms of action, substrate specificities and excision kinetics.

    PubMed

    Dizdaroglu, Miral; Coskun, Erdem; Jaruga, Pawel

    Endogenous and exogenous reactive species cause oxidatively induced DNA damage in living organisms by a variety of mechanisms. As a result, a plethora of mutagenic and/or cytotoxic products are formed in cellular DNA. This type of DNA damage is repaired by base excision repair, although nucleotide excision repair also plays a limited role. DNA glycosylases remove modified DNA bases from DNA by hydrolyzing the glycosidic bond leaving behind an apurinic/apyrimidinic (AP) site. Some of them also possess an accompanying AP-lyase activity that cleaves the sugar-phosphate chain of DNA. Since the first discovery of a DNA glycosylase, many studies have elucidated the mechanisms of action, substrate specificities and excision kinetics of these enzymes present in all living organisms. For this purpose, most studies used single- or double-stranded oligodeoxynucleotides with a single DNA lesion embedded at a defined position. High-molecular weight DNA with multiple base lesions has been used in other studies with the advantage of the simultaneous investigation of many DNA base lesions as substrates. Differences between the substrate specificities and excision kinetics of DNA glycosylases have been found when these two different substrates were used. Some DNA glycosylases possess varying substrate specificities for either purine-derived lesions or pyrimidine-derived lesions, whereas others exhibit cross-activity for both types of lesions. Laboratory animals with knockouts of the genes of DNA glycosylases have also been used to provide unequivocal evidence for the substrates, which had previously been found in in vitro studies, to be the actual substrates in vivo as well. On the basis of the knowledge gained from the past studies, efforts are being made to discover small molecule inhibitors of DNA glycosylases that may be used as potential drugs in cancer therapy.

  7. 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

  8. 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

  9. Evaluation of Damage and Fracture Mechanisms of Different Characteristic Honeycomb Structures Under Thermomechanical Loading

    NASA Astrophysics Data System (ADS)

    Settet, A. T.; Nour, A.; Zahloul, H.; Naceur, H.

    2014-11-01

    A model able to predict the delamination mechanisms of composite honeycomb structures under thermal loading is presented. The use of a simulation software for some applications may not be sufficient to obtain the results expected; hence, the interest in developing modular calculation codes which would allow one to determine the rigidity matrix of a honeycomb panel, the deformation of its members, the field of shear strains, strains, and stresses in the panel plane on varying the physical parameters and checking the strength of each layer and of the entire panel. In order to test the reliability of the program developed, the results obtained are compared with those given in the literature. A specific model of Young's modulus under thermal loads is proposed, which takes into consideration the heat flux function, the thermal conductivity, the convection heat-transfer coefficients of the surrounding area inside and outside the panel, the exchange area in contact with air, the thickness of the honeycomb core, the upper and lower skins, and the adhesive layer. To verify the fracture strength of each panel, the Tsai-Wu criterion is used.

  10. 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.

  11. 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

    2014-08-05

    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.

  12. 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.

  13. Antimicrobial activity of melanoidins against Escherichia coli is mediated by a membrane-damage mechanism.

    PubMed

    Rurián-Henares, Jose A; Morales, Francisco J

    2008-04-09

    Melanoidins are brown polymeric material formed during thermal processing of food and widely distributed in the Western diet. Three water-soluble fractions were isolated from both commercial coffee and biscuit by sequential ultrafiltration steps (3 and 10 kDa cutoff). Biscuits were enzymatically digested to solubilize the protein-linked melanoidin fraction. Antimicrobial activity of melanoidins was evaluated against a Gram-negative reference pathogenic bacterium (Escherichia coli). The high-molecular-weight fraction of water-soluble melanoidins (>10 kDa) exerted the highest antimicrobial activity. The mechanism of action was further investigated by cell integrity and outer- and inner-membrane permeabilization assays. At the minimum inhibitory concentration, melanoidins provoked irreversible cell membrane disruption, which was independent of the bacterial transmembrane potential. Results indicate that water-soluble melanoidins killed pathogenic bacteria strains ( E. coli) by causing irreversible changes in both the inner and outer membranes. Likely, it allows for interference with biosynthetic processes, such as the inhibition of nutrient transport and macromolecular precursors.

  14. Probing irradiation induced DNA damage mechanisms using excited state Car-Parrinello molecular dynamics.

    PubMed

    Markwick, Phineus R L; Doltsinis, Nikos L; Schlitter, Jürgen

    2007-01-28

    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. 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.

  16. Thermodynamical Framework for Ductile Damage and Plasticity

    NASA Astrophysics Data System (ADS)

    César de Sá, José M. A.; Andrade, Filipe X. C.; Andrade Pires, Francisco M.

    2010-05-01

    Many models employed for the prediction of plastic deformation rely exclusively on elastoplastic theories, disregarding significant effects of internal degradation [1]. Constitutive models based on the Continuum Damage Mechanics theory provide more realistic predictions since damage is taken into account as an internal variable. In the present contribution, Lemaire's model for ductile damage [2] is questioned under the assumption of the principle of maximum inelastic dissipation [3]. The model is enhanced with a nonlocal formulation where the damage variable is spatially averaged by means of an integral operator [4]. Thermodynamical admissibility of the nonlocal model is checked by applying the global version of the Clausius-Duhem inequality [5]. Results from numerical analysis show that the constitutive model is insensitive to spatial discretization.

  17. 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.

  18. Enhanced dissolution rate and synchronized release of drugs in binary systems through formulation: Amorphous naproxen-cimetidine mixtures prepared by mechanical activation.

    PubMed

    Allesø, Morten; Chieng, Norman; Rehder, Sönke; Rantanen, Jukka; Rades, Thomas; Aaltonen, Jaakko

    2009-05-21

    Naproxen, a non-steroidal anti-inflammatory drug (NSAID), is a biopharmaceutics classification system (BCS) class II drug whose bioavailability is rate-limited by its dissolution. Cimetidine is sometimes co-administered with naproxen for the treatment of NSAID-induced gastro-intestinal disorders. Hence, there is interest in the design of new formulations that offer (1) concomitant release of both drugs, and (2) an enhanced dissolution rate of naproxen. This study investigates the formation of amorphous binary systems with naproxen and cimetidine. The binary mixtures of all tested molar ratios were found to become amorphous upon co-milling for 60 min at 4 degrees C. In contrast, pure naproxen could not be transformed to the amorphous state by mechanical activation. The 1:1 sample was the most physically stable when stored for 33 days at 40 degrees C, even though it did not have the highest T(g) when compared to the 1:2 sample. The 1:1 sample was further stored for 186 days and remained amorphous under all conditions. Raman spectroscopy suggested a 1:1 solid-state interaction between the imidazole ring of cimetidine and the carboxylic acid moiety of naproxen in the co-milled amorphous sample. Thus, the stabilization of the amorphous binary system is dictated by molecular-level interactions rather than bulk-level phenomena. No recrystallization of either drug in the 1:1 co-milled sample was observed during dissolution testing, with naproxen and cimetidine having a four and two times higher intrinsic dissolution rate, respectively, compared to their crystalline counterparts. Further, the release of the two drugs could be synchronized using this formulation approach.

  19. Fracture and damage; Winter Annual Meeting of the American Society of Mechanical Engineers, Anaheim, CA, Nov. 8-13, 1992

    NASA Technical Reports Server (NTRS)

    Nagar, Arvind (Editor)

    1992-01-01

    The latest developments in the area of fracture and damage at high temperatures are discussed, in particular: modeling; analysis and experimental techniques for interface damage in composites including the effects of residual stresses and temperatures; and crack growth, inelastic deformation and fracture parameters for isotropic materials. Also included are damage modeling and experiments at elevated temperatures.

  20. High order ADER schemes for a unified first order hyperbolic formulation of continuum mechanics: Viscous heat-conducting fluids and elastic solids

    SciTech Connect

    Dumbser, Michael; Peshkov, Ilya; Romenski, Evgeniy; Zanotti, Olindo

    2016-06-01

    Highlights: • High order schemes for a unified first order hyperbolic formulation of continuum mechanics. • The mathematical model applies simultaneously to fluid mechanics and solid mechanics. • Viscous fluids are treated in the frame of hyper-elasticity as generalized visco-plastic solids. • Formal asymptotic analysis reveals the connection with the Navier–Stokes equations. • The distortion tensor A in the model appears to be well-suited for flow visualization. - Abstract: 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

  1. 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.

  2. Response to 'Comment on 'Bohmian mechanics with complex action: A new trajectory-based formulation of quantum mechanics'' [J. Chem. Phys. 127, 197101 (2007)

    SciTech Connect

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

    2007-11-21

    In their comment, Sanz and Miret-Artes (SMA) describe previous trajectory-based formalisms based on the quantum Hamilton-Jacobi (QHJ) formalism. In this reply, we highlight our unique contributions: the identification of the smallness of the quantum force in the complex QHJ and its solution using complex trajectories. SMA also raise the question of how the term locality should be used in quantum mechanics. We suggest that at least certain aspects of nonlocality can depend on the method used to solve the problem.

  3. 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.

  4. Advanced Glycation End-Products Reduce Collagen Molecular Sliding to Affect Collagen Fibril Damage Mechanisms but Not Stiffness

    PubMed Central

    Fessel, Gion; Li, Yufei; Diederich, Vincent; Guizar-Sicairos, Manuel; Schneider, Philipp; Sell, David R.; Monnier, Vincent M.; Snedeker, Jess G.

    2014-01-01

    Advanced glycation end-products (AGE) contribute to age-related connective tissue damage and functional deficit. The documented association between AGE formation on collagens and the correlated progressive stiffening of tissues has widely been presumed causative, despite the lack of mechanistic understanding. The present study investigates precisely how AGEs affect mechanical function of the collagen fibril – the supramolecular functional load-bearing unit within most tissues. We employed synchrotron small-angle X-ray scattering (SAXS) and carefully controlled mechanical testing after introducing AGEs in explants of rat-tail tendon using the metabolite methylglyoxal (MGO). Mass spectrometry and collagen fluorescence verified substantial formation of AGEs by the treatment. Associated mechanical changes of the tissue (increased stiffness and failure strength, decreased stress relaxation) were consistent with reports from the literature. SAXS analysis revealed clear changes in molecular deformation within MGO treated fibrils. Underlying the associated increase in tissue strength, we infer from the data that MGO modified collagen fibrils supported higher loads to failure by maintaining an intact quarter-staggered conformation to nearly twice the level of fibril strain in controls. This apparent increase in fibril failure resistance was characterized by reduced side-by-side sliding of collagen molecules within fibrils, reflecting lateral molecular interconnectivity by AGEs. Surprisingly, no change in maximum fibril modulus (2.5 GPa) accompanied the changes in fibril failure behavior, strongly contradicting the widespread assumption that tissue stiffening in ageing and diabetes is directly related to AGE increased fibril stiffness. We conclude that AGEs can alter physiologically relevant failure behavior of collagen fibrils, but that tissue level changes in stiffness likely occur at higher levels of tissue architecture. PMID:25364829

  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. [Protective effect of Angelica sinensis polysaccharides on subacute renal damages induced by D-galactose in mice and its mechanism].

    PubMed

    Fan, Yan-ling; Xia, Jie-yu; Jia, Dao-yong; Zhang, Meng-si; Zhang, Yan-yan; Wang, Lu; Huang, Guo-ning; Wang, Ya-ping

    2015-11-01

    To explore the protective effect of Angelica sinensis polysaccharides(ASP) on subacute renal damages induced by D-galactose in mice and its mechanism. Male C57BL/6J mice were randomly divided into 3 groups, with 10 mice in each group. The D-galactose model group was subcutaneously injected with D-galactose (120 mg x kg(-1)), qd x 42; the ASP + D-galactose model group was intraperitoneally injected with ASP since the 8th day of the replication of the D-galactose model, qd x 35; and the normal control group was subcutaneously injected with saline at the same dose and time. On the 2nd day of after the injection, the peripheral blood was collected to measure the content of BUN, Crea, UA, Cys-C; paraffin sections were made to observe the renal histomorphology by HE staining; senescence-associated β-g-alactosidase (SA-β-Gal) stain was used to observe the relative optical density (ROD) in renal tissues; transmission electron microscopy was assayed to observe the renal ultrastructure; the renal tissue homogenate was prepared to measure the content of SOD, GSH-PX, MDA; the content of AGEs and 8-OH-dG were measured by ELISA. According to the result, compared with the D-galactose model group, the ASP + D-galactose model group showed obviously decreases in the content of BUN, Crea, UA, Cysc, AGES, 8-OH-dG, the number of hardening renal corpuscle, renal capsular space and renal tubular lumen, ROD of SA-β-Gal staining positive kidney cells, mesangial cells, basement membrane thickness, podocyte secondary processes fusion and MDA and increases in the number of normal renal corpuscle, ribosome and rough endoplasmic reticulum in podocytes, the activity of SOD and GSH-PX. In Conclusion, A. sinensis polysaccharides can antagonize kidney subacute damages induced by D-galactose in mice. Its protective mechanism may be correlated with the inhibition of the oxidative stress injury.

  7. 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.

  8. Elucidating the digital control mechanism for DNA damage repair with the p53–Mdm2 system: single cell data analysis and ensemble modelling

    PubMed Central

    Ogunnaike, Babatunde A

    2005-01-01

    Recent experimental evidence about DNA damage response using the p53–Mdm2 system has raised some fundamental questions about the control mechanism employed. In response to DNA damage, an ensemble of cells shows a damped oscillation in p53 expression whose amplitude increases with increased DNA damage—consistent with ‘analogue’ control. Recent experimental results, however, show that the single cell response is a series of discrete pulses in p53; and with increase in DNA damage, neither the height nor the duration of the pulses change, but the mean number of pulses increase—consistent with ‘digital’ control. Here we present a system engineering model that uses published data to elucidate this mechanism and resolve the dilemma of how digital behaviour at the single cell level can manifest as analogue ensemble behaviour. First, we develop a dynamic model of the p53–Mdm2 system that produces non-oscillatory responses to a stress signal. Second, we develop a probability model of the distribution of pulses in a cell population, and combine the two with the simplest digital control algorithm to show how oscillatory responses whose amplitudes grow with DNA damage can arise from single cell behaviour in which each single pulse response is independent of the extent of DNA damage. A stochastic simulation of the hypothesized control mechanism reproduces experimental observations remarkably well. PMID:16849229

  9. Modelling of elastoplastic damage in concrete due to desiccation shrinkage

    NASA Astrophysics Data System (ADS)

    Bourgeois, F.; Burlion, N.; Shao, J. F.

    2002-07-01

    We present a numerical modelling of elastoplastic damage due to drying shrinkage of concrete in the framework of mechanics of partially saturated porous media. An elastoplastic model coupled with isotropic damage is first formulated. Two plastic flow mechanisms are involved, controlled by applied stress and suction, respectively. A general concept of net effective stress is used in take into account effects of capillary pressure and material damage on stress-controlled plastic deformation. Damage evolution depends both on elastic and plastic strains. The model's parameters are determined or chosen from relevant experimental data. Comparisons between numerical simulations and experimental data are presented to show the capacity of model to reproduce mains features of concrete behaviour under mechanical loading and during drying shrinkage of concrete. An example of application concerning drying of a concrete wall is finally presented. The results obtained allow to show potential capacity of proposed model for numerical modelling of complex coupling processes in concrete structures.

  10. Therapeutic time window of cannabidiol treatment on delayed ischemic damage via high-mobility group box1-inhibiting mechanism.

    PubMed

    Hayakawa, Kazuhide; Irie, Keiichi; Sano, Kazunori; Watanabe, Takuya; Higuchi, Sei; Enoki, Makiko; Nakano, Takafumi; Harada, Kazuhiko; Ishikane, Shin; Ikeda, Tomoaki; Fujioka, Masayuki; Orito, Kensuke; Iwasaki, Katsunori; Mishima, Kenichi; Fujiwara, Michihiro

    2009-09-01

    Cannabidiol decreases cerebral infarction and high-mobility group box1 (HMGB1) in plasma in ischemic early phase. However, plasma HMGB1 levels in ischemic delayed phase reach higher concentration with the progressing brain injury. In this study, we investigated the therapeutic time window of cannabidiol on functional deficits, glial HMGB1 and plasma HMGB1 levels in a 4 h mouse middle cerebral artery (MCA) occlusion model. Cannabidiol-treated mice were divided into 3 groups as follows: group (a) treated from day 1, group (b) treated from day 3, group (c) treated from day 5 after MCA occlusion. Moreover, minocycline, microglia inhibitor, and fluorocitrate, an inhibitor of astroglial metabolism, were used to compare with cannabidiol-treated group. Repeated treatment with cannabidiol from 1 and 3 d at the latest after cerebral ischemia improved functional deficits and survival rates. However, cannabidiol from 5 d could not improve the ischemic damage as well as fluorocitrate-treated group. Moreover, both group (a), group (b) and minocycline but not group (c) and fluorocitrate-treated group had a decrease in the number of Iba1 expressing HMGB1 positive cells and HMGB1 levels in plasma. Cannabidiol may provide therapeutic possibilities for the progressing brain injury via HMGB1-inhibiting mechanism.

  11. A study of mechanical processing damage in brittle materials. Annual progress report, 1 April 1988--31 March 1989

    SciTech Connect

    Khuri-Yakub, B.T.

    1989-04-01

    The first project deals with examining ceramics when they are in the green state, and evaluating the effect of density and mechanical property variations on the final hot-pressed parts. The second aspect of the project deals with the direct characterization of surface and near-surface defects that are induced by machining operations. For the ultrasonic inspection of green ceramics, it is necessary to introduce ultrasound in the sample without immersing it in water. The author`s approach is to develop air transducers based on using new types of matching layers. The paper describes the development of these air transducers. The work on the characterization of machining damage in ceramics considered the special problem of ball bearings. Ball bearings may be the first wide-range industrial application for hot-pressed ceramic materials. The major problem with the ball bearings is their sensitivity to small surface and near-surface defects. Presently, inspection is performed by optical microscopy. The author developed an amplitude and phase acoustic microscopy method and constructed a special fixture to rotate the ball bearings under a focused transducer.

  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 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

  14. Repeated exposures to roadside particulate matter extracts suppresses pulmonary defense mechanisms, resulting in lipid and protein oxidative damage.