Experimental Verification of Computational Models for Laminated Composites

NASA Technical Reports Server (NTRS)

Harris, Charles E.; Coats, Timothy W.; Glaessgen, Edward H.

1999-01-01

The objective of the research reported herein is to develop a progressive damage methodology capable of predicting the residual strength of continuous fiber-reinforced, laminated, polymer matrix composites with through-penetration damage. The fracture behavior of center-notch tension panels with thin crack-like slits was studied. Since fibers are the major load-carrying constituent in polymer matrix composites, predicting the residual strength of a laminate requires a criterion for fiber fracture. The effects on fiber strain due to other damage mechanisms such as matrix cracking and delaminations must also be modeled. Therefore, the research herein examines the damage mechanisms involved in translaminate fracture and identifies the toughening mechanisms responsible for damage growth resistance in brittle epoxy matrix systems. The mechanics of matrix cracking and fiber fracture are discussed as is the mathematical framework for the progressive damage model developed by the authors. The progressive damage analysis algorithms have been implemented into a general purpose finite element code developed by NASA, the Computational Structural Mechanics Testbed (COMET). Damage growth is numerically simulated and the analytical residual strength predictions are compared to experimental results for a variety of notched panel configurations and materials systems.

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma

PubMed Central

Nickerson, John M.; Gao, Feng-juan; Sun, Zhongmou; Chen, Xin-ya; Zhang, Shu-jie; Gao, Feng; Chen, Jun-yi; Luo, Yi; Wang, Yan; Sun, Xing-huai

2015-01-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. PMID:25478814

A case-study in the clinical epidemiology of psoriatic arthritis: multistate models and causal arguments

PubMed Central

O'Keeffe, Aidan G; Tom, Brian D M; Farewell, Vernon T

2011-01-01

In psoriatic arthritis, permanent joint damage characterizes disease progression and represents a major debilitating aspect of the disease. Understanding the process of joint damage will assist in the treatment and disease management of patients. Multistate models provide a means to examine patterns of disease, such as symmetric joint damage. Additionally, the link between damage and the dynamic course of disease activity (represented by joint swelling and stress pain) at both the individual joint level and otherwise can be represented within a correlated multistate model framework. Correlation is reflected through the use of random effects for progressive models and robust variance estimation for non-progressive models. Such analyses, undertaken with data from a large psoriatic arthritis cohort, are discussed and the extent to which they permit causal reasoning is considered. For this, emphasis is given to the use of the Bradford Hill criteria for causation in observational studies and the concept of local (in)dependence to capture the dynamic nature of the relationships. PMID:22163372

Investigation of Micro-Scale Architectural Effects on Damage of Composites

NASA Technical Reports Server (NTRS)

Stier, Bertram; Bednarcyk, Brett A.; Simon, Jaan W.; Reese, Stefanie

2015-01-01

This paper presents a three-dimensional, energy based, anisotropic, stiffness reduction, progressive damage model for composite materials and composite material constituents. The model has been implemented as a user-defined constitutive model within the Abaqus finite element software package and applied to simulate the nonlinear behavior of a damaging epoxy matrix within a unidirectional composite material. Three different composite microstructures were considered as finite element repeating unit cells, with appropriate periodicity conditions applied at the boundaries. Results representing predicted transverse tensile, longitudinal shear, and transverse shear stress-strain curves are presented, along with plots of the local fields indicating the damage progression within the microstructure. It is demonstrated that the damage model functions appropriately at the matrix scale, enabling localization of the damage to simulate failure of the composite material. The influence of the repeating unit cell geometry and the effect of the directionality of the applied loading are investigated and discussed.

Progressive Damage Analysis of Bonded Composite Joints

NASA Technical Reports Server (NTRS)

Leone, Frank A., Jr.; Girolamo, Donato; Davila, Carlos G.

2012-01-01

The present work is related to the development and application of progressive damage modeling techniques to bonded joint technology. The joint designs studied in this work include a conventional composite splice joint and a NASA-patented durable redundant joint. Both designs involve honeycomb sandwich structures with carbon/epoxy facesheets joined using adhesively bonded doublers.Progressive damage modeling allows for the prediction of the initiation and evolution of damage within a structure. For structures that include multiple material systems, such as the joint designs under consideration, the number of potential failure mechanisms that must be accounted for drastically increases the complexity of the analyses. Potential failure mechanisms include fiber fracture, intraply matrix cracking, delamination, core crushing, adhesive failure, and their interactions. The bonded joints were modeled using highly parametric, explicitly solved finite element models, with damage modeling implemented via custom user-written subroutines. Each ply was discretely meshed using three-dimensional solid elements. Layers of cohesive elements were included between each ply to account for the possibility of delaminations and were used to model the adhesive layers forming the joint. Good correlation with experimental results was achieved both in terms of load-displacement history and the predicted failure mechanism(s).

A Novel Multiscale Physics Based Progressive Failure Methodology for Laminated Composite Structures

NASA Technical Reports Server (NTRS)

Pineda, Evan J.; Waas, Anthony M.; Bednarcyk, Brett A.; Collier, Craig S.; Yarrington, Phillip W.

2008-01-01

A variable fidelity, multiscale, physics based finite element procedure for predicting progressive damage and failure of laminated continuous fiber reinforced composites is introduced. At every integration point in a finite element model, progressive damage is accounted for at the lamina-level using thermodynamically based Schapery Theory. Separate failure criteria are applied at either the global-scale or the microscale in two different FEM models. A micromechanics model, the Generalized Method of Cells, is used to evaluate failure criteria at the micro-level. The stress-strain behavior and observed failure mechanisms are compared with experimental results for both models.

Damage and strength of composite materials: Trends, predictions, and challenges

NASA Technical Reports Server (NTRS)

Obrien, T. Kevin

1994-01-01

Research on damage mechanisms and ultimate strength of composite materials relevant to scaling issues will be addressed in this viewgraph presentation. The use of fracture mechanics and Weibull statistics to predict scaling effects for the onset of isolated damage mechanisms will be highlighted. The ability of simple fracture mechanics models to predict trends that are useful in parametric or preliminary designs studies will be reviewed. The limitations of these simple models for complex loading conditions will also be noted. The difficulty in developing generic criteria for the growth of these mechanisms needed in progressive damage models to predict strength will be addressed. A specific example for a problem where failure is a direct consequence of progressive delamination will be explored. A damage threshold/fail-safety concept for addressing composite damage tolerance will be discussed.

An Enriched Shell Finite Element for Progressive Damage Simulation in Composite Laminates

NASA Technical Reports Server (NTRS)

McElroy, Mark W.

2016-01-01

A formulation is presented for an enriched shell nite element capable of progressive damage simulation in composite laminates. The element uses a discrete adaptive splitting approach for damage representation that allows for a straightforward model creation procedure based on an initially low delity mesh. The enriched element is veri ed for Mode I, Mode II, and mixed Mode I/II delamination simulation using numerical benchmark data. Experimental validation is performed using test data from a delamination-migration experiment. Good correlation was found between the enriched shell element model results and the numerical and experimental data sets. The work presented in this paper is meant to serve as a rst milestone in the enriched element's development with an ultimate goal of simulating three-dimensional progressive damage processes in multidirectional laminates.

Multiple Damage Progression Paths in Model-Based Prognostics

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Goebel, Kai Frank

2011-01-01

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

Progressive damage and rupture in polymers

NASA Astrophysics Data System (ADS)

Talamini, Brandon; Mao, Yunwei; Anand, Lallit

2018-02-01

Progressive damage, which eventually leads to failure, is ubiquitous in biological and synthetic polymers. The simplest case to consider is that of elastomeric materials which can undergo large reversible deformations with negligible rate dependence. In this paper we develop a theory for modeling progressive damage and rupture of such materials. We extend the phase-field method, which is widely used to describe the damage and fracture of brittle materials, to elastomeric materials undergoing large deformations. A central feature of our theory is the recognition that the free energy of elastomers is not entirely entropic in nature - there is also an energetic contribution from the deformation of the bonds in the chains. It is the energetic part in the free energy which is the driving force for progressive damage and fracture.

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma.

PubMed

Wu, Ji-Hong; Zhang, Sheng-Hai; Nickerson, John M; Gao, Feng-Juan; Sun, Zhongmou; Chen, Xin-Ya; Zhang, Shu-Jie; Gao, Feng; Chen, Jun-Yi; Luo, Yi; Wang, Yan; Sun, Xing-Huai

2015-02-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Fuselage Versus Subcomponent Panel Response Correlation Based on ABAQUS Explicit Progressive Damage Analysis Tools

NASA Technical Reports Server (NTRS)

Gould, Kevin E.; Satyanarayana, Arunkumar; Bogert, Philip B.

2016-01-01

Analysis performed in this study substantiates the need for high fidelity vehicle level progressive damage analyses (PDA) structural models for use in the verification and validation of proposed sub-scale structural models and to support required full-scale vehicle level testing. PDA results are presented that capture and correlate the responses of sub-scale 3-stringer and 7-stringer panel models and an idealized 8-ft diameter fuselage model, which provides a vehicle level environment for the 7-stringer sub-scale panel model. Two unique skin-stringer attachment assumptions are considered and correlated in the models analyzed: the TIE constraint interface versus the cohesive element (COH3D8) interface. Evaluating different interfaces allows for assessing a range of predicted damage modes, including delamination and crack propagation responses. Damage models considered in this study are the ABAQUS built-in Hashin procedure and the COmplete STress Reduction (COSTR) damage procedure implemented through a VUMAT user subroutine using the ABAQUS/Explicit code.

A Progressive Damage Model for Predicting Permanent Indentation and Impact Damage in Composite Laminates

NASA Astrophysics Data System (ADS)

Ji, Zhaojie; Guan, Zhidong; Li, Zengshan

2017-10-01

In this paper, a progressive damage model was established on the basis of ABAQUS software for predicting permanent indentation and impact damage in composite laminates. Intralaminar and interlaminar damage was modelled based on the continuum damage mechanics (CDM) in the finite element model. For the verification of the model, low-velocity impact tests of quasi-isotropic laminates with material system of T300/5228A were conducted. Permanent indentation and impact damage of the laminates were simulated and the numerical results agree well with the experiments. It can be concluded that an obvious knee point can be identified on the curve of the indentation depth versus impact energy. Matrix cracking and delamination develops rapidly with the increasing impact energy, while considerable amount of fiber breakage only occurs when the impact energy exceeds the energy corresponding to the knee point. Predicted indentation depth after the knee point is very sensitive to the parameter μ which is proposed in this paper, and the acceptable value of this parameter is in range from 0.9 to 1.0.

Damage-Based Time-Dependent Modeling of Paraglacial to Postglacial Progressive Failure of Large Rock Slopes

NASA Astrophysics Data System (ADS)

Riva, Federico; Agliardi, Federico; Amitrano, David; Crosta, Giovanni B.

2018-01-01

Large alpine rock slopes undergo long-term evolution in paraglacial to postglacial environments. Rock mass weakening and increased permeability associated with the progressive failure of deglaciated slopes promote the development of potentially catastrophic rockslides. We captured the entire life cycle of alpine slopes in one damage-based, time-dependent 2-D model of brittle creep, including deglaciation, damage-dependent fluid occurrence, and rock mass property upscaling. We applied the model to the Spriana rock slope (Central Alps), affected by long-term instability after Last Glacial Maximum and representing an active threat. We simulated the evolution of the slope from glaciated conditions to present day and calibrated the model using site investigation data and available temporal constraints. The model tracks the entire progressive failure path of the slope from deglaciation to rockslide development, without a priori assumptions on shear zone geometry and hydraulic conditions. Complete rockslide differentiation occurs through the transition from dilatant damage to a compacting basal shear zone, accounting for observed hydraulic barrier effects and perched aquifer formation. Our model investigates the mechanical role of deglaciation and damage-controlled fluid distribution in the development of alpine rockslides. The absolute simulated timing of rock slope instability development supports a very long "paraglacial" period of subcritical rock mass damage. After initial damage localization during the Lateglacial, rockslide nucleation initiates soon after the onset of Holocene, whereas full mechanical and hydraulic rockslide differentiation occurs during Mid-Holocene, supporting a key role of long-term damage in the reported occurrence of widespread rockslide clusters of these ages.

Adhesive Characterization and Progressive Damage Analysis of Bonded Composite Joints

NASA Technical Reports Server (NTRS)

Girolamo, Donato; Davila, Carlos G.; Leone, Frank A.; Lin, Shih-Yung

2014-01-01

The results of an experimental/numerical campaign aimed to develop progressive damage analysis (PDA) tools for predicting the strength of a composite bonded joint under tensile loads are presented. The PDA is based on continuum damage mechanics (CDM) to account for intralaminar damage, and cohesive laws to account for interlaminar and adhesive damage. The adhesive response is characterized using standard fracture specimens and digital image correlation (DIC). The displacement fields measured by DIC are used to calculate the J-integrals, from which the associated cohesive laws of the structural adhesive can be derived. A finite element model of a sandwich conventional splice joint (CSJ) under tensile loads was developed. The simulations indicate that the model is capable of predicting the interactions of damage modes that lead to the failure of the joint.

A thermodynamic approach to nonlinear ultrasonics for material state awareness and prognosis

NASA Astrophysics Data System (ADS)

Chillara, Vamshi Krishna

2017-11-01

We develop a thermodynamic framework for modeling nonlinear ultrasonic damage sensing and prognosis in materials undergoing progressive damage. The framework is based on the internal variable approach and relies on the construction of a pseudo-elastic strain energy function that captures the energetics associated with the damage progression. The pseudo-elastic strain energy function is composed of two energy functions—one that describes how a material stores energy in an elastic fashion and the other describes how material dissipates energy or stores it in an inelastic fashion. Experimental motivation for the choice of the above two functionals is discussed and some specific choices pertaining to damage progression during fatigue and creep are presented. The thermodynamic framework is employed to model the nonlinear response of material undergoing stress relaxation and creep-like degradation. For each of the above cases, evolution of the nonlinearity parameter with damage as well as with macroscopic measurables like accumulated plastic strain is obtained.

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

NASA Technical Reports Server (NTRS)

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

1998-01-01

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

Comparison of Damage Path Predictions for Composite Laminates by Explicit and Standard Finite Element Analysis Tools

NASA Technical Reports Server (NTRS)

Bogert, Philip B.; Satyanarayana, Arunkumar; Chunchu, Prasad B.

2006-01-01

Splitting, ultimate failure load and the damage path in center notched composite specimens subjected to in-plane tension loading are predicted using progressive failure analysis methodology. A 2-D Hashin-Rotem failure criterion is used in determining intra-laminar fiber and matrix failures. This progressive failure methodology has been implemented in the Abaqus/Explicit and Abaqus/Standard finite element codes through user written subroutines "VUMAT" and "USDFLD" respectively. A 2-D finite element model is used for predicting the intra-laminar damages. Analysis results obtained from the Abaqus/Explicit and Abaqus/Standard code show good agreement with experimental results. The importance of modeling delamination in progressive failure analysis methodology is recognized for future studies. The use of an explicit integration dynamics code for simple specimen geometry and static loading establishes a foundation for future analyses where complex loading and nonlinear dynamic interactions of damage and structure will necessitate it.

Modeling damage evolution in a hybrid ceramic matrix composite under static tensile load

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

Bonora, N.; Newaz, G.

In this investigation, damage evolution in a unidirectional hybrid ceramic composite made from Nicalon and SiC fibers in a Lithium Aluminosilicate (LAS) glass matrix was studied. The static stress-strain response of the composite exhibited a linear response followed by load drop in a progressive manner. Careful experiments were conducted stopping the tests at various strain levels and using replication technique, scanning and optical microscopy to monitor the evolution of damage in these composites. It was observed that the constituents of the composite failed in a sequential manner at increasing strain levels. The matrix cracks were followed by SiC fiber failuresmore » near ultimate tensile stress. After that, the load drop was associated with progressive failure of the Nicalon fibers. Identification of these failure modes were critical to the development of a concentric cylinder model representing all three constituent phases to predict the constitutive response of the CMC computationally. The strain-to-failure of the matrix and fibers were used to progressively fail the constituents in the model and the overall experimental constitutive response of the CMC was recovered. A strain based analytical representation was developed relating stiffness loss to applied strain. Based on this formulation, damage evolution and its consequence on tensile stress-strain response was predicted for room temperature behavior of hybrid CMCs. The contribution of the current work is that the proposed strain-damage phenomenological model can capture the damage evolution and the corresponding material response for continuous fiber-reinforced CMCs. The modeling approach shows much promise for the complex damage processes observed in hybrid CMCs.« less

Simulating Initial and Progressive Failure of Open-Hole Composite Laminates under Tension

NASA Astrophysics Data System (ADS)

Guo, Zhangxin; Zhu, Hao; Li, Yongcun; Han, Xiaoping; Wang, Zhihua

2016-12-01

A finite element (FE) model is developed for the progressive failure analysis of fiber reinforced polymer laminates. The failure criterion for fiber and matrix failure is implemented in the FE code Abaqus using user-defined material subroutine UMAT. The gradual degradation of the material properties is controlled by the individual fracture energies of fiber and matrix. The failure and damage in composite laminates containing a central hole subjected to uniaxial tension are simulated. The numerical results show that the damage model can be used to accurately predicte the progressive failure behaviour both qualitatively and quantitatively.

Progressive failure methodologies for predicting residual strength and life of laminated composites

NASA Technical Reports Server (NTRS)

Harris, Charles E.; Allen, David H.; Obrien, T. Kevin

1991-01-01

Two progressive failure methodologies currently under development by the Mechanics of Materials Branch at NASA Langley Research Center are discussed. The damage tolerance/fail safety methodology developed by O'Brien is an engineering approach to ensuring adequate durability and damage tolerance by treating only delamination onset and the subsequent delamination accumulation through the laminate thickness. The continuum damage model developed by Allen and Harris employs continuum damage laws to predict laminate strength and life. The philosophy, mechanics framework, and current implementation status of each methodology are presented.

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

NASA Technical Reports Server (NTRS)

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

1996-01-01

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

Cohesive Laws and Progressive Damage Analysis of Composite Bonded Joints, a Combined Numerical/Experimental Approach

NASA Technical Reports Server (NTRS)

Girolamo, Donato; Davila, Carlos G.; Leone, Frank A.; Lin, Shih-Yung

2015-01-01

The results of an experimental/numerical campaign aimed to develop progressive damage analysis (PDA) tools for predicting the strength of a composite bonded joint under tensile loads are presented. The PDA is based on continuum damage mechanics (CDM) to account for intralaminar damage, and cohesive laws to account for interlaminar and adhesive damage. The adhesive response is characterized using standard fracture specimens and digital image correlation (DIC). The displacement fields measured by DIC are used to calculate the J-integrals, from which the associated cohesive laws of the structural adhesive can be derived. A finite element model of a sandwich conventional splice joint (CSJ) under tensile loads was developed. The simulations, in agreement with experimental tests, indicate that the model is capable of predicting the interactions of damage modes that lead to the failure of the joint.

Characterization of damaged skin by impedance spectroscopy: chemical damage by dimethyl sulfoxide.

PubMed

White, Erick A; Orazem, Mark E; Bunge, Annette L

2013-10-01

To relate changes in the electrochemical impedance spectra to the progression and mechanism of skin damage arising from exposure to dimethyl sulfoxide (DMSO). Electrochemical impedance spectra measured before and after human cadaver skin was treated with neat DMSO or phosphate buffered saline (control) for 1 h or less were compared with electrical circuit models representing two contrasting theories describing the progression of DMSO damage. Flux of a model lipophilic compound (p-chloronitrobenzene) was also measured. The impedance spectra collected before and after 1 h treatment with DMSO were consistent with a single circuit model; whereas, the spectra collected after DMSO exposure for 0.25 h were consistent with the model circuits observed before and after DMSO treatment for 1 h combined in series. DMSO treatments did not significantly change the flux of p-chloronitrobenzene compared to control. Impedance measurements of human skin exposed to DMSO for less than about 0.5 h were consistent with the presence of two layers: one damaged irreversibly and one unchanged. The thickness of the damaged layer increased proportional to the square-root of treatment time until about 0.5 h, when DMSO affected the entire stratum corneum. Irreversible DMSO damage altered the lipophilic permeation pathway minimally.

Study on Collapse Mechanism of Steel Frame Structure under High Temperature and Blast Loading

NASA Astrophysics Data System (ADS)

Baoxin, Qi; Yan, Shi; Bi, Jialiang

2018-03-01

Numerical simulation analysis for collapsing process and mechanism of steel frame structures under the combined effects of fire and explosion is performed in this paper. First of all, a new steel constitutive model considering fire (high temperature softening effect) and blast (strain rate effect) is established. On the basis of the traditional Johnson-Cook model and the Perzyna model, the relationship between strain and scaled distance as well as the EOUROCODE3 standard heating curve taking into account the temperature effect parameters is introduced, and a modified Johnson-Cook constitutive model is established. Then, the influence of considering the scaled distance is introduced in order to more effectively describe the destruction and collapse phenomena of steel frame structures. Some conclusions are obtained based on the numerical analysis that the destruction will be serious and even progressively collapse with decreasing of the temperature of the steel column for the same scaled distance under the combined effects of fire and blast; the damage will be serious with decreasing of the scaled distance of the steel column under the same temperature under the combined effects of fire and blast; in the case of the combined effects of fire and blast happening in the side-spans, the partial progressive collapse occurs as the scaled distance is less than or equal to 1.28; six kinds of damages which are no damage, minor damage, moderate damage, severe damage, critical collapse, and progressive collapse.

Continuum Fatigue Damage Modeling for Use in Life Extending Control

NASA Technical Reports Server (NTRS)

Lorenzo, Carl F.

1994-01-01

This paper develops a simplified continuum (continuous wrp to time, stress, etc.) fatigue damage model for use in Life Extending Controls (LEC) studies. The work is based on zero mean stress local strain cyclic damage modeling. New nonlinear explicit equation forms of cyclic damage in terms of stress amplitude are derived to facilitate the continuum modeling. Stress based continuum models are derived. Extension to plastic strain-strain rate models are also presented. Application of these models to LEC applications is considered. Progress toward a nonzero mean stress based continuum model is presented. Also, new nonlinear explicit equation forms in terms of stress amplitude are also derived for this case.

Probabilistic Fatigue Damage Prognosis Using a Surrogate Model Trained Via 3D Finite Element Analysis

NASA Technical Reports Server (NTRS)

Leser, Patrick E.; Hochhalter, Jacob D.; Newman, John A.; Leser, William P.; Warner, James E.; Wawrzynek, Paul A.; Yuan, Fuh-Gwo

2015-01-01

Utilizing inverse uncertainty quantification techniques, structural health monitoring can be integrated with damage progression models to form probabilistic predictions of a structure's remaining useful life. However, damage evolution in realistic structures is physically complex. Accurately representing this behavior requires high-fidelity models which are typically computationally prohibitive. In the present work, a high-fidelity finite element model is represented by a surrogate model, reducing computation times. The new approach is used with damage diagnosis data to form a probabilistic prediction of remaining useful life for a test specimen under mixed-mode conditions.

Detailed Post-Soft Impact Progressive Damage Assessment for Hybrid Structure Jet Engines

NASA Technical Reports Server (NTRS)

Siddens, Aaron; Bayandor, Javid; Celestina, Mark L.

2014-01-01

Currently, certification of engine designs for resistance to bird strike is reliant on physical tests. Predictive modeling of engine structural damage has mostly been limited to evaluation of individual forward section components, such as fan blades within a fixed frame of reference, to direct impact with a bird. Such models must be extended to include interactions among engine components under operating conditions to evaluate the full extent of engine damage. This paper presents the results of a study aim to develop a methodology for evaluating bird strike damage in advanced propulsion systems incorporating hybrid composite/metal structures. The initial degradation and failure of individual fan blades struck by a bird were investigated. Subsequent damage to other fan blades and engine components due to resultant violent fan assembly vibrations and fragmentation was further evaluated. Various modeling parameters for the bird and engine components were investigated to determine guidelines for accurately capturing initial damage and progressive failure of engine components. Then, a novel hybrid structure modeling approach was investigated and incorporated into the crashworthiness methodology. Such a tool is invaluable to the process of design, development, and certification of future advanced propulsion systems.

Modelling low velocity impact induced damage in composite laminates

NASA Astrophysics Data System (ADS)

Shi, Yu; Soutis, Constantinos

2017-12-01

The paper presents recent progress on modelling low velocity impact induced damage in fibre reinforced composite laminates. It is important to understand the mechanisms of barely visible impact damage (BVID) and how it affects structural performance. To reduce labour intensive testing, the development of finite element (FE) techniques for simulating impact damage becomes essential and recent effort by the composites research community is reviewed in this work. The FE predicted damage initiation and propagation can be validated by Non Destructive Techniques (NDT) that gives confidence to the developed numerical damage models. A reliable damage simulation can assist the design process to optimise laminate configurations, reduce weight and improve performance of components and structures used in aircraft construction.

An elastic failure model of indentation damage. [of brittle structural ceramics

NASA Technical Reports Server (NTRS)

Liaw, B. M.; Kobayashi, A. S.; Emery, A. F.

1984-01-01

A mechanistically consistent model for indentation damage based on elastic failure at tensile or shear overloads, is proposed. The model accommodates arbitrary crack orientation, stress relaxation, reduction and recovery of stiffness due to crack opening and closure, and interfacial friction due to backward sliding of closed cracks. This elastic failure model was implemented by an axisymmetric finite element program which was used to simulate progressive damage in a silicon nitride plate indented by a tungsten carbide sphere. The predicted damage patterns and the permanent impression matched those observed experimentally. The validation of this elastic failure model shows that the plastic deformation postulated by others is not necessary to replicate the indentation damage of brittle structural ceramics.

Radiation induced pulmonary fibrosis as a model of progressive fibrosis: Contributions of DNA damage, inflammatory response and cellular senescence genes.

PubMed

Beach, Tyler A; Johnston, Carl J; Groves, Angela M; Williams, Jacqueline P; Finkelstein, Jacob N

2017-04-01

Purpose/Aim of Study: Studies of pulmonary fibrosis (PF) have resulted in DNA damage, inflammatory response, and cellular senescence being widely hypothesized to play a role in the progression of the disease. Utilizing these aforementioned terms, genomics databases were interrogated along with the term, "pulmonary fibrosis," to identify genes common among all 4 search terms. Findings were compared to data derived from a model of radiation-induced progressive pulmonary fibrosis (RIPF) to verify that these genes are similarly expressed, supporting the use of radiation as a model for diseases involving PF, such as human idiopathic pulmonary fibrosis (IPF). In an established model of RIPF, C57BL/6J mice were exposed to 12.5 Gy thorax irradiation and sacrificed at 24 hours, 1, 4, 12, and 32 weeks following exposure, and lung tissue was compared to age-matched controls by RNA sequencing. Of 176 PF associated gene transcripts identified by database interrogation, 146 (>82%) were present in our experimental model, throughout the progression of RIPF. Analysis revealed that nearly 85% of PF gene transcripts were associated with at least 1 other search term. Furthermore, of 22 genes common to all four terms, 16 were present experimentally in RIPF. This illustrates the validity of RIPF as a model of progressive PF/IPF based on the numbers of transcripts reported in both literature and observed experimentally. Well characterized genes and proteins are implicated in this model, supporting the hypotheses that DNA damage, inflammatory response and cellular senescence are associated with the pathogenesis of PF.

Analysis Methods for Progressive Damage of Composite Structures

NASA Technical Reports Server (NTRS)

Rose, Cheryl A.; Davila, Carlos G.; Leone, Frank A.

2013-01-01

This document provides an overview of recent accomplishments and lessons learned in the development of general progressive damage analysis methods for predicting the residual strength and life of composite structures. These developments are described within their State-of-the-Art (SoA) context and the associated technology barriers. The emphasis of the authors is on developing these analysis tools for application at the structural level. Hence, modeling of damage progression is undertaken at the mesoscale, where the plies of a laminate are represented as a homogenous orthotropic continuum. The aim of the present effort is establish the ranges of validity of available models, to identify technology barriers, and to establish the foundations of the future investigation efforts. Such are the necessary steps towards accurate and robust simulations that can replace some of the expensive and time-consuming "building block" tests that are currently required for the design and certification of aerospace structures.

Damage Model and Progressive Failure Analyses for Filament Wound Composite Laminates

NASA Astrophysics Data System (ADS)

Ribeiro, Marcelo Leite; Vandepitte, Dirk; Tita, Volnei

2013-10-01

Recent improvements in manufacturing processes and materials properties associated with excellent mechanical characteristics and low weight have made composite materials very attractive for application on civil aircraft structures. However, even new designs are still very conservative, because the composite failure phenomenon is very complex. Several failure criteria and theories have been developed to describe the damage process and how it evolves, but the solution of the problem is still open. Moreover, modern filament winding techniques have been used to produce a wide variety of structural shapes not only cylindrical parts, but also “flat” laminates. Therefore, this work presents the development of a damage model and its application to simulate the progressive failure of flat composite laminates made using a filament winding process. The damage model was implemented as a UMAT (User Material Subroutine), in ABAQUSTM Finite Element (FE) framework. Progressive failure analyses were carried out using FE simulation in order to simulate the failure of flat filament wound composite structures under different loading conditions. In addition, experimental tests were performed in order to identify parameters related to the material model, as well as to evaluate both the potential and the limitations of the model. The difference between numerical and the average experimental results in a four point bending set-up is only 1.6 % at maximum load amplitude. Another important issue is that the model parameters are not so complicated to be identified. This characteristic makes this model very attractive to be applied in an industrial environment.

A mechanics framework for a progressive failure methodology for laminated composites

NASA Technical Reports Server (NTRS)

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

1989-01-01

A laminate strength and life prediction methodology has been postulated for laminated composites which accounts for the progressive development of microstructural damage to structural failure. A damage dependent constitutive model predicts the stress redistribution in an average sense that accompanies damage development in laminates. Each mode of microstructural damage is represented by a second-order tensor valued internal state variable which is a strain like quantity. The mechanics framework together with the global-local strategy for predicting laminate strength and life is presented in the paper. The kinematic effects of damage are represented by effective engineering moduli in the global analysis and the results of the global analysis provide the boundary conditions for the local ply level stress analysis. Damage evolution laws are based on experimental results.

Numerical Simulation for Predicting Fatigue Damage Progress in Notched CFRP Laminates by Using Cohesive Elements

NASA Astrophysics Data System (ADS)

Okabe, Tomonaga; Yashiro, Shigeki

This study proposes the cohesive zone model (CZM) for predicting fatigue damage growth in notched carbon-fiber-reinforced composite plastic (CFRP) cross-ply laminates. In this model, damage growth in the fracture process of cohesive elements due to cyclic loading is represented by the conventional damage mechanics model. We preliminarily investigated whether this model can appropriately express fatigue damage growth for a circular crack embedded in isotropic solid material. This investigation demonstrated that this model could reproduce the results with the well-established fracture mechanics model plus the Paris' law by tuning adjustable parameters. We then numerically investigated the damage process in notched CFRP cross-ply laminates under tensile cyclic loading and compared the predicted damage patterns with those in experiments reported by Spearing et al. (Compos. Sci. Technol. 1992). The predicted damage patterns agreed with the experiment results, which exhibited the extension of multiple types of damage (e.g., splits, transverse cracks and delaminations) near the notches.

Comparison of Damage Models for Predicting the Non-Linear Response of Laminates Under Matrix Dominated Loading Conditions

NASA Technical Reports Server (NTRS)

Schuecker, Clara; Davila, Carlos G.; Rose, Cheryl A.

2010-01-01

Five models for matrix damage in fiber reinforced laminates are evaluated for matrix-dominated loading conditions under plane stress and are compared both qualitatively and quantitatively. The emphasis of this study is on a comparison of the response of embedded plies subjected to a homogeneous stress state. Three of the models are specifically designed for modeling the non-linear response due to distributed matrix cracking under homogeneous loading, and also account for non-linear (shear) behavior prior to the onset of cracking. The remaining two models are localized damage models intended for predicting local failure at stress concentrations. The modeling approaches of distributed vs. localized cracking as well as the different formulations of damage initiation and damage progression are compared and discussed.

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

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

A Damage-Dependent Finite Element Analysis for Fiber-Reinforced Composite Laminates

NASA Technical Reports Server (NTRS)

Coats, Timothy W.; Harris, Charles E.

1998-01-01

A progressive damage methodology has been developed to predict damage growth and residual strength of fiber-reinforced composite structure with through penetrations such as a slit. The methodology consists of a damage-dependent constitutive relationship based on continuum damage mechanics. Damage is modeled using volume averaged strain-like quantities known as internal state variables and is represented in the equilibrium equations as damage induced force vectors instead of the usual degradation and modification of the global stiffness matrix.

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

PubMed

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

2009-12-01

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

A Progressive Damage Model for unidirectional Fibre Reinforced Composites with Application to Impact and Penetration Simulation

NASA Astrophysics Data System (ADS)

Kerschbaum, M.; Hopmann, C.

2016-06-01

The computationally efficient simulation of the progressive damage behaviour of continuous fibre reinforced plastics is still a challenging task with currently available computer aided engineering methods. This paper presents an original approach for an energy based continuum damage model which accounts for stress-/strain nonlinearities, transverse and shear stress interaction phenomena, quasi-plastic shear strain components, strain rate effects, regularised damage evolution and consideration of load reversal effects. The physically based modelling approach enables experimental determination of all parameters on ply level to avoid expensive inverse analysis procedures. The modelling strategy, implementation and verification of this model using commercially available explicit finite element software are detailed. The model is then applied to simulate the impact and penetration of carbon fibre reinforced cross-ply specimens with variation of the impact speed. The simulation results show that the presented approach enables a good representation of the force-/displacement curves and especially well agreement with the experimentally observed fracture patterns. In addition, the mesh dependency of the results were assessed for one impact case showing only very little change of the simulation results which emphasises the general applicability of the presented method.

Assessment of Intralaminar Progressive Damage and Failure Analysis Using an Efficient Evaluation Framework

NASA Technical Reports Server (NTRS)

Hyder, Imran; Schaefer, Joseph; Justusson, Brian; Wanthal, Steve; Leone, Frank; Rose, Cheryl

2017-01-01

Reducing the timeline for development and certification for composite structures has been a long standing objective of the aerospace industry. This timeline can be further exacerbated when attempting to integrate new fiber-reinforced composite materials due to the large number of testing required at every level of design. computational progressive damage and failure analysis (PDFA) attempts to mitigate this effect; however, new PDFA methods have been slow to be adopted in industry since material model evaluation techniques have not been fully defined. This study presents an efficient evaluation framework which uses a piecewise verification and validation (V&V) approach for PDFA methods. Specifically, the framework is applied to evaluate PDFA research codes within the context of intralaminar damage. Methods are incrementally taken through various V&V exercises specifically tailored to study PDFA intralaminar damage modeling capability. Finally, methods are evaluated against a defined set of success criteria to highlight successes and limitations.

Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding.

PubMed

Reissig, Kathrin; Silver, Andrew; Hartig, Roland; Schinlauer, Antje; Walluscheck, Diana; Guenther, Thomas; Siedentopf, Sandra; Ross, Jochen; Vo, Diep-Khanh; Roessner, Albert; Poehlmann-Nitsche, Angela

2017-01-01

Dysregulation of c-Jun N -terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases. In both phases, Chk1 was linked to DNA damage response bypass by suppressing JNK activation following oxidative stress, promoting cell cycle progression despite DNA damage. Simultaneously, activated Chk1 was bound to chromatin. This triggered histone acetylation and the binding of histone acetyltransferases and transcription factors to chromatin. Thus, chromatin-immobilized activated Chk1 executed a dual function by suppressing DNA damage response and simultaneously inducing chromatin modulation. This caused undetected DNA damage and increased cellular proliferation through failure to transmit the appropriate DNA damage signal. Findings in vitro were corroborated by chromatin accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in vivo. Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel therapeutic strategy to prevent UC-related tumor progression.

Computational Aerodynamics of Shuttle Orbiter Damage Scenarios in Support of the Columbia Accident Investigation

NASA Technical Reports Server (NTRS)

Bibb, Karen L.; Prabhu, Ramadas K.

2004-01-01

In support of the Columbia Accident Investigation, inviscid computations of the aerodynamic characteristics for various Shuttle Orbiter damage scenarios were performed using the FELISA unstructured CFD solver. Computed delta aerodynamics were compared with the reconstructed delta aerodynamics in order to postulate a progression of damage through the flight trajectory. By performing computations at hypervelocity flight and CF4 tunnel conditions, a bridge was provided between wind tunnel testing in Langley's 20-Inch CF4 facility and the flight environment experienced by Columbia during re-entry. The rapid modeling capability of the unstructured methodology allowed the computational effort to keep pace with the wind tunnel and, at times, guide the wind tunnel efforts. These computations provided a detailed view of the flowfield characteristics and the contribution of orbiter components (such as the vertical tail and wing) to aerodynamic forces and moments that were unavailable from wind tunnel testing. The damage scenarios are grouped into three categories. Initially, single and multiple missing full RCC panels were analyzed to determine the effect of damage location and magnitude on the aerodynamics. Next is a series of cases with progressive damage, increasing in severity, in the region of RCC panel 9. The final group is a set of wing leading edge and windward surface deformations that model possible structural deformation of the wing skin due to internal heating of the wing structure. By matching the aerodynamics from selected damage scenarios to the reconstructed flight aerodynamics, a progression of damage that is consistent with the flight data, debris forensics, and wind tunnel data is postulated.

DAMAGE MODELING OF INJECTION-MOLDED SHORT- AND LONG-FIBER THERMOPLASTICS

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

Nguyen, Ba Nghiep; Kunc, Vlastimil; Bapanapalli, Satish K.

2009-10-30

This article applies the recent anisotropic rotary diffusion – reduced strain closure (ARD-RSC) model for predicting fiber orientation and a new damage model for injection-molded long-fiber thermoplastics (LFTs) to analyze progressive damage leading to total failure of injection-molded long-glass-fiber/polypropylene (PP) specimens. The ARD-RSC model was implemented in a research version of the Autodesk Moldflow Plastics Insight (MPI) processing code, and it has been used to simulate injection-molding of a long-glass-fiber/PP plaque. The damage model combines micromechanical modeling with a continuum damage mechanics description to predict the nonlinear behavior due to plasticity coupled with damage in LFTs. This model has beenmore » implemented in the ABAQUS finite element code via user-subroutines and has been used in the damage analyses of tensile specimens removed from the injection-molded long-glass-fiber/PP plaques. Experimental characterization and mechanical testing were performed to provide input data to support and validate both process modeling and damage analyses. The predictions are in agreement with the experimental results.« less

Meso-Scale Progressive Damage Behavior Characterization of Triaxial Braided Composites under Quasi-Static Tensile Load

NASA Astrophysics Data System (ADS)

Ren, Yiru; Zhang, Songjun; Jiang, Hongyong; Xiang, Jinwu

2018-04-01

Based on continuum damage mechanics (CDM), a sophisticated 3D meso-scale finite element (FE) model is proposed to characterize the progressive damage behavior of 2D Triaxial Braided Composites (2DTBC) with 60° braiding angle under quasi-static tensile load. The modified Von Mises strength criterion and 3D Hashin failure criterion are used to predict the damage initiation of the pure matrix and fiber tows. A combining interface damage and friction constitutive model is applied to predict the interface damage behavior. Murakami-Ohno stiffness degradation scheme is employed to predict the damage evolution process of each constituent. Coupling with the ordinary and translational symmetry boundary conditions, the tensile elastic response including tensile strength and failure strain of 2DTBC are in good agreement with the available experiment data. The numerical results show that the main failure modes of the composites under axial tensile load are pure matrix cracking, fiber and matrix tension failure in bias fiber tows, matrix tension failure in axial fiber tows and interface debonding; the main failure modes of the composites subjected to transverse tensile load are free-edge effect, matrix tension failure in bias fiber tows and interface debonding.

PRELIMINARY PROGRESS IN THE DEVELOPMENT OF DUCTILE-PHASE TOUGHENED TUNGSTEN FOR PLASMA-FACING MATERIALS: DUAL-PHASE FINITE ELEMENT DAMAGE MODELS

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

Henager, Charles H.; Nguyen, Ba Nghiep; Kurtz, Richard J.

The objective of this study is to develop a finite element continuum damage model suitable for modeling deformation, cracking, and crack bridging for W-Cu, W-Ni-Fe, and other ductile phase toughened W-composites, or more generally, any multi-phase composite structure where two or more phases undergo cooperative deformation in a composite system.

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

NASA Technical Reports Server (NTRS)

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

1992-01-01

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

A new multi-layer approach for progressive damage simulation in composite laminates based on isogeometric analysis and Kirchhoff-Love shells. Part II: impact modeling

NASA Astrophysics Data System (ADS)

Pigazzini, M. S.; Bazilevs, Y.; Ellison, A.; Kim, H.

2017-11-01

In this two-part paper we introduce a new formulation for modeling progressive damage in laminated composite structures. We adopt a multi-layer modeling approach, based on isogeometric analysis, where each ply or lamina is represented by a spline surface, and modeled as a Kirchhoff-Love thin shell. Continuum damage mechanics is used to model intralaminar damage, and a new zero-thickness cohesive-interface formulation is introduced to model delamination as well as permitting laminate-level transverse shear compliance. In Part I of this series we focus on the presentation of the modeling framework, validation of the framework using standard Mode I and Mode II delamination tests, and assessment of its suitability for modeling thick laminates. In Part II of this series we focus on the application of the proposed framework to modeling and simulation of damage in composite laminates resulting from impact. The proposed approach has significant accuracy and efficiency advantages over existing methods for modeling impact damage. These stem from the use of IGA-based Kirchhoff-Love shells to represent the individual plies of the composite laminate, while the compliant cohesive interfaces enable transverse shear deformation of the laminate. Kirchhoff-Love shells give a faithful representation of the ply deformation behavior, and, unlike solids or traditional shear-deformable shells, do not suffer from transverse-shear locking in the limit of vanishing thickness. This, in combination with higher-order accurate and smooth representation of the shell midsurface displacement field, allows us to adopt relatively coarse in-plane discretizations without sacrificing solution accuracy. Furthermore, the thin-shell formulation employed does not use rotational degrees of freedom, which gives additional efficiency benefits relative to more standard shell formulations.

A new multi-layer approach for progressive damage simulation in composite laminates based on isogeometric analysis and Kirchhoff-Love shells. Part I: basic theory and modeling of delamination and transverse shear

NASA Astrophysics Data System (ADS)

Bazilevs, Y.; Pigazzini, M. S.; Ellison, A.; Kim, H.

2017-11-01

In this two-part paper we introduce a new formulation for modeling progressive damage in laminated composite structures. We adopt a multi-layer modeling approach, based on Isogeometric Analysis (IGA), where each ply or lamina is represented by a spline surface, and modeled as a Kirchhoff-Love thin shell. Continuum Damage Mechanics is used to model intralaminar damage, and a new zero-thickness cohesive-interface formulation is introduced to model delamination as well as permitting laminate-level transverse shear compliance. In Part I of this series we focus on the presentation of the modeling framework, validation of the framework using standard Mode I and Mode II delamination tests, and assessment of its suitability for modeling thick laminates. In Part II of this series we focus on the application of the proposed framework to modeling and simulation of damage in composite laminates resulting from impact. The proposed approach has significant accuracy and efficiency advantages over existing methods for modeling impact damage. These stem from the use of IGA-based Kirchhoff-Love shells to represent the individual plies of the composite laminate, while the compliant cohesive interfaces enable transverse shear deformation of the laminate. Kirchhoff-Love shells give a faithful representation of the ply deformation behavior, and, unlike solids or traditional shear-deformable shells, do not suffer from transverse-shear locking in the limit of vanishing thickness. This, in combination with higher-order accurate and smooth representation of the shell midsurface displacement field, allows us to adopt relatively coarse in-plane discretizations without sacrificing solution accuracy. Furthermore, the thin-shell formulation employed does not use rotational degrees of freedom, which gives additional efficiency benefits relative to more standard shell formulations.

Damage Simulation in Non-Crimp Fabric Composite Plates Subjected to Impact Loads

NASA Technical Reports Server (NTRS)

Satyanarayana, Arunkumar; Bogert, Philip B.; Aitharaju, Venkat; Aashat, Satvir; Kia, Hamid

2014-01-01

Progressive failure analysis (PFA) of non-crimp fabric (NCF) composite laminates subjected to low velocity impact loads was performed using the COmplete STress Reduction (COSTR) damage model implemented through VUMAT and UMAT41 user subroutines in the frame works of the commercial finite element programs ABAQUS/Explicit and LS-DYNA, respectively. To validate the model, low velocity experiments were conducted and detailed correlations between the predictions and measurements for both intra-laminar and inter-laminar failures were made. The developed material and damage model predicts the peak impact load and duration very close with the experimental results. Also, the simulation results of delamination damage between the ply interfaces, in-plane matrix damages and fiber damages were all in good agreement with the measurements from the non-destructive evaluation data.

Micromechanics Fatigue Damage Analysis Modeling for Fabric Reinforced Ceramic Matrix Composites

NASA Technical Reports Server (NTRS)

Min, J. B.; Xue, D.; Shi, Y.

2013-01-01

A micromechanics analysis modeling method was developed to analyze the damage progression and fatigue failure of fabric reinforced composite structures, especially for the brittle ceramic matrix material composites. A repeating unit cell concept of fabric reinforced composites was used to represent the global composite structure. The thermal and mechanical properties of the repeating unit cell were considered as the same as those of the global composite structure. The three-phase micromechanics, the shear-lag, and the continuum fracture mechanics models were integrated with a statistical model in the repeating unit cell to predict the progressive damages and fatigue life of the composite structures. The global structure failure was defined as the loss of loading capability of the repeating unit cell, which depends on the stiffness reduction due to material slice failures and nonlinear material properties in the repeating unit cell. The present methodology is demonstrated with the analysis results evaluated through the experimental test performed with carbon fiber reinforced silicon carbide matrix plain weave composite specimens.

Investigation of Time Series Representations and Similarity Measures for Structural Damage Pattern Recognition

PubMed Central

Swartz, R. Andrew

2013-01-01

This paper investigates the time series representation methods and similarity measures for sensor data feature extraction and structural damage pattern recognition. Both model-based time series representation and dimensionality reduction methods are studied to compare the effectiveness of feature extraction for damage pattern recognition. The evaluation of feature extraction methods is performed by examining the separation of feature vectors among different damage patterns and the pattern recognition success rate. In addition, the impact of similarity measures on the pattern recognition success rate and the metrics for damage localization are also investigated. The test data used in this study are from the System Identification to Monitor Civil Engineering Structures (SIMCES) Z24 Bridge damage detection tests, a rigorous instrumentation campaign that recorded the dynamic performance of a concrete box-girder bridge under progressively increasing damage scenarios. A number of progressive damage test case datasets and damage test data with different damage modalities are used. The simulation results show that both time series representation methods and similarity measures have significant impact on the pattern recognition success rate. PMID:24191136

Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding

PubMed Central

Silver, Andrew; Guenther, Thomas; Siedentopf, Sandra; Ross, Jochen; Vo, Diep-Khanh; Roessner, Albert

2017-01-01

Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases. In both phases, Chk1 was linked to DNA damage response bypass by suppressing JNK activation following oxidative stress, promoting cell cycle progression despite DNA damage. Simultaneously, activated Chk1 was bound to chromatin. This triggered histone acetylation and the binding of histone acetyltransferases and transcription factors to chromatin. Thus, chromatin-immobilized activated Chk1 executed a dual function by suppressing DNA damage response and simultaneously inducing chromatin modulation. This caused undetected DNA damage and increased cellular proliferation through failure to transmit the appropriate DNA damage signal. Findings in vitro were corroborated by chromatin accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in vivo. Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel therapeutic strategy to prevent UC-related tumor progression. PMID:28751935

GENOA-PFA: Progressive Fracture in Composites Simulated Computationally

NASA Technical Reports Server (NTRS)

Murthy, Pappu L. N.

2000-01-01

GENOA-PFA is a commercial version of the Composite Durability Structural Analysis (CODSTRAN) computer program that simulates the progression of damage ultimately leading to fracture in polymer-matrix-composite (PMC) material structures under various loading and environmental conditions. GENOA-PFA offers several capabilities not available in other programs developed for this purpose, making it preferable for use in analyzing the durability and damage tolerance of complex PMC structures in which the fiber reinforcements occur in two- and three-dimensional weaves and braids. GENOA-PFA implements a progressive-fracture methodology based on the idea that a structure fails when flaws that may initially be small (even microscopic) grow and/or coalesce to a critical dimension where the structure no longer has an adequate safety margin to avoid catastrophic global fracture. Damage is considered to progress through five stages: (1) initiation, (2) growth, (3) accumulation (coalescence of propagating flaws), (4) stable propagation (up to the critical dimension), and (5) unstable or very rapid propagation (beyond the critical dimension) to catastrophic failure. The computational simulation of progressive failure involves formal procedures for identifying the five different stages of damage and for relating the amount of damage at each stage to the overall behavior of the deteriorating structure. In GENOA-PFA, mathematical modeling of the composite physical behavior involves an integration of simulations at multiple, hierarchical scales ranging from the macroscopic (lamina, laminate, and structure) to the microscopic (fiber, matrix, and fiber/matrix interface), as shown in the figure. The code includes algorithms to simulate the progression of damage from various source defects, including (1) through-the-thickness cracks and (2) voids with edge, pocket, internal, or mixed-mode delaminations.

A Microstructurally Inspired Damage Model for Early Venous Thrombus

PubMed Central

Rausch, Manuel K.; Humphrey, Jay D.

2015-01-01

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

Environmental Barrier Coating Fracture, Fatigue and High-Heat-Flux Durability Modeling and Stochastic Progressive Damage Simulation

NASA Technical Reports Server (NTRS)

Zhu, Dongming; Nemeth, Noel N.

2017-01-01

Advanced environmental barrier coatings will play an increasingly important role in future gas turbine engines because of their ability to protect emerging light-weight SiC/SiC ceramic matrix composite (CMC) engine components, further raising engine operating temperatures and performance. Because the environmental barrier coating systems are critical to the performance, reliability and durability of these hot-section ceramic engine components, a prime-reliant coating system along with established life design methodology are required for the hot-section ceramic component insertion into engine service. In this paper, we have first summarized some observations of high temperature, high-heat-flux environmental degradation and failure mechanisms of environmental barrier coating systems in laboratory simulated engine environment tests. In particular, the coating surface cracking morphologies and associated subsequent delamination mechanisms under the engine level high-heat-flux, combustion steam, and mechanical creep and fatigue loading conditions will be discussed. The EBC compostion and archtechture improvements based on advanced high heat flux environmental testing, and the modeling advances based on the integrated Finite Element Analysis Micromechanics Analysis Code/Ceramics Analysis and Reliability Evaluation of Structures (FEAMAC/CARES) program will also be highlighted. The stochastic progressive damage simulation successfully predicts mud flat damage pattern in EBCs on coated 3-D specimens, and a 2-D model of through-the-thickness cross-section. A 2-parameter Weibull distribution was assumed in characterizing the coating layer stochastic strength response and the formation of damage was therefore modeled. The damage initiation and coalescence into progressively smaller mudflat crack cells was demonstrated. A coating life prediction framework may be realized by examining the surface crack initiation and delamination propagation in conjunction with environmental degradation under high-heat-flux and environment load test conditions.

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.

Prediction of functional loss in glaucoma from progressive optic disc damage.

PubMed

Medeiros, Felipe A; Alencar, Luciana M; Zangwill, Linda M; Bowd, Christopher; Sample, Pamela A; Weinreb, Robert N

2009-10-01

To evaluate the ability of progressive optic disc damage detected by assessment of longitudinal stereophotographs to predict future development of functional loss in those with suspected glaucoma. The study included 639 eyes of 407 patients with suspected glaucoma followed up for an average of 8.0 years with annual standard automated perimetry visual field and optic disc stereophotographs. All patients had normal and reliable standard automated perimetry results at baseline. Conversion to glaucoma was defined as development of 3 consecutive abnormal visual fields during follow-up. Presence of progressive optic disc damage was evaluated by grading longitudinally acquired simultaneous stereophotographs. Other predictive factors included age, intraocular pressure, central corneal thickness, pattern standard deviation, and baseline stereophotograph grading. Hazard ratios for predicting visual field loss were obtained by extended Cox models, with optic disc progression as a time-dependent covariate. Predictive accuracy was evaluated using a modified R(2) index. Progressive optic disc damage had a hazard ratio of 25.8 (95% confidence interval, 16.0-41.7) and was the most important risk factor for development of visual field loss with an R(2) of 79%. The R(2)s for other predictive factors ranged from 6% to 26%. Presence of progressive optic disc damage on stereophotographs was a highly predictive factor for future development of functional loss in glaucoma. These findings suggest the importance of careful monitoring of the optic disc appearance and a potential role for longitudinal assessment of the optic disc as an end point in clinical trials and as a reference for evaluation of diagnostic tests in glaucoma.

White and gray matter damage in primary progressive MS: The chicken or the egg?

PubMed

Bodini, Benedetta; Chard, Declan; Altmann, Daniel R; Tozer, Daniel; Miller, David H; Thompson, Alan J; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

2016-01-12

The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex ("primary WM damage model"); and (2) cortical abnormalities predict later changes in connected WM tracts ("primary GM damage model"). Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. © 2015 American Academy of Neurology.

Impact Damage and Strain Rate Effects for Toughened Epoxy Composite Structures

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Minnetyan, Levon

2006-01-01

Structural integrity of composite systems under dynamic impact loading is investigated herein. The GENOA virtual testing software environment is used to implement the effects of dynamic loading on fracture progression and damage tolerance. Combinations of graphite and glass fibers with a toughened epoxy matrix are investigated. The effect of a ceramic coating for the absorption of impact energy is also included. Impact and post impact simulations include verification and prediction of (1) Load and Impact Energy, (2) Impact Damage Size, (3) Maximum Impact Peak Load, (4) Residual Strength, (5) Maximum Displacement, (6) Contribution of Failure Modes to Failure Mechanisms, (7) Prediction of Impact Load Versus Time, and (8) Damage, and Fracture Pattern. A computer model is utilized for the assessment of structural response, progressive fracture, and defect/damage tolerance characteristics. Results show the damage progression sequence and the changes in the structural response characteristics due to dynamic impact. The fundamental premise of computational simulation is that the complete evaluation of composite fracture requires an assessment of ply and subply level damage/fracture processes as the structure is subjected to loads. Simulation results for the graphite/epoxy composite were compared with the impact and tension failure test data, correlation and verification was obtained that included: (1) impact energy, (2) damage size, (3) maximum impact peak load, (4) residual strength, (5) maximum displacement, and (6) failure mechanisms of the composite structure.

A continuum model for damage evolution in laminated composites

NASA Technical Reports Server (NTRS)

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

1991-01-01

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

An Interface Damage Model for the Simulation of Delamination Under Variable-Mode Ratio in Composite Materials

NASA Technical Reports Server (NTRS)

Turon, Albert; Camanho, Pedro P.; Costa, Josep; Davila, Carlos G.

2004-01-01

A thermodynamically consistent damage model for the simulation of progressive delamination under variable mode ratio is presented. The model is formulated in the context of the Damage Mechanics (DM). The constitutive equations that result from the variation of the free energy with damage are used to model the initiation and propagation of delamination. A new delamination initiation criterion is developed to assure that the formulation can account for changes in the loading mode in a thermodynamically consistent way. Interfacial penetration of two adjacent layers after complete decohesion is prevented by the formulation of the free energy. The model is implemented into the commercial finite element code ABAQUS by means of a user-written decohesion element. Finally, the numerical predictions given by the model are compared with experimental results.

Modelling of Damage Evolution in Braided Composites: Recent Developments

NASA Astrophysics Data System (ADS)

Wang, Chen; Roy, Anish; Silberschmidt, Vadim V.; Chen, Zhong

2017-12-01

Composites reinforced with woven or braided textiles exhibit high structural stability and excellent damage tolerance thanks to yarn interlacing. With their high stiffness-to-weight and strength-to-weight ratios, braided composites are attractive for aerospace and automotive components as well as sports protective equipment. In these potential applications, components are typically subjected to multi-directional static, impact and fatigue loadings. To enhance material analysis and design for such applications, understanding mechanical behaviour of braided composites and development of predictive capabilities becomes crucial. Significant progress has been made in recent years in development of new modelling techniques allowing elucidation of static and dynamic responses of braided composites. However, because of their unique interlacing geometric structure and complicated failure modes, prediction of damage initiation and its evolution in components is still a challenge. Therefore, a comprehensive literature analysis is presented in this work focused on a review of the state-of-the-art progressive damage analysis of braided composites with finite-element simulations. Recently models employed in the studies on mechanical behaviour, impact response and fatigue analyses of braided composites are presented systematically. This review highlights the importance, advantages and limitations of as-applied failure criteria and damage evolution laws for yarns and composite unit cells. In addition, this work provides a good reference for future research on FE simulations of braided composites.

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.

Modeling Progressive Damage Using Local Displacement Discontinuities Within the FEAMAC Multiscale Modeling Framework

NASA Technical Reports Server (NTRS)

Ranatunga, Vipul; Bednarcyk, Brett A.; Arnold, Steven M.

2010-01-01

A method for performing progressive damage modeling in composite materials and structures based on continuum level interfacial displacement discontinuities is presented. The proposed method enables the exponential evolution of the interfacial compliance, resulting in unloading of the tractions at the interface after delamination or failure occurs. In this paper, the proposed continuum displacement discontinuity model has been used to simulate failure within both isotropic and orthotropic materials efficiently and to explore the possibility of predicting the crack path, therein. Simulation results obtained from Mode-I and Mode-II fracture compare the proposed approach with the cohesive element approach and Virtual Crack Closure Techniques (VCCT) available within the ABAQUS (ABAQUS, Inc.) finite element software. Furthermore, an eccentrically loaded 3-point bend test has been simulated with the displacement discontinuity model, and the resulting crack path prediction has been compared with a prediction based on the extended finite element model (XFEM) approach.

Early axonal damage and progressive myelin pathology define the kinetics of CNS histopathology in a mouse model of multiple sclerosis.

PubMed

Recks, Mascha S; Stormanns, Eva R; Bader, Jonas; Arnhold, Stefan; Addicks, Klaus; Kuerten, Stefanie

2013-10-01

Studies of MS histopathology are largely dependent on suitable animal models. While light microscopic analysis gives an overview of tissue pathology, it falls short in evaluating detailed changes in nerve fiber morphology. The ultrastructural data presented here and obtained from studies of myelin oligodendrocyte glycoprotein (MOG):35-55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice delineate that axonal damage and myelin pathology follow different kinetics in the disease course. While myelin pathology accumulated with disease progression, axonal damage coincided with the initial clinical disease symptoms and remained stable over time. This pattern applied both to irreversible axolysis and early axonal pathology. Notably, these histopathological patterns were reflected by the normal-appearing white matter (NAWM), suggesting that the NAWM is also in an active neurodegenerative state. The data underline the need for neuroprotection in MS and suggest the MOG model as a highly valuable tool for the assessment of different therapeutic strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

Modeling Geometry and Progressive Failure of Material Interfaces in Plain Weave Composites

NASA Technical Reports Server (NTRS)

Hsu, Su-Yuen; Cheng, Ron-Bin

2010-01-01

A procedure combining a geometrically nonlinear, explicit-dynamics contact analysis, computer aided design techniques, and elasticity-based mesh adjustment is proposed to efficiently generate realistic finite element models for meso-mechanical analysis of progressive failure in textile composites. In the procedure, the geometry of fiber tows is obtained by imposing a fictitious expansion on the tows. Meshes resulting from the procedure are conformal with the computed tow-tow and tow-matrix interfaces but are incongruent at the interfaces. The mesh interfaces are treated as cohesive contact surfaces not only to resolve the incongruence but also to simulate progressive failure. The method is employed to simulate debonding at the material interfaces in a ceramic-matrix plain weave composite with matrix porosity and in a polymeric matrix plain weave composite without matrix porosity, both subject to uniaxial cyclic loading. The numerical results indicate progression of the interfacial damage during every loading and reverse loading event in a constant strain amplitude cyclic process. However, the composites show different patterns of damage advancement.

Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats.

PubMed

Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi

2015-12-01

The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules. © 2015 Chugai Pharmaceutical Co., Ltd. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Accelerated hand bone mineral density loss is associated with progressive joint damage in hands and feet in recent-onset rheumatoid arthritis.

PubMed

Güler-Yüksel, Melek; Klarenbeek, Naomi B; Goekoop-Ruiterman, Yvonne P M; de Vries-Bouwstra, Jeska K; van der Kooij, Sjoerd M; Gerards, Andreas H; Ronday, H Karel; Huizinga, Tom W J; Dijkmans, Ben A C; Allaart, Cornelia F; Lems, Willem F

2010-01-01

To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years. In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years. 68% of the patients had accelerated hand BMD loss (>-0.003 g/cm2) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage. In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year.

Stochastic-Strength-Based Damage Simulation Tool for Ceramic Matrix and Polymer Matrix Composite Structures

NASA Technical Reports Server (NTRS)

Nemeth, Noel N.; Bednarcyk, Brett A.; Pineda, Evan J.; Walton, Owen J.; Arnold, Steven M.

2016-01-01

Stochastic-based, discrete-event progressive damage simulations of ceramic-matrix composite and polymer matrix composite material structures have been enabled through the development of a unique multiscale modeling tool. This effort involves coupling three independently developed software programs: (1) the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC), (2) the Ceramics Analysis and Reliability Evaluation of Structures Life Prediction Program (CARES/ Life), and (3) the Abaqus finite element analysis (FEA) program. MAC/GMC contributes multiscale modeling capabilities and micromechanics relations to determine stresses and deformations at the microscale of the composite material repeating unit cell (RUC). CARES/Life contributes statistical multiaxial failure criteria that can be applied to the individual brittle-material constituents of the RUC. Abaqus is used at the global scale to model the overall composite structure. An Abaqus user-defined material (UMAT) interface, referred to here as "FEAMAC/CARES," was developed that enables MAC/GMC and CARES/Life to operate seamlessly with the Abaqus FEA code. For each FEAMAC/CARES simulation trial, the stochastic nature of brittle material strength results in random, discrete damage events, which incrementally progress and lead to ultimate structural failure. This report describes the FEAMAC/CARES methodology and discusses examples that illustrate the performance of the tool. A comprehensive example problem, simulating the progressive damage of laminated ceramic matrix composites under various off-axis loading conditions and including a double notched tensile specimen geometry, is described in a separate report.

A simple nonlocal damage model for predicting failure of notched laminates

NASA Technical Reports Server (NTRS)

Kennedy, T. C.; Nahan, M. F.

1995-01-01

The ability to predict failure loads in notched composite laminates is a requirement in a variety of structural design circumstances. A complicating factor is the development of a zone of damaged material around the notch tip. The objective of this study was to develop a computational technique that simulates progressive damage growth around a notch in a manner that allows the prediction of failure over a wide range of notch sizes. This was accomplished through the use of a relatively simple, nonlocal damage model that incorporates strain-softening. This model was implemented in a two-dimensional finite element program. Calculations were performed for two different laminates with various notch sizes under tensile loading, and the calculations were found to correlate well with experimental results.

Analysis of Discrete-Source Damage Progression in a Tensile Stiffened Composite Panel

NASA Technical Reports Server (NTRS)

Wang, John T.; Lotts, Christine G.; Sleight, David W.

1999-01-01

This paper demonstrates the progressive failure analysis capability in NASA Langley s COMET-AR finite element analysis code on a large-scale built-up composite structure. A large-scale five stringer composite panel with a 7-in. long discrete source damage was analyzed from initial loading to final failure including the geometric and material nonlinearities. Predictions using different mesh sizes, different saw cut modeling approaches, and different failure criteria were performed and assessed. All failure predictions have a reasonably good correlation with the test result.

Comparison of MELCOR and SCDAP/RELAP5 results for a low-pressure, short-term station blackout at Browns Ferry

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

Carbajo, J.J.

1995-12-31

This study compares results obtained with two U.S. Nuclear Regulatory Commission (NRC)-sponsored codes, MELCOR version 1.8.3 (1.8PQ) and SCDAP/RELAP5 Mod3.1 release C, for the same transient - a low-pressure, short-term station blackout accident at the Browns Ferry nuclear plant. This work is part of MELCOR assessment activities to compare core damage progression calculations of MELCOR against SCDAP/RELAP5 since the two codes model core damage progression very differently.

Application of Interface Technology in Progressive Failure Analysis of Composite Panels

NASA Technical Reports Server (NTRS)

Sleight, D. W.; Lotts, C. G.

2002-01-01

A progressive failure analysis capability using interface technology is presented. The capability has been implemented in the COMET-AR finite element analysis code developed at the NASA Langley Research Center and is demonstrated on composite panels. The composite panels are analyzed for damage initiation and propagation from initial loading to final failure using a progressive failure analysis capability that includes both geometric and material nonlinearities. Progressive failure analyses are performed on conventional models and interface technology models of the composite panels. Analytical results and the computational effort of the analyses are compared for the conventional models and interface technology models. The analytical results predicted with the interface technology models are in good correlation with the analytical results using the conventional models, while significantly reducing the computational effort.

Fatigue Damage of Collagenous Tissues: Experiment, Modeling and Simulation Studies

PubMed Central

Martin, Caitlin; Sun, Wei

2017-01-01

Mechanical fatigue damage is a critical issue for soft tissues and tissue-derived materials, particularly for musculoskeletal and cardiovascular applications; yet, our understanding of the fatigue damage process is incomplete. Soft tissue fatigue experiments are often difficult and time-consuming to perform, which has hindered progress in this area. However, the recent development of soft-tissue fatigue-damage constitutive models has enabled simulation-based fatigue analyses of tissues under various conditions. Computational simulations facilitate highly controlled and quantitative analyses to study the distinct effects of various loading conditions and design features on tissue durability; thus, they are advantageous over complex fatigue experiments. Although significant work to calibrate the constitutive models from fatigue experiments and to validate predictability remains, further development in these areas will add to our knowledge of soft-tissue fatigue damage and will facilitate the design of durable treatments and devices. In this review, the experimental, modeling, and simulation efforts to study collagenous tissue fatigue damage are summarized and critically assessed. PMID:25955007

Ballistic damage in hybrid composite laminates

NASA Astrophysics Data System (ADS)

Phadnis, Vaibhav A.; Pandya, Kedar S.; Naik, Niranjan K.; Roy, Anish; Silberschmidt, Vadim V.

2015-07-01

Ballistic damage of hybrid woven-fabric composites made of plain-weave E-glass- fabric/epoxy and 8H satin-weave T300 carbon-fabric/epoxy is studied using a combination of experimental tests, microstructural studies and finite-element (FE) analysis. Ballistic tests were conducted with a single-stage gas gun. Fibre damage and delamination were observed to be dominating failure modes. A ply-level FE model was developed, with a fabric-reinforced ply modelled as a homogeneous orthotropic material with capacity to sustain progressive stiffness degradation due to fibre/matrix cracking, fibre breaking and plastic deformation under shear loading. Simulated damage patterns on the front and back faces of fabric-reinforced composite plates provided an insight into their damage mechanisms under ballistic loading.

A Damage Model for the Simulation of Delamination in Advanced Composites under Variable-Mode Loading

NASA Technical Reports Server (NTRS)

Turon, A.; Camanho, P. P.; Costa, J.; Davila, C. G.

2006-01-01

A thermodynamically consistent damage model is proposed for the simulation of progressive delamination in composite materials under variable-mode ratio. The model is formulated in the context of Damage Mechanics. A novel constitutive equation is developed to model the initiation and propagation of delamination. A delamination initiation criterion is proposed to assure that the formulation can account for changes in the loading mode in a thermodynamically consistent way. The formulation accounts for crack closure effects to avoid interfacial penetration of two adjacent layers after complete decohesion. The model is implemented in a finite element formulation, and the numerical predictions are compared with experimental results obtained in both composite test specimens and structural components.

Double dissociation of semantic categories in Alzheimer's disease.

PubMed

Gonnerman, L M; Andersen, E S; Devlin, J T; Kempler, D; Seidenberg, M S

1997-04-01

Data that demonstrate distinct patterns of semantic impairment in Alzheimer's disease (AD) are presented. Findings suggest that while groups of mild-moderate patients may not display category specific impairments, some individual patients do show selective impairment of either natural kinds or artifacts. We present a model of semantic organization in which category specific impairments arise from damage to distributed features underlying different types of categories. We incorporate the crucial notions of intercorrelations and distinguishing features, allowing us to demonstrate (1) how category specific impairments can result from widespread damage and (2) how selective deficits in AD reflect different points in the progression of impairment. The different patterns of impairment arise from an interaction between the nature of the semantic categories and the progression of damage.

Progressive Fracture of Fiber Composite Build-Up Structures

NASA Technical Reports Server (NTRS)

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

1997-01-01

Damage progression and fracture of built-up composite structures is evaluated by using computational simulation. The objective is to examine the behavior and response of a stiffened composite (0/ +/- 45/90)(sub s6) laminate panel by simulating the damage initiation, growth, accumulation, progression and propagation to structural collapse. An integrated computer code, CODSTRAN, was augmented for the simulation of the progressive damage and fracture of built-up composite structures under mechanical loading. Results show that damage initiation and progression have significant effect on the structural response. Influence of the type of loading is investigated on the damage initiation, propagation and final fracture of the build-up composite panel.

Progressive Fracture of Fiber Composite Build-Up Structures

NASA Technical Reports Server (NTRS)

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

1997-01-01

Damage progression and fracture of built-up composite structures is evaluated by using computational simulation. The objective is to examine the behavior and response of a stiffened composite (0 +/-45/90)(sub s6) laminate panel by simulating the damage initiation, growth, accumulation, progression and propagation to structural collapse. An integrated computer code CODSTRAN was augmented for the simulation of the progressive damage and fracture of built-up composite structures under mechanical loading. Results show that damage initiation and progression to have significant effect on the structural response. Influence of the type of loading is investigated on the damage initiation, propagation and final fracture of the build-up composite panel.

Prediction of progressive damage and strength of plain weave composites using the finite element method

NASA Astrophysics Data System (ADS)

Srirengan, Kanthikannan

The overall objective of this research was to develop the finite element code required to efficiently predict the strength of plain weave composite structures. Towards which, three-dimensional conventional progressive damage analysis was implemented to predict the strength of plain weave composites subjected to periodic boundary conditions. Also, modal technique for three-dimensional global/local stress analysis was developed to predict the failure initiation in plain weave composite structures. The progressive damage analysis was used to study the effect of quadrature order, mesh refinement and degradation models on the predicted damage and strength of plain weave composites subjected to uniaxial tension in the warp tow direction. A 1/32sp{nd} part of the representative volume element of a symmetrically stacked configuration was analyzed. The tow geometry was assumed to be sinusoidal. Graphite/Epoxy system was used. Maximum stress criteria and combined stress criteria were used to predict failure in the tows and maximum principal stress criterion was used to predict failure in the matrix. Degradation models based on logical reasoning, micromechanics idealization and experimental comparisons were used to calculate the effective material properties with of damage. Modified Newton-Raphson method was used to determine the incremental solution for each applied strain level. Using a refined mesh and the discount method based on experimental comparisons, the progressive damage and the strength of plain weave composites of waviness ratios 1/3 and 1/6 subjected to uniaxial tension in the warp direction have been characterized. Plain weave composites exhibit a brittle response in uniaxial tension. The strength decreases significantly with the increase in waviness ratio. Damage initiation and collapse were caused dominantly due to intra-tow cracking and inter-tow debonding respectively. The predicted strength of plain weave composites of racetrack geometry and waviness ratio 1/25.7 was compared with analytical predictions and experimental findings and was found to match well. To evaluate the performance of the modal technique, failure initiation in a short woven composite cantilevered plate subjected to end moment and transverse end load was predicted. The global/local predictions were found to reasonably match well with the conventional finite element predictions.

Large Area Nondestructive Evaluation of a Fatigue Loaded Composite Structure

NASA Technical Reports Server (NTRS)

Zalameda, Joseph N.; Burke, Eric R.; Horne, Michael R.; Madaras, Eric I.

2016-01-01

Large area nondestructive evaluation (NDE) inspections are required for fatigue testing of composite structures to track damage initiation and growth. Of particular interest is the progression of damage leading to ultimate failure to validate damage progression models. In this work, passive thermography and acoustic emission NDE were used to track damage growth up to failure of a composite three-stringer panel. Fourteen acoustic emission sensors were placed on the composite panel. The signals from the array were acquired simultaneously and allowed for acoustic emission location. In addition, real time thermal data of the composite structure were acquired during loading. Details are presented on the mapping of the acoustic emission locations directly onto the thermal imagery to confirm areas of damage growth leading to ultimate failure. This required synchronizing the acoustic emission and thermal data with the applied loading. In addition, processing of the thermal imagery which included contrast enhancement, removal of optical barrel distortion and correction of angular rotation before mapping the acoustic event locations are discussed.

CFD Assessment of Aerodynamic Degradation of a Subsonic Transport Due to Airframe Damage

NASA Technical Reports Server (NTRS)

Frink, Neal T.; Pirzadeh, Shahyar Z.; Atkins, Harold L.; Viken, Sally A.; Morrison, Joseph H.

2010-01-01

A computational study is presented to assess the utility of two NASA unstructured Navier-Stokes flow solvers for capturing the degradation in static stability and aerodynamic performance of a NASA General Transport Model (GTM) due to airframe damage. The approach is to correlate computational results with a substantial subset of experimental data for the GTM undergoing progressive losses to the wing, vertical tail, and horizontal tail components. The ultimate goal is to advance the probability of inserting computational data into the creation of advanced flight simulation models of damaged subsonic aircraft in order to improve pilot training. Results presented in this paper demonstrate good correlations with slope-derived quantities, such as pitch static margin and static directional stability, and incremental rolling moment due to wing damage. This study further demonstrates that high fidelity Navier-Stokes flow solvers could augment flight simulation models with additional aerodynamic data for various airframe damage scenarios.

Multiscale Fatigue Life Prediction for Composite Panels

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Yarrington, Phillip W.; Arnold, Steven M.

2012-01-01

Fatigue life prediction capabilities have been incorporated into the HyperSizer Composite Analysis and Structural Sizing Software. The fatigue damage model is introduced at the fiber/matrix constituent scale through HyperSizer s coupling with NASA s MAC/GMC micromechanics software. This enables prediction of the micro scale damage progression throughout stiffened and sandwich panels as a function of cycles leading ultimately to simulated panel failure. The fatigue model implementation uses a cycle jumping technique such that, rather than applying a specified number of additional cycles, a specified local damage increment is specified and the number of additional cycles to reach this damage increment is calculated. In this way, the effect of stress redistribution due to damage-induced stiffness change is captured, but the fatigue simulations remain computationally efficient. The model is compared to experimental fatigue life data for two composite facesheet/foam core sandwich panels, demonstrating very good agreement.

Progressive Fracture of Fiber Composite Builtup Structures

NASA Technical Reports Server (NTRS)

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

1996-01-01

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

Investigation of progressive failure robustness and alternate load paths for damage tolerant structures

NASA Astrophysics Data System (ADS)

Marhadi, Kun Saptohartyadi

Structural optimization for damage tolerance under various unforeseen damage scenarios is computationally challenging. It couples non-linear progressive failure analysis with sampling-based stochastic analysis of random damage. The goal of this research was to understand the relationship between alternate load paths available in a structure and its damage tolerance, and to use this information to develop computationally efficient methods for designing damage tolerant structures. Progressive failure of a redundant truss structure subjected to small random variability was investigated to identify features that correlate with robustness and predictability of the structure's progressive failure. The identified features were used to develop numerical surrogate measures that permit computationally efficient deterministic optimization to achieve robustness and predictability of progressive failure. Analysis of damage tolerance on designs with robust progressive failure indicated that robustness and predictability of progressive failure do not guarantee damage tolerance. Damage tolerance requires a structure to redistribute its load to alternate load paths. In order to investigate the load distribution characteristics that lead to damage tolerance in structures, designs with varying degrees of damage tolerance were generated using brute force stochastic optimization. A method based on principal component analysis was used to describe load distributions (alternate load paths) in the structures. Results indicate that a structure that can develop alternate paths is not necessarily damage tolerant. The alternate load paths must have a required minimum load capability. Robustness analysis of damage tolerant optimum designs indicates that designs are tailored to specified damage. A design Optimized under one damage specification can be sensitive to other damages not considered. Effectiveness of existing load path definitions and characterizations were investigated for continuum structures. A load path definition using a relative compliance change measure (U* field) was demonstrated to be the most useful measure of load path. This measure provides quantitative information on load path trajectories and qualitative information on the effectiveness of the load path. The use of the U* description of load paths in optimizing structures for effective load paths was investigated.

A Large-scale Finite Element Model on Micromechanical Damage and Failure of Carbon Fiber/Epoxy Composites Including Thermal Residual Stress

NASA Astrophysics Data System (ADS)

Liu, P. F.; Li, X. K.

2018-06-01

The purpose of this paper is to study micromechanical progressive failure properties of carbon fiber/epoxy composites with thermal residual stress by finite element analysis (FEA). Composite microstructures with hexagonal fiber distribution are used for the representative volume element (RVE), where an initial fiber breakage is assumed. Fiber breakage with random fiber strength is predicted using Monte Carlo simulation, progressive matrix damage is predicted by proposing a continuum damage mechanics model and interface failure is simulated using Xu and Needleman's cohesive model. Temperature dependent thermal expansion coefficients for epoxy matrix are used. FEA by developing numerical codes using ANSYS finite element software is divided into two steps: 1. Thermal residual stresses due to mismatch between fiber and matrix are calculated; 2. Longitudinal tensile load is further exerted on the RVE to perform progressive failure analysis of carbon fiber/epoxy composites. Numerical convergence is solved by introducing the viscous damping effect properly. The extended Mori-Tanaka method that considers interface debonding is used to get homogenized mechanical responses of composites. Three main results by FEA are obtained: 1. the real-time matrix cracking, fiber breakage and interface debonding with increasing tensile strain is simulated. 2. the stress concentration coefficients on neighbouring fibers near the initial broken fiber and the axial fiber stress distribution along the broken fiber are predicted, compared with the results using the global and local load-sharing models based on the shear-lag theory. 3. the tensile strength of composite by FEA is compared with those by the shear-lag theory and experiments. Finally, the tensile stress-strain curve of composites by FEA is applied to the progressive failure analysis of composite pressure vessel.

A Large-scale Finite Element Model on Micromechanical Damage and Failure of Carbon Fiber/Epoxy Composites Including Thermal Residual Stress

NASA Astrophysics Data System (ADS)

Liu, P. F.; Li, X. K.

2017-09-01

The purpose of this paper is to study micromechanical progressive failure properties of carbon fiber/epoxy composites with thermal residual stress by finite element analysis (FEA). Composite microstructures with hexagonal fiber distribution are used for the representative volume element (RVE), where an initial fiber breakage is assumed. Fiber breakage with random fiber strength is predicted using Monte Carlo simulation, progressive matrix damage is predicted by proposing a continuum damage mechanics model and interface failure is simulated using Xu and Needleman's cohesive model. Temperature dependent thermal expansion coefficients for epoxy matrix are used. FEA by developing numerical codes using ANSYS finite element software is divided into two steps: 1. Thermal residual stresses due to mismatch between fiber and matrix are calculated; 2. Longitudinal tensile load is further exerted on the RVE to perform progressive failure analysis of carbon fiber/epoxy composites. Numerical convergence is solved by introducing the viscous damping effect properly. The extended Mori-Tanaka method that considers interface debonding is used to get homogenized mechanical responses of composites. Three main results by FEA are obtained: 1. the real-time matrix cracking, fiber breakage and interface debonding with increasing tensile strain is simulated. 2. the stress concentration coefficients on neighbouring fibers near the initial broken fiber and the axial fiber stress distribution along the broken fiber are predicted, compared with the results using the global and local load-sharing models based on the shear-lag theory. 3. the tensile strength of composite by FEA is compared with those by the shear-lag theory and experiments. Finally, the tensile stress-strain curve of composites by FEA is applied to the progressive failure analysis of composite pressure vessel.

Modelling Pre-eruptive Progressive Damage in Basaltic Volcanoes: Consequences for the Pre-eruptive Process

NASA Astrophysics Data System (ADS)

Got, J. L.; Amitrano, D.; Carrier, A.; Marsan, D.; Jouanne, F.; Vogfjord, K. S.

2017-12-01

At Grimsvötn volcano, high-quality earthquake and continuous GPS data were recorded by the Icelandic Meteorological Office during its 2004-2011 inter-eruptive period and exhibited remarkable patterns : acceleration of the cumulated earthquake number, and a 2-year exponential decrease in displacement rate followed by a 4-year constant inflation rate. We proposed a model with one magma reservoir in a non-linear elastic damaging edifice, with incompressible magma and a constant pressure at the base of the magma conduit. We first modelled seismicity rate and damage as a function of time, and show that Kachanov's elastic brittle damage law may be used to express the decrease of the effective shear modulus with time. We then derived simple analytical expressions for the magma reservoir overpressure and the surface displacement as a function of time. We got a very good fit of the seismicity and surface displacement data by adjusting only three phenomenological parameters and computed magma reservoir overpressure, magma flow and strain power as a function of time. Overpressure decrease is controlled by damage and shear modulus decrease. Displacement increases, although overpressure is decreasing, because shear modulus decreases more than overpressure. Normalized strain power reaches a maximum 0.25 value. This maximum is a physical limit, after which the elasticity laws are no longer valid, earthquakes cluster, cumulative number of earthquakes departs from the model. State variable extrema provide four reference times that may be used to assess the mechanical state and dynamics of the volcanic edifice. We also performed the spatial modelling of the progressive damage and strain localization around a pressurized magma reservoir. We used Kachanov's damage law and finite element modelling of an initially elastic volcanic edifice pressurized by a spherical magma reservoir, with a constant pressure in the reservoir and various external boundary conditions. At each node of the model, Young's modulus is decreased if deviatoric stress locally reaches the Mohr-Coulomb plastic threshold. For a compressive horizontal stress, the result shows a complex strain localization pattern, showing reverse and normal faulting very similar to what is obtained from analog modelling and observed at volcanic resurgent domes.

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

PubMed

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

2016-07-01

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

Fe model predicting the increase in seismic resistance induced by the progressive FRP strengthening on already damaged masonry arches subjected to settlement

NASA Astrophysics Data System (ADS)

Stockdale, G.; Milani, G.

2017-11-01

In seismic regions, the retrofitting of masonry structures subjected to differential foundation settlements is of the upmost importance. This practice however poses significant challenges, most notably in the consideration of historical monuments where the integrity of the original structure must be weighted alongside public safety. Fiber reinforced polymers (FRPs), when appropriately applied, provide the potential to balance this duality of heritage preservation and modern safety. Using an advanced FE point of view, this work studies the seismic response of a progressive reinforcement strategy aimed at strengthening and controlling the failure mechanism for masonry arches that exist in a damaged state induced through a differential abutment settlement. A heterogeneous FE approach of a semi-circular block and mortar arch on continuously spreading supports is examined. In this model hinge formation is obtained by assigning a damage plasticity behavior to the mortar joints. Strategically placed FRPs, designed through the utilization of the Italian CNR recommendations for externally bonded FRP systems, are applied through the Abaqus birth and death approach and introduced to the spreading support model after settlement. Finally, the structural behavior of the reinforced and unreinforced models are examined for a seismic response.

Wireless vibration monitoring for damage detection of highway bridges

NASA Astrophysics Data System (ADS)

Whelan, Matthew J.; Gangone, Michael V.; Janoyan, Kerop D.; Jha, Ratneshwar

2008-03-01

The development of low-cost wireless sensor networks has resulted in resurgence in the development of ambient vibration monitoring methods to assess the in-service condition of highway bridges. However, a reliable approach towards assessing the health of an in-service bridge and identifying and localizing damage without a priori knowledge of the vibration response history has yet to be formulated. A two-part study is in progress to evaluate and develop existing and proposed damage detection schemes. The first phase utilizes a laboratory bridge model to investigate the vibration response characteristics induced through introduction of changes to structural members, connections, and support conditions. A second phase of the study will validate the damage detection methods developed from the laboratory testing with progressive damage testing of an in-service highway bridge scheduled for replacement. The laboratory bridge features a four meter span, one meter wide, steel frame with a steel and cement board deck composed of sheet layers to regulate mass loading and simulate deck wear. Bolted connections and elastomeric bearings provide a means for prescribing variable local stiffness and damping effects to the laboratory model. A wireless sensor network consisting of fifty-six accelerometers accommodated by twenty-eight local nodes facilitates simultaneous, real-time and high-rate acquisition of the vibrations throughout the bridge structure. Measurement redundancy is provided by an array of wired linear displacement sensors as well as a scanning laser vibrometer. This paper presents the laboratory model and damage scenarios, a brief description of the developed wireless sensor network platform, an overview of available test and measurement instrumentation within the laboratory, and baseline measurements of dynamic response of the laboratory bridge model.

Investigation of Tapered Roller Bearing Damage Detection Using Oil Debris Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Krieder, Gary; Fichter, Thomas

2006-01-01

A diagnostic tool was developed for detecting fatigue damage to tapered roller bearings. Tapered roller bearings are used in helicopter transmissions and have potential for use in high bypass advanced gas turbine aircraft engines. This diagnostic tool was developed and evaluated experimentally by collecting oil debris data from failure progression tests performed by The Timken Company in their Tapered Roller Bearing Health Monitoring Test Rig. Failure progression tests were performed under simulated engine load conditions. Tests were performed on one healthy bearing and three predamaged bearings. During each test, data from an on-line, in-line, inductance type oil debris sensor was monitored and recorded for the occurrence of debris generated during failure of the bearing. The bearing was removed periodically for inspection throughout the failure progression tests. Results indicate the accumulated oil debris mass is a good predictor of damage on tapered roller bearings. The use of a fuzzy logic model to enable an easily interpreted diagnostic metric was proposed and demonstrated.

Micromechanical modeling of short glass-fiber reinforced thermoplastics-Isotropic damage of pseudograins

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

Kammoun, S.; Brassart, L.; Doghri, I.

A micromechanical damage modeling approach is presented to predict the overall elasto-plastic behavior and damage evolution in short fiber reinforced composite materials. The practical use of the approach is for injection molded thermoplastic parts reinforced with short glass fibers. The modeling is proceeded as follows. The representative volume element is decomposed into a set of pseudograins, the damage of which affects progressively the overall stiffness and strength up to total failure. Each pseudograin is a two-phase composite with aligned inclusions having same aspect ratio. A two-step mean-field homogenization procedure is adopted. In the first step, the pseudograins are homogenized individuallymore » according to the Mori-Tanaka scheme. The second step consists in a self-consistent homogenization of homogenized pseudograins. An isotropic damage model is applied at the pseudograin level. The model is implemented as a UMAT in the finite element code ABAQUS. Model is shown to reproduce the strength and the anisotropy (Lankford coefficient) during uniaxial tensile tests on samples cut under different directions relative to the injection flow direction.« less

Micromechanical modeling of short glass-fiber reinforced thermoplastics-Isotropic damage of pseudograins

NASA Astrophysics Data System (ADS)

Kammoun, S.; Brassart, L.; Robert, G.; Doghri, I.; Delannay, L.

2011-05-01

A micromechanical damage modeling approach is presented to predict the overall elasto-plastic behavior and damage evolution in short fiber reinforced composite materials. The practical use of the approach is for injection molded thermoplastic parts reinforced with short glass fibers. The modeling is proceeded as follows. The representative volume element is decomposed into a set of pseudograins, the damage of which affects progressively the overall stiffness and strength up to total failure. Each pseudograin is a two-phase composite with aligned inclusions having same aspect ratio. A two-step mean-field homogenization procedure is adopted. In the first step, the pseudograins are homogenized individually according to the Mori-Tanaka scheme. The second step consists in a self-consistent homogenization of homogenized pseudograins. An isotropic damage model is applied at the pseudograin level. The model is implemented as a UMAT in the finite element code ABAQUS. Model is shown to reproduce the strength and the anisotropy (Lankford coefficient) during uniaxial tensile tests on samples cut under different directions relative to the injection flow direction.

Influence of Shear Stiffness Degradation on Crack Paths in Uni-Directional Composite Laminates

NASA Technical Reports Server (NTRS)

Satyanarayana, Arunkumar; Bogert, Phil B.

2017-01-01

Influence of shear stiffness degradation in an element, due to damage, on crack paths in uni-directional laminates has been demonstrated. A new shear stiffness degradation approach to improve crack path prediction has been developed and implemented in an ABAQUS/Explicit frame work using VUMAT. Three progressive failure analysis models, built-in ABAQUS (TradeMark), original COmplete STress Reduction (COSTR) and the modified COSTR damage models have been utilized in this study to simulate crack paths in five unidirectional notched laminates, 15deg, 30deg, 45deg, 60deg and 75deg under uniaxial tension load. Results such as crack paths and load vs. edge displacement curves are documented in this report. Modified COSTR damage model shows better accuracy in predicting crack paths in all the uni-directional laminates compared to the ABAQUS (TradeMark) and the original COSTR damage models.

Increased plasma Kidney Injury Molecule-1 suggests early progressive renal decline in non-proteinuric patients with Type 1 diabetes

PubMed Central

Nowak, Natalia; Skupien, Jan; Niewczas, Monika A.; Yamanouchi, Masayuki; Major, Melissa; Croall, Stephanie; Smiles, Adam; Warram, James H.; Bonventre, Joseph V.; Krolewski, Andrzej S.

2015-01-01

Progressively decreasing glomerular filtration rate (GFR), or renal decline, is seen in patients with type 1 diabetes (T1D) and normoalbuminuria or microalbuminuria. Here we examined the associations of kidney injury molecule-1 (KIM-1) in plasma and urine with the risk of renal decline and determine whether those associations are independent of markers of glomerular damage. The study group comprised patients with T1D from the 2nd Joslin Kidney Study of which 259 had normoalbuminuria and 203 had microalbuminuria. Serial measurements over 4 to 10 years of follow-up (median 8 years) of serum creatinine and cystatin C were used jointly to estimate eGFRcr-cys slopes and time of onset of CKD stage 3 or higher. Baseline urinary excretion of IgG2 and albumin were used as markers of glomerular damage, and urinary excretion of KIM-1 and its plasma concentration were used as markers of proximal tubular damage. All patients had normal renal function at baseline. During follow-up, renal decline (eGFRcr-cys loss 3.3% or more per year) developed in 96 patients and 62 progressed to CKD stage 3. For both outcomes, the risk rose with increasing baseline levels of plasma KIM-1. In multivariable models, elevated baseline plasma KIM-1 was strongly associated with risk of early progressive renal decline, regardless of baseline clinical characteristics, serum TNFR1 or markers of glomerular damage. Thus, damage to proximal tubules may play an independent role in the development of early progressive renal decline in non-proteinuric patients with T1D. PMID:26509588

Physical Biology of Axonal Damage.

PubMed

de Rooij, Rijk; Kuhl, Ellen

2018-01-01

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

The EST Model for Predicting Progressive Damage and Failure of Open Hole Bending Specimens

NASA Technical Reports Server (NTRS)

Joseph, Ashith P. K.; Waas, Anthony M.; Pineda, Evan J.

2016-01-01

Progressive damage and failure in open hole composite laminate coupons subjected to flexural loading is modeled using Enhanced Schapery Theory (EST). Previous studies have demonstrated that EST can accurately predict the strength of open hole coupons under remote tensile and compressive loading states. This homogenized modeling approach uses single composite shell elements to represent the entire laminate in the thickness direction and significantly reduces computational cost. Therefore, when delaminations are not of concern or are active in the post-peak regime, the version of EST presented here is a good engineering tool for predicting deformation response. Standard coupon level tests provides all the input data needed for the model and they are interpreted in conjunction with finite element (FE) based simulations. Open hole bending test results of three different IM7/8552 carbon fiber composite layups agree well with EST predictions. The model is able to accurately capture the curvature change and deformation localization in the specimen at and during the post catastrophic load drop event.

A Progressive Damage Methodology for Residual Strength Predictions of Center-Crack Tension Composite Panels

NASA Technical Reports Server (NTRS)

Coats, Timothy William

1996-01-01

An investigation of translaminate fracture and a progressive damage methodology was conducted to evaluate and develop a residual strength prediction capability for laminated composites with through penetration notches. This is relevant to the damage tolerance of an aircraft fuselage that might suffer an in-flight accident such as an uncontained engine failure. An experimental characterization of several composite materials systems revealed an R-curve type of behavior. Fractographic examinations led to the postulate that this crack growth resistance could be due to fiber bridging, defined here as fractured fibers of one ply bridged by intact fibers of an adjacent ply. The progressive damage methodology is currently capable of predicting the initiation and growth of matrix cracks and fiber fracture. Using two difference fiber failure criteria, residual strength was predicted for different size panel widths and notch lengths. A ply discount fiber failure criterion yielded extremely conservative results while an elastic-perfectly plastic fiber failure criterion showed that the fiber bridging concept is valid for predicting residual strength for tensile dominated failure loads. Furthermore, the R-curves predicted by the model using the elastic-perfectly plastic fiber criterion compared very well with the experimental R-curves.

Development of an engineering analysis of progressive damage in composites during low velocity impact

NASA Technical Reports Server (NTRS)

Humphreys, E. A.

1981-01-01

A computerized, analytical methodology was developed to study damage accumulation during low velocity lateral impact of layered composite plates. The impact event was modeled as perfectly plastic with complete momentum transfer to the plate structure. A transient dynamic finite element approach was selected to predict the displacement time response of the plate structure. Composite ply and interlaminar stresses were computed at selected time intervals and subsequently evaluated to predict layer and interlaminar damage. The effects of damage on elemental stiffness were then incorporated back into the analysis for subsequent time steps. Damage predicted included fiber failure, matrix ply failure and interlaminar delamination.

Thermography Inspection for Early Detection of Composite Damage in Structures During Fatigue Loading

NASA Technical Reports Server (NTRS)

Zalameda, Joseph N.; Burke, Eric R.; Parker, F. Raymond; Seebo, Jeffrey P.; Wright, Christopher W.; Bly, James B.

2012-01-01

Advanced composite structures are commonly tested under controlled loading. Understanding the initiation and progression of composite damage under load is critical for validating design concepts and structural analysis tools. Thermal nondestructive evaluation (NDE) is used to detect and characterize damage in composite structures during fatigue loading. A difference image processing algorithm is demonstrated to enhance damage detection and characterization by removing thermal variations not associated with defects. In addition, a one-dimensional multilayered thermal model is used to characterize damage. Lastly, the thermography results are compared to other inspections such as non-immersion ultrasonic inspections and computed tomography X-ray.

Numerical Implementation of a Multiple-ISV Thermodynamically-Based Work Potential Theory for Modeling Progressive Damage and Failure in Fiber-Reinforced Laminates

NASA Technical Reports Server (NTRS)

Pineda, Evan J.; Waas, Anthony M.

2011-01-01

A thermodynamically-based work potential theory for modeling progressive damage and failure in fiber-reinforced laminates is presented. The current, multiple-internal state variable (ISV) formulation, enhanced Schapery theory (EST), utilizes separate ISVs for modeling the effects of damage and failure. Damage is considered to be the effect of any structural changes in a material that manifest as pre-peak non-linearity in the stress versus strain response. Conversely, failure is taken to be the effect of the evolution of any mechanisms that results in post-peak strain softening. It is assumed that matrix microdamage is the dominant damage mechanism in continuous fiber-reinforced polymer matrix laminates, and its evolution is controlled with a single ISV. Three additional ISVs are introduced to account for failure due to mode I transverse cracking, mode II transverse cracking, and mode I axial failure. Typically, failure evolution (i.e., post-peak strain softening) results in pathologically mesh dependent solutions within a finite element method (FEM) setting. Therefore, consistent character element lengths are introduced into the formulation of the evolution of the three failure ISVs. Using the stationarity of the total work potential with respect to each ISV, a set of thermodynamically consistent evolution equations for the ISVs is derived. The theory is implemented into commercial FEM software. Objectivity of total energy dissipated during the failure process, with regards to refinements in the FEM mesh, is demonstrated. The model is also verified against experimental results from two laminated, T800/3900-2 panels containing a central notch and different fiber-orientation stacking sequences. Global load versus displacement, global load versus local strain gage data, and macroscopic failure paths obtained from the models are compared to the experiments.

Effect of temperature and tree species on damage progression caused by whitespotted sawyer (Coleoptera: Cerambycidae) larvae in recently burned logs.

PubMed

Bélanger, Sébastien; Bauce, Eric; Berthiaume, Richard; Long, Bernard; Labrie, Jacques; Daigle, Louis-Frédéric; Hébert, Christian

2013-06-01

The whitespotted sawyer, Monochamus scutellatus scutellatus (Say) (Coleoptera: Ce-rambycidae), is one of the most damaging wood-boring insects in recently burned boreal forests of North America. In Canada, salvage logging after wildfire contributes to maintaining the timber volume required by the forest industry, but larvae of this insect cause significant damage that reduces the economic value of lumber products. This study aimed to estimate damage progression as a function of temperature in recently burned black spruce (Picea mariana (Miller) Britton, Sterns, and Poggenburg) and jack pine (Pinus banksiana Lambert) trees. Using axial tomographic technology, we modeled subcortical development and gallery depth progression rates as functions of temperature for both tree species. Generally, these rates were slightly faster in black spruce than in jack pine logs. Eggs laid on logs kept at 12 degrees C did not hatch or larvae were unable to establish themselves under the bark because no larval development was observed. At 16 degrees C, larvae stayed under the bark for > 200 d before penetrating into the sapwood. At 20 degrees C, half of the larvae entered the sapwood after 30-50 d, but gallery depth progression stopped for approximately 70 d, suggesting that larvae went into diapause. The other half of the larvae entered the sapwood only after 100-200 d. At 24 and 28 degrees C, larvae entered the sapwood after 26-27 and 21 d, respectively. At 28 degrees C, gallery depth progressed at a rate of 1.44 mm/d. Temperature threshold for subcortical development was slightly lower in black spruce (12.9 degrees C) than in jack pine (14.6 degrees C) and it was 1 degrees C warmer for gallery depth progression for both tree species. These results indicate that significant damage may occur within a few months after fire during warm summers, particularly in black spruce, which highlights the importance of beginning postfire salvage logging as soon as possible to reduce economic losses.

CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis.

PubMed

Romme Christensen, Jeppe; Börnsen, Lars; Khademi, Mohsen; Olsson, Tomas; Jensen, Poul Erik; Sørensen, Per Soelberg; Sellebjerg, Finn

2013-06-01

The mechanism underlying disease progression in progressive multiple sclerosis (MS) is uncertain. Pathological studies found widespread inflammation in progressive MS brains correlating with disease progression and axonal damage. To study cerebrospinal fluid (CSF) biomarkers and clarify whether inflammation and axonal damage are associated in progressive MS. Using enzyme-linked immunosorbent assay (ELISA), we analysed CSF from 40 secondary progressive (SPMS), 21 primary progressive (PPMS), and 36 relapsing-remitting (RRMS) and 20 non-inflammatory neurological disease (NIND) patients. Twenty-two of the SPMS patients participated in an MBP8298 peptide clinical trial and had CSF follow-up after one year. Compared to NIND patients, inflammatory biomarkers osteopontin and matrix metalloproteinase-9 (MMP9) were increased in all MS patients while CXCL13 was increased in RRMS and SPMS patients. Biomarkers of axonal damage (NFL) and demyelination (MBP) were increased in all MS patients. In progressive MS patients CSF levels of osteopontin and CXCL13 correlated with NFL while osteopontin and MMP9 correlated with MBP. MBP8298 treatment did not affect the levels of the biomarkers after one year of treatment. All biomarkers were continuously increased after one year of follow-up except MBP, which decreased. CSF biomarkers of inflammation, axonal damage and demyelination are continuously increased in progressive MS patients and correlate. These findings parallel pathology studies, emphasise a relationship between inflammation, axonal damage and demyelination and support the use of CSF biomarkers in progressive MS clinical trials.

Some dissociating factors in the analysis of structural and functional progressive damage in open-angle glaucoma.

PubMed

Hudson, C J W; Kim, L S; Hancock, S A; Cunliffe, I A; Wild, J M

2007-05-01

To identify the presence, and origin, of any "dissociating factors" inherent to the techniques for evaluating progression that mask the relationship between structural and functional progression in open-angle glaucoma (OAG). 23 patients (14 with OAG and 9 with ocular hypertension (OHT)) who had received serial Heidelberg Retina Tomograph (HRT II) and Humphrey Field Analyser (HFA) examinations for >or=5 years (mean 78.4 months (SD 9.5), range 60-101 months) were identified. Evidence of progressive disease was retrospectively evaluated in one eye of each patient using the Topographic Change Analysis (TCA) and Glaucoma Progression Analysis (GPA) for the HRT II and HFA, respectively. Six patients were stable by both techniques; four exhibited both structural and functional progression; seven exhibited structural progression, only, and six showed functional progression, only. Three types of dissociating factors were identified. TCA failed to identify progressive structural damage in the presence of advanced optic nerve head damage. GPA failed to identify progressive functional damage at stimulus locations, with sensitivities exhibiting test-retest variability beyond the maximum stimulus luminance of the perimeter, and where a perimetric learning effect was apparent. The three dissociating factors accounted for nine of the 13 patients who exhibited a lack of concordance between structural and functional progressive damage.

Cross-country transferability of multi-variable damage models

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

Micromechanics Based Failure Analysis of Heterogeneous Materials

NASA Astrophysics Data System (ADS)

Sertse, Hamsasew M.

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

Evaluation of a Progressive Failure Analysis Methodology for Laminated Composite Structures

NASA Technical Reports Server (NTRS)

Sleight, David W.; Knight, Norman F., Jr.; Wang, John T.

1997-01-01

A progressive failure analysis methodology has been developed for predicting the nonlinear response and failure of laminated composite structures. The progressive failure analysis uses C plate and shell elements based on classical lamination theory to calculate the in-plane stresses. Several failure criteria, including the maximum strain criterion, Hashin's criterion, and Christensen's criterion, are used to predict the failure mechanisms. The progressive failure analysis model is implemented into a general purpose finite element code and can predict the damage and response of laminated composite structures from initial loading to final failure.

Rad53 regulates replication fork restart after DNA damage in Saccharomyces cerevisiae

PubMed Central

Szyjka, Shawn J.; Aparicio, Jennifer G.; Viggiani, Christopher J.; Knott, Simon; Xu, Weihong; Tavaré, Simon; Aparicio, Oscar M.

2008-01-01

Replication fork stalling at a DNA lesion generates a damage signal that activates the Rad53 kinase, which plays a vital role in survival by stabilizing stalled replication forks. However, evidence that Rad53 directly modulates the activity of replication forks has been lacking, and the nature of fork stabilization has remained unclear. Recently, cells lacking the Psy2–Pph3 phosphatase were shown to be defective in dephosphorylation of Rad53 as well as replication fork restart after DNA damage, suggesting a mechanistic link between Rad53 deactivation and fork restart. To test this possibility we examined the progression of replication forks in methyl-methanesulfonate (MMS)-damaged cells, under different conditions of Rad53 activity. Hyperactivity of Rad53 in pph3Δ cells slows fork progression in MMS, whereas deactivation of Rad53, through expression of dominant-negative Rad53-KD, is sufficient to allow fork restart during recovery. Furthermore, combined deletion of PPH3 and PTC2, a second, unrelated Rad53 phosphatase, results in complete replication fork arrest and lethality in MMS, demonstrating that Rad53 deactivation is a key mechanism controlling fork restart. We propose a model for regulation of replication fork progression through damaged DNA involving a cycle of Rad53 activation and deactivation that coordinates replication restart with DNA repair. PMID:18628397

Delayed mTOR inhibition with low dose of everolimus reduces TGFβ expression, attenuates proteinuria and renal damage in the renal mass reduction model.

PubMed

Kurdián, Melania; Herrero-Fresneda, Inmaculada; Lloberas, Nuria; Gimenez-Bonafe, Pepita; Coria, Virginia; Grande, María T; Boggia, José; Malacrida, Leonel; Torras, Joan; Arévalo, Miguel A; González-Martínez, Francisco; López-Novoa, José M; Grinyó, Josep; Noboa, Oscar

2012-01-01

The immunosuppressive mammalian target of rapamycin (mTOR) inhibitors are widely used in solid organ transplantation, but their effect on kidney disease progression is controversial. mTOR has emerged as one of the main pathways regulating cell growth, proliferation, differentiation, migration, and survival. The aim of this study was to analyze the effects of delayed inhibition of mTOR pathway with low dose of everolimus on progression of renal disease and TGFβ expression in the 5/6 nephrectomy model in Wistar rats. This study evaluated the effects of everolimus (0.3 mg/k/day) introduced 15 days after surgical procedure on renal function, proteinuria, renal histology and mechanisms of fibrosis and proliferation. Everolimus treated group (EveG) showed significantly less proteinuria and albuminuria, less glomerular and tubulointerstitial damage and fibrosis, fibroblast activation cell proliferation, when compared with control group (CG), even though the EveG remained with high blood pressure. Treatment with everolimus also diminished glomerular hypertrophy. Everolimus effectively inhibited the increase of mTOR developed in 5/6 nephrectomy animals, without changes in AKT mRNA or protein abundance, but with an increase in the pAKT/AKT ratio. Associated with this inhibition, everolimus blunted the increased expression of TGFβ observed in the remnant kidney model. Delayed mTOR inhibition with low dose of everolimus significantly prevented progressive renal damage and protected the remnant kidney. mTOR and TGFβ mRNA reduction can partially explain this anti fibrotic effect. mTOR can be a new target to attenuate the progression of chronic kidney disease even in those nephropathies of non-immunologic origin.

Delayed mTOR Inhibition with Low Dose of Everolimus Reduces TGFβ Expression, Attenuates Proteinuria and Renal Damage in the Renal Mass Reduction Model

PubMed Central

Kurdián, Melania; Herrero-Fresneda, Inmaculada; Lloberas, Nuria; Gimenez-Bonafe, Pepita; Coria, Virginia; Grande, María T.; Boggia, José; Malacrida, Leonel; Torras, Joan; Arévalo, Miguel A.; González-Martínez, Francisco; López-Novoa, José M.; Grinyó, Josep; Noboa, Oscar

2012-01-01

Background The immunosuppressive mammalian target of rapamycin (mTOR) inhibitors are widely used in solid organ transplantation, but their effect on kidney disease progression is controversial. mTOR has emerged as one of the main pathways regulating cell growth, proliferation, differentiation, migration, and survival. The aim of this study was to analyze the effects of delayed inhibition of mTOR pathway with low dose of everolimus on progression of renal disease and TGFβ expression in the 5/6 nephrectomy model in Wistar rats. Methods This study evaluated the effects of everolimus (0.3 mg/k/day) introduced 15 days after surgical procedure on renal function, proteinuria, renal histology and mechanisms of fibrosis and proliferation. Results Everolimus treated group (EveG) showed significantly less proteinuria and albuminuria, less glomerular and tubulointerstitial damage and fibrosis, fibroblast activation cell proliferation, when compared with control group (CG), even though the EveG remained with high blood pressure. Treatment with everolimus also diminished glomerular hypertrophy. Everolimus effectively inhibited the increase of mTOR developed in 5/6 nephrectomy animals, without changes in AKT mRNA or protein abundance, but with an increase in the pAKT/AKT ratio. Associated with this inhibition, everolimus blunted the increased expression of TGFβ observed in the remnant kidney model. Conclusion Delayed mTOR inhibition with low dose of everolimus significantly prevented progressive renal damage and protected the remnant kidney. mTOR and TGFβ mRNA reduction can partially explain this anti fibrotic effect. mTOR can be a new target to attenuate the progression of chronic kidney disease even in those nephropathies of non-immunologic origin. PMID:22427849

Multi-scale finite element model of growth plate damage during the development of slipped capital femoral epiphysis.

PubMed

Farzaneh, S; Paseta, O; Gómez-Benito, M J

2015-04-01

Slipped capital femoral epiphysis (SCFE) is one of the most common disorders of adolescent hips. A number of works have related the development of SCFE to mechanical factors. Due to the difficulty of diagnosing SCFE in its early stages, the disorder often progresses over time, resulting in serious side effects. Therefore, the development of a tool to predict the initiation of damage in the growth plate is needed. Because the growth plate is a heterogeneous structure, to develop a precise and reliable model, it is necessary to consider this structure from both macro- and microscale perspectives. Thus, the main objective of this work is to develop a numerical multi-scale model that links damage occurring at the microscale to damage occurring at the macroscale. The use of this model enables us to predict which regions of the growth plate are at high risk of damage. First, we have independently analyzed the microscale to simulate the microstructure under shear and tensile tests to calibrate the damage model. Second, we have employed the model to simulate damage occurring in standardized healthy and affected femurs during the heel-strike stage of stair climbing. Our results indicate that on the macroscale, damage is concentrated in the medial region of the growth plate in both healthy and affected femurs. Furthermore, damage to the affected femur is greater than damage to the healthy femur from both the micro- and macrostandpoints. Maximal damage is observed in territorial matrices. Furthermore, simulations illustrate that little damage occurs in the reserve zone. These findings are consistent with previous findings reported in well-known experimental works.

White and gray matter damage in primary progressive MS

PubMed Central

Chard, Declan; Altmann, Daniel R.; Tozer, Daniel; Miller, David H.; Thompson, Alan J.; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

2016-01-01

Objective: The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex (“primary WM damage model”); and (2) cortical abnormalities predict later changes in connected WM tracts (“primary GM damage model”). Methods: Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. Results: The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. Conclusion: These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. PMID:26674332

Modeling Ductile-Phase Toughened Tungsten for Plasma-Facing Materials: Progress in Damage Finite Element Analysis of the Tungsten-Copper Bend Bar Tests

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

Nguyen, Ba Nghiep; Henager, Charles H.; Kurtz, Richard J.

The objective of this study is to investigate the deformation behavior of ductile phase toughened W-composites such as W-Cu and W-Ni-Fe by means of a multiscale finite element model that involves a microstructural dual-phase model where the constituent phases (i.e., W, Cu, Ni-Fe) are finely discretized and are described by a continuum damage model. Such a model is suitable for modeling deformation, cracking, and crack bridging for W-Cu, W-Ni-Fe, and other ductile phase toughened W-composites, or more generally, any multi-phase composite structure where two or more phases undergo cooperative deformation in a composite system. Our current work focuses on simulatingmore » the response and damage development of the W-Cu specimen subjected to three-point bending.« less

Predicting Failure Progression and Failure Loads in Composite Open-Hole Tension Coupons

NASA Technical Reports Server (NTRS)

Arunkumar, Satyanarayana; Przekop, Adam

2010-01-01

Failure types and failure loads in carbon-epoxy [45n/90n/-45n/0n]ms laminate coupons with central circular holes subjected to tensile load are simulated using progressive failure analysis (PFA) methodology. The progressive failure methodology is implemented using VUMAT subroutine within the ABAQUS(TradeMark)/Explicit nonlinear finite element code. The degradation model adopted in the present PFA methodology uses an instantaneous complete stress reduction (COSTR) approach to simulate damage at a material point when failure occurs. In-plane modeling parameters such as element size and shape are held constant in the finite element models, irrespective of laminate thickness and hole size, to predict failure loads and failure progression. Comparison to published test data indicates that this methodology accurately simulates brittle, pull-out and delamination failure types. The sensitivity of the failure progression and the failure load to analytical loading rates and solvers precision is demonstrated.

Using Non-linear Homogenization to Improve the Performance of Macroscopic Damage Models of Trabecular Bone.

PubMed

Levrero-Florencio, Francesc; Pankaj, Pankaj

2018-01-01

Realistic macro-level finite element simulations of the mechanical behavior of trabecular bone, a cellular anisotropic material, require a suitable constitutive model; a model that incorporates the mechanical response of bone for complex loading scenarios and includes post-elastic phenomena, such as plasticity (permanent deformations) and damage (permanent stiffness reduction), which bone is likely to experience. Some such models have been developed by conducting homogenization-based multiscale finite element simulations on bone micro-structure. While homogenization has been fairly successful in the elastic regime and, to some extent, in modeling the macroscopic plastic response, it has remained a challenge with respect to modeling damage. This study uses a homogenization scheme to upscale the damage behavior from the tissue level (microscale) to the organ level (macroscale) and assesses the suitability of different damage constitutive laws. Ten cubic specimens were each subjected to 21 strain-controlled load cases for a small range of macroscopic post-elastic strains. Isotropic and anisotropic criteria were considered, density and fabric relationships were used in the formulation of the damage law, and a combined isotropic/anisotropic law with tension/compression asymmetry was formulated, based on the homogenized results, as a possible alternative to the currently used single scalar damage criterion. This computational study enhances the current knowledge on the macroscopic damage behavior of trabecular bone. By developing relationships of damage progression with bone's micro-architectural indices (density and fabric) the study also provides an aid for the creation of more precise macroscale continuum models, which are likely to improve clinical predictions.

Feasibility study of modeling liver thermal damage using minimally invasive optical method adequate for in situ measurement.

PubMed

Zhao, Jinzhe; Zhao, Qi; Jiang, Yingxu; Li, Weitao; Yang, Yamin; Qian, Zhiyu; Liu, Jia

2018-06-01

Liver thermal ablation techniques have been widely used for the treatment of liver cancer. Kinetic model of damage propagation play an important role for ablation prediction and real-time efficacy assessment. However, practical methods for modeling liver thermal damage are rare. A minimally invasive optical method especially adequate for in situ liver thermal damage modeling is introduced in this paper. Porcine liver tissue was heated by water bath under different temperatures. During thermal treatment, diffuse reflectance spectrum of liver was measured by optical fiber and used to deduce reduced scattering coefficient (μ ' s ). Arrhenius parameters were obtained through non-isothermal heating approach with damage marker of μ ' s . Activation energy (E a ) and frequency factor (A) was deduced from these experiments. A pair of averaged value is 1.200 × 10 5  J mol -1 and 4.016 × 10 17  s -1 . The results were verified for their reasonableness and practicality. Therefore, it is feasible to modeling liver thermal damage based on minimally invasive measurement of optical property and in situ kinetic analysis of damage progress with Arrhenius model. These parameters and this method are beneficial for preoperative planning and real-time efficacy assessment of liver ablation therapy. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Progressive Failure Studies of Composite Panels with and without Cutouts

NASA Technical Reports Server (NTRS)

Jaunky, Navin; Ambur, Damodar R.; Davila, Carlos G.; Hilburger, Mark; Bushnell, Dennis M. (Technical Monitor)

2001-01-01

Progressive failure analyses results are presented for composite panels with and without a cutout and subjected to in-plane shear loading and compression loading well into their postbuckling regime. Ply damage modes such as matrix cracking, fiber-matrix shear, and fiber failure are modeled by degrading the material properties. Results from finite element analyses are compared with experimental data. Good agreement between experimental data and numerical results are observed for most structural configurations when initial geometric imperfections are appropriately modeled.

Progressive Failure Studies of Composite Panels With and Without Cutouts

NASA Technical Reports Server (NTRS)

Ambur, Damodar R.; Jaunky, Navin; Davila, Carlos G.; Hilburger, Mark

2001-01-01

Progressive failure analyses results are presented for composite panels with and without a cutout and are subjected to in-plane shear loading and compression loading well into their post-buckling regime. Ply damage modes such as matrix cracking, fiber-matrix shear, and fiber failure are modeled by degrading the material properties. Results from finite element analyses are compared with experimental data. Good agreement between experimental data and numerical results are observed for most structural configurations when initial geometric imperfections are appropriately modeled.

Probabilistic Assessment of Fracture Progression in Composite Structures

NASA Technical Reports Server (NTRS)

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

1999-01-01

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

TPS In-Flight Health Monitoring Project Progress Report

NASA Technical Reports Server (NTRS)

Kostyk, Chris; Richards, Lance; Hudston, Larry; Prosser, William

2007-01-01

Progress in the development of new thermal protection systems (TPS) is reported. New approaches use embedded lightweight, sensitive, fiber optic strain and temperature sensors within the TPS. Goals of the program are to develop and demonstrate a prototype TPS health monitoring system, develop a thermal-based damage detection algorithm, characterize limits of sensor/system performance, and develop ea methodology transferable to new designs of TPS health monitoring systems. Tasks completed during the project helped establish confidence in understanding of both test setup and the model and validated system/sensor performance in a simple TPS structure. Other progress included complete initial system testing, commencement of the algorithm development effort, generation of a damaged thermal response characteristics database, initial development of a test plan for integration testing of proven FBG sensors in simple TPS structure, and development of partnerships to apply the technology.

Observation of the initiation and progression of damage in compressively loaded composite plates containing a cutout

NASA Technical Reports Server (NTRS)

Waas, A.; Babcock, C., Jr.

1986-01-01

A series of experiments was carried out to determine the mechanism of failure in compressively loaded laminated plates with a circular cutout. Real time holographic interferometry and photomicrography are used to observe the progression of failure. These observations together with post experiment plate sectioning and deplying for interior damage observation provide useful information for modelling the failure process. It is revealed that the failure is initiated as a localised instability in the zero layers, at the hole surface. With increasing load extensive delamination cracking is observed. The progression of failure is by growth of these delaminations induced by delamination buckling. Upon reaching a critical state, catastrophic failure of the plate is observed. The levels of applied load and the rate at which these events occur depend on the plate stacking sequence.

Assessment of compressive failure process of cortical bone materials using damage-based model.

PubMed

Ng, Theng Pin; R Koloor, S S; Djuansjah, J R P; Abdul Kadir, M R

2017-02-01

The main failure factors of cortical bone are aging or osteoporosis, accident and high energy trauma or physiological activities. However, the mechanism of damage evolution coupled with yield criterion is considered as one of the unclear subjects in failure analysis of cortical bone materials. Therefore, this study attempts to assess the structural response and progressive failure process of cortical bone using a brittle damaged plasticity model. For this reason, several compressive tests are performed on cortical bone specimens made of bovine femur, in order to obtain the structural response and mechanical properties of the material. Complementary finite element (FE) model of the sample and test is prepared to simulate the elastic-to-damage behavior of the cortical bone using the brittle damaged plasticity model. The FE model is validated in a comparative method using the predicted and measured structural response as load-compressive displacement through simulation and experiment. FE results indicated that the compressive damage initiated and propagated at central region where maximum equivalent plastic strain is computed, which coincided with the degradation of structural compressive stiffness followed by a vast amount of strain energy dissipation. The parameter of compressive damage rate, which is a function dependent on damage parameter and the plastic strain is examined for different rates. Results show that considering a similar rate to the initial slope of the damage parameter in the experiment would give a better sense for prediction of compressive failure. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Thermodynamically-Based Mesh Objective Work Potential Theory for Predicting Intralaminar Progressive Damage and Failure in Fiber-Reinforced Laminates

NASA Technical Reports Server (NTRS)

Pineda, Evan J.; Waas, Anthony M.

2012-01-01

A thermodynamically-based work potential theory for modeling progressive damage and failure in fiber-reinforced laminates is presented. The current, multiple-internal state variable (ISV) formulation, enhanced Schapery theory (EST), utilizes separate ISVs for modeling the effects of damage and failure. Damage is considered to be the effect of any structural changes in a material that manifest as pre-peak non-linearity in the stress versus strain response. Conversely, failure is taken to be the effect of the evolution of any mechanisms that results in post-peak strain softening. It is assumed that matrix microdamage is the dominant damage mechanism in continuous fiber-reinforced polymer matrix laminates, and its evolution is controlled with a single ISV. Three additional ISVs are introduced to account for failure due to mode I transverse cracking, mode II transverse cracking, and mode I axial failure. Typically, failure evolution (i.e., post-peak strain softening) results in pathologically mesh dependent solutions within a finite element method (FEM) setting. Therefore, consistent character element lengths are introduced into the formulation of the evolution of the three failure ISVs. Using the stationarity of the total work potential with respect to each ISV, a set of thermodynamically consistent evolution equations for the ISVs is derived. The theory is implemented into commercial FEM software. Objectivity of total energy dissipated during the failure process, with regards to refinements in the FEM mesh, is demonstrated. The model is also verified against experimental results from two laminated, T800/3900-2 panels containing a central notch and different fiber-orientation stacking sequences. Global load versus displacement, global load versus local strain gage data, and macroscopic failure paths obtained from the models are compared to the experiments.

Damage progression in Composite Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon

1996-01-01

A computational simulation tool is used to evaluate the various stages of damage progression in composite materials during Iosipescu sheat testing. Unidirectional composite specimens with either the major or minor material axis in the load direction are considered. Damage progression characteristics are described for each specimen using two types of boundary conditions. A procedure is outlined regarding the use of computational simulation in composites testing. Iosipescu shear testing using the V-notched beam specimen is a convenient method to measure both shear strength and shear stiffness simultaneously. The evaluation of composite test response can be made more productive and informative via computational simulation of progressive damage and fracture. Computational simulation performs a complete evaluation of laminated composite fracture via assessment of ply and subply level damage/fracture processes.

Coupling continuous damage and debris fragmentation for energy absorption prediction by cfrp structures during crushing

NASA Astrophysics Data System (ADS)

Espinosa, Christine; Lachaud, Frédéric; Limido, Jérome; Lacome, Jean-Luc; Bisson, Antoine; Charlotte, Miguel

2015-05-01

Energy absorption during crushing is evaluated using a thermodynamic based continuum damage model inspired from the Matzenmiller-Lubliner-Taylors model. It was found that for crash-worthiness applications, it is necessary to couple the progressive ruin of the material to a representation of the matter openings and debris generation. Element kill technique (erosion) and/or cohesive elements are efficient but not predictive. A technique switching finite elements into discrete particles at rupture is used to create debris and accumulated mater during the crushing of the structure. Switching criteria are evaluated using the contribution of the different ruin modes in the damage evolution, energy absorption, and reaction force generation.

Radiographic progression in weight-bearing joints of patients with rheumatoid arthritis after TNF-blocking therapies.

PubMed

Seki, Eiko; Matsushita, Isao; Sugiyama, Eiji; Taki, Hirohumi; Shinoda, Koichiro; Hounoki, Hiroyuki; Motomura, Hiraku; Kimura, Tomoatsu

2009-04-01

The aim of the present study was to assess the influence of tumor necrosis factor (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid arthritis. Changes in clinical variables and radiological findings in 213 weight-bearing joints (69 hip joints, 63 knee joints, and 81 ankle joints) of 42 consecutive patients were investigated at baseline and at 1 year of TNF-blocking therapies. Structural damage to the weight-bearing joints was assessed using the Larsen scoring method. Detailed comparisons of the sizes and locations of erosions were performed for each set of radiographs of the respective joints. Assessment of radiographs of the 213 weight-bearing joints indicated progression of the Larsen grade in eight joints. Another five joints without Larsen grade progression showed apparent radiographic progression of joint damage based on increases in bony erosions. Overall, 13 joints (6%) of eight patients (19%) showed progression of joint damage after 1 year of TNF-blocking therapies. Analysis of each baseline grade indicated that radiographic progression of joint damage was inhibited in most grade 0-II joints. On the other hand, all hip and knee joints with pre-existing damage of grade III/IV showed apparent progression even in patients with good response. The results further suggested that radiographic progression may occur in less damaged joints when the patients were non-responders to the therapy. Among the weight-bearing joints, ankle joints showed different radiographic behavior and four ankle joints displayed improvement of radiographic damage. Early initiation of anti-TNF therapy should be necessary especially when the patients are starting to show early structural damage in weight-bearing joints.

Characterization of Damage Progression in SCS-6/timetal 21S (0)4 Under Thermomechanical Fatigue Loadings

NASA Technical Reports Server (NTRS)

Castelli, Michael G.

1994-01-01

A detailed experimental investigation was performed at a single maximum cyclic stress (sigma max) level to physically characterize the progression of thermomechanical fatigue (lW) damage in continuously reinforced (0 deg) SCS-6/Timetal 21S, a titanium matrix composite. In-phase (IP) and out of-phase (OP) loadings were investigated at sigma max = 1000 MPa with a temperature cycle from 150 to 6500 C. Damage progression, in terms of macroscopic property degradation, was experimentally quantified through an advanced TMF test methodology which incorporates explicit measurements of the isothermal static moduli at the TMF temperature extremes and the coefficient of thermal expansion (CTE) as functions of the TMF cycles. Detailed characterization of the physical damage progression at the microstructural level was performed by interrupting multiple TMF tests at various stages of mechanical property degradation and analyzing the microstructure through extensive destructive metallography. Further, the extent of damage was also quantified through residual static strength measurements. Results indicated that damage initiation occurred very early in cyclic life (N less than 0.1Nf) for both the IP and OP TMF loadings. IP TMF damage was found to be dominated by fiber breakage with a physical damage progression in the microstructure which was difficult to quantify. OP TMF loadings produced matrix cracking exclusively associated with surface initiations. Here, damage progression was easily distinguished in terms of both the number of cracks and their relative inward progressions toward the outer fiber rows with increased cycling. The point at which the leading cracks reached the outer fiber rows (when localized fiber/matrix de-bonding and matrix crack bridging occurred) appeared to be reflected in the macroscopic property degradation curves.

Computational Implementation of a Thermodynamically Based Work Potential Model For Progressive Microdamage and Transverse Cracking in Fiber-Reinforced Laminates

NASA Technical Reports Server (NTRS)

Pineda, Evan J.; Waas, Anthony M.; Bednarcyk, Brett A.; Collier, Craig S.

2012-01-01

A continuum-level, dual internal state variable, thermodynamically based, work potential model, Schapery Theory, is used capture the effects of two matrix damage mechanisms in a fiber-reinforced laminated composite: microdamage and transverse cracking. Matrix microdamage accrues primarily in the form of shear microcracks between the fibers of the composite. Whereas, larger transverse matrix cracks typically span the thickness of a lamina and run parallel to the fibers. Schapery Theory uses the energy potential required to advance structural changes, associated with the damage mechanisms, to govern damage growth through a set of internal state variables. These state variables are used to quantify the stiffness degradation resulting from damage growth. The transverse and shear stiffness of the lamina are related to the internal state variables through a set of measurable damage functions. Additionally, the damage variables for a given strain state can be calculated from a set of evolution equations. These evolution equations and damage functions are implemented into the finite element method and used to govern the constitutive response of the material points in the model. Additionally, an axial failure criterion is included in the model. The response of a center-notched, buffer strip-stiffened panel subjected to uniaxial tension is investigated and results are compared to experiment.

Stochastic-Strength-Based Damage Simulation of Ceramic Matrix Composite Laminates

NASA Technical Reports Server (NTRS)

Nemeth, Noel N.; Mital, Subodh K.; Murthy, Pappu L. N.; Bednarcyk, Brett A.; Pineda, Evan J.; Bhatt, Ramakrishna T.; Arnold, Steven M.

2016-01-01

The Finite Element Analysis-Micromechanics Analysis Code/Ceramics Analysis and Reliability Evaluation of Structures (FEAMAC/CARES) program was used to characterize and predict the progressive damage response of silicon-carbide-fiber-reinforced reaction-bonded silicon nitride matrix (SiC/RBSN) composite laminate tensile specimens. Studied were unidirectional laminates [0] (sub 8), [10] (sub 8), [45] (sub 8), and [90] (sub 8); cross-ply laminates [0 (sub 2) divided by 90 (sub 2),]s; angled-ply laminates [plus 45 (sub 2) divided by -45 (sub 2), ]s; doubled-edge-notched [0] (sub 8), laminates; and central-hole laminates. Results correlated well with the experimental data. This work was performed as a validation and benchmarking exercise of the FEAMAC/CARES program. FEAMAC/CARES simulates stochastic-based discrete-event progressive damage of ceramic matrix composite and polymer matrix composite material structures. It couples three software programs: (1) the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC), (2) the Ceramics Analysis and Reliability Evaluation of Structures Life Prediction Program (CARES/Life), and (3) the Abaqus finite element analysis program. MAC/GMC contributes multiscale modeling capabilities and micromechanics relations to determine stresses and deformations at the microscale of the composite material repeating-unit-cell (RUC). CARES/Life contributes statistical multiaxial failure criteria that can be applied to the individual brittle-material constituents of the RUC, and Abaqus is used to model the overall composite structure. For each FEAMAC/CARES simulation trial, the stochastic nature of brittle material strength results in random, discrete damage events that incrementally progress until ultimate structural failure.

Progressive Damage Analyses of Skin/Stringer Debonding

NASA Technical Reports Server (NTRS)

Daville, Carlos G.; Camanho, Pedro P.; deMoura, Marcelo F.

2004-01-01

The debonding of skin/stringer constructions is analyzed using a step-by-step simulation of material degradation based on strain softening decohesion elements and a ply degradation procedure. Decohesion elements with mixed-mode capability are placed at the interface between the skin and the flange to simulate the initiation and propagation of the delamination. In addition, the initiation and accumulation of fiber failure and matrix damage is modeled using Hashin-type failure criteria and their corresponding material degradation schedules. The debonding predictions using simplified three-dimensional models correlate well with test results.

Uncertainty in urban flood damage assessment due to urban drainage modelling and depth-damage curve estimation.

PubMed

Freni, G; La Loggia, G; Notaro, V

2010-01-01

Due to the increased occurrence of flooding events in urban areas, many procedures for flood damage quantification have been defined in recent decades. The lack of large databases in most cases is overcome by combining the output of urban drainage models and damage curves linking flooding to expected damage. The application of advanced hydraulic models as diagnostic, design and decision-making support tools has become a standard practice in hydraulic research and application. Flooding damage functions are usually evaluated by a priori estimation of potential damage (based on the value of exposed goods) or by interpolating real damage data (recorded during historical flooding events). Hydraulic models have undergone continuous advancements, pushed forward by increasing computer capacity. The details of the flooding propagation process on the surface and the details of the interconnections between underground and surface drainage systems have been studied extensively in recent years, resulting in progressively more reliable models. The same level of was advancement has not been reached with regard to damage curves, for which improvements are highly connected to data availability; this remains the main bottleneck in the expected flooding damage estimation. Such functions are usually affected by significant uncertainty intrinsically related to the collected data and to the simplified structure of the adopted functional relationships. The present paper aimed to evaluate this uncertainty by comparing the intrinsic uncertainty connected to the construction of the damage-depth function to the hydraulic model uncertainty. In this way, the paper sought to evaluate the role of hydraulic model detail level in the wider context of flood damage estimation. This paper demonstrated that the use of detailed hydraulic models might not be justified because of the higher computational cost and the significant uncertainty in damage estimation curves. This uncertainty occurs mainly because a large part of the total uncertainty is dependent on depth-damage curves. Improving the estimation of these curves may provide better results in term of uncertainty reduction than the adoption of detailed hydraulic models.

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

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

Sevilla, M D

1980-09-01

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

Estrogens and progression of diabetic kidney damage.

PubMed

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

2011-01-01

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

Progression of white matter damage in progressive supranuclear palsy with predominant parkinsonism.

PubMed

Caso, Francesca; Agosta, Federica; Ječmenica-Lukić, Milica; Petrović, Igor; Meani, Alessandro; Kostic, Vladimir S; Filippi, Massimo

2018-04-01

Progressive supranuclear palsy with predominant parkinsonism (PSP-P) accounts for 14-35% of all PSP cases. A few cross-sectional MRI studies in PSP-P showed a remarkable white matter (WM) damage. Progression of brain structural damage in these patients remains unknown. Longitudinal clinical, cognitive and diffusion tensor (DT) MRI data were obtained over a mean 1.6 year follow up in 10 PSP-P patients. At study entry, patients were compared with 36 healthy controls. Voxelwise statistical analysis of white matter DT MRI data (mean, axial and radial diffusivity, and fractional anisotropy) was carried out using tract-based spatial statistics. During the 1.6 year follow up, PSP-P patients showed significant decline of motor, cognitive and mood disturbances. DT MRI analysis revealed at baseline a widespread pattern of WM alterations. Over time, PSP-P patients exhibited progression of WM damage in supratentorial tracts compared to baseline. No WM changes were detected in cerebellar WM. In PSP-P patients, WM damage significantly progressed over time. Longitudinal DT MRI measures are a potential in vivo marker of disease progression in PSP-P. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gear Damage Detection Using Oil Debris Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.

2001-01-01

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

Numerical Predictions of Damage and Failure in Carbon Fiber Reinforced Laminates Using a Thermodynamically-Based Work Potential Theory

NASA Technical Reports Server (NTRS)

Pineda, Evan Jorge; Waas, Anthony M.

2013-01-01

A thermodynamically-based work potential theory for modeling progressive damage and failure in fiber-reinforced laminates is presented. The current, multiple-internal state variable (ISV) formulation, referred to as enhanced Schapery theory (EST), utilizes separate ISVs for modeling the effects of damage and failure. Consistent characteristic lengths are introduced into the formulation to govern the evolution of the failure ISVs. Using the stationarity of the total work potential with respect to each ISV, a set of thermodynamically consistent evolution equations for the ISVs are derived. The theory is implemented into a commercial finite element code. The model is verified against experimental results from two laminated, T800/3900-2 panels containing a central notch and different fiber-orientation stacking sequences. Global load versus displacement, global load versus local strain gage data, and macroscopic failure paths obtained from the models are compared against the experimental results.

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

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

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

1995-12-31

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

Progression of cartilage damage and meniscal pathology over 30 months is associated with an increase in radiographic tibiofemoral joint space narrowing in persons with knee OA--the MOST study.

PubMed

Crema, M D; Nevitt, M C; Guermazi, A; Felson, D T; Wang, K; Lynch, J A; Marra, M D; Torner, J; Lewis, C E; Roemer, F W

2014-10-01

To determine the association of MRI-assessed worsening of tibiofemoral cartilage damage, meniscal damage, meniscal extrusion, separately and together, with progression of radiographic joint space narrowing (JSN). The Multicenter Osteoarthitis Study (MOST) Study is a cohort study of subjects with or at risk for knee osteoarthritis (OA). Knees with radiographic OA Kellgren-Lawrence grade 2 at baseline and with baseline and 30-month 1.0 T MRIs were selected for reading using the WORMS system for cartilage damage, meniscal damage, and meniscal extrusion. The association of worsening of cartilage damage, meniscal damage, and/or meniscal extrusion with increases in the JSN was performed using logistic regression. A total of 276 knees (one per subject) were included (women 68.5%, mean age 62.9 ± 7.8, mean body mass index (BMI) 30.2 ± 5.0). Worsening of each MRI feature was associated with any increase in JSN (P < 0.01). Worsening of cartilage damage was more frequently observed than worsening of meniscal damage and extrusion, and was significantly associated with both slow and fast progression of JSN. An increasing risk of JSN worsening was associated with increasing number of worsening MRI features (P for trend < 0.0001). Worsening of tibiofemoral cartilage damage, meniscal damage, and meniscal extrusion are independent predictors of JSN progression in the same compartment. Worsening of cartilage damage is more frequently observed in JSN when compared to meniscal worsening. A strong cumulative effect on JSN progression is observed for worsening of more than one MRI feature. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Radiographic changes and factors associated with subsequent progression of damage in weight-bearing joints of patients with rheumatoid arthritis under TNF-blocking therapies-three-year observational study.

PubMed

Matsushita, Isao; Motomura, Hiraku; Seki, Eiko; Kimura, Tomoatsu

2017-07-01

The long-term effects of tumor necrosis factor (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid arthritis (RA) have not been fully characterized. The purpose of this study was to assess the radiographic changes of weight-bearing joints in patients with RA during 3-year of TNF-blocking therapies and to identify factors related to the progression of joint damage. Changes in clinical variables and radiological findings in 243 weight-bearing joints (63 hips, 54 knees, 71 ankles, and 55 subtalar joints) in 38 consecutive patients were investigated during three years of treatment with TNF-blocking agents. Multivariate logistic regression analysis was used to identify risk factors for the progression of weight-bearing joint damage. Seventeen (14.5%) of proximal weight-bearing joints (hips and knees) showed apparent radiographic progression during three years of treatment, whereas none of the proximal weight-bearing joints showed radiographic evidence of improvement or repair. In contrast, distal weight-bearing joints (ankle and subtalar joints) displayed radiographic progression and improvement in 20 (15.9%) and 8 (6.3%) joints, respectively. Multivariate logistic analysis for proximal weight-bearing joints identified the baseline Larsen grade (p < 0.001, OR:24.85, 95%CI: 5.07-121.79) and disease activity at one year after treatment (p = 0.003, OR:3.34, 95%CI:1.50-7.46) as independent factors associated with the progression of joint damage. On the other hand, multivariate analysis for distal weight-bearing joints identified disease activity at one year after treatment (p < 0.001, OR:2.13, 95%CI:1.43-3.18) as an independent factor related to the progression of damage. Baseline Larsen grade was strongly associated with the progression of damage in the proximal weight-bearing joints. Disease activity after treatment was an independent factor for progression of damage in proximal and distal weight-bearing joints. Early treatment with TNF-blocking agents and tight control of disease activity are necessary to prevent the progression of damage of the weight-bearing joints.

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

NASA Technical Reports Server (NTRS)

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

2001-01-01

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

Predicting knee replacement damage in a simulator machine using a computational model with a consistent wear factor.

PubMed

Zhao, Dong; Sakoda, Hideyuki; Sawyer, W Gregory; Banks, Scott A; Fregly, Benjamin J

2008-02-01

Wear of ultrahigh molecular weight polyethylene remains a primary factor limiting the longevity of total knee replacements (TKRs). However, wear testing on a simulator machine is time consuming and expensive, making it impractical for iterative design purposes. The objectives of this paper were first, to evaluate whether a computational model using a wear factor consistent with the TKR material pair can predict accurate TKR damage measured in a simulator machine, and second, to investigate how choice of surface evolution method (fixed or variable step) and material model (linear or nonlinear) affect the prediction. An iterative computational damage model was constructed for a commercial knee implant in an AMTI simulator machine. The damage model combined a dynamic contact model with a surface evolution model to predict how wear plus creep progressively alter tibial insert geometry over multiple simulations. The computational framework was validated by predicting wear in a cylinder-on-plate system for which an analytical solution was derived. The implant damage model was evaluated for 5 million cycles of simulated gait using damage measurements made on the same implant in an AMTI machine. Using a pin-on-plate wear factor for the same material pair as the implant, the model predicted tibial insert wear volume to within 2% error and damage depths and areas to within 18% and 10% error, respectively. Choice of material model had little influence, while inclusion of surface evolution affected damage depth and area but not wear volume predictions. Surface evolution method was important only during the initial cycles, where variable step was needed to capture rapid geometry changes due to the creep. Overall, our results indicate that accurate TKR damage predictions can be made with a computational model using a constant wear factor obtained from pin-on-plate tests for the same material pair, and furthermore, that surface evolution method matters only during the initial "break in" period of the simulation.

Progressive Damage and Fracture in Composites Under Dynamic Loading

NASA Technical Reports Server (NTRS)

Minnetyan, Levon

1994-01-01

A computational simulation tool is used to evaluate the various stages of damage progression in composite materials during losipescu shear testing. Unidirectional composite specimens with either the major or minor material axis in the load direction are considered. Damage progression characteristics are described for each specimen using two types of boundary conditions. A procedure is outlined regarding the use of computational simulation in the testing of composite materials.

Characterization of impact damage in woven fiber composites using fiber Bragg grating sensing and NDE

NASA Astrophysics Data System (ADS)

Hiche, Cristobal; Liu, Kuang C.; Seaver, Mark; Wei, Jun; Chattopadhyay, Aditi

2009-03-01

Woven fiber composites are currently being investigated due to their advantages over other materials, making them suitable for low weight, high stiffness, and high interlaminar fracture toughness applications such as missiles, body armor, satellites, and many other aerospace applications. Damage characterization of woven fabrics is a complex task due to their tendency to exhibit different failure modes based on the weave configuration, orientation, ply stacking and other variables. A multiscale model is necessary to accurately predict progressive damage. The present research is an experimental study on damage characterization of three different woven fiber laminates under low energy impact using Fiber Bragg Grating (FBG) sensors and flash thermography. A correlation between the measured strain from FBG sensors and the damaged area obtained from flash thermography imaging has been developed. It was observed that the peak strain in the fabrics were strongly dependent on the weave geometry and decreased at different rates as damage area increased due to dissimilar failure modes. Experimental observations were validated with the development of a multiscale model. A FBG sensor placement model was developed which showed that FBG sensor location and orientation plays a key role in the sensing capabilities of strain on the samples.

Combined meso-scale modeling and experimental investigation of the effect of mechanical damage on the transport properties of cementitious composites

NASA Astrophysics Data System (ADS)

Raghavan, Balaji; Niknezhad, Davood; Bernard, Fabrice; Kamali-Bernard, Siham

2016-09-01

The transport properties of cementitious composites such as concrete are important indicators of their durability, and are known to be heavily influenced by mechanical loading. In the current work, we use meso-scale hygro-mechanical modeling with a morphological 3D two phase mortar-aggregate model, in conjunction with experimentally obtained properties, to investigate the coupling between mechanical loading and damage and the permeability of the composite. The increase in permeability of a cylindrical test specimen at 28% aggregate fraction during a uniaxial displacement-controlled compression test at 85% of the peak load was measured using a gas permeameter. The mortar's mechanical behavior is assumed to follow the well-known compression damaged plasticity (CDP) model with isotropic damage, at varying thresholds, and obtained from different envelope curves. The damaged intrinsic permeability of the mortar evolves according to a logarithmic matching law with progressive loading. We fit the matching law parameters to the experimental result for the test specimen by inverse identification using our meso-scale model. We then subject a series of virtual composite specimens to quasi-static uniaxial compressive loading with varying boundary conditions to obtain the simulated damage and strain evolutions, and use the damage data and the previously identified parameters to determine the evolution of the macroscopic permeability tensor for the specimens, using a network model. We conduct a full parameter study by varying aggregate volume fraction, granulometric distribution, loading/boundary conditions and "matching law" parameters, as well as for different strain-damage thresholds and uniaxial loading envelope curves. Based on this study, we propose Avrami equation-based upper and lower bounds for the evolution of the damaged permeability of the composite.

Simulating the Impact Response of Composite Airframe Components

NASA Technical Reports Server (NTRS)

Jackson, Karen E.; Littell, Justin D.; Fasanella, Edwin L.

2014-01-01

In 2010, NASA Langley Research Center obtained residual hardware from the US Army's Survivable Affordable Repairable Airframe Program (SARAP). The hardware consisted of a composite fuselage section that was representative of the center section of a Black Hawk helicopter. The section was fabricated by Sikorsky Aircraft Corporation and designated the Test Validation Article (TVA). The TVA was subjected to a vertical drop test in 2008 to evaluate a tilting roof concept to limit the intrusion of overhead mass items, such as the rotor transmission, into the fuselage cabin. As a result of the 2008 test, damage to the hardware was limited primarily to the roof. Consequently, when the post-test article was obtained in 2010, the roof area was removed and the remaining structure was cut into six different types of test specimens including: (1) tension and compression coupons for material property characterization, (2) I-beam sections, (3) T-sections, (4) cruciform sections, (5) a large subfloor section, and (6) a forward framed fuselage section. In 2011, NASA and Sikorsky entered into a cooperative research agreement to study the impact responses of composite airframe structures and to evaluate the capabilities of the explicit transient dynamic finite element code, LS-DYNA®, to simulate these responses including damage initiation and progressive failure. Finite element models of the composite specimens were developed and impact simulations were performed. The properties of the composite material were represented using both a progressive in-plane damage model (Mat 54) and a continuum damage mechanics model (Mat 58) in LS-DYNA. This paper provides test-analysis comparisons of time history responses and the location and type of damage for representative I-beam, T-section, and cruciform section components.

Indentation-flexure and low-velocity impact damage in graphite/epoxy laminates

NASA Technical Reports Server (NTRS)

Kwon, Young S.; Sankar, Bhavani V.

1992-01-01

Static indentation and low velocity impact tests were performed on quasi-isotropic and cross ply graphite/epoxy composite laminates. The load deflection relations in static tests and impact force history in the impact tests were recorded. The damage was assessed by using ultrasonic C-scanning and photomicrographic techniques. The static behavior of the laminates and damage progression during loading, unloading, and reloading were explained by a simple plate delamination model. A good correlation existed between the static and impact responses. It was found that results from a few static indentation-flexture tests can be used to predict the response and damage in composite laminates due to a class of low velocity impact events.

S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas.

PubMed

Rector, Jeff; Kapil, Sasha; Treude, Kelly J; Kumm, Phyllis; Glanzer, Jason G; Byrne, Brendan M; Liu, Shengqin; Smith, Lynette M; DiMaio, Dominick J; Giannini, Peter; Smith, Russell B; Oakley, Greg G

2017-02-07

Oral cancers are easily accessible compared to many other cancers. Nevertheless, oral cancer is often diagnosed late, resulting in a poor prognosis. Most oral cancers are squamous cell carcinomas that predominantly develop from cell hyperplasias and dysplasias. DNA damage is induced in these tissues directly or indirectly in response to oncogene-induced deregulation of cellular proliferation. Consequently, a DNA Damage response (DDR) and a cell cycle checkpoint is activated. As dysplasia transitions to cancer, proteins involved in DNA damage and checkpoint signaling are mutated or silenced decreasing cell death while increasing genomic instability and allowing continued tumor progression. Hyperphosphorylation of Replication Protein A (RPA), including phosphorylation of Ser4 and Ser8 of RPA2, is a well-known indicator of DNA damage and checkpoint activation. In this study, we utilize S4S8-RPA phosphorylation as a marker for cancer development and progression in oral squamous cell carcinomas (OSCC). S4S8-RPA phosphorylation was observed to be low in normal cells, high in dysplasias, moderate in early grade tumors, and low in late stage tumors, essentially supporting the model of the DDR as an early barrier to tumorigenesis in certain types of cancers. In contrast, overall RPA expression was not correlative to DDR activation or tumor progression. Utilizing S4S8-RPA phosphorylation to indicate competent DDR activation in the future may have clinical significance in OSCC treatment decisions, by predicting the susceptibility of cancer cells to first-line platinum-based therapies for locally advanced, metastatic and recurrent OSCC.

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

PubMed Central

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

2013-01-01

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

DaDyn-RS: a tool for the time-dependent simulation of damage, fluid pressure and long-term instability in alpine rock slopes

NASA Astrophysics Data System (ADS)

Riva, Federico; Agliardi, Federico; Amitrano, David; Crosta, Giovanni B.

2017-04-01

Large mountain slopes in alpine environments undergo a complex long-term evolution from glacial to postglacial environments, through a transient period of paraglacial readjustment. During and after this transition, the interplay among rock strength, topographic relief, and morpho-climatic drivers varying in space and time can lead to the development of different types of slope instability, from sudden catastrophic failures to large, slow, long-lasting yet potentially catastrophic rockslides. Understanding the long-term evolution of large rock slopes requires accounting for the time-dependence of deglaciation unloading, permeability and fluid pressure distribution, displacements and failure mechanisms. In turn, this is related to a convincing description of rock mass damage processes and to their transition from a sub-critical (progressive failure) to a critical (catastrophic failure) character. Although mechanisms of damage occurrence in rocks have been extensively studied in the laboratory, the description of time-dependent damage under gravitational load and variable external actions remains difficult. In this perspective, starting from a time-dependent model conceived for laboratory rock deformation, we developed Dadyn-RS, a tool to simulate the long-term evolution of real, large rock slopes. Dadyn-RS is a 2D, FEM model programmed in Matlab, which combines damage and time-to-failure laws to reproduce both diffused damage and strain localization meanwhile tracking long-term slope displacements from primary to tertiary creep stages. We implemented in the model the ability to account for rock mass heterogeneity and property upscaling, time-dependent deglaciation, as well as damage-dependent fluid pressure occurrence and stress corrosion. We first tested DaDyn-RS performance on synthetic case studies, to investigate the effect of the different model parameters on the mechanisms and timing of long-term slope behavior. The model reproduces complex interactions between topography, deglaciation rate, mechanical properties and fluid pressure occurrence, resulting in different kinematics, damage patterns and timing of slope instabilities. We assessed the role of groundwater on slope damage and deformation mechanisms by introducing time-dependent pressure cycling within simulations. Then, we applied DaDyn-RS to real slopes located in the Italian Central Alps, affected by an active rockslide and a Deep Seated Gravitational Slope Deformation, respectively. From Last Glacial Maximum to present conditions, our model allows reproducing in an explicitly time-dependent framework the progressive development of damage-induced permeability, strain localization and shear band differentiation at different times between the Lateglacial period and the Mid-Holocene climatic transition. Different mechanisms and timings characterize different styles of slope deformations, consistently with available dating constraints. DaDyn-RS is able to account for different long-term slope dynamics, from slow creep to the delayed transition to fast-moving rockslides.

Damage Progression in Bolted Composites

NASA Technical Reports Server (NTRS)

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

1998-01-01

Structural durability, damage tolerance, and progressive fracture characteristics of bolted graphite/epoxy composite laminates are evaluated via computational simulation. Constituent material properties and stress and strain limits are scaled up to the structure level to evaluate the overall damage and fracture propagation for bolted composites. Single and double bolted composite specimens with various widths and bolt spacings are evaluated. The effect of bolt spacing is investigated with regard to the structural durability of a bolted joint. Damage initiation, growth, accumulation, and propagation to fracture are included in the simulations. Results show the damage progression sequence and structural fracture resistance during different degradation stages. A procedure is outlined for the use of computational simulation data in the assessment of damage tolerance, determination of sensitive parameters affecting fracture, and interpretation of experimental results with insight for design decisions.

Damage Progression in Bolted Composites

NASA Technical Reports Server (NTRS)

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

1998-01-01

Structural durability,damage tolerance,and progressive fracture characteristics of bolted graphite/epoxy composite laminates are evaluated via computational simulation. Constituent material properties and stress and strain limits are scaled up to the structure level to evaluate the overall damage and fracture propagation for bolted composites. Single and double bolted composite specimens with various widths and bolt spacings are evaluated. The effect of bolt spacing is investigated with regard to the structural durability of a bolted joint. Damage initiation, growth, accumulation, and propagation to fracture are included in the simulations. Results show the damage progression sequence and structural fracture resistance during different degradation stages. A procedure is outlined for the use of computational simulation data in the assessment of damage tolerance, determination of sensitive parameters affecting fracture, and interpretation of experimental results with insight for design decisions.

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 is provided. Then, the paper describes how the model is embedded within the prognostic framework and how the prognostics performance is assessed using observations from run-to-failure experiments

Mito-Apocynin Prevents Mitochondrial Dysfunction, Microglial Activation, Oxidative Damage, and Progressive Neurodegeneration in MitoPark Transgenic Mice.

PubMed

Langley, Monica; Ghosh, Anamitra; Charli, Adhithiya; Sarkar, Souvarish; Ay, Muhammet; Luo, Jie; Zielonka, Jacek; Brenza, Timothy; Bennett, Brian; Jin, Huajun; Ghaisas, Shivani; Schlichtmann, Benjamin; Kim, Dongsuk; Anantharam, Vellareddy; Kanthasamy, Arthi; Narasimhan, Balaji; Kalyanaraman, Balaraman; Kanthasamy, Anumantha G

2017-11-10

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor deficits and degeneration of dopaminergic neurons. Caused by a number of genetic and environmental factors, mitochondrial dysfunction and oxidative stress play a role in neurodegeneration in PD. By selectively knocking out mitochondrial transcription factor A (TFAM) in dopaminergic neurons, the transgenic MitoPark mice recapitulate many signature features of the disease, including progressive motor deficits, neuronal loss, and protein inclusions. In the present study, we evaluated the neuroprotective efficacy of a novel mitochondrially targeted antioxidant, Mito-apocynin, in MitoPark mice and cell culture models of neuroinflammation and mitochondrial dysfunction. Oral administration of Mito-apocynin (10 mg/kg, thrice a week) showed excellent central nervous system bioavailability and significantly improved locomotor activity and coordination in MitoPark mice. Importantly, Mito-apocynin also partially attenuated severe nigrostriatal degeneration in MitoPark mice. Mechanistic studies revealed that Mito-apo improves mitochondrial function and inhibits NOX2 activation, oxidative damage, and neuroinflammation. The properties of Mito-apocynin identified in the MitoPark transgenic mouse model strongly support potential clinical applications for Mito-apocynin as a viable neuroprotective and anti-neuroinflammatory drug for treating PD when compared to conventional therapeutic approaches. Collectively, our data demonstrate, for the first time, that a novel orally active apocynin derivative improves behavioral, inflammatory, and neurodegenerative processes in a severe progressive dopaminergic neurodegenerative model of PD. Antioxid. Redox Signal. 27, 1048-1066.

Effects of tempol and redox-cycling nitroxides in models of oxidative stress

PubMed Central

Wilcox, Christopher S.

2010-01-01

Tempol is a redox cycling nitroxide that promotes the metabolism of many reactive oxygen species (ROS) and improves nitric oxide bioavailability. It has been studied extensively in animal models of oxidative stress. Tempol has been shown to preserve mitochondria against oxidative damage and improve tissue oxygenation. Tempol improved insulin responsiveness in models of diabetes mellitus and improved the dyslipidemia, reduced the weight gain and prevented diastolic dysfunction and heart failure in fat-fed models of the metabolic syndrome. Tempol protected many organs, including the heart and brain, from ischemia/reperfusion damage. Tempol prevented podocyte damage, glomerulosclerosis, proteinuria and progressive loss of renal function in models of salt and mineralocorticosteroid excess. It reduced brain or spinal cord damage after ischemia or trauma and exerted a spinal analgesic action. Tempol improved survival in several models of shock. It protected normal cells from radiation while maintaining radiation sensitivity of tumor cells. Its paradoxical pro-oxidant action in tumor cells accounted for a reduction in spontaneous tumor formation. Tempol was effective in some models of neurodegeneration. Thus, tempol has been effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage and many of the diseases associated with aging. Indeed, tempol given from birth prolonged the life span of normal mice. However, presently tempol has been used only in human subjects as a topical agent to prevent radiation-induced alopecia. PMID:20153367

Development of GENOA Progressive Failure Parallel Processing Software Systems

NASA Technical Reports Server (NTRS)

Abdi, Frank; Minnetyan, Levon

1999-01-01

A capability consisting of software development and experimental techniques has been developed and is described. The capability is integrated into GENOA-PFA to model polymer matrix composite (PMC) structures. The capability considers the physics and mechanics of composite materials and structure by integration of a hierarchical multilevel macro-scale (lamina, laminate, and structure) and micro scale (fiber, matrix, and interface) simulation analyses. The modeling involves (1) ply layering methodology utilizing FEM elements with through-the-thickness representation, (2) simulation of effects of material defects and conditions (e.g., voids, fiber waviness, and residual stress) on global static and cyclic fatigue strengths, (3) including material nonlinearities (by updating properties periodically) and geometrical nonlinearities (by Lagrangian updating), (4) simulating crack initiation. and growth to failure under static, cyclic, creep, and impact loads. (5) progressive fracture analysis to determine durability and damage tolerance. (6) identifying the percent contribution of various possible composite failure modes involved in critical damage events. and (7) determining sensitivities of failure modes to design parameters (e.g., fiber volume fraction, ply thickness, fiber orientation. and adhesive-bond thickness). GENOA-PFA progressive failure analysis is now ready for use to investigate the effects on structural responses to PMC material degradation from damage induced by static, cyclic (fatigue). creep, and impact loading in 2D/3D PMC structures subjected to hygrothermal environments. Its use will significantly facilitate targeting design parameter changes that will be most effective in reducing the probability of a given failure mode occurring.

Glomerular and tubular damage markers in individuals with progressive albuminuria.

PubMed

Nauta, Ferdau L; Scheven, Lieneke; Meijer, Esther; van Oeveren, Wim; de Jong, Paul E; Bakker, Stephan J L; Gansevoort, Ron T

2013-07-01

Albuminuria is associated with risk for renal and cardiovascular disease. It is difficult to predict which persons will progress in albuminuria. This study investigated whether assessment of urinary markers associated with damage to different parts of the nephron may help identify individuals that will progress in albuminuria. Individuals were selected from a prospective community-based cohort study with serial follow-up and defined as "progressors" if they belonged to the quintile of participants with the most rapid annual increase in albuminuria, and reached an albuminuria ≥150 mg/d during follow-up. Patients with known renal disease or macroalbuminuria at baseline were excluded. Each progressor was matched to two control participants, based on baseline albuminuria, age, and sex. Furthermore, damage markers were measured in a separate set of healthy individuals. After a median follow-up of 8.6 years, 183 of 8394 participants met the criteria for progressive albuminuria. Baseline clinical characteristics were comparable between progressors and matched controls (n=366). Both had higher baseline albuminuria than the overall population. Urinary excretion of the glomerular damage marker IgG was significantly higher in progressors, whereas urinary excretion of proximal tubular damage markers and inflammatory markers was lower in these individuals compared with controls. Healthy individuals (n=109) had the lowest values for all urinary damage markers measured. These data suggest that albuminuria associated with markers of glomerular damage is more likely to progress, whereas albuminuria associated with markers of tubulointerstitial damage is more likely to remain stable.

Intralaminar and Interlaminar Progressive Failure Analysis of Composite Panels with Circular Cutouts

NASA Technical Reports Server (NTRS)

Goyal, Vinay K.; Jaunky, Navin; Johnson, Eric R.; Ambur, Damodar

2002-01-01

A progressive failure methodology is developed and demonstrated to simulate the initiation and material degradation of a laminated panel due to intralaminar and interlaminar failures. Initiation of intralaminar failure can be by a matrix-cracking mode, a fiber-matrix shear mode, and a fiber failure mode. Subsequent material degradation is modeled using damage parameters for each mode to selectively reduce lamina material properties. The interlaminar failure mechanism such as delamination is simulated by positioning interface elements between adjacent sublaminates. A nonlinear constitutive law is postulated for the interface element that accounts for a multi-axial stress criteria to detect the initiation of delamination, a mixed-mode fracture criteria for delamination progression, and a damage parameter to prevent restoration of a previous cohesive state. The methodology is validated using experimental data available in the literature on the response and failure of quasi-isotropic panels with centrally located circular cutouts loaded into the postbuckling regime. Very good agreement between the progressive failure analyses and the experimental results is achieved if the failure analyses includes the interaction of intralaminar and interlaminar failures.

On the Nonlinear Behavior of a Glass-Ceramic Seal and its Application in Planar SOFC Systems

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

Nguyen, Ba Nghiep; Koeppel, Brian J.; Vetrano, John S.

2006-06-01

This paper studies the nonlinear behavior of a glass-ceramic seal used in planar solid oxide fuel cells (SOFCs). To this end, a viscoelastic damage model has been developed that can capture the nonlinear material response due to both progressive damage in the glass-ceramic material and viscous flow of the residual glass in this material. The model has been implemented in the MSC MARC finite element code, and its validation has been carried out using the experimental relaxation test data obtained for this material at 700oC, 750oC, and 800oC. Finally, it has been applied to the simulation of a SOFC stackmore » under thermal cycling conditions. The areas of potential damage have been predicted.« less

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

NASA Astrophysics Data System (ADS)

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

2010-02-01

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

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.

Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury.

PubMed

Yang, Yi; Kimura-Ohba, Shihoko; Thompson, Jeffrey F; Salayandia, Victor M; Cossé, Melissa; Raz, Limor; Jalal, Fakhreya Y; Rosenberg, Gary A

2018-06-01

Vascular cognitive impairment is a major cause of dementia caused by chronic hypoxia, producing progressive damage to white matter (WM) secondary to blood-brain barrier (BBB) opening and vascular dysfunction. Tight junction proteins (TJPs), which maintain BBB integrity, are lost in acute ischemia. Although angiogenesis is critical for neurovascular remodeling, less is known about its role in chronic hypoxia. To study the impact of TJP degradation and angiogenesis during pathological progression of WM damage, we used the spontaneously hypertensive/stroke prone rats with unilateral carotid artery occlusion and Japanese permissive diet to model WM damage. MRI and IgG immunostaining showed regions with BBB damage, which corresponded with decreased endothelial TJPs, claudin-5, occludin, and ZO-1. Affected WM had increased expression of angiogenic factors, Ki67, NG2, VEGF-A, and MMP-3 in vascular endothelial cells and pericytes. To facilitate the study of angiogenesis, we treated rats with minocycline to block BBB disruption, reduce WM lesion size, and extend survival. Minocycline-treated rats showed increased VEGF-A protein, TJP formation, and oligodendrocyte proliferation. We propose that chronic hypoxia disrupts TJPs, increasing vascular permeability, and initiating angiogenesis in WM. Minocycline facilitated WM repair by reducing BBB damage and enhancing expression of TJPs and angiogenesis, ultimately preserving oligodendrocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

Contact fatigue of human enamel: Experiments, mechanisms and modeling.

PubMed

Gao, S S; An, B B; Yahyazadehfar, M; Zhang, D; Arola, D D

2016-07-01

Cyclic contact between natural tooth structure and engineered ceramics is increasingly common. Fatigue of the enamel due to cyclic contact is rarely considered. The objectives of this investigation were to evaluate the fatigue behavior of human enamel by cyclic contact, and to assess the extent of damage over clinically relevant conditions. Cyclic contact experiments were conducted using the crowns of caries-free molars obtained from young donors. The cuspal locations were polished flat and subjected to cyclic contact with a spherical indenter of alumina at 2Hz. The progression of damage was monitored through the evolution in contact displacement, changes in the contact hysteresis and characteristics of the fracture pattern. The contact fatigue life diagram exhibited a decrease in cycles to failure with increasing cyclic load magnitude. Two distinct trends were identified, which corresponded to the development and propagation of a combination of cylindrical and radial cracks. Under contact loads of less than 400N, enamel rod decussation resisted the growth of subsurface cracks. However, at greater loads the damage progressed rapidly and accelerated fatigue failure. Overall, cyclic contact between ceramic appliances and natural tooth structure causes fatigue of the enamel. The extent of damage is dependent on the magnitude of cyclic stress and the ability of the decussation to arrest the fatigue damage. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tau depletion prevents progressive blood-brain barrier damage in a mouse model of tauopathy.

PubMed

Blair, Laura J; Frauen, Haley D; Zhang, Bo; Nordhues, Bryce A; Bijan, Sara; Lin, Yen-Chi; Zamudio, Frank; Hernandez, Lidice D; Sabbagh, Jonathan J; Selenica, Maj-Linda B; Dickey, Chad A

2015-01-31

The blood-brain barrier (BBB) is damaged in tauopathies, including progressive supranuclear palsy (PSP) and Alzheimer's disease (AD), which is thought to contribute to pathogenesis later in the disease course. In AD, BBB dysfunction has been associated with amyloid beta (Aß) pathology, but the role of tau in this process is not well characterized. Since increased BBB permeability is found in tauopathies without Aß pathology, like PSP, we suspected that tau accumulation alone could not only be sufficient, but even more important than Aß for BBB damage. Longitudinal evaluation of brain tissue from the tetracycline-regulatable rTg4510 tau transgenic mouse model showed progressive IgG, T cell and red blood cell infiltration. The Evans blue (EB) dye that is excluded from the brain when the BBB is intact also permeated the brains of rTg4510 mice following peripheral administration, indicative of a bonafide BBB defect, but this was only evident later in life. Thus, despite the marked brain atrophy and inflammation that occurs earlier in this model, BBB integrity is maintained. Interestingly, BBB dysfunction emerged at the same time that perivascular tau emerged around major hippocampal blood vessels. However, when tau expression was suppressed using doxycycline, BBB integrity was preserved, suggesting that the BBB can be stabilized in a tauopathic brain by reducing tau levels. For the first time, these data demonstrate that tau alone can initiate breakdown of the BBB, but the BBB is remarkably resilient, maintaining its integrity in the face of marked brain atrophy, neuroinflammation and toxic tau accumulation. Moreover, the BBB can recover integrity when tau levels are reduced. Thus, late stage interventions targeting tau may slow the vascular contributions to cognitive impairment and dementia that occur in tauopathies.

Recent Developments of the Florida Public Hurricane Loss Model

NASA Astrophysics Data System (ADS)

Cocke, S.; Shin, D. W.; Annane, B.

2016-12-01

Catastrophe models are used extensively by the insurance industry to estimate losses due to natural hazards such as hurricanes and earthquakes. In the state of Florida, primary insurers for hurricane damage to residential properties are required by law to use certified catastrophe models to establish their premiums and capital reserves. The Florida Public Hurricane Loss Model (FPHLM) is one of only five certified catastrophe models in Florida, and the only non-commercial model certified. The FPHLM has been funded through the Florida Legislature and is overseen by the Florida Office of Insurance Regulation (OIR). The model was developed by a consortium of universities and private consultants primary located in Florida, but includes some partners outside of the state. The FPHLM has met Florida requirements since 2006 and has undergone continuous evolution to maintain state-of-the-art capabilities and changes in state requirements established by the Florida Commission on Hurricane Loss Projection Methodology. Recently the model has been undergoing major enhancement to incorporate damage due to flooding, which not only includes hurricane floods but floods due to all potential natural hazards. This work is being done in anticipation of future changes in the National Flood Insurance Program (NFIP) that will bring private insurers to the flood market. The model will incorporate a surge model as well as an inland flood model. We will present progress on these recent enhancements along with additional progress of the model.

Mixed-Mode Decohesion Elements for Analyses of Progressive Delamination

NASA Technical Reports Server (NTRS)

Davila, Carlos G.; Camanho, Pedro P.; deMoura, Marcelo F.

2001-01-01

A new 8-node decohesion element with mixed mode capability is proposed and demonstrated. The element is used at the interface between solid finite elements to model the initiation and propagation of delamination. A single displacement-based damage parameter is used in a strain softening law to track the damage state of the interface. The method can be used in conjunction with conventional material degradation procedures to account for inplane and intra-laminar damage modes. The accuracy of the predictions is evaluated in single mode delamination tests, in the mixed-mode bending test, and in a structural configuration consisting of the debonding of a stiffener flange from its skin.

Prospects for development of unified global flood observation and prediction systems (Invited)

NASA Astrophysics Data System (ADS)

Lettenmaier, D. P.

2013-12-01

Floods are among the most damaging of natural hazards, with global flood losses in 2011 alone estimated to have exceeded $100B. Historically, flood economic damages have been highest in the developed world (due in part to encroachment on historical flood plains), but loss of life, and human impacts have been greatest in the developing world. However, as the 2011 Thailand floods show, industrializing countries, many of which do not have well developed flood protection systems, are increasingly vulnerable to economic damages as they become more industrialized. At present, unified global flood observation and prediction systems are in their infancy; notwithstanding that global weather forecasting is a mature field. The summary for this session identifies two evolving capabilities that hold promise for development of more sophisticated global flood forecast systems: global hydrologic models and satellite remote sensing (primarily of precipitation, but also of flood inundation). To this I would add the increasing sophistication and accuracy of global precipitation analysis (and forecast) fields from numerical weather prediction models. In this brief overview, I will review progress in all three areas, and especially the evolution of hydrologic data assimilation which integrates modeling and data sources. I will also comment on inter-governmental and inter-agency cooperation, and related issues that have impeded progress in the development and utilization of global flood observation and prediction systems.

An enhancement to the NA4 gear vibration diagnostic parameter

NASA Technical Reports Server (NTRS)

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

1994-01-01

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

VALPROIC ACID-INDUCED BRAIN DAMAGE IN RATS AS A MODEL FOR AUTISM. (R824758)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

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

NASA Technical Reports Server (NTRS)

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

2009-01-01

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

Numerical simulation of the effect of regular and sub-caliber projectiles on military bunkers

NASA Astrophysics Data System (ADS)

Jiricek, Pavel; Foglar, Marek

2015-09-01

One of the most demanding topics in blast and impact engineering is the modelling of projectile impact. To introduce this topic, a set of numerical simulations was undertaken. The simulations study the impact of regular and sub-calibre projectile on Czech pre-WW2 military bunkers. The penetrations of the military objects are well documented and can be used for comparison. The numerical model composes of a part from a wall of a military object. The concrete block is subjected to an impact of a regular and sub-calibre projectile. The model is divided into layers to simplify the evaluation of the results. The simulations are processed within ANSYS AUTODYN software. A nonlinear material model of with damage and incorporated strain-rate effect was used. The results of the numerical simulations are evaluated in means of the damage of the concrete block. Progress of the damage is described versus time. The numerical simulation provides good agreement with the documented penetrations.

Glomerular and Tubular Damage Markers in Individuals with Progressive Albuminuria

PubMed Central

Nauta, Ferdau L.; Scheven, Lieneke; Meijer, Esther; van Oeveren, Wim; de Jong, Paul E.; Bakker, Stephan J.L.

2013-01-01

Summary Background and objectives Albuminuria is associated with risk for renal and cardiovascular disease. It is difficult to predict which persons will progress in albuminuria. This study investigated whether assessment of urinary markers associated with damage to different parts of the nephron may help identify individuals that will progress in albuminuria. Design, setting, participants, & measurements Individuals were selected from a prospective community-based cohort study with serial follow-up and defined as “progressors” if they belonged to the quintile of participants with the most rapid annual increase in albuminuria, and reached an albuminuria ≥150 mg/d during follow-up. Patients with known renal disease or macroalbuminuria at baseline were excluded. Each progressor was matched to two control participants, based on baseline albuminuria, age, and sex. Furthermore, damage markers were measured in a separate set of healthy individuals. Results After a median follow-up of 8.6 years, 183 of 8394 participants met the criteria for progressive albuminuria. Baseline clinical characteristics were comparable between progressors and matched controls (n=366). Both had higher baseline albuminuria than the overall population. Urinary excretion of the glomerular damage marker IgG was significantly higher in progressors, whereas urinary excretion of proximal tubular damage markers and inflammatory markers was lower in these individuals compared with controls. Healthy individuals (n=109) had the lowest values for all urinary damage markers measured. Conclusions These data suggest that albuminuria associated with markers of glomerular damage is more likely to progress, whereas albuminuria associated with markers of tubulointerstitial damage is more likely to remain stable. PMID:23539232

Creep fatigue life prediction for engine hot section materials (isotropic): Fourth year progress review

NASA Technical Reports Server (NTRS)

Nelson, Richard S.; Schoendorf, John F.

1986-01-01

As gas turbine technology continues to advance, the need for advanced life prediction methods for hot section components is becoming more and more evident. The complex local strain and temperature histories at critical locations must be accurately interpreted to account for the effects of various damage mechanisms (such as fatigue, creep, and oxidation) and their possible interactions. As part of the overall NASA HOST effort, this program is designed to investigate these fundamental damage processes, identify modeling strategies, and develop practical models which can be used to guide the early design and development of new engines and to increase the durability of existing engines.

Literature Reviews on Modeling Internal Geometry of Textile Composites and Rate-Independent Continuum Damage

NASA Technical Reports Server (NTRS)

Su-Yuen, Hsu

2011-01-01

Textile composite materials have good potential for constructing composite structures where the effects of three-dimensional stresses are critical or geometric complexity is a manufacturing concern. There is a recent interest in advancing competence within Langley Research Center for modeling the degradation of mechanical properties of textile composites. In an initial effort, two critical areas are identified to pursue: (1) Construction of internal geometry of textile composites, and (2) Rate-independent continuum damage mechanics. This report documents reviews on the two subjects. Various reviewed approaches are categorized, their assumptions, methods, and progress are briefed, and then critiques are presented. Each review ends with recommended research.

Beyond debuttressing: Mechanics of paraglacial rock slope damage during repeat glacial cycles

NASA Astrophysics Data System (ADS)

Grämiger, Lorenz M.; Moore, Jeffrey R.; Gischig, Valentin S.; Ivy-Ochs, Susan; Loew, Simon

2017-04-01

Cycles of glaciation impose mechanical stresses on underlying bedrock as glaciers advance, erode, and retreat. Fracture initiation and propagation constitute rock mass damage and act as preparatory factors for slope failures; however, the mechanics of paraglacial rock slope damage remain poorly characterized. Using conceptual numerical models closely based on the Aletsch Glacier region of Switzerland, we explore how in situ stress changes associated with fluctuating ice thickness can drive progressive rock mass failure preparing future slope instabilities. Our simulations reveal that glacial cycles as purely mechanical loading and unloading phenomena produce relatively limited new damage. However, ice fluctuations can increase the criticality of fractures in adjacent slopes, which may in turn increase the efficacy of fatigue processes. Bedrock erosion during glaciation promotes significant new damage during first deglaciation. An already weakened rock slope is more susceptible to damage from glacier loading and unloading and may fail completely. We find that damage kinematics are controlled by discontinuity geometry and the relative position of the glacier; ice advance and retreat both generate damage. We correlate model results with mapped landslides around the Great Aletsch Glacier. Our result that most damage occurs during first deglaciation agrees with the relative age of the majority of identified landslides. The kinematics and dimensions of a slope failure produced in our models are also in good agreement with characteristics of instabilities observed in the field. Our results extend simplified assumptions of glacial debuttressing, demonstrating in detail how cycles of ice loading, erosion, and unloading drive paraglacial rock slope damage.

Structural Health Monitoring challenges on the 10-MW offshore wind turbine model

NASA Astrophysics Data System (ADS)

Di Lorenzo, E.; Kosova, G.; Musella, U.; Manzato, S.; Peeters, B.; Marulo, F.; Desmet, W.

2015-07-01

The real-time structural damage detection on large slender structures has one of its main application on offshore Horizontal Axis Wind Turbines (HAWT). The renewable energy market is continuously pushing the wind turbine sizes and performances. This is the reason why nowadays offshore wind turbines concepts are going toward a 10 MW reference wind turbine model. The aim of the work is to perform operational analyses on the 10-MW reference wind turbine finite element model using an aeroelastic code in order to obtain long-time-low- cost simulations. The aeroelastic code allows simulating the damages in several ways: by reducing the edgewise/flapwise blades stiffness, by adding lumped masses or considering a progressive mass addiction (i.e. ice on the blades). The damage detection is then performed by means of Operational Modal Analysis (OMA) techniques. Virtual accelerometers are placed in order to simulate real measurements and to estimate the modal parameters. The feasibility of a robust damage detection on the model has been performed on the HAWT model in parked conditions. The situation is much more complicated in case of operating wind turbines because the time periodicity of the structure need to be taken into account. Several algorithms have been implemented and tested in the simulation environment. They are needed in order to carry on a damage detection simulation campaign and develop a feasible real-time damage detection method. In addition to these algorithms, harmonic removal tools are needed in order to dispose of the harmonics due to the rotation.

Swollen joint count in psoriatic arthritis is associated with progressive radiological damage in hands and feet.

PubMed

Simon, P; Pfoehler, C; Bergner, R; Schreiber, M; Pfreundschuh, M; Assmann, G

2012-01-01

Psoriatic arthritis (PsA) may progress to joint damage. Determining clinical predictors of joint damage assessed by radiography is important. The aim of this study was to determine clinical factors as possible predictors for radiological damage in hands and feet of PsA patients with a 12-month follow-up. We conducted a retrospective study on 53 PsA patients who were taking disease-modifying anti-rheumatic drugs (DMARDs) and/or tumour necrosis factor (TNF)-alpha-blockers at a fixed dosage. The patients were observed in 118 follow-up visits (intervals of 12 months ± 3 months), according to a clinical and radiological protocol which included the documentation of the number of swollen and tender joints in hands and feet, the applied therapy, psoriasis, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and global health assessment. Outcome was defined as radiographic damage of hands and feet (Ratingen score). For the statistical analysis the Chi-Square test for 2x2 crosstables (with Fisher's correction, as required) was used. Progressive radiological damage was more frequent among patients with an increasing swollen joint count (8 of 26 visits; 30.8%) than among those with a stable or decreased number of swollen joints (5 of 89 visits; 5.6%; p=0.001). The analysis of the patients stratified into the different treatment modalities resulted in a significant higher rate of radiological progress (20.8%) in patients on DMARD therapy compared with TNF-alpha blocking agents (0%) (p=0.009). During a 12-month follow-up of PsA patients, an increasing number of swollen joints heralds progression of radiological damage. TNF-alpha-blocker therapy appears to be superior to DMARDs in the protection from radiological progress.

Increased oxidative phosphorylation in response to acute and chronic DNA damage

PubMed Central

Brace, Lear E; Vose, Sarah C; Stanya, Kristopher; Gathungu, Rose M; Marur, Vasant R; Longchamp, Alban; Treviño-Villarreal, Humberto; Mejia, Pedro; Vargas, Dorathy; Inouye, Karen; Bronson, Roderick T; Lee, Chih-Hao; Neilan, Edward; Kristal, Bruce S; Mitchell, James R

2016-01-01

Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can damage DNA, however the potential of acute or chronic DNA damage to modulate cellular and/or organismal energy metabolism remains largely unexplored. We modeled chronic endogenous genotoxic stress using a DNA repair-deficient Csa−/−|Xpa−/− mouse model of CS. Exogenous genotoxic stress was modeled in mice in vivo and primary cells in vitro treated with different genotoxins giving rise to diverse spectrums of lesions, including ultraviolet radiation, intrastrand crosslinking agents and ionizing radiation. Both chronic endogenous and acute exogenous genotoxic stress increased mitochondrial fatty acid oxidation (FAO) on the organismal level, manifested by increased oxygen consumption, reduced respiratory exchange ratio, progressive adipose loss and increased FAO in tissues ex vivo. In multiple primary cell types, the metabolic response to different genotoxins manifested as a cell-autonomous increase in oxidative phosphorylation (OXPHOS) subsequent to a transient decline in steady-state NAD+ and ATP levels, and required the DNA damage sensor PARP-1 and energy-sensing kinase AMPK. We conclude that increased FAO/OXPHOS is a general, beneficial, adaptive response to DNA damage on cellular and organismal levels, illustrating a fundamental link between genotoxic stress and energy metabolism driven by the energetic cost of DNA damage. Our study points to therapeutic opportunities to mitigate detrimental effects of DNA damage on primary cells in the context of radio/chemotherapy or progeroid syndromes. PMID:28721274

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

NASA Astrophysics Data System (ADS)

Fan, Linfeng; Lehmann, Peter; Or, Dani

2015-10-01

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

Fatigue loading of tendon

PubMed Central

Shepherd, Jennifer H; Screen, Hazel R C

2013-01-01

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

Investigation of Sideband Index Response to Prototype Gear Tooth Damage

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.

2013-01-01

The objective of this analysis was to evaluate the ability of gear condition indicators (CI) to detect contact fatigue damage on spiral bevel gear teeth. Tests were performed in the NASA Glenn Spiral Bevel Gear Fatigue Rig on eight prototype gear sets (pinion/gear). Damage was initiated and progressed on the gear and pinion teeth. Vibration data was measured during damage progression at varying torque values while varying damage modes to the gear teeth were observed and documented with inspection photos. Sideband indexes (SI) and root mean square (RMS) CIs were calculated from the time synchronous averaged vibration data. Results found that both CIs respond differently to varying torque levels, damage levels and damage modes

AUTEN-67 (Autophagy Enhancer-67) Hampers the Progression of Neurodegenerative Symptoms in a Drosophila model of Huntington's Disease.

PubMed

Billes, Viktor; Kovács, Tibor; Hotzi, Bernadette; Manzéger, Anna; Tagscherer, Kinga; Komlós, Marcell; Tarnóci, Anna; Pádár, Zsolt; Erdős, Attila; Bjelik, Annamaria; Legradi, Adam; Gulya, Károly; Gulyás, Balázs; Vellai, Tibor

2016-05-07

Autophagy, a lysosome-mediated self-degradation process of eukaryotic cells, serves as a main route for the elimination of cellular damage [1-3]. Such damages include aggregated, oxidized or misfolded proteins whose accumulation can cause various neurodegenerative pathologies, including Huntington's disease (HD). Here we examined whether enhanced autophagic activity can alleviate neurophatological features in a Drosophila model of HD (the transgenic animals express a human mutant Huntingtin protein with a long polyglutamine repeat, 128Q). We have recently identified an autophagy-enhancing small molecule, AUTEN-67 (autophagy enhancer 67), with potent neuroprotective effects [4]. AUTEN-67 was applied to induce autophagic activity in the HD model used in this study. We showed that AUTEN-67 treatment interferes with the progressive accumulation of ubiquitinated proteins in the brain of Drosophila transgenic for the pathological 128Q form of human Huntingtin protein. The compound significantly improved the climbing ability and moderately extended the mean life span of these flies. Furthermore, brain tissue samples from human patients diagnosed for HD displayed increased levels of the autophagy substrate SQSTM1/p62 protein, as compared with controls. These results imply that AUTEN-67 impedes the progression of neurodegenerative symptoms characterizing HD, and that autophagy is a promising therapeutic target for treating this pathology. In humans, AUTEN-67 may have the potential to delay the onset and decrease the severity of HD.

Two-Dimensional Nonlinear Finite Element Analysis of CMC Microstructures

NASA Technical Reports Server (NTRS)

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

2012-01-01

A research program has been developed to quantify the effects of the microstructure of a woven ceramic matrix composite and its variability on the effective properties and response of the material. In order to characterize and quantify the variations in the microstructure of a five harness satin weave, chemical vapor infiltrated (CVI) SiC/SiC composite material, specimens were serially sectioned and polished to capture images that detailed the fiber tows, matrix, and porosity. Open source quantitative image analysis tools were then used to isolate the constituents, from which two dimensional finite element models were generated which approximated the actual specimen section geometry. A simplified elastic-plastic model, wherein all stress above yield is redistributed to lower stress regions, is used to approximate the progressive damage behavior for each of the composite constituents. Finite element analyses under in-plane tensile loading were performed to examine how the variability in the local microstructure affected the macroscopic stress-strain response of the material as well as the local initiation and progression of damage. The macroscopic stress-strain response appeared to be minimally affected by the variation in local microstructure, but the locations where damage initiated and propagated appeared to be linked to specific aspects of the local microstructure.

Damaging effects of visible light. Comprehensive progress report

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

None

1981-01-01

Research progress is reported on studies of retinal light damage. A myriad of variables effect the production of light damage. These include age, prior light history, body temperature, vitamin A status, intensity, wavelength and duration of light. The intensity-duration function and the age function have been studied in detail in rats. Studies have been begun on the wavelength variable. (ACR)

Tapered Roller Bearing Damage Detection Using Decision Fusion Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Kreider, Gary; Fichter, Thomas

2006-01-01

A diagnostic tool was developed for detecting fatigue damage of tapered roller bearings. Tapered roller bearings are used in helicopter transmissions and have potential for use in high bypass advanced gas turbine aircraft engines. A diagnostic tool was developed and evaluated experimentally by collecting oil debris data from failure progression tests conducted using health monitoring hardware. Failure progression tests were performed with tapered roller bearings under simulated engine load conditions. Tests were performed on one healthy bearing and three pre-damaged bearings. During each test, data from an on-line, in-line, inductance type oil debris sensor and three accelerometers were monitored and recorded for the occurrence of bearing failure. The bearing was removed and inspected periodically for damage progression throughout testing. Using data fusion techniques, two different monitoring technologies, oil debris analysis and vibration, were integrated into a health monitoring system for detecting bearing surface fatigue pitting damage. The data fusion diagnostic tool was evaluated during bearing failure progression tests under simulated engine load conditions. This integrated system showed improved detection of fatigue damage and health assessment of the tapered roller bearings as compared to using individual health monitoring technologies.

Two-Dimensional Nonlinear Finite Element Analysis of CMC Microstructures

NASA Technical Reports Server (NTRS)

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

2011-01-01

Detailed two-dimensional finite element analyses of the cross-sections of a model CVI (chemical vapor infiltrated) SiC/SiC (silicon carbide fiber in a silicon carbide matrix) ceramic matrix composites are performed. High resolution images of the cross-section of this composite material are generated using serial sectioning of the test specimens. These images are then used to develop very detailed finite element models of the cross-sections using the public domain software OOF2 (Object Oriented Analysis of Material Microstructures). Examination of these images shows that these microstructures have significant variability and irregularity. How these variabilities manifest themselves in the variability in effective properties as well as the stress distribution, damage initiation and damage progression is the overall objective of this work. Results indicate that even though the macroscopic stress-strain behavior of various sections analyzed is very similar, each section has a very distinct damage pattern when subjected to in-plane tensile loads and this damage pattern seems to follow the unique architectural and microstructural details of the analyzed sections.

Orchestration of DNA Damage Checkpoint Dynamics across the Human Cell Cycle.

PubMed

Chao, Hui Xiao; Poovey, Cere E; Privette, Ashley A; Grant, Gavin D; Chao, Hui Yan; Cook, Jeanette G; Purvis, Jeremy E

2017-11-22

Although molecular mechanisms that prompt cell-cycle arrest in response to DNA damage have been elucidated, the systems-level properties of DNA damage checkpoints are not understood. Here, using time-lapse microscopy and simulations that model the cell cycle as a series of Poisson processes, we characterize DNA damage checkpoints in individual, asynchronously proliferating cells. We demonstrate that, within early G1 and G2, checkpoints are stringent: DNA damage triggers an abrupt, all-or-none cell-cycle arrest. The duration of this arrest correlates with the severity of DNA damage. After the cell passes commitment points within G1 and G2, checkpoint stringency is relaxed. By contrast, all of S phase is comparatively insensitive to DNA damage. This checkpoint is graded: instead of halting the cell cycle, increasing DNA damage leads to slower S phase progression. In sum, we show that a cell's response to DNA damage depends on its exact cell-cycle position and that checkpoints are phase-dependent, stringent or relaxed, and graded or all-or-none. Copyright © 2017 Elsevier Inc. All rights reserved.

Predicting remaining life by fusing the physics of failure modeling with diagnostics

NASA Astrophysics Data System (ADS)

Kacprzynski, G. J.; Sarlashkar, A.; Roemer, M. J.; Hess, A.; Hardman, B.

2004-03-01

Technology that enables failure prediction of critical machine components (prognostics) has the potential to significantly reduce maintenance costs and increase availability and safety. This article summarizes a research effort funded through the U.S. Defense Advanced Research Projects Agency and Naval Air System Command aimed at enhancing prognostic accuracy through more advanced physics-of-failure modeling and intelligent utilization of relevant diagnostic information. H-60 helicopter gear is used as a case study to introduce both stochastic sub-zone crack initiation and three-dimensional fracture mechanics lifing models along with adaptive model updating techniques for tuning key failure mode variables at a local material/damage site based on fused vibration features. The overall prognostic scheme is aimed at minimizing inherent modeling and operational uncertainties via sensed system measurements that evolve as damage progresses.

The possible mechanism of Parkinson's disease progressive damage and the preventive effect of GM1 in the rat model induced by 6-hydroxydopamine.

PubMed

Xu, Renshi; Zhou, Yiyi; Fang, Xin; Lu, Yi; Li, Jiao; Zhang, Jie; Deng, Xia; Li, Shujuan

2014-12-10

The progressive pathogenesis and prevention of Parkinson's disease (PD) remains unknown at present. Therefore, the present study aimed to investigate the possible progressive pathogenesis and prevention of PD. Our study investigated the content of glutamate, mitochondria calcium, calmodulin, malonaldehyde and trace elements in striatum, cerebral cortex and hippocampus tissues; and the expression of bcl-2, bax and neuronal nitric oxide synthase (nNOS) in substantia nigra and striatum; and the change of apomorphine induced rotation behavior; and the treatmental effect of monosialotetrahexosylganglioside (GM1) intraperitoneal administration for 14 days in a PD rat model induced by 6-hydroxydopamine. The results revealed that the content of glutamate significantly decreased, and that of mitochondria calcium, calmodulin, malonaldehyde and ferrum significantly increased in striatum, cerebral cortex and hippocampus tissues; the content of magnesium significantly decreased, and that of cuprum and zinc significantly increased in cerebral cortex; the expression of bcl-2 significantly decreased, and that of bax and nNOS significantly increased in substantia nigra and striatum in PD rat. GM1 can partially improve the apomorphine induced rotation behavior and changes of glutamate, mitochondria calcium, calmodulin content in striatum of PD rat. Data suggested that dysfunction of excitatory amino acids neurotransmitter, calcium homeostasis disorder, abnormal metabolism of oxygen free radicals, abnormal trace elements distribution and/or deposition and excessive apoptosis participated in the progressive process of PD, and that GM1 could partially prevent the progressive damage. Copyright © 2014 Elsevier B.V. All rights reserved.

[Research Progress and Prospect of Applications of Finite Element Method in Lumbar Spine Biomechanics].

PubMed

Zhang, Zhenjun; Li, Yang; Liao, Zhenhua; Liu, Weiqiang

2016-12-01

Based on the application of finite element analysis in spine biomechanics,the research progress of finite element method applied in lumbar spine mechanics is reviewed and the prospect is forecasted.The related works,including lumbar ontology modeling,clinical application research,and occupational injury and protection,are summarized.The main research areas of finite element method are as follows:new accurate modeling process,the optimized simulation method,diversified clinical effect evaluation,and the clinical application of artificial lumbar disc.According to the recent research progress,the application prospects of finite element method,such as automation and individuation of modeling process,evaluation and analysis of new operation methods and simulation of mechanical damage and dynamic response,are discussed.The purpose of this paper is to provide the theoretical reference and practical guidance for the clinical lumbar problems by reviewing the application of finite element method in the field of the lumbar spine biomechanics.

Damage-mitigating control of a reusable rocket engine for high performance and extended life

NASA Technical Reports Server (NTRS)

Ray, Asok; Dai, Xiaowen

1995-01-01

The goal of damage mitigating control in reusable rocket engines is to achieve high performance with increased durability of mechanical structures such that functional lives of the critical components are increased. The major benefit is an increase in structural durability with no significant loss of performance. This report investigates the feasibility of damage mitigating control of reusable rocket engines. Phenomenological models of creep and thermo-mechanical fatigue damage have been formulated in the state-variable setting such that these models can be combined with the plant model of a reusable rocket engine, such as the Space Shuttle Main Engine (SSME), for synthesizing an optimal control policy. Specifically, a creep damage model of the main thrust chamber wall is analytically derived based on the theories of sandwich beam and viscoplasticity. This model characterizes progressive bulging-out and incremental thinning of the coolant channel ligament leading to its eventual failure by tensile rupture. The objective is to generate a closed form solution of the wall thin-out phenomenon in real time where the ligament geometry is continuously updated to account for the resulting deformation. The results are in agreement with those obtained from the finite element analyses and experimental observation for both Oxygen Free High Conductivity (OFHC) copper and a copper-zerconium-silver alloy called NARloy-Z. Due to its computational efficiency, this damage model is suitable for on-line applications of life prediction and damage mitigating control, and also permits parametric studies for off-line synthesis of damage mitigating control systems. The results are presented to demonstrate the potential of life extension of reusable rocket engines via damage mitigating control. The control system has also been simulated on a testbed to observe how the damage at different critical points can be traded off without any significant loss of engine performance. The research work reported here is built upon concepts derived from the disciplines of Controls, Thermo-fluids, Structures, and Materials. The concept of damage mitigation, as presented in this report, is not restricted to control of rocket engines. It can be applied to any system where structural durability is an important issue.

Damage and failure modelling of hybrid three-dimensional textile composites: a mesh objective multi-scale approach

PubMed Central

Patel, Deepak K.

2016-01-01

This paper is concerned with predicting the progressive damage and failure of multi-layered hybrid textile composites subjected to uniaxial tensile loading, using a novel two-scale computational mechanics framework. These composites include three-dimensional woven textile composites (3DWTCs) with glass, carbon and Kevlar fibre tows. Progressive damage and failure of 3DWTCs at different length scales are captured in the present model by using a macroscale finite-element (FE) analysis at the representative unit cell (RUC) level, while a closed-form micromechanics analysis is implemented simultaneously at the subscale level using material properties of the constituents (fibre and matrix) as input. The N-layers concentric cylinder (NCYL) model (Zhang and Waas 2014 Acta Mech. 225, 1391–1417; Patel et al. submitted Acta Mech.) to compute local stress, srain and displacement fields in the fibre and matrix is used at the subscale. The 2-CYL fibre–matrix concentric cylinder model is extended to fibre and (N−1) matrix layers, keeping the volume fraction constant, and hence is called the NCYL model where the matrix damage can be captured locally within each discrete layer of the matrix volume. The influence of matrix microdamage at the subscale causes progressive degradation of fibre tow stiffness and matrix stiffness at the macroscale. The global RUC stiffness matrix remains positive definite, until the strain softening response resulting from different failure modes (such as fibre tow breakage, tow splitting in the transverse direction due to matrix cracking inside tow and surrounding matrix tensile failure outside of fibre tows) are initiated. At this stage, the macroscopic post-peak softening response is modelled using the mesh objective smeared crack approach (Rots et al. 1985 HERON 30, 1–48; Heinrich and Waas 2012 53rd AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics and Materials Conference, Honolulu, HI, 23–26 April 2012. AIAA 2012-1537). Manufacturing-induced geometric imperfections are included in the simulation, where the FE mesh of the unit cell is generated directly from micro-computed tomography (MCT) real data using a code Simpleware. Results from multi-scale analysis for both an idealized perfect geometry and one that includes geometric imperfections are compared with experimental results (Pankow et al. 2012 53rd AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics and Materials Conference, Honolulu, HI, 23–26 April 2012. AIAA 2012-1572). This article is part of the themed issue ‘Multiscale modelling of the structural integrity of composite materials’. PMID:27242294

Damage and failure modelling of hybrid three-dimensional textile composites: a mesh objective multi-scale approach.

PubMed

Patel, Deepak K; Waas, Anthony M

2016-07-13

This paper is concerned with predicting the progressive damage and failure of multi-layered hybrid textile composites subjected to uniaxial tensile loading, using a novel two-scale computational mechanics framework. These composites include three-dimensional woven textile composites (3DWTCs) with glass, carbon and Kevlar fibre tows. Progressive damage and failure of 3DWTCs at different length scales are captured in the present model by using a macroscale finite-element (FE) analysis at the representative unit cell (RUC) level, while a closed-form micromechanics analysis is implemented simultaneously at the subscale level using material properties of the constituents (fibre and matrix) as input. The N-layers concentric cylinder (NCYL) model (Zhang and Waas 2014 Acta Mech. 225, 1391-1417; Patel et al. submitted Acta Mech.) to compute local stress, srain and displacement fields in the fibre and matrix is used at the subscale. The 2-CYL fibre-matrix concentric cylinder model is extended to fibre and (N-1) matrix layers, keeping the volume fraction constant, and hence is called the NCYL model where the matrix damage can be captured locally within each discrete layer of the matrix volume. The influence of matrix microdamage at the subscale causes progressive degradation of fibre tow stiffness and matrix stiffness at the macroscale. The global RUC stiffness matrix remains positive definite, until the strain softening response resulting from different failure modes (such as fibre tow breakage, tow splitting in the transverse direction due to matrix cracking inside tow and surrounding matrix tensile failure outside of fibre tows) are initiated. At this stage, the macroscopic post-peak softening response is modelled using the mesh objective smeared crack approach (Rots et al. 1985 HERON 30, 1-48; Heinrich and Waas 2012 53rd AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics and Materials Conference, Honolulu, HI, 23-26 April 2012 AIAA 2012-1537). Manufacturing-induced geometric imperfections are included in the simulation, where the FE mesh of the unit cell is generated directly from micro-computed tomography (MCT) real data using a code Simpleware Results from multi-scale analysis for both an idealized perfect geometry and one that includes geometric imperfections are compared with experimental results (Pankow et al. 2012 53rd AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics and Materials Conference, Honolulu, HI, 23-26 April 2012 AIAA 2012-1572). This article is part of the themed issue 'Multiscale modelling of the structural integrity of composite materials'. © 2016 The Author(s).

New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections

USDA-ARS?s Scientific Manuscript database

Toxoplasma gondii, the most common parasitic infection of the human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we developed novel models to facilitate drug development: EGS strain T. gondi...

Adaptive measurement selection for progressive damage estimation

NASA Astrophysics Data System (ADS)

Zhou, Wenfan; Kovvali, Narayan; Papandreou-Suppappola, Antonia; Chattopadhyay, Aditi; Peralta, Pedro

2011-04-01

Noise and interference in sensor measurements degrade the quality of data and have a negative impact on the performance of structural damage diagnosis systems. In this paper, a novel adaptive measurement screening approach is presented to automatically select the most informative measurements and use them intelligently for structural damage estimation. The method is implemented efficiently in a sequential Monte Carlo (SMC) setting using particle filtering. The noise suppression and improved damage estimation capability of the proposed method is demonstrated by an application to the problem of estimating progressive fatigue damage in an aluminum compact-tension (CT) sample using noisy PZT sensor measurements.

From the left to the right: How the brain compensates progressive loss of language function.

PubMed

Thiel, Alexander; Habedank, Birgit; Herholz, Karl; Kessler, Josef; Winhuisen, Lutz; Haupt, Walter F; Heiss, Wolf-Dieter

2006-07-01

In normal right-handed subjects language production usually is a function oft the left brain hemisphere. Patients with aphasia following brain damage to the left hemisphere have a considerable potential to compensate for the loss of this function. Sometimes, but not always, areas of the right hemisphere which are homologous to language areas of the left hemisphere in normal subjects are successfully employed for compensation but this integration process may need time to develop. We investigated right-handed patients with left hemisphere brain tumors as a model of continuously progressive brain damage to left hemisphere language areas using functional neuroimaging and transcranial magnetic stimulation (TMS) to identify factors which determine successful compensation of lost language function. Only patients with slowly progressing brain lesions recovered right-sided language function as detected by TMS. In patients with rapidly progressive lesions no right-sided language function was found and language performance was linearly correlated with the lateralization of language related brain activation to the left hemisphere. It can thus be concluded that time is the factor which determines successful integration of the right hemisphere into the language network for compensation of lost left hemisphere language function.

Protein phosphatase 2A inhibition enhances radiation sensitivity and reduces tumor growth in chordoma.

PubMed

Hao, Shuyu; Song, Hua; Zhang, Wei; Seldomridge, Ashlee; Jung, Jinkyu; Giles, Amber J; Hutchinson, Marsha-Kay; Cao, Xiaoyu; Colwell, Nicole; Lita, Adrian; Larion, Mioara; Maric, Dragan; Abu-Asab, Mones; Quezado, Martha; Kramp, Tamalee; Camphausen, Kevin; Zhuang, Zhengping; Gilbert, Mark R; Park, Deric M

2018-05-18

Standard therapy for chordoma consists of surgical resection followed by high-dose irradiation. Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase involved in signal transduction, cell cycle progression, cell differentiation, and DNA repair. LB100 is a small-molecule inhibitor of PP2A designed to sensitize cancer cells to DNA damage from irradiation and chemotherapy. A recently completed phase I trial of LB100 in solid tumors demonstrated its safety. Here, we show the therapeutic potential of LB100 in chordoma. Three patient-derived chordoma cell lines were used: U-CH1, JHC7, and UM-Chor1. Cell proliferation was determined with LB100 alone and in combination with irradiation. Cell cycle progression was assessed by flow cytometry. Quantitative γ-H2AX immunofluorescence and immunoblot evaluated the effect of LB100 on radiation-induced DNA damage. Ultrastructural evidence for nuclear damage was investigated using Raman imaging and transmission electron microscopy. A xenograft model was established to determine potential clinical utility of adding LB100 to irradiation. PP2A inhibition in concert with irradiation demonstrated in vitro growth inhibition. The combination of LB100 and radiation also induced accumulation at the G2/M phase of the cell cycle, the stage most sensitive to radiation-induced damage. LB100 enhanced radiation-induced DNA double-strand breaks. Animals implanted with chordoma cells and treated with the combination of LB100 and radiation demonstrated tumor growth delay. Combining LB100 and radiation enhanced DNA damage-induced cell death and delayed tumor growth in an animal model of chordoma. PP2A inhibition by LB100 treatment may improve the effectiveness of radiation therapy for chordoma.

Urinary tract infection in small children: the evolution of renal damage over time.

PubMed

Swerkersson, Svante; Jodal, Ulf; Sixt, Rune; Stokland, Eira; Hansson, Sverker

2017-10-01

Our objective was to analyze the evolution of kidney damage over time in small children with urinary tract infection (UTI) and factors associated with progression of renal damage. From a cohort of 1003 children <2 years of age with first-time UTI, a retrospective analysis of 103 children was done. Children were selected because of renal damage at index 99m Tc-dimercaptosuccinic acid (DMSA) scintigraphy at least 3 months after UTI, and a late DMSA scan was performed after at least 2 years. Damage was classified as progression when there was a decline in differential renal function (DRF) by ≥4%, as regression when there was complete or partial resolution of uptake defects. Of 103 children, 20 showed progression, 20 regression, and 63 remained unchanged. There were no differences between groups regarding gender or age. In the progression group, 16/20 (80%) children had vesicoureteral reflux (VUR) grade III-V and 13 (65%) had recurrent UTI. In multivariable regression analysis, both VUR grade III-V and recurrent UTI were associated with progression. In the regression group, 16/20 (80%) had no VUR or grade I-II, and two (10%) had recurrent UTI. Most small children with febrile UTI do not develop renal damage and if they do the majority remain unchanged or regress over time. However, up to one-fifth of children with renal damage diagnosed after UTI are at risk of renal deterioration. These children are characterized by the presence of VUR grades III-V and recurrent febrile UTI and may benefit from follow-up.

Effects of Aftershock Declustering in Risk Modeling: Case Study of a Subduction Sequence in Mexico

NASA Astrophysics Data System (ADS)

Kane, D. L.; Nyst, M.

2014-12-01

Earthquake hazard and risk models often assume that earthquake rates can be represented by a stationary Poisson process, and that aftershocks observed in historical seismicity catalogs represent a deviation from stationarity that must be corrected before earthquake rates are estimated. Algorithms for classifying individual earthquakes as independent mainshocks or as aftershocks vary widely, and analysis of a single catalog can produce considerably different earthquake rates depending on the declustering method implemented. As these rates are propagated through hazard and risk models, the modeled results will vary due to the assumptions implied by these choices. In particular, the removal of large aftershocks following a mainshock may lead to an underestimation of the rate of damaging earthquakes and potential damage due to a large aftershock may be excluded from the model. We present a case study based on the 1907 - 1911 sequence of nine 6.9 <= Mw <= 7.9 earthquakes along the Cocos - North American plate subduction boundary in Mexico in order to illustrate the variability in risk under various declustering approaches. Previous studies have suggested that subduction zone earthquakes in Mexico tend to occur in clusters, and this particular sequence includes events that would be labeled as aftershocks in some declustering approaches yet are large enough to produce significant damage. We model the ground motion for each event, determine damage ratios using modern exposure data, and then compare the variability in the modeled damage from using the full catalog or one of several declustered catalogs containing only "independent" events. We also consider the effects of progressive damage caused by each subsequent event and how this might increase or decrease the total losses expected from this sequence.

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

NASA Technical Reports Server (NTRS)

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

1996-01-01

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

Clinical synovitis in a particular joint is associated with progression of erosions and joint space narrowing in that same joint, but not in patients initially treated with infliximab.

PubMed

Klarenbeek, N B; Güler-Yüksel, M; van der Heijde, D M F M; Hulsmans, H M J; Kerstens, P J S M; Molenaar, T H E; de Sonnaville, P B J; Huizinga, T W J; Dijkmans, B A C; Allaart, C F

2010-12-01

To assess the relationship between joint tenderness, swelling and joint damage progression in individual joints and to evaluate the influence of treatment on these relationships. First-year data of the Behandel Strategieën (BeSt) study were used, in which patients recently diagnosed as having rheumatoid arthritis (RA) were randomly assigned into four different treatment strategies. Baseline and 1-year x-rays of the hands and feet were assessed using the Sharp-van der Heijde score (SHS). With generalised estimating equations, 3-monthly assessments of tender and swollen joints of year 1 were related to erosion progression, joint space narrowing (JSN) progression and total SHS progression at the individual joint level (definition > 0.5 SHS units) in year 1, corrected for potential confounders and within-patient correlation for multiple joints per patient. During year 1, 59% of all 13 959 joints analysed were ever tender and 45% ever swollen, 2.1% showed erosion progression, 1.9% JSN progression and 3.6% SHS progression. Swelling and tenderness were both independently associated with erosion and JSN progression with comparable OR, although with higher OR in the hands than in the feet. Local swelling and tenderness were not associated with local damage progression in patients initially treated with infliximab. Clinical signs of synovitis are associated with erosion and JSN progression in individual joints after 1 year in RA. A disconnect between synovitis and joint damage progression was observed at joint level in patients who were treated with methotrexate and infliximab as initial treatment, confirming the disconnect between synovitis and the development of joint damage in tumour necrosis factor blockers seen at patient level.

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

English, Shawn A.; Briggs, Timothy M.; Nelson, Stacy M.

Simulations of low velocity impact with a flat cylindrical indenter upon a carbon fiber fabric reinforced polymer laminate are rigorously validated. Comparison of the impact energy absorption between the model and experiment is used as the validation metric. Additionally, non-destructive evaluation, including ultrasonic scans and three-dimensional computed tomography, provide qualitative validation of the models. The simulations include delamination, matrix cracks and fiber breaks. An orthotropic damage and failure constitutive model, capable of predicting progressive damage and failure, is developed in conjunction and described. An ensemble of simulations incorporating model parameter uncertainties is used to predict a response distribution which ismore » then compared to experimental output using appropriate statistical methods. Lastly, the model form errors are exposed and corrected for use in an additional blind validation analysis. The result is a quantifiable confidence in material characterization and model physics when simulating low velocity impact in structures of interest.« less

Quantitative validation of carbon-fiber laminate low velocity impact simulations

DOE PAGES

English, Shawn A.; Briggs, Timothy M.; Nelson, Stacy M.

2015-09-26

Simulations of low velocity impact with a flat cylindrical indenter upon a carbon fiber fabric reinforced polymer laminate are rigorously validated. Comparison of the impact energy absorption between the model and experiment is used as the validation metric. Additionally, non-destructive evaluation, including ultrasonic scans and three-dimensional computed tomography, provide qualitative validation of the models. The simulations include delamination, matrix cracks and fiber breaks. An orthotropic damage and failure constitutive model, capable of predicting progressive damage and failure, is developed in conjunction and described. An ensemble of simulations incorporating model parameter uncertainties is used to predict a response distribution which ismore » then compared to experimental output using appropriate statistical methods. Lastly, the model form errors are exposed and corrected for use in an additional blind validation analysis. The result is a quantifiable confidence in material characterization and model physics when simulating low velocity impact in structures of interest.« less

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.

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

NASA Technical Reports Server (NTRS)

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

2007-01-01

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

Micromechanical Modeling of Anisotropic Damage-Induced Permeability Variation in Crystalline Rocks

NASA Astrophysics Data System (ADS)

Chen, Yifeng; Hu, Shaohua; Zhou, Chuangbing; Jing, Lanru

2014-09-01

This paper presents a study on the initiation and progress of anisotropic damage and its impact on the permeability variation of crystalline rocks of low porosity. This work was based on an existing micromechanical model considering the frictional sliding and dilatancy behaviors of microcracks and the recovery of degraded stiffness when the microcracks are closed. By virtue of an analytical ellipsoidal inclusion solution, lower bound estimates were formulated through a rigorous homogenization procedure for the damage-induced effective permeability of the microcracks-matrix system, and their predictive limitations were discussed with superconducting penny-shaped microcracks, in which the greatest lower bounds were obtained for each homogenization scheme. On this basis, an empirical upper bound estimation model was suggested to account for the influences of anisotropic damage growth, connectivity, frictional sliding, dilatancy, and normal stiffness recovery of closed microcracks, as well as tensile stress-induced microcrack opening on the permeability variation, with a small number of material parameters. The developed model was calibrated and validated by a series of existing laboratory triaxial compression tests with permeability measurements on crystalline rocks, and applied for characterizing the excavation-induced damage zone and permeability variation in the surrounding granitic rock of the TSX tunnel at the Atomic Energy of Canada Limited's (AECL) Underground Research Laboratory (URL) in Canada, with an acceptable agreement between the predicted and measured data.

Design and analysis of compound flexible skin based on deformable honeycomb

NASA Astrophysics Data System (ADS)

Zou, Tingting; Zhou, Li

2017-04-01

In this study, we focused at the development and verification of a robust framework for surface crack detection in steel pipes using measured vibration responses; with the presence of multiple progressive damage occurring in different locations within the structure. Feature selection, dimensionality reduction, and multi-class support vector machine were established for this purpose. Nine damage cases, at different locations, orientations and length, were introduced into the pipe structure. The pipe was impacted 300 times using an impact hammer, after each damage case, the vibration data were collected using 3 PZT wafers which were installed on the outer surface of the pipe. At first, damage sensitive features were extracted using the frequency response function approach followed by recursive feature elimination for dimensionality reduction. Then, a multi-class support vector machine learning algorithm was employed to train the data and generate a statistical model. Once the model is established, decision values and distances from the hyper-plane were generated for the new collected data using the trained model. This process was repeated on the data collected from each sensor. Overall, using a single sensor for training and testing led to a very high accuracy reaching 98% in the assessment of the 9 damage cases used in this study.

Detection of surface cracking in steel pipes based on vibration data using a multi-class support vector machine classifier

NASA Astrophysics Data System (ADS)

Mustapha, S.; Braytee, A.; Ye, L.

2017-04-01

In this study, we focused at the development and verification of a robust framework for surface crack detection in steel pipes using measured vibration responses; with the presence of multiple progressive damage occurring in different locations within the structure. Feature selection, dimensionality reduction, and multi-class support vector machine were established for this purpose. Nine damage cases, at different locations, orientations and length, were introduced into the pipe structure. The pipe was impacted 300 times using an impact hammer, after each damage case, the vibration data were collected using 3 PZT wafers which were installed on the outer surface of the pipe. At first, damage sensitive features were extracted using the frequency response function approach followed by recursive feature elimination for dimensionality reduction. Then, a multi-class support vector machine learning algorithm was employed to train the data and generate a statistical model. Once the model is established, decision values and distances from the hyper-plane were generated for the new collected data using the trained model. This process was repeated on the data collected from each sensor. Overall, using a single sensor for training and testing led to a very high accuracy reaching 98% in the assessment of the 9 damage cases used in this study.

Implementation of near-infrared spectroscopy in a rat model of cardiac arrest and resuscitation

NASA Astrophysics Data System (ADS)

Rodriguez, Juan G.; Xiao, Feng; Ferrara, Davon; Ewing, Jennifer; Zhang, Shu; Alexander, Steven; Battarbee, Harold

2002-07-01

Transient global cerebral ischemia accompanying cardiac arrest (CA) often leads to permanent brain damage with poor neurological outcome. The precise chain of events underlying the cerebral damage after CA is still not fully understood. Progress in this area may profit from the development of new non-invasive tools that provide real-time information on the vascular and cellular processes preceding the damage. One way to assess these processes is through near-IR spectroscopy, which has demonstrated the ability to quantify changes in blood volume, hemoglobin oxygenation, cytochrome oxidase redox state, and tissue water content. Here we report on the successful implementation of this form of spectroscopy in a rat model of asphyxial CA and resuscitation, under hypothermic and normothermic conditions. Preliminary results are shown that provide a new temporal insight into the cerebral circulation during CA and post-resuscitation.

EMRinger: side chain–directed model and map validation for 3D cryo-electron microscopy

DOE PAGES

Barad, Benjamin A.; Echols, Nathaniel; Wang, Ray Yu-Ruei; ...

2015-08-17

Advances in high-resolution cryo-electron microscopy (cryo-EM) require the development of validation metrics to independently assess map quality and model geometry. We report that EMRinger is a tool that assesses the precise fitting of an atomic model into the map during refinement and shows how radiation damage alters scattering from negatively charged amino acids. EMRinger (https://github.com/fraser-lab/EMRinger) will be useful for monitoring progress in resolving and modeling high-resolution features in cryo-EM.

DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice.

PubMed

Wang, Degui; Yu, Tianyu; Liu, Yongqiang; Yan, Jun; Guo, Yingli; Jing, Yuhong; Yang, Xuguang; Song, Yanfeng; Tian, Yingxia

2016-12-02

Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages. Copyright © 2016 Elsevier Inc. All rights reserved.

Failure analysis of single-bolted joint for lightweight composite laminates and metal plate

NASA Astrophysics Data System (ADS)

Li, Linjie; Qu, Junli; Liu, Xiangdong

2018-01-01

A three-dimensional progressive damage model was developed in ANSYS to predict the damage accumulation of single bolted joint in composite laminates under in-plane tensile loading. First, we describe the formulation and algorithm of this model. Second, we calculate the failure loads of the joint in fibre reinforced epoxy laminated composite plates and compare it with the experiment results, which validates that our model can appropriately simulate the ultimate tensile strength of the joints and the whole process of failure of structure. Finally, this model is applied to study the failure process of the light-weight composite material (USN125). The study also has a great potential to provide a strong basis for bolted joints design in composite Laminates as well as a simple tool for comparing different laminate geometries and bolt arrangements.

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

NASA Technical Reports Server (NTRS)

Waller, J. M.; Nichols, C. T.; Wentzel, D. J.; Saulsberry R. L.

2010-01-01

Broad-band modal acoustic emission (AE) data was used to characterize micromechanical damage progression in uniaxial IM7 and T1000 carbon fiber-epoxy tows and an IM7 composite overwrapped pressure vessel (COPV) subjected to an intermittent load hold tensile stress profile known to activate the Felicity ratio (FR). Damage progression was followed by inspecting the Fast Fourier Transforms (FFTs) associated with acoustic emission events. FFT analysis revealed the occurrence of cooperative micromechanical damage events in a frequency range between 100 kHz and 1 MHz. Evidence was found for the existence of a universal damage parameter, referred to here as the critical Felicity ratio, or Felicity ratio at rupture (FR*), which had a value close to 0.96 for the tows and the COPV tested. The implications of using FR* to predict failure in carbon/epoxy composite materials and related composite components such as COPVs are discussed. Trends in the FFT data are also discussed; namely, the difference between the low and high energy events, the difference between early and late-life events, comparison of IM7 and T1000 damage progression, and lastly, the similarity of events occurring at the onset of significant acoustic emission used to calculate the FR.

A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome.

PubMed

Morris, Gerwyn; Maes, Michael

2013-12-01

This paper proposes a neuro-immune model for Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). A wide range of immunological and neurological abnormalities have been reported in people suffering from ME/CFS. They include abnormalities in proinflammatory cytokines, raised production of nuclear factor-κB, mitochondrial dysfunctions, autoimmune responses, autonomic disturbances and brain pathology. Raised levels of oxidative and nitrosative stress (O&NS), together with reduced levels of antioxidants are indicative of an immuno-inflammatory pathology. A number of different pathogens have been reported either as triggering or maintaining factors. Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared. Subsequent activation of autoreactive T cells conspiring with O&NS pathways cause further damage and provoke chronic activation of immuno-inflammatory pathways. The subsequent upregulation of proinflammatory compounds may activate microglia via the vagus nerve. Elevated proinflammatory cytokines together with raised O&NS conspire to produce mitochondrial damage. The subsequent ATP deficit together with inflammation and O&NS are responsible for the landmark symptoms of ME/CFS, including post-exertional malaise. Raised levels of O&NS subsequently cause progressive elevation of autoimmune activity facilitated by molecular mimicry, bystander activation or epitope spreading. These processes provoke central nervous system (CNS) activation in an attempt to restore immune homeostatsis. This model proposes that the antagonistic activities of the CNS response to peripheral inflammation, O&NS and chronic immune activation are responsible for the remitting-relapsing nature of ME/CFS. Leads for future research are suggested based on this neuro-immune model.

Progressive Fracture of Laminated Fiber-Reinforced Composite Stiffened Plate Under Pressure

NASA Technical Reports Server (NTRS)

Gotsis, Pascalis K.; Abdi, Frank; Chamis, Christos C.; Tsouros, Konstantinos

2007-01-01

S-Glass/epoxy laminated fiber-reinforced composite stiffened plate structure with laminate configuration (0/90)5 was simulated to investigate damage and fracture progression, under uniform pressure. For comparison reasons a simple plate was examined, in addition with the stiffened plate. An integrated computer code was used for the simulation. The damage initiation began with matrix failure in tension, continuous with damage and/or fracture progression as a result of additional matrix failure and fiber fracture and followed by additional interply delamination. Fracture through the thickness began when the damage accumulation was 90%. After that stage, the cracks propagate rapidly and the structures collapse. The collapse load for the simple plate is 21.57 MPa (3120 psi) and for the stiffened plate 25.24 MPa (3660 psi).

Epigenomic maintenance through dietary intervention can facilitate DNA repair process to slow down the progress of premature aging.

PubMed

Ghosh, Shampa; Sinha, Jitendra Kumar; Raghunath, Manchala

2016-09-01

DNA damage caused by various sources remains one of the most researched topics in the area of aging and neurodegeneration. Increased DNA damage causes premature aging. Aging is plastic and is characterised by the decline in the ability of a cell/organism to maintain genomic stability. Lifespan can be modulated by various interventions like calorie restriction, a balanced diet of macro and micronutrients or supplementation with nutrients/nutrient formulations such as Amalaki rasayana, docosahexaenoic acid, resveratrol, curcumin, etc. Increased levels of DNA damage in the form of double stranded and single stranded breaks are associated with decreased longevity in animal models like WNIN/Ob obese rats. Erroneous DNA repair can result in accumulation of DNA damage products, which in turn result in premature aging disorders such as Hutchinson-Gilford progeria syndrome. Epigenomic studies of the aging process have opened a completely new arena for research and development of drugs and therapeutic agents. We propose here that agents or interventions that can maintain epigenomic stability and facilitate the DNA repair process can slow down the progress of premature aging, if not completely prevent it. © 2016 IUBMB Life, 68(9):717-721, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

DNA Damage and Pulmonary Hypertension

PubMed Central

Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

2016-01-01

Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

Real-Time Prognostics of a Rotary Valve Actuator

NASA Technical Reports Server (NTRS)

Daigle, Matthew

2015-01-01

Valves are used in many domains and often have system-critical functions. As such, it is important to monitor the health of valves and their actuators and predict remaining useful life. In this work, we develop a model-based prognostics approach for a rotary valve actuator. Due to limited observability of the component with multiple failure modes, a lumped damage approach is proposed for estimation and prediction of damage progression. In order to support the goal of real-time prognostics, an approach to prediction is developed that does not require online simulation to compute remaining life, rather, a function mapping the damage state to remaining useful life is found offline so that predictions can be made quickly online with a single function evaluation. Simulation results demonstrate the overall methodology, validating the lumped damage approach and demonstrating real-time prognostics.

Baseline 24-2 Central Visual Field Damage Is Predictive of Global Progressive Field Loss.

PubMed

Garg, Aakriti; De Moraes, C Gustavo; Cioffi, George A; Girkin, Christopher A; Medeiros, Felipe A; Weinreb, Robert N; Zangwill, Linda M; Liebmann, Jeffrey M

2018-03-01

Central visual field (VF) damage in glaucoma patients can significantly hinder daily activities. The present study investigates whether the presence of localized baseline damage to the central 10 degrees of the VF is predictive of faster global mean deviation (MD) progression. Prospective cohort study. Eyes from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES) with established glaucoma and VF loss and a minimum of 5 24-2 VFs were eligible. Baseline central 24-2 damage was defined as any of the 12 central-most points with total deviation (TD) values at P < 0.5% on 2 consecutive examinations. Progression was determined using trend-based and event-based criteria: (1) rates of MD change significantly faster than zero and (2) >-5 dB MD loss over the entire follow-up. A total of 827 eyes of 584 patients were studied. Mean rate of MD change of the entire sample was -0.15 dB/year (95% CI: -0.19 to -0.12, P < .001). Eyes with baseline central damage progressed faster than those without (difference: β central  = -0.07 dB/year, 95% CI: -0.11 to -0.01, P = .011) and were more likely to experience MD loss greater than 5 dB (hazard ratio = 3.0 [95% CI: 2.1-4.1, P < .001]). These differences remained significant after adjusting for confounders. The presence of central VF damage at baseline is significantly associated with more rapid global progression. Detection of central VF damage aids in stratification of high-risk patients who may need intensive surveillance and aggressive treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Damage prognosis of adhesively-bonded joints in laminated composite structural components of unmanned aerial vehicles

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

Farrar, Charles R; Gobbato, Maurizio; Conte, Joel

2009-01-01

The extensive use of lightweight advanced composite materials in unmanned aerial vehicles (UAVs) drastically increases the sensitivity to both fatigue- and impact-induced damage of their critical structural components (e.g., wings and tail stabilizers) during service life. The spar-to-skin adhesive joints are considered one of the most fatigue sensitive subcomponents of a lightweight UAV composite wing with damage progressively evolving from the wing root. This paper presents a comprehensive probabilistic methodology for predicting the remaining service life of adhesively-bonded joints in laminated composite structural components of UAVs. Non-destructive evaluation techniques and Bayesian inference are used to (i) assess the current statemore » of damage of the system and, (ii) update the probability distribution of the damage extent at various locations. A probabilistic model for future loads and a mechanics-based damage model are then used to stochastically propagate damage through the joint. Combined local (e.g., exceedance of a critical damage size) and global (e.g.. flutter instability) failure criteria are finally used to compute the probability of component failure at future times. The applicability and the partial validation of the proposed methodology are then briefly discussed by analyzing the debonding propagation, along a pre-defined adhesive interface, in a simply supported laminated composite beam with solid rectangular cross section, subjected to a concentrated load applied at mid-span. A specially developed Eliler-Bernoulli beam finite element with interlaminar slip along the damageable interface is used in combination with a cohesive zone model to study the fatigue-induced degradation in the adhesive material. The preliminary numerical results presented are promising for the future validation of the methodology.« less

Protective effects of L-type fatty acid-binding protein (L-FABP) in proximal tubular cells against glomerular injury in anti-GBM antibody-mediated glomerulonephritis

PubMed Central

Kanaguchi, Yasuhiko; Suzuki, Yusuke; Osaki, Ken; Sugaya, Takeshi; Horikoshi, Satoshi

2011-01-01

Background. In glomerulonephritis (GN), an overload of free fatty acids (FFA) bound to albumin in urinary protein may induce oxidative stress in the proximal tubules. Human liver-type fatty acid-binding protein (hL-FABP) expressed in human proximal tubules, but not rodents, participates in intracellular FFA metabolism and exerts anti-oxidative effects on the progression of tubulointerstitial damage. We examined whether tubular enhancement of this anti-oxidative action modulates the progression of glomerular damage in immune-mediated GN in hL-FABP chromosomal gene transgenic (Tg) mice. Methods. Anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) was induced in Tg and wild-type mice (WT). Proteinuria, histopathology, polymorphonuclear (PMN) influx, expression of tubulointerstitial markers for oxidative stress 4-hydroxy-2-Nonenal (HNE) and fibrosis (α-smooth muscle actin), proximal tubular damage (Kim-1), Peroxisome Proliferator-Activated Receptor γ (PPAR γ) and inflammatory cytokines [Monocyte Chemotactic Protein-1, tumor necrosis factor-alpha (TNF-α) and Transforming growth factor beta (TGF-β)] were analyzed. The mice were also treated with an angiotensin type II receptor blocker (ARB). Results. The urinary protein level in Tg mice decreased significantly during the acute phase (∼Day 5). Tg mice survived for a significantly longer time than WT mice, with an attenuation of tubulointerstitial damage score and expression of each tubulointerstitial damage marker observed at Day 7. Expression of inflammatory cytokines on Day 7 was higher in WT mice than Tg mice and correlated strongly with PPARγ expression in WT mice, but not in Tg mice. Interestingly, Tg mice showed insufficient PMN influx at 3 and 6 h, with simultaneous elevation of urinary L-FABP and reduction in HNE expression. The two strains of mice showed different types of glomerular damage, with mild mesangial proliferation in Tg mice and severe endothelial swelling with vascular thrombosis in WT mice. The glomerular damage in Tg mice was improved by administration of an ARB. Conclusions. The present experimental model suggests that tubular enhancement of L-FABP may protect mice with anti-GBM GN from progression of both tubulointerstitial and glomerular injury. PMID:21525165

Protective effects of L-type fatty acid-binding protein (L-FABP) in proximal tubular cells against glomerular injury in anti-GBM antibody-mediated glomerulonephritis.

PubMed

Kanaguchi, Yasuhiko; Suzuki, Yusuke; Osaki, Ken; Sugaya, Takeshi; Horikoshi, Satoshi; Tomino, Yasuhiko

2011-11-01

In glomerulonephritis (GN), an overload of free fatty acids (FFA) bound to albumin in urinary protein may induce oxidative stress in the proximal tubules. Human liver-type fatty acid-binding protein (hL-FABP) expressed in human proximal tubules, but not rodents, participates in intracellular FFA metabolism and exerts anti-oxidative effects on the progression of tubulointerstitial damage. We examined whether tubular enhancement of this anti-oxidative action modulates the progression of glomerular damage in immune-mediated GN in hL-FABP chromosomal gene transgenic (Tg) mice. Anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) was induced in Tg and wild-type mice (WT). Proteinuria, histopathology, polymorphonuclear (PMN) influx, expression of tubulointerstitial markers for oxidative stress 4-hydroxy-2-Nonenal (HNE) and fibrosis (α-smooth muscle actin), proximal tubular damage (Kim-1), Peroxisome Proliferator-Activated Receptor γ (PPAR γ) and inflammatory cytokines [Monocyte Chemotactic Protein-1, tumor necrosis factor-alpha (TNF-α) and Transforming growth factor beta (TGF-β)] were analyzed. The mice were also treated with an angiotensin type II receptor blocker (ARB). The urinary protein level in Tg mice decreased significantly during the acute phase (~Day 5). Tg mice survived for a significantly longer time than WT mice, with an attenuation of tubulointerstitial damage score and expression of each tubulointerstitial damage marker observed at Day 7. Expression of inflammatory cytokines on Day 7 was higher in WT mice than Tg mice and correlated strongly with PPARγ expression in WT mice, but not in Tg mice. Interestingly, Tg mice showed insufficient PMN influx at 3 and 6 h, with simultaneous elevation of urinary L-FABP and reduction in HNE expression. The two strains of mice showed different types of glomerular damage, with mild mesangial proliferation in Tg mice and severe endothelial swelling with vascular thrombosis in WT mice. The glomerular damage in Tg mice was improved by administration of an ARB. The present experimental model suggests that tubular enhancement of L-FABP may protect mice with anti-GBM GN from progression of both tubulointerstitial and glomerular injury.

Simulation of Complex Cracking in Plain Weave C/SiC Composite under Biaxial Loading

NASA Technical Reports Server (NTRS)

Cheng, Ron-Bin; Hsu, Su-Yuen

2012-01-01

Finite element analysis is performed on a mesh, based on computed geometry of a plain weave C/SiC composite with assumed internal stacking, to reveal the pattern of internal damage due to biaxial normal cyclic loading. The simulation encompasses intertow matrix cracking, matrix cracking inside the tows, and separation at the tow-intertow matrix and tow-tow interfaces. All these dissipative behaviors are represented by traction-separation cohesive laws. Not aimed at quantitatively predicting the overall stress-strain relation, the simulation, however, does not take the actual process of fiber debonding into account. The fiber tows are represented by a simple rule-of-mixture model where the reinforcing phase is a hypothetical one-dimensional material. Numerical results indicate that for the plain weave C/SiC composite, 1) matrix-crack initiation sites are primarily determined by large intertow matrix voids and interlayer tow-tow contacts, 2) the pattern of internal damage strongly depends on the loading path and initial stress, 3) compressive loading inflicts virtually no damage evolution. KEY WORDS: ceramic matrix composite, plain weave, cohesive model, brittle failure, smeared crack model, progressive damage, meso-mechanical analysis, finite element.

A Closer Look at Schlemm's Canal Cell Physiology: Implications for Biomimetics.

PubMed

Dautriche, Cula N; Tian, Yangzi; Xie, Yubing; Sharfstein, Susan T

2015-09-21

Among ocular pathologies, glaucoma is the second leading cause of progressive vision loss, expected to affect 80 million people worldwide by 2020. A primary cause of glaucoma appears to be damage to the conventional outflow tract. Conventional outflow tissues, a composite of the trabecular meshwork and the Schlemm's canal, regulate and maintain homeostatic responses to intraocular pressure. In glaucoma, filtration of aqueous humor into the Schlemm's canal is hindered, leading to an increase in intraocular pressure and subsequent damage to the optic nerve, with progressive vision loss. The Schlemm's canal encompasses a unique endothelium. Recent advances in culturing and manipulating Schlemm's canal cells have elucidated several aspects of their physiology, including ultrastructure, cell-specific marker expression, and biomechanical properties. This review highlights these advances and discusses implications for engineering a 3D, biomimetic, in vitro model of the Schlemm's canal endothelium to further advance glaucoma research, including drug testing and gene therapy screening.

A study of elevated temperature testing techniques for the fatigue behavior of PMCS: Application to T650-35/AMB21

NASA Technical Reports Server (NTRS)

Gyekenyesi, Andrew L.; Gastelli, Michael G.; Ellis, John R.; Burke, Christopher S.

1995-01-01

An experimental study was conducted to investigate the mechanical behavior of a T650-35/AMB21 eight-harness satin weave polymer composite system. Emphasis was placed on the development and refinement of techniques used in elevated temperature uniaxial PMC testing. Issues such as specimen design, gripping, strain measurement, and temperature control and measurement were addressed. Quasi-static tensile and fatigue properties (R(sub sigma) = 0.1) were examined at room and elevated temperatures. Stiffness degradation and strain accumulation during fatigue cycling were recorded to monitor damage progression and provide insight for future analytical modeling efforts. Accomplishments included an untabbed dog-bone specimen design which consistently failed in the gage section, accurate temperature control and assessment, and continuous in-situ strain measurement capability during fatigue loading at elevated temperatures. Finally, strain accumulation and stiffness degradation during fatigue cycling appeared to be good indicators of damage progression.

Predictive modeling of composite material degradation using piezoelectric wafer sensors electromechanical impedance spectroscopy

NASA Astrophysics Data System (ADS)

Gresil, Matthieu; Yu, Lingyu; Sutton, Mike; Guo, Siming; Pollock, Patrick

2012-04-01

The advancement of composite materials in aircraft structures has led to on increased need for effective structural health monitoring (SHM) technologies that are able to detect and assess damage present in composites structures. The work presented in this paper is interested in understanding using self-sensing piezoelectric wafer active sensors (PWAS) to conduct electromechanical impedance spectroscopy (EMIS) in glass fiber reinforced plastic (GFRP) to perform structures health monitoring. PWAS are bonded to the composite material and the EMIS method is used to analyze the changes in the structural resonance and anti-resonance. As the damage progresses in the specimen, the impedance spectrum will change. In addition, multi-physics based finite element method (MP-FEM) is used to model the electromechanical behavior of a free PWAS and its interaction with the host structure on which it is bonded. The MPFEM permits the input and the output variables to be expressed directly in electric terms while the two way electromechanical conversion is done internally in the MP_FEM formulation. To reach the goal of using the EMIS approach to detect damage, several damages models are generated on laminated GFRP structures. The effects of the modeling are carefully studied through experimental validation. A good match has been observed for low and very high frequencies.

Infective dementias.

PubMed

Ironside, J W; Bell, J E

2007-12-01

A wide range of infectious diseases can result in dementia, although the identity and nature of these diseases has changed over time. Two of the most significant current groups in terms of scientific complexity are HIV/AIDS and prion diseases. In these disorders, dementia occurs either as a consequence of targeting the brain and selectively damaging neurones, or by an indirect effect of neuroinflammation. In prion diseases, both direct neurotoxicity and neuroinflammation may act to result in neuronal damage. In HIV encephalitis, the progression of the dementia is slower, perhaps reflecting indirect damage that appears to result from neuroinflammation as a main cause of neuronal death. An ever-increasing range of model systems is now available to study the neuronal damage in infectious dementias, ranging from cell culture systems to animal models, some of which, particularly in the case of prion diseases, are very well characterised and amenable to controlled manipulation in terms of both host and agent parameters. As valuable as these experimental models are, they do not allow a direct approach to an understanding of dementia, the complexities of which cannot readily be studied in vitro or in animal models, but they do allow studies of interventions and therapeutic strategies. This review summarises the current state of knowledge regarding the major infective dementias.

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

PubMed

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

2013-06-01

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

Progressive Failure Studies of Stiffened Panels Subjected to Shear Loading

NASA Technical Reports Server (NTRS)

Ambur, Damodar R.; Jaunky, Navin; Hilburger, Mark W.; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

Experimental and analytical results are presented for progressive failure of stiffened composite panels with and without a notch and subjected to in plane shear loading well into their postbuckling regime. Initial geometric imperfections are included in the finite element models. Ply damage modes such as matrix cracking, fiber-matrix shear, and fiber failure are modeled by degrading the material properties. Experimental results from the test include strain field data from video image correlation in three dimensions in addition to other strain and displacement measurements. Results from nonlinear finite element analyses are compared with experimental data. Good agreement between experimental data and numerical results are observed for the stitched stiffened composite panels studied.

Damage tolerance modeling and validation of a wireless sensory composite panel for a structural health monitoring system

NASA Astrophysics Data System (ADS)

Talagani, Mohamad R.; Abdi, Frank; Saravanos, Dimitris; Chrysohoidis, Nikos; Nikbin, Kamran; Ragalini, Rose; Rodov, Irena

2013-05-01

The paper proposes the diagnostic and prognostic modeling and test validation of a Wireless Integrated Strain Monitoring and Simulation System (WISMOS). The effort verifies a hardware and web based software tool that is able to evaluate and optimize sensorized aerospace composite structures for the purpose of Structural Health Monitoring (SHM). The tool is an extension of an existing suite of an SHM system, based on a diagnostic-prognostic system (DPS) methodology. The goal of the extended SHM-DPS is to apply multi-scale nonlinear physics-based Progressive Failure analyses to the "as-is" structural configuration to determine residual strength, remaining service life, and future inspection intervals and maintenance procedures. The DPS solution meets the JTI Green Regional Aircraft (GRA) goals towards low weight, durable and reliable commercial aircraft. It will take advantage of the currently developed methodologies within the European Clean sky JTI project WISMOS, with the capability to transmit, store and process strain data from a network of wireless sensors (e.g. strain gages, FBGA) and utilize a DPS-based methodology, based on multi scale progressive failure analysis (MS-PFA), to determine structural health and to advice with respect to condition based inspection and maintenance. As part of the validation of the Diagnostic and prognostic system, Carbon/Epoxy ASTM coupons were fabricated and tested to extract the mechanical properties. Subsequently two composite stiffened panels were manufactured, instrumented and tested under compressive loading: 1) an undamaged stiffened buckling panel; and 2) a damaged stiffened buckling panel including an initial diamond cut. Next numerical Finite element models of the two panels were developed and analyzed under test conditions using Multi-Scale Progressive Failure Analysis (an extension of FEM) to evaluate the damage/fracture evolution process, as well as the identification of contributing failure modes. The comparisons between predictions and test results were within 10% accuracy.

Spatio-Temporal Modelling of the Pre-Eruptive Strain Localization in a Volcanic Edifice Using a Maxwell-Elasto-Brittle Rheology

NASA Astrophysics Data System (ADS)

Dansereau, V.; Got, J. L.

2017-12-01

Before a volcanic eruption, the pressurization of the volcanic edifice by a magma reservoir induces earthquakes and damage in the edifice; damage lowers the strength of the edifice and decreases its elastic properties. Anelastic deformations cumulate and lead to rupture and eruption. These deformations translate into surface displacements, measurable via GPS or InSAR (e.g., Kilauea, southern flank, or Piton de la Fournaise, eastern flank).Attempts to represent these processes are usually based on a linear-elastic rheology. More recently, linear elastic-perfectly plastic or elastic-brittle damage approaches were used to explain the time evolution of the surface displacements in basaltic volcanoes before an eruption. However these models are non-linear elastic, and can not account for the anelastic deformation that occurs during the pre-eruptive process. Therefore, they can not be used to represent the complete eruptive cycle, comprising loading and unloading phases. Here we present a new rheological approach for modelling the eruptive cycle called Maxwell-Elasto-Brittle, which incorporates a viscous-like relaxation of the stresses in an elastic-brittle damage framework. This mechanism allows accounting for the anelastic deformations that cumulate and lead to rupture and eruption. The inclusion of healing processes in this model is another step towards a complete spatio-temporal representation of the eruptive cycle. Plane-strain Maxwell-EB modelling of the deformation of a magma reservoir and volcanic edifice will be presented. The model represents the propagation of damage towards the surface and the progressive localization of the deformation along faults under the pressurization of the magma reservoir. This model allows a complete spatio-temporal representation of the rupture process. We will also discuss how available seismicity records and time series of surface displacements could be used jointly to constrain the model.

A Biaxial-Bending Test to Observe the Growth of Interacting Delaminations in a Composite Laminate Plate

NASA Technical Reports Server (NTRS)

McElroy, Mark; Jackson, Wade; Pankow, Mark

2016-01-01

It is not easy to isolate the damage mechanisms associated with low-velocity impact in composites using traditional experiments. In this work, a new experiment is presented with the goal of generating data representative of progressive damage processes caused by low-velocity impact in composite materials. Carbon fiber reinforced polymer test specimens were indented quasi-statically such that a biaxial-bending state of deformation was achieved. As a result, a three-dimensional damage process, involving delamination and delamination-migration, was observed and documented using ultrasonic and x-ray computed tomography. Results from two different layups are presented in this paper. Delaminations occurred at up to three different interfaces and interacted with one another via transverse matrix cracks. Although this damage pattern is much less complex than that of low-velocity impact on a plate, it is more complex than that of a standard delamination coupon test and provides a way to generate delamination, matrix cracking, and delamination-migration in a controlled manner. By limiting the damage process in the experiment to three delaminations, the same damage mechanisms seen during impact could be observed but in a simplified manner. This type of data is useful in stages of model development and validation when the model is capable of simulating simple tests, but not yet capable of simulating more complex and realistic damage scenarios.

Molecular pathogenesis of malignant melanoma: a different perspective from the studies of melanocytic nevus and acral melanoma.

PubMed

Takata, Minoru; Murata, Hiroshi; Saida, Toshiaki

2010-02-01

The Clark model for melanoma progression emphasizes a series of histopathological changes beginning from benign melanocytic nevus to melanoma via dysplastic nevus. Several models of the genetic basis of melanoma development and progression are based on this Clark's multi-step model, and predict that the acquisition of a BRAF mutation can be a founder event in melanocytic neoplasia. However, our recent investigations have challenged this view, showing the polyclonality of BRAF mutations in melanocytic nevi. Furthermore, it is suggested that many melanomas, including acral and mucosal melanomas, arise de novo, not from melanocytic nevus. While mutations of the BRAF gene are frequent in melanomas on non-chronic sun damaged skin which are prevalent in Caucasians, acral and mucosal melanomas harbor mutations of the KIT gene as well as the amplifications of cyclin D1 or cyclin-dependent kinase 4 gene. Amplifications of the cyclin D1 gene are detected in normal-looking 'field melanocytes', which represent a latent progression phase of acral melanoma that precedes the stage of atypical melanocyte proliferation in the epidermis. Based on these observations, we propose an alternative genetic progression model for melanoma.

Computational Simulation of Composite Structural Fatigue

NASA Technical Reports Server (NTRS)

Minnetyan, Levon; Chamis, Christos C. (Technical Monitor)

2005-01-01

Progressive damage and fracture of composite structures subjected to monotonically increasing static, tension-tension cyclic, pressurization, and flexural cyclic loading are evaluated via computational simulation. Constituent material properties, stress and strain limits are scaled up to the structure level to evaluate the overall damage and fracture propagation for composites. Damage initiation, growth, accumulation, and propagation to fracture due to monotonically increasing static and cyclic loads are included in the simulations. Results show the number of cycles to failure at different temperatures and the damage progression sequence during different degradation stages. A procedure is outlined for use of computational simulation data in the assessment of damage tolerance, determination of sensitive parameters affecting fracture, and interpretation of results with insight for design decisions.

Computational Simulation of Composite Structural Fatigue

NASA Technical Reports Server (NTRS)

Minnetyan, Levon

2004-01-01

Progressive damage and fracture of composite structures subjected to monotonically increasing static, tension-tension cyclic, pressurization, and flexural cyclic loading are evaluated via computational simulation. Constituent material properties, stress and strain limits are scaled up to the structure level to evaluate the overall damage and fracture propagation for composites. Damage initiation, growth, accumulation, and propagation to fracture due to monotonically increasing static and cyclic loads are included in the simulations. Results show the number of cycles to failure at different temperatures and the damage progression sequence during different degradation stages. A procedure is outlined for use of computational simulation data in the assessment of damage tolerance, determination of sensitive parameters affecting fracture, and interpretation of results with insight for design decisions.

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

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Saulsberry, Regor L.

2009-01-01

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

Frequency of radiographic damage and progression in individual joints in children with juvenile idiopathic arthritis.

PubMed

Giancane, Gabriella; Pederzoli, Silvia; Norambuena, Ximena; Ioseliani, Maka; Sato, Juliana; Gallo, Maria Chiara; Negro, Giorgia; Pistorio, Angela; Ruperto, Nicolino; Martini, Alberto; Ravelli, Angelo

2014-01-01

To evaluate the presence and progression of radiographic joint damage, as assessed with the adapted Sharp/van der Heijde score (SHS), in individual joints in the hand and wrist in patients with juvenile idiopathic arthritis (JIA) and to compare progression of damage among different JIA categories. A total of 372 radiographs of both wrists and hands obtained at first observation and at last followup visit (after 1-10 years) in 186 children with polyarticular-course JIA were evaluated. All radiographs were scored using the adapted SHS by 2 independent readers. Radiographic assessment included evaluation of joint space narrowing (JSN) and erosions on baseline and last followup radiographs and of progression of radiographic changes from baseline to last followup radiographs. Both JSN and erosions occurred in all adapted SHS areas. Overall, radiographic damage and progression were more common in the wrist and less common in metacarpophalangeal (MCP) joints. The hamate and capitate areas appeared particularly vulnerable to cartilage loss. Erosions were identified most frequently in the hamate and capitate bones as well as in the second and third metacarpal bases. Patients with extended oligoarthritis were distinctly less susceptible to JSN in hand joints, whereas patients with polyarthritis showed a greater tendency to developing erosions in hand joints. Radiographic joint damage and progression in our patients with JIA were seen most commonly in the wrist and less commonly in MCP joints. The frequency and localization of structural abnormalities differed markedly across disease categories. Copyright © 2014 by the American College of Rheumatology.

Oxidative Stress during the Progression of β-Amyloid Pathology in the Neocortex of the Tg2576 Mouse Model of Alzheimer's Disease.

PubMed

Porcellotti, Sara; Fanelli, Francesca; Fracassi, Anna; Sepe, Sara; Cecconi, Francesco; Bernardi, Cinzia; Cimini, AnnaMaria; Cerù, Maria Paola; Moreno, Sandra

2015-01-01

Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive neurodegeneration. Pathogenetic mechanisms, triggered by β-amyloid (Aβ) accumulation, include oxidative stress, derived from energy homeostasis deregulation and involving mitochondria and peroxisomes. We here addressed the oxidative stress status and the elicited cellular response at the onset and during the progression of Aβ pathology, studying the neocortex of Tg2576 model of AD. Age-dependent changes of oxidative damage markers, antioxidant enzymes, and related transcription factors were analysed in relation to the distribution of Aβ peptide and oligomers, by a combined molecular/morphological approach. Nucleic acid oxidative damage, accompanied by defective antioxidant defences, and decreased PGC1α expression are already detected in 3-month-old Tg2576 neurons. Conversely, PPARα is increased in these cells, with its cytoplasmic localization suggesting nongenomic, anti-inflammatory actions. At 6 months, when intracellular Aβ accumulates, PMP70 is downregulated, indicating impairment of fatty acids peroxisomal translocation and their consequent harmful accumulation. In 9-month-old Tg2576 neocortex, Aβ oligomers and acrolein deposition correlate with GFAP, GPX1, and PMP70 increases, supporting a compensatory response, involving astroglial peroxisomes. At severe pathological stages, when senile plaques disrupt cortical cytoarchitecture, antioxidant capacity is gradually lost. Overall, our data suggest early therapeutic intervention in AD, also targeting peroxisomes.

Effective properties of dispersed phase reinforced composite materials with perfect and imperfect interfaces

NASA Astrophysics Data System (ADS)

Han, Ru

This thesis focuses on the analysis of dispersed phase reinforced composite materials with perfect as well as imperfect interfaces using the Boundary Element Method (BEM). Two problems of interest are considered, namely, to determine the limitations in the use of effective properties and the analysis of failure progression at the inclusion-matrix interface. The effective moduli (effective Young's modulus, effective Poisson's ratio, effective shear modulus, and effective bulk modulus) of composite materials can be determined at the mesoscopic level using three-dimensional parallel BEM simulations. By comparing the mesoscopic BEM results and the macroscopic results based on effective properties, limitations in the effective property approach can be determined. Decohesion is an important failure mode associated with fiber-reinforced composite materials. Analysis of failure progression at the fiber-matrix interface in fiber-reinforced composite materials is considered using a softening decohesion model consistent with thermodynamic concepts. In this model, the initiation of failure is given directly by a failure criterion. Damage is interpreted by the development of a discontinuity of displacement. The formulation describing the potential development of damage is governed by a discrete decohesive constitutive equation. Numerical simulations are performed using the direct boundary element method. Incremental decohesion simulations illustrate the progressive evolution of debonding zones and the propagation of cracks along the interfaces. The effect of decohesion on the macroscopic response of composite materials is also investigated.

Progression and recovery of Parkinsonism in a chronic progressive MPTP-induction model in the marmoset without persistent molecular and cellular damage.

PubMed

Franke, S K; van Kesteren, R E; Wubben, J A M; Hofman, S; Paliukhovich, I; van der Schors, R C; van Nierop, P; Smit, A B; Philippens, I H C H M

2016-01-15

Chronic exposure to low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in marmoset monkeys was used to model the prodromal stage of Parkinson's disease (PD), and to investigate mechanisms underlying disease progression and recovery. Marmosets were subcutaneously injected with MPTP for a period of 12weeks, 0.5mg/kg once per week, and clinical signs of Parkinsonism, motor- and non-motor behaviors were recorded before, during and after exposure. In addition, postmortem immunohistochemistry and proteomics analysis were performed. MPTP-induced parkinsonian clinical symptoms increased in severity during exposure, and recovered after MPTP administration was ended. Postmortem analyses, after the recovery period, revealed no alteration of the number and sizes of tyrosine hydroxylase (TH)-positive dopamine (DA) neurons in the substantia nigra. Also levels of TH in putamen and caudate nucleus were unaltered, no differences were observed in DA, serotonin or nor-adrenalin levels in the caudate nucleus, and proteomics analysis revealed no global changes in protein expression in these brain areas between treatment groups. Our findings indicate that parkinsonian symptoms can occur without detectable damage at the cellular or molecular level. Moreover, we show that parkinsonian symptoms may be reversible when diagnosed and treated early. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.

PubMed

Hayami, Tadashi; Pickarski, Maureen; Zhuo, Ya; Wesolowski, Gregg A; Rodan, Gideon A; Duong, Le T

2006-02-01

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction, subchondral bone sclerosis, and osteophyte formation. Subchondral bone stiffness has been proposed to initiate and/or contribute to cartilage deterioration in OA. The purpose of this study was to characterize subchondral bone remodeling, cartilage damage, and osteophytosis during the disease progression in two models of surgically induced OA. Rat knee joints were subjected either to anterior cruciate ligament transection (ACLT) alone or in combination with resection of medial menisci (ACLT + MMx). Histopathological changes in the surgical joints were compared with sham at 1, 2, 4, 6, and 10 weeks post-surgery. Using a modified Mankin scoring system, we demonstrate that articular cartilage damage occurs within 2 weeks post-surgery in both surgical models. Detectable cartilage surface damage and proteoglycan loss were observed as early as 1 week post-surgery. These were followed by the increases in vascular invasion into cartilage, in loss of chondrocyte number and in cell clustering. Histomorphometric analysis revealed subchondral bone loss in both models within 2 weeks post-surgery followed by significant increases in subchondral bone volume relative to sham up to 10 weeks post-surgery. Incidence of osteophyte formation was optimally observed in ACLT joints at 10 weeks and in ACLT + MMx joints at 6 weeks post-surgery. In summary, the two surgically induced rat OA models share many characteristics seen in human and other animal models of OA, including progressive articular cartilage degradation, subchondral bone sclerosis, and osteophyte formation. Moreover, increased subchondral bone resorption is associated with early development of cartilage lesions, which precedes significant cartilage thinning and subchondral bone sclerosis. Together, these findings support a role for bone remodeling in OA pathogenesis and suggest that these rat models are suitable for evaluating bone resorption inhibitors as potential disease-modifying pharmaco-therapies.

Integrating Condition Indicators and Usage Parameters for Improved Spiral Bevel Gear Health Monitoring

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Handschuh, Robert F.; Delgado, Irebert R.

2013-01-01

The objective of this study was to illustrate the importance of combining Health Usage Monitoring Systems (HUMS) data with usage monitoring system data when detecting rotorcraft transmission health. Six gear sets were tested in the NASA Glenn Spiral Bevel Gear Fatigue Rig. Damage was initiated and progressed on the gear and pinion teeth. Damage progression was measured by debris generation and documented with inspection photos at varying torque values. A contact fatigue analysis was applied to the gear design indicating the effect temperature, load and reliability had on gear life. Results of this study illustrated the benefits of combining HUMS data and actual usage data to indicate progression of damage for spiral bevel gears.

Integrating Condition Indicators and Usage Parameters for Improved Spiral Bevel Gear Health Monitoring

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Handschuh, Robert F.; Delgado, Irebert, R.

2013-01-01

The objective of this study was to illustrate the importance of combining Health Usage Monitoring Systems (HUMS) data with usage monitoring system data when detecting rotorcraft transmission health. Three gear sets were tested in the NASA Glenn Spiral Bevel Gear Fatigue Rig. Damage was initiated and progressed on the gear and pinion teeth. Damage progression was measured by debris generation and documented with inspection photos at varying torque values. A contact fatigue analysis was applied to the gear design indicating the effect temperature, load and reliability had on gear life. Results of this study illustrated the benefits of combining HUMS data and actual usage data to indicate progression of damage for spiral bevel gears.

Fukushima Daiichi Unit 1 Uncertainty Analysis-Exploration of Core Melt Progression Uncertain Parameters-Volume II.

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

Denman, Matthew R.; Brooks, Dusty Marie

Sandia National Laboratories (SNL) has conducted an uncertainty analysi s (UA) on the Fukushima Daiichi unit (1F1) accident progression wit h the MELCOR code. Volume I of the 1F1 UA discusses the physical modeling details and time history results of the UA. Volume II of the 1F1 UA discusses the statistical viewpoint. The model used was developed for a previous accident reconstruction investigation jointly sponsored by the US Department of Energy (DOE) and Nuclear Regulatory Commission (NRC). The goal of this work was to perform a focused evaluation of uncertainty in core damage progression behavior and its effect on keymore » figures - of - merit (e.g., hydrogen production, fraction of intact fuel, vessel lower head failure) and in doing so assess the applicability of traditional sensitivity analysis techniques .« less

Floating Node Method and Virtual Crack Closure Technique for Modeling Matrix Cracking-Delamination Interaction

NASA Technical Reports Server (NTRS)

DeCarvalho, N. V.; Chen, B. Y.; Pinho, S. T.; Baiz, P. M.; Ratcliffe, J. G.; Tay, T. E.

2013-01-01

A novel approach is proposed for high-fidelity modeling of progressive damage and failure in composite materials that combines the Floating Node Method (FNM) and the Virtual Crack Closure Technique (VCCT) to represent multiple interacting failure mechanisms in a mesh-independent fashion. In this study, the approach is applied to the modeling of delamination migration in cross-ply tape laminates. Delamination, matrix cracking, and migration are all modeled using fracture mechanics based failure and migration criteria. The methodology proposed shows very good qualitative and quantitative agreement with experiments.

Floating Node Method and Virtual Crack Closure Technique for Modeling Matrix Cracking-Delamination Migration

NASA Technical Reports Server (NTRS)

DeCarvalho, Nelson V.; Chen, B. Y.; Pinho, Silvestre T.; Baiz, P. M.; Ratcliffe, James G.; Tay, T. E.

2013-01-01

A novel approach is proposed for high-fidelity modeling of progressive damage and failure in composite materials that combines the Floating Node Method (FNM) and the Virtual Crack Closure Technique (VCCT) to represent multiple interacting failure mechanisms in a mesh-independent fashion. In this study, the approach is applied to the modeling of delamination migration in cross-ply tape laminates. Delamination, matrix cracking, and migration are all modeled using fracture mechanics based failure and migration criteria. The methodology proposed shows very good qualitative and quantitative agreement with experiments.

DNA damage checkpoint recovery and cancer development

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

Wang, Haiyong; Zhang, Xiaoshan; Teng, Lisong, E-mail: lsteng@zju.edu.cn

2015-06-10

Cell cycle checkpoints were initially presumed to function as a regulator of cell cycle machinery in response to different genotoxic stresses, and later found to play an important role in the process of tumorigenesis by acting as a guard against DNA over-replication. As a counterpart of checkpoint activation, the checkpoint recovery machinery is working in opposition, aiming to reverse the checkpoint activation and resume the normal cell cycle. The DNA damage response (DDR) and oncogene induced senescence (OIS) are frequently found in precancerous lesions, and believed to constitute a barrier to tumorigenesis, however, the DDR and OIS have been observedmore » to be diminished in advanced cancers of most tissue origins. These findings suggest that when progressing from pre-neoplastic lesions to cancer, DNA damage checkpoint barriers are overridden. How the DDR checkpoint is bypassed in this process remains largely unknown. Activated cytokine and growth factor-signaling pathways were very recently shown to suppress the DDR and to promote uncontrolled cell proliferation in the context of oncovirus infection. In recent decades, data from cell line and tumor models showed that a group of checkpoint recovery proteins function in promoting tumor progression; data from patient samples also showed overexpression of checkpoint recovery proteins in human cancer tissues and a correlation with patients' poor prognosis. In this review, the known cell cycle checkpoint recovery proteins and their roles in DNA damage checkpoint recovery are reviewed, as well as their implications in cancer development. This review also provides insight into the mechanism by which the DDR suppresses oncogene-driven tumorigenesis and tumor progression. - Highlights: • DNA damage checkpoint works as a barrier to cancer initiation. • DDR machinary response to genotoxic and oncogenic stress in similar way. • Checkpoint recovery pathways provide active signaling in cell cycle control. • Checkpoint recovery pathway plays a role in overriding tumor barrier in tumorigenesis. • Recovery protein dysregulation and human cancer development is correlated.« less

Modified stoke ankylosing spondylitis spinal score as an outcome measure to assess the impact of treatment on structural progression in ankylosing spondylitis.

PubMed

van der Heijde, Désirée; Braun, Jürgen; Deodhar, Atul; Baraliakos, Xenofon; Landewé, Robert; Richards, Hanno B; Porter, Brian; Readie, Aimee

2018-05-30

In ankylosing spondylitis (AS), structural damage that occurs as a result of syndesmophyte formation and ankylosis of the vertebral column is irreversible. Structural damage is currently assessed by conventional radiography and scoring systems that reliably assess radiographic structural damage are needed to capture the differential effects of drugs on structural damage progression. The validity of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) as a primary outcome measure in evaluating the effect of AS treatments on radiographic progression rates was assessed in this review. The mSASSS has not been used, to date, as a primary outcome measure in a prospective randomized controlled clinical trial of biologic therapy in AS. This review of the medical literature confirmed that the mSASSS is the most validated and widely used method for assessing radiographic progression in AS, correlating with worsening measures of disease signs and symptoms, spinal mobility and physical function, with a 2-year interval being required to ensure sufficient sensitivity to change.

Physiotherapy in Rheumatoid Arthritis

PubMed Central

Kavuncu, Vural; Evcik, Deniz

2004-01-01

Rheumatoid arthritis (RA) is a chronic and painful clinical condition that leads to progressive joint damage, disability, deterioration in quality of life, and shortened life expectancy. Even mild inflammation may result in irreversible damage and permanent disability. The clinical course according to symptoms may be either intermittent or progressive in patients with RA. In most patients, the clinical course is progressive, and structural damage develops in the first 2 years. The aim of RA management is to achieve pain relief and prevent joint damage and functional loss. Physiotherapy and rehabilitation applications significantly augment medical therapy by improving the management of RA and reducing handicaps in daily living for patients with RA. In this review, the application of physiotherapy modalities is examined, including the use of cold/heat applications, electrical stimulation, and hydrotherapy. Rehabilitation treatment techniques for patients with RA such as joint protection strategies, massage, exercise, and patient education are also presented. PMID:15266230

On mechanical mechanism of damage evolution in articular cartilage.

PubMed

Men, Yu-Tao; Jiang, Yan-Long; Chen, Ling; Zhang, Chun-Qiu; Ye, Jin-Duo

2017-09-01

Superficial lesions of cartilage are the direct indication of osteoarthritis. To investigate the mechanical mechanism of cartilage with micro-defect under external loading, a new plain strain numerical model with micro-defect was proposed and damage evolution progression in cartilage over time has been simulated, the parameter were studied including load style, velocity of load and degree of damage. The new model consists of the hierarchical structure of cartilage and depth-dependent arched fibers. The numerical results have shown that not only damage of the cartilage altered the distribution of the stress but also matrix and fiber had distinct roles in affecting cartilage damage, and damage in either matrix or fiber could promote each other. It has been found that the superficial cracks in cartilage spread preferentially along the tangent direction of the fibers. It is the arched distribution form of fibers that affects the crack spread of cartilage, which has been verified by experiment. During the process of damage evolution, its extension direction and velocity varied constantly with the damage degree. The rolling load could cause larger stress and strain than sliding load. Strain values of the matrix initially increased and then decreased gradually with the increase of velocity, and velocity had a greater effect on matrix than fibers. Damage increased steadily before reaching 50%, sharply within 50 to 85%, and smoothly and slowly after 85%. The finding of the paper may help to understand the mechanical mechanism why the cracks in cartilage spread preferentially along the tangent direction of the fibers. Copyright © 2017 Elsevier B.V. All rights reserved.

Induction of cross-tolerance between protective effect of morphine and nicotine in 6-hydroxydopamine-induce neurotoxicity in SH-SY5Y human dopaminergic neuroblastoma cells.

PubMed

Elyasi, Leila; Eftekhar-Vaghefi, Seyed Hassan; Asadi-Shekaaria, Majid; Esmaeili-Mahani, Saeed

2018-06-27

Parkinson's disease is a progressive neurodegenerative disease characterized by progressive and selective death of dopaminergic neurons. It has been reported that nicotine and morphine have protective roles during neuronal damage in Parkinson's disease. In addition, the induction of cross-tolerance between their biological effects has been shown in numerous reports. Here, we investigated the effects of nicotine and morphine on 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of Parkinson's disease. Cell damage was induced by 150 μM 6-OHDA and the cells viability was examined by MTT assay. Intracellular reactive oxygen species, calcium level and mitochondrial membrane potential were determined by fluorescence spectrophotometer method. Biochemical markers of apoptosis were also evaluated by immunoblotting. The data showed that morphine and nicotine prevent 6-OHDA- induced cell damage and apoptosis. However, the protective effects of nicotine were not observed in chronic morphine-pretreated cells. Morphine had no protective effects in chronic nicotine-incubated cells. A cross-tolerance between protective effects of morphine and nicotine was occurred in 6-OHDA-induced SH-SY5Y cell toxicity.

Three-dimensional characterisation and simulation of deformation and damage during Taylor impact in PTFE

NASA Astrophysics Data System (ADS)

Resnyansky, A. D.; McDonald, S. A.; Withers, P. J.; Bourne, N. K.; Millett, J. C. F.; Brown, E. N.; Rae, P. J.

2014-05-01

The current work presents Taylor impact experiments interrogating the effect of dynamic, high-pressure loading on polytetrafluoroethylene (PTFE). In particular, X-ray microtomography has been used to characterise the damage imparted to cylindrical samples due to impact at different velocities. Distinct regions of deformation are present and controlled by fracture within the polymer, with the extent of the deformed region and increasing propagation of fractures from the impact face showing a clear trend with increasing impact velocity. A two-phase rate sensitive strength model is implemented in the CTH hydrocode and used for simulation of the problem. The high-pressure phase transition of PTFE into Phase III within the crystalline domains from the polymer at normal conditions is managed by suitable phase transition kinetics within the model. The experimental observations are discussed with respect to the multi-phase model hydrocode predictions of the shock response from Taylor impact simulations. The damage and its progress are shown to correlate well with the onset of the phase transition and its evolution following the impact velocity increase.

Simulation of fatigue damage in ferroelectric polycrystals under mechanical/electrical loading

NASA Astrophysics Data System (ADS)

Kozinov, S.; Kuna, M.

2018-07-01

The reliability of smart-structures made of ferroelectric ceramics is essentially reduced by the formation of cracks under the action of external electrical and/or mechanical loading. In the current research a numerical model for low-cycle fatigue in ferroelectric mesostructures is proposed. In the finite element simulations a combination of two user element routines is utilized. The first one is used to model a micromechanical ferroelectric domain switching behavior inside the grains. The second one is used to simulate fatigue damage of grain boundaries by a cohesive zone model (EMCCZM) based on an electromechanical cyclic traction-separation law (TSL). For numerical simulations a scanning electron microscope image of the ceramic's grain structure was digitalized and meshed. The response of this mesostructure to cyclic electrical or mechanical loading is systematically analyzed. As a result of the simulations, the distribution of electric potential, field, displacement and polarization as well as mechanical stresses and deformations inside the grains are obtained. At the grain boundaries, the formation and evolution of damage are analyzed until final failure and induced degradation of electric permittivity. It is found that the proposed model correctly mimics polycrystalline behavior during poling processes and progressive damage under cyclic electromechanical loading. To the authors' knowledge, it is the first model and numerical analysis of ferroelectric polycrystals taking into account both domain reorientation and cohesive modeling of intergranular fracture. It can help to understand failure mechanisms taking place in ferroelectrics during fatigue processes.

Advances in Micromechanics Modeling of Composites Structures for Structural Health Monitoring

NASA Astrophysics Data System (ADS)

Moncada, Albert

Although high performance, light-weight composites are increasingly being used in applications ranging from aircraft, rotorcraft, weapon systems and ground vehicles, the assurance of structural reliability remains a critical issue. In composites, damage is absorbed through various fracture processes, including fiber failure, matrix cracking and delamination. An important element in achieving reliable composite systems is a strong capability of assessing and inspecting physical damage of critical structural components. Installation of a robust Structural Health Monitoring (SHM) system would be very valuable in detecting the onset of composite failure. A number of major issues still require serious attention in connection with the research and development aspects of sensor-integrated reliable SHM systems for composite structures. In particular, the sensitivity of currently available sensor systems does not allow detection of micro level damage; this limits the capability of data driven SHM systems. As a fundamental layer in SHM, modeling can provide in-depth information on material and structural behavior for sensing and detection, as well as data for learning algorithms. This dissertation focuses on the development of a multiscale analysis framework, which is used to detect various forms of damage in complex composite structures. A generalized method of cells based micromechanics analysis, as implemented in NASA's MAC/GMC code, is used for the micro-level analysis. First, a baseline study of MAC/GMC is performed to determine the governing failure theories that best capture the damage progression. The deficiencies associated with various layups and loading conditions are addressed. In most micromechanics analysis, a representative unit cell (RUC) with a common fiber packing arrangement is used. The effect of variation in this arrangement within the RUC has been studied and results indicate this variation influences the macro-scale effective material properties and failure stresses. The developed model has been used to simulate impact damage in a composite beam and an airfoil structure. The model data was verified through active interrogation using piezoelectric sensors. The multiscale model was further extended to develop a coupled damage and wave attenuation model, which was used to study different damage states such as fiber-matrix debonding in composite structures with surface bonded piezoelectric sensors.

Investigation of Spiral Bevel Gear Condition Indicator Validation via AC-29-2C Combining Test Rig Damage Progression Data with Fielded Rotorcraft Data

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.

2015-01-01

This is the final of three reports published on the results of this project. In the first report, results were presented on nineteen tests performed in the NASA Glenn Spiral Bevel Gear Fatigue Test Rig on spiral bevel gear sets designed to simulate helicopter fielded failures. In the second report, fielded helicopter HUMS data from forty helicopters were processed with the same techniques that were applied to spiral bevel rig test data. Twenty of the forty helicopters experienced damage to the spiral bevel gears, while the other twenty helicopters had no known anomalies within the time frame of the datasets. In this report, results from the rig and helicopter data analysis will be compared for differences and similarities in condition indicator (CI) response. Observations and findings using sub-scale rig failure progression tests to validate helicopter gear condition indicators will be presented. In the helicopter, gear health monitoring data was measured when damage occurred and after the gear sets were replaced at two helicopter regimes. For the helicopters or tails, data was taken in the flat pitch ground 101 rotor speed (FPG101) regime. For nine tails, data was also taken at 120 knots true airspeed (120KTA) regime. In the test rig, gear sets were tested until damage initiated and progressed while gear health monitoring data and operational parameters were measured and tooth damage progression documented. For the rig tests, the gear speed was maintained at 3500RPM, a one hour run-in was performed at 4000 in-lb gear torque, than the torque was increased to 8000 in-lbs. The HUMS gear condition indicator data evaluated included Figure of Merit 4 (FM4), Root Mean Square (RMS) or Diagnostic Algorithm 1(DA1), + 3 Sideband Index (SI3) and + 1 Sideband Index (SI1). These were selected based on their sensitivity in detecting contact fatigue damage modes from analytical, experimental and historical helicopter data. For this report, the helicopter dataset was reduced to fourteen tails and the test rig data set was reduced to eight tested gear sets. The damage modes compared were separated into three cases. For case one, both the gear and pinion showed signs of contact fatigue or scuffing damage. For case two, only the pinion showed signs of contact fatigue damage or scuffing. Case three was limited to the gear tests when scuffing occurred immediately after the gear run-in. Results of this investigation highlighted the importance of understanding the complete monitored systems, for both the helicopter and test rig, before interpreting health monitoring data. Further work is required to better define these two systems that include better state awareness of the fielded systems, new sensing technologies, new experimental methods or models that quantify the effect of system design on CI response and new methods for setting thresholds that take into consideration the variance of each system.

Tracking brain damage in progressive supranuclear palsy: a longitudinal MRI study.

PubMed

Agosta, Federica; Caso, Francesca; Ječmenica-Lukić, Milica; Petrović, Igor N; Valsasina, Paola; Meani, Alessandro; Copetti, Massimiliano; Kostić, Vladimir S; Filippi, Massimo

2018-01-18

In this prospective, longitudinal, multiparametric MRI study, we investigated clinical as well as brain grey matter and white matter (WM) regional changes in patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). Twenty-one patients with PSP-RS were evaluated at baseline relative to 36 healthy controls and after a mean follow-up of 1.4 years with clinical rating scales, neuropsychological tests and MRI scans. Relative to controls, patients with PSP-RS showed at baseline a typical pattern of brain damage, including midbrain atrophy, frontal cortical thinning and widespread WM involvement of the main infratentorial and supratentorial tracts that exceeded cortical damage. Longitudinal study showed that PSP-RS exhibited no further changes in cortical thinning, which remained relatively focal, while midbrain atrophy and WM damage significantly progressed. Corpus callosum and frontal WM tract changes correlated with the progression of both disease severity and behavioural dysfunction. This study demonstrated the feasibility of carrying out longitudinal diffusion tensor MRI in patients with PSP-RS and its sensitivity to identifying the progression of pathology. Longitudinal midbrain volume loss and WM changes are associated with PSP disease course. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage.

PubMed

Romme Christensen, Jeppe; Komori, Mika; von Essen, Marina Rode; Ratzer, Rikke; Börnsen, Lars; Bielekova, Bibi; Sellebjerg, Finn

2018-05-01

Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA). In all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL. These findings validate CSF sCD27 as a responsive and sensitive biomarker of intrathecal inflammation in progressive MS, capturing residual inflammation after treatment. Importantly, CSF sCD27 correlates with NFL, consistent with residual inflammation after anti-inflammatory treatment being associated with axonal damage.

FAA/NASA International Symposium on Advanced Structural Integrity Methods for Airframe Durability and Damage Tolerance

NASA Technical Reports Server (NTRS)

Harris, Charles E. (Editor)

1994-01-01

International technical experts in durability and damage tolerance of metallic airframe structures were assembled to present and discuss recent research findings and the development of advanced design and analysis methods, structural concepts, and advanced materials. The symposium focused on the dissemination of new knowledge and the peer-review of progress on the development of advanced methodologies. Papers were presented on: structural concepts for enhanced durability, damage tolerance, and maintainability; new metallic alloys and processing technology; fatigue crack initiation and small crack effects; fatigue crack growth models; fracture mechanics failure, criteria for ductile materials; structural mechanics methodology for residual strength and life prediction; development of flight load spectra for design and testing; and advanced approaches to resist corrosion and environmentally assisted fatigue.

FAA/NASA International Symposium on Advanced Structural Integrity Methods for Airframe Durability and Damage Tolerance, part 2

NASA Technical Reports Server (NTRS)

Harris, Charles E. (Editor)

1994-01-01

The international technical experts in the areas of durability and damage tolerance of metallic airframe structures were assembled to present and discuss recent research findings and the development of advanced design and analysis methods, structural concepts, and advanced materials. The principal focus of the symposium was on the dissemination of new knowledge and the peer-review of progress on the development of advanced methodologies. Papers were presented on the following topics: structural concepts for enhanced durability, damage tolerance, and maintainability; new metallic alloys and processing technology; fatigue crack initiation and small crack effects; fatigue crack growth models; fracture mechanics failure criteria for ductile materials; structural mechanics methodology for residual strength and life prediction; development of flight load spectra for design and testing; and corrosion resistance.

Continuum modeling of neuronal cell under blast loading

PubMed Central

Jérusalem, Antoine; Dao, Ming

2012-01-01

Traumatic brain injuries have recently been put under the spotlight as one of the most important causes of accidental brain dysfunctions. Significant experimental and modeling efforts are thus ongoing to study the associated biological, mechanical and physical mechanisms. In the field of cell mechanics, progresses are also being made at the experimental and modeling levels to better characterize many of the cell functions such as differentiation, growth, migration and death, among others. The work presented here aims at bridging both efforts by proposing a continuum model of neuronal cell submitted to blast loading. In this approach, cytoplasm, nucleus and membrane (plus cortex) are differentiated in a representative cell geometry, and different material constitutive models are adequately chosen for each one. The material parameters are calibrated against published experimental work of cell nanoindentation at multiple rates. The final cell model is ultimately subjected to blast loading within a complete fluid-structure interaction computational framework. The results are compared to the nanoindentation simulation and the specific effects of the blast wave on the pressure and shear levels at the interfaces are identified. As a conclusion, the presented model successfully captures some of the intrinsic intracellular phenomena occurring during its deformation under blast loading and potentially leading to cell damage. It suggests more particularly the localization of damage at the nucleus membrane similarly to what has already been observed at the overall cell membrane. This degree of damage is additionally predicted to be worsened by a longer blast positive phase duration. As a conclusion, the proposed model ultimately provides a new three dimensional computational tool to evaluate intracellular damage during blast loading. PMID:22562014

Genetic mouse models of brain ageing and Alzheimer's disease.

PubMed

Bilkei-Gorzo, Andras

2014-05-01

Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria

PubMed Central

Peng, Linyuan; Tang, Xiaolong; Meng, Fanbiao; Ao, Ying; Zhou, Mingyan; Wang, Ming; Cao, Xinyue; Qin, Baoming; Wang, Zimei; Zhou, Zhongjun; Wang, Guangming; Gao, Zhengliang; Xu, Jun

2018-01-01

DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans, but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases. PMID:29717979

Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria.

PubMed

Qian, Minxian; Liu, Zuojun; Peng, Linyuan; Tang, Xiaolong; Meng, Fanbiao; Ao, Ying; Zhou, Mingyan; Wang, Ming; Cao, Xinyue; Qin, Baoming; Wang, Zimei; Zhou, Zhongjun; Wang, Guangming; Gao, Zhengliang; Xu, Jun; Liu, Baohua

2018-05-02

DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans , but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases. © 2018, Qian et al.

Immune-Mediated Inflammation in the Pathogenesis of Emphysema: Insights from Mouse Models

PubMed Central

Craig, John M.; Scott, Alan L.; Mitzner, Wayne

2017-01-01

The cellular mechanisms that result in the initiation and progression of emphysema are clearly complex. A growing body of human data combined with discoveries from mouse models utilizing cigarette smoke exposure or protease administration have improved our understanding of emphysema development by implicating specific cell types that may be important for the pathophysiology of COPD. The most important aspects of emphysematous damage appear to be oxidative or protease stress and sustained macrophage activation and infiltration of other immune cells leading to epithelial damage and cell death. Despite the identification of these associated processes and cell types in many experimental studies, the reasons why cigarette smoke and other pollutants result in unremitting damage instead of injury resolution are still uncertain. We propose an important role for macrophages in the sequence of events that lead and maintain this chronic tissue pathologic process in emphysema. This model involves chronic activation of macrophage subtypes that precludes proper healing of the lung. Further elucidation of the cross-talk between epithelial cells that release damage-associated signals and the cellular immune effectors that respond to these cues is a critical step in the development of novel therapeutics that can restore proper lung structure and function to those afflicted with emphysema. PMID:28164246

A Patient-Specific Foot Model for the Estimate of Ankle Joint Forces in Patients with Juvenile Idiopathic Arthritis.

PubMed

Prinold, Joe A I; Mazzà, Claudia; Di Marco, Roberto; Hannah, Iain; Malattia, Clara; Magni-Manzoni, Silvia; Petrarca, Maurizio; Ronchetti, Anna B; Tanturri de Horatio, Laura; van Dijkhuizen, E H Pieter; Wesarg, Stefan; Viceconti, Marco

2016-01-01

Juvenile idiopathic arthritis (JIA) is the leading cause of childhood disability from a musculoskeletal disorder. It generally affects large joints such as the knee and the ankle, often causing structural damage. Different factors contribute to the damage onset, including altered joint loading and other mechanical factors, associated with pain and inflammation. The prediction of patients' joint loading can hence be a valuable tool in understanding the disease mechanisms involved in structural damage progression. A number of lower-limb musculoskeletal models have been proposed to analyse the hip and knee joints, but juvenile models of the foot are still lacking. This paper presents a modelling pipeline that allows the creation of juvenile patient-specific models starting from lower limb kinematics and foot and ankle MRI data. This pipeline has been applied to data from three children with JIA and the importance of patient-specific parameters and modelling assumptions has been tested in a sensitivity analysis focused on the variation of the joint reaction forces. This analysis highlighted the criticality of patient-specific definition of the ankle joint axes and location of the Achilles tendon insertions. Patient-specific detection of the Tibialis Anterior, Tibialis Posterior, and Peroneus Longus origins and insertions were also shown to be important.

Boldine Improves Kidney Damage in the Goldblatt 2K1C Model Avoiding the Increase in TGF-β.

PubMed

Gómez, Gonzalo I; Velarde, Victoria

2018-06-25

Boldine, a major aporphine alkaloid found in the Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of kidney damage in renovascular hypertension (RVH). The activation of the renin-angiotensin system (RAS) is crucial to the development and progression of hypertensive renal damage and TGF-β is closely associated with the activation of RAS. In the present study, we assessed the effect of boldine on the progression of kidney disease using the 2K1C hypertension model and identifying mediators in the RAS, such as TGF-β, that could be modulated by this alkaloid. Toward this hypothesis, rats ( n = 5/group) were treated with boldine (50 mg/kg/day, gavage) for six weeks after 2K1C surgery (pressure ≥ 180 mmHg). Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive substances (TBARS). The evolution of systolic blood pressure (SBP) was followed weekly. Alpha-smooth muscle actin (α-SMA) and Col III were used as markers of kidney damage; ED-1 and osteopontin (OPN) were used as markers of inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF-β. Boldine treatment reduced the UProt/UCrea ratio, plasma TBARS, and slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED-1, and OPN were lower when compared to 2K1C rats. Boldine prevented the increase in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney damage. These results suggest that boldine could potentially be used as a nutraceutic.

TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.

PubMed

Harley, Margaret E; Murina, Olga; Leitch, Andrea; Higgs, Martin R; Bicknell, Louise S; Yigit, Gökhan; Blackford, Andrew N; Zlatanou, Anastasia; Mackenzie, Karen J; Reddy, Kaalak; Halachev, Mihail; McGlasson, Sarah; Reijns, Martin A M; Fluteau, Adeline; Martin, Carol-Anne; Sabbioneda, Simone; Elcioglu, Nursel H; Altmüller, Janine; Thiele, Holger; Greenhalgh, Lynn; Chessa, Luciana; Maghnie, Mohamad; Salim, Mahmoud; Bober, Michael B; Nürnberg, Peter; Jackson, Stephen P; Hurles, Matthew E; Wollnik, Bernd; Stewart, Grant S; Jackson, Andrew P

2016-01-01

DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions.

The elastic and inelastic behavior of woven graphite fabric reinforced polyimide composites

NASA Astrophysics Data System (ADS)

Searles, Kevin H.

In many aerospace and conventional engineering applications, load-bearing composite structures are designed with the intent of being subjected to uniaxial stresses that are predominantly tensile or compressive. However, it is likely that biaxial and possibly triaxial states of stress will exist throughout the in-service life of the structure or component. The existing paradigm suggests that unidirectional tape materials are superior under uniaxial conditions since the vast majority of fibers lie in-plane and can be aligned to the loading axis. This may be true, but not without detriment to impact performance, interlaminar strength, strain to failure and complexity of part geometry. In circumstances where a sufficient balance of these properties is required, composites based on woven fabric reinforcements become attractive choices. In this thesis, the micro- and mesoscale elastic behavior of composites based on 8HS woven graphite fabric architectures and polyimide matrices is studied analytically and numerically. An analytical model is proposed to predict the composite elastic constants and is verified using numerical strain energy methods of equivalence. The model shows good agreement with the experiments and numerical strain energy equivalence. Lamina stresses generated numerically from in-plane shear loading show substantial shear and transverse normal stress concentrations in the transverse undulated tow which potentially leads to intralaminar damage. The macroscale inelastic behavior of the same composites is also studied experimentally and numerically. On an experimental basis, the biaxial and modified biaxial Iosipescu test methods are employed to study the weaker-mode shear and biaxial failure properties at room and elevated temperatures. On a numerical basis, the macroscale inelastic shear behavior of the composites is studied. Structural nonlinearities and material nonlinearities are identified and resolved. In terms of specimen-to-fixture interactions, load eccentricities, geometric (large strains and rotations) nonlinearities and boundary contact (friction) nonlinearities are explored. In terms of material nonlinearities, anisotropic plasticity and progressive damage are explored. A progressive damage criterion is proposed which accounts for the elastic strain energy densities in three directions. Of the types of nonlinearities studied, the nonlinear shear stress-strain behavior of the composites is principally from progressive intralaminar damage. Structural nonlinearities and elastoplastic deformation appear to be inconsequential.

The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis.

PubMed

Scalfari, Antonio; Romualdi, Chiara; Nicholas, Richard S; Mattoscio, Miriam; Magliozzi, Roberta; Morra, Aldo; Monaco, Salvatore; Muraro, Paolo A; Calabrese, Massimiliano

2018-05-16

To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS). In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS. Fifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP. Extensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy. © 2018 American Academy of Neurology.

Drosophila Models of Parkinson's Disease: Discovering Relevant Pathways and Novel Therapeutic Strategies

PubMed Central

Muñoz-Soriano, Verónica; Paricio, Nuria

2011-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder and is mainly characterized by the selective and progressive loss of dopaminergic neurons, accompanied by locomotor defects. Although most PD cases are sporadic, several genes are associated with rare familial forms of the disease. Analyses of their function have provided important insights into the disease process, demonstrating that three types of cellular defects are mainly involved in the formation and/or progression of PD: abnormal protein aggregation, oxidative damage, and mitochondrial dysfunction. These studies have been mainly performed in PD models created in mice, fruit flies, and worms. Among them, Drosophila has emerged as a very valuable model organism in the study of either toxin-induced or genetically linked PD. Indeed, many of the existing fly PD models exhibit key features of the disease and have been instrumental to discover pathways relevant for PD pathogenesis, which could facilitate the development of therapeutic strategies. PMID:21512585

Dark Agouti rat model of chemotherapy-induced mucositis: establishment and current state of the art.

PubMed

Vanhoecke, Barbara; Bateman, Emma; Mayo, Bronwen; Vanlancker, Eline; Stringer, Andrea; Thorpe, Daniel; Keefe, Dorothy

2015-06-01

Mucositis is a major oncological problem. The entire gastrointestinal and genitourinary tract and also other mucosal surfaces can be affected in recipients of radiotherapy, and/or chemotherapy. Major progress has been made in recent years in understanding the mechanisms of oral and small intestinal mucositis, which appears to be more prominent than colonic damage. This progress is largely due to the development of representative laboratory animal models of mucositis. This review focuses on the development and establishment of the Dark Agouti rat mammary adenocarcinoma model by the Mucositis Research Group of the University of Adelaide over the past 20 years to characterize the mechanisms underlying methotrexate-, 5-fluorouracil-, and irinotecan-induced mucositis. It also aims to summarize the results from studies using different animal model systems to identify new molecular and cellular markers of mucositis. © 2015 by the Society for Experimental Biology and Medicine.

Protein Carbonylation in Human Smokers and Mammalian Models of Exposure to Cigarette Smoke: Focus on Redox Proteomic Studies.

PubMed

Dalle-Donne, Isabella; Colombo, Graziano; Gornati, Rosalba; Garavaglia, Maria L; Portinaro, Nicola; Giustarini, Daniela; Bernardini, Giovanni; Rossi, Ranieri; Milzani, Aldo

2017-03-10

Oxidative stress is one mechanism whereby tobacco smoking affects human health, as reflected by increased levels of several biomarkers of oxidative stress/damage isolated from tissues and biological fluids of active and passive smokers. Many investigations of cigarette smoke (CS)-induced oxidative stress/damage have been carried out in mammalian animal and cellular models of exposure to CS. Animal models allow the investigation of many parameters that are similar to those measured in human smokers. In vitro cell models may provide new information on molecular and functional differences between cells of smokers and nonsmokers. Recent Advances: Over the past decade or so, a growing number of researches highlighted that CS induces protein carbonylation in different tissues and body fluids of smokers as well as in in vivo and in vitro models of exposure to CS. We review recent findings on protein carbonylation in smokers and models thereof, focusing on redox proteomic studies. We also discuss the relevance and limitations of these models of exposure to CS and critically assess the congruence between the smoker's condition and laboratory models. The identification of protein targets is crucial for understanding the mechanism(s) by which carbonylated proteins accumulate and potentially affect cellular functions. Recent progress in redox proteomics allows the enrichment, identification, and characterization of specific oxidative protein modifications, including carbonylation. Therefore, redox proteomics can be a powerful tool to gain new insights into the onset and/or progression of CS-related diseases and to develop strategies to prevent and/or treat them. Antioxid. Redox Signal. 26, 406-426.

Oxidative Stress as a Mechanism Involved in Kidney Damage After Subchronic Exposure to Vanadium Inhalation and Oral Sweetened Beverages in a Mouse Model.

PubMed

Espinosa-Zurutuza, Maribel; González-Villalva, Adriana; Albarrán-Alonso, Juan Carlos; Colín-Barenque, Laura; Bizarro-Nevares, Patricia; Rojas-Lemus, Marcela; López-Valdéz, Nelly; Fortoul, Teresa I

Kidney diseases have notably increased in the last few years. This is partially explained by the increase in metabolic syndrome, diabetes, and systemic blood hypertension. However, there is a segment of the population that has neither of the previous risk factors, yet suffers kidney damage. Exposure to atmospheric pollutants has been suggested as a possible risk factor. Air-suspended particles carry on their surface a variety of fuel combustion-related residues such as metals, and vanadium is one of these. Vanadium might produce oxidative stress resulting in the damage of some organs such as the kidney. Additionally, in countries like Mexico, the ingestion of sweetened beverages is a major issue; whether these beverages alone are responsible for direct kidney damage or whether their ingestion promotes the progression of an existing renal damage generates controversy. In this study, we report the combined effect of vanadium inhalation and sweetened beverages ingestion in a mouse model. Forty CD-1 male mice were distributed in 4 groups: control, vanadium inhalation, 30% sucrose in drinking water, and vanadium inhalation plus sucrose 30% in drinking water. Our results support that vanadium inhalation and the ingestion of 30% sucrose induce functional and histological kidney damage and an increase in oxidative stress biomarkers, which were higher in the combined effect of vanadium plus 30% sucrose. The results also support that the ingestion of 30% sucrose alone without hyperglycemia also produces kidney damage.

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

Stout, D.K.

Flaws are noted in equilibrium growth models which ignore the facts that labor is no longer homogeneous, national governments can no longer guarantee a managed demand, and technical progress is not an independent force. The pace of technical progress is the major variable and increases with competition and certainty in the growth of demand. The outlook for technical progress is examined in the context of productivity, using microprocessor development for illustration. The author takes an optimistic view of new developments in that they do not bring the self-destructive possibility of overpopulation, irreversible damage to the environment, or nuclear war anymore » closer, while having a positive chance to promote a more rewarding relationship between education, work, and life style. The opportunities for positive humanistic changes through microprocessing are confirmed. (DCK)« less

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

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

Liu, Yongming; Oskay, Caglar

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

DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice

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

Wang, Degui; Yu, Tianyu; Liu, Yongqiang

Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenicmore » mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages. - Highlights: • This study explore contribution of DNA damage to neurodegeneration in Parkinson's disease mice. • A53T-α-Syn MEF cells show a prolonged DNA damage repair process and senescense phenotype. • DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice. • DNA damage decrease the number of nigrostriatal dopaminergic neurons. • Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages.« less

A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model

PubMed Central

’t Hart, Bert A.; Dunham, Jordon; Faber, Bart W.; Laman, Jon D.; van Horssen, Jack; Bauer, Jan; Kap, Yolanda S.

2017-01-01

The absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus). The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34–56 from human myelin oligodendrocyte glycoprotein (MOG) formulated with a mineral oil [incomplete Freund’s adjuvant (IFA)]. Pathological aspects include demyelination of cortical gray matter with microglia activation, oxidative stress, and redistribution of iron. When the peptide is formulated in complete Freund’s adjuvant, which contains mycobacteria that relay strong activation signals to myeloid cells, oxidative damage pathways are strongly boosted leading to more intensive pathology. The proven absence of immune potentiating danger signals in the MOG34–56/IFA formulation implies that a narrow population of antigen-experienced T cells present in the monkey’s immune repertoire is activated. This novel pathway involves the interplay of lymphocryptovirus-infected B cells with MHC class Ib/Caja-E restricted CD8+ CD56+ cytotoxic T lymphocytes. PMID:28744286

B-Type Natriuretic Peptide Deletion Leads to Progressive Hypertension, Associated Organ Damage, and Reduced Survival: Novel Model for Human Hypertension.

PubMed

Holditch, Sara J; Schreiber, Claire A; Nini, Ryan; Tonne, Jason M; Peng, Kah-Whye; Geurts, Aron; Jacob, Howard J; Burnett, John C; Cataliotti, Alessandro; Ikeda, Yasuhiro

2015-07-01

Altered myocardial structure and function, secondary to chronically elevated blood pressure, are leading causes of heart failure and death. B-type natriuretic peptide (BNP), a guanylyl cyclase A agonist, is a cardiac hormone integral to cardiovascular regulation. Studies have demonstrated a causal relationship between reduced production or impaired BNP release and the development of human hypertension. However, the consequences of BNP insufficiency on blood pressure and hypertension-associated complications remain poorly understood. Therefore, the goal of this study was to create and characterize a novel model of BNP deficiency to investigate the effects of BNP absence on cardiac and renal structure, function, and survival. Genetic BNP deletion was generated in Dahl salt-sensitive rats. Compared with age-matched controls, BNP knockout rats demonstrated adult-onset hypertension. Increased left ventricular mass with hypertrophy and substantially augmented hypertrophy signaling pathway genes, developed in young adult knockout rats, which preceded hypertension. Prolonged hypertension led to increased cardiac stiffness, cardiac fibrosis, and thrombi formation. Significant elongation of the QT interval was detected at 9 months in knockout rats. Progressive nephropathy was also noted with proteinuria, fibrosis, and glomerular alterations in BNP knockout rats. End-organ damage contributed to a significant decline in overall survival. Systemic BNP overexpression reversed the phenotype of genetic BNP deletion. Our results demonstrate the critical role of BNP defect in the development of systemic hypertension and associated end-organ damage in adulthood. © 2015 American Heart Association, Inc.

A review on PARP1 inhibitors: Pharmacophore modeling, virtual and biological screening studies to identify novel PARP1 inhibitors.

PubMed

Singh, Sardar Shamshair; Sarma, Jagarlapudi A R P; Narasu, Lakshmi; Dayam, Raveendra; Xu, Shili; Neamati, Nouri

2014-01-01

A tremendous research on Poly (ADP-ribose) polymerase (PARP) pertaining to cancer and ischemia is in very rapid progress. PARP's are a specific class of enzymes that repairs the damaged DNA. Recent findings suggest also that PARP-1 is the most abundantly expressed nuclear enzyme which involves in various therapeutic areas like inflammation, stroke, cardiac ischemia, cancer and diabetes. The current review describes the overview on clinical candidates of PARP1 and its current status in clinical trials. This paper also covers identification of potent PARP1 inhibitors using structure and ligand based pharmacophore models. Finally 36 potential hits were identified from the virtual screening of pharmacophore models and screened for PARP1 activity. 15 actives were identified as potent PARP1 inhibitors and further optimization of these analogues are in progress.

Modeling the Progression of Epithelial Leak Caused by Overdistension

PubMed Central

Hamlington, Katharine L.; Ma, Baoshun; Smith, Bradford J.; Bates, Jason H. T.

2016-01-01

Mechanical ventilation is necessary for treatment of the acute respiratory distress syndrome but leads to overdistension of the open regions of the lung and produces further damage. Although we know that the excessive stresses and strains disrupt the alveolar epithelium, we know little about the relationship between epithelial strain and epithelial leak. We have developed a computational model of an epithelial monolayer to simulate leak progression due to overdistension and to explain previous experimental findings in mice with ventilator-induced lung injury. We found a nonlinear threshold-type relationship between leak area and increasing stretch force. After the force required to initiate the leak was reached, the leak area increased at a constant rate with further increases in force. Furthermore, this rate was slower than the rate of increase in force, especially at end-expiration. Parameter manipulation changed only the leak-initiating force; leak area growth followed the same trend once this force was surpassed. These results suggest that there is a particular force (analogous to ventilation tidal volume) that must not be exceeded to avoid damage and that changing cell physical properties adjusts this threshold. This is relevant for the development of new ventilator strategies that avoid inducing further injury to the lung. PMID:26951764

Neurotrophic factors and corneal nerve regeneration

PubMed Central

Sacchetti, Marta; Lambiase, Alessandro

2017-01-01

The cornea has unique features that make it a useful model for regenerative medicine studies. It is an avascular, transparent, densely innervated tissue and any pathological changes can be easily detected by slit lamp examination. Corneal sensitivity is provided by the ophthalmic branch of the trigeminal nerve that elicits protective reflexes such as blinking and tearing and exerts trophic support by releasing neuromediators and growth factors. Corneal nerves are easily evaluated for both function and morphology using standard instruments such as corneal esthesiometer and in vivo confocal microscope. All local and systemic conditions that are associated with damage of the trigeminal nerve cause the development of neurotrophic keratitis, a rare degenerative disease. Neurotrophic keratitis is characterized by impairment of corneal sensitivity associated with development of persistent epithelial defects that may progress to corneal ulcer, melting and perforation. Current neurotrophic keratitis treatments aim at supporting corneal healing and preventing progression of corneal damage. Novel compounds able to stimulate corneal nerve recovery are in advanced development stage. Among them, nerve growth factor eye drops showed to be safe and effective in stimulating corneal healing and improving corneal sensitivity in patients with neurotrophic keratitis. Neurotrophic keratitis represents an useful model to evaluate in clinical practice novel neuro-regenerative drugs. PMID:28966630

Finite Element Model for Failure Study of Two-Dimensional Triaxially Braided Composite

NASA Technical Reports Server (NTRS)

Li, Xuetao; Binienda, Wieslaw K.; Goldberg, Robert K.

2010-01-01

A new three-dimensional finite element model of two-dimensional triaxially braided composites is presented in this paper. This meso-scale modeling technique is used to examine and predict the deformation and damage observed in tests of straight sided specimens. A unit cell based approach is used to take into account the braiding architecture as well as the mechanical properties of the fiber tows, the matrix and the fiber tow-matrix interface. A 0 deg / plus or minus 60 deg. braiding configuration has been investigated by conducting static finite element analyses. Failure initiation and progressive degradation has been simulated in the fiber tows by use of the Hashin failure criteria and a damage evolution law. The fiber tow-matrix interface was modeled by using a cohesive zone approach to capture any fiber-matrix debonding. By comparing the analytical results to those obtained experimentally, the applicability of the developed model was assessed and the failure process was investigated.

Preventing Collateral Damage in Crohn’s Disease: The Lémann Index

PubMed Central

Fiorino, Gionata; Bonifacio, Cristiana; Peyrin-Biroulet, Laurent

2016-01-01

Crohn’s disease [CD] is a chronic progressive and destructive condition. Half of all CD patients will develop bowel damage at 10 years. As in rheumatic diseases, preventing the organ damage consequent to CD complications [fistula, abscess, and/or stricture] is emerging as a new therapeutic goal for these patients in clinical practice. This might be the only way to alter disease course, as surgery is often required for disease complications. Similar to the joint damage in rheumatoid arthritis, bowel damage has also emerged as a new endpoint in disease-modification trials such as the REACT trial. Recently, the Lemann Index [LI] has been developed to measure CD-related bowel damage, and to assess damage progression over time, in order to evaluate the impact of therapeutic strategies in terms of preventing bowel damage. While validation is pending, recent reports suggested that bowel damage is reversible by anti-tumour necrosis factor [TNF] therapy. The Lémann index may play a key role in CD management, and should be implemented in all upcoming disease-modification trials in CD. PMID:26744441

Remedying CERCLA`s natural resource damages provision: Incorporation of the public trust doctrine into natural resource damage actions

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

Chase, A.R.

When Congress enacted the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), it ushered in a sweeping approach to controlling the environmental effects of improper hazardous waste disposal. CERCLA`s cleanup provisions, which focus on removal and remediation of hazardous substances from inactive hazardous waste sites, have progressed through more than a decade of litigation and a great deal of public debate. However, CERCLA`s natural resource damage provisions have not shared this same degree of progress.

Modeling Quasi-Static and Fatigue-Driven Delamination Migration

NASA Technical Reports Server (NTRS)

De Carvalho, N. V.; Ratcliffe, J. G.; Chen, B. Y.; Pinho, S. T.; Baiz, P. M.; Tay, T. E.

2014-01-01

An approach was proposed and assessed for the high-fidelity modeling of progressive damage and failure in composite materials. It combines the Floating Node Method (FNM) and the Virtual Crack Closure Technique (VCCT) to represent multiple interacting failure mechanisms in a mesh-independent fashion. Delamination, matrix cracking, and migration were captured failure and migration criteria based on fracture mechanics. Quasi-static and fatigue loading were modeled within the same overall framework. The methodology proposed was illustrated by simulating the delamination migration test, showing good agreement with the available experimental data.

Mechanical behavior, damage tolerance and durability of fiber metal laminates for aircraft structures

NASA Astrophysics Data System (ADS)

Wu, Guocai

This study systematically explores the mechanical behavior, damage tolerance and durability of fiber metal laminates, a promising candidate materials system for next generation aerospace structures. The experimental results indicated that GLARE laminates exhibited a bilinear deformation behavior under static in-plane loading. Both an analytical constitutive model based on a modified classical lamination theory which incorporates the elasto-plastic behavior of aluminum alloy and a numerical simulation based on finite element modeling are used to predict the nonlinear stress-strain response and deformation behavior of GLARE laminates. The blunt notched strength of GLARE laminates increased with decreasing specimen width and decreasing hole diameter. The notched strength of GLARE laminates was evaluated based on a modified point stress criterion. A computer simulation based on finite element method was performed to study stress concentration and distribution around the notch and verify the analytical and experimental results of notched strength. Good agreement is obtained between the model predictions and experimental results. Experimental results also indicate that GLARE laminates exhibited superior impact properties to those of monolithic 2024-T3 aluminum alloy at low velocity impact loading. The GLARE 5-2/1 laminate with 0°/90°/90°/0° fiber configuration exhibits a better impact resistance than the GLARE 4-3/2 laminate with 0°/90°/0° fiber orientation. The characteristic impact energies, the damage area, and the permanent deflection of laminates are used to evaluate the impact damage resistance. The post-impact residual tensile strength under various damage states ranging from the plastic dent, barely visible impact damage (BVID), clearly visible impact damage (CVID) up to the complete perforation was also measured and compared. The post-impact fatigue behavior under various stress levels and impact damage states was extensively explored. The damage initiation and progression, failure modes and crack propagation under different loading conditions were investigated and identified with microscopy, SEM, X-ray radiography, and by chemically removing outer aluminum layers.

Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: inner versus outer retina, parafovea versus peripheral fovea.

PubMed

de Sisternes, Luis; Hu, Julia; Rubin, Daniel L; Marmor, Michael F

2015-05-01

To evaluate the relative involvement of inner and outer retina in hydroxychloroquine (HCQ) retinopathy while on the drug, and after drug cessation, using data from spectral-domain optical coherence tomography (SD-OCT). A total of 102 SD-OCT scans were obtained from 11 patients (classified as having early, moderate, or severe stages of toxicity) over a period of 4 years after cessation of HCQ. The inner and outer retina boundaries were identified automatically to measure thickness and characterize progression topographically. The segmentation of retinal layers was verified in SD-OCT cross-sections for all eyes and scans included in this study (a total of 102 scans). Topographic analysis showed that inner retina was not involved in HCQ toxicity to any meaningful degree, either between stages of retinopathy or after the drug is stopped. The characteristic bull's eye pattern of outer macula thinning appears when comparing moderate retinopathy (before any RPE damage) to the early stage. Later damage, as toxicity evolved to a severe stage, was diffuse across most of the macula. If the drug was stopped at an early or moderate stage, progression was limited to the first year and occurred diffusely without parafoveal localization. Hydroxychloroquine retinopathy primarily involves outer retina (photoreceptors). Outer retinal thinning while using HCQ initially involves the parafovea, but becomes diffuse across the macula as damage progresses or after drug cessation. When HCQ is stopped at an early or moderate stage (before RPE damage), progression seems to be limited to the first year.

Development of a Model of Chronic Kidney Disease in the C57BL/6 Mouse with Properties of Progressive Human CKD

PubMed Central

Cruz, Gaile L.; Lu, Chao; Carlisle, Rachel E.; Werner, Kaitlyn E.; Ask, Kjetil; Dickhout, Jeffrey G.

2015-01-01

Chronic kidney disease (CKD) is a major healthcare problem with increasing prevalence in the population. CKD leads to end stage renal disease and increases the risk of cardiovascular disease. As such, it is important to study the mechanisms underlying CKD progression. To this end, an animal model was developed to allow the testing of new treatment strategies or molecular targets for CKD prevention. Many underlying risk factors result in CKD but the disease itself has common features, including renal interstitial fibrosis, tubular epithelial cell loss through apoptosis, glomerular damage, and renal inflammation. Further, CKD shows differences in prevalence between the genders with premenopausal women being relatively resistant to CKD. We sought to develop and characterize an animal model with these common features of human CKD in the C57BL/6 mouse. Mice of this genetic background have been used to produce transgenic strains that are commercially available. Thus, a CKD model in this strain would allow the testing of the effects of numerous genes on the severity or progression of CKD with minimal cost. This paper describes such a mouse model of CKD utilizing angiotensin II and deoxycorticosterone acetate as inducers. PMID:26064882

Constitutive behavior and progressive mechanical failure of electrodes in lithium-ion batteries

NASA Astrophysics Data System (ADS)

Zhang, Chao; Xu, Jun; Cao, Lei; Wu, Zenan; Santhanagopalan, Shriram

2017-07-01

The electrodes of lithium-ion batteries (LIB) are known to be brittle and to fail earlier than the separators during an external crush event. Thus, the understanding of mechanical failure mechanism for LIB electrodes (anode and cathode) is critical for the safety design of LIB cells. In this paper, we present experimental and numerical studies on the constitutive behavior and progression of failure in LIB electrodes. Mechanical tests were designed and conducted to evaluate the constitutive properties of porous electrodes. Constitutive models were developed to describe the stress-strain response of electrodes under uniaxial tensile and compressive loads. The failure criterion and a damage model were introduced to model their unique tensile and compressive failure behavior. The failure mechanism of LIB electrodes was studied using the blunt rod test on dry electrodes, and numerical models were built to simulate progressive failure. The different failure processes were examined and analyzed in detail numerically, and correlated with experimentally observed failure phenomena. The test results and models improve our understanding of failure behavior in LIB electrodes, and provide constructive insights on future development of physics-based safety design tools for battery structures under mechanical abuse.

Constitutive behavior and progressive mechanical failure of electrodes in lithium-ion batteries

DOE PAGES

Zhang, Chao; Xu, Jun; Cao, Lei; ...

2017-05-05

The electrodes of lithium-ion batteries (LIB) are known to be brittle and to fail earlier than the separators during an external crush event. Thus, the understanding of mechanical failure mechanism for LIB electrodes (anode and cathode) is critical for the safety design of LIB cells. In this paper, we present experimental and numerical studies on the constitutive behavior and progression of failure in LIB electrodes. Mechanical tests were designed and conducted to evaluate the constitutive properties of porous electrodes. Constitutive models were developed to describe the stress-strain response of electrodes under uniaxial tensile and compressive loads. The failure criterion andmore » a damage model were introduced to model their unique tensile and compressive failure behavior. The failure mechanism of LIB electrodes was studied using the blunt rod test on dry electrodes, and numerical models were built to simulate progressive failure. The different failure processes were examined and analyzed in detail numerically, and correlated with experimentally observed failure phenomena. Finally, the test results and models improve our understanding of failure behavior in LIB electrodes, and provide constructive insights on future development of physics-based safety design tools for battery structures under mechanical abuse.« less

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

NASA Astrophysics Data System (ADS)

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

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

Finite element modelling of aluminum alloy 2024-T3 under transverse impact loading

NASA Astrophysics Data System (ADS)

Abdullah, Ahmad Sufian; Kuntjoro, Wahyu; Yamin, A. F. M.

2017-12-01

Fiber metal laminate named GLARE is a new aerospace material which has great potential to be widely used in future lightweight aircraft. It consists of aluminum alloy 2024-T3 and glass-fiber reinforced laminate. In order to produce reliable finite element model of impact response or crashworthiness of structure made of GLARE, one can initially model and validate the finite element model of the impact response of its constituents separately. The objective of this study was to develop a reliable finite element model of aluminum alloy 2024-T3 under low velocity transverse impact loading using commercial software ABAQUS. Johnson-Cook plasticity and damage models were used to predict the alloy's material properties and impact behavior. The results of the finite element analysis were compared to the experiment that has similar material and impact conditions. Results showed good correlations in terms of impact forces, deformation and failure progressions which concluded that the finite element model of 2024-T3 aluminum alloy under low velocity transverse impact condition using Johnson-Cook plastic and damage models was reliable.

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

English, Shawn Allen; Nelson, Stacy Michelle; Briggs, Timothy

Presented is a model verification and validation effort using low - velocity impact (LVI) of carbon fiber reinforced polymer laminate experiments. A flat cylindrical indenter impacts the laminate with enough energy to produce delamination, matrix cracks and fiber breaks. Included in the experimental efforts are ultrasonic scans of the damage for qualitative validation of the models. However, the primary quantitative metrics of validation are the force time history measured through the instrumented indenter and initial and final velocities. The simulations, whi ch are run on Sandia's Sierra finite element codes , consist of all physics and material parameters of importancemore » as determined by a sensitivity analysis conducted on the LVI simulation. A novel orthotropic damage and failure constitutive model that is cap able of predicting progressive composite damage and failure is described in detail and material properties are measured, estimated from micromechanics or optimized through calibration. A thorough verification and calibration to the accompanying experiment s are presented. Specia l emphasis is given to the four - point bend experiment. For all simulations of interest, the mesh and material behavior is verified through extensive convergence studies. An ensemble of simulations incorporating model parameter unc ertainties is used to predict a response distribution which is then compared to experimental output. The result is a quantifiable confidence in material characterization and model physics when simulating this phenomenon in structures of interest.« less

Exploring the existence of a stayer population with mover-stayer counting process models: application to joint damage in psoriatic arthritis.

PubMed

Yiu, Sean; Farewell, Vernon T; Tom, Brian D M

2017-08-01

Many psoriatic arthritis patients do not progress to permanent joint damage in any of the 28 hand joints, even under prolonged follow-up. This has led several researchers to fit models that estimate the proportion of stayers (those who do not have the propensity to experience the event of interest) and to characterize the rate of developing damaged joints in the movers (those who have the propensity to experience the event of interest). However, when fitted to the same data, the paper demonstrates that the choice of model for the movers can lead to widely varying conclusions on a stayer population, thus implying that, if interest lies in a stayer population, a single analysis should not generally be adopted. The aim of the paper is to provide greater understanding regarding estimation of a stayer population by comparing the inferences, performance and features of multiple fitted models to real and simulated data sets. The models for the movers are based on Poisson processes with patient level random effects and/or dynamic covariates, which are used to induce within-patient correlation, and observation level random effects are used to account for time varying unobserved heterogeneity. The gamma, inverse Gaussian and compound Poisson distributions are considered for the random effects.

Highlighting the DNA damage response with ultrashort laser pulses in the near infrared and kinetic modeling

PubMed Central

Ferrando-May, Elisa; Tomas, Martin; Blumhardt, Philipp; Stöckl, Martin; Fuchs, Matthias; Leitenstorfer, Alfred

2013-01-01

Our understanding of the mechanisms governing the response to DNA damage in higher eucaryotes crucially depends on our ability to dissect the temporal and spatial organization of the cellular machinery responsible for maintaining genomic integrity. To achieve this goal, we need experimental tools to inflict DNA lesions with high spatial precision at pre-defined locations, and to visualize the ensuing reactions with adequate temporal resolution. Near-infrared femtosecond laser pulses focused through high-aperture objective lenses of advanced scanning microscopes offer the advantage of inducing DNA damage in a 3D-confined volume of subnuclear dimensions. This high spatial resolution results from the highly non-linear nature of the excitation process. Here we review recent progress based on the increasing availability of widely tunable and user-friendly technology of ultrafast lasers in the near infrared. We present a critical evaluation of this approach for DNA microdamage as compared to the currently prevalent use of UV or VIS laser irradiation, the latter in combination with photosensitizers. Current and future applications in the field of DNA repair and DNA-damage dependent chromatin dynamics are outlined. Finally, we discuss the requirement for proper simulation and quantitative modeling. We focus in particular on approaches to measure the effect of DNA damage on the mobility of nuclear proteins and consider the pros and cons of frequently used analysis models for FRAP and photoactivation and their applicability to non-linear photoperturbation experiments. PMID:23882280

Tempol Moderately Extends Survival in a hSOD1G93A ALS Rat Model by Inhibiting Neuronal Cell Loss, Oxidative Damage and Levels of Non-Native hSOD1G93A Forms

PubMed Central

Linares, Edlaine; Seixas, Luciana V.; dos Prazeres, Janaina N.; Ladd, Fernando V. L.; Ladd, Aliny A. B. L.; Coppi, Antonio A.; Augusto, Ohara

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive dysfunction and death of motor neurons by mechanisms that remain unclear. Evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. Cyclic nitroxides are an alternative worth exploring because they are multifunctional antioxidants that display low toxicity in vivo. Here, we examine the effects of the cyclic nitroxide tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) on ALS onset and progression in transgenic female rats over-expressing the mutant hSOD1G93A . Starting at 7 weeks of age, a high dose of tempol (155 mg/day/rat) in the rat´s drinking water had marginal effects on the disease onset but decelerated disease progression and extended survival by 9 days. In addition, tempol protected spinal cord tissues as monitored by the number of neuronal cells, and the reducing capability and levels of carbonylated proteins and non-native hSOD1 forms in spinal cord homogenates. Intraperitoneal tempol (26 mg/rat, 3 times/week) extended survival by 17 days. This group of rats, however, diverted to a decelerated disease progression. Therefore, it was inconclusive whether the higher protective effect of the lower i.p. dose was due to higher tempol bioavailability, decelerated disease development or both. Collectively, the results show that tempol moderately extends the survival of ALS rats while protecting their cellular and molecular structures against damage. Thus, the results provide proof that cyclic nitroxides are alternatives worth to be further tested in animal models of ALS. PMID:23405225

Peripheral Blood Mitochondrial DNA Damage as a Potential Noninvasive Biomarker of Diabetic Retinopathy

PubMed Central

Mishra, Manish; Lillvis, John; Seyoum, Berhane; Kowluru, Renu A.

2016-01-01

Purpose In the development of diabetic retinopathy, retinal mitochondria become dysfunctional, and mitochondrial DNA (mtDNA) is damaged. Because retinopathy is a progressive disease, and circulating glucose levels are high in diabetes, our aim was to investigate if peripheral blood mtDNA damage can serve as a potential biomarker of diabetic retinopathy. Methods Peripheral blood mtDNA damage was investigated by extended-length PCR in rats and mice, diabetic for 10 to 12 months (streptozotocin-induced, type 1 model), and in 12- and 40-week-old Zucker diabetic fatty rats (ZDF, type 2). Mitochondrial copy number (in gDNA) and transcription (in cDNA) were quantified by qPCR. Similar parameters were measured in blood from diabetic patients with/without retinopathy. Results Peripheral blood from diabetic rodents had significantly increased mtDNA damage and decreased copy numbers and transcription. Lipoic acid administration in diabetic rats, or Sod2 overexpression or MMP-9 knockdown in mice, the therapies that prevent diabetic retinopathy, also ameliorated blood mtDNA damage and restored copy numbers and transcription. Although blood from 40-week-old ZDF rats had significant mtDNA damage, 12-week-old rats had normal mtDNA. Diabetic patients with retinopathy had increased blood mtDNA damage, and decreased transcription and copy numbers compared with diabetic patients without retinopathy and nondiabetic individuals. Conclusions Type 1 diabetic rodents with oxidative stress modulated by pharmacologic/genetic means, and type 2 animal model and patients with/without diabetic retinopathy, demonstrate a strong relation between peripheral blood mtDNA damage and diabetic retinopathy, and suggest the possibility of use of peripheral blood mtDNA as a noninvasive biomarker of diabetic retinopathy. PMID:27494345

Scalable Computing of the Mesh Size Effect on Modeling Damage Mechanics in Woven Armor Composites

DTIC Science & Technology

2008-12-01

manner of a user defined material subroutine to provide overall stress increments to, the parallel LS-DYNA3D a Lagrangian explicit code used in...finite element code, as a user defined material subroutine . The ability of this subroutine to model the effect of the progressions of a select number...is added as a user defined material subroutine to parallel LS-DYNA3D. The computations of the global mesh are handled by LS-DYNA3D and are spread

Quantification of joint inflammation in rheumatoid arthritis by time-resolved diffuse optical spectroscopy and tracer kinetic modeling

NASA Astrophysics Data System (ADS)

Ioussoufovitch, Seva; Morrison, Laura B.; Lee, Ting-Yim; St. Lawrence, Keith; Diop, Mamadou

2015-03-01

Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation, which can cause progressive joint damage and disability. Diffuse optical spectroscopy (DOS) and imaging have the potential to become potent monitoring tools for RA. We devised a method that combined time-resolved DOS and tracer kinetics modeling to rapidly and reliably quantify blood flow in the joint. Preliminary results obtained from two animals show that the technique can detect joint inflammation as early as 5 days after onset.

TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism

PubMed Central

Leitch, Andrea; Higgs, Martin R.; Bicknell, Louise S.; Yigit, Gökhan; Blackford, Andrew N.; Zlatanou, Anastasia; Mackenzie, Karen J.; Reddy, Kaalak; Halachev, Mihail; McGlasson, Sarah; Reijns, Martin A. M.; Fluteau, Adeline; Martin, Carol-Anne; Sabbioneda, Simone; Elcioglu, Nursel H.; Altmüller, Janine; Thiele, Holger; Greenhalgh, Lynn; Chessa, Luciana; Maghnie, Mohamad; Salim, Mahmoud; Bober, Michael B.; Nürnberg, Peter; Jackson, Stephen P.; Hurles, Matthew E.; Wollnik, Bernd; Stewart, Grant S.; Jackson, Andrew P.

2015-01-01

DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism/Seckel syndrome. We establish that TRAIP relocalizes to sites of DNA damage where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to UV irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a novel component of the DNA damage response to replication-blocking DNA lesions. PMID:26595769

A Progressive Damage Methodology for Residual Strength Predictions of Notched Composite Panels

NASA Technical Reports Server (NTRS)

Coats, Timothy W.; Harris, Charles E.

1998-01-01

The translaminate fracture behavior of carbon/epoxy structural laminates with through-penetration notches was investigated to develop a residual strength prediction methodology for composite structures. An experimental characterization of several composite materials systems revealed a fracture resistance behavior that was very similar to the R-curve behavior exhibited by ductile metals. Fractographic examinations led to the postulate that the damage growth resistance was primarily due to fractured fibers in the principal load-carrying plies being bridged by intact fibers of the adjacent plies. The load transfer associated with this bridging mechanism suggests that a progressive damage analysis methodology will be appropriate for predicting the residual strength of laminates with through-penetration notches. A progressive damage methodology developed by the authors was used to predict the initiation and growth of matrix cracks and fiber fracture. Most of the residual strength predictions for different panel widths, notch lengths, and material systems were within about 10% of the experimental failure loads.

Progressive Fracture of Composite Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon

2001-01-01

This report includes the results of a research in which the COmposite Durability STRuctural ANalysis (CODSTRAN) computational simulation capabilities were augmented and applied to various structures for demonstration of the new features and verification. The first chapter of this report provides an introduction to the computational simulation or virtual laboratory approach for the assessment of damage and fracture progression characteristics in composite structures. The second chapter outlines the details of the overall methodology used, including the failure criteria and the incremental/iterative loading procedure with the definitions of damage, fracture, and equilibrium states. The subsequent chapters each contain an augmented feature of the code and/or demonstration examples. All but one of the presented examples contains laminated composite structures with various fiber/matrix constituents. For each structure simulated, damage initiation and progression mechanisms are identified and the structural damage tolerance is quantified at various degradation stages. Many chapters contain the simulation of defective and defect free structures to evaluate the effects of existing defects on structural durability.

Fault Damage Zone Permeability in Crystalline Rocks from Combined Field and Laboratory Measurements: Can we Predict Damage Zone Permeability?

NASA Astrophysics Data System (ADS)

Mitchell, T. M.; Faulkner, D. R.

2009-04-01

Models predicting crustal fluid flow are important for a variety of reasons; for example earthquake models invoking fluid triggering, predicting crustal strength modelling flow surrounding deep waste repositories or the recovery of natural resources. Crustal fluid flow is controlled by both the bulk transport properties of rocks as well as heterogeneities such as faults. In nature, permeability is enhanced in the damage zone of faults, where fracturing occurs on a wide range of scales. Here we analyze the contribution of microfracture damage on the permeability of faults that cut through low porosity, crystalline rocks by combining field and laboratory measurements. Microfracture densities surrounding strike-slip faults with well-constrained displacements ranging over 3 orders of magnitude (~0.12 m - 5000 m) have been analyzed. The faults studied are excellently exposed within the Atacama Fault Zone, where exhumation from 6-10 km has occurred. Microfractures in the form of fluid inclusion planes (FIPs) show a log-linear decrease in fracture density with perpendicular distance from the fault core. Damage zone widths defined by the density of FIPs scale with fault displacement, and an empirical relationship for microfracture density distribution throughout the damage zone with displacement is derived. Damage zone rocks will have experienced differential stresses that were less than, but some proportion of, the failure stress. As such, permeability data from progressively loaded, initially intact laboratory samples, in the pre-failure region provide useful insights into fluid flow properties of various parts of the damage zone. The permeability evolution of initially intact crystalline rocks under increasing differential load leading to macroscopic failure was determined at water pore pressures of 50 MPa and effective pressure of 10 MPa. Permeability is seen to increase by up to, and over, two orders of magnitude prior to macroscopic failure. Further experiments were stopped at various points in the loading history in order to correlate microfracture density within the samples with permeability. By combining empirical relationships determined from both quantitative fieldwork and experiments we present a new model that allows microfracture permeability distribution throughout the damage zone to be determined as function of increasing fault displacement.

Transcription factor Nrf2 hyperactivation in early-phase renal ischemia-reperfusion injury prevents tubular damage progression.

PubMed

Nezu, Masahiro; Souma, Tomokazu; Yu, Lei; Suzuki, Takafumi; Saigusa, Daisuke; Ito, Sadayoshi; Suzuki, Norio; Yamamoto, Masayuki

2017-02-01

Acute kidney injury is a devastating disease with high morbidity in hospitalized patients and contributes to the pathogenesis of chronic kidney disease. An underlying mechanism of acute kidney injury involves ischemia-reperfusion injury which, in turn, induces oxidative stress and provokes organ damage. Nrf2 is a master transcription factor that regulates the cellular response to oxidative stress. Here, we examined the role of Nrf2 in the progression of ischemia-reperfusion injury-induced kidney damage in mice using genetic and pharmacological approaches. Both global and tubular-specific Nrf2 activation enhanced gene expression of antioxidant and NADPH synthesis enzymes, including glucose-6-phosphate dehydrogenase, and ameliorated both the initiation of injury in the outer medulla and the progression of tubular damage in the cortex. Myeloid-specific Nrf2 activation was ineffective. Short-term administration of the Nrf2 inducer CDDO during the initial phase of injury ameliorated the late phase of tubular damage. This inducer effectively protected the human proximal tubular cell line HK-2 from oxidative stress-mediated cell death while glucose-6-phosphate dehydrogenase knockdown increased intracellular reactive oxygen species. These findings demonstrate that tubular hyperactivation of Nrf2 in the initial phase of injury prevents the progression of reactive oxygen species-mediated tubular damage by inducing antioxidant enzymes and NADPH synthesis. Thus, Nrf2 may be a promising therapeutic target for preventing acute kidney injury to chronic kidney disease transition. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Fatigue Analysis of Notched Laminates: A Time-Efficient Macro-Mechanical Approach

NASA Technical Reports Server (NTRS)

Naghipour, P.; Pineda, E. J.; Bednarcyk, B. A.; Arnold, S. M.; Waas, A. M.

2016-01-01

A coupled transversely isotropic deformation and damage fatigue model is implemented within the finite element method and was utilized along with a static progressive damage model to predict the fatigue life, stiffness degradation as a function of number of cycles, and post-fatigue tension and compression response of notched, multidirectional laminates. Initially, the material parameters for the fatigue model were obtained utilizing micromechanics simulations and the provided [0], [90] and [plus or minus 45] experimental composite laminate S-N (stress-cycle) data. Within the fatigue damage model, the transverse and shear properties of the plies were degraded with an isotropic scalar damage variable. The damage in the longitudinal (fiber) ply direction was suppressed, and only the strength of the fiber was degraded as a function of fatigue cycles. A maximum strain criterion was used to capture the failure in each element, and once this criterion was satisfied, the longitudinal stiffness of the element was decreased by a factor of 10 (sup 4). The resulting, degraded properties were then used to calculate the new stress state. This procedure was repeated until final failure of the composite laminate was achieved or a specified number of cycles reached. For post-fatigue tension and compression behavior, four internal state variables were used to control the damage and failure. The predictive capability of the above-mentioned approach was assessed by performing blind predictions of the notched multidirectional IM7/977-3 composite laminates response under fatigue and post-fatigue tensile and compressive loading, followed by a recalibration phase. Although three different multidirectional laminates were analyzed in the course of this study, only detailed results (i.e., stiffness degradation and post-fatigue stress-train curves as well as damage evolution states for a single laminate ([30/60/90/minus 30/minus 60] (sub 2s)) are discussed in detail here.

Risk Factors and Predictors of Significant Chondral Surface Change From Primary to Revision Anterior Cruciate Ligament Reconstruction: A MOON and MARS Cohort Study.

PubMed

Magnussen, Robert A; Borchers, James R; Pedroza, Angela D; Huston, Laura J; Haas, Amanda K; Spindler, Kurt P; Wright, Rick W; Kaeding, Christopher C; Allen, Christina R; Anderson, Allen F; Cooper, Daniel E; DeBerardino, Thomas M; Dunn, Warren R; Lantz, Brett A; Mann, Barton; Stuart, Michael J; Albright, John P; Amendola, Annunziato; Andrish, Jack T; Annunziata, Christopher C; Arciero, Robert A; Bach, Bernard R; Baker, Champ L; Bartolozzi, Arthur R; Baumgarten, Keith M; Bechler, Jeffery R; Berg, Jeffrey H; Bernas, Geoffrey A; Brockmeier, Stephen F; Brophy, Robert H; Bush-Joseph, Charles A; Butler, J Brad; Campbell, John D; Carey, James L; Carpenter, James E; Cole, Brian J; Cooper, Jonathan M; Cox, Charles L; Creighton, R Alexander; Dahm, Diane L; David, Tal S; Flanigan, David C; Frederick, Robert W; Ganley, Theodore J; Garofoli, Elizabeth A; Gatt, Charles J; Gecha, Steven R; Giffin, James Robert; Hame, Sharon L; Hannafin, Jo A; Harner, Christopher D; Harris, Norman Lindsay; Hechtman, Keith S; Hershman, Elliott B; Hoellrich, Rudolf G; Hosea, Timothy M; Johnson, David C; Johnson, Timothy S; Jones, Morgan H; Kamath, Ganesh V; Klootwyk, Thomas E; Levy, Bruce A; Ma, C Benjamin; Maiers, G Peter; Marx, Robert G; Matava, Matthew J; Mathien, Gregory M; McAllister, David R; McCarty, Eric C; McCormack, Robert G; Miller, Bruce S; Nissen, Carl W; O'Neill, Daniel F; Owens, Brett D; Parker, Richard D; Purnell, Mark L; Ramappa, Arun J; Rauh, Michael A; Rettig, Arthur C; Sekiya, Jon K; Shea, Kevin G; Sherman, Orrin H; Slauterbeck, James R; Smith, Matthew V; Spang, Jeffrey T; Svoboda, Steven J; Taft, Timothy N; Tenuta, Joachim J; Tingstad, Edwin M; Vidal, Armando F; Viskontas, Darius G; White, Richard A; Williams, James S; Wolcott, Michelle L; Wolf, Brian R; York, James J

2018-03-01

Articular cartilage health is an important issue following anterior cruciate ligament (ACL) injury and primary ACL reconstruction. Factors present at the time of primary ACL reconstruction may influence the subsequent progression of articular cartilage damage. Larger meniscus resection at primary ACL reconstruction, increased patient age, and increased body mass index (BMI) are associated with increased odds of worsened articular cartilage damage at the time of revision ACL reconstruction. Case-control study; Level of evidence, 3. Subjects who had primary and revision data in the databases of the Multicenter Orthopaedics Outcomes Network (MOON) and Multicenter ACL Revision Study (MARS) were included. Reviewed data included chondral surface status at the time of primary and revision surgery, meniscus status at the time of primary reconstruction, primary reconstruction graft type, time from primary to revision ACL surgery, as well as demographics and Marx activity score at the time of revision. Significant progression of articular cartilage damage was defined in each compartment according to progression on the modified Outerbridge scale (increase ≥1 grade) or >25% enlargement in any area of damage. Logistic regression identified predictors of significant chondral surface change in each compartment from primary to revision surgery. A total of 134 patients were included, with a median age of 19.5 years at revision surgery. Progression of articular cartilage damage was noted in 34 patients (25.4%) in the lateral compartment, 32 (23.9%) in the medial compartment, and 31 (23.1%) in the patellofemoral compartment. For the lateral compartment, patients who had >33% of the lateral meniscus excised at primary reconstruction had 16.9-times greater odds of progression of articular cartilage injury than those with an intact lateral meniscus ( P < .001). For the medial compartment, patients who had <33% of the medial meniscus excised at the time of the primary reconstruction had 4.8-times greater odds of progression of articular cartilage injury than those with an intact medial meniscus ( P = .02). Odds of significant chondral surface change increased by 5% in the lateral compartment and 6% in the medial compartment for each increased year of age ( P ≤ .02). For the patellofemoral compartment, the use of allograft in primary reconstruction was associated with a 15-fold increased odds of progression of articular cartilage damage relative to a patellar tendon autograft ( P < .001). Each 1-unit increase in BMI at the time of revision surgery was associated with a 10% increase in the odds of progression of articular cartilage damage ( P = .046) in the patellofemoral compartment. Excision of the medial and lateral meniscus at primary ACL reconstruction increases the odds of articular cartilage damage in the corresponding compartment at the time of revision ACL reconstruction. Increased age is a risk factor for deterioration of articular cartilage in both tibiofemoral compartments, while increased BMI and the use of allograft for primary ACL reconstruction are associated with an increased risk of progression in the patellofemoral compartment.

Deep particle bed dryout model based on flooding

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

Kuan, P.

1987-01-01

Examination of the damaged Three Mile island Unit 2 (TMI-2) reactor indicates that a deep (approx. 1-m) bed of relatively large (approx. 1-mm) particles was formed in the core. Cooling of such beds is crucial to the arrest of core damage progression. The Lipinski model, based on flows in the bed, has been used to predict the coolability, but uncertainties exist in the turbulent permeability. Models based on flooding at the top of the bed either have a dimensional viscosity term, or no viscosity dependence, thus limiting their applicability. This paper presents a dimensionless correlation based on flooding data thatmore » involves a liquid Reynolds number. The derived dryout model from this correlation is compared with data for deep beds of large particles at atmospheric pressure, and with other models over a wide pressure range. It is concluded that the present model can give quite accurate predictions for the dryout heat flux of particle beds formed during a light water reactor accident and it is easy to use and agrees with the Lipinski n = 5 model, which requires iterative calculations.« less

Real time acousto-ultrasonic NDE technique for monitoring damage in ceramic composites under dynamic loads

NASA Technical Reports Server (NTRS)

Tiwari, Anil

1995-01-01

Research effort was directed towards developing a near real-time, acousto-ultrasonic (AU), nondestructive evaluation (NDE) tool to study the failure mechanisms of ceramic composites. Progression of damage is monitored in real-time by observing the changes in the received AU signal during the actual test. During the real-time AU test, the AU signals are generated and received by the AU transducers attached to the specimen while it is being subjected to increasing quasi-static loads or cyclic loads (10 Hz, R = 1.0). The received AU signals for 64 successive pulses were gated in the time domain (T = 40.96 micro sec) and then averaged every second over ten load cycles and stored in a computer file during fatigue tests. These averaged gated signals are representative of the damage state of the specimen at that point of its fatigue life. This is also the first major attempt in the development and application of real-time AU for continuously monitoring damage accumulation during fatigue without interrupting the test. The present work has verified the capability of the AU technique to assess the damage state in silicon carbide/calcium aluminosilicate (SiC/CAS) and silicon carbide/ magnesium aluminosilicate (SiC/MAS) ceramic composites. Continuous monitoring of damage initiation and progression under quasi-static ramp loading in tension to failure of unidirectional and cross-ply SiC/CAS and quasi-isotropic SiC/MAS ceramic composite specimens at room temperature was accomplished using near real-time AU parameters. The AU technique was shown to be able to detect the stress levels for the onset and saturation of matrix cracks, respectively. The critical cracking stress level is used as a design stress for brittle matrix composites operating at elevated temperatures. The AU technique has found that the critical cracking stress level is 10-15% below the level presently obtained for design purposes from analytical models. An acousto-ultrasonic stress-strain response (AUSSR) model for unidirectional and cross-ply ceramic composites was formulated. The AUSSR model predicts the strain response to increasing stress levels using real-time AU data and classical laminated plate theory. The Weibull parameters of the AUSSR model are used to calculate the design stress for thermo-structural applications. Real-time AU together with the AUSSR model was used to study the failure mechanisms of SiC/CAS ceramic composites under static and fatigue loading. An S-N curve was generated for a cross-ply SiC/CAS ceramic composite material. The AU results are corroborated and complemented by other NDE techniques, namely, in-situ optical microscope video recordings and edge replication.

Neonatal hypoglycemia.

PubMed

Straussman, Sharon; Levitsky, Lynne L

2010-02-01

Hypoglycemia in the newborn may be associated with both acute decompensation and long-term neuronal loss. Studies of the cause of hypoglycemic brain damage and the relationship of hypoglycemia to disorders associated with hyperinsulinism have aided in our understanding of this common clinical finding. A recent consensus workshop concluded that there has been little progress toward a precise numerical definition of neonatal hypoglycemia. Nonetheless, newer brain imaging modalities have provided insight into the relationship between neuronal energy deficiency and central nervous system damage. Laboratory studies have begun to reveal the mechanism of hypoglycemic damage. In addition, there is new information about hyperinsulinemic hypoglycemia of genetic, environmental, and iatrogenic origin. The quantitative definition of hypoglycemia in the newborn remains elusive because it is a surrogate marker for central nervous system energy deficiency. Nonetheless, the recognition that hyperinsulinemic hypoglycemia, which produces profound central nervous system energy deficiency, is most likely to lead to long-term central nervous system damage, has altered management of children with hypoglycemia. In addition, imaging studies on neonates and laboratory evaluation in animal models have provided insight into the mechanism of neuronal damage.

Neural Regeneration in Caenorhabditis elegans

PubMed Central

El Bejjani, Rachid; Hammarlund, Marc

2013-01-01

Axon regeneration is a medically relevant process that can repair damaged neurons. This review describes current progress in understanding axon regeneration in the model organism Caenorhabditis elegans. Factors that regulate axon regeneration in C. elegans have broadly similar roles in vertebrate neurons. This means that using C. elegans as a tool to leverage discovery is a legitimate strategy for identifying conserved mechanisms of axon regeneration. PMID:22974301

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.

Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice.

PubMed

Ruscitti, Francesca; Ravanetti, Francesca; Essers, Jeroen; Ridwan, Yanto; Belenkov, Sasha; Vos, Wim; Ferreira, Francisca; KleinJan, Alex; van Heijningen, Paula; Van Holsbeke, Cedric; Cacchioli, Antonio; Villetti, Gino; Stellari, Franco Fabio

2017-01-01

The intratracheal instillation of bleomycin in mice induces early damage to alveolar epithelial cells and development of inflammation followed by fibrotic tissue changes and represents the most widely used model of pulmonary fibrosis to investigate human IPF. Histopathology is the gold standard for assessing lung fibrosis in rodents, however it precludes repeated and longitudinal measurements of disease progression and does not provide information on spatial and temporal distribution of tissue damage. Here we investigated the use of the Micro-CT technique to allow the evaluation of disease onset and progression at different time-points in the mouse bleomycin model of lung fibrosis. Micro-CT was throughout coupled with histological analysis for the validation of the imaging results. In bleomycin-instilled and control mice, airways and lung morphology changes were assessed and reconstructed at baseline, 7, 14 and 21 days post-treatment based on Micro-CT images. Ashcroft score, percentage of collagen content and percentage of alveolar air area were detected on lung slides processed by histology and subsequently compared with Micro-CT parameters. Extent (%) of fibrosis measured by Micro-CT correlated with Ashcroft score, the percentage of collagen content and the percentage of alveolar air area ( r 2  = 0.91; 0.77; 0.94, respectively). Distal airway radius also correlated with the Ashcroft score, the collagen content and alveolar air area percentage ( r 2  = 0.89; 0.78; 0.98, respectively). Micro-CT data were in good agreement with histological read-outs as micro-CT was able to quantify effectively and non-invasively disease progression longitudinally and to reduce the variability and number of animals used to assess the damage. This suggests that this technique is a powerful tool for understanding experimental pulmonary fibrosis and that its use could translate into a more efficient drug discovery process, also helping to fill the gap between preclinical setting and clinical practice.

Evaluation of a Region-of-Interest Approach for Detecting Progressive Glaucomatous Macular Damage on Optical Coherence Tomography.

PubMed

Wu, Zhichao; Weng, Denis S D; Thenappan, Abinaya; Ritch, Robert; Hood, Donald C

2018-04-01

To evaluate a manual region-of-interest (ROI) approach for detecting progressive macular ganglion cell complex (GCC) changes on optical coherence tomography (OCT) imaging. One hundred forty-six eyes with a clinical diagnosis of glaucoma or suspected glaucoma with macular OCT scans obtained at least 1 year apart were evaluated. Changes in the GCC thickness were identified using a manual ROI approach (ROI M ), whereby region(s) of observed or suspected glaucomatous damage were manually identified when using key features from the macular OCT scan on the second visit. Progression was also evaluated using the global GCC thickness and an automatic ROI approach (ROI A ), where contiguous region(s) that fell below the 1% lower normative limit and exceeded 288 μm 2 in size were evaluated. Longitudinal signal-to-noise ratios (SNRs) were calculated for progressive changes detected by each of these methods using individualized estimates of test-retest variability and age-related changes, obtained from 303 glaucoma and 394 healthy eyes, respectively. On average, the longitudinal SNR for the global thickness, ROI A and ROI M methods were -0.90 y -1 , -0.91 y -1 , and -1.03 y -1 , respectively, and was significantly more negative for the ROI M compared with the global thickness ( P = 0.003) and ROI A methods ( P = 0.021). Progressive glaucomatous macular GCC changes were optimally detected with a manual ROI approach. These findings suggests that an approach based on a qualitative evaluation of OCT imaging information and consideration of known patterns of damage can improve the detection of progressive glaucomatous macular damage.

Accelerated Aging Experiments for Prognostics of Damage Growth in Composite Materials

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Goebel, Kai Frank; Larrosa, Cecilia C.; Janapati, Vishnuvardhan; Roy, Surajit; Chang, Fu-Kuo

2011-01-01

Composite structures are gaining importance for use in the aerospace industry. Compared to metallic structures their behavior is less well understood. This lack of understanding may pose constraints on their use. One possible way to deal with some of the risks associated with potential failure is to perform in-situ monitoring to detect precursors of failures. Prognostic algorithms can be used to predict impending failures. They require large amounts of training data to build and tune damage model for making useful predictions. One of the key aspects is to get confirmatory feedback from data as damage progresses. These kinds of data are rarely available from actual systems. The next possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to stress carbon-carbon composite coupons with various layups. Piezoelectric disc sensors were used to periodically interrogate the system. Analysis showed distinct differences in the signatures of growing failures between data collected at conditions. Periodic X-radiographs were taken to assess the damage ground truth. Results after signal processing showed clear trends of damage growth that were correlated to damage assessed from the X-ray images.

Response of Honeycomb Core Sandwich Panel with Minimum Gage GFRP Face-Sheets to Compression Loading After Impact

NASA Technical Reports Server (NTRS)

McQuigg, Thomas D.; Kapania, Rakesh K.; Scotti, Stephen J.; Walker, Sandra P.

2011-01-01

A compression after impact study has been conducted to determine the residual strength of three sandwich panel constructions with two types of thin glass fiber reinforced polymer face-sheets and two hexagonal honeycomb Nomex core densities. Impact testing is conducted to first determine the characteristics of damage resulting from various impact energy levels. Two modes of failure are found during compression after impact tests with the density of the core precipitating the failure mode present for a given specimen. A finite element analysis is presented for prediction of the residual compressive strength of the impacted specimens. The analysis includes progressive damage modeling in the face-sheets. Preliminary analysis results were similar to the experimental results; however, a higher fidelity core material model is expected to improve the correlation.

Vitamin E Supplementation Reduces Cellular Loss in the Brain of a Premature Aging Mouse Model.

PubMed

La Fata, G; van Vliet, N; Barnhoorn, S; Brandt, R M C; Etheve, S; Chenal, E; Grunenwald, C; Seifert, N; Weber, P; Hoeijmakers, J H J; Mohajeri, M H; Vermeij, W P

2017-01-01

Aging is a highly complex biological process driven by multiple factors. Its progression can partially be influenced by nutritional interventions. Vitamin E is a lipid-soluble anti-oxidant that is investigated as nutritional supplement for its ability to prevent or delay the onset of specific aging pathologies, including neurodegenerative disorders. We aimed here to investigate the effect of vitamin E during aging progression in a well characterized mouse model for premature aging. Xpg-/- animals received diets with low (~2.5 mg/kg feed), medium (75 mg/kg feed) or high (375 mg/kg feed) vitamin E concentration and their phenotype was monitored during aging progression. Vitamin E content was analyzed in the feed, for stability reasons, and in mouse plasma, brain, and liver, for effectiveness of the treatment. Subsequent age-related changes were monitored for improvement by increased vitamin E or worsening by depletion in both liver and nervous system, organs sensitive to oxidative stress. Mice supplemented with high levels of vitamin E showed a delayed onset of age-related body weight decline and appearance of tremors when compared to mice with a low dietary vitamin E intake. DNA damage resulting in liver abnormalities such as changes in polyploidy, was considerably prevented by elevated amounts of vitamin E. Additionally, immunohistochemical analyses revealed that high intake of vitamin E, when compared with low and medium levels of vitamin E in the diet, reduces the number of p53-positive cells throughout the brain, indicative of a lower number of cells dying due to DNA damage accumulated over time. Our data underline a neuroprotective role of vitamin E in the premature aging animal model used in this study, likely via a reduction of oxidative stress, and implies the importance of improved nutrition to sustain health.

Frontal lobe damage impairs process and content in semantic memory: evidence from category-specific effects in progressive non-fluent aphasia.

PubMed

Reilly, Jamie; Rodriguez, Amy D; Peelle, Jonathan E; Grossman, Murray

2011-06-01

Portions of left inferior frontal cortex have been linked to semantic memory both in terms of the content of conceptual representation (e.g., motor aspects in an embodied semantics framework) and the cognitive processes used to access these representations (e.g., response selection). Progressive non-fluent aphasia (PNFA) is a neurodegenerative condition characterized by progressive atrophy of left inferior frontal cortex. PNFA can, therefore, provide a lesion model for examining the impact of frontal lobe damage on semantic processing and content. In the current study we examined picture naming in a cohort of PNFA patients across a variety of semantic categories. An embodied approach to semantic memory holds that sensorimotor features such as self-initiated action may assume differential importance for the representation of manufactured artifacts (e.g., naming hand tools). Embodiment theories might therefore predict that patients with frontal damage would be differentially impaired on manufactured artifacts relative to natural kinds, and this prediction was borne out. We also examined patterns of naming errors across a wide range of semantic categories and found that naming error distributions were heterogeneous. Although PNFA patients performed worse overall on naming manufactured artifacts, there was no reliable relationship between anomia and manipulability across semantic categories. These results add to a growing body of research arguing against a purely sensorimotor account of semantic memory, suggesting instead a more nuanced balance of process and content in how the brain represents conceptual knowledge. Copyright © 2010 Elsevier Srl. All rights reserved.

Micromechanical simulation of damage progression in carbon phenolic composites

NASA Technical Reports Server (NTRS)

Slattery, Kerry T.

1993-01-01

Carbon/phenolic composites are used extensively as ablative insulating materials in the nozzle region of solid rocket motors. The current solid rocket motor (RSRM) on the space shuttle is fabricated from woven rayon cloth which is carbonized and then impregnated with the phenolic resin. These plies are layed up in the desired configuration and cured to form the finished part. During firing, the surface of the carbon/phenolic insulation is exposed to 5000 F gases from the rocket exhaust. The resin pyrolizes and the material chars to a depth which progresses with time. The rate of charring and erosion are generally predictable, and the insulation depth is designed to allow adequate safety margins over the firing time of the motor. However, anomalies in the properties and response of the carbon/phenolic materials can lead to severe material damage which may decrease safety margins to unacceptable levels. Three macro damage modes which were observed in fired nozzles are: ply lift, 'wedge out', and pocketing erosion. Ply lift occurs in materials with plies oriented nearly parallel to the surface. The damage occurs in a region below the charred material where material temperatures are relatively low - about 500 F. Wedge out occurs at the intersection of nozzle components whose plies are oriented at about 45 deg. The corner of the block of material breaks off along a ply interface. Pocketing erosion occurs in material with plies oriented normal to the surface. Thermal expansion is restrained in two directions resulting in large tensile strains and material failure normal to the surface. When a large section of material is removed as a result of damage, the insulation thickness is reduced which may lead to failure of the nozzle due to excessive heating of critical components. If these damage events cannot be prevented with certainty, the designer must increase the thickness of the insulator thus adding to both weight and cost. One of the difficulties in developing a full understanding of these macro damage mechanisms is that the loading environment and the material response to that environment are extremely complex. These types of damage are usually only observed in actual motor firings. Therefore, it is difficult and expensive to evaluate the reliability of new materials. Standard material tests which measure mechanical and thermal properties of test specimens can only provide a partial picture of how the material will respond in the service environment. The development of the ANALOG test procedure which can combine high heating rates and mechanical loads on a specimen will improve the understanding of the interactive effects of the various loads on the system. But a mechanistic model of material response which can account for the heterogeneity of the material, the progression of various micromechanical damage mechanisms, and the interaction of mechanical and thermal stresses on the material is required to accurately correlate material tests with response to service environments. A model based on fundamental damage mechanisms which is calibrated and verified under a variety of loading conditions will provide a general tool for predicting the response of rocket nozzles. The development of a micromechanical simulation technique was initiated and demonstrated to be effective for studying across-ply tensile failure of carbon/phenolic composites.

Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE.

PubMed

Tak, Paul P; Rigby, William; Rubbert-Roth, Andrea; Peterfy, Charles; van Vollenhoven, Ronald F; Stohl, William; Healy, Emma; Hessey, Eva; Reynard, Mark; Shaw, Tim

2012-03-01

In the IMAGEstudy, rituximab plus methotrexate (MTX) inhibited joint damage and improved clinical outcomes at 1 year in MTX-naïve patients with early active rheumatoid arthritis. The aim of this study was to assess joint damage progression and clinical outcomes over 2 years. Patients (n=755) were randomised to receive rituximab 2×500 mg+MTX, 2×1000 mg+MTX or placebo+MTX. The placebo-controlled period continued to week 104. Two-year end points were defined as secondary or exploratory and included change in total Genant-modified Sharp score (mTSS), total erosion score and joint space narrowing score from baseline to week 104. Clinical efficacy and physical function end points were also assessed. At 2 years, rituximab 2×1000 mg+MTX maintained inhibition of progressive joint damage versus MTX alone (mTSS change 0.41 vs 1.95; p<0.0001 (79% inhibition)), and a higher proportion of patients receiving rituximab 2×1000 mg+MTX had no radiographic progression over 2 years compared with those receiving MTX alone (57% vs 37%; p<0.0001). Contrary to 1-year results, exploratory analysis of rituximab 2×500 mg+MTX at 2 years showed that progressive joint damage was slowed by ∼61% versus placebo+MTX (mTSS, exploratory p=0.0041). Improvements in clinical signs and symptoms and physical function seen after 1 year in rituximab-treated patients versus those receiving placebo were maintained at year 2. Safety profiles were similar between groups. Treatment with rituximab 2×1000 mg+MTX was associated with sustained improvements in radiographic, clinical and functional outcomes over 2 years. Clinical trials.gov identifier NCT00299104.

[Progressive damage monitoring of corrugated composite skins by the FBG spectral characteristics].

PubMed

Zhang, Yong; Wang, Bang-Feng; Lu, Ji-Yun; Gu, Li-Li; Su, Yong-Gang

2014-03-01

In the present paper, a method of monitoring progressive damage of composite structures by non-uniform fiber Bragg grating (FBG) reflection spectrum is proposed. Due to the finite element analysis of corrugated composite skins specimens, the failure process under tensile load and corresponding critical failure loads of corrugated composite skin was predicated. Then, the non-uniform reflection spectrum of FBG sensor could be reconstructed and the corresponding relationship between layer failure order sequence of corrugated composite skin and FBG sensor reflection spectrums was acquired. A monitoring system based on FBG non-uniform reflection spectrum, which can be used to monitor progressive damage of corrugated composite skins, was built. The corrugated composite skins were stretched under this FBG non-uniform reflection spectrum monitoring system. The results indicate that real-time spectrums acquired by FBG non-uniform reflection spectrum monitoring system show the same trend with the reconstruction reflection spectrums. The maximum error between the corresponding failure and the predictive value is 8.6%, which proves the feasibility of using FBG sensor to monitor progressive damage of corrugated composite skin. In this method, the real-time changes in the FBG non-uniform reflection spectrum within the scope of failure were acquired through the way of monitoring and predicating, and at the same time, the progressive damage extent and layer failure sequence of corru- gated composite skin was estimated, and without destroying the structure of the specimen, the method is easy and simple to operate. The measurement and transmission section of the system are completely composed of optical fiber, which provides new ideas and experimental reference for the field of dynamic monitoring of smart skin.

Progressive paralysis associated with diffuse astrocyte anaplasia in delta 202 mice homozygous for a transgene encoding the SV40 T antigen.

PubMed

López-Revilla, Rubén; Soto-Zárate, Carlos; Ridaura, Cecilia; Chávez-Dueñas, Lucía; Paul, Dieter

2004-03-01

A convenient transgenic astrocytoma model in delta202 mice, homozygous for a construct encoding the early region of the SV40 virus genome, is described. In the offspring of crosses between delta202 mice heterozygous for the transgene nearly 60% were transgenic; one third of these developed progressive paralysis starting in the hindlimbs at approximately 35 days of age and died at 90 +/- 30 days of age. In affected mice proliferating-non-neuronal cells immunostained with antibodies to the GFAP, an astrocyte marker, whose number increased with age were found in the white matter of the brain, cerebellum and spinal cord, and progressive degeneration and necrosis of spinal motoneurons was observed that-may explain the paralysis. The early onset and reproducible time course of the neurological disease suggest that homozygous delta202 mice, whose proliferating astrocytes appear to damage spinal motoneurons, are a useful model to study astrocyte differentiation, function and tumorigenesis.

An Irreversible Constitutive Law for Modeling the Delamination Process using Interface Elements

NASA Technical Reports Server (NTRS)

Goyal, Vinay K.; Johnson, Eric R.; Davila, Carlos G.; Jaunky, Navin; Ambur, Damodar (Technical Monitor)

2002-01-01

An irreversible constitutive law is postulated for the formulation of interface elements to predict initiation and progression of delamination in composite structures. An exponential function is used for the constitutive law such that it satisfies a multi-axial stress criterion for the onset of delamination, and satisfies a mixed mode fracture criterion for the progression of delamination. A damage parameter is included to prevent the restoration of the previous cohesive state between the interfacial surfaces. To demonstrate the irreversibility capability of the constitutive law, steady-state crack growth is simulated for quasi-static loading-unloading cycle of various fracture test specimens.

An Irreversible Constitutive Law for Modeling the Delamination Process Using Interface Elements

NASA Technical Reports Server (NTRS)

Goyal, Vinay K.; Johnson, Eric R.; Davila, Carlos G.; Jaunky, Navin; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

An irreversible constitutive law is postulated for the formulation of interface elements to predict initiation and progression of delamination in composite structures. An exponential function is used for the constitutive law such that it satisfies a multi-axial stress criterion for the onset of delamination, and satisfies a mixed mode fracture criterion for the progression of delamination. A damage parameter is included to prevent the restoration of the previous cohesive state between the interfacial surfaces. To demonstrate the irreversibility capability of the constitutive law, steady-state crack growth is simulated for quasi-static loading-unloading cycle of various fracture test specimens.

Ice bridges and ridges in the Maxwell-EB sea ice rheology

NASA Astrophysics Data System (ADS)

Dansereau, Véronique; Weiss, Jérôme; Saramito, Pierre; Lattes, Philippe; Coche, Edmond

2017-09-01

This paper presents a first implementation of a new rheological model for sea ice on geophysical scales. This continuum model, called Maxwell elasto-brittle (Maxwell-EB), is based on a Maxwell constitutive law, a progressive damage mechanism that is coupled to both the elastic modulus and apparent viscosity of the ice cover and a Mohr-Coulomb damage criterion that allows for pure (uniaxial and biaxial) tensile strength. The model is tested on the basis of its capability to reproduce the complex mechanical and dynamical behaviour of sea ice drifting through a narrow passage. Idealized as well as realistic simulations of the flow of ice through Nares Strait are presented. These demonstrate that the model reproduces the formation of stable ice bridges as well as the stoppage of the flow, a phenomenon occurring within numerous channels of the Arctic. In agreement with observations, the model captures the propagation of damage along narrow arch-like kinematic features, the discontinuities in the velocity field across these features dividing the ice cover into floes, the strong spatial localization of the thickest, ridged ice, the presence of landfast ice in bays and fjords and the opening of polynyas downstream of the strait. The model represents various dynamical behaviours linked to an overall weakening of the ice cover and to the shorter lifespan of ice bridges, with implications in terms of increased ice export through narrow outflow pathways of the Arctic.

Assessment of impact damage of composite rocket motor cases

NASA Technical Reports Server (NTRS)

Paris, Henry G.

1994-01-01

This contract reviewed the available literature on mechanisms of low velocity impact damage in filament wound rocket motor cases, MDE methods to quantify damage, critical coupon level test methods, manufacturing and material process variables and empirical and analytical modeling off impact damage. The critical design properties for rocket motor cases are biaxial hoop and axial tensile strength. Low velocity impact damage is insidious because it can create serious nonvisible damage at very low impact velocities. In thick rocket motor cases the prevalent low velocity impact damage is fiber fracture and matrix cracking adjacent to the front face. In contrast, low velocity loading of thin wall cylinders induces flexure, depending on span length and the flexure induces delamination and tensile cracking on the back face wall opposed to impact occurs due to flexural stresses imposed by impact loading. Important NDE methods for rocket motor cases are non-contacting methods that allow inspection from one side. Among these are vibrothermography, and pulse-echo methods based on acoustic-ultrasonic methods. High resolution techniques such as x-ray computed tomography appear to have merit for accurate geometrical characterization of local damage to support development of analytical models of micromechanics. The challenge of coupon level testing is to reproduce the biaxial stress state that the full scale article experiences, and to determine how to scale the composite structure to model full sized behavior. Biaxial tensile testing has been performed by uniaxially tensile loading internally pressurized cylinders. This is experimentally difficult due to gripping problems and pressure containment. Much prior work focused on uniaxial tensile testing of model filament wound cylinders. Interpretation of the results of some studies is complicated by the fact that the fabrication process did not duplicate full scale manufacturing. It is difficult to scale results from testing subscale cylinders since there are significant differences in out time of the resins relative to full scale cylinder fabrication, differences in hoop fiber tensioning and unsatisfactory coupon configurations. It appears that development of a new test method for subscale cylinders is merited. Damage tolerance may be improved by material optimization that uses fiber treatments and matrix modifications to control the fiber matrix interface bonding. It is difficult to develop process optimization in subscale cylinders without also modeling the longer out times resins experience in full scale testing. A major breakthrough in characterizing the effect of impact damage on residual strength, and understanding how to scale results of subscale evaluations, will be a sound micromechanical model that described progressive failure of the composite. Such models will utilize a three dimensional stress analysis due to the complex nature of low velocity impact stresses in thick composites. When these models are coupled with non-contact NDE methods that geometrically characterize the damage and acoustic methods that characterize the effective local elastic properties, accurate assessment of residual strength from impact damage may be possible. Directions for further development are suggested.

Assessment of impact damage of composite rocket motor cases

NASA Astrophysics Data System (ADS)

Paris, Henry G.

1994-02-01

This contract reviewed the available literature on mechanisms of low velocity impact damage in filament wound rocket motor cases, MDE methods to quantify damage, critical coupon level test methods, manufacturing and material process variables and empirical and analytical modeling off impact damage. The critical design properties for rocket motor cases are biaxial hoop and axial tensile strength. Low velocity impact damage is insidious because it can create serious nonvisible damage at very low impact velocities. In thick rocket motor cases the prevalent low velocity impact damage is fiber fracture and matrix cracking adjacent to the front face. In contrast, low velocity loading of thin wall cylinders induces flexure, depending on span length and the flexure induces delamination and tensile cracking on the back face wall opposed to impact occurs due to flexural stresses imposed by impact loading. Important NDE methods for rocket motor cases are non-contacting methods that allow inspection from one side. Among these are vibrothermography, and pulse-echo methods based on acoustic-ultrasonic methods. High resolution techniques such as x-ray computed tomography appear to have merit for accurate geometrical characterization of local damage to support development of analytical models of micromechanics. The challenge of coupon level testing is to reproduce the biaxial stress state that the full scale article experiences, and to determine how to scale the composite structure to model full sized behavior. Biaxial tensile testing has been performed by uniaxially tensile loading internally pressurized cylinders. This is experimentally difficult due to gripping problems and pressure containment. Much prior work focused on uniaxial tensile testing of model filament wound cylinders. Interpretation of the results of some studies is complicated by the fact that the fabrication process did not duplicate full scale manufacturing. It is difficult to scale results from testing subscale cylinders since there are significant differences in out time of the resins relative to full scale cylinder fabrication, differences in hoop fiber tensioning and unsatisfactory coupon configurations. It appears that development of a new test method for subscale cylinders is merited. Damage tolerance may be improved by material optimization that uses fiber treatments and matrix modifications to control the fiber matrix interface bonding. It is difficult to develop process optimization in subscale cylinders without also modeling the longer out times resins experience in full scale testing. A major breakthrough in characterizing the effect of impact damage on residual strength, and understanding how to scale results of subscale evaluations, will be a sound micromechanical model that described progressive failure of the composite.

Response and representation of ductile damage under varying shock loading conditions in tantalum

DOE PAGES

Bronkhorst, C. A.; Gray, III, G. T.; Addessio, F. L.; ...

2016-02-25

The response of polycrystalline metals, which possess adequate mechanisms for plastic deformation under extreme loading conditions, is often accompanied by the formation of pores within the structure of the material. This large deformation process is broadly identified as progressive with nucleation, growth, coalescence, and failure the physical path taken over very short periods of time. These are well known to be complex processes strongly influenced by microstructure, loading path, and the loading profile, which remains a significant challenge to represent and predict numerically. In the current study, the influence of loading path on the damage evolution in high-purity tantalum ismore » presented. Tantalum samples were shock loaded to three different peak shock stresses using both symmetric impact, and two different composite flyer plate configurations such that upon unloading the three samples displayed nearly identical “pull-back” signals as measured via rear-surface velocimetry. While the “pull-back” signals observed were found to be similar in magnitude, the sample loaded to the highest peak stress nucleated a connected field of ductile fracture which resulted in complete separation, while the two lower peak stresses resulted in incipient damage. The damage evolution in the “soft” recovered tantalum samples was quantified using optical metallography, electron-back-scatter diffraction, and tomography. These experiments are examined numerically through the use of a model for shock-induced porosity evolution during damage. The model is shown to describe the response of the tantalum reasonably well under strongly loaded conditions but less well in the nucleation dominated regime. As a result, numerical results are also presented as a function of computational mesh density and discussed in the context of improved representation of the influence of material structure upon macro-scale models of ductile damage.« less

Interleukin-22 drives nitric oxide-dependent DNA damage and dysplasia in a murine model of colitis-associated cancer

PubMed Central

Sheh, A; Muthupalani, S; Bryant, EM; Puglisi, DA; Holcombe, H; Conaway, EA; Parry, NAP; Bakthavatchalu, V; Short, SP; Williams, CS; Wogan, GN; Tannenbaum, SR; Fox, JG; Horwitz, BH

2017-01-01

The risk of colon cancer is increased in patients with Crohn's disease and ulcerative colitis. Inflammation-induced DNA damage could be an important link between inflammation and cancer, although the pathways that link inflammation and DNA damage are incompletely defined. RAG2-deficient mice infected with Helicobacter hepaticus (Hh) develop colitis that progresses to lower bowel cancer. This process depends on nitric oxide (NO), a molecule with known mutagenic potential. We have previously hypothesized that production of NO by macrophages could be essential for Hh-driven carcinogenesis, however, whether Hh-infection induces DNA damage in this model and whether this depends on NO has not been determined. Here, we demonstrate that Hh infection of RAG2-deficient mice rapidly induces expression of iNOS and the development of DNA double-stranded breaks (DSBs) specifically in proliferating crypt epithelial cells. Generation of DSBs depended on iNOS activity, and further, induction of iNOS, the generation of DSBs, and the subsequent development of dysplasia were inhibited by depletion of the Hh-induced cytokine IL-22. These results demonstrate a strong association between Hh-induced DNA damage and the development of dysplasia, and further suggest that IL-22 dependent induction of iNOS within crypt epithelial cells rather than macrophages is a driving force in this process. PMID:28198364

Chronic inflammation-related DNA damage response: a driving force of gastric cardia carcinogenesis

PubMed Central

Guo, Yi; Tian, Dongping; Yun, Hailong; Chen, Donglin; Su, Min

2015-01-01

Gastric cardia cancer (GCC) is a highly aggressive disease associated with chronic inflammation. To investigate the relationship between DNA damage response (DDR) and chronic inflammation, we collected 100 non-tumor gastric cardia specimens of Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. A significantly higher proportion of severe chronic inflammation was found in dysplastic epithelia (80.9%) in comparison with that in non-dysplastic tissues (40.7%) (P<0.001). Immunohistochemical analysis demonstrated that DNA damage response was parallel with the chronic inflammation degrees from normal to severe inflammation (P<0.05). We found that DNA damage response was progressively increased with the progression of precancerous lesions (P<0.05). These findings provide pathological evidence that persistent chronic inflammation-related DNA damage response may be a driving force of gastric cardia carcinogenesis. Based on these findings, DNA damage response in non-malignant tissues may become a promising biomedical marker for predicting malignant transformation in the gastric cardia. PMID:25650663

Chronic inflammation-related DNA damage response: a driving force of gastric cardia carcinogenesis.

PubMed

Lin, Runhua; Xiao, Dejun; Guo, Yi; Tian, Dongping; Yun, Hailong; Chen, Donglin; Su, Min

2015-02-20

Gastric cardia cancer (GCC) is a highly aggressive disease associated with chronic inflammation. To investigate the relationship between DNA damage response (DDR) and chronic inflammation, we collected 100 non-tumor gastric cardia specimens of Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. A significantly higher proportion of severe chronic inflammation was found in dysplastic epithelia (80.9%) in comparison with that in non-dysplastic tissues (40.7%) (P<0.001). Immunohistochemical analysis demonstrated that DNA damage response was parallel with the chronic inflammation degrees from normal to severe inflammation (P<0.05). We found that DNA damage response was progressively increased with the progression of precancerous lesions (P<0.05). These findings provide pathological evidence that persistent chronic inflammation-related DNA damage response may be a driving force of gastric cardia carcinogenesis. Based on these findings, DNA damage response in non-malignant tissues may become a promising biomedical marker for predicting malignant transformation in the gastric cardia.

A Mechanistic Thermal Fatigue Model for SnAgCu Solder Joints

NASA Astrophysics Data System (ADS)

Borgesen, Peter; Wentlent, Luke; Hamasha, Sa'd.; Khasawneh, Saif; Shirazi, Sam; Schmitz, Debora; Alghoul, Thaer; Greene, Chris; Yin, Liang

2018-02-01

The present work offers both a complete, quantitative model and a conservative acceleration factor expression for the life span of SnAgCu solder joints in thermal cycling. A broad range of thermal cycling experiments, conducted over many years, has revealed a series of systematic trends that are not compatible with common damage functions or constitutive relations. Complementary mechanical testing and systematic studies of the evolution of the microstructure and damage have led to a fundamental understanding of the progression of thermal fatigue and failure. A special experiment was developed to allow the effective deconstruction of conventional thermal cycling experiments and the finalization of our model. According to this model, the evolution of damage and failure in thermal cycling is controlled by a continuous recrystallization process which is dominated by the coalescence and rotation of dislocation cell structures continuously added to during the high-temperature dwell. The dominance of this dynamic recrystallization contribution is not consistent with the common assumption of a correlation between the number of cycles to failure and the total work done on the solder joint in question in each cycle. It is, however, consistent with an apparent dependence on the work done during the high-temperature dwell. Importantly, the onset of this recrystallization is delayed by pinning on the Ag3Sn precipitates until these have coarsened sufficiently, leading to a model with two terms where one tends to dominate in service and the other in accelerated thermal cycling tests. Accumulation of damage under realistic service conditions with varying dwell temperatures and times is also addressed.

Structural Evaluation of Exo-Skeletal Engine Fan Blades

NASA Technical Reports Server (NTRS)

Kuguoglu, Latife; Abumeri, Galib; Chamis, Christos C.

2003-01-01

The available computational simulation capability is used to demonstrate the structural viability of composite fan blades of innovative Exo-Skeletal Engine (ESE) developed at NASA Glenn Research Center for a subsonic mission. Full structural analysis and progressive damage evaluation of ESE composite fan blade is conducted through the NASA in-house computational simulation software system EST/BEST. The results of structural assessment indicate that longitudinal stresses acting on the blade are in compression. At a design speed of 2000 rpm, pressure and suction surface outer most ply stresses in longitudinal, transverse and shear direction are much lower than the corresponding composite ply strengths. Damage is initiated at 4870 rpm and blade fracture takes place at rotor speed of 7735 rpm. Damage volume is 51 percent. The progressive damage, buckling, stress and strength results indicate that the design at hand is very sound because of the factor of safety, damage tolerance, and buckling load of 6811 rpm.

Cytokines and STATs in Liver Fibrosis.

PubMed

Kong, Xiaoni; Horiguchi, Norio; Mori, Masatomo; Gao, Bin

2012-01-01

Liver fibrosis, or cirrhosis, is a common end-stage condition of many chronic liver diseases after incomplete recovery from hepatocyte damage. During fibrosis progression, hepatocellular damage and inflammation trigger complex cellular events that result in collagen deposition and the disruption of the normal liver architecture. Hepatic stellate cell activation and transdifferentiation into myofibroblasts are key events in liver fibrogenesis. Research findings from cell culture and animal models have revealed that the Janus kinase-signal transducer and activator of transcription (Jak-STAT) signaling pathway, which can be activated by many cytokines, growth factors, and hormones, plays a critical role in hepatic fibrogenesis. This review summarizes the biological significance of diverse cytokines and their downstream signaling protein STATs in hepatic fibrogenesis.

Cytokines and STATs in Liver Fibrosis

PubMed Central

Kong, Xiaoni; Horiguchi, Norio; Mori, Masatomo; Gao, Bin

2012-01-01

Liver fibrosis, or cirrhosis, is a common end-stage condition of many chronic liver diseases after incomplete recovery from hepatocyte damage. During fibrosis progression, hepatocellular damage and inflammation trigger complex cellular events that result in collagen deposition and the disruption of the normal liver architecture. Hepatic stellate cell activation and transdifferentiation into myofibroblasts are key events in liver fibrogenesis. Research findings from cell culture and animal models have revealed that the Janus kinase-signal transducer and activator of transcription (Jak-STAT) signaling pathway, which can be activated by many cytokines, growth factors, and hormones, plays a critical role in hepatic fibrogenesis. This review summarizes the biological significance of diverse cytokines and their downstream signaling protein STATs in hepatic fibrogenesis. PMID:22493582

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

PubMed

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

2016-06-30

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

Glial degeneration with oxidative damage drives neuronal demise in MPSII disease

PubMed Central

Zalfa, Cristina; Verpelli, Chiara; D'Avanzo, Francesca; Tomanin, Rosella; Vicidomini, Cinzia; Cajola, Laura; Manara, Renzo; Sala, Carlo; Scarpa, Maurizio; Vescovi, Angelo Luigi; De Filippis, Lidia

2016-01-01

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression. PMID:27512952

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology.

PubMed

Bodas, Manish; Vij, Neeraj

2017-05-04

Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease. The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown. To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described. Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity. In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models. Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention. While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.

White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis.

PubMed

Meijer, Kim A; Muhlert, Nils; Cercignani, Mara; Sethi, Varun; Ron, Maria A; Thompson, Alan J; Miller, David H; Chard, Declan; Geurts, Jeroen Jg; Ciccarelli, Olga

2016-10-01

While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind. The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients. Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS). A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance (R 2  = 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major. Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients. © The Author(s), 2016.

Glial degeneration with oxidative damage drives neuronal demise in MPSII disease.

PubMed

Zalfa, Cristina; Verpelli, Chiara; D'Avanzo, Francesca; Tomanin, Rosella; Vicidomini, Cinzia; Cajola, Laura; Manara, Renzo; Sala, Carlo; Scarpa, Maurizio; Vescovi, Angelo Luigi; De Filippis, Lidia

2016-08-11

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression.

Foreign body impact event damage formation in composite structures

NASA Technical Reports Server (NTRS)

Bucinell, Ronald B.

1994-01-01

This report discusses a methodology that can be used to assess the effect of foreign body impacts on composite structural integrity. The described effort focuses on modeling the effect of a central impact on a 5 3/4 inch filament wound test article. The discussion will commence with details of the material modeling that was used to establish the input properties for the analytical model. This discussion is followed by an overview of the impact assessment methodology. The progress on this effort to date is reviewed along with a discussion of tasks that have yet to be completed.

Life extending control for rocket engines

NASA Technical Reports Server (NTRS)

Lorenzo, C. F.; Saus, J. R.; Ray, A.; Carpino, M.; Wu, M.-K.

1992-01-01

The concept of life extending control is defined. A brief discussion of current fatigue life prediction methods is given and the need for an alternative life prediction model based on a continuous functional relationship is established. Two approaches to life extending control are considered: (1) the implicit approach which uses cyclic fatigue life prediction as a basis for control design; and (2) the continuous life prediction approach which requires a continuous damage law. Progress on an initial formulation of a continuous (in time) fatigue model is presented. Finally, nonlinear programming is used to develop initial results for life extension for a simplified rocket engine (model).

Battle Damage Modeling

DTIC Science & Technology

2010-05-01

has been an increasing move towards armor systems which are both structural and protection components at the same time. Analysis of material response...the materials can move. As the FE analysis progresses the component will move while the mesh remains motionless (Figure 4). Individual nodes and cells...this parameter. This subroutine needs many inputs, such as the speed of sound in the material , the FE size mesh and the safety factor, which prevents

Modeling of Progressive Damage in Fiber-Reinforced Ceramic Matrix Composites

DTIC Science & Technology

1996-03-01

ALAN V. LAIR , Committee Member Professor and Department Head Department of Mathematics and Statistics DAVID D. ROBERTSON, Committee Member Major...other committee members, Prof. Peter Torvik, Prof. Alan Lair , and, representing the dean, Prof. Kirk Mathews for their support and time spent in...34 Journal of Composites Technology and Research, In press (1996). 177. Sorensen B.F. and Talreja R. "Effects of Nonuniformity of Fiber Distribution On

Linear Static Behavior of Damaged Laminated Composite Plates and Shells

PubMed Central

2017-01-01

A mathematical scheme is proposed here to model a damaged mechanical configuration for laminated and sandwich structures. In particular, two kinds of functions defined in the reference domain of plates and shells are introduced to weaken their mechanical properties in terms of engineering constants: a two-dimensional Gaussian function and an ellipse shaped function. By varying the geometric parameters of these distributions, several damaged configurations are analyzed and investigated through a set of parametric studies. The effect of a progressive damage is studied in terms of displacement profiles and through-the-thickness variations of stress, strain, and displacement components. To this end, a posteriori recovery procedure based on the three-dimensional equilibrium equations for shell structures in orthogonal curvilinear coordinates is introduced. The theoretical framework for the two-dimensional shell model is based on a unified formulation able to study and compare several Higher-order Shear Deformation Theories (HSDTs), including Murakami’s function for the so-called zig-zag effect. Thus, various higher-order models are used and compared also to investigate the differences which can arise from the choice of the order of the kinematic expansion. Their ability to deal with several damaged configurations is analyzed as well. The paper can be placed also in the field of numerical analysis, since the solution to the static problem at issue is achieved by means of the Generalized Differential Quadrature (GDQ) method, whose accuracy and stability are proven by a set of convergence analyses and by the comparison with the results obtained through a commercial finite element software. PMID:28773170

Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes

DOE PAGES

Polyzos, Aris; Holt, Amy; Brown, Christopher; ...

2016-02-21

Oxidative damage to mitochondria (MT) is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic antioxidant, XJB-5-131, which directly targets MT, the primary site and primary target of oxidative damage. XJB-5-131 prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington's disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or improves it, and reduces a grayingmore » phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.« less

Ageing mechanisms and associated lipid changes.

PubMed

Kolovou, Genovefa; Katsiki, Niki; Pavlidis, Antonis; Bilianou, Helen; Goumas, George; Mikhailidis, Dimitri P

2014-01-01

Ageing is related to slowdown/breakdown of the somatotropic axis (i.e. the somatopause) leading to many physiological changes. The somatopause is accompanied by DNA and other macromolecule damage, and is characterized by a progressive decline in vitality and tissue function. We still do not have a definitive understanding of the mechanism( s) of ageing. Several overlapping theories have been proposed such as: 1) The free radical theory, 2) Mitochondrial Ageing, 3) The Glycation Theory, 4) Protein Damage and Maintenance in Ageing, and, 5) DNA Damage and Repair. Furthermore, several models of ageing were introduced such as genetically programmed senescence, telomere shortening, genomic instability, heterochromatin loss, altered epigenetic patterns and long lived cells. There are certain lipid modifications associated with the somatopause, characterized mainly by an increase in total cholesterol and triglyceride levels in both genders. In this review we consider the mechanisms of ageing and the associated changes in lipid metabolism according to gender.

Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes

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

Polyzos, Aris; Holt, Amy; Brown, Christopher

Oxidative damage to mitochondria (MT) is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic antioxidant, XJB-5-131, which directly targets MT, the primary site and primary target of oxidative damage. XJB-5-131 prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington's disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or improves it, and reduces a grayingmore » phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.« less

Analytical Prediction of Damage Growth in Notched Composite Panels Loaded in Axial Compression

NASA Technical Reports Server (NTRS)

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

1999-01-01

A progressive failure analysis method based on shell elements is developed for the computation of damage initiation and growth in stiffened thick-skin stitched graphite-epoxy panels loaded in axial compression. The analysis method involves a step-by-step simulation of material degradation based on ply-level failure mechanisms. High computational efficiency is derived from the use of superposed layers of shell elements to model each ply orientation in the laminate. Multiple integration points through the thickness are used to obtain the correct bending effects through the thickness without the need for ply-by-ply evaluations of the state of the material. The analysis results are compared with experimental results for three stiffened panels with notches oriented at 0, 15 and 30 degrees to the panel width dimension. A parametric study is performed to investigate the damage growth retardation characteristics of the Kevlar stitch lines in the pan

Effect of disease stage on progression of hydroxychloroquine retinopathy.

PubMed

Marmor, Michael F; Hu, Julia

2014-09-01

Hydroxychloroquine sulfate retinopathy can progress after the drug is stopped. It is not clear how this relates to the stage of retinopathy or whether early screening with modern imaging technology can prevent progression and visual loss. To determine the relationship between progression of retinopathy and the severity of disease using objective data from optical coherence tomography and assess the value of early screening for the toxic effects of hydroxychloroquine. Clinical findings in patients with hydroxychloroquine retinopathy were monitored with repeated anatomical and functional examinations for 13 to 40 months after the drug was stopped in a referral practice in a university medical center. Eleven patients participated, with the severity of toxic effects categorized as early (patchy parafoveal damage shown on field or objective testing), moderate (a 50%-100% parafoveal ring of optical coherence tomography thinning but intact retinal pigment epithelium), and severe (visible bull's-eye damage). Visual acuity, white 10-2 visual field pattern density plots, fundus autofluorescence, spectral-density optical coherence tomography cross sections, thickness (from cube diagrams), and ellipsoid zone length. Visual acuity and visual fields showed no consistent change. Fundus autofluorescence showed little or no change except in severe cases in which the bull's-eye damage expanded progressively. Optical coherence tomography cross sections showed little visible change in early and moderate cases but progressive foveal thinning (approximately 7 μm/y) and loss of ellipsoid zone (in the range of 100 μm/y) in severe cases, which was confirmed by quantitative measurements. The measurements also showed some foveal thinning (approximately 4 μm/y) and deepening of parafoveal loss in moderate cases, but the breadth of the ellipsoid zone remained constant in both early and moderate cases. A few cases showed a suggestion of ellipsoid zone improvement. Patients with hydroxychloroquine retinopathy involving the retinal pigment epithelium demonstrated progressive damage on optical coherence tomography for at least 3 years after the drug was discontinued, including loss of foveal thickness and cone structure. Cases recognized before retinal pigment epithelium damage retained foveal architecture with little retinal thinning. Early recognition of hydroxychloroquine toxic effects before any fundus changes are visible, using visual fields and optical coherence tomography (along with fundus autofluorescence and multifocal electroretinography as indicated), will greatly minimize late progression and the risk of visual loss.

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

PubMed

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

2016-11-29

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

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

PubMed Central

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

2016-01-01

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

Thermal barrier coating life prediction model development, phase 1

NASA Technical Reports Server (NTRS)

Demasi, Jeanine T.; Ortiz, Milton

1989-01-01

The objective of this program was to establish a methodology to predict thermal barrier coating (TBC) life on gas turbine engine components. The approach involved experimental life measurement coupled with analytical modeling of relevant degradation modes. Evaluation of experimental and flight service components indicate the predominant failure mode to be thermomechanical spallation of the ceramic coating layer resulting from propagation of a dominant near interface crack. Examination of fractionally exposed specimens indicated that dominant crack formation results from progressive structural damage in the form of subcritical microcrack link-up. Tests conducted to isolate important life drivers have shown MCrAlY oxidation to significantly affect the rate of damage accumulation. Mechanical property testing has shown the plasma deposited ceramic to exhibit a non-linear stress-strain response, creep and fatigue. The fatigue based life prediction model developed accounts for the unusual ceramic behavior and also incorporates an experimentally determined oxide rate model. The model predicts the growth of this oxide scale to influence the intensity of the mechanic driving force, resulting from cyclic strains and stresses caused by thermally induced and externally imposed mechanical loads.

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.

Evaluation of a Region-of-Interest Approach for Detecting Progressive Glaucomatous Macular Damage on Optical Coherence Tomography

PubMed Central

Weng, Denis S. D.; Thenappan, Abinaya; Ritch, Robert; Hood, Donald C.

2018-01-01

Purpose To evaluate a manual region-of-interest (ROI) approach for detecting progressive macular ganglion cell complex (GCC) changes on optical coherence tomography (OCT) imaging. Methods One hundred forty-six eyes with a clinical diagnosis of glaucoma or suspected glaucoma with macular OCT scans obtained at least 1 year apart were evaluated. Changes in the GCC thickness were identified using a manual ROI approach (ROIM), whereby region(s) of observed or suspected glaucomatous damage were manually identified when using key features from the macular OCT scan on the second visit. Progression was also evaluated using the global GCC thickness and an automatic ROI approach (ROIA), where contiguous region(s) that fell below the 1% lower normative limit and exceeded 288 μm2 in size were evaluated. Longitudinal signal-to-noise ratios (SNRs) were calculated for progressive changes detected by each of these methods using individualized estimates of test–retest variability and age-related changes, obtained from 303 glaucoma and 394 healthy eyes, respectively. Results On average, the longitudinal SNR for the global thickness, ROIA and ROIM methods were −0.90 y−1, −0.91 y−1, and −1.03 y−1, respectively, and was significantly more negative for the ROIM compared with the global thickness (P = 0.003) and ROIA methods (P = 0.021). Conclusions Progressive glaucomatous macular GCC changes were optimally detected with a manual ROI approach. Translational Relevance These findings suggests that an approach based on a qualitative evaluation of OCT imaging information and consideration of known patterns of damage can improve the detection of progressive glaucomatous macular damage. PMID:29616153

Mechanistic Biomarkers in Acetaminophen-induced Hepatotoxicity and Acute Liver Failure: From Preclinical Models to Patients

PubMed Central

McGill, Mitchell R.; Jaeschke, Hartmut

2015-01-01

SUMMARY Introduction Drug hepatotoxicity is a major clinical issue. Acetaminophen (APAP) overdose is especially common. Serum biomarkers used to follow patient progress reflect either liver injury or function, but focus on biomarkers that can provide insight into the basic mechanisms of hepatotoxicity is increasing and enabling us to translate mechanisms of toxicity from animal models to humans. Areas covered We review recent advances in mechanistic serum biomarker research in drug hepatotoxicity. Specifically, biomarkers for reactive drug intermdiates, mitochondrial dysfunction, nuclear DNA damage, mode of cell death and inflammation are discussed, as well as microRNAs. Emphasis is placed on APAP-induced liver injury. Expert Opinion Several serum biomarkers of reactive drug intermediates, mitochondrial damage, nuclear DNA damage, apoptosis and necrosis, and inflammation have been described. These studies have provided evidence that mitochondrial damage is critical in APAP hepatotoxicity in humans, while apoptosis has only a minor role, and inflammation is important for recovery and regeneration after APAP overdose. Additionally, mechanistic serum biomarkers have been shown to predict outcome as well as, or better than, some clinical scores. In the future, such biomarkers will help determine the need for liver transplantation and, with improved understanding of the human pathophysiology, identify novel therapeutic targets. PMID:24836926

Progressive glomerular and tubular damage in sickle cell trait and sickle cell anemia mouse models.

PubMed

Saraf, Santosh L; Sysol, Justin R; Susma, Alexandru; Setty, Suman; Zhang, Xu; Gudehithlu, Krishnamurthy P; Arruda, Jose A L; Singh, Ashok K; Machado, Roberto F; Gordeuk, Victor R

2018-02-02

Homozygosity for the hemoglobin (Hb) S mutation (HbSS, sickle cell anemia) results in hemoglobin polymerization under hypoxic conditions leading to vaso-occlusion and hemolysis. Sickle cell anemia affects 1:500 African Americans and is a strong risk factor for kidney disease, although the mechanisms are not well understood. Heterozygous inheritance (HbAS; sickle cell trait) affects 1:10 African Americans and is associated with an increased risk for kidney disease in some reports. Using transgenic sickle mice, we investigated the histopathologic, ultrastructural, and gene expression differences with the HbS mutation. Consistent with progressive glomerular damage, we observed progressively greater urine protein concentrations (P = 0.03), glomerular hypertrophy (P = 0.002), and glomerular cellularity (P = 0.01) in HbAA, HbAS, and HbSS mice, respectively. Ultrastructural studies demonstrated progressive podocyte foot process effacement, glomerular basement membrane thickening with reduplication, and tubular villous atrophy with the HbS mutation. Gene expression studies highlighted the differential expression of several genes involved in prostaglandin metabolism (AKR1C18), heme and iron metabolism (HbA-A2, HMOX1, SCL25A37), electrolyte balance (SLC4A1, AQP6), immunity (RSAD2, C3, UBE2O), fatty acid metabolism (FASN), hypoxia hall-mark genes (GCK, SDC3, VEGFA, ETS1, CP, BCL2), as well as genes implicated in other forms of kidney disease (PODXL, ELMO1, FRMD3, MYH9, APOA1). Pathway analysis highlighted increased gene enrichment in focal adhesion, extracellular matrix-receptor interaction, and axon guidance pathways. In summary, using transgenic sickle mice, we observed that inheritance of the HbS mutation is associated with glomerular and tubular damage and identified several candidate genes and pathways for future investigation in sickle cell trait and sickle cell anemia-related kidney disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Data Fusion Tool for Spiral Bevel Gear Condition Indicator Data

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Antolick, Lance J.; Branning, Jeremy S.; Thomas, Josiah

2014-01-01

Tests were performed on two spiral bevel gear sets in the NASA Glenn Spiral Bevel Gear Fatigue Test Rig to simulate the fielded failures of spiral bevel gears installed in a helicopter. Gear sets were tested until damage initiated and progressed on two or more gear or pinion teeth. During testing, gear health monitoring data was collected with two different health monitoring systems. Operational parameters were measured with a third data acquisition system. Tooth damage progression was documented with photographs taken at inspection intervals throughout the test. A software tool was developed for fusing the operational data and the vibration based gear condition indicator (CI) data collected from the two health monitoring systems. Results of this study illustrate the benefits of combining the data from all three systems to indicate progression of damage for spiral bevel gears. The tool also enabled evaluation of the effectiveness of each CI with respect to operational conditions and fault mode.

Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

PubMed

Abdelhak, Ahmed; Junker, Andreas; Brettschneider, Johannes; Kassubek, Jan; Ludolph, Albert C; Otto, Markus; Tumani, Hayrettin

2015-07-31

Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs.

Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

PubMed Central

Abdelhak, Ahmed; Junker, Andreas; Brettschneider, Johannes; Kassubek, Jan; Ludolph, Albert C.; Otto, Markus; Tumani, Hayrettin

2015-01-01

Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs. PMID:26263977

Modeling Space Radiation with Radiomimetic Agent Bleomycin

NASA Technical Reports Server (NTRS)

Lu, Tao

2017-01-01

Space radiation consists of proton and helium from solar particle events (SPE) and high energy heavy ions from galactic cosmic ray (GCR). This mixture of radiation with particles at different energy levels has different effects on biological systems. Currently, majority studies of radiation effects on human were based on single-source radiation due to the limitation of available method to model effects of space radiation on living organisms. While NASA Space Radiation Laboratory is working on advanced switches to make it possible to have a mixed field radiation with particles of different energies, the radiation source will be limited. Development of an easily available experimental model for studying effects of mixed field radiation could greatly speed up our progress in our understanding the molecular mechanisms of damage and responses from exposure to space radiation, and facilitate the discovery of protection and countermeasures against space radiation, which is critical for the mission to Mars. Bleomycin, a radiomimetic agent, has been widely used to study radiation induced DNA damage and cellular responses. Previously, bleomycin was often compared to low low Linear Energy Transfer (LET) gamma radiation without defined characteristics. Our recent work demonstrated that bleomycin could induce complex clustered DNA damage in human fibroblasts that is similar to DNA damage induced by high LET radiation. These type of DNA damage is difficult to repair and can be visualized by gamma-H2Ax staining weeks after the initial insult. The survival ratio between early and late plating of human fibroblasts after bleomycin treatment is between low LET and high LET radiation. Our results suggest that bleomycin induces DNA damage and other cellular stresses resembling those resulted from mixed field radiation with both low and high LET particles. We hypothesize that bleomycin could be used to mimic space radiation in biological systems. Potential advantages and limitations of using bleomycin to treat biological specimen as an easily available model to study effects of space radiation on biological systems and to develop countermeasures for space radiation associated risks will be discussed.

Environmental barrier coating (EBC) durability modeling using a progressive failure analysis approach

NASA Astrophysics Data System (ADS)

Abdul-Aziz, Ali; Abumeri, Galib; Troha, William; Bhatt, Ramakrishna T.; Grady, Joseph E.; Zhu, D.

2012-04-01

Ceramic matrix composites (CMCs) are getting the attention of most engine manufacturers and aerospace firms for turbine engine and other related applications. This is because of their potential weight advantage and performance benefits. As a protecting guard for these materials, a highly specialized form of environmental barrier coating (EBC) is being developed and explored for high temperature applications that are greater than 1100 °C1,2. The EBCs are typically a multilayer of coatings and are on the order of hundreds of microns thick. CMCs are generally porous materials and this feature is somewhat beneficial since it allows some desirable infiltration of the EBC. Their degradation usually includes coating interface oxidation as opposed to moisture induced matrix degradation which is generally seen at a higher temperature. A variety of factors such as residual stresses, coating process related flaws, and casting conditions may influence the strength of degradation. The cause of such defects which cause cracking and other damage is that not much energy is absorbed during fracture of these materials. Therefore, an understanding of the issues that control crack deflection and propagation along interfaces is needed to maximize the energy dissipation capabilities of layered ceramics. Thus, evaluating components and subcomponents made out of CMCs under gas turbine engine conditions is suggested to demonstrate that these material will perform as expected and required under these aggressive environmental circumstances. Progressive failure analysis (PFA) is applied to assess the damage growth of the coating under combined thermal and mechanical loading conditions. The PFA evaluation is carried out using a full-scale finite element model to account for the average material failure at the microscopic or macroscopic levels. The PFA life prediction evaluation identified the root cause for damage initiation and propagation. It indicated that delamination type damage initiated mainly in the bond and intermediate coating materials then propagated to the substrate. Results related to damage initiation and propagation; behavior and life assessment of the coating at the interface of the EBC/CMC are presented and discussed.

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

NASA Technical Reports Server (NTRS)

Slattery, Kerry T.; Hackett, Robert M.

1991-01-01

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

Test-Free Fracture Toughness

NASA Technical Reports Server (NTRS)

Minnetyan, Levon; Chamis, Christos C. (Technical Monitor)

2003-01-01

Computational simulation results can give the prediction of damage growth and progression and fracture toughness of composite structures. The experimental data from literature provide environmental effects on the fracture behavior of metallic or fiber composite structures. However, the traditional experimental methods to analyze the influence of the imposed conditions are expensive and time consuming. This research used the CODSTRAN code to model the temperature effects, scaling effects and the loading effects of fiber/braided composite specimens with and without fiber-optic sensors on the damage initiation and energy release rates. The load-displacement relationship and fracture toughness assessment approach is compared with the test results from literature and it is verified that the computational simulation, with the use of established material modeling and finite element modules, adequately tracks the changes of fracture toughness and subsequent fracture propagation for any fiber/braided composite structure due to the change of fiber orientations, presence of large diameter optical fibers, and any loading conditions.

Test-Free Fracture Toughness

NASA Technical Reports Server (NTRS)

Minnetyan, Levon; Chamis, Christos C. (Technical Monitor)

2003-01-01

Computational simulation results can give the prediction of damage growth and progression and fracture toughness of composite structures. The experimental data from literature provide environmental effects on the fracture behavior of metallic or fiber composite structures. However, the traditional experimental methods to analyze the influence of the imposed conditions are expensive and time consuming. This research used the CODSTRAN code to model the temperature effects, scaling effects and the loading effects of fiberbraided composite specimens with and without fiber-optic sensors on the damage initiation and energy release rates. The load-displacement relationship and fracture toughness assessment approach is compared with the test results from literature and it is verified that the computational simulation, with the use of established material modeling and finite element modules, adequately tracks the changes of fracture toughness and subsequent fracture propagation for any fiberbraided composite structure due to the change of fiber orientations, presence of large diameter optical fibers, and any loading conditions.

Genotoxin induced mutagenesis in the model plant Physcomitrella patens.

PubMed

Holá, Marcela; Kozák, Jaroslav; Vágnerová, Radka; Angelis, Karel J

2013-01-01

The moss Physcomitrella patens is unique for the high frequency of homologous recombination, haploid state, and filamentous growth during early stages of the vegetative growth, which makes it an excellent model plant to study DNA damage responses. We used single cell gel electrophoresis (comet) assay to determine kinetics of response to Bleomycin induced DNA oxidative damage and single and double strand breaks in wild type and mutant lig4 Physcomitrella lines. Moreover, APT gene when inactivated by induced mutations was used as selectable marker to ascertain mutational background at nucleotide level by sequencing of the APT locus. We show that extensive repair of DSBs occurs also in the absence of the functional LIG4, whereas repair of SSBs is seriously compromised. From analysis of induced mutations we conclude that their accumulation rather than remaining lesions in DNA and blocking progression through cell cycle is incompatible with normal plant growth and development and leads to sensitive phenotype.

Genotoxin Induced Mutagenesis in the Model Plant Physcomitrella patens

PubMed Central

Holá, Marcela; Kozák, Jaroslav; Vágnerová, Radka; Angelis, Karel J.

2013-01-01

The moss Physcomitrella patens is unique for the high frequency of homologous recombination, haploid state, and filamentous growth during early stages of the vegetative growth, which makes it an excellent model plant to study DNA damage responses. We used single cell gel electrophoresis (comet) assay to determine kinetics of response to Bleomycin induced DNA oxidative damage and single and double strand breaks in wild type and mutant lig4 Physcomitrella lines. Moreover, APT gene when inactivated by induced mutations was used as selectable marker to ascertain mutational background at nucleotide level by sequencing of the APT locus. We show that extensive repair of DSBs occurs also in the absence of the functional LIG4, whereas repair of SSBs is seriously compromised. From analysis of induced mutations we conclude that their accumulation rather than remaining lesions in DNA and blocking progression through cell cycle is incompatible with normal plant growth and development and leads to sensitive phenotype. PMID:24383055

A Systems Thinking approach to post-disaster restoration of maritime transportation systems

USGS Publications Warehouse

Lespier, Lizzette Pérez; Long, Suzanna K.; Shoberg, Thomas G.

2015-01-01

A Systems Thinking approach is used to examine elements of a maritime transportation system that are most likely to be impacted by an extreme event. The majority of the literature uses a high-level view that can fail to capture the damage at the sub-system elements. This work uses a system dynamics simulation for a better view and understanding of the Port of San Juan, Puerto Rico, as a whole system and uses Hurricane Georges (1998), as a representative disruptive event. The model focuses on the impacts of natural disasters at the sub-system level with a final goal of determining the sequence needed to restore an ocean-going port to its pre-event state. This work in progress details model development and outlines steps for using real-world information to assist maritime port manager planning and recommendations for best practices to mitigate disaster damage.

Long-term disability progression in primary progressive multiple sclerosis: a 15-year study.

PubMed

Rocca, Maria A; Sormani, Maria Pia; Rovaris, Marco; Caputo, Domenico; Ghezzi, Angelo; Montanari, Enrico; Bertolotto, Antonio; Laroni, Alice; Bergamaschi, Roberto; Martinelli, Vittorio; Comi, Giancarlo; Filippi, Massimo

2017-11-01

Prognostic markers of primary progressive multiple sclerosis evolution are needed. We investigated the added value of magnetic resonance imaging measures of brain and cervical cord damage in predicting long-term clinical worsening of primary progressive multiple sclerosis compared to simple clinical assessment. In 54 patients, conventional and diffusion tensor brain scans and cervical cord T1-weighted scans were acquired at baseline and after 15 months. Clinical evaluation was performed after 5 and 15 years in 49 patients. Lesion load, brain and cord atrophy, mean diffusivity and fractional anisotropy values from the brain normal-appearing white matter and grey matter were obtained. Using linear regression models, we screened the clinical and imaging variables as independent predictors of 15-year disability change (measured on the expanded disability status scale). At 15 years, 90% of the patients had disability progression. Integrating clinical and imaging variables at 15 months predicted disability changes at 15 years better than clinical factors at 5 years (R2 = 61% versus R2 = 57%). The model predicted long-term disability change with a precision within one point in 38 of 49 patients (77.6%). Integration of clinical and imaging measures allows identification of primary progressive multiple sclerosis patients at risk of long-term disease progression 4 years earlier than when using clinical assessment alone. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bile duct ligation in developing rats: temporal progression of liver, kidney, and brain damage.

PubMed

Sheen, Jiunn-Ming; Huang, Li-Tung; Hsieh, Chih-Sung; Chen, Chih-Cheng; Wang, Jia-Yi; Tain, You-Lin

2010-08-01

Cholestatic liver disease may result in progressive end-stage liver disease and other extrahepatic complications. We explored the temporal progression of bile duct ligation (BDL)-induced cholestasis in developing rats, focusing on brain cognition and liver and kidney pathology, to elucidate whether these findings were associated with asymmetric dimethylarginine and oxidative stress alterations. Three groups of young male Sprague-Dawley rats were studied: one group underwent laparotomy (sham), another group underwent laparotomy and BDL for 2 weeks (BDL2), and a third group underwent laparotomy and BDL for 4 weeks (BDL4). The effect of BDL on liver was represented by transforming growth factor beta1 levels and histology activity index scores, which were worse in the BDL4 rats than in the BDL2 rats. BDL4 rats also exhibited more severe spatial memory deficits than BDL2 rats. In addition, renal injury was more progressive in BDL4 rats than in BDL2 rats because BDL4 rats displayed higher Cr levels, elevated tubulointerstitial injury scores, neutrophil gelatinase-associated lipocalin, and symmetric dimethylarginine levels. Our findings highlight the fact that young BDL rats exhibit similar trends of progression of liver, kidney, and brain damage. Further studies are needed to better delineate the nature of progression of organ damage in young cholestatic rats. Copyright 2010 Elsevier Inc. All rights reserved.

Abnormal Mitochondrial Dynamics and Synaptic Degeneration as Early Events in Alzheimer’s Disease: Implications to Mitochondria-Targeted Antioxidant Therapeutics

PubMed Central

Reddy, P. Hemachandra; Tripathy, Raghav; Troung, Quang; Thirumala, Karuna; Reddy, Tejaswini P.; Anekonda, Vishwanath; Shirendeb, Ulziibat P.; Calkins, Marcus J.; Reddy, Arubala P.; Mao, Peizhong; Manczak, Maria

2011-01-01

Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer’s disease (AD) progression. Loss of synapses and synaptic damage are the best correlate of cognitive deficits found in AD patients. Recent research on amyloid bet (Aβ) and mitochondria in AD revealed that Aβ accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (AβPP) transgenic mice revealed that reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that Aβ is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in Aβ-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD. PMID:22037588

Radiological and Pathological Correlation in Anti-MDA5 Antibody-positive Interstitial Lung Disease: Rapidly Progressive Perilobular Opacities and Diffuse Alveolar Damage.

PubMed

Chino, Haruka; Sekine, Akimasa; Baba, Tomohisa; Iwasawa, Tae; Okudela, Koji; Takemura, Tamiko; Itoh, Harumi; Sato, Shinji; Suzuki, Yasuo; Ogura, Takashi

2016-01-01

We herein present the first case of rapidly progressive interstitial lung disease (RP-ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody evaluated by surgical lung biopsy (SLB). High-resolution CT scan revealed perilobular opacities, which rapidly became thicker and formed consolidation, resulting in remarkable loss of lung volume. Specimens taken from SLB revealed membranous organization with alveolar occlusion, dilation of alveolar ducts, and sacs with collapsed alveoli, which are typical features of diffuse alveolar damage (DAD). Rapidly progressive perilobular opacities may be characteristic of RP-ILD with anti-MDA5 antibody and DAD.

Thermo-hydro-mechanical stresses during repeat glacial cycles as preparatory factors for paraglacial rock slope instabilities

NASA Astrophysics Data System (ADS)

Grämiger, Lorenz; Moore, Jeffrey R.; Gischig, Valentin; Loew, Simon

2015-04-01

Glaciation and deglaciation contribute to stress redistribution in alpine valley rock slopes, generating rock mass damage. However, the physical processes contributing to slope instability during glacial cycles are not well understood, and the mechanical reasoning remains vague. In addition to glacier loading and unloading, thermal strains affect newly exposed bedrock while changes in hillslope hydrology modify effective stresses. Together these can generate damage and reduce rock slope stability over time. Here we explore the role of coupled thermo-hydro-mechanical (THM) stress changes in driving long-term progressive damage and conditioning paraglacial rock slope failure in the Aletsch glacier region of Switzerland. We develop a 2D numerical model using the distinct element code UDEC, creating a fractured rock slope containing rock mass elements of intact rock, discontinuities, and fault zones. Topography, rock properties and glacier history are all loosely based on real conditions in the Aletsch valley. In-situ stresses representing pre-LGM conditions with inherent rock mass damage are initialized. We model stress changes through multiple glacier cycles during the Lateglacial and Holocene; stress redistribution is not only induced by glacier loading, but also by changes in bedrock temperatures and transient hillslope hydrology. Each THM response mechanism is tied to the changing ice extents, therefore stress changes and resulting rock mass damage can be explored in both space and time. We analyze cyclic THM stresses and resulting damage during repeat glacial cycles, and compare spatiotemporal outputs with the mapped landslide distribution in the Aletsch region. Our results extend the concept of glacial debuttressing, lead to improved understanding of the rock mass response to glacial cycles, and clarify coupled interactions driving paraglacial rock mass damage.

Longitudinal diffusion tensor magnetic resonance imaging study of radiation-induced white matter damage in a rat model.

PubMed

Wang, Silun; Wu, Ed X; Qiu, Deqiang; Leung, Lucullus H T; Lau, Ho-Fai; Khong, Pek-Lan

2009-02-01

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (lambda(//)), and radial diffusivity (lambda( perpendicular)) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in lambda(//) from 4 to 40 weeks postradiation, and an increase in lambda( perpendicular) with return to baseline in lambda(//) at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in lambda(//) correlated with reactive astrogliosis (P < 0.01) and lambda( perpendicular) correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in lambda(//) and lambda( perpendicular). DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression

PubMed Central

Barr, Alexis R.; Cooper, Samuel; Heldt, Frank S.; Butera, Francesca; Stoy, Henriette; Mansfeld, Jörg; Novák, Béla; Bakal, Chris

2017-01-01

Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases. High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4Cdt2 and SCFSkp2 couple to degrade p21 prior to the G1/S transition. Mathematical modelling reveals that a bistable switch, created by CRL4Cdt2, promotes irreversible S-phase entry by keeping p21 levels low, preventing premature S-phase exit upon DNA damage. Thus, we characterize how p21 regulates the proliferation-quiescence decision to maintain genomic stability. PMID:28317845

Longitudinal magnetic resonance imaging study shows progressive pyramidal and callosal damage in Friedreich's ataxia.

PubMed

Rezende, Thiago J R; Silva, Cynthia B; Yassuda, Clarissa L; Campos, Brunno M; D'Abreu, Anelyssa; Cendes, Fernando; Lopes-Cendes, Iscia; França, Marcondes C

2016-01-01

Spinal cord and peripheral nerves are classically known to be damaged in Friedreich's ataxia, but the extent of cerebral involvement in the disease and its progression over time are not yet characterized. The aim of this study was to evaluate longitudinally cerebral damage in Friedreich's ataxia. We enrolled 31 patients and 40 controls, which were evaluated at baseline and after 1 and 2 years. To assess gray matter, we employed voxel-based morphometry and cortical thickness measurements. White matter was evaluated using diffusion tensor imaging. Statistical analyses were both cross-sectional and longitudinal (corrected for multiple comparisons). Group comparison between patients and controls revealed widespread macrostructural differences at baseline: gray matter atrophy in the dentate nuclei, brainstem, and precentral gyri; and white matter atrophy in the cerebellum and superior cerebellar peduncles, brainstem, and periventricular areas. We did not identify any longitudinal volumetric change over time. There were extensive microstructural alterations, including superior cerebellar peduncles, corpus callosum, and pyramidal tracts. Longitudinal analyses identified progressive microstructural abnormalities at the corpus callosum, pyramidal tracts, and superior cerebellar peduncles after 1 year of follow-up. Patients with Friedreich's ataxia present more widespread gray and white matter damage than previously reported, including not only infratentorial areas, but also supratentorial structures. Furthermore, patients with Friedreich's ataxia have progressive microstructural abnormalities amenable to detection in a short-term follow-up. © 2015 International Parkinson and Movement Disorder Society.

Meso-Scale Modelling of Deformation, Damage and Failure in Dual Phase Steels

NASA Astrophysics Data System (ADS)

Sari Sarraf, Iman

Advanced high strength steels (AHSS), such as dual phase (DP) and transformation induced plasticity (TRIP) steels, offer high ductility, formability, and strength, as well as high strength-to-weight ratio and improved crash resistance. Dual phase steels belong to a family of high strength grades which consist of martensite, responsible for strengthening, distributed in a ductile ferrite matrix which accommodates the deformation throughout the forming process. It has been shown that the predominant damage mechanism and failure in DP steels depends on the ferrite and martensite grain sizes and their morphology, and can range from a mixture of brittle and ductile rupture to completely ductile rupture in a quasi-static uniaxial tension test. In this study, a hybrid finite element cellular automata model, initially proposed by Anton Shterenlikht (2003), was developed to evaluate the forming behaviour and predict the onset of instability and damage evolution in a dual phase steel. In this model, the finite element constitutive model is used to represent macro-level strain gradients and a damage variable, and two different cell arrays are designed to represent the ductile and brittle fracture modes in meso-scale. In the FE part of the model, a modified Rousselier ductile damage model is developed to account for nucleation, growth and coalescence of voids. Also, several rate-dependent hardening models were developed and evaluated to describe the work hardening flow curve of DP600. Based on statistical analysis and simulation results, a modified Johnson-Cook (JC) model and a multiplicative combination of the Voce-modified JC functions were found to be the most accurate hardening models. The developed models were then implemented in a user-defined material subroutine (VUMAT) for ABAQUS/Explicit finite element simulation software to simulate uniaxial tension tests at strain rates ranging from 0.001 1/s to 1000 1/s, Marciniak tests, and electrohydraulic free-forming (EHFF). The modified Rousselier model could successfully predict the dynamic behaviour, the onset of instability and damage progress in DP600 tensile test specimens. Also, the forming limit curve (FLC) as well as the final damage geometry in DP600 Marciniak specimens was successfully predicted and compared with experiments. A hybrid FE+CA model was utilized to predict the major fracture mode of DP600 and DP780 sheet specimens under different deformation conditions. This hybrid model is able to predict quasi-cleavage fracture in ultra-fine and coarse-grained DP600 and DP780 at low and high strain rates. The numerical results showed the capabilities of the proposed model to predict that higher martensite volume fraction, greater ferrite grain sizes and higher strain rates promote the brittle fracture mechanism whereas finer grain sizes and higher temperature alter the dominant fracture mechanism to ductile mode.

Progressive brain damage, synaptic reorganization and NMDA activation in a model of epileptogenic cortical dysplasia.

PubMed

Colciaghi, Francesca; Finardi, Adele; Nobili, Paola; Locatelli, Denise; Spigolon, Giada; Battaglia, Giorgio Stefano

2014-01-01

Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.

Investigation of Bearing Fatigue Damage Life Prediction Using Oil Debris Monitoring

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Bolander, Nathan; Haynes, Chris; Toms, Allison M.

2011-01-01

Research was performed to determine if a diagnostic tool for detecting fatigue damage of helicopter tapered roller bearings can be used to determine remaining useful life (RUL). The taper roller bearings under study were installed on the tail gearbox (TGB) output shaft of UH- 60M helicopters, removed from the helicopters and subsequently installed in a bearing spall propagation test rig. The diagnostic tool was developed and evaluated experimentally by collecting oil debris data during spall progression tests on four bearings. During each test, data from an on-line, in-line, inductance type oil debris sensor was monitored and recorded for the occurrence of pitting damage. Results from the four bearings tested indicate that measuring the debris generated when a bearing outer race begins to spall can be used to indicate bearing damage progression and remaining bearing life.

Log-gamma linear-mixed effects models for multiple outcomes with application to a longitudinal glaucoma study

PubMed Central

Zhang, Peng; Luo, Dandan; Li, Pengfei; Sharpsten, Lucie; Medeiros, Felipe A.

2015-01-01

Glaucoma is a progressive disease due to damage in the optic nerve with associated functional losses. Although the relationship between structural and functional progression in glaucoma is well established, there is disagreement on how this association evolves over time. In addressing this issue, we propose a new class of non-Gaussian linear-mixed models to estimate the correlations among subject-specific effects in multivariate longitudinal studies with a skewed distribution of random effects, to be used in a study of glaucoma. This class provides an efficient estimation of subject-specific effects by modeling the skewed random effects through the log-gamma distribution. It also provides more reliable estimates of the correlations between the random effects. To validate the log-gamma assumption against the usual normality assumption of the random effects, we propose a lack-of-fit test using the profile likelihood function of the shape parameter. We apply this method to data from a prospective observation study, the Diagnostic Innovations in Glaucoma Study, to present a statistically significant association between structural and functional change rates that leads to a better understanding of the progression of glaucoma over time. PMID:26075565

Three-Dimensional High Fidelity Progressive Failure Damage Modeling of NCF Composites

NASA Technical Reports Server (NTRS)

Aitharaju, Venkat; Aashat, Satvir; Kia, Hamid G.; Satyanarayana, Arunkumar; Bogert, Philip B.

2017-01-01

Performance prediction of off-axis laminates is of significant interest in designing composite structures for energy absorption. Phenomenological models available in most of the commercial programs, where the fiber and resin properties are smeared, are very efficient for large scale structural analysis, but lack the ability to model the complex nonlinear behavior of the resin and fail to capture the complex load transfer mechanisms between the fiber and the resin matrix. On the other hand, high fidelity mesoscale models, where the fiber tows and matrix regions are explicitly modeled, have the ability to account for the complex behavior in each of the constituents of the composite. However, creating a finite element model of a larger scale composite component could be very time consuming and computationally very expensive. In the present study, a three-dimensional mesoscale model of non-crimp composite laminates was developed for various laminate schemes. The resin material was modeled as an elastic-plastic material with nonlinear hardening. The fiber tows were modeled with an orthotropic material model with brittle failure. In parallel, new stress based failure criteria combined with several damage evolution laws for matrix stresses were proposed for a phenomenological model. The results from both the mesoscale and phenomenological models were compared with the experiments for a variety of off-axis laminates.

Dysregulation of mitochondrial calcium signaling and superoxide flashes cause mitochondrial genomic DNA damage in Huntington disease.

PubMed

Wang, Jiu-Qiang; Chen, Qian; Wang, Xianhua; Wang, Qiao-Chu; Wang, Yun; Cheng, He-Ping; Guo, Caixia; Sun, Qinmiao; Chen, Quan; Tang, Tie-Shan

2013-02-01

Huntington disease (HD) is an inherited, fatal neurodegenerative disorder characterized by the progressive loss of striatal medium spiny neurons. Indications of oxidative stress are apparent in brain tissues from both HD patients and HD mouse models; however, the origin of this oxidant stress remains a mystery. Here, we used a yeast artificial chromosome transgenic mouse model of HD (YAC128) to investigate the potential connections between dysregulation of cytosolic Ca(2+) signaling and mitochondrial oxidative damage in HD cells. We found that YAC128 mouse embryonic fibroblasts exhibit a strikingly higher level of mitochondrial matrix Ca(2+) loading and elevated superoxide generation compared with WT cells, indicating that both mitochondrial Ca(2+) signaling and superoxide generation are dysregulated in HD cells. The excessive mitochondrial oxidant stress is critically dependent on mitochondrial Ca(2+) loading in HD cells, because blocking mitochondrial Ca(2+) uptake abolished elevated superoxide generation. Similar results were obtained using neurons from HD model mice and fibroblast cells from HD patients. More importantly, mitochondrial Ca(2+) loading in HD cells caused a 2-fold higher level of mitochondrial genomic DNA (mtDNA) damage due to the excessive oxidant generation. This study provides strong evidence to support a new causal link between dysregulated mitochondrial Ca(2+) signaling, elevated mitochondrial oxidant stress, and mtDNA damage in HD. Our results also indicate that reducing mitochondrial Ca(2+) uptake could be a therapeutic strategy for HD.

Experimental Investigation of the Acoustic Nonlinear Behavior in Granular Polymer Bonded Explosives with Progressive Fatigue Damage

PubMed Central

Yang, Zhanfeng; Tian, Yong; Li, Weibin; Zhou, Haiqiang; Zhang, Weibin; Li, Jingming

2017-01-01

The measurement of acoustic nonlinear response is known as a promising technique to characterize material micro-damages. In this paper, nonlinear ultrasonic approach is used to characterize the evolution of fatigue induced micro-cracks in polymer bonded explosives. The variations of acoustic nonlinearity with respect to fatigue cycles in the specimens are obtained in this investigation. The present results show a significant increase of acoustic nonlinearity with respect to fatigue cycles. The experimental observation of the correlation between the acoustic nonlinearity and fatigue cycles in carbon/epoxy laminates, verifies that an acoustic nonlinear response can be used to evaluate the progressive fatigue damage in the granular polymer bonded explosives. The sensitivity comparison of nonlinear and linear parameters of ultrasonic waves in the specimens shows that nonlinear acoustic parameters are more promising indicators to fatigue induced micro-damage than linear ones. The feasibility study of the micro-damage assessment of polymer bonded explosives by nonlinear ultrasonic technique in this work can be applied to damage identification, material degradation monitoring, and lifetime prediction of the explosive parts. PMID:28773017

Experimental Investigation of the Acoustic Nonlinear Behavior in Granular Polymer Bonded Explosives with Progressive Fatigue Damage.

PubMed

Yang, Zhanfeng; Tian, Yong; Li, Weibin; Zhou, Haiqiang; Zhang, Weibin; Li, Jingming

2017-06-16

The measurement of acoustic nonlinear response is known as a promising technique to characterize material micro-damages. In this paper, nonlinear ultrasonic approach is used to characterize the evolution of fatigue induced micro-cracks in polymer bonded explosives. The variations of acoustic nonlinearity with respect to fatigue cycles in the specimens are obtained in this investigation. The present results show a significant increase of acoustic nonlinearity with respect to fatigue cycles. The experimental observation of the correlation between the acoustic nonlinearity and fatigue cycles in carbon/epoxy laminates, verifies that an acoustic nonlinear response can be used to evaluate the progressive fatigue damage in the granular polymer bonded explosives. The sensitivity comparison of nonlinear and linear parameters of ultrasonic waves in the specimens shows that nonlinear acoustic parameters are more promising indicators to fatigue induced micro-damage than linear ones. The feasibility study of the micro-damage assessment of polymer bonded explosives by nonlinear ultrasonic technique in this work can be applied to damage identification, material degradation monitoring, and lifetime prediction of the explosive parts.

Experimental Investigation on the Fatigue Mechanical Properties of Intermittently Jointed Rock Models Under Cyclic Uniaxial Compression with Different Loading Parameters

NASA Astrophysics Data System (ADS)

Liu, Yi; Dai, Feng; Dong, Lu; Xu, Nuwen; Feng, Peng

2018-01-01

Intermittently jointed rocks, widely existing in many mining and civil engineering structures, are quite susceptible to cyclic loading. Understanding the fatigue mechanism of jointed rocks is vital to the rational design and the long-term stability analysis of rock structures. In this study, the fatigue mechanical properties of synthetic jointed rock models under different cyclic conditions are systematically investigated in the laboratory, including four loading frequencies, four maximum stresses, and four amplitudes. Our experimental results reveal the influence of the three cyclic loading parameters on the mechanical properties of jointed rock models, regarding the fatigue deformation characteristics, the fatigue energy and damage evolution, and the fatigue failure and progressive failure behavior. Under lower loading frequency or higher maximum stress and amplitude, the jointed specimen is characterized by higher fatigue deformation moduli and higher dissipated hysteresis energy, resulting in higher cumulative damage and lower fatigue life. However, the fatigue failure modes of jointed specimens are independent of cyclic loading parameters; all tested jointed specimens exhibit a prominent tensile splitting failure mode. Three different crack coalescence patterns are classified between two adjacent joints. Furthermore, different from the progressive failure under static monotonic loading, the jointed rock specimens under cyclic compression fail more abruptly without evident preceding signs. The tensile cracks on the front surface of jointed specimens always initiate from the joint tips and then propagate at a certain angle with the joints toward the direction of maximum compression.

Heart Repair and Regeneration: Recent Insights from Zebrafish Studies

PubMed Central

Lien, Ching-Ling; Harrison, Michael R.; Tuan, Tai-Lan; Starnes, Vaughn A

2012-01-01

Cardiovascular disease is the leading cause of death in United States and worldwide. Failure to properly repair or regenerate damaged cardiac tissues after myocardial infarction is a major cause of heart failure. In contrast to humans and other mammals, zebrafish hearts regenerate after substantial injury or tissue damage. Here, we review recent progress in studying zebrafish heart regeneration, addressing the molecular and cellular responses in the three tissue layers of the heart: myocardium, epicardium, and endocardium. We also compare different injury models utilized to study zebrafish heart regeneration, and discuss the differences in responses to injury between mammalian and zebrafish hearts. By learning how zebrafish hearts regenerate naturally, we can better design therapeutic strategies for repairing human hearts after myocardial infarction. PMID:22818295

Process compensated resonance testing modeling for damage evolution and uncertainty quantification

NASA Astrophysics Data System (ADS)

Biedermann, Eric; Heffernan, Julieanne; Mayes, Alexander; Gatewood, Garrett; Jauriqui, Leanne; Goodlet, Brent; Pollock, Tresa; Torbet, Chris; Aldrin, John C.; Mazdiyasni, Siamack

2017-02-01

Process Compensated Resonance Testing (PCRT) is a nondestructive evaluation (NDE) method based on the fundamentals of Resonant Ultrasound Spectroscopy (RUS). PCRT is used for material characterization, defect detection, process control and life monitoring of critical gas turbine engine and aircraft components. Forward modeling and model inversion for PCRT have the potential to greatly increase the method's material characterization capability while reducing its dependence on compiling a large population of physical resonance measurements. This paper presents progress on forward modeling studies for damage mechanisms and defects in common to structural materials for gas turbine engines. Finite element method (FEM) models of single crystal (SX) Ni-based superalloy Mar-M247 dog bones and Ti-6Al-4V cylindrical bars were created, and FEM modal analyses calculated the resonance frequencies for the samples in their baseline condition. Then the frequency effects of superalloy creep (high-temperature plastic deformation) and macroscopic texture (preferred crystallographic orientation of grains detrimental to fatigue properties) were evaluated. A PCRT sorting module for creep damage in Mar-M247 was trained with a virtual database made entirely of modeled design points. The sorting module demonstrated successful discrimination of design points with as little as 1% creep strain in the gauge section from a population of acceptable design points with a range of material and geometric variation. The resonance frequency effects of macro-scale texture in Ti-6Al-4V were quantified with forward models of cylinder samples. FEM-based model inversion was demonstrated for Mar-M247 bulk material properties and variations in crystallographic orientation. PCRT uncertainty quantification (UQ) was performed using Monte Carlo studies for Mar-M247 that quantified the overall uncertainty in resonance frequencies resulting from coupled variation in geometry, material properties, crystallographic orientation and creep damage. A model calibration process was also developed that evaluates inversion fitting to differences from a designated reference sample rather than absolute property values, yielding a reduction in fit error.

SIV Infection Impairs the Central Nervous System in Chinese Rhesus Macaques.

PubMed

Liu, Hang; Xiao, Qian-Hao; Liu, Jin-Biao; Li, Jie-Liang; Zhou, Li; Xian, Qiao-Yang; Wang, Yong; Zhang, Jing; Wang, Xu; Ho, Wen-Zhe; Zhuang, Ke

2016-09-01

The central nervous system (CNS) impairment is a consequence seen in SIV infection of rhesus macaques of Indian-origin, which is more common in infected macaques with rapid disease progression than in those with conventional disease progression. Here, we investigated the CNS damages in SIVmac239-infected Chinese rhesus macaques. We demonstrated that SIV infection of Chinese macaques could cause neuropathological impairments, which was evidenced by appearance of SIV-RNA positive cells, the infiltration of activated macrophages and abundant multinucleated giant cells (MNGCs) in the different regions of the brains. The animals with high viremia and short survival time (average of 16 weeks, rapid progression, RP) had severer neuropathological changes than those with conventional progression (CP). As compared with the RP animals, CP macaques had lower viremia and much longer survival time (average of 154 weeks). These findings indicate that SIVmac239 infection of Chinese rhesus macaque can be used as a suitable animal model and alternative resource for nueroAIDS research.

Correlate Life Predictions and Condition Indicators in Helicopter Tail Gearbox Bearings

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Bolander, Nathan; Haynes, Chris; Branning, Jeremy; Wade, Daniel R.

2010-01-01

Research to correlate bearing remaining useful life (RUL) predictions with Helicopter Health Usage Monitoring Systems (HUMS) condition indicators (CI) to indicate the damage state of a transmission component has been developed. Condition indicators were monitored and recorded on UH-60M (Black Hawk) tail gearbox output shaft thrust bearings, which had been removed from helicopters and installed in a bearing spall propagation test rig. Condition indicators monitoring the tail gearbox output shaft thrust bearings in UH-60M helicopters were also recorded from an on-board HUMS. The spal-lpropagation data collected in the test rig was used to generate condition indicators for bearing fault detection. A damage progression model was also developed from this data. Determining the RUL of this component in a helicopter requires the CI response to be mapped to the damage state. The data from helicopters and a test rig were analyzed to determine if bearing remaining useful life predictions could be correlated with HUMS condition indicators (CI). Results indicate data fusion analysis techniques can be used to map the CI response to the damage levels.

Impact force as a scaling parameter

NASA Technical Reports Server (NTRS)

Poe, Clarence C., Jr.; Jackson, Wade C.

1994-01-01

The Federal Aviation Administration (FAR PART 25) requires that a structure carry ultimate load with nonvisible impact damage and carry 70 percent of limit flight loads with discrete damage. The Air Force has similar criteria (MIL-STD-1530A). Both civilian and military structures are designed by a building block approach. First, critical areas of the structure are determined, and potential failure modes are identified. Then, a series of representative specimens are tested that will fail in those modes. The series begins with tests of simple coupons, progresses through larger and more complex subcomponents, and ends with a test on a full-scale component, hence the term 'building block.' In order to minimize testing, analytical models are needed to scale impact damage and residual strength from the simple coupons to the full-scale component. Using experiments and analysis, the present paper illustrates that impact damage can be better understood and scaled using impact force than just kinetic energy. The plate parameters considered are size and thickness, boundary conditions, and material, and the impact parameters are mass, shape, and velocity.

Radiation damage to nucleoprotein complexes in macromolecular crystallography

DOE PAGES

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

2015-01-30

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

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

Zhang, Chao; Xu, Jun; Cao, Lei

The electrodes of lithium-ion batteries (LIB) are known to be brittle and to fail earlier than the separators during an external crush event. Thus, the understanding of mechanical failure mechanism for LIB electrodes (anode and cathode) is critical for the safety design of LIB cells. In this paper, we present experimental and numerical studies on the constitutive behavior and progression of failure in LIB electrodes. Mechanical tests were designed and conducted to evaluate the constitutive properties of porous electrodes. Constitutive models were developed to describe the stress-strain response of electrodes under uniaxial tensile and compressive loads. The failure criterion andmore » a damage model were introduced to model their unique tensile and compressive failure behavior. The failure mechanism of LIB electrodes was studied using the blunt rod test on dry electrodes, and numerical models were built to simulate progressive failure. The different failure processes were examined and analyzed in detail numerically, and correlated with experimentally observed failure phenomena. Finally, the test results and models improve our understanding of failure behavior in LIB electrodes, and provide constructive insights on future development of physics-based safety design tools for battery structures under mechanical abuse.« less

Nonhuman primate models of neuro AIDS

PubMed Central

Williams, Rachel; Bokhari, Sirosh; Silverstein, Peter; Pinson, David; Kumar, Anil; Buch, Shilpa

2009-01-01

Human Immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS), also manifests neurological complications. HIV-associated dementia (HAD) is the most severe form of HIV-induced neurocognitive disorders. HIV encephalitis (HIVE), the pathological correlate of HAD, is characterized by the formation of multinucleated giant cells and microglial nodules, astrocytosis, and neuronal damage and loss. Pathological evaluation of HAD disease progression in humans is not possible, with the only data collected being from individuals who have succumbed to the disorder, a snap shot of end-stage disease at best. Therefore, pertinent animal models have been developed to alleviate this gap of knowledge in the field of neurovirology and neuroinflammation. In general, the most widely used animal models are the simian immunodeficiency virus (SIV) and the chimeric simian/human immunodeficiency virus (SHIV) macaque model systems. Although both SIV and SHIV model systems are able to potentiate neuroinvasion and the concomitant neuropathology similar to that seen in the human syndromes, the innate differences between the two in disease pathogenesis and progression make for two separate, yet effective, systems for the study of HIV-associated neuropathology. PMID:18780230

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

PubMed Central

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

2017-01-01

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

Combined delivery of sorafenib and a MEK inhibitor using CXCR4-targeted nanoparticles reduces hepatic fibrosis and prevents tumor development

PubMed Central

Sung, Yun-Chieh; Liu, Ya-Chi; Chao, Po-Han; Chang, Chih-Chun; Jin, Pei-Ru; Lin, Ts-Ting; Lin, Ja-An; Cheng, Hui-Teng; Wang, Jane; Lai, Charles P.; Chen, Ling-Hsuan; Wu, Anthony Y.; Ho, Ting-Lun; Chiang, Tsaiyu; Gao, Dong-Yu; Duda, Dan G.; Chen, Yunching

2018-01-01

Liver damage and fibrosis are precursors of hepatocellular carcinoma (HCC). In HCC patients, sorafenib—a multikinase inhibitor drug—has been reported to exert anti-fibrotic activity. However, incomplete inhibition of RAF activity by sorafenib may also induce paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in malignant cells. The consequence of this effect in non-malignant disease (hepatic fibrosis) remains unknown. This study aimed to examine the effects of sorafenib on activated hepatic stellate cells (HSCs), and develop effective therapeutic approaches to treat liver fibrosis and prevent cancer development. Methods: We first examined the effects of sorafenib in combination with MEK inhibitors on fibrosis pathogenesis in vitro and in vivo. To improve the bioavailability and absorption by activated HSCs, we developed CXCR4-targeted nanoparticles (NPs) to co-deliver sorafenib and a MEK inhibitor to mice with liver damage. Results: We found that sorafenib induced MAPK activation in HSCs, and promoted their myofibroblast differentiation. Combining sorafenib with a MEK inhibitor suppressed both paradoxical MAPK activation and HSC activation in vitro, and alleviated liver fibrosis in a CCl4-induced murine model of liver damage. Furthermore, treatment with sorafenib/MEK inhibitor-loaded CXCR4-targeted NPs significantly suppressed hepatic fibrosis progression and further prevented fibrosis-associated HCC development and liver metastasis. Conclusions: Our results show that combined delivery of sorafenib and a MEK inhibitor via CXCR4-targeted NPs can prevent activation of ERK in activated HSCs and has anti-fibrotic effects in the CCl4-induced murine model. Targeting HSCs represents a promising strategy to prevent the development and progression of fibrosis-associated HCC. PMID:29463989

Characterization of Retinal Vascular and Neural Damage in a Novel Model of Diabetic Retinopathy.

PubMed

Weerasekera, Lakshini Y; Balmer, Lois A; Ram, Ramesh; Morahan, Grant

2015-06-01

Diabetic retinopathy (DR) is a major cause of blindness globally. Investigating the underlying mechanisms of DR would be aided by a suitable mouse model that developed key features seen in the human disease, and did so without carrying genetic modifications. This study was undertaken to produce such a model. Our panel of Collaborative Cross strains was screened for DR-like features after induction of diabetes by intravenous injection with alloxan or streptozotocin. Both flat-mounted whole-retina and histologic sections were studied for the presence of retinal lesions. Progression of DR was also studied by histologic examination of the retinal vascular and neural structure at various time points after diabetes onset. In addition, microarray investigations were conducted on retinas from control and diabetic mice. Features of DR such as degenerated pericytes, acellular capillaries, minor vascular proliferation, gliosis of Müller cells, and loss of ganglion cells were noted as early as day 7 in some mice. These lesions became more evident with time. After 21 days of diabetes, severe vascular proliferation, microaneurysms, preretinal damage, increased Müller cell gliosis, and damage to the outer retina were all obvious. Microarray studies found significant differential expression of multiple genes known to be involved in DR. The FOT_FB strain provides a useful model to investigate the pathogenesis of DR and to develop treatments for this vision-threatening disease.

Control of Mucosal Candidiasis in the Zebrafish Swim Bladder Depends on Neutrophils That Block Filament Invasion and Drive Extracellular-Trap Production

PubMed Central

Gratacap, Remi L.; Scherer, Allison K.; Seman, Brittany G.

2017-01-01

ABSTRACT Candida albicans is a ubiquitous mucosal commensal that is normally prevented from causing acute or chronic invasive disease. Neutrophils contribute to protection in oral infection but exacerbate vulvovaginal candidiasis. To dissect the role of neutrophils during mucosal candidiasis, we took advantage of a new, transparent zebrafish swim bladder infection model. Intravital microscopic tracking of individual animals revealed that the blocking of neutrophil recruitment leads to rapid mortality in this model through faster disease progression. Conversely, artificial recruitment of neutrophils during early infection reduces disease pressure. Noninvasive longitudinal tracking showed that mortality is a consequence of C. albicans breaching the epithelial barrier and invading surrounding tissues. Accordingly, we found that a hyperfilamentous C. albicans strain breaches the epithelial barrier more frequently and causes mortality in immunocompetent zebrafish. A lack of neutrophils at the infection site is associated with less fungus-associated extracellular DNA and less damage to fungal filaments, suggesting that neutrophil extracellular traps help to protect the epithelial barrier from C. albicans breach. We propose a homeostatic model where C. albicans disease pressure is balanced by neutrophil-mediated damage of fungi, maintaining this organism as a commensal while minimizing the risk of damage to host tissue. The unequaled ability to dissect infection dynamics at a high spatiotemporal resolution makes this zebrafish model a unique tool for understanding mucosal host-pathogen interactions. PMID:28607100

Quantification of birefringence readily measures the level of muscle damage in zebrafish

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

Berger, Joachim, E-mail: Joachim.Berger@Monash.edu; Sztal, Tamar; Currie, Peter D.

2012-07-13

Highlights: Black-Right-Pointing-Pointer Report of an unbiased quantification of the birefringence of muscle of fish larvae. Black-Right-Pointing-Pointer Quantification method readily identifies level of overall muscle damage. Black-Right-Pointing-Pointer Compare zebrafish muscle mutants for level of phenotype severity. Black-Right-Pointing-Pointer Proposed tool to survey treatments that aim to ameliorate muscular dystrophy. -- Abstract: Muscular dystrophies are a group of genetic disorders that progressively weaken and degenerate muscle. Many zebrafish models for human muscular dystrophies have been generated and analysed, including dystrophin-deficient zebrafish mutants dmd that model Duchenne Muscular Dystrophy. Under polarised light the zebrafish muscle can be detected as a bright area in anmore » otherwise dark background. This light effect, called birefringence, results from the diffraction of polarised light through the pseudo-crystalline array of the muscle sarcomeres. Muscle damage, as seen in zebrafish models for muscular dystrophies, can readily be detected by a reduction in the birefringence. Therefore, birefringence is a very sensitive indicator of overall muscle integrity within larval zebrafish. Unbiased documentation of the birefringence followed by densitometric measurement enables the quantification of the birefringence of zebrafish larvae. Thereby, the overall level of muscle integrity can be detected, allowing the identification and categorisation of zebrafish muscle mutants. In addition, we propose that the establish protocol can be used to analyse treatments aimed at ameliorating dystrophic zebrafish models.« less

Nonlinear and progressive failure aspects of transport composite fuselage damage tolerance

NASA Technical Reports Server (NTRS)

Walker, Tom; Ilcewicz, L.; Murphy, Dan; Dopker, Bernhard

1993-01-01

The purpose is to provide an end-user's perspective on the state of the art in life prediction and failure analysis by focusing on subsonic transport fuselage issues being addressed in the NASA/Boeing Advanced Technology Composite Aircraft Structure (ATCAS) contract and a related task-order contract. First, some discrepancies between the ATCAS tension-fracture test database and classical prediction methods is discussed, followed by an overview of material modeling work aimed at explaining some of these discrepancies. Finally, analysis efforts associated with a pressure-box test fixture are addressed, as an illustration of modeling complexities required to model and interpret tests.

Fast Prediction of Blast Damage from Airbursts: An Empirical Monte Carlo approach

NASA Astrophysics Data System (ADS)

Brown, Peter G.; Stokan, Ed

2016-10-01

The February 15, 2013 Chelyabinsk airburst was the first modern bolide whose associated shockwave caused blast damage at the ground (Popova et al., 2013). Near-Earth Object (NEO) impacts in the Chelyabinsk-size range (~20 m) are expected to occur every few decades (Boslough et al., 2015) and therefore we expect ground damage from meteoric airbursts to be the next planetary defense threat to be confronted. With pre-impact detections of small NEOs certain to become more common, decision makers will be faced with estimating blast damage from impactors with uncertain physical properties on short timescales.High fidelity numerical bolide entry models have been developed in recent years (eg. Boslough and Crawford, 2008; Shuvalov et al., 2013), but the wide range in a priori data about strength, fragmentation behavior, and other physical properties for a specific impactor make predictions of bolide behavior difficult. The long computational running times for hydrocode models make the exploration of a wide parameter space challenging in the days to hours before an actual impact.Our approach to this problem is to use an analytical bolide entry model, the triggered-progressive fragmentation model (TPFM) developed by ReVelle (2005) within a Monte Carlo formalism. In particular, we couple this model with empirical constraints on the statistical spread in strength for meter-scale impactors from Brown et al (2015) based on the observed height at maximum bolide brightness. We also use the correlation of peak bolide brightness with total energy as given by Brown (2016) as a proxy for fragmentation behaviour. Using these constraints, we are able to quickly generate a large set of realizations of probable bolide energy deposition curves and produce simple estimates of expected blast damage using existing analytical relations.We validate this code with the known parameters of the Chelyabinsk airburst and explore how changes to the entry conditions of the observed bolide may have modified the blast damage at the ground. We will also present how this approach could be used in an actual short-warning impact scenario.

Modeling of delamination in carbon/epoxy composite laminates under four point bending for damage detection and sensor placement optimization

NASA Astrophysics Data System (ADS)

Adu, Stephen Aboagye

Laminated carbon fiber-reinforced polymer composites (CFRPs) possess very high specific strength and stiffness and this has accounted for their wide use in structural applications, most especially in the aerospace industry, where the trade-off between weight and strength is critical. Even though they possess much larger strength ratio as compared to metals like aluminum and lithium, damage in the metals mentioned is rather localized. However, CFRPs generate complex damage zones at stress concentration, with damage progression in the form of matrix cracking, delamination and fiber fracture or fiber/matrix de-bonding. This thesis is aimed at performing; stiffness degradation analysis on composite coupons, containing embedded delamination using the Four-Point Bend Test. The Lamb wave-based approach as a structural health monitoring (SHM) technique is used for damage detection in the composite coupons. Tests were carried-out on unidirectional composite coupons, obtained from panels manufactured with pre-existing defect in the form of embedded delamination in a laminate of stacking sequence [06/904/0 6]T. Composite coupons were obtained from panels, fabricated using vacuum assisted resin transfer molding (VARTM), a liquid composite molding (LCM) process. The discontinuity in the laminate structure due to the de-bonding of the middle plies caused by the insertion of a 0.3 mm thick wax, in-between the middle four (4) ninety degree (90°) plies, is detected using lamb waves generated by surface mounted piezoelectric (PZT) actuators. From the surface mounted piezoelectric sensors, response for both undamaged (coupon with no defect) and damaged (delaminated coupon) is obtained. A numerical study of the embedded crack propagation in the composite coupon under four-point and three-point bending was carried out using FEM. Model validation was then carried out comparing the numerical results with the experimental. Here, surface-to-surface contact property was used to model the composite coupon under simply supported boundary conditions. Theoretically calculated bending stiffness's and maximum deflection were compared with that of the experimental case and the numerical. After the FEA model was properly benchmarked with test data and exact solution, data obtained from the FEM model were used for sensor placement optimization.

Increased chondrocyte apoptosis is associated with progression of osteoarthritis in spontaneous Guinea pig models of the disease.

PubMed

Zamli, Zaitunnatakhin; Adams, Michael A; Tarlton, John F; Sharif, Mohammed

2013-08-29

Osteoarthritis (OA) is the most common joint disease characterised by degradation of articular cartilage and bone remodelling. For almost a decade chondrocyte apoptosis has been investigated as a possible mechanism of cartilage damage in OA, but its precise role in initiation and/or progression of OA remains to the determined. The aim of this study is to determine the role of chondrocyte apoptosis in spontaneous animal models of OA. Right tibias from six male Dunkin Hartley (DH) and Bristol Strain 2 (BS2) guinea pigs were collected at 10, 16, 24 and 30 weeks of age. Fresh-frozen sections of tibial epiphysis were microscopically scored for OA, and immunostained with caspase-3 and TUNEL for apoptotic chondrocytes. The DH strain had more pronounced cartilage damage than BS2, especially at 30 weeks. At this time point, the apoptotic chondrocytes were largely confined to the deep zone of articular cartilage (AC) with a greater percentage in the medial side of DH than BS2 (DH: 5.7%, 95% CI: 4.2-7.2), BS2: 4.8%, 95% CI: 3.8-5.8), p > 0.05). DH had a significant progression of chondrocyte death between 24 to 30 weeks during which time significant changes were observed in AC fibrillation, proteoglycan depletion and overall microscopic OA score. A strong correlation (p ≤ 0.01) was found between chondrocyte apoptosis and AC fibrillation (r = 0.3), cellularity (r = 0.4) and overall microscopic OA scores (r = 0.4). Overall, the rate of progression in OA and apoptosis over the study period was greater in the DH (versus BS2) and the medial AC (versus lateral). Chondrocyte apoptosis was higher at the later stage of OA development when the cartilage matrix was hypocellular and highly fibrillated, suggesting that chondrocyte apoptosis is a late event in OA.

Alzheimer's disease Braak Stage progressions: reexamined and redefined as Borrelia infection transmission through neural circuits.

PubMed

MacDonald, Alan B

2007-01-01

Brain structure in health is a dynamic energized equation incorporating chemistry, neuronal structure, and circuitry components. The chemistry "piece" is represented by multiple neurotransmitters such as Acetylcholine, Serotonin, and Dopamine. The neuronal structure "piece" incorporates synapses and their connections. And finally circuits of neurons establish "architectural blueprints" of anatomic wiring diagrams of the higher order of brain neuron organizations. In Alzheimer's disease, there are progressive losses in all of these components. Brain structure crumbles. The deterioration in Alzheimer's is ordered, reproducible, and stepwise. Drs. Braak and Braak have described stages in the Alzheimer disease continuum. "Progressions" through Braak Stages benchmark "Regressions" in Cognitive function. Under the microscope, the Stages of Braak commence in brain regions near to the hippocampus, and over time, like a tsunami wave of destruction, overturn healthy brain regions, with neurofibrillary tangle damaged neurons "marching" through the temporal lobe, neocortex and occipital cortex. In effect the destruction ascends from the limbic regions to progressively destroy the higher brain centers. Rabies infection also "begins low and finishes high" in its wave of destruction of brain tissue. Herpes Zoster infections offer the paradigm of clinical latency of infection inside of nerves before the "marching commences". Varicella Zoster virus enters neurons in the pediatric years. Dormant virus remains inside the neurons for 50-80 years, tissue damage late in life (shingles) demonstrates the "march of the infection" down neural pathways (dermatomes) as linear areas of painful blisters loaded with virus from a childhood infection. Amalgamation of Zoster with Rabies models produces a hybrid model to explain all of the Braak Stages of Alzheimer's disease under a new paradigm, namely "Alzheimer's neuroborreliosis" in which latent Borrelia infections ascend neural circuits through the hippocampus to the higher brain centers, creating a trail of neurofibrillary tangle injured neurons in neural circuits of cholinergic neurons by transsynaptic transmission of infection from nerve to nerve.

Experimental animal models of encapsulating peritoneal sclerosis.

PubMed

Hoff, Catherine M

2005-04-01

Encapsulating peritoneal sclerosis (EPS) is an infrequent, but extremely serious complication of long-term peritoneal dialysis. The cause of EPS is unclear, but the low incidence suggests that it is most likely multifactorial. The elucidation of developmental pathways and predictive markers of EPS would facilitate the identification and management of high-risk patients. Animal models are often used to define pathways of disease progression and to test strategies for treatment and prevention in the patient population. Ideally such models could help to define the cause of EPS and its developmental pathways, to facilitate the identification of contributing factors and predictive markers, and to provide a system to test therapeutic strategies. Researchers have studied several rodent models of EPS that rely on chronic chemical irritation (for example, bleach, low-pH solution, chlorhexidine gluconate) to induce peritoneal sclerosis and abdominal encapsulation. Development in all models is progressive, with inflammation giving way to peritoneal fibrosis or sclerosis with accumulating membrane damage, culminating in cocoon formation. Microscopic findings are similar to those proposed as diagnostic criteria for clinical EPS: an initial inflammatory infiltrate and submesothelial thickening, collagen deposition, and activation and proliferation of peritoneal fibroblasts. The potential to block progression of peritoneal sclerosis in these models by anti-inflammatory, antifibrotic, and anti-angiogenic agents, and by inhibitors of the renin-angiotensin system have been demonstrated. Animal models based on clinically relevant risk factors (for example, uremia, peritonitis, and long-term exposure to dialysis solutions) now represent the next step in model development.

A Framework for Performing Multiscale Stochastic Progressive Failure Analysis of Composite Structures

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steven M.

2006-01-01

A framework is presented that enables coupled multiscale analysis of composite structures. The recently developed, free, Finite Element Analysis - Micromechanics Analysis Code (FEAMAC) software couples the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) with ABAQUS to perform micromechanics based FEA such that the nonlinear composite material response at each integration point is modeled at each increment by MAC/GMC. As a result, the stochastic nature of fiber breakage in composites can be simulated through incorporation of an appropriate damage and failure model that operates within MAC/GMC on the level of the fiber. Results are presented for the progressive failure analysis of a titanium matrix composite tensile specimen that illustrate the power and utility of the framework and address the techniques needed to model the statistical nature of the problem properly. In particular, it is shown that incorporating fiber strength randomness on multiple scales improves the quality of the simulation by enabling failure at locations other than those associated with structural level stress risers.

A Framework for Performing Multiscale Stochastic Progressive Failure Analysis of Composite Structures

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steven M.

2007-01-01

A framework is presented that enables coupled multiscale analysis of composite structures. The recently developed, free, Finite Element Analysis-Micromechanics Analysis Code (FEAMAC) software couples the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) with ABAQUS to perform micromechanics based FEA such that the nonlinear composite material response at each integration point is modeled at each increment by MAC/GMC. As a result, the stochastic nature of fiber breakage in composites can be simulated through incorporation of an appropriate damage and failure model that operates within MAC/GMC on the level of the fiber. Results are presented for the progressive failure analysis of a titanium matrix composite tensile specimen that illustrate the power and utility of the framework and address the techniques needed to model the statistical nature of the problem properly. In particular, it is shown that incorporating fiber strength randomness on multiple scales improves the quality of the simulation by enabling failure at locations other than those associated with structural level stress risers.

Progressive changes in chromatin structure and DNA damage response signals in bone marrow and peripheral blood during myelomagenesis.

PubMed

Gkotzamanidou, M; Terpos, E; Bamia, C; Kyrtopoulos, S A; Sfikakis, P P; Dimopoulos, M A; Souliotis, V L

2014-05-01

The molecular pathways implicated in multiple myeloma (MM) development are rather unknown. We studied epigenetic and DNA damage response (DDR) signals at selected model loci (N-ras, p53, d-globin) in bone marrow plasma cells and peripheral blood mononuclear cells (PBMCs) from patients with monoclonal gammopathy of undetermined significance (MGUS; n=20), smoldering/asymptomatic MM (SMM; n=29) and MM (n=18), as well as in healthy control-derived PBMCs (n=20). In both tissues analyzed, a progressive, significant increase in the looseness of local chromatin structure, gene expression levels and DNA repair efficiency from MGUS to SMM and finally to MM was observed (all P<0.002). Following ex vivo treatment with melphalan, a gradual suppression of the apoptotic pathway occurred in samples collected at different stages of myelomagenesis, with the severity and duration of the inhibition of RNA synthesis, p53 phosphorylation at serine15 and induction of apoptosis being higher in MGUS than SMM and lowest in MM patients (all P<0.0103). Interestingly, for all endpoints analyzed, a strong correlation between plasma cells and corresponding PBMCs was observed (all P<0.0003). We conclude that progressive changes in chromatin structure, transcriptional activity and DDR pathways during myelomagenesis occur in malignant plasma cells and that these changes are also reflected in PBMCs.

[Rapidly progressive glomerulonephritis: a diagnostic and therapeutic emergency].

PubMed

Halfon, Matthieu; Teta, Daniel; Rotman, Samuel; Pruijm, Menno; Humbert, Antoine

2014-02-26

Rapidly progressive glomerulonephritis (RPG) is a rare clinical syndrome characterized by kidney damage that can lead to irreversible kidney failure. RPG can be caused by primary glomerular disease or can be part of a systemic autoimmune disorder. All RPG have a similar pathophysiology (proliferation of cells in Bowman's capsule and formation of crescents) and clinical evolution (rapidly progressive kidney failure with proteinuria and an active urine sediment). Immunosuppressive therapy and sometimes plasma exchanges are required. Overall- and kidney survival are closely linked to the blood creatinine level at presentation, the percentage of damaged glomeruli, and to the underlying cause. RPG is therefore a diagnostic and therapeutic emergency that needs quick referral to a nephrologist.

Quantification of Energy Release in Composite Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon

2003-01-01

Energy release rate is usually suggested as a quantifier for assessing structural damage tolerance. Computational prediction of energy release rate is based on composite mechanics with micro-stress level damage assessment, finite element structural analysis and damage progression tracking modules. This report examines several issues associated with energy release rates in composite structures as follows: Chapter I demonstrates computational simulation of an adhesively bonded composite joint and validates the computed energy release rates by comparison with acoustic emission signals in the overall sense. Chapter II investigates the effect of crack plane orientation with respect to fiber direction on the energy release rates. Chapter III quantifies the effects of contiguous constraint plies on the residual stiffness of a 90 ply subjected to transverse tensile fractures. Chapter IV compares ICAN and ICAN/JAVA solutions of composites. Chapter V examines the effects of composite structural geometry and boundary conditions on damage progression characteristics.

Quantification of Energy Release in Composite Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon; Chamis, Christos C. (Technical Monitor)

2003-01-01

Energy release rate is usually suggested as a quantifier for assessing structural damage tolerance. Computational prediction of energy release rate is based on composite mechanics with micro-stress level damage assessment, finite element structural analysis and damage progression tracking modules. This report examines several issues associated with energy release rates in composite structures as follows: Chapter I demonstrates computational simulation of an adhesively bonded composite joint and validates the computed energy release rates by comparison with acoustic emission signals in the overall sense. Chapter II investigates the effect of crack plane orientation with respect to fiber direction on the energy release rates. Chapter III quantifies the effects of contiguous constraint plies on the residual stiffness of a 90 deg ply subjected to transverse tensile fractures. Chapter IV compares ICAN and ICAN/JAVA solutions of composites. Chapter V examines the effects of composite structural geometry and boundary conditions on damage progression characteristics.

Foveal damage in habitual poppers users.

PubMed

Audo, Isabelle; El Sanharawi, Mohamed; Vignal-Clermont, Catherine; Villa, Antoine; Morin, Annie; Conrath, John; Fompeydie, Dominique; Sahel, José-Alain; Gocho-Nakashima, Kiyoko; Goureau, Olivier; Paques, Michel

2011-06-01

To describe foveal damage in habitual use of poppers, a popular recreational drug. Retrospective observational case series. Six patients with bilateral vision loss after chronic popper inhalation were seen in 4 university-based ophthalmology departments. Symptoms, medical history, ophthalmic examination, and functional and morphological tests are described. All patients experienced progressive bilateral vision loss, with central photopsia in 2 cases. Initial visual acuities ranged from 20/50 to 20/25. In all patients, a bilateral yellow foveal spot was present that, by optical coherence tomography, was associated with disruption of the outer segments of foveal cones. Functional and anatomical damage was restricted to the fovea. The poppers involved were identified as isopropyl nitrite in 3 cases. Four patients showed anatomical and/or functional improvement over several months after discontinuing popper inhalation. Repeated inhalation of poppers may be associated with prolonged bilateral vision loss due to the disruption of foveal cone outer segments. Retinal damage may progressively improve following drug discontinuation.

The potential influence of radiation-induced microenvironments in neoplastic progression

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

1998-01-01

Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

Acquired pit of the optic nerve: a risk factor for progression of glaucoma.

PubMed

Ugurlu, S; Weitzman, M; Nduaguba, C; Caprioli, J

1998-04-01

To examine acquired pit of the optic nerve as a risk factor for progression of glaucoma. In a retrospective longitudinal study, 25 open-angle glaucoma patients with acquired pit of the optic nerve were compared with a group of 24 open-angle glaucoma patients without acquired pit of the optic nerve. The patients were matched for age, mean intraocular pressure, baseline ratio of neuroretinal rim area to disk area, visual field damage, and duration of follow-up. Serial optic disk photographs and visual fields of both groups were evaluated by three independent observers for glaucomatous progression. Of 46 acquired pits of the optic nerve in 37 eyes of 25 patients, 36 pits were located inferiorly (76%) and 11 superiorly (24%; P < .001). Progression of optic disk damage occurred in 16 patients (64%) in the group with acquired pit and in three patients (12.5%) in the group without acquired pit (P < .001). Progression of visual field loss occurred in 14 patients (56%) in the group with acquired pit and in six (25%) in the group without pit (P=.04). Bilateral acquired pit of the optic nerve was present in 12 patients (48%). Disk hemorrhages were observed more frequently in the group with acquired pit (10 eyes, 40%) compared with the group without pit (two eyes, 8%; P=.02). Among patients with glaucoma, patients with acquired pit of the optic nerve represent a subgroup who are at increased risk for progressive optic disk damage and visual field loss.

Superoxide Dismutase (SOD)-mimetic M40403 Is Protective in Cell and Fly Models of Paraquat Toxicity

PubMed Central

Filograna, Roberta; Godena, Vinay K.; Sanchez-Martinez, Alvaro; Ferrari, Emanuele; Casella, Luigi; Beltramini, Mariano; Bubacco, Luigi; Whitworth, Alexander J.; Bisaglia, Marco

2016-01-01

Parkinson disease is a debilitating and incurable neurodegenerative disorder affecting ∼1–2% of people over 65 years of age. Oxidative damage is considered to play a central role in the progression of Parkinson disease and strong evidence links chronic exposure to the pesticide paraquat with the incidence of the disease, most probably through the generation of oxidative damage. In this work, we demonstrated in human SH-SY5Y neuroblastoma cells the beneficial role of superoxide dismutase (SOD) enzymes against paraquat-induced toxicity, as well as the therapeutic potential of the SOD-mimetic compound M40403. Having verified the beneficial effects of superoxide dismutation in cells, we then evaluated the effects using Drosophila melanogaster as an in vivo model. Besides protecting against the oxidative damage induced by paraquat treatment, our data demonstrated that in Drosophila M40403 was able to compensate for the loss of endogenous SOD enzymes, acting both at a cytosolic and mitochondrial level. Because previous clinical trials have indicated that the M40403 molecule is well tolerated in humans, this study may have important implication for the treatment of Parkinson disease. PMID:26953346

Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.

PubMed

Kabu, Shushi; Gao, Yue; Kwon, Brian K; Labhasetwar, Vinod

2015-12-10

Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed toward regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neuroregenerative recovery is possible and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI. Copyright © 2015 Elsevier B.V. All rights reserved.

Electrical Resistance of SiC/SiC Ceramic Matrix Composites for Damage Detection and Life-Prediction

NASA Technical Reports Server (NTRS)

Smith, Craig; Morscher, Gregory; Xia, Zhenhai

2009-01-01

Ceramic matrix composites (CMC) are suitable for high temperature structural applications such as turbine airfoils and hypersonic thermal protection systems due to their low density high thermal conductivity. The employment of these materials in such applications is limited by the ability to accurately monitor and predict damage evolution. Current nondestructive methods such as ultrasound, x-ray, and thermal imaging are limited in their ability to quantify small scale, transverse, in-plane, matrix cracks developed over long-time creep and fatigue conditions. CMC is a multifunctional material in which the damage is coupled with the material s electrical resistance, providing the possibility of real-time information about the damage state through monitoring of resistance. Here, resistance measurement of SiC/SiC composites under mechanical load at both room temperature monotonic and high temperature creep conditions, coupled with a modal acoustic emission technique, can relate the effects of temperature, strain, matrix cracks, fiber breaks, and oxidation to the change in electrical resistance. A multiscale model can in turn be developed for life prediction of in-service composites, based on electrical resistance methods. Results of tensile mechanical testing of SiC/SiC composites at room and high temperatures will be discussed. Data relating electrical resistivity to composite constituent content, fiber architecture, temperature, matrix crack formation, and oxidation will be explained, along with progress in modeling such properties.

The impacts of tropical cyclones on the net carbon balance of eastern US forests (1851-2000)

NASA Astrophysics Data System (ADS)

Fisk, J. P.; Hurtt, G. C.; Chambers, J. Q.; Zeng, H.; Dolan, K. A.; Negrón-Juárez, R. I.

2013-12-01

In temperate forests of the eastern US, tropical cyclones are a principal agent of catastrophic wind damage, with dramatic impacts on the structure and functioning of forests. Substantial progress has been made to quantify forest damage and resulting gross carbon emissions from tropical cyclones. However, the net effect of storms on the carbon balance of forests depends not only on the biomass lost in single events, but also on the uptake during recovery from a mosaic of past events. This study estimates the net impacts of tropical cyclones on the carbon balance of US forests over the period 1851-2000. To track both disturbance and recovery and to isolate the effects of storms, a modeling framework is used combining gridded historical estimates of mortality and damage with a mechanistic model using an ensemble approach. The net effect of tropical cyclones on the carbon balance is shown to depend strongly on the spatial and temporal scales of analysis. On average, tropical cyclones contribute a net carbon source over latter half of the 19th century. However, throughout much of the 20th century a regional carbon sink is estimated resulting from periods of forest recovery exceeding damage. The large-scale net annual flux resulting from tropical cyclones varies by up to 50 Tg C yr-1, an amount equivalent to 17%-36% of the US forest carbon sink.

Prevalent cartilage damage and cartilage loss over time are associated with incident bone marrow lesions in the tibiofemoral compartments: the MOST Study

PubMed Central

Crema, Michel D.; Felson, David T.; Roemer, Frank W.; Wang, Ke; Marra, Monica D.; Nevitt, Michael C.; Lynch, John A.; Torner, James; Lewis, Cora E.; Guermazi, Ali

2012-01-01

Objective To assess the association of prevalent cartilage damage and cartilage loss over time with incident bone marrow lesions (BMLs) in the same subregion of the tibiofemoral compartments as detected on magnetic resonance imaging (MRI). Methods The Multicenter Osteoarthritis Study is an observational study of individuals with or at risk for knee osteoarthritis (OA). Subjects whose baseline and 30-month follow-up MRIs were read for findings of OA were included. MRI was performed with a 1.0T extremity system. Tibiofemoral compartments were divided into 10 subregions. Cartilage morphology was scored from 0 to 6 and BMLs were scored from 0 to 3. Prevalent cartilage damage and cartilage loss over time were considered predictors of incident BMLs. Associations were assessed using logistic regression, with adjustments for potential confounders. Results Medially, incident BMLs were associated with baseline cartilage damage (adjusted odds ratio (OR) 3.9 [95% CI 3.0, 5.1]), incident cartilage loss (7.3 [95% CI 5.0, 10.7]) and progression of cartilage loss (7.6 [95% CI 5.1, 11.3]) Laterally, incident BMLs were associated with baseline cartilage damage (4.1 [95% CI 2.6, 6.3]), incident cartilage loss (6.0 [95% CI 3.1, 11.8]), and progression of cartilage loss (11.9 [95% CI 6.2, 23.0]). Conclusion Prevalent cartilage damage and cartilage loss over time are strongly associated with incident BMLs in the same subregion, supporting the significance of the close interrelation of the osteochondral unit in the progression of knee OA. PMID:23178289

Polyethylene damage and deformation on fixed-bearing, non-conforming unicondylar knee replacements corresponding to progressive changes in alignment and fixation.

PubMed

Harman, Melinda K; Schmitt, Sabine; Rössing, Sven; Banks, Scott A; Sharf, Hans-Peter; Viceconti, Marco; Hodge, W Andrew

2010-07-01

Deviations from nominal alignment of unicondylar knee replacements impact knee biomechanics, including the load and stress distribution at the articular contact surfaces. This study characterizes relationships between the biomechanical environment, distinguished by progressive changes in alignment and fixation, and articular damage and deformation in a consecutive series of retrieved unicondylar knee replacements. Twenty seven fixed-bearing, non-conforming unicondylar knee replacements of one design were retrieved after 2 to 13 years of in vivo function. The in vivo biomechanical environment was characterized by grading component migration measured from full-length radiographs and grading component fixation based on intraoperative manual palpation. Articular damage patterns and linear deformation on the polyethylene inserts were measured using optical photogrammetry and contact point digitization. Articular damage patterns and surface deformation on the explanted polyethylene inserts corresponded to progressive changes in component alignment and fixation. Component migration produced higher deformation rates, whereas loosening contributed to larger damage areas but lower deformation rates. Migration and loosening of the femoral component, but not the tibial component, were factors contributing to large regions of abrasion concentrated on the articular periphery. Classifying component migration and fixation at revision proved useful for distinguishing common biomechanical conditions associated with the varied polyethylene damage patterns and linear deformation for this fixed-bearing, non-conforming design. Pre-clinical evaluations of unicondylar knee replacements that are capable of reproducing variations in clinical alignment and predicting the observed wear mechanisms are necessary to better understand the impact of knee biomechanics and design on unicondylar knee replacement longevity. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

The role of tectonic damage and brittle rock fracture in the development of large rock slope failures

NASA Astrophysics Data System (ADS)

Brideau, Marc-André; Yan, Ming; Stead, Doug

2009-01-01

Rock slope failures are frequently controlled by a complex combination of discontinuities that facilitate kinematic release. These discontinuities are often associated with discrete folds, faults, and shear zones, and/or related tectonic damage. The authors, through detailed case studies, illustrate the importance of considering the influence of tectonic structures not only on three-dimensional kinematic release but also in the reduction of rock mass properties due to induced damage. The case studies selected reflect a wide range of rock mass conditions. In addition to active rock slope failures they include two major historic failures, the Hope Slide, which occurred in British Columbia in 1965 and the Randa rockslides which occurred in Switzerland in 1991. Detailed engineering geological mapping combined with rock testing, GIS data analysis and for selected case numerical modelling, have shown that specific rock slope failure mechanisms may be conveniently related to rock mass classifications such as the Geological Strength Index (GSI). The importance of brittle intact rock fracture in association with pre-existing rock mass damage is emphasized though a consideration of the processes involved in the progressive-time dependent development not only of though-going failure surfaces but also lateral and rear-release mechanisms. Preliminary modelling data are presented to illustrate the importance of intact rock fracture and step-path failure mechanisms; and the results are discussed with reference to selected field observations. The authors emphasize the importance of considering all forms of pre-existing rock mass damage when assessing potential or operative failure mechanisms. It is suggested that a rock slope rock mass damage assessment can provide an improved understanding of the potential failure mode, the likely hazard presented, and appropriate methods of both analysis and remedial treatment.

Matcha, a powdered green tea, ameliorates the progression of renal and hepatic damage in type 2 diabetic OLETF rats.

PubMed

Yamabe, Noriko; Kang, Ki Sung; Hur, Jong Moon; Yokozawa, Takako

2009-08-01

Matcha, a powdered green tea produced by grinding with a stone mill, has been popularly used in the traditional tea ceremony and foods in Japan. Matcha is well known to be richer in some nutritional elements and epigallocatechin 3-O-gallate than other green teas. In our previous study, epigallocatechin 3-O-gallate exhibited protective effects against renal damage in a rat model of diabetic nephropathy. In the present study, we investigated the preventive effects of Matcha (50, 100, or 200 mg/kg/day) on the progression of hepatic and renal damage in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats were orally administered Matcha for 16 weeks, and we assessed biochemical parameters in the serum, liver, and kidney and expression levels of major products of advanced glycation end products (AGEs), N(6)-(carboxylmethyl)lysine (CML) and N(6)-(carboxylethyl)lysine (CEL), receptor for AGE (RAGE), and sterol regulatory element binding proteins (SREBPs)-1 and -2. Serum total protein levels were significantly increased by Matcha administration, whereas the serum albumin and glycosylated protein levels as well as the renal glucose and triglyceride levels were only slightly or not at all affected. However, Matcha treatment significantly lowered the glucose, triglyceride, and total cholesterol levels in the serum and liver, renal AGE levels, and the serum thiobarbituric acid-reactive substances levels. In addition, Matcha supplementation resulted in decreases in the renal CML, CEL, and RAGE expressions as well as an increase in hepatic SREBP-2 expression, but not that of SREBP-1. These results suggest that Matcha protects against hepatic and renal damage through the suppression of renal AGE accumulation, by decreases in hepatic glucose, triglyceride, and total cholesterol levels, and by its antioxidant activities.

The Saccharomyces cerevisiae RAD9, RAD17, RAD24 and MEC3 genes are required for tolerating irreparable, ultraviolet-induced DNA damage.

PubMed Central

Paulovich, A G; Armour, C D; Hartwell, L H

1998-01-01

In wild-type Saccharomyces cerevisiae, a checkpoint slows the rate of progression of an ongoing S phase in response to exposure to a DNA-alkylating agent. Mutations that eliminate S phase regulation also confer sensitivity to alkylating agents, leading us to suggest that, by regulating the S phase rate, cells are either better able to repair or better able to replicate damaged DNA. In this study, we determine the effects of mutations that impair S phase regulation on the ability of excision repair-defective cells to replicate irreparably UV-damaged DNA. We assay survival after UV irradiation, as well as the genetic consequences of replicating a damaged template, namely mutation and sister chromatid exchange induction. We find that RAD9, RAD17, RAD24, and MEC3 are required for UV-induced (although not spontaneous) mutagenesis, and that RAD9 and RAD17 (but not REV3, RAD24, and MEC3) are required for maximal induction of replication-dependent sister chromatid exchange. Therefore, checkpoint genes not only control cell cycle progression in response to damage, but also play a role in accommodating DNA damage during replication. PMID:9725831

The Saccharomyces cerevisiae RAD9, RAD17, RAD24 and MEC3 genes are required for tolerating irreparable, ultraviolet-induced DNA damage.

PubMed

Paulovich, A G; Armour, C D; Hartwell, L H

1998-09-01

In wild-type Saccharomyces cerevisiae, a checkpoint slows the rate of progression of an ongoing S phase in response to exposure to a DNA-alkylating agent. Mutations that eliminate S phase regulation also confer sensitivity to alkylating agents, leading us to suggest that, by regulating the S phase rate, cells are either better able to repair or better able to replicate damaged DNA. In this study, we determine the effects of mutations that impair S phase regulation on the ability of excision repair-defective cells to replicate irreparably UV-damaged DNA. We assay survival after UV irradiation, as well as the genetic consequences of replicating a damaged template, namely mutation and sister chromatid exchange induction. We find that RAD9, RAD17, RAD24, and MEC3 are required for UV-induced (although not spontaneous) mutagenesis, and that RAD9 and RAD17 (but not REV3, RAD24, and MEC3) are required for maximal induction of replication-dependent sister chromatid exchange. Therefore, checkpoint genes not only control cell cycle progression in response to damage, but also play a role in accommodating DNA damage during replication.

46 CFR 42.20-12 - Conditions of equilibrium.

Code of Federal Regulations, 2013 CFR

2013-10-01

... § 42.15-65. (b) Progressive flooding. If pipes, ducts, or tunnels are situated within the assumed extent of damage penetration as defined in § 42.20-11 (a) and (b), progressive flooding cannot extend to..., heel, and trim, is below the lower edge of any opening through which progressive flooding can take...

46 CFR 42.20-12 - Conditions of equilibrium.

Code of Federal Regulations, 2012 CFR

2012-10-01

... § 42.15-65. (b) Progressive flooding. If pipes, ducts, or tunnels are situated within the assumed extent of damage penetration as defined in § 42.20-11 (a) and (b), progressive flooding cannot extend to..., heel, and trim, is below the lower edge of any opening through which progressive flooding can take...

46 CFR 42.20-12 - Conditions of equilibrium.

Code of Federal Regulations, 2014 CFR

2014-10-01

... § 42.15-65. (b) Progressive flooding. If pipes, ducts, or tunnels are situated within the assumed extent of damage penetration as defined in § 42.20-11 (a) and (b), progressive flooding cannot extend to..., heel, and trim, is below the lower edge of any opening through which progressive flooding can take...

Myocardial infarction increases progressive visual field defects in well treated early primary open angle glaucoma--a prospective case control study.

PubMed

Mondal, Lakshmikanta; Baidya, Krishnapada; Choudhury, Himadri; Roy, Rupam

2013-06-01

The purpose of the study was to evaluate the progression of glaucomatous field damage in patients with stable primary open angle glaucoma after an attack of myocardial infarction. In this case control study, 62 open angle glaucoma patients were selected and regularly followed up. Among 62 patients, 9 had an attack of myocardial infarction. The intra-ocular pressure and visual field progression of both the groups (myocardial infarction versus no myocardial infarction) were analysed. Three (33.3%) out of 9 patients who had suffered from myocardial infarction showed progressive visual field loss whereas only 9 (16.9%) out of 53 patients who did not suffer from myocardial infarction, showed progressive field changes. Both the groups had stable target intra-ocular pressure between 14 and 16 mm Hg. Myocardial infarction may adversely influence the progression of primary open angle glaucoma which is suspected to result from ischaemia induced neuronal loss and only control of intraocular pressure is not the only solution. We have to look for other drugs that prevents ischaemia induced neuronal damage.

Kinetics and cellular sources of cathelicidin during the course of experimental latent tuberculous infection and progressive pulmonary tuberculosis.

PubMed

Castañeda-Delgado, J; Hernández-Pando, R; Serrano, C J; Aguilar-León, D; León-Contreras, J; Rivas-Santiago, C; Méndez, R; González-Curiel, I; Enciso-Moreno, A; Rivas-Santiago, B

2010-09-01

In spite of advances in immunology on mycobacterial infection, there are few studies on the role of anti-microbial peptides in tuberculosis. The cathelin-related anti-microbial peptide (CRAMP) is the only cathelicidin isolated from mice. In this work we investigated the cellular sources and the production kinetics of this molecule during experimental tuberculosis, using two well-characterized models of latent or chronic infection and progressive disease. The lung of non-infected control mice expressed CRAMP at very low levels. In both models of experimental tuberculosis the main cells immunolabelled for CRAMP were bronchial epithelial cells, macrophages and pneumocytes types II and I. After intratracheal infection with a high bacilli dose (H37Rv strain) in Balb/c mice to produce progressive disease, a high CRAMP gene expression was induced showing three peaks: very early after 1 day of infection, at day 21 when the peak of protective immunity in this model is raised, and at day 28 when the progressive phase starts and the immunoelectronmicroscopy study showed intense immunolabelling in the cell wall and cytoplasm of intracellular bacilli, as well as in cytoplasmic vacuoles. Interestingly, at day 60 post-infection, when advanced progressive disease is well established, characterized by high bacillary loads and extensive tissue damage, CRAMP gene expression decreased but strong CRAMP immunostaining was detected in vacuolated macrophages filled with bacilli. Thus, cathelicidin is highly produced during experimental pulmonary tuberculosis from diverse cellular sources and could have significant participation in its pathogenesis. © 2010 British Society for Immunology.

Progressive Fracture and Damage Tolerance of Composite Pressure Vessels

NASA Technical Reports Server (NTRS)

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

1997-01-01

Structural performance (integrity, durability and damage tolerance) of fiber reinforced composite pressure vessels, designed for pressured shelters for planetary exploration, is investigated via computational simulation. An integrated computer code is utilized for the simulation of damage initiation, growth, and propagation under pressure. Aramid fibers are considered in a rubbery polymer matrix for the composite system. Effects of fiber orientation and fabrication defect/accidental damages are investigated with regard to the safety and durability of the shelter. Results show the viability of fiber reinforced pressure vessels as damage tolerant shelters for planetary colonization.

Impact damage in composite plates

NASA Technical Reports Server (NTRS)

Shahid, I.; Lee, S.; Chang, F. K.; Shah, B. M.

1995-01-01

The objective of this research paper was to link two computer codes, PDCOMP (for Progressive Damage Analysis for Laminated Composites) and 3DIMPACT (for the prediction of the extent of delaminations in laminated composites resulting from point impact loads), in order to predict impact damage by taking into account local damage and material degradation and to estimate residual stiffness of composites after impact. The resulting graphs and analysis versus test results are presented along with the conclusive results of the codes' performances.

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

PubMed Central

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

2013-01-01

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

Experimental Hypersonic Aerodynamic Characteristics of the Space Shuttle Orbiter for a Range of Damage Scenarios

NASA Technical Reports Server (NTRS)

Brauckmann, Gregory J.; Scallion, William I.

2004-01-01

Aerodynamic tests in support of the Columbia accident investigation were conducted in two hypersonic wind tunnels at the NASA Langley Research Center, the 20-Inch Mach 6 Air Tunnel and the 20-Inch CF4 Tunnel. The primary purpose of these tests was to measure the forces and moments generated by a variety of outer mold line alterations (damage scenarios) using 0.0075-scale models of the Space Shuttle Orbiter. Simultaneously acquired global heat transfer mappings were obtained for a majority of the configurations tested. Test parametrics included angles of attack from 38 to 42 deg, unit Reynolds numbers from 0.3 x 10(exp 6) to 3.0 x 10(exp 6) per foot, and normal shock density ratios of 5 (Mach 6 air) and 12 (CF4). The damage scenarios evaluated included asymmetric boundary layer transition, gouges in the windward surface thermal protection system tiles, wing leading edge damage (partially and fully missing reinforced carbon-carbon (RCC) panels), deformation of the wing windward surface, and main landing gear and/or door deployment. The measured aerodynamic increments for the damage scenarios examined were generally small in magnitude, as were the flight-derived values during most of the entry prior to loss of communication. A progressive damage scenario is presented that qualitatively matches the flight observations for the STS-107 entry.

Tissue damage negatively regulates LPS-induced macrophage necroptosis.

PubMed

Li, Z; Scott, M J; Fan, E K; Li, Y; Liu, J; Xiao, G; Li, S; Billiar, T R; Wilson, M A; Jiang, Y; Fan, J

2016-09-01

Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mφ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mφ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mφ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules.

Tissue damage negatively regulates LPS-induced macrophage necroptosis

PubMed Central

Li, Z; Scott, M J; Fan, E K; Li, Y; Liu, J; Xiao, G; Li, S; Billiar, T R; Wilson, M A; Jiang, Y; Fan, J

2016-01-01

Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mφ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mφ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mφ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules. PMID:26943325

Material State Awareness for Composites Part II: Precursor Damage Analysis and Quantification of Degraded Material Properties Using Quantitative Ultrasonic Image Correlation (QUIC)

PubMed Central

Patra, Subir; Banerjee, Sourav

2017-01-01

Material state awareness of composites using conventional Nondestructive Evaluation (NDE) method is limited by finding the size and the locations of the cracks and the delamination in a composite structure. To aid the progressive failure models using the slow growth criteria, the awareness of the precursor damage state and quantification of the degraded material properties is necessary, which is challenging using the current NDE methods. To quantify the material state, a new offline NDE method is reported herein. The new method named Quantitative Ultrasonic Image Correlation (QUIC) is devised, where the concept of microcontinuum mechanics is hybrid with the experimentally measured Ultrasonic wave parameters. This unique combination resulted in a parameter called Nonlocal Damage Entropy for the precursor awareness. High frequency (more than 25 MHz) scanning acoustic microscopy is employed for the proposed QUIC. Eight woven carbon-fiber-reinforced-plastic composite specimens were tested under fatigue up to 70% of their remaining useful life. During the first 30% of the life, the proposed nonlocal damage entropy is plotted to demonstrate the degradation of the material properties via awareness of the precursor damage state. Visual proofs for the precursor damage states are provided with the digital images obtained from the micro-optical microscopy, the scanning acoustic microscopy and the scanning electron microscopy. PMID:29258256

Shear capacity assessment of corrosion-damaged reinforced concrete beams : final report.

DOT National Transportation Integrated Search

2003-12-01

This study investigated how the shear capacity of reinforced concrete bridge beams is affected by corrosion damage to the shear stirrups. It described the changes that occur in shear capacity and concrete cracking as shear stirrup corrosion progresse...

Non-cytotoxic Concentration of Cisplatin Decreases Neuroplasticity-Related Proteins and Neurite Outgrowth Without Affecting the Expression of NGF in PC12 Cells.

PubMed

Ferreira, Rafaela Scalco; Dos Santos, Neife Aparecida Guinaim; Martins, Nádia Maria; Fernandes, Laís Silva; Dos Santos, Antonio Cardozo

2016-11-01

Cisplatin is the most effective and neurotoxic platinum chemotherapeutic agent. It induces a peripheral neuropathy characterized by distal axonal degeneration that might progress to degeneration of cell bodies and apoptosis. Most symptoms occur nearby distal axonal branches and axonal degeneration might induce peripheral neuropathy regardless neuronal apoptosis. The toxic mechanism of cisplatin has been mainly associated with DNA damage, but cisplatin might also affect neurite outgrowth. Nevertheless, the neurotoxic mechanism of cisplatin remains unclear. We investigated the early effects of cisplatin on axonal plasticity by using non-cytotoxic concentrations of cisplatin and PC12 cells as a model of neurite outgrowth and differentiation. PC12 cells express NGF-receptors (trkA) and respond to NGF by forming neurites, branches and synaptic vesicles. For comparison, we used a neuronal model (SH-SY5Y cells) that does not express trkA nor responds to NGF. Cisplatin did not change NGF expression in PC12 cells and decreased neurite outgrowth in both models, suggesting a NGF/trkA independent mechanism. It also reduced axonal growth (GAP-43) and synaptic (synapsin I and synaptophysin) proteins in PC12 cells, without inducing mitochondrial damage or apoptosis. Therefore, cisplatin might affect axonal plasticity before DNA damage, NGF/trkA down-regulation, mitochondrial damage or neuronal apoptosis. This is the first study to show that neuroplasticity-related proteins might be early targets of the neurotoxic action of cisplatin and their role on cisplatin-induced peripheral neuropathy should be investigated in vivo.

31 CFR 341.8 - Payment or redemption during lifetime of owner.

Code of Federal Regulations, 2014 CFR

2014-07-01

... chores. (4) Cancer which is inoperable and progressive. (5) Damage to the brain or brain abnormality...) Certain progressive diseases which have resulted in the physical loss or atrophy of a limb, such as...

31 CFR 341.8 - Payment or redemption during lifetime of owner.

Code of Federal Regulations, 2012 CFR

2012-07-01

... progressive. (5) Damage to the brain or brain abnormality which has resulted in severe loss of judgment... substantial, gainful activity: (1) Loss of use of two limbs. (2) Certain progressive diseases which have...

31 CFR 341.8 - Payment or redemption during lifetime of owner.

Code of Federal Regulations, 2011 CFR

2011-07-01

... progressive. (5) Damage to the brain or brain abnormality which has resulted in severe loss of judgment... substantial, gainful activity: (1) Loss of use of two limbs. (2) Certain progressive diseases which have...

31 CFR 341.8 - Payment or redemption during lifetime of owner.

Code of Federal Regulations, 2013 CFR

2013-07-01

... progressive. (5) Damage to the brain or brain abnormality which has resulted in severe loss of judgment... substantial, gainful activity: (1) Loss of use of two limbs. (2) Certain progressive diseases which have...

Material State Awareness for Composites Part I: Precursor Damage Analysis Using Ultrasonic Guided Coda Wave Interferometry (CWI).

PubMed

Patra, Subir; Banerjee, Sourav

2017-12-16

Detection of precursor damage followed by the quantification of the degraded material properties could lead to more accurate progressive failure models for composite materials. However, such information is not readily available. In composite materials, the precursor damages-for example matrix cracking, microcracks, voids, interlaminar pre-delamination crack joining matrix cracks, fiber micro-buckling, local fiber breakage, local debonding, etc.-are insensitive to the low-frequency ultrasonic guided-wave-based online nondestructive evaluation (NDE) or Structural Health Monitoring (SHM) (~100-~500 kHz) systems. Overcoming this barrier, in this article, an online ultrasonic technique is proposed using the coda part of the guided wave signal, which is often neglected. Although the first-arrival wave packets that contain the fundamental guided Lamb wave modes are unaltered, the coda wave packets however carry significant information about the precursor events with predictable phase shifts. The Taylor-series-based modified Coda Wave Interferometry (CWI) technique is proposed to quantify the stretch parameter to compensate the phase shifts in the coda wave as a result of precursor damage in composites. The CWI analysis was performed on five woven composite-fiber-reinforced-laminate specimens, and the precursor events were identified. Next, the precursor damage states were verified using high-frequency Scanning Acoustic Microscopy (SAM) and optical microscopy imaging.

Brain effect of insulin and clonazepam in diabetic rats under depressive-like behavior.

PubMed

Wayhs, Carlos Alberto Yasin; Mescka, Caroline Paula; Vanzin, Camila Simioni; Ribas, Graziela Schmitt; Guerreiro, Gilian; Nin, Maurício Schüler; Manfredini, Vanusa; Barros, Helena Maria Tannhauser; Vargas, Carmen Regla

2013-12-01

Diabetes mellitus is characterized by hyperglycemia resulting from defects on insulin secretion, insulin action, or both. It has recently become clear that the central nervous system is not spared from the deleterious effects of diabetes, since diabetic encephalopathy was recognized as a complication of this heterogeneous metabolic disorder. There is a well recognized association between depression and diabetes, once prevalence of depression in diabetic patients is higher than in general population, and clonazepam is being used to treat this complication. Oxidative stress is widely accepted as playing a key mediatory role in the development and progression of diabetes and its complications. In this work we analyzed DNA damage by comet assay and lipid damage in prefrontal cortex, hippocampus and striatum of streptozotocin-induced diabetic rats submitted to the forced swimming test. It was verified that the diabetic group presented DNA and lipid damage in the brain areas evaluated, when compared to the control groups. Additionally, a significant reduction of the DNA and lipid damage in animals treated with insulin and/or clonazepam was observed. These data suggest that the association of these two drugs could protect against DNA and lipid damage in diabetic rats submitted to the forced swimming test, an animal model of depression.

Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis.

PubMed

Camps, Montserrat; Rückle, Thomas; Ji, Hong; Ardissone, Vittoria; Rintelen, Felix; Shaw, Jeffrey; Ferrandi, Chiara; Chabert, Christian; Gillieron, Corine; Françon, Bernard; Martin, Thierry; Gretener, Denise; Perrin, Dominique; Leroy, Didier; Vitte, Pierre-Alain; Hirsch, Emilio; Wymann, Matthias P; Cirillo, Rocco; Schwarz, Matthias K; Rommel, Christian

2005-09-01

Phosphoinositide 3-kinases (PI3K) have long been considered promising drug targets for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. But the lack of specificity, isoform selectivity and poor biopharmaceutical profile of PI3K inhibitors have so far hampered rigorous disease-relevant target validation. Here we describe the identification and development of specific, selective and orally active small-molecule inhibitors of PI3Kgamma (encoded by Pik3cg). We show that Pik3cg(-/-) mice are largely protected in mouse models of rheumatoid arthritis; this protection correlates with defective neutrophil migration, further validating PI3Kgamma as a therapeutic target. We also describe that oral treatment with a PI3Kgamma inhibitor suppresses the progression of joint inflammation and damage in two distinct mouse models of rheumatoid arthritis, reproducing the protective effects shown by Pik3cg(-/-) mice. Our results identify selective PI3Kgamma inhibitors as potential therapeutic molecules for the treatment of chronic inflammatory disorders such as rheumatoid arthritis.

Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

PubMed

Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

2015-01-01

Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

Adverse Health Effects of Thirdhand Smoke: From Cell to Animal Models.

PubMed

Hang, Bo; Wang, Pin; Zhao, Yue; Sarker, Altaf; Chenna, Ahmed; Xia, Yankai; Snijders, Antoine M; Mao, Jian-Hua

2017-04-28

The newly identified smoke hazard, thirdhand smoke (THS), has gained public attention in recent years but its health impact and biological effects are largely unknown. THS may be defined by "the four Rs": tobacco chemicals that remain, react, re-emit, and/or are resuspended long after active smoking has ceased. This review summarizes recent research progress in the effects of THS on genotoxicity, metabolism and early life development using cellular and animal models. We first reported that THS generated in laboratory systems caused significant DNA damage in human cell lines. Our finding that THS significantly induces oxidative base lesions has been confirmed in skin wounds of mice models exposed to THS. THS also induced metabolomic changes in human reproductive cell lines. Furthermore, we demonstrated that early exposure to THS not only negatively impacts body weight in both male and female mice, but also induces persistent changes to immunological parameters in peripheral blood in these mice. These results indicate that THS is genotoxic at realistic experimental doses and that there may be a window of susceptibility for some forms of cellular damage induced by THS.

Mucosal tolerance disruption favors disease progression in an extraorbital lacrimal gland excision model of murine dry eye.

PubMed

Guzmán, Mauricio; Keitelman, Irene; Sabbione, Florencia; Trevani, Analía S; Giordano, Mirta N; Galletti, Jeremías G

2016-10-01

Dry eye is a highly prevalent immune disorder characterized by a dysfunctional tear film and a Th1/Th17 T cell response at the ocular surface. The specificity of these pathogenic effector T cells remains to be determined, but auto-reactivity is considered likely. However, we have previously shown that ocular mucosal tolerance to an exogenous antigen is disrupted in a scopolamine-induced murine dry eye model and that it is actually responsible for disease progression. Here we report comparable findings in an entirely different murine model of dry eye that involves resection of the extraorbital lacrimal glands but no systemic muscarinic receptor blockade. Upon ocular instillation of ovalbumin, a delayed breakdown in mucosal tolerance to this antigen was observed in excised but not in sham-operated mice, which was mediated by interferon γ- and interleukin 17-producing antigen-specific T cells. Consistently, antigen-specific regulatory T cells were detectable in sham-operated but not in excised mice. As for other models of ocular surface disorders, epithelial activation of the NF-κB pathway by desiccating stress was determinant in the mucosal immune outcome. Underscoring the role of mucosal tolerance disruption in dry eye pathogenesis, its prevention by a topical NF-κB inhibitor led to reduced corneal damage in excised mice. Altogether these results show that surgically originated desiccating stress also initiates an abnormal Th1/Th17 T cell response to harmless exogenous antigens that reach the ocular surface. This event might actually contribute to corneal damage and challenges the conception of dry eye as a strictly autoimmune disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Photokinetic Drug Delivery: Light-Enhanced Permeation in an In Vitro Eye Model.

PubMed

Godley, Bernard F; Kraft, Edward R; Giannos, Steven A; Zhao, Zhen-Yang; Haag, Anthony M; Wen, Julie W

2015-12-01

To investigate light-enhanced molecular movement as a potential technology for drug delivery. To do this, we developed an in vitro eye model while representing similar concentration gradient conditions and compositions found in the eye. The eye model unit was fabricated by inserting a cross-linked type I collagen membrane in a spectrophotometer cuvette with 1% hyaluronic acid as the drug recipient medium. Photokinetic delivery was studied by illuminating 1 mg/mL methotrexate (MTX) placed in the drug donor compartment on top of the membrane, with noncoherent 450 nm light at 8.2 mW from an LED source pulsed at 25 cycles per second, placed in contact with the solution. A modified UV-visual spectrophotometer was employed to rapidly determine the concentration of MTX, at progressive 1 mm distances away from the membrane, within the viscous recipient medium of the model eye after 1 h. A defined, progressive concentration gradient was observed within the nonagitated drug recipient media, diminishing with greater distances from the membrane. Transport of MTX through the membrane was significantly enhanced (ranging from 2 to 3 times, P < 0.05 to P ≤ 0.001) by photokinetic methods compared with control conditions by determining drug concentrations at 4 defined distances from the membrane. According to scanning electron microscopy images, no structural damage or shunts were created on the surface of the cross-linked gelatin membrane. The application of pulsed noncoherent visible light significantly enhances the permeation of MTX through a cross-linked collagen membrane and hyaluronic acid recipient medium without causing structural damage to the membrane.

Adenosine A2A Receptor Activation and Macrophage-mediated Experimental Glomerulonephritis

PubMed Central

Garcia, Gabriela E.; Truong, Luan D.; Li, Ping; Zhang, Ping; Du, Jie; Chen, Jiang-Fan; Feng, Lili

2010-01-01

In immune-induced inflammation, leukocytes are key mediators of tissue damage. Since A2A adenosine receptors (A2AR) are endogenous suppressors of inflammation, we examined cellular and molecular mechanisms of kidney damage to determine whether selective activation of A2AR will suppress inflammation in a rat model of glomerulonephritis. Activation of A2AR reduced the degree of kidney injury in both the acute inflammatory phase and the progressive phase of glomerulonephritis. This protection against acute and chronic inflammation was associated with suppression of the glomerular expression of the MDC/CCL22 chemokine and down-regulation of MIP-1α/CCL3, RANTES/CCL5, MIP-1β/CCL4, and MCP-1/CCL2 chemokines. The expression of anti-inflammatory cytokines, IL-4 and IL-10, also increased. The mechanism for these anti-inflammatory responses to the A2AR agonist was suppression of macrophages function. A2AR expression was increased in macrophages, macrophage-derived chemokines were reduced in response to the A2AR agonist, and chemokines not expressed in macrophages did not respond to A2AR activation. Thus, activation of the A2AR on macrophages inhibits immune-associated inflammation. In glomerulonephritis, A2AR activation modulates inflammation and tissue damage even in the progressive phase of glomerulonephritis. Accordingly, pharmacological activation of A2AR could be developed into a novel treatment for glomerulonephritis and other macrophage-related inflammatory diseases. PMID:17898087

A composite measure to explore visual disability in primary progressive multiple sclerosis.

PubMed

Poretto, Valentina; Petracca, Maria; Saiote, Catarina; Mormina, Enricomaria; Howard, Jonathan; Miller, Aaron; Lublin, Fred D; Inglese, Matilde

2017-01-01

Optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can provide complementary information on visual system damage in multiple sclerosis (MS). The objective of this paper is to determine whether a composite OCT/MRI score, reflecting cumulative damage along the entire visual pathway, can predict visual deficits in primary progressive multiple sclerosis (PPMS). Twenty-five PPMS patients and 20 age-matched controls underwent neuro-ophthalmologic evaluation, spectral-domain OCT, and 3T brain MRI. Differences between groups were assessed by univariate general linear model and principal component analysis (PCA) grouped instrumental variables into main components. Linear regression analysis was used to assess the relationship between low-contrast visual acuity (LCVA), OCT/MRI-derived metrics and PCA-derived composite scores. PCA identified four main components explaining 80.69% of data variance. Considering each variable independently, LCVA 1.25% was significantly predicted by ganglion cell-inner plexiform layer (GCIPL) thickness, thalamic volume and optic radiation (OR) lesion volume (adjusted R 2 0.328, p  = 0.00004; adjusted R 2 0.187, p  = 0.002 and adjusted R 2 0.180, p  = 0.002). The PCA composite score of global visual pathway damage independently predicted both LCVA 1.25% (adjusted R 2 value 0.361, p  = 0.00001) and LCVA 2.50% (adjusted R 2 value 0.323, p  = 0.00003). A multiparametric score represents a more comprehensive and effective tool to explain visual disability than a single instrumental metric in PPMS.

Acoustic Emission of Large PRSEUS Structures (Pultruded Rod Stitched Efficient Unitized Structure)

NASA Technical Reports Server (NTRS)

Horne, Michael R.; Juarez, Peter D.

2016-01-01

In the role of structural health monitoring (SHM), Acoustic Emission (AE) analysis is being investigated as an effective method for tracking damage development in large composite structures under load. Structures made using Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) for damage tolerant, light, and economical airframe construction are being pursued by The Boeing Company and NASA under the Environmentally Responsible Aircraft initiative (ERA). The failure tests of two PRSEUS substructures based on the Boeing Hybrid Wing Body fuselage concept were conducted during third quarter 2011 and second quarter 2015. One fundamental concern of these tests was determining the effectiveness of the stitched integral stiffeners to inhibit damage progression. By design, severe degradation of load carrying capability should not occur prior to Design Ultimate Load (DUL). While minor damage prior to DUL was anticipated, the integral stitching should not fail since this would allow a stiffener-skin delamination to progress rapidly and alter the transfer of load into the stiffeners. In addition, the stiffeners should not fracture because they are fundamental to structural integrity. Getting the best information from each AE sensor is a primary consideration because a sparse network of sensors is implemented. Sensitivity to stiffener-contiguous degradation is supported by sensors near the stiffeners, which increases the coverage per sensor via AE waveguide actions. Some sensors are located near potentially critical areas or "critical zones" as identified by numerical analyses. The approach is compared with the damage progression monitored by other techniques (e.g. ultrasonic C-scan).

Dynamical Signatures of Structural Connectivity Damage to a Model of the Brain Posed at Criticality.

PubMed

Haimovici, Ariel; Balenzuela, Pablo; Tagliazucchi, Enzo

2016-12-01

Synchronization of brain activity fluctuations is believed to represent communication between spatially distant neural processes. These interareal functional interactions develop in the background of a complex network of axonal connections linking cortical and subcortical neurons, termed the human "structural connectome." Theoretical considerations and experimental evidence support the view that the human brain can be modeled as a system operating at a critical point between ordered (subcritical) and disordered (supercritical) phases. Here, we explore the hypothesis that pathologies resulting from brain injury of different etiologies are related to this model of a critical brain. For this purpose, we investigate how damage to the integrity of the structural connectome impacts on the signatures of critical dynamics. Adopting a hybrid modeling approach combining an empirical weighted network of human structural connections with a conceptual model of critical dynamics, we show that lesions located at highly transited connections progressively displace the model toward the subcritical regime. The topological properties of the nodes and links are of less importance when considered independently of their weight in the network. We observe that damage to midline hubs such as the middle and posterior cingulate cortex is most crucial for the disruption of criticality in the model. However, a similar effect can be achieved by targeting less transited nodes and links whose connection weights add up to an equivalent amount. This implies that brain pathology does not necessarily arise due to insult targeted at well-connected areas and that intersubject variability could obscure lesions located at nonhub regions. Finally, we discuss the predictions of our model in the context of clinical studies of traumatic brain injury and neurodegenerative disorders.

Progress Report for the Joint Services Electronic Program for the Period April 1, 1989 through March 31, 1990 (Coordinated Science Laboratory, University of Illinois at Urbana-Champaign)

DTIC Science & Technology

1990-06-30

since the projected ion range is of the order of lattice constants. Thus, we have extended our thermal-dopant incorporation model and have developed...bombardment results in residual lattice damage, which degrades electrical and optical properties. Obviously, at sufficiently high acceleration energies...understand the details of collisional lattice dynamics and ion-induced defect for- mation and annihilation. In addition, the simulations are providing, for

The Effects of Repeated Low-Dose Sarin Exposure

DTIC Science & Technology

2005-08-01

support the idea that there is a triphasic NT model for onset and progression of seizures and subsequent brain damage upon acute exposure to OP ChE...An ACh microbore column (1x530 mm ID, 10 µm UniJet, BAS #MF-8904) coupled with AChE/choline oxidase immobilized enzyme reactor (BAS # MF-8903) was...peroxidase to the electrode for the reduction of hydrogen peroxide that was generated from the immobilized enzyme reactor . The detector was set at (-)1.0

Prognostics for Ground Support Systems: Case Study on Pneumatic Valves

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Goebel, Kai

2011-01-01

Prognostics technologies determine the health (or damage) state of a component or sub-system, and make end of life (EOL) and remaining useful life (RUL) predictions. Such information enables system operators to make informed maintenance decisions and streamline operational and mission-level activities. We develop a model-based prognostics methodology for pneumatic valves used in ground support equipment for cryogenic propellant loading operations. These valves are used to control the flow of propellant, so failures may have a significant impact on launch availability. Therefore, correctly predicting when valves will fail enables timely maintenance that avoids launch delays and aborts. The approach utilizes mathematical models describing the underlying physics of valve degradation, and, employing the particle filtering algorithm for joint state-parameter estimation, determines the health state of the valve and the rate of damage progression, from which EOL and RUL predictions are made. We develop a prototype user interface for valve prognostics, and demonstrate the prognostics approach using historical pneumatic valve data from the Space Shuttle refueling system.

23 CFR 668.103 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... be primarily attributable to gradual and progressive deterioration or lack of proper maintenance. The... the disaster occurrence for the purpose of: (1) Minimizing the extent of the damage, (2) Protecting... maintenance. Work usually done by highway agencies in repairing damage normally expected from seasonal and...

23 CFR 668.103 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... be primarily attributable to gradual and progressive deterioration or lack of proper maintenance. The... the disaster occurrence for the purpose of: (1) Minimizing the extent of the damage, (2) Protecting... maintenance. Work usually done by highway agencies in repairing damage normally expected from seasonal and...

23 CFR 668.103 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... be primarily attributable to gradual and progressive deterioration or lack of proper maintenance. The... the disaster occurrence for the purpose of: (1) Minimizing the extent of the damage, (2) Protecting... maintenance. Work usually done by highway agencies in repairing damage normally expected from seasonal and...

Oxidative Injury and Iron Redistribution Are Pathological Hallmarks of Marmoset Experimental Autoimmune Encephalomyelitis.

PubMed

Dunham, Jordon; Bauer, Jan; Campbell, Graham R; Mahad, Don J; van Driel, Nikki; van der Pol, Susanne M A; 't Hart, Bert A; Lassmann, Hans; Laman, Jon D; van Horssen, Jack; Kap, Yolanda S

2017-06-01

Oxidative damage and iron redistribution are associated with the pathogenesis and progression of multiple sclerosis (MS), but these aspects are not entirely replicated in rodent experimental autoimmune encephalomyelitis (EAE) models. Here, we report that oxidative burst and injury as well as redistribution of iron are hallmarks of the MS-like pathology in the EAE model in the common marmoset. Active lesions in the marmoset EAE brain display increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p22phox, p47phox, and gp91phox) and inducible nitric oxide synthase immunoreactivity within lesions with active inflammation and demyelination, coinciding with enhanced expression of mitochondrial heat-shock protein 70 and superoxide dismutase 1 and 2. The EAE lesion-associated liberation of iron (due to loss of iron-containing myelin) was associated with altered expression of the iron metabolic markers FtH1, lactoferrin, hephaestin, and ceruloplasmin. The enhanced expression of oxidative damage markers in inflammatory lesions indicates that the enhanced antioxidant enzyme expression could not counteract reactive oxygen and nitrogen species-induced cellular damage, as is also observed in MS brains. This study demonstrates that oxidative injury and aberrant iron distribution are prominent pathological hallmarks of marmoset EAE thus making this model suitable for therapeutic intervention studies aimed at reducing oxidative stress and associated iron dysmetabolism. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Discrete Analysis of Damage and Shear Banding in Argillaceous Rocks

NASA Astrophysics Data System (ADS)

Dinç, Özge; Scholtès, Luc

2018-05-01

A discrete approach is proposed to study damage and failure processes taking place in argillaceous rocks which present a transversely isotropic behavior. More precisely, a dedicated discrete element method is utilized to provide a micromechanical description of the mechanisms involved. The purpose of the study is twofold: (1) presenting a three-dimensional discrete element model able to simulate the anisotropic macro-mechanical behavior of the Callovo-Oxfordian claystone as a particular case of argillaceous rocks; (2) studying how progressive failure develops in such material. Material anisotropy is explicitly taken into account in the numerical model through the introduction of weakness planes distributed at the interparticle scale following predefined orientation and intensity. Simulations of compression tests under plane-strain and triaxial conditions are performed to clarify the development of damage and the appearance of shear bands through micromechanical analyses. The overall mechanical behavior and shear banding patterns predicted by the numerical model are in good agreement with respect to experimental observations. Both tensile and shear microcracks emerging from the modeling also present characteristics compatible with microstructural observations. The numerical results confirm that the global failure of argillaceous rocks is well correlated with the mechanisms taking place at the local scale. Specifically, strain localization is shown to directly result from shear microcracking developing with a preferential orientation distribution related to the orientation of the shear band. In addition, localization events presenting characteristics similar to shear bands are observed from the early stages of the loading and might thus be considered as precursors of strain localization.

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

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

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

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

Mesenchymal stem cells protective effect in adriamycin model of nephropathy.

PubMed

Magnasco, Alberto; Corselli, Mirko; Bertelli, Roberta; Ibatici, Adalberto; Peresi, Monica; Gaggero, Gabriele; Cappiello, Valentina; Chiavarina, Barbara; Mattioli, Girolamo; Gusmano, Rosanna; Ravetti, Jean Louis; Frassoni, Francesco; Ghiggeri, Gian Marco

2008-01-01

Mesenchymal stem cells (MSCs) may be of value in regeneration of renal tissue after damage; however, lack of biological knowledge and variability of results in animal models limit their utilization. We studied the effects of MSCs on podocytes in vitro and in vivo utilizing adriamycin (ADR) as a model of renal toxicity. The in vivo experimental approach was carried out in male Sprague-Dawley rats (overall 60 animals) treated with different ADR schemes to induce acute and chronic nephrosis. MSCs were given a) concomitantly to ADR in tail vein or b) in aorta and c) in tail vein 60 days after ADR. Homing was assessed with PKH26-MSCs. MSCs rescued podocytes from apoptosis induced by ADR in vitro. The maximal effect (80% rescue) was obtained with MSCs/podocytes coculture ratio of 1:1 for 72 h. All rats treated with ADR developed nephrosis. MSCs did not modify the clinical parameters (i.e., proteinuria, serum creatinine, lipids) but protected the kidney from severe glomerulosclerosis when given concomitantly to ADR. Rats given MSCs 60 days after ADR developed the same severe renal damage. Only a few MSCs were found in renal tubule-interstitial areas 1-24 h after injection and no MSCs were detected in glomeruli. MSCs reduced apoptosis of podocytes treated with ADR in vitro. Early and repeated MSCs infusion blunted glomerular damage in chronic ADR-induced nephropathy. MSCs did not modify proteinuria and progression to renal failure, which implies lack of regenerative potential in this model.

Prevalent cartilage damage and cartilage loss over time are associated with incident bone marrow lesions in the tibiofemoral compartments: the MOST study.

PubMed

Crema, M D; Felson, D T; Roemer, F W; Wang, K; Marra, M D; Nevitt, M C; Lynch, J A; Torner, J; Lewis, C E; Guermazi, A

2013-02-01

To assess the association of prevalent cartilage damage and cartilage loss over time with incident bone marrow lesions (BMLs) in the same subregion of the tibiofemoral compartments as detected on magnetic resonance imaging (MRI). The Multicenter Osteoarthritis Study is an observational study of individuals with or at risk for knee osteoarthritis (OA). Subjects whose baseline and 30-month follow-up MRIs were read for findings of OA were included. MRI was performed with a 1.0 T extremity system. Tibiofemoral compartments were divided into 10 subregions. Cartilage morphology was scored from 0 to 6 and BMLs were scored from 0 to 3. Prevalent cartilage damage and cartilage loss over time were considered predictors of incident BMLs. Associations were assessed using logistic regression, with adjustments for potential confounders. Medially, incident BMLs were associated with baseline cartilage damage (adjusted odds ratio (OR) 3.9 [95% confidence interval (CI) 3.0, 5.1]), incident cartilage loss (7.3 [95% CI 5.0, 10.7]) and progression of cartilage loss (7.6 [95% CI 5.1, 11.3]) Laterally, incident BMLs were associated with baseline cartilage damage (4.1 [95% CI 2.6, 6.3]), incident cartilage loss (6.0 [95% CI 3.1, 11.8]), and progression of cartilage loss (11.9 [95% CI 6.2, 23.0]). Prevalent cartilage damage and cartilage loss over time are strongly associated with incident BMLs in the same subregion, supporting the significance of the close interrelation of the osteochondral unit in the progression of knee OA. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Treatment of hypertension and metabolic syndrome: lowering blood pressure is not enough for organ protection, new approach-arterial destiffening.

PubMed

Zimlichman, Reuven

2014-10-01

Cardiovascular risk factors (CVRFs) have been shown to induce end organ damage. Until now, the main approach to reduce CVRF-induced end organ damage was by normalization of CVRFs; this approach was found effective to reduce damage and cardiovascular (CV) events. However, a residual risk always remained even when CVRFs were optimally balanced. An additional risk factor which has an immense effect on the progression of end organ damage is aging. Aging is accompanied by gradual stiffening of the arteries which finally leads to CV events. Until recently, the process of arterial aging was considered as unmodifiable, but this has changed. Arterial stiffening caused by the aging process is similar to the changes seen as a result of CVRF-induced arterial damage. Actually, the presence of CVRFs causes faster arterial stiffening, and the extent of damage is proportional to the severity of the CVRF, the length of its existence, the patient's genetic factors, etc. Conventional treatments of osteoporosis and of hormonal decline at menopause are potential additional approaches to positively affect progression of arterial stiffening. The new approach to further decrease progression of arteriosclerosis, thus preventing events, is the prevention of age-associated arterial structural changes. This approach should further decrease age-associated arterial stiffening. A totally new promising approach is to study the possibility of affecting collagen, elastin, and other components of connective tissue that participate in the process of arterial stiffening. Reduction of pulse pressure by intervention in arterial stiffening process by novel methods as breaking collagen cross-links or preventing their formation is an example of future directions in treatment. This field is of enormous potential that might be revolutionary in inducing further significant reduction of cardiovascular events.

Progressive Cortical Neuronal Damage and Extracranial-Intracranial Bypass Surgery in Patients with Misery Perfusion.

PubMed

Yamauchi, H; Kagawa, S; Kishibe, Y; Takahashi, M; Higashi, T

2017-05-01

Misery perfusion may cause selective neuronal damage in atherosclerotic ICA or MCA disease. Bypass surgery can improve misery perfusion and may prevent neuronal damage. On the other hand, surgery conveys a risk for neuronal damage. The purpose of this retrospective study was to determine whether progression of cortical neuronal damage in surgically treated patients with misery perfusion is larger than that in surgically treated patients without misery perfusion or medically treated patients with misery perfusion. We evaluated the distribution of benzodiazepine receptors twice by using PET and 11 C-labeled flumazenil in 18 surgically treated patients with atherosclerotic ICA or MCA disease (9 with misery perfusion and 9 without) and no perioperative stroke before and after bypass surgery; in 8 medically treated patients with misery perfusion and no intervening ischemic event; and in 7 healthy controls. We quantified abnormal decreases in the benzodiazepine receptors of the cerebral cortex within the MCA distribution and compared changes in the benzodiazepine receptor index among the 3 groups. The change in the benzodiazepine receptor index in surgically treated patients with misery perfusion (27.5 ± 15.6) during 7 ± 5 months was significantly larger than that in surgically treated patients without misery perfusion (-5.2 ± 9.4) during 6 ± 4 months ( P < .001) and in medically treated patients with misery perfusion (3.2 ± 15.4) during 16 ± 6 months ( P < .01). Progression of cortical neuronal damage in surgically treated patients with misery perfusion and no perioperative stroke may occur and may be larger than that in medically treated patients with misery perfusion and no intervening ischemic event. © 2017 by American Journal of Neuroradiology.

Estimation of fatigue life using electromechanical impedance technique

NASA Astrophysics Data System (ADS)

Lim, Yee Yan; Soh, Chee Kiong

2010-04-01

Fatigue induced damage is often progressive and gradual in nature. Structures subjected to large number of fatigue load cycles will encounter the process of progressive crack initiation, propagation and finally fracture. Monitoring of structural health, especially for the critical components, is therefore essential for early detection of potential harmful crack. Recent advent of smart materials such as piezo-impedance transducer adopting the electromechanical impedance (EMI) technique and wave propagation technique are well proven to be effective in incipient damage detection and characterization. Exceptional advantages such as autonomous, real-time and online, remote monitoring may provide a cost-effective alternative to the conventional structural health monitoring (SHM) techniques. In this study, the main focus is to investigate the feasibility of characterizing a propagating fatigue crack in a structure using the EMI technique as well as estimating its remaining fatigue life using the linear elastic fracture mechanics (LEFM) approach. Uniaxial cyclic tensile load is applied on a lab-sized aluminum beam up to failure. Progressive shift in admittance signatures measured by the piezo-impedance transducer (PZT patch) corresponding to increase of loading cycles reflects effectiveness of the EMI technique in tracing the process of fatigue damage progression. With the use of LEFM, prediction of the remaining life of the structure at different cycles of loading is possible.

Curcumin protects neuronal cells against status-epilepticus-induced hippocampal damage through induction of autophagy and inhibition of necroptosis.

PubMed

Wang, Jin; Liu, Yuan; Li, Xiao-Hui; Zeng, Xiang-Chang; Li, Jian; Zhou, Jun; Xiao, Bo; Hu, Kai

2017-05-01

Status epilepticus, the most severe form of epilepsy, is characterized by progressive functional and structural damage in the hippocampus, ultimately leading to the development and clinical appearance of spontaneous, recurrent seizures. Although the pathogenesis underlying epileptogenesis processes remains unclear, a substantial body of evidence has shown that status epilepticus acts as an important initial factor in triggering epileptogenesis. Notably, besides classical cell death mechanisms such as apoptosis and necrosis, 2 novel regulators of cell fate known as necroptosis and autophagy, are demonstrated to be involved in neuronal damage in various neurodegenerative and neuropsychiatric disorders. However, whether necroptosis and autophagy play a role in post-status-epilepticus rat hippocampus and other epilepsy mechanisms deserves further research effort. In addition, research is needed to determine whether compounds from traditional Chinese herbs possess antiepileptic effects through the modulation of necroptosis and autophagy. In this study, we found that curcumin, a polyphenolic phytochemical extracted from the Curcuma longa plant, protects neuronal cells against status-epilepticus-induced hippocampal neuronal damage in the lithium-pilocarpine-induced status epilepticus rat model through induction of autophagy and inhibition of necroptosis.

Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation.

PubMed

Johansson, P I; Ostrowski, S R

2010-12-01

Acute coagulopathy of trauma predicts a poor clinical outcome. Tissue trauma activates the sympathoadrenal system resulting in high circulating levels of catecholamines that influence hemostasis dose-dependently through immediate effects on the two major compartments of hemostasis, i.e., the circulating blood and the vascular endothelium. There appears to be a dose-dependency with regards to injury severity and the hemostatic response to trauma evaluated in whole blood by viscoelastic assays like thrombelastography (TEG), changing from normal to hypercoagulable, to hypocoagulable and finally hyperfibrinolytic in severely injured patients. Since high catecholamine levels may directly damage the endothelium and thereby promote systemic coagulation activation, we hypothesize that the progressive hypocoagulability and ultimate hyperfibrinolysis observed in whole blood with increasing injury severity, is an evolutionary developed response that counterbalances the injury and catecholamine induced endothelial activation and damage. Given this, the rise in circulating catecholamines in trauma patients may favor a switch from hyper- to hypocoagulability in the blood to keep the progressively more procoagulant microvasculature open. The hypothesis delineated in the present paper thus infers that the state of the fluid phase, including its cellular elements, is a consequence of the degree of the tissue injury and importantly, critically related to the degree of endothelial damage, with a progressively more procoagulant endothelium inducing a gradient of increasing anticoagulation towards the fluid phase. The implications of this hypothesis may include targeted treatment strategies according to the degree of sympathoadrenal response as evaluated by whole blood viscoelastical hemostatic assays in trauma patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effect of Long-Term Systolic Blood Pressure Trajectory on Kidney Damage in the Diabetic Population: A Prospective Study in a Community-Based Chinese Cohort.

PubMed

Li, Jian-Chao; Tian, Jun; Wu, Shou-Ling; Wang, Zhi-Jun; Zhang, Xiao-Fei; Jia, Dao; Ding, Rong-Jing; Xiao, Xiong-Fu; Fan, Yu-Bo; Hu, Da-Yi

2018-05-20

Previous studies have shown that hypertension is an important factor contributing to the occurrence and progression of diabetic kidney damage. However, the relationship between the patterns of blood pressure (BP) trajectory and kidney damage in the diabetic population remains unclear. This prospective study investigated the effect of long-term systolic BP (SBP) trajectory on kidney damage in the diabetic population based on an 8-year follow-up community-based cohort. This study included 4556 diabetic participants among 101,510 participants. BP, estimated glomerular filtration rate (eGFR), and urinary protein were measured every 2 years from 2006 to 2014. SBP trajectory was identified by the censored normal modeling. Five discrete SBP trajectories were identified according to SBP range and the changing pattern over time. Kidney damage was evaluated through eGFR and urinary protein value. A multivariate logistic regression model was used to analyze the influence of different SBP trajectory groups on kidney damage. We identified five discrete SBP trajectories: low-stable group (n = 864), moderate-stable group (n = 1980), moderate increasing group (n = 609), elevated decreasing group, (n = 679), and elevated stable group (n = 424). The detection rate of kidney damage in the low-stable group (SBP: 118-124 mmHg) was the lowest among the five groups. The detection rate of each kidney damage index was higher in the elevated stable group (SBP: 159-172 mmHg) compared with the low-stable group. For details, the gap was 4.14 (11.6% vs. 2.8%) in eGFR <60 ml·min -1 ·1.73 m -2 and 3.66 (17.2% vs. 4.7%), 3.38 (25.0% vs. 7.4%), and 1.8 (10.6% vs. 5.9%) times in positive urinary protein, eGFR <60 ml·min -1 ·1.73 m -2 and/or positive urinary protein, and eGFR decline ≥30%, respectively (P < 0.01). An elevated stable SBP trajectory is an independent risk factor for kidney damage in the diabetic population.

Unraveling cellular pathways contributing to drug-induced liver injury by dynamical modeling.

PubMed

Kuijper, Isoude A; Yang, Huan; Van De Water, Bob; Beltman, Joost B

2017-01-01

Drug-induced liver injury (DILI) is a significant threat to human health and a major problem in drug development. It is hard to predict due to its idiosyncratic nature and which does not show up in animal trials. Hepatic adaptive stress response pathway activation is generally observed in drug-induced liver injury. Dynamical pathway modeling has the potential to foresee adverse effects of drugs before they go in trial. Ordinary differential equation modeling can offer mechanistic insight, and allows us to study the dynamical behavior of stress pathways involved in DILI. Areas covered: This review provides an overview on the progress of the dynamical modeling of stress and death pathways pertinent to DILI, i.e. pathways relevant for oxidative stress, inflammatory stress, DNA damage, unfolded proteins, heat shock and apoptosis. We also discuss the required steps for applying such modeling to the liver. Expert opinion: Despite the strong progress made since the turn of the century, models of stress pathways have only rarely been specifically applied to describe pathway dynamics for DILI. We argue that with minor changes, in some cases only to parameter values, many of these models can be repurposed for application in DILI research. Combining both dynamical models with in vitro testing might offer novel screening methods for the harmful side-effects of drugs.

Do Genetic Susceptibility Variants Associate with Disease Severity in Early Active Rheumatoid Arthritis?

PubMed

Scott, Ian C; Rijsdijk, Frühling; Walker, Jemma; Quist, Jelmar; Spain, Sarah L; Tan, Rachael; Steer, Sophia; Okada, Yukinori; Raychaudhuri, Soumya; Cope, Andrew P; Lewis, Cathryn M

2015-07-01

Genetic variants affect both the development and severity of rheumatoid arthritis (RA). Recent studies have expanded the number of RA susceptibility variants. We tested the hypothesis that these associated with disease severity in a clinical trial cohort of patients with early, active RA. We evaluated 524 patients with RA enrolled in the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trials. We tested validated susceptibility variants - 69 single-nucleotide polymorphisms (SNP), 15 HLA-DRB1 alleles, and amino acid polymorphisms in 6 HLA molecule positions - for their associations with progression in Larsen scoring, 28-joint Disease Activity Scores, and Health Assessment Questionnaire (HAQ) scores over 2 years using linear mixed-effects and latent growth curve models. HLA variants were associated with joint destruction. The *04:01 SNP (rs660895, p = 0.0003), *04:01 allele (p = 0.0002), and HLA-DRβ1 amino acids histidine at position 13 (p = 0.0005) and valine at position 11 (p = 0.0012) significantly associated with radiological progression. This association was only significant in anticitrullinated protein antibody (ACPA)-positive patients, suggesting that while their effects were not mediated by ACPA, they only predicted joint damage in ACPA-positive RA. Non-HLA variants did not associate with radiograph damage (assessed individually and cumulatively as a weighted genetic risk score). Two SNP - rs11889341 (STAT4, p = 0.0001) and rs653178 (SH2B3-PTPN11, p = 0.0004) - associated with HAQ scores over 6-24 months. HLA susceptibility variants play an important role in determining radiological progression in early, active ACPA-positive RA. Genome-wide and HLA-wide analyses across large populations are required to better characterize the genetic architecture of radiological progression in RA.

Postischemic dementia with Alzheimer phenotype: selectively vulnerable versus resistant areas of the brain and neurodegeneration versus β-amyloid peptide.

PubMed

Pluta, Ryszard; Jabłoński, Mirosław; Czuczwar, Stanisław J

2012-01-01

The road to clarity for postischemic dementia mechanisms has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution. Importantly, brain ischemia is a leading cause of death and cognitive impairment worldwide. However, the mechanisms of progressive cognitive decline following brain ischemia are not yet certain. Data from animal models and clinical pioneering studies of brain ischemia have demonstrated an increase in expression and processing of amyloid precursor protein to a neurotoxin oligomeric β-amyloid peptide. Functional and memory brain restoration after ischemic brain injury is delayed and incomplete due to a lesion related increase in the amount of the neurotoxin amyloid protein. Moreover, ischemic injury is strongly accelerated by aging, too. In this review, we will present our current thinking about biogenesis of amyloid from the amyloid precursor protein in ischemic brain injury, and how this factor presents etiological, therapeutic and diagnostic targets that are now under consideration. Progressive injury of the ischemic brain parenchyma may be caused not only by degeneration of selectively vulnerable neurons destroyed during ischemia but also by acute and chronic damage of resistant areas of the brain and progressive damage in the blood-brain barrier. We propose that in postischemic dementia an initial ischemic injury precedes the cerebrovascular and brain parenchyma accumulation of Alzheimer disease related neurotoxin β-amyloid peptide, which in turn amplifies the neurovascular dysfunction triggering focal ischemic episodes as a vicious cycle preceding final neurodegenerative pathology. Persistent ischemic blood-brain barrier insufficiency with accumulation of neurotoxin β-amyloid protein in the brain tissue, especially in extracellular perivascular space and blood-brain barrier microvessels, may gradually, over a lifetime, progress to brain atrophy and to full-blown ischemic dementia with Alzheimer phenotype.

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

PubMed

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

2011-08-31

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

Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres

PubMed Central

Valerio-Santiago, Mauricio; de los Santos-Velázquez, Ana Isabel; Monje-Casas, Fernando

2013-01-01

When chromosomal DNA is damaged, progression through the cell cycle is halted to provide the cells with time to repair the genetic material before it is distributed between the mother and daughter cells. In Saccharomyces cerevisiae, this cell cycle arrest occurs at the G2/M transition. However, it is also necessary to restrain exit from mitosis by maintaining Bfa1-Bub2, the inhibitor of the Mitotic Exit Network (MEN), in an active state. While the role of Bfa1 and Bub2 in the inhibition of mitotic exit when the spindle is not properly aligned and the spindle position checkpoint is activated has been extensively studied, the mechanism by which these proteins prevent MEN function after DNA damage is still unclear. Here, we propose that the inhibition of the MEN is specifically required when telomeres are damaged but it is not necessary to face all types of chromosomal DNA damage, which is in agreement with previous data in mammals suggesting the existence of a putative telomere-specific DNA damage response that inhibits mitotic exit. Furthermore, we demonstrate that the mechanism of MEN inhibition when telomeres are damaged relies on the Rad53-dependent inhibition of Bfa1 phosphorylation by the Polo-like kinase Cdc5, establishing a new key role of this kinase in regulating cell cycle progression. PMID:24130507

Progressive Muscle Atrophy and Weakness After Treatment by Mantle Field Radiotherapy in Hodgkin Lymphoma Survivors

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

Leeuwen-Segarceanu, Elena M. van, E-mail: e.segarceanu@antoniusziekenhuis.nl; Dorresteijn, Lucille D.A.; Pillen, Sigrid

Purpose: To describe the damage to the muscles and propose a pathophysiologic mechanism for muscle atrophy and weakness after mantle field radiotherapy in Hodgkin lymphoma (HL) survivors. Methods and Materials: We examined 12 patients treated by mantle field radiotherapy between 1969 and 1998. Besides evaluation of their symptoms, the following tests were performed: dynamometry; ultrasound of the sternocleidomastoid, biceps, and antebrachial flexor muscles; and needle electromyography of the neck, deltoid, and ultrasonographically affected arm muscles. Results: Ten patients (83%) experienced neck complaints, mostly pain and muscle weakness. On clinical examination, neck flexors were more often affected than neck extensors. Onmore » ultrasound, the sternocleidomastoid was severely atrophic in 8 patients, but abnormal echo intensity was seen in only 3 patients. Electromyography of the neck muscles showed mostly myogenic changes, whereas the deltoid, biceps, and antebrachial flexor muscles seemed to have mostly neurogenic damage. Conclusions: Many patients previously treated by mantle field radiotherapy develop severe atrophy and weakness of the neck muscles. Neck muscles within the radiation field show mostly myogenic damage, and muscles outside the mantle field show mostly neurogenic damage. The discrepancy between echo intensity and atrophy suggests that muscle damage is most likely caused by an extrinsic factor such as progressive microvascular fibrosis. This is also presumed to cause damage to nerves within the radiated field, resulting in neurogenic damage of the deltoid and arm muscles.« less

Stochastic Modeling of Empirical Storm Loss in Germany

NASA Astrophysics Data System (ADS)

Prahl, B. F.; Rybski, D.; Kropp, J. P.; Burghoff, O.; Held, H.

2012-04-01

Based on German insurance loss data for residential property we derive storm damage functions that relate daily loss with maximum gust wind speed. Over a wide range of loss, steep power law relationships are found with spatially varying exponents ranging between approximately 8 and 12. Global correlations between parameters and socio-demographic data are employed to reduce the number of local parameters to 3. We apply a Monte Carlo approach to calculate German loss estimates including confidence bounds in daily and annual resolution. Our model reproduces the annual progression of winter storm losses and enables to estimate daily losses over a wide range of magnitude.

Monosodium urate crystal deposition associated with the progress of radiographic grade at the sacroiliac joint in axial SpA: a dual-energy CT study.

PubMed

Zhu, Junqing; Li, Aiwu; Jia, Ertao; Zhou, Yi; Xu, Juan; Chen, Shixian; Huang, Yinger; Xiao, Xiang; Li, Juan

2017-05-02

Previous studies have revealed that ankylosing spondylitis (AS), as the progenitor of axial spondyloarthritis (AxSpA), has been characterized by the insidiously progressive nature of sacroiliitis and spondylitis. Dual-energy computed tomography (DECT) has recently been used to analyse the deposition of monosodium urate (MSU) crystals with higher sensitivity and specificity. However, it remains unclear whether the existence of the MSU crystal deposition detected by DECT at the sacroiliac joint in patients with AxSpA also is associated with the existing structural damage. Here, we performed this study to show the DECT MSU crystal deposits in AxSpA patients without coexisting gout and to ascertain the relationship between the MSU crystal deposition and the structural joint damage of sacroiliac joints. One hundred and eighty-six AxSpA patients without coexisting gout were recruited. The plain radiographs of the sacroiliac joint were obtained, along with the DECT scans at the pelvis and the clinical variables. All statistics based on the left or right sacroiliac joint damage grading (0-4) were calculated independently. Bivariate analysis and ordinal logistic regression was performed between the clinical features and radiographic grades at the sacroiliac joint. At the pelvis, large quantities of MSU crystal deposition were found in patients with AxSpA. The average MSU crystal volume at the left sacroiliac joint, the right sacroiliac joint, and the pelvis were 0.902 ± 1.345, 1.074 ± 1.878, and 5.272 ± 9.044 cm 3 , values which were correlated with serum uric acid concentrations (r = 0.727, 0.740, 0.896; p < 0.001). In bivariate analysis, wide clinical variables were associated with the changes in sacroiliac joint damage. Further, the AxSpA duration, BASFI score, and the volume of MSU crystal at both sides of sacroiliac joint were associated with the progress of radiographic grade at the sacroiliac joints in the ordinal logistic models (left AOR = 1.180, 3.800, 1.920; right AOR = 1.190, 3.034, 1.418; p < 0.01). Large quantities of MSU crystal deposition detected by DECT were found at the pelvis in AxSpA patients without coexisting gout. In addition to AxSpA duration and BASFI score, the MSU crystal deposition at the sacroiliac joint is associated with the progress of radiographic grade at sacroiliac joints in those patients.

Computational simulation of progressive fracture in fiber composites

NASA Technical Reports Server (NTRS)

Chamis, C. C.

1986-01-01

Computational methods for simulating and predicting progressive fracture in fiber composite structures are presented. These methods are integrated into a computer code of modular form. The modules include composite mechanics, finite element analysis, and fracture criteria. The code is used to computationally simulate progressive fracture in composite laminates with and without defects. The simulation tracks the fracture progression in terms of modes initiating fracture, damage growth, and imminent global (catastrophic) laminate fracture.

Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques.

PubMed

Sugimoto, Chie; Merino, Kristen M; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A; Wakao, Hiroshi; Mori, Kazuyasu; Kim, Woong-Ki; Veazey, Ronald S; Didier, Elizabeth S; Kuroda, Marcelo J

2017-09-01

Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4 + T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU + ] CD163 + ), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants. IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model, this work was performed to address why infants infected with SIV progress more quickly to AIDS than do adults. Earlier we reported that in adult rhesus macaques, increasing monocyte turnover reflected tissue macrophage damage by SIV and was predictive of terminal disease progression to AIDS. Here we report that uninfected infant rhesus macaques exhibited a higher physiological baseline monocyte turnover rate than adults. Furthermore, once infected with SIV, infants displayed further increased monocyte turnover that may have facilitated the accelerated progression to AIDS. These results support a role for monocytes and macrophages in the pathogenesis of SIV/HIV and begin to explain why infants are more prone to rapid disease progression. Copyright © 2017 American Society for Microbiology.

Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques

PubMed Central

Sugimoto, Chie; Merino, Kristen M.; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A.; Wakao, Hiroshi; Kim, Woong-Ki; Veazey, Ronald S.; Didier, Elizabeth S.

2017-01-01

ABSTRACT Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4+ T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU+] CD163+), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants. IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model, this work was performed to address why infants infected with SIV progress more quickly to AIDS than do adults. Earlier we reported that in adult rhesus macaques, increasing monocyte turnover reflected tissue macrophage damage by SIV and was predictive of terminal disease progression to AIDS. Here we report that uninfected infant rhesus macaques exhibited a higher physiological baseline monocyte turnover rate than adults. Furthermore, once infected with SIV, infants displayed further increased monocyte turnover that may have facilitated the accelerated progression to AIDS. These results support a role for monocytes and macrophages in the pathogenesis of SIV/HIV and begin to explain why infants are more prone to rapid disease progression. PMID:28566378