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Sample records for acute mechanical damage

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  2. Synthesis of a Novel Photopolymerized Nanocomposite Hydrogel for Treatment of Acute Mechanical Damage to Cartilage

    PubMed Central

    Schlichting, Kathryn; Copeland-Johnson, Trishelle M.; Goodman, Matthew; Lipert, Robert J.; Prozorov, Tanya; Liu, Xunpei; McKinley, Todd O.; Lin, Zhiqun; Martin, James A.; Mallapragada, Surya K.

    2014-01-01

    Intraarticular fractures initiate a cascade of pathobiologic and pathomechanical events that culminate in posttraumatic osteoarthritis (PTOA). Hallmark features of PTOA include destruction of the cartilage matrix in combination with loss of chondrocytes and acute mechanical damage (AMD). Currently, treatment of intraarticular fractures essentially is completely focused on restoration of the macroanatomy of the joint. However, current treatment ignores AMD sustained by cartilage at the time of injury. We are exploring aggressive biomaterial-based interventions designed to treat the primary pathologic components of AMD. This study describes the development of a novel injectable copolymer solution that forms gels at physiological temperatures that can be photocrosslinked, and can form nanocomposite gels insitu through mineralization. The injectable copolymer solution will allow the material to fill cracks in the cartilage after trauma. The mechanical properties of the nanocomposite are similar to that of native cartilage, as measured by compressive and shear testing. It thereby has the potential to mechanically stabilize and restore local structural integrity to acutely injured cartilage. Additionally, the insitu mineralization ensures good adhesion at the interface between the biomaterial and cartilage, as measured through tensile and shear testing. Therefore, we have successfully developed a new injectable insitu forming nanocomposite with mechanical properties of similar magnitude to that of native cartilage, and which can bond well to native cartilage. This material has the potential to stabilize injured cartilage and prevent PTOA. PMID:21530694

  3. The Effect of Acute Microgravity on Mechanically-Induced Membrane Damage and Membrane-Membrane Fusion Events

    NASA Technical Reports Server (NTRS)

    Clarke, Mark, S. F.; Vanderburg, Charles R.; Feedback, Daniel L.

    2001-01-01

    Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". This response is characterized by both membrane rupture and membrane resealing events mediated by membrane-membrane fusion. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

  4. The effect of acute microgravity on mechanically-induced membrane damage and membrane-membrane fusion events

    NASA Technical Reports Server (NTRS)

    Clarke, M. S.; Vanderburg, C. R.; Feeback, D. L.; McIntire, L. V. (Principal Investigator)

    2001-01-01

    Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". Both membrane rupture and membrane resealing events mediated by membrane-membrane fusion characterize this response. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

  5. Damage mechanics in engineering materials

    SciTech Connect

    Voyiadjis, G.Z.; Woody Ju, J.W.; Chaboche, J.L.

    1998-12-31

    This book contains thirty peer-reviewed papers that are based on the presentations made at the symposium on Damage Mechanics in Engineering Materials on the occasion of the Joint ASME/ASCE/SES Mechanics Conference (McNU97), held in Evanston, Illinois, June 28--July 2, 1997. The key area of discussion was on the constitutive modeling of damage mechanics in engineering materials encompassing the following topics: macromechanics/micromechanical constitutive modeling, experimental procedures, numerical modeling, inelastic behavior, interfaces, damage, fracture, failure, computational methods. The book is divided into six parts: study of damage mechanics; localization and damage; damage in brittle materials; damage in metals and metal matrix composites; computational aspects of damage models; damage in polymers and elastomers.

  6. Pleiotropic effects of spongean alkaloids on mechanisms of cell death, cell cycle progression and DNA damage response (DDR) of acute myeloid leukemia (AML) cells.

    PubMed

    Stuhldreier, Fabian; Kassel, Stefanie; Schumacher, Lena; Wesselborg, Sebastian; Proksch, Peter; Fritz, Gerhard

    2015-05-28

    We investigated cytotoxic mechanisms evoked by the spongean alkaloids aaptamine (Aa) and aeroplysinin-1 (Ap), applied alone and in combination with daunorubicin, employing acute myeloid leukemia (AML) cells. Aa and Ap reduced the viability of AML cells in a dose dependent manner with IC50 of 10-20 µM. Ap triggered apoptotic cell death more efficiently than Aa. Both alkaloids increased the protein level of S139-phosphorylated H2AX (γH2AX), which however was independent of the induction of DNA damage. Expression of the senescence markers p21 and p16 was increased, while the phosphorylation level of p-Chk-2 was reduced following Aa treatment. As a function of dose, Aa and Ap protected or sensitized AML cells against daunorubicin. Protection by Aa was paralleled by reduced formation of ROS and lower level of DNA damage. Both Aa and Ap attenuated daunorubicin-stimulated activation of the DNA damage response (DDR) as reflected on the levels of γH2AX, p-Kap-1 and p-Chk-1. Specifically Ap restored the decrease in S10 phosphorylation of histone H3 resulting from daunorubicin treatment. The cytoprotective effects of Aa and Ap were independent of daunorubicin import/export. Both Aa and Ap abrogated daunorubicin-induced accumulation of cells in S-phase. Inhibition of DNA synthesis was specific for Ap. The data show that Aa and Ap have both congruent and agent-specific pleiotropic effects that are preferential for anticancer drugs. Since Ap showed a broader spectrum of anticancer activities, this compound is suggested as novel lead compound for forthcoming in vivo studies elucidating the usefulness of spongean alkaloids in AML therapy. PMID:25697484

  7. Involvement of leukotrienes in acute gastric damage.

    PubMed

    Boughton-Smith, N K

    1989-01-01

    The leukotrienes have potent inflammatory actions which could be of importance in gastric mucosal integrity. In animals, LTC4 produces vasoconstriction in the gastric mucosa. Furthermore, acute gastric damage produced by ethanol is accompanied by marked increases in the mucosal formation of LTC4 and LTB4. Depending on the extent of protection, prostaglandins either have no effect or prevent the increases in leukotriene formation which accompany ethanol-induced damage. Various non-specific inhibitors of leukotriene synthesis prevent ethanol and indomethacin-induced damage to the gastric mucosa. However, a novel selective 5-lipoxygenase inhibitor (BW A4C) had no effect on these models of acute gastric damage at doses which completely inhibited gastric mucosal leukotriene synthesis. These studies cast doubt on the role of the leukotrienes in these models of acute gastric damage. However, the potent biological actions of the leukotrienes may be of importance in the pathogenesis of other forms of gastric damage, or as mediators of chronic gastric ulceration or inflammation. PMID:2657289

  8. Loss of extracellular superoxide dismutase leads to acute lung damage in the presence of ambient air: a potential mechanism underlying adult respiratory distress syndrome.

    PubMed

    Gongora, Maria Carolina; Lob, Heinrich E; Landmesser, Ulf; Guzik, Tomasz J; Martin, W David; Ozumi, Kiyoski; Wall, Susan M; Wilson, David Scott; Murthy, Niren; Gravanis, Michael; Fukai, Tohru; Harrison, David G

    2008-10-01

    The extracellular superoxide dismutase 3 (SOD3) is highly expressed in both blood vessels and lungs. In different models of pulmonary injury, SOD3 is reduced; however, it is unclear whether this contributes to lung injury. To study the role of acute SOD3 reduction in lung injury, the SOD3 gene was deleted in adult mice by using the Cre-Lox technology. Acute reduction of SOD3 led to a fivefold increase in lung superoxide, marked inflammatory cell infiltration, a threefold increase in the arterial-alveolar gradient, respiratory acidosis, histological changes similar to those observed in adult respiratory distress syndrome, and 85% mortality. Treatment with the SOD mimetic MnTBAP and intranasal administration of SOD-containing polyketal microparticles reduced mortality, prevented the histological alterations, and reduced lung superoxide levels. To understand how mice with the SOD3 embryonic deletion survived without lung injury, gene array analysis was performed. These data demonstrated the up-regulation of 37 genes and down-regulation of nine genes, including those involved in cell signaling, inflammation, and gene transcription in SOD3-/- mice compared with either mice with acute SOD3 reduction or wild-type controls. These studies show that SOD3 is essential for survival in the presence of ambient oxygen and that acute loss of this enzyme can lead to severe lung damage. Strategies either to prevent SOD3 inactivation or to augment its levels might prove useful in the treatment of acute lung injury. PMID:18787098

  9. Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP

    PubMed Central

    Mukherjee, Rajarshi; Mareninova, Olga A; Odinokova, Irina V; Huang, Wei; Murphy, John; Chvanov, Michael; Javed, Muhammad A; Wen, Li; Booth, David M; Cane, Matthew C; Awais, Muhammad; Gavillet, Bruno; Pruss, Rebecca M; Schaller, Sophie; Molkentin, Jeffery D; Tepikin, Alexei V; Petersen, Ole H; Pandol, Stephen J; Gukovsky, Ilya; Criddle, David N; Gukovskaya, Anna S; Sutton, Robert

    2016-01-01

    Objective Acute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established. Design We investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis. Results MPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished. Conclusions This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease. PMID:26071131

  10. [Organ damage and cardiorenal syndrome in acute heart failure].

    PubMed

    Casado Cerrada, Jesús; Pérez Calvo, Juan Ignacio

    2014-03-01

    Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this syndrome. PMID:24930080

  11. Huperzine A ameliorates damage induced by acute myocardial infarction in rats through antioxidant, anti-apoptotic and anti-inflammatory mechanisms.

    PubMed

    Sui, Xizhong; Gao, Changqing

    2014-01-01

    Huperzine A (HupA), an alkaloid used in traditional Chinese medicine and isolated from Huperzia serrata, has been shown to possess diverse biological activities. The present study was undertaken to evaluate the cardioprotective potential of HupA in myocardial ischemic damage using a rat model of acute myocardial infarction. HupA significantly diminished the infarct size and inhibited the activities of myocardial enzymes, including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT). A significantly reduced activity of malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD), of the non-enzymatic scavenger enzyme, glutathione (GSH), as well as of glutathione peroxidase (GSH-PX) were found in the HupA-treated groups. Furthermore, decreased protein levels of caspase-3 and Bax, and increased levels of Bcl-2 were observed in the infarcted hearts of the rats treated with various concentrations of HupA. In addition, treatment with HupA markedly inhibited the expression of the nuclear factor-κB (NF-κB) subunit p65, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). These findings suggest that the cardioprotective potential of HupA is associated with its antioxidant, anti-apoptotic and anti-inflammatory properties in acute myocardial infarction in rats. PMID:24190328

  12. Acute traumatic anterior glenohumeral dislocation complicated by axillary nerve damage: a case report

    PubMed Central

    Kazemi, Mohsen

    1998-01-01

    An elite soccer player presented with a classic acute anterior dislocation of the glenohumeral joint complicated by axillary nerve damage. The incidence, mechanism of injury, clinical presentation, conservative treatment and rehabilitation of the anterior glenohumeral joint dislocation and associated axillary nerve damage are discussed in this paper. ImagesFigure 3

  13. Recent Advances in Composite Damage Mechanics

    NASA Technical Reports Server (NTRS)

    Reifsnider, Ken; Case, Scott; Iyengar, Nirmal

    1996-01-01

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

  14. Genetic damage in multiple organs of acutely exercised rats.

    PubMed

    Pozzi, Renan; Rosa, Jose C; Eguchi, Ricardo; Oller do Nascimento, Claudia M; Oyama, Lila M; Aguiar, Odair; Chaves, Marcelo D; Ribeiro, Daniel A

    2010-12-01

    The aim of this study was to investigate the effects of acute exercise on genomic damage in an animal model. Male adult Wistar rats were divided into the following groups: control and acute exercised (experimental). For this purpose, 15 animals were accustomed to running on a rodent treadmill for 15 min per day for 5 days (10-20 m min(-1); 08 grade). After 4 days at rest, active animals ran on the treadmill (22 m min(-1), 58 grade) till exhaustion. Cells from peripheral blood, liver, heart, and brain were collected after 0, 2, and 6 h after exercise. The results showed that acute exercise was able to induce genetic damage in peripheral blood cells after 2 and 6 h of exercise, whereas liver pointed out genetic damage for all periods evaluated. No genetic damage was induced either in brain or in heart cells. In conclusion, our results suggest that acute exercise could contribute to the genetic damage in peripheral blood and liver cells. It seems that liver is a sensitive organ to the genotoxic insult after acute exercise. PMID:20979236

  15. Retinal Light Damage: Mechanisms and Protection

    PubMed Central

    Organisciak, Daniel T.; Vaughan, Dana K.

    2009-01-01

    By its action on rhodopsin, light triggers the well-known visual transduction cascade, but can also induce cell damage and death through phototoxic mechanisms -- a comprehensive understanding of which is still elusive despite more than 40 years of research. Herein, we integrate recent experimental findings to address several hypotheses of retinal light damage, premised in part on the close anatomical and metabolic relationships between the photoreceptors and the retinal pigment epithelium. We begin by reviewing the salient features of light damage, recently joined by evidence for retinal remodeling which has implications for the prognosis of recovery of function in retinal degenerations. We then consider select factors that influence the progression of the damage process and the extent of visual cell loss. Traditional, genetically-modified, and emerging animal models are discussed, with particular emphasis on cone visual cells. Exogenous and endogenous retinal protective factors are explored, with implications for light damage mechanisms and some suggested avenues for future research. Synergies are known to exist between our long term light environment and photoreceptor cell death in retinal disease. Understanding the molecular mechanisms of light damage in a variety of animal models can provide valuable insights into the effects of light in clinical disorders and may form the basis of future therapies to prevent or delay visual cell loss. PMID:19951742

  16. Mechanisms of Diabetes-Induced Liver Damage

    PubMed Central

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

    2016-01-01

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

  17. Volatile Emission of Mechanically Damaged Almonds

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Methamphetamine causes acute hyperthermia-dependent liver damage.

    PubMed

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-10-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

  19. Methamphetamine causes acute hyperthermia-dependent liver damage

    PubMed Central

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-01-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

  20. Nucleation in models of damage mechanics

    NASA Astrophysics Data System (ADS)

    Gran, J. D.; Rundle, J. B.; Klein, W.; Turcotte, D. L.

    2010-12-01

    A variety of studies have modeled the physics of material deformation and damage as examples of generalized phase transitions, involving either critical phenomena or spinodal nucleation. Here we study two cellular automaton models of damage mechanics which. The first model is a modified slider-block model with failure threshold weakening. A block is considered partially damaged after its first slip, and any subsequent failure of that block will occur at reduced failure threshold. Damage here is defined as the fraction of blocks that have a reduced failure threshold. The threshold weakening parameter is viewed as a scaling field similar to the occupation probability in site percolation. The second model is time-dependent fiber-bundle model, where the time to failure for each element is specified from a Poissonian distribution and the hazard rate is assumed to have a power-law dependence on stress. Damage here is defined to be the fraction of blocks or fibers that have failed. Because there is no healing, catastrophic failure occurs. The transient behavior prior to rupture propagation is studied and scaling laws are obtained. We compare both models to mean-field percolation which has been shown to be representative of spinodal nucleation and to laboratory experiments that display power-law behavior.

  1. Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage

    PubMed Central

    Mishima, Eikan; Inoue, Chisako; Saigusa, Daisuke; Inoue, Ryusuke; Ito, Koki; Suzuki, Yusuke; Jinno, Daisuke; Tsukui, Yuri; Akamatsu, Yosuke; Araki, Masatake; Araki, Kimi; Shimizu, Ritsuko; Shinke, Haruka; Suzuki, Takehiro; Takeuchi, Yoichi; Shima, Hisato; Akiyama, Yasutoshi; Toyohara, Takafumi; Suzuki, Chitose; Saiki, Yoshikatu; Tominaga, Teiji; Miyagi, Shigehito; Kawagisihi, Naoki; Soga, Tomoyoshi; Ohkubo, Takayoshi; Yamamura, Kenichi; Imai, Yutaka; Masuda, Satohiro; Sabbisetti, Venkata; Ichimura, Takaharu; Mount, David B.; Bonventre, Joseph V.; Ito, Sadayoshi; Tomioka, Yoshihisa; Itoh, Kunihiko

    2014-01-01

    Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases, including AKI and CKD. Thus, early detection of oxidative tissue damage is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we show that oxidative stress induces a direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation and occurs much earlier than DNA damage. In various models of tissue damage (ischemic reperfusion, toxic injury, and irradiation), the levels of circulating tRNA derivatives increased rapidly. In humans, the levels of circulating tRNA derivatives also increased under conditions of acute renal ischemia, even before levels of other known tissue damage markers increased. Notably, the level of circulating free m1A correlated with mortality in the general population (n=1033) over a mean follow-up of 6.7 years. Compared with healthy controls, patients with CKD had higher levels of circulating free m1A, which were reduced by treatment with pitavastatin (2 mg/d; n=29). Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis. PMID:24833129

  2. Vorinostat Induces Reactive Oxygen Species and DNA Damage in Acute Myeloid Leukemia Cells

    PubMed Central

    Pettersson, Filippa; Retrouvey, Hélène; Skoulikas, Sophia; Miller, Wilson H.

    2011-01-01

    Histone deacetylase inhibitors (HDACi) are promising anti-cancer agents, however, their mechanisms of action remain unclear. In acute myeloid leukemia (AML) cells, HDACi have been reported to arrest growth and induce apoptosis. In this study, we elucidate details of the DNA damage induced by the HDACi vorinostat in AML cells. At clinically relevant concentrations, vorinostat induces double-strand breaks and oxidative DNA damage in AML cell lines. Additionally, AML patient blasts treated with vorinostat display increased DNA damage, followed by an increase in caspase-3/7 activity and a reduction in cell viability. Vorinostat-induced DNA damage is followed by a G2-M arrest and eventually apoptosis. We found that pre-treatment with the antioxidant N-acetyl cysteine (NAC) reduces vorinostat-induced DNA double strand breaks, G2-M arrest and apoptosis. These data implicate DNA damage as an important mechanism in vorinostat-induced growth arrest and apoptosis in both AML cell lines and patient-derived blasts. This supports the continued study and development of vorinostat in AMLs that may be sensitive to DNA-damaging agents and as a combination therapy with ionizing radiation and/or other DNA damaging agents. PMID:21695163

  3. Damage Control Mechanisms in Articular Cartilage

    PubMed Central

    Martin, James A; Scherb, MB; Lembke, Lois A; Buckwalter, Joseph

    2000-01-01

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

  4. Oxidant conditioning protects cartilage from mechanically induced damage.

    PubMed

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

    2010-07-01

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

  5. Endothelial Glycocalyx Damage Is Associated with Leptospirosis Acute Kidney Injury

    PubMed Central

    Libório, Alexandre Braga; Braz, Marcelo Boecker Munoz; Seguro, Antonio Carlos; Meneses, Gdayllon C.; Neves, Fernanda Macedo de Oliveira; Pedrosa, Danielle Carvalho; Cavalcanti, Luciano Pamplona de Góes; Martins, Alice Maria Costa; Daher, Elizabeth de Francesco

    2015-01-01

    Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P < 0.001) and syndecan-1 (73.7 ± 15.9 versus 21.2 ± 7.9 ng/mL, P < 0.001) compared with exposed controls. Patients with leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinase-associated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKI-associated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage. PMID:25624405

  6. [Definition and biomarkers of acute renal damage: new perspectives].

    PubMed

    Seijas, M; Baccino, C; Nin, N; Lorente, J A

    2014-01-01

    The RIFLE and AKIN criteria have definitely help out to draw attention to the relationship between a deterioration of renal function that produces a small increase in serum creatinine and a worse outcome. However, the specific clinical utility of using these criteria remains to be well-defined. It is believed that the main use of these criteria is for the design of epidemiological studies and clinical trials to define inclusion criteria and objectives of an intervention. AKI adopting term, re-summoning former ARF terminology, it is appropriate to describe the clinical condition characterized by damage to kidney, in the same way as the term is used to describe acute lung damage where the lung injury situation still has not increased to a situation of organ failure (dysfunction). The serum and urine biomarkers (creatinine, urea, and diuresis) currently in use are not sensitive or specific for detecting kidney damage, limiting treatment options and potentially compromising the outcome. New biomarkers are being studied in order to diagnose an earlier and more specific AKI, with the potential to change the definition criteria of AKI with different stages, currently based in diuresis and serum creatinine. PMID:24880198

  7. Damage mechanisms in shock wave lithotripsy (SWL)

    NASA Astrophysics Data System (ADS)

    Lokhandwalla, Murtuza

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

  8. Damage mechanisms in nanolayered metallic composites

    SciTech Connect

    Misra, A.; Kung, H.; Hammon, D. L.; Hoagland R. G.; Nastasi, Michael Anthony,

    2002-01-01

    The strengths of metallic multilayers, composed of alternating layers o f soft metals such as Cu and Nb, approach the theoretical limit of material strengih when the bilayer periods are on the order of a few nanometers. We have investigated the damage mechanisms in these ultra-high strength nanolayered composite inaterials subjected to monotonic deformation. Large strain plastic deformation such as rooin temperature rolling does not lead to any dislocation cell structure formation within the layers indicating that the deformation and dislocation storage mechanisms in nanostructured materials are completely different from the bulk. In bulk metals, dislocation pile-ups lead to heterogeneous slip, but in nano-materials, deformation by single disloqations on closely spaced glide planes results in more homogeneously distributed slip. The implications of the high tensile strengths and hoinogencous slip on the fatigue properties of nanolayered materials are also discussed.

  9. Mechanism of frost damage to concrete

    NASA Astrophysics Data System (ADS)

    Sun, Zhenhua

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

  10. Damage and fracture mechanics of composite materials

    NASA Astrophysics Data System (ADS)

    Abdussalam, Saleh Ramadan

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

  11. One damage law for different mechanisms

    NASA Astrophysics Data System (ADS)

    Lemaitre, J.; Sermage, J. P.

    1997-07-01

    We consider here a general three-dimensional kinetic damage law. It uses the thermodynamic of irreversible processes formalism and the phenomenological aspects of isotropic damage. It gives the damage rate as a function of its associated variable, the strain energy density release rate and the accumulated plastic strain rate. Associated with different plastic constitutive equations, this damage law takes into account brittle damage, ductile damage, low and high cycle fatigue and creep damage. In this paper we mainly focus on creep-fatigue interaction and high cycle fatigue. Associated to a viscoplastic constitutive equation having kinematic hardening, the damage law gives the non linear creep-fatigue interaction. The agreement with experiments is good. Associated to plastic constitutive equations also having kinematic hardening but introduced in a micromechanical two scale model based on the self-consistent scheme, it models the non linear accumulation of damage induced by a succession of sequences of different amplitudes as well as the effect of the mean stress and the influence of non proportional loading.

  12. Cardiac troponins as indicators of acute myocardial damage in dogs.

    PubMed

    Burgener, Iwan A; Kovacevic, Alan; Mauldin, G Neal; Lombard, Christophe W

    2006-01-01

    Cardiac troponin I (cTnI) and T (cTnT) have a high sequence homology across phyla and are sensitive and specific markers of myocardial damage. The purpose of this study was to evaluate the Cardiac Reader, a human point-of-care system for the determination of cTnT and myoglobin, and the Abbott Axsym System for the determination of cTnI and creatine kinase isoenzyme MB (CK-MB) in healthy dogs and in dogs at risk for acute myocardial damage because of gastric dilatation-volvulus (GDV) and blunt chest trauma (BCT). In healthy dogs (n = 56), cTnI was below detection limits (<0.1 microg/L) in 35 of 56 dogs (reference range 0-0.7 microg/L), and cTnT was not measurable (<0.05 ng/mL) in all but 1 dog. At presentation, cTnI, CK-MB, myoglobin, and lactic acid were all significantly higher in dogs with GDV (n = 28) and BCT (n = 8) than in control dogs (P < .001), but cTnT was significantly higher only in dogs with BCT (P = .033). Increased cTnI or cTnT values were found in 26 of 28 (highest values 1.1-369 microg/L) and 16 of 28 dogs (0.1-1.7 ng/mL) with GDV, and in 6 of 8 (2.3-82.4 microg/L) and 3 of 8 dogs (0.1-0.29 ng/mL) with BCT, respectively. In dogs suffering from GDV, cTnI and cTnT increased further within the first 48 hours (P < .001). Increased cardiac troponins suggestive of myocardial damage occurred in 93% of dogs with GDV and 75% with BCT. cTnI appeared more sensitive, but cTnT may be a negative prognostic indicator in GDV. Both systems tested seemed applicable for the measurement of canine cardiac troponins, with the Cardiac Reader particularly suitable for use in emergency settings. PMID:16594583

  13. Mechanical Properties of Shock-Damaged Rocks

    NASA Technical Reports Server (NTRS)

    He, Hongliang; Ahrens, T. J.

    1994-01-01

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

  14. Damage mechanisms in components for fiber lasers and amplifiers

    NASA Astrophysics Data System (ADS)

    Carter, Adrian; Samson, Bryce N.; Tankala, Kanishka; Machewirth, David P.; Khitrov, Victor; Manyam, Upendra H.; Gonthier, Francois; Seguin, Francois

    2005-02-01

    In this paper we review the damage mechanisms that need to be considered when building high power fibre lasers. More specifically we look at thermal issues, optically induced coating damage, bulk and surface damage thresholds of the host glass. We also discuss the reliability of tapered fibre bundles and Bragg gratings at these power densities.

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

    PubMed

    Iatridis, J C James C; ap Gwynn, Iolo

    2004-08-01

    Intervertebral disc degeneration results in disorganization of the laminate structure of the annulus that may arise from mechanical microfailure. Failure mechanisms in the annulus were investigated using composite lamination theory and other analyses to calculate stresses in annulus layers, interlaminar shear stress, and the region of stress concentration around a fiber break. Scanning electron microscopy (SEM) was used to evaluate failure patterns in the annulus and evaluate novel structural features of the disc tissue. Stress concentrations in the annulus due to an isolated fiber break were localized to approximately 5 microm away from the break, and only considered a likely cause of annulus fibrosus failure (i.e., radial tears in the annulus) under extreme loading conditions or when collagen damage occurs over a relatively large region. Interlaminar shear stresses were calculated to be relatively large, to increase with layer thickness (as reported with degeneration), and were considered to be associated with propagation of circumferential tears in the annulus. SEM analysis of intervertebral disc annulus fibrosus tissue demonstrated a clear laminate structure, delamination, matrix cracking, and fiber failure. Novel structural features noted with SEM also included the presence of small tubules that appear to run along the length of collagen fibers in the annulus and a distinct collagenous structure representative of a pericellular matrix in the nucleus region. PMID:15212921

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

    PubMed Central

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

    2014-01-01

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

  17. Structural and mechanical repair of diffuse damage in cortical bone in vivo.

    PubMed

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

    2014-12-01

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

  18. Phenomenological approach to mechanical damage growth analysis.

    PubMed

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

    2008-10-01

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

  19. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

    PubMed

    Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

    2013-08-01

    Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage. PMID:23636618

  20. Neuroprotection by gonadal steroid hormones in acute brain damage requires cooperation with astroglia and microglia.

    PubMed

    Johann, Sonja; Beyer, Cordian

    2013-09-01

    The neuroactive steroids 17β-estradiol and progesterone control a broad spectrum of neural functions. Besides their roles in the regulation of classical neuroendocrine loops, they strongly influence motor and cognitive systems, behavior, and modulate brain performance at almost every level. Such a statement is underpinned by the widespread and lifelong expression pattern of all types of classical and non-classical estrogen and progesterone receptors in the CNS. The life-sustaining power of neurosteroids for tattered or seriously damaged neurons aroused interest in the scientific community in the past years to study their ability for therapeutic use under neuropathological challenges. Documented by excellent studies either performed in vitro or in adequate animal models mimicking acute toxic or chronic neurodegenerative brain disorders, both hormones revealed a high potency to protect neurons from damage and saved neural systems from collapse. Unfortunately, neurons, astroglia, microglia, and oligodendrocytes are comparably target cells for both steroid hormones. This hampers the precise assignment and understanding of neuroprotective cellular mechanisms activated by both steroids. In this article, we strive for a better comprehension of the mutual reaction between these steroid hormones and the two major glial cell types involved in the maintenance of brain homeostasis, astroglia and microglia, during acute traumatic brain injuries such as stroke and hypoxia. In particular, we attempt to summarize steroid-activated cellular signaling pathways and molecular responses in these cells and their contribution to dampening neuroinflammation and neural destruction. This article is part of a Special Issue entitled 'CSR 2013'. PMID:23196064

  1. Acute and long term respiratory damage following inhalation of ammonia.

    PubMed Central

    Leduc, D; Gris, P; Lheureux, P; Gevenois, P A; De Vuyst, P; Yernault, J C

    1992-01-01

    A lifelong non-smoker who was the victim of a massive accidental exposure to anhydrous ammonia gas was followed up for 10 years. In the acute phase the patient presented with severe tracheobronchitis and respiratory failure, caused by very severe burns of the respiratory mucosa. After some improvement he was left with severe and fixed airways obstruction. Isotope studies of mucociliary clearance, computed tomography, and bronchography showed mild bronchiectasis. It is concluded that acute exposure to high concentrations of ammonia may lead to acute respiratory injury but also to long term impairment of respiratory function. Images PMID:1440475

  2. Ultrastructure damage of oviduct telocytes in rat model of acute salpingitis

    PubMed Central

    Yang, Jian; Chi, Chi; Liu, Zhen; Yang, Gang; Shen, Zong-Ji; Yang, Xiao-Jun

    2015-01-01

    Acute salpingitis (AS) is an inflammatory disease which causes severe damage to a subset of classically described cells lining in oviduct wall and contributes to interstitial fibrosis and fertility problems. Telocytes (TCs), a newly discovered peculiar type of stromal cells, have been identified in many organs, including oviduct, with proposed multiple potential bio-functions. However, with recent increasing reports regarding TCs alterations in disease-affected tissues, there is still lack of evidence about TCs involvement in AS-affected oviduct tissues and potential pathophysiological roles. We presently identified normal TCs by their characteristic ultrastructural features and immunophenotype. However, in AS-affected oviduct tissues, TCs displayed multiple ultrastructural damage both in cellular body and prolongations, with obvious loss of TCs and development of tissue fibrosis. Furthermore, TCs lose their interstitial 3-D network connected by homocellular or heterocellular junctions between TCs and adjacent cells. And especially, TCs connected to the activated immunocytes (mononuclear cells, eosinophils) and affected local immune state (repression or activation). Meanwhile, massive neutrophils infiltration and overproduced Inducible Nitric Oxide Synthase (iNOS), COX-2, suggested mechanism of inflammatory-induced TCs damage. Consequently, TCs damage might contribute to AS-induced structural and reproductive functional abnormalities of oviduct, probably via: (i) substances, energy and functional insufficiency, presumably, e.g. TC-specific genetic material profiles, ion channels, cytoskeletal elements, Tps dynamics, etc., (ii) impaired TCs-mediated multicellular signalling, such as homeostasis/angiogenesis, tissue repair/regeneration, neurotransmission, (iii) derangement of 3-D network and impaired mechanical support for TCs-mediated multicellular signals within the stromal compartment, consequently induced interstitial fibrosis, (iv) involvement in local

  3. Damage progression in mechanically fastened composite structural joints

    SciTech Connect

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

    1994-12-31

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

  4. Laser damage mechanisms in conductive widegap semiconductor films.

    PubMed

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

    2016-08-01

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

  5. [Mitochondrial dysfunction and compensatory mechanisms in liver cells during acute carbon tetrachloride-induced rat intoxication].

    PubMed

    Zavodnik, I B

    2015-01-01

    Electron-transport chain and redox-balance of mitochondria are important targets that are damaged during intoxication. The aim of the present work was to estimate the role of impairments in cellular bioenergetic function in the development of liver damage during acute carbon tetrachloride intoxication in rats and to elucidate possible compensatory mechanisms. Acute CCl4-induced rat intoxication (0.8 g/kg or 4 g/kg) resulted in considerable impairments of respiratory and synthetic mitochondrial functions; their manifestations depended on the dose of the toxic agent and the duration of the intoxication increased and accompanied by complete uncoupling of oxidation and phosphorylation processes in liver mitochondria. The intoxication induced considerable liver damage and accumulation of NO in blood plasma and liver tissue. The changes of some parameters of liver mitochondrial functional activity demonstrate an oscillative pattern, reflecting compensatory mechanisms during intoxication that involved increased reduced glutathione level and enhanced succinate dehydrogenase activity. PMID:26716745

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

    SciTech Connect

    Bhattcharya, B.; Ellingwood, B.

    1998-02-01

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

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

    PubMed Central

    Gruntman, Michal; Novoplansky, Ariel

    2011-01-01

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

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

    PubMed Central

    Nagode, Marko

    2014-01-01

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

  9. Theories of elastoplasticity coupled with continuum damage mechanics

    NASA Astrophysics Data System (ADS)

    Hansen, N. R.

    1993-01-01

    Inelastic material constitutive relations for elastoplasticity coupled with continuum damage mechanics are investigated. For elastoplasticity, continuum damage mechanics, and the coupled formulations, rigorous thermodynamic frameworks are derived. The elastoplasticity framework is shown to be sufficiently general to encompass J(sub 2) plasticity theories including general isotropic and kinematic hardening relations. The concepts of an intermediate undamaged configuration and a fictitious deformation gradient are used to develop a damage representation theory. An empirically-based, damage evolution theory is proposed to overcome some observed deficiencies. Damage deactivation, which is the negation of the effects of damage under certain loading conditions, is investigated. An improved deactivation algorithm is developed for both damaged elasticity and coupled elastoplasticity formulations. The applicability of coupled formulations is validated by comparing theoretical predictions to experimental data for a spectrum of materials and loads paths. The pressure-dependent brittle-to-ductile transitional behavior of concrete is replicated. The deactivation algorithm is validated using tensile and compression data for concrete. For a ductile material, the behavior of an aluminum alloy is simulated including the temperature-dependent ductile-to-brittle behavior features. The direct application of a coupled model to fatigue is introduced. In addition, the deactivation algorithm in conjunction with an assumed initial damage and strain is introduced as a novel method of simulating the densification phenomenon in cellular solids.

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

    NASA Astrophysics Data System (ADS)

    Meng, Qinghua; Wang, Zhenqing

    2016-05-01

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

  11. Modeling of glass fracture damage using continuum damage mechanics - Static spherical indentation

    SciTech Connect

    Sun, Xin; Khaleel, Mohammad A.

    2004-07-01

    Continuum damage mechanics based constitutive model is used to study the stone-impact resistance of automotive windshields. An axisymmetric finite element model is created to simulate the transient dynamic response and impact induced damge tensors for laminated glass layers subject to stone-impact loading. The windshield glass consists of two glass outer layers laminated by a thin poly-vinyl butyral (PVB) layer. The constitutive behavior of the glass layers is simulated suing continuum damage mechanics model with linear damage evolution. The PVB layer is modeled with linear viscoelastic solid. The model is used to predict and examine damage patterns on different glass surfaces for different windshield designs including variations in ply thickness and curvatures.

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

    SciTech Connect

    Kochevar, K.E.

    1981-07-01

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

  13. Molecular mechanisms of cisplatin cytotoxicity in acute promyelocytic leukemia cells

    PubMed Central

    Kumar, Sanjay; Tchounwou, Paul B.

    2015-01-01

    Cis-diamminedichloroplatinum (II) (cisplatin) is a widely used anti-tumor drug for the treatment of a broad range of human malignancies with successful therapeutic outcomes for head and neck, ovarian, and testicular cancers. It has been found to inhibit cell cycle progression and to induce oxidative stress and apoptosis in acute promyelocytic leukemia (APL) cells. However, its molecular mechanisms of cytotoxic action are poorly understood. We hypothesized that cisplatin induces cytotoxicity through DNA adduct formation, oxidative stress, transcriptional factors (p53 and AP-1), cell cycle regulation, stress signaling and apoptosis in APL cells. We used the APL cell line as a model, and applied a variety of molecular tools to elucidate the cytototoxic mode of action of cisplatin. We found that cisplatin inhibited cell proliferation by a cytotoxicity, characterized by DNA damage and modulation of oxidative stress. Cisplatin also activated p53 and phosphorylated activator protein (AP-1) component, c-Jun at serine (63, 73) residue simultaneously leading to cell cycle arrest through stimulation of p21 and down regulation of cyclins and cyclin dependent kinases in APL cell lines. It strongly activated the intrinsic pathway of apoptosis through alteration of the mitochondrial membrane potential, release of cytochrome C, and up-regulation of caspase 3 activity. It also down regulated the p38MAPK pathway. Overall, this study highlights the molecular mechanisms that underline cisplatin toxicity to APL cells, and provides insights into selection of novel targets and/or design of therapeutic agents to treat APL. PMID:26486083

  14. Acute and late gastrointestinal toxicity after radiotherapy in prostate cancer patients: Consequential late damage

    SciTech Connect

    Heemsbergen, Wilma D. . E-mail: w.heemsbergen@nki.nl; Peeters, Stephanie T.H.; Koper, Peter; Hoogeman, Mischa S.; Lebesque, Joos V.

    2006-09-01

    Purpose: Late gastrointestinal (GI) toxicity after radiotherapy can be partly explained by late effects of acute toxicity (consequential late damage). We studied whether there is a direct relationship between acute and late GI toxicity. Patients and Methods: A total of 553 evaluable patients from the Dutch dose escalation trial (68 Gy vs. 78 Gy) were included. We defined three outcomes for acute reactions: 1) maximum Radiation Therapy Oncology Group acute toxicity, 2) maximum acute mucous discharge (AMD), and 3) maximum acute proctitis. Within a multivariable model, late endpoints (overall toxicity and five toxicity indicators) were studied as a function of acute toxicity, pretreatment symptoms, and relevant dose parameters. Results: At multivariable analysis, AMD and acute proctitis were strong predictors for overall toxicity, 'intermittent bleeding,' and 'incontinence pads' (p {<=} 0.01). For 'stools {>=}6/day' all three were strong predictors. No significant associations were found for 'severe bleeding' and 'use of steroids.' The predictive power of the dose parameters remained at the same level or became weaker for most late endpoints. Conclusions: Acute GI toxicity is an independent significant predictor of late GI toxicity. This suggests a significant consequential component in the development of late GI toxicity.

  15. Electrical self-healing of mechanically damaged zinc oxide nanobelts.

    PubMed

    Zang, Jianfeng; Xu, Zhi-Hui; Webb, Richard A; Li, Xiaodong

    2011-01-12

    We report the observation of remarkable electrical self-healing in mechanically damaged ZnO nanobelts. Nanoindentation into intrinsically defect-free ZnO nanobelts induces deformation and crack damage, causing a dramatic electrical signal decrease. Two self-healing regimes in the nanoindented ZnO nanobelts are revealed. The physical mechanism for the observed phenomena is analyzed in terms of the nanoindentation-induced dislocations, the short-range atomic diffusion in nanostructures, and the local heating of the dislocation zone in the electrical measurement. PMID:21121680

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

    SciTech Connect

    Blau, Peter Julian; Lowe, Tracie M

    2008-01-01

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

  17. Pathobiochemical mechanisms during the acute phase response.

    PubMed

    Kleesiek, K; Greiling, H

    1984-01-01

    The acute phase response is characterised by the following sequence of principle phenomena: (1) an early local inflammatory reaction, (2) formation of inflammatory humoral factors inducing a systemic reaction, (3) stimulation of glycoprotein synthesis predominantly in the hepatocytes, and (4) an increase in the plasma concentration of acute phase proteins, when the rate of biosynthesis exceeds the degradation rate. Inflammatory mediators (lysosomal enzymes, oxygen derived radicals, prostaglandins) are mainly released during phagocytosis by granulocytes and macrophages. The signal reaching the hepatocytes is not yet clearly identified. A leukocyte endogenous mediator (LEM) released by macrophages is described. There is evidence that prostaglandins and probably proteinase alpha 2-macroglobulin complexes are also involved. The hepatic acute phase protein synthesis is modulated by hormones (insulin, cortisol, somatotropin). The biochemical events in the hepatocyte include an increase in protein synthesis and the regulatory control of the glycosylation of polypeptide precursors. The secreted glycoproteins serve variously as inhibitors or mediators of the inflammatory processes. PMID:6208159

  18. Mechanical Data for Use in Damage Tolerance Analyses

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

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

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

    PubMed

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

    2015-02-01

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

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

    SciTech Connect

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

    2012-10-03

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  2. Lightning Strike Induced Damage Mechanisms of Carbon Fiber Composites

    NASA Astrophysics Data System (ADS)

    Kawakami, Hirohide

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

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

    PubMed

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

    2010-08-01

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

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

    NASA Astrophysics Data System (ADS)

    Yan, Chengyong

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

  5. Carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute spinal cord injury in rats.

    PubMed

    Liu, Da; Huang, Ying; Li, Bin; Jia, Changqing; Liang, Feng; Fu, Qin

    2015-02-01

    Acute spinal cord injury (SCI) leads to permanent functional deficits via mechanical injury and secondary mechanisms, but the therapeutic strategy for SCI is limited. Carvedilol has been shown to possess multiple biological and pharmacological properties. The of the present study was to investigate the possible protective effect of carvedilol in SCI rats. An acute SCI rat model was established and neurological function was tested. After carvedilol (10 mg/kg, oral gavage) treatment for 21 days, the status of osteoporosis, neuron damage, astrocyte activation, inflammation, oxidative stress and apoptosis were evaluated in rats. Carvedilol significantly improved locomotor activity that was decreased by SCI. In addition, carvedilol promoted bone growth by regulating the expression of nuclear factor-κB ligand (receptor activator of nuclear factor-κB ligand; RANKL) and osteoprotegerin (OPG), inactivating osteoclasts and thereby increasing bone mineral density in tibias. In addition, carvedilol reduced SCI-induced neural damage, increased neuron number and reduced astrocyte activation in the spinal cord. Furthermore, the production and mRNA expression of tumour necrosis factor-α, interleukin (IL)-1β and IL-6 were significantly reduced, reduced glutathione content and superoxide dismutase activity were markedly increased and malondialdehyde content was markedly decreased in the spinal cords of carvedilol-treated rats. These results indicate that carvedilol exhibits anti-inflammatory and anti-oxidative effects in SCI rats. In addition, the expression of Fas and Fas ligand was reduced by carvedilol treatment, which, in turn, reduced cleaved caspase 3 expression and finally decreased the number of apoptotic cells in the spinal cord. In conclusion, carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute SCI in rats. PMID:25424914

  6. Obatoclax Potentiates the Cytotoxic Effect of Cytarabine on Acute Myeloid Leukemia Cells by Enhancing DNA Damage

    PubMed Central

    Xie, Chengzhi; Edwards, Holly; Caldwell, J. Timothy; Wang, Guan; Taub, Jeffrey W.; Ge, Yubin

    2014-01-01

    Resistance to cytarabine and anthracycline-based chemotherapy is a major cause of treatment failure for acute myeloid leukemia (AML) patients. Overexpression of Bcl-2, Bcl-xL, and/or Mcl-1 has been associated with chemoresistance in AML cell lines and with poor clinical outcome of AML patients. Thus, inhibitors of anti-apoptotic Bcl-2 family proteins could be novel therapeutic agents. In this study, we investigated how clinically achievable concentrations of obatoclax, a pan-Bcl-2 inhibitor, potentiate the antileukemic activity of cytarabine in AML cells. MTT assays in AML cell lines and diagnostic blasts, as well as flow cytometry analyses in AML cell lines revealed synergistic antileukemic activity between cytarabine and obatoclax. Bax activation was detected in the combined, but not the individual, drug treatments. This was accompanied by significantly increased loss of mitochondrial membrane potential. Most importantly, in AML cells treated with the combination, enhanced early induction of DNA double-strand breaks (DSBs) preceded a decrease of Mcl-1 levels, nuclear translocation of Bcl-2, Bcl-xL, and Mcl-1, and apoptosis. These results indicate that obatoclax enhances cytarabine-induced apoptosis by enhancing DNA DSBs. This novel mechanism provides compelling evidence for the clinical use of BH3 mimetics in combination with DNA-damaging agents in AML and possibly a broader range of malignancies. PMID:25308513

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

    NASA Astrophysics Data System (ADS)

    Banan, Roshanak

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

  8. The Potential Neural Mechanisms of Acute Indirect Vibration

    PubMed Central

    2011-01-01

    There is strong evidence to suggest that acute indirect vibration acts on muscle to enhance force, power, flexibility, balance and proprioception suggesting neural enhancement. Nevertheless, the neural mechanism(s) of vibration and its potentiating effect have received little attention. One proposal suggests that spinal reflexes enhance muscle contraction through a reflex activity known as tonic vibration stretch reflex (TVR), which increases muscle activation. However, TVR is based on direct, brief, and high frequency vibration (>100 Hz) which differs to indirect vibration, which is applied to the whole body or body parts at lower vibration frequency (5-45 Hz). Likewise, muscle tuning and neuromuscular aspects are other candidate mechanisms used to explain the vibration phenomenon. But there is much debate in terms of identifying which neural mechanism(s) are responsible for acute vibration; due to a number of studies using various vibration testing protocols. These protocols include: different methods of application, vibration variables, training duration, exercise types and a range of population groups. Therefore, the neural mechanism of acute vibration remain equivocal, but spinal reflexes, muscle tuning and neuromuscular aspects are all viable factors that may contribute in different ways to increasing muscular performance. Additional research is encouraged to determine which neural mechanism(s) and their contributions are responsible for acute vibration. Testing variables and vibration applications need to be standardised before reaching a consensus on which neural mechanism(s) occur during and post-vibration. Key points There is strong evidence to suggest that acute indirect vibration acts on muscle to enhance force, power, flexibility, balance and proprioception, but little attention has been given to the neural mechanism(s) of acute indirect vibration. Current findings suggest that acute vibration exposure may cause a neural response, but there is little

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

    PubMed

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

    2015-08-01

    observations. Our results indicate that the proposed CDAC model is capable of simulating both initial small magnitude damage as well as complete failure of AC tissue. The results of this study may help to elucidate the mechanisms of AC tissue damage, which initiate and propagate OA. PMID:26043366

  10. Oxidative stress, inflammation, and DNA damage in multiple organs of mice acutely exposed to amorphous silica nanoparticles

    PubMed Central

    Nemmar, Abderrahim; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Kazzam, Elsadig E; Ali, Badreldin H

    2016-01-01

    The use of amorphous silica (SiO2) in biopharmaceutical and industrial fields can lead to human exposure by injection, skin penetration, ingestion, or inhalation. However, the in vivo acute toxicity of amorphous SiO2 nanoparticles (SiNPs) on multiple organs and the mechanisms underlying these effects are not well understood. Presently, we investigated the acute (24 hours) effects of intraperitoneally administered 50 nm SiNPs (0.25 mg/kg) on systemic toxicity, oxidative stress, inflammation, and DNA damage in the lung, heart, liver, kidney, and brain of mice. Lipid peroxidation was significantly increased by SiNPs in the lung, liver, kidney, and brain, but was not changed in the heart. Similarly, superoxide dismutase and catalase activities were significantly affected by SiNPs in all organs studied. While the concentration of tumor necrosis factor α was insignificantly increased in the liver and brain, its increase was statistically significant in the lung, heart, and kidney. SiNPs induced a significant elevation in pulmonary and renal interleukin 6 and interleukin-1 beta in the lung, liver, and brain. Moreover, SiNPs caused a significant increase in DNA damage, assessed by comet assay, in all the organs studied. SiNPs caused leukocytosis and increased the plasma activities of lactate dehydrogenase, creatine kinase, alanine aminotranferase, and aspartate aminotransferase. These results indicate that acute systemic exposure to SiNPs causes oxidative stress, inflammation, and DNA damage in several major organs, and highlight the need for thorough evaluation of SiNPs before they can be safely used in human beings. PMID:27022259

  11. Mechanism study of goldenseal-associated DNA damage.

    PubMed

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

    2013-07-31

    Goldenseal has been used for the treatment of a wide variety of ailments including gastrointestinal disturbances, urinary tract disorders, and inflammation. The five major alkaloid constituents in goldenseal are berberine, palmatine, hydrastine, hydrastinine, and canadine. When goldenseal was evaluated by the National Toxicology Program (NTP) in the standard 2-year bioassay, goldenseal induced an increase in liver tumors in rats and mice; however, the mechanism of goldenseal-associated liver carcinogenicity remains unknown. In this study, the toxicity of the five goldenseal alkaloid constituents was characterized, and their toxic potencies were compared. As measured by the Comet assay and the expression of γ-H2A.X, berberine, followed by palmatine, appeared to be the most potent DNA damage inducer in human hepatoma HepG2 cells. Berberine and palmatine suppressed the activities of both topoisomerase (Topo) I and II. In berberine-treated cells, DNA damage was shown to be directly associated with the inhibitory effect of Topo II, but not Topo I by silencing gene of Topo I or Topo II. In addition, DNA damage was also observed when cells were treated with commercially available goldenseal extracts and the extent of DNA damage was positively correlated to the berberine content. Our findings suggest that the Topo II inhibitory effect may contribute to berberine- and goldenseal-induced genotoxicity and tumorigenicity. PMID:23747414

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

    PubMed

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

    2016-01-01

    Neuronal survival depends on multiple factors that comprise a well-fueled energy metabolism, trophic input, clearance of toxic substances, appropriate redox environment, integrity of blood-brain barrier, suppression of programmed cell death pathways and cell cycle arrest. Disturbances of brain homeostasis lead to acute or chronic alterations that might ultimately cause neuronal death with consequent impairment of neurological function. Although we understand most of these processes well when they occur independently from one another, we still lack a clear grasp of the concerted cellular and molecular mechanisms activated upon neuronal damage that intervene in protecting damaged neurons from death. In this review, we summarize a handful of endogenously activated mechanisms that balance molecular cues so as to determine whether neurons recover from injury or die. We center our discussion on mechanisms that have been identified to participate in stroke, although we consider different scenarios of chronic neurodegeneration as well. We discuss two central processes that are involved in endogenous repair and that, when not regulated, could lead to tissue damage, namely, trophic support and neuroinflammation. We emphasize the need to construct integrated models of neuronal degeneration and survival that, in the end, converge in neuronal fate after injury. Under neurodegenerative conditions, endogenously activated mechanisms balance out molecular cues that determine whether neurons contend toxicity or die. Many processes involved in endogenous repair may as well lead to tissue damage depending on the strength of stimuli. Signaling mediated by trophic factors and neuroinflammation are examples of these processes as they regulate different mechanisms that mediate neuronal demise including necrosis, apoptosis, necroptosis, pyroptosis and autophagy. In this review, we discuss recent findings on balanced regulation and their involvement in neuronal death. PMID:26376102

  13. Mechanisms of vessel damage in photodynamic therapy (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Fingar, Victor H.; Wieman, Thomas J.

    1992-06-01

    Vessel constriction and platelet aggregation are observed within the first minutes of light exposure to photosensitized tissues and lead to blood flow stasis, tissue hypoxia, and nutrient depravation. The mechanism for these vessel changes remains unknown, although the release of eicosanoids is implicated. We propose the following hypothesis: Photodynamic therapy results in specific perturbations of endothelial cells which results in a combination of membrane damage, mitochondrial damage, and rearrangement of cytoskeletal proteins. This results in cellular stress which leads to interruption of tight junctions along the endothelium and cell rounding. Cell rounding exposes the basement membrane proteins causing activation of platelets and leukocytes. Activated platelets and leukocytes release thromboxane and other eicosanoids. These eicosanoids induce vasoconstriction, platelet aggregation, increases in vessel permeability, and blood flow stasis.

  14. Acute liver damage induced by 2-nitropropane in rats: effect of diphenyl diselenide on antioxidant defenses.

    PubMed

    Borges, Lysandro P; Nogueira, Cristina Wayne; Panatieri, Rodrigo B; Rocha, João Batista Teixeira; Zeni, Gilson

    2006-03-25

    The effect of post-treatment with diphenyl diselenide on liver damage induced by 2-nitropropane (2-NP) was examined in male rats. Rats were pre-treated with a single dose of 2-NP (100 mg/kg body weight dissolved in canola oil). Afterward, the animals were post-treated with a dose of diphenyl diselenide (10, 50 or 100 micromol/kg). The parameters that indicate tissue damage such as liver histopathology, plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), urea and creatinine were determined. Since the liver damage induced by 2-NP is related to oxidative damage, lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and ascorbic acid level were also evaluated. Diphenyl diselenide (50 and 100 micromol/kg) effectively restored the increase of ALT and AST activities and urea level when compared to the 2-NP group. At the higher dose, diphenyl diselenide decreased GGT activity. Treatment with diphenyl diselenide, at all doses, effectively ameliorated the increase of hepatic and renal lipid peroxidation when compared to 2-NP group. 2-NP reduced CAT activity and neither alter SOD activity nor ascorbic acid level. This study points out the involvement of CAT activity in 2-NP-induced acute liver damage and suggests that the post-treatment with diphenyl diselenide was effective in restoring the hepatic damage induced by 2-NP. PMID:16445897

  15. Relaxin for the Treatment of Acute Decompensated Heart Failure: Pharmacology, Mechanisms of Action, and Clinical Evidence.

    PubMed

    Ng, Tien M H; Goland, Sorel; Elkayam, Uri

    2016-01-01

    Acute heart failure remains a major cause of morbidity, and its treatment requires an increasing investment of the health care system. Whereas success in treating chronic heart failure has been achieved over the last decades, several pharmacological approaches for acute heart failure have been introduced but have failed to demonstrate any clinical benefit. Serelaxin is a recombinant human relaxin-2 vasoactive peptide that causes systemic and renal vasodilation. Data suggest that the clinical benefits may be attributable to a potential combination of multiple actions of serelaxin, including improving systemic, cardiac, and renal hemodynamics, and protecting cells and organs from damage via neurohormonal, anti-inflammatory, antiremodeling, antifibrotic, anti-ischemic, and proangiogenic effects. Recently, a number of clinical trials have demonstrated that serelaxin infusion over 48 hours improved dyspnea with more rapid relief of congestion during the first days after admission for heart failure. In addition, administration of serelaxin diminished cardiac, renal, and hepatic damage, which were associated with improved long-term mortality. Available data support substantial clinical benefits and significant promise for serelaxin as a treatment option for patients with acute heart failure. This review focuses on the pharmacology and mechanisms of action of serelaxin and provides a detailed discussion of the clinical evidence for this novel therapy in acute heart failure. PMID:26331289

  16. Acute radiation-induced pulmonary damage: a clinical study on the response to fractionated radiation therapy.

    PubMed

    Mah, K; Van Dyk, J; Keane, T; Poon, P Y

    1987-02-01

    Acute radiation-induced pulmonary damage can be a significant cause of morbidity in radiation therapy of the thorax. A prospective, clinical study was conducted to obtain dose-response data on acute pulmonary damage caused by fractionated radiation therapy. The endpoint was a visible increase in lung density within the irradiated volume on a computed tomographic (CT) examination as observed independently by three diagnostic radiologists. Fifty-four patients with various malignancies of the thorax completed the study. CT chest scans were taken before and at preselected times following radiotherapy. To represent different fractionation schedules of equivalent biological effect, the estimated single dose (ED) model, ED = D X N-0.377 X T-0.058 was used in which D was the average lung dose within the high dose region in cGy, N was the number of fractions, and T was the overall treatment time in days. Patients were grouped according to ED and the percent incidence of pulmonary damage for each group was determined. Total average lung doses ranged from 29.8 Gy to 53.6 Gy given in 10 to 30 fractions over a range of 12 to 60 days. Five patient groups with incidence ranging from 30% (ED of 930) to 90% (ED of 1150) were obtained. The resulting dose-response curve predicted a 50% incidence level at an ED value (ED50) of 1000 +/- 40 ED units. This value represents fractionation schedules equivalent to a total average lung dose of 32.9 Gy given in 15 fractions over 19 days. Over the linear portion of the dose-response curve, a 5% increase in ED (or total dose if N and T remain constant), predicts a 12% increase in the incidence of acute radiation-induced pulmonary damage. PMID:3818385

  17. EphB1 Suppression in Acute Myelogenous Leukemia: Regulating the DNA Damage Control System

    PubMed Central

    Kampen, K.R.; Scherpen, F.J.G.; Garcia-Manero, G.; Yang, H.; Kaspers, G.J.L.; Cloos, J.; Zwaan, C.M.; van den Heuvel-Eibrink, M.M.; Kornblau, S.M.; De Bont, E.S.J.M.

    2016-01-01

    Loss of ephrin receptor (EphB1) expression may associate with aggressive cancer phenotypes; however, the mechanism of action remains unclear. To gain detailed insight into EphB1 function in acute myelogenous leukemia (AML), comprehensive analysis of EphB1 transcriptional regulation was conducted. In AML cells, EphB1 transcript was inversely correlated with EphB1 promoter methylation. The presence of EphB1 allowed EfnB1 ligand–mediated p53 DNA binding, leading to restoration of the DNA damage response (DDR) cascade by the activation of ATR, Chk1, p53, p21, p38, CDK1tyr15, and Bax, and downregulation of HSP27 and Bcl2. Comparatively, reintroduction of EphB1 expression in EphB1-methylated AML cells enhanced the same cascade of ATR, Chk1, p21, and CDK1tyr15, which consequently enforced programmed cell death. Interestingly, in pediatric AML samples, EphB1 peptide phosphorylation and mRNA expression were actively suppressed as compared with normal bone marrow, and a significant percentage of the primary AML specimens had EphB1 promoter hyper-methylation. Finally, EphB1 repression associated with a poor overall survival in pediatric AML. Combined, the contribution of EphB1 to the DDR system reveals a tumor-suppressor function for EphB1 in pediatric AML. Implications The tumor-suppressor function of EphB1 is clinically relevant across many malignancies, suggesting that EphB1 is an important regulator of common cancer cell trans forming pathways. PMID:25944917

  18. A new mechanism for radiation damage processes in alkali halides

    NASA Astrophysics Data System (ADS)

    Dubinko, V. I.; Turkin, A. A.; Vainshtein, D. I.; den Hartog, H. W.

    1999-12-01

    We present a theory of radiation damage formation in alkali halides based on a new mechanism of dislocation climb, which involves the production of VF centers (self-trapped hole neighboring a cation vacancy) as a result of the absorption of H centers of dislocation lines. We consider the evolution of all experimentally observed extended defects: metal colloids, gas bubbles, and vacancy voids. Voids are shown to arise and grow large due to the reaction between F and VF centers at the surface of halogen bubbles. Voids can ignite a back reaction between the radiolytic products resulting in decomposition of the irradiated material.

  19. Hygrothermal damage mechanisms in graphite-epoxy composites

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

    Lee, Hyeonseok; Sohn, Hoon

    2014-02-18

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

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

    NASA Astrophysics Data System (ADS)

    Lee, Hyeonseok; Sohn, Hoon

    2014-02-01

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

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

    PubMed

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

    2016-07-01

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

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

    SciTech Connect

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

    2014-05-15

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

  5. αKlotho deficiency in acute kidney injury contributes to lung damage.

    PubMed

    Ravikumar, Priya; Li, Liping; Ye, Jianfeng; Shi, Mingjun; Taniguchi, Masatomo; Zhang, Jianning; Kuro-O, Makoto; Hu, Ming Chang; Moe, Orson W; Hsia, Connie C W

    2016-04-01

    αKlotho is a circulating protein that originates predominantly from the kidney and exerts cytoprotective effects in distant sites. We previously showed in rodents that the lung is particularly vulnerable to αKlotho deficiency. Because acute lung injury is a common and serious complication of acute kidney injury (AKI), we hypothesized that αKlotho deficiency in AKI contributes to lung injury. To test the hypothesis, we created AKI by renal artery ischemia-reperfusion in rats and observed the development of alveolar interstitial edema and increased pulmonary oxidative damage to DNA, protein, and lipids. Administration of αKlotho-containing conditioned media 6 h post-AKI did not alter plasma creatinine but improved recovery of endogenous αKlotho production 3 days post-AKI, reduced lung edema and oxidative damage, and increased endogenous antioxidative capacity in the lung. Intravenously injected αKlotho rapidly exits alveolar capillaries as a macromolecule, suggesting transcytosis and direct access to the epithelium. To explore the epithelial action of αKlotho, we simulated oxidative stress in vitro by adding hydrogen peroxide to cultured A549 lung epithelial cells. Purified recombinant αKlotho directly protected cells at 20 pM with half-maximal effects at 40-50 pM, which is compatible with circulating αKlotho levels. Addition of recombinant αKlotho activated an antioxidant response element reporter and increased the levels of target proteins of the nuclear factor erythroid-derived 2 related factor system. In summary, αKlotho deficiency in AKI contributes to acute lung injury by reducing endogenous antioxidative capacity and increasing oxidative damage in the lung. αKlotho replacement partially reversed these abnormalities and mitigated pulmonary complications in AKI. PMID:26718784

  6. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    PubMed

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one. PMID:25847268

  7. [Pharmacological correction of toxic liver damage in patients with heavy forms of acute ethanol intoxication].

    PubMed

    Shikalova, I A; Shilov, V V; Vasil'ev, S A; Batotsyrenov, B V; Loladze, A T

    2012-01-01

    The efficiency of using remaxol and ademethionine in the therapy of patients with heavy acute alcohol intoxication on the background of toxic liver damage has been studied. The administration of remaxol led to improvement of the clinical treatment of alcohol intoxication, which is manifested by a decrease in the rate and duration of delirium tremens (from 33.9 to 10.8%), frequency of secondary lung disorders (from 18.5 to 3.1%), duration of stay in hospital (from 7.3 +/- 0.6 to 5.6 +/- 0.3 days), and total therapy duration (from 11.8 +/- 1.05 to 5.6 +/- 0.3 days). The results of biochemical investigations confirmed that remaxol and ademethionine provide effective treatment of the toxic liver damage. Remaxol decreases the degree of metabolic disorders to a greater extent than does ademethionine. PMID:22702109

  8. Personalizing mechanical ventilation for acute respiratory distress syndrome.

    PubMed

    Berngard, S Clark; Beitler, Jeremy R; Malhotra, Atul

    2016-03-01

    Lung-protective ventilation with low tidal volumes remains the cornerstone for treating patient with acute respiratory distress syndrome (ARDS). Personalizing such an approach to each patient's unique physiology may improve outcomes further. Many factors should be considered when mechanically ventilating a critically ill patient with ARDS. Estimations of transpulmonary pressures as well as individual's hemodynamics and respiratory mechanics should influence PEEP decisions as well as response to therapy (recruitability). This summary will emphasize the potential role of personalized therapy in mechanical ventilation. PMID:27076966

  9. Personalizing mechanical ventilation for acute respiratory distress syndrome

    PubMed Central

    Beitler, Jeremy R.; Malhotra, Atul

    2016-01-01

    Lung-protective ventilation with low tidal volumes remains the cornerstone for treating patient with acute respiratory distress syndrome (ARDS). Personalizing such an approach to each patient’s unique physiology may improve outcomes further. Many factors should be considered when mechanically ventilating a critically ill patient with ARDS. Estimations of transpulmonary pressures as well as individual’s hemodynamics and respiratory mechanics should influence PEEP decisions as well as response to therapy (recruitability). This summary will emphasize the potential role of personalized therapy in mechanical ventilation. PMID:27076966

  10. Platelet microparticle number is associated with the extent of myocardial damage in acute myocardial infarction

    PubMed Central

    Puspitawati, Ira; Gharini, Putrika Prastuti Ratna; Setianto, Budi Yuli

    2016-01-01

    Introduction Activated platelets generate microparticles. Increased platelet microparticles occur in acute myocardial infarction (AMI) and contribute to intracoronary thrombosis and subsequent myocardial injury. This study aimed to investigate the impact of platelet microparticles on intracoronary thrombosis by assessing the relationship between platelet microparticles and the extent of myocardial damage in AMI. Material and methods This was a cross sectional study. The subjects were patients with acute coronary syndrome (ACS). Forty-one consecutive subjects with ACS admitted to intensive cardiovascular care unit were enrolled. The clinical spectrum of ACS comprised AMI (n = 26), both ST-elevation AMI (STEMI) and non-ST-elevation AMI (NSTEMI), and unstable angina (n = 15). Platelet microparticles were isolated from peripheral venous blood and detected with anti-CD42b-PE by the flow cytometry method. The extent of myocardial damage was determined by measuring the peak level of serial cardiac enzymes within 24 h of admission. Results Subjects with AMI had a significantly higher number of platelet microparticles than those with unstable angina (4855 ±4509/µl vs. 2181 ±1923/µl respectively; p = 0.036). Subjects with STEMI had the highest number of platelet microparticles, but no significant difference was detected as compared to those with NSTEMI (5775 ±5680/µl vs. 3601 ±1632/µl). The number of platelet microparticles in AMI was positively associated with the extent of myocardial damage (peak CK-MB: r = 0.408, p = 0.019 and peak GOT: r = 0.384, p = 0.026). Conclusions The number of platelet microparticles was increased in AMI as compared to unstable angina and associated with the extent of myocardial damage. PMID:27279844

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

    PubMed Central

    Barnum, Kevin J; O’Connell, Matthew J

    2015-01-01

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

  12. [Importance of mechanical assist devices in acute circulatory arrest].

    PubMed

    Ferrari, Markus Wolfgang

    2016-03-01

    Mechanical assist devices are indicated for hemodynamic stabilization in acute circulatory arrest if conventional means of cardiopulmonary resuscitation are unable to re-establish adequate organ perfusion. Their temporary use facilitates further diagnostic and therapeutic options in selected patients, e.g. coronary angiography followed by revascularization.External thorax compression devices allow sufficient cardiac massage in case of preclinical or in-hospital circulatory arrest, especially under complex transfer conditions. These devices perform standardized thorax compressions at a rate of 80-100 per minute. Invasive mechanical support devices are used in the catheter laboratory or in the intensive care unit. Axial turbine pumps, e.g. the Impella, continuously pump blood from the left ventricle into the aortic root. The Impella can also provide right ventricle support by pumping blood from the vena cava into the pulmonary artery. So-called emergency systems or ECMO devices consist of a centrifugal pump and a membrane oxygenator allowing complete takeover of cardiac and pulmonary functions. Withdrawing blood from the right atrium and vena cava, oxygenated blood is returned to the abdominal aorta. Isolated centrifugal pumps provide left heart support without an oxygenator after transseptal insertion of a venous cannula into the left atrium.Mechanical assist devices are indicated for acute organ protection and hemodynamic stabilization for diagnostic and therapeutic measures as well as bridge to myocardial recovery. Future technical developments and better insights into the pathophysiology of mechanical circulatory support will broaden the spectrum of indications of such devices in acute circulatory arrest. PMID:26860409

  13. UNDERSTANDING DAMAGE MECHANISMS IN FERRITIC/MARTENSITIC STEELS

    SciTech Connect

    Swindeman, R.W.; Maziasz, P.J.; Swindeman, M.J.

    2003-04-22

    Advanced ferritic/martensitic steels are being used extensively in fossil energy applications. New steels such as 2 1/4Cr-W-V (T23, T24), 3Cr-W-V, 9Cr-Mo-V (T91), 7Cr-W-V, 9Cr-W-V (T92 and T911), and 12Cr-W-V (T122, SAVE 12, and NF12) are examples of tubing being used in boilers and heat recovery steam generators (1). Other products for these new steels include piping, plates, and forgings. There is concern about the high-temperature performance of the advanced steels for several reasons. First, they exhibit a higher sensitivity to temperature than the 300 series stainless steels that they often replace. Second, they tend to be metallurgically unstable and undergo significant degradation at service temperatures in the creep range. Third, the experience base is limited in regard to duration. Fourth, they will be used for thick-section, high-pressure components that require high levels of integrity. To better understand the potential limitations of these steels, damage models are being developed that consider metallurgical factors as well as mechanical performance factors. Grade 91 steel was chosen as representative of these steels for evaluation of cumulative damage models since laboratory and service exposures of grade 91 exceed 100,000 hours.

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

    PubMed

    Gardiner, Barry; Berry, Peter; Moulia, Bruno

    2016-04-01

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

  15. Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier*

    PubMed Central

    Zhang, Xi-ping; Zhang, Jie; Song, Qiao-ling; Chen, Han-qin

    2007-01-01

    Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gutorigin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP’s severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP’s process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemical reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP. PMID:18257123

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

    SciTech Connect

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

    2004-03-01

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

  17. Damage and failure mechanisms associated with photoablation of biological tissues

    SciTech Connect

    Antoun, T.; Seaman, L.; Curran, D.; Glinsky, M.

    1996-05-01

    This paper aims to examine the processes associated with failure of the cornea and other collagenous tissues during photoablation. Two different constitutive models are applied to simulate a series of laser deposition experiments into porcine reticular dermis (1), a biological tissue similar to the cornea in composition and photoablation characteristics. The first of our constitutive models, DFRACT, is a physically motivated, micromechanical model based on the nucleation and growth of spherical voids (2). The second is a relatively simple model that allows the material to vaporize and thermally soften. The simulation results reproduce the prominent features observed experimentally thereby shedding a new light on the operative mechanisms during photoablation. The good qualitative agreement between the simulated stress histories and the stress histories measured during the experiments also demonstrates the effectiveness of micromechanical damage and failure modeling as a viable tool for optimizing existing laser surgery procedures and designing new ones. {copyright} {ital 1996 American Institute of Physics.}

  18. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    SciTech Connect

    Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  19. Contribution of damage-associated molecular patterns to transfusion-related acute lung injury in cardiac surgery

    PubMed Central

    Müller, Marcella C.A.; Tuinman, Pieter R.; Vlaar, Alexander P.; Tuip, Anita M.; Maijoor, Kelly; Achouiti, Achmed; van t Veer, Cornelis; Vroom, Margreeth B.; Juffermans, Nicole P.

    2014-01-01

    Background The incidence of transfusion-related acute lung injury (TRALI) in cardiac surgery patients is high and this condition contributes to an adverse outcome. Damage-associated molecular pattern (DAMP) molecules, HMGB1 and S100A12, are thought to mediate inflammatory changes in acute respiratory distress syndrome. We aimed to determine whether DAMP are involved in the pathogenesis of TRALI in cardiac surgery patients. Materials and methods This was a secondary analysis of a prospective observational trial in cardiac surgery patients admitted to the Intensive Care Unit of a university hospital in the Netherlands. Fourteen TRALI cases were randomly matched with 32 transfused and non-transfused controls. Pulmonary levels of HMGB1, S100A12 and inflammatory cytokines (interleukins-1β, -6, and -8 and tumour necrosis factor-α) were determined when TRALI evolved. In addition, systemic and pulmonary levels of soluble receptor for advanced glycation end products (sRAGE) were determined. Results HMGB1 expression and levels of sRAGE in TRALI patients did not differ from those in controls. There was a trend towards higher S100A12 levels in TRALI patients compared to the controls. Furthermore, S100A12 levels were associated with increased levels of markers of pulmonary inflammation, prolonged cardiopulmonary bypass, hypoxemia and duration of mechanical ventilation. Conclusion No evidence was found that HMGB1 and sRAGE contribute to the development of TRALI. S100A12 is associated with duration of cardiopulmonary bypass, pulmonary inflammation, hypoxia and prolonged mechanical ventilation and may contribute to acute lung injury in cardiac surgery patients. PMID:24887223

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

    PubMed

    Ross, E D; Stewart, R S

    1987-03-01

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

  1. Mechanical Thrombectomy in Acute Ischemic Stroke: A Systematic Review.

    PubMed

    Lambrinos, Anna; Schaink, Alexis K; Dhalla, Irfan; Krings, Timo; Casaubon, Leanne K; Sikich, Nancy; Lum, Cheemun; Bharatha, Aditya; Pereira, Vitor Mendes; Stotts, Grant; Saposnik, Gustavo; Kelloway, Linda; Xie, Xuanqian; Hill, Michael D

    2016-07-01

    Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke. PMID:27071728

  2. Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

    PubMed Central

    Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S.

    2013-01-01

    ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. PMID:23919993

  3. DNA Damage Focus Analysis in Blood Samples of Minipigs Reveals Acute Partial Body Irradiation

    PubMed Central

    Lamkowski, Andreas; Forcheron, Fabien; Agay, Diane; Ahmed, Emad A.; Drouet, Michel; Meineke, Viktor; Scherthan, Harry

    2014-01-01

    Radiation accidents frequently involve acute high dose partial body irradiation leading to victims with radiation sickness and cutaneous radiation syndrome that implements radiation-induced cell death. Cells that are not lethally hit seek to repair ionizing radiation (IR) induced damage, albeit at the expense of an increased risk of mutation and tumor formation due to misrepair of IR-induced DNA double strand breaks (DSBs). The response to DNA damage includes phosphorylation of histone H2AX in the vicinity of DSBs, creating foci in the nucleus whose enumeration can serve as a radiation biodosimeter. Here, we investigated γH2AX and DNA repair foci in peripheral blood lymphocytes of Göttingen minipigs that experienced acute partial body irradiation (PBI) with 49 Gy (±6%) Co-60 γ-rays of the upper lumbar region. Blood samples taken 4, 24 and 168 hours post PBI were subjected to γ-H2AX, 53BP1 and MRE11 focus enumeration. Peripheral blood lymphocytes (PBL) of 49 Gy partial body irradiated minipigs were found to display 1–8 DNA damage foci/cell. These PBL values significantly deceed the high foci numbers observed in keratinocyte nuclei of the directly γ-irradiated minipig skin regions, indicating a limited resident time of PBL in the exposed tissue volume. Nonetheless, PBL samples obtained 4 h post IR in average contained 2.2% of cells displaying a pan-γH2AX signal, suggesting that these received a higher IR dose. Moreover, dispersion analysis indicated partial body irradiation for all 13 minipigs at 4 h post IR. While dose reconstruction using γH2AX DNA repair foci in lymphocytes after in vivo PBI represents a challenge, the DNA damage focus assay may serve as a rapid, first line indicator of radiation exposure. The occurrence of PBLs with pan-γH2AX staining and of cells with relatively high foci numbers that skew a Poisson distribution may be taken as indicator of acute high dose partial body irradiation, particularly when samples are available early after

  4. DNA damage focus analysis in blood samples of minipigs reveals acute partial body irradiation.

    PubMed

    Lamkowski, Andreas; Forcheron, Fabien; Agay, Diane; Ahmed, Emad A; Drouet, Michel; Meineke, Viktor; Scherthan, Harry

    2014-01-01

    Radiation accidents frequently involve acute high dose partial body irradiation leading to victims with radiation sickness and cutaneous radiation syndrome that implements radiation-induced cell death. Cells that are not lethally hit seek to repair ionizing radiation (IR) induced damage, albeit at the expense of an increased risk of mutation and tumor formation due to misrepair of IR-induced DNA double strand breaks (DSBs). The response to DNA damage includes phosphorylation of histone H2AX in the vicinity of DSBs, creating foci in the nucleus whose enumeration can serve as a radiation biodosimeter. Here, we investigated γH2AX and DNA repair foci in peripheral blood lymphocytes of Göttingen minipigs that experienced acute partial body irradiation (PBI) with 49 Gy (± 6%) Co-60 γ-rays of the upper lumbar region. Blood samples taken 4, 24 and 168 hours post PBI were subjected to γ-H2AX, 53BP1 and MRE11 focus enumeration. Peripheral blood lymphocytes (PBL) of 49 Gy partial body irradiated minipigs were found to display 1-8 DNA damage foci/cell. These PBL values significantly deceed the high foci numbers observed in keratinocyte nuclei of the directly γ-irradiated minipig skin regions, indicating a limited resident time of PBL in the exposed tissue volume. Nonetheless, PBL samples obtained 4 h post IR in average contained 2.2% of cells displaying a pan-γH2AX signal, suggesting that these received a higher IR dose. Moreover, dispersion analysis indicated partial body irradiation for all 13 minipigs at 4 h post IR. While dose reconstruction using γH2AX DNA repair foci in lymphocytes after in vivo PBI represents a challenge, the DNA damage focus assay may serve as a rapid, first line indicator of radiation exposure. The occurrence of PBLs with pan-γH2AX staining and of cells with relatively high foci numbers that skew a Poisson distribution may be taken as indicator of acute high dose partial body irradiation, particularly when samples are available early after IR

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

    PubMed

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

    2012-04-01

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

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

    PubMed

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

    2016-01-01

    Epidemiological studies suggest a correlation between increased airborne particulate matter (PM) and adverse health effects. The mechanisms of PM-health effects are believed to involve oxidative stress and inflammation. To evaluate the ability of PM promoting skin tissue damage, one of the main organs exposed to outdoor pollutants, we analyzed the effect of concentrated ambient particles (CAPs) in a reconstructed human epidermis (RHE) model. RHE tissues were exposed to 25 or 100 µg/ml CAPs for 24 or 48 h. Data showed that RHE seems to be more susceptible to CAPs-induced toxicity after 48 h exposure than after 24 h. We found a local reactive O(2) species (ROS) production increase generated from metals present on the particle, which contributes to lipids oxidation. Furthermore, as a consequence of altered redox status, NFkB nucleus translocation was increase upon CAPs exposure, as well as cyclooxygenase 2 and cytochrome P450 levels, which may be involved in the inflammatory response initiated by PM. CAPs also triggered an apoptotic process in skin. Surprisingly, by transition electron microscopy analysis we showed that CAPs were able to penetrate skin tissues. These findings contribute to the understanding of the cutaneous pathophysiological mechanisms initiated by CAPs exposure, where oxidative stress and inflammation may play predominant roles. PMID:26507108

  7. Preemptive mechanical ventilation can block progressive acute lung injury

    PubMed Central

    Sadowitz, Benjamin; Jain, Sumeet; Kollisch-Singule, Michaela; Satalin, Joshua; Andrews, Penny; Habashi, Nader; Gatto, Louis A; Nieman, Gary

    2016-01-01

    Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS. PMID:26855896

  8. Preemptive mechanical ventilation can block progressive acute lung injury.

    PubMed

    Sadowitz, Benjamin; Jain, Sumeet; Kollisch-Singule, Michaela; Satalin, Joshua; Andrews, Penny; Habashi, Nader; Gatto, Louis A; Nieman, Gary

    2016-02-01

    Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS. PMID:26855896

  9. Acute crack cocaine exposure induces genetic damage in multiple organs of rats.

    PubMed

    Moretti, Eduardo Gregolin; Yujra, Veronica Quispe; Claudio, Samuel Rangel; Silva, Marcelo Jose Dias; Vilegas, Wagner; Pereira, Camilo Dias Seabra; de Oliveira, Flavia; Ribeiro, Daniel Araki

    2016-04-01

    Crack cocaine is a very toxic product derived from cocaine. The aim of this study was to evaluate genetic damage in multiple organs of rats following acute exposure to crack cocaine. A total of 20 Wistar rats were distributed into four groups (n = 5), as follows: 0, 4.5, 9, and 18 mg/kg body weight (b.w.) of crack cocaine administered by intraperitoneal route (i.p.). All animals were killed 24 h after intraperitoneal (i.p.) injection. The results showed that crack cocaine increased the number of micronucleated cells in bone marrow cells exposed to 18 mg/kg crack cocaine (p < 0.05). Peripheral blood and liver cells presented genetic damage as depicted by single cell gel (comet) assay at 9 and 18 mg/kg doses (p < 0.05). Immunohistochemistry data revealed significant increase in 8-hydroxy-20-deoxyguanosine (8-OHdG) immunoexpression in hepatocytes of animals exposed to crack cocaine at 9 and 18 mg/kg (p < 0.05) when compared with negative controls. Taken together, our results demonstrate that crack cocaine is able to induce genomic damage in multiple organs of Wistar rats. PMID:26825523

  10. Protective effect of diphenyl diselenide on acute liver damage induced by 2-nitropropane in rats.

    PubMed

    Borges, Lysandro P; Borges, Vanessa Corralo; Moro, Angelica Venturini; Nogueira, Cristina Wayne; Rocha, Joao Batista Teixeira; Zeni, Gilson

    2005-05-15

    The effect of diphenyl diselenide, (PhSe)2, administration on 2-nitropropane (2-NP)-induced hepatic damage was examined in male rats. Rats were pre-treated with a single dose of diphenyl diselenide (10, 50 or 100 micromol/kg). Afterward, they received only one dose of 2-NP (100 mg/kg body weight dissolved in olive oil). The parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alpha-fetoprotein (AFP), creatinine and urea were determined. Since toxicity induced by 2-NP is related to oxidative stress, lipid peroxidation was also evaluated. Diphenyl diselenide (100 micromol/kg) significantly reduced plasma ALT, gamma-GGT, AFP levels when compared to 2-NP group. Treatment with diphenyl diselenide, at all doses, effectively protects the increase of lipid peroxidation when compared to 2-NP group. Histological examination revealed that 2-NP treatment causes a moderate swelling and degenerative alterations on hepatocytes and diphenyl diselenide (100 micromol/kg) protects against these alterations. Diphenyl diselenide (50 and 100 micromol/kg) significantly decreased the urea level. This study evidences the protective effect of diphenyl diselenide by 2-NP-induced acute hepatic damage. PMID:15804453

  11. Neuronal mechanism for acute mechanosensitivity in tactile-foraging waterfowl

    PubMed Central

    Schneider, Eve R.; Mastrotto, Marco; Laursen, Willem J.; Schulz, Vincent P.; Goodman, Jena B.; Funk, Owen H.; Gallagher, Patrick G.; Gracheva, Elena O.; Bagriantsev, Sviatoslav N.

    2014-01-01

    Relying almost exclusively on their acute sense of touch, tactile-foraging birds can feed in murky water, but the cellular mechanism is unknown. Mechanical stimuli activate specialized cutaneous end organs in the bill, innervated by trigeminal afferents. We report that trigeminal ganglia (TG) of domestic and wild tactile-foraging ducks exhibit numerical expansion of large-diameter mechanoreceptive neurons expressing the mechano-gated ion channel Piezo2. These features are not found in visually foraging birds. Moreover, in the duck, the expansion of mechanoreceptors occurs at the expense of thermosensors. Direct mechanical stimulation of duck TG neurons evokes high-amplitude depolarizing current with a low threshold of activation, high signal amplification gain, and slow kinetics of inactivation. Together, these factors contribute to efficient conversion of light mechanical stimuli into neuronal excitation. Our results reveal an evolutionary strategy to hone tactile perception in vertebrates at the level of primary afferents. PMID:25246547

  12. Damage in total knee replacements from mechanical overload.

    PubMed

    Zimmerman, William F; Miller, Mark A; Cleary, Richard J; Izant, Timothy H; Mann, Kenneth A

    2016-07-01

    The mechanical loads acting across the knee joint following total knee replacements (TKR) during activities of daily living have recently been measured using instrumented TKRs. Using a series of postmortem retrieved TKR constructs we investigated whether these mechanical loads could result in damage to the implant bone interface or supporting bone in the tibia. Eighteen cemented en bloc tibial components (0 to 22 years in service) were loaded under axial compression in increments from 1 to 10 times body weight and digital image correlation was used to measure bone strain and interface micromotion during loading and unloading. Failure was considered to occur when micromotion exceeded 150µm or compressive bone strain exceeded 7300με. The results show that all retrieved specimens had sufficient bone strength to support most activities of daily living, but ~40% would be at risk under larger physiologic loads that might occur secondary to a higher impacts such as jogging or a stumble. The tray-bone micromotion (regression model R(2)=0.48, p=0.025) was greater for donors with lower age at implantation (p=0.0092). Proximal bone strain (model R(2)=0.46, p=0.03) was greater for donors with longer time in service (p=0.021). Distal bone strain (model R(2)=0.58, p=0.005) was greater for donors with more time in service (p=0.0054) and lower peri-implant BMD (p=0.049). High mechanical overload of a single or repetitive nature may be an initiating factor in aseptic loosening of total joint arthroplasties and should be avoided in order to prolong the life of the implant. PMID:27237382

  13. Acute ZnO nanoparticles exposure induces developmental toxicity, oxidative stress and DNA damage in embryo-larval zebrafish.

    PubMed

    Zhao, Xuesong; Wang, Shutao; Wu, Yuan; You, Hong; Lv, Lina

    2013-07-15

    Nano-scale zinc oxide (nano-ZnO) is widely used in various industrial and commercial applications. However, the available toxicological information was inadequate to assess the potential ecological risk of nano-ZnO to aquatic organisms and the publics. In this study, the developmental toxicity, oxidative stress and DNA damage of nano-ZnO embryos were investigated in the embryo-larval zebrafish, the toxicity of Zn(2+) releasing from nano-ZnO were also investigated to ascertain the relationship between the nano-ZnO and corresponding Zn(2+). Zebrafish embryos were exposed to 1, 5, 10, 20, 50, and 100mg/L nano-ZnO and 0.59, 2.15, 3.63, 4.07, 5.31, and 6.04 mg/L Zn(2+) for 144 h post-fertilisation (hpf), respectively. Up to 144 hpf, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and malondialdehyde (MDA) contents, the genes related to oxidative damage, reactive oxygen species (ROS) generation and DNA damage in zebrafish embryos were measured. The nano-ZnO was found to exert a dose-dependent toxicity to zebrafish embryos and larvae, reducing the hatching rate and inducing malformation and the acute toxicity to zebrafish embryos was greater than that of the Zn(2+) solution. The generation of ROS was significantly increased at 50 and 100mg/L nano-ZnO. DNA damage of zebrafish embryo was evaluated by single-cell gel electrophoresis and was enhanced with increasing nano-ZnO concentration. Moreover, the transcriptional expression of mitochondrial inner membrane genes related to ROS production, such as Bcl-2, in response to oxidative damage, such as Nqo1, and related to antioxidant response element such as Gstp2 were significantly down-regulated in the nano-ZnO treatment groups. However, the nano-ZnO up-regulated the transcriptional expression of Ucp2-related to ROS production. In conclusion, nano-ZnO induces developmental toxicity, oxidative stress and DNA damage on zebrafish embryos and the dissolved Zn(2+) only partially

  14. Mechanical ventilation of patients with acute lung injury.

    PubMed

    Sessler, C N

    1998-10-01

    Ventilatory management of patients with acute lung injury (ALI), particularly its most severe subset, acute respiratory distress syndrome (ARDS), is complex. Newer lung protective strategies emphasize measures to enhance alveolar recruitment and avoid alveolar overdistention, thus minimizing the risk of ventilator-induced lung injury (VILI). Key components of such strategies include the use of smaller-than-conventional tidal volumes which maintain peak transpulmonary pressure below the pressure associated with overdistention, and titration of positive end-expiratory pressure to promote maximal alveolar recruitment. Novel techniques, including prone positioning, inverse ratio ventilation, tracheal gas insufflation, and high frequency ventilation, are considerations in severe ARDS. No single approach is best for all patients; adjustment of ventilatory parameters to individual characteristics, such as lung mechanics and gas exchange, is required. PMID:9891634

  15. [Acute respiratory distress syndrome: definitions, mechanisms and treatment].

    PubMed

    Urso, Domenico Lorenzo

    2006-01-01

    Acute respiratory distress syndrome is a secondary acute respiratory insufficiency caused by an inflammatory syndrome which is characterized by an increased of permeability pulmonary edema, associated with many other clinic anomalies, radiological and pathophysiological not directly caused by, but with which it could coexist, a left atrial hypertension. The illness, characterized by refractory hypoxemia, recognizes several causes, which have direct or indirect harm on the cells of the membrane alveolus-capillary. In spite of the improvements in the therapeutic approach, during these last 40 years, represented by the aid of the mechanical ventilation and the use of selective pulmonary vasodilators, this condition is life threatening and often lethal: 90% of mortality rate amongst those older than 65 years. PMID:16913178

  16. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.

    PubMed

    Chang, Jianhui; Luo, Yi; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  17. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice

    PubMed Central

    Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  18. Cortical activity evoked by an acute painful tissue-damaging stimulus in healthy adult volunteers

    PubMed Central

    Williams, Gemma; Lee, Amy; Meek, Judith; Slater, Rebeccah; Olhede, Sofia; Fitzgerald, Maria

    2013-01-01

    Everyday painful experiences are usually single events accompanied by tissue damage, and yet most experimental studies of cutaneous nociceptive processing in the brain use repeated laser, thermal, or electrical stimulations that do not damage the skin. In this study the nociceptive activity in the brain evoked by tissue-damaging skin lance was analyzed with electroencephalography (EEG) in 20 healthy adult volunteers (13 men and 7 women) aged 21–40 yr. Time-frequency analysis of the evoked activity revealed a distinct late event-related vertex potential (lance event-related potential, LERP) at 100–300 ms consisting of a phase-locked energy increase between 1 and 20 Hz (delta-beta bands). A pairwise comparison between lance and sham control stimulation also revealed a period of ultralate stronger desynchronization after lance in the delta band (1–5 Hz). Skin application of mustard oil before lancing, which sensitizes a subpopulation of nociceptors expressing the cation channel TRPA1, did not affect the ultralate desynchronization but reduced the phase-locked energy increase in delta and beta bands, suggesting a central interaction between different modalities of nociceptive inputs. Verbal descriptor screening of individual pain experience revealed that lance pain is predominantly due to Aδ fiber activation, but when individuals describe lances as C fiber mediated, an ultralate delta band event-related desynchronization occurs in the brain-evoked activity. We conclude that pain evoked by acute tissue damage is associated with distinct Aδ and C fiber-mediated patterns of synchronization and desynchronization of EEG oscillations in the brain. PMID:23427303

  19. Acute O3 damage on first year coppice sprouts of aspen and maple sprouts in an open-air experiment

    SciTech Connect

    Darbah, J.N.; Nagy, J.; Jones, W. S.; Burton, A. J.; Kubiske, M. E.

    2011-10-01

    We studied the effect of high ozone (O{sub 3}) concentration (110-490 nmol mol{sup -1}) on regenerating aspen (Populus tremuloides) and maple (Acer saccharum) trees at an open-air O{sub 3} pollution experiment near Rhinelander WI USA. This study is the first of its kind to examine the effects of acute O{sub 3} exposure on aspen and maple sprouts after the parent trees, which were grown under elevated O{sub 3} and/or CO{sub 2} for 12 years, were harvested. Acute O{sub 3} damage was not uniform within the crowns of aspen suckers; it was most severe in the mature, fully expanded photosynthesizing leaves. Young expanding leaves showed no visible signs of acute O{sub 3} damage contrary to expectations. Stomatal conductance played a primary role in the severity of acute O{sub 3} damage as it directly controlled O{sub 3} uptake. Maple sprouts, which had lower stomatal conductance, smaller stomatal aperture, higher stomatal density and larger leaf surface area, were tolerant of acute O{sub 3} exposure. Moreover, elevated CO{sub 2} did not ameliorate the adverse effects of acute O{sub 3} dose on aspen and maple sprouts, in contrast to its ability to counteract the effects of long-term chronic exposure to lower O{sub 3} levels.

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

    PubMed Central

    Nakad, Rania; Schumacher, Björn

    2016-01-01

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

  1. Gastroprotective Effect of Cochinchina momordica Seed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model

    PubMed Central

    Lim, Ji Hwan; Kim, Joo-Hyun; Lee, Byoung Hwan; Seo, Pyoung Ju; Kang, Jung Mook; Jo, So Young; Park, Ji Hyun; Nam, Ryoung Hee; Chang, Hyun; Kwon, Jin-Won; Lee, Dong Ho

    2014-01-01

    Background/Aims The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. Methods The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. Results All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. Conclusions SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats. PMID:24516701

  2. Diving bradycardia: a mechanism of defence against hypoxic damage.

    PubMed

    Alboni, Paolo; Alboni, Marco; Gianfranchi, Lorella

    2011-06-01

    A feature of all air-breathing vertebrates, diving bradycardia is triggered by apnoea and accentuated by immersion of the face or whole body in cold water. Very little is known about the afferents of diving bradycardia, whereas the efferent part of the reflex circuit is constituted by the cardiac vagal fibres. Diving bradycardia is associated with vasoconstriction of selected vascular beds and a reduction in cardiac output. The diving response appears to be more pronounced in mammals than in birds. In humans, the bradycardic response to diving varies greatly from person to person; the reduction in heart rate generally ranges from 15 to 40%, but a small proportion of healthy individuals can develop bradycardia below 20 beats/min. During prolonged dives, bradycardia becomes more pronounced because of activation of the peripheral chemoreceptors by a reduction in the arterial partial pressure of oxygen (O2), responsible for slowing of heart rate. The vasoconstriction is associated with a redistribution of the blood flow, which saves O2 for the O2-sensitive organs, such as the heart and brain. The results of several investigations carried out both in animals and in humans show that the diving response has an O2-conserving effect, both during exercise and at rest, thus lengthening the time to the onset of serious hypoxic damage. The diving response can therefore be regarded as an important defence mechanism for the organism. PMID:21330930

  3. Arterial damages in acute elbow dislocations: which diagnostic tests are required?

    PubMed

    Lutter, Christoph; Pfefferkorn, Ronny; Schoeffl, Volker

    2016-01-01

    Blunt vessel injuries of peripheral arteries caused by a direct trauma are rare. Studies have described the frequency of arterial ruptures following closed elbow dislocations in 0.3-1.7% of all cases. However, arterial damage does not always necessarily appear as a complete rupture of the vessel with a loss of peripheral circulation and ischaemic symptoms; a relatively strong periarticular system of collaterals can maintain circulation. Furthermore, the traumatic dislocation can also cause intimal tears, arterial dissections and aneurysms or thrombosis. In all cases of vessel injury, including total disruption, a peripheral pulse might still be palpable. 3 weeks after an acute elbow dislocation, we have diagnosed a patient with a long-segment stenosis of the brachial artery and a thrombosis of the radial artery. Therefore, the close anatomic proximity to the neurovascular structures should always be considered in cases of elbow dislocations, even if peripheral pulses are traceable. PMID:27436035

  4. Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response

    PubMed Central

    Xing, Meichun; Wang, Xiaohui; Palmai-Pallag, Timea; Shen, Huahao; Helleday, Thomas; Hickson, Ian D.; Ying, Songmin

    2015-01-01

    The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found that MUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damage response that ultimately activates cellular senescence. Moreover, we show that MUS81 is required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replication following replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity. PMID:26415217

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

    PubMed

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

    2016-02-01

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

  6. Genotoxic evaluation of Mikania laevigata extract on DNA damage caused by acute coal dust exposure.

    PubMed

    Freitas, Tiago P; Heuser, Vanina D; Tavares, Priscila; Leffa, Daniela D; da Silva, Gabriela A; Citadini-Zanette, Vanilde; Romão, Pedro R T; Pinho, Ricardo A; Streck, Emilio L; Andrade, Vanessa M

    2009-06-01

    In the present article, we report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100 mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80 mg/kg) and xylazine (20 mg/kg), and gross mineral coal dust (3 mg/0.3 mL saline) (groups 2 and 4) or saline solution (0.3 mL) (groups 1 and 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation. PMID:19627217

  7. Selective Cyclooxygenase-2 Inhibition Protects Against Myocardial Damage in Experimental Acute Ischemia

    PubMed Central

    Carnieto, Alberto; Dourado, Paulo Magno Martins; da Luz, Protásio Lemos; Chagas, Antonio Carlos Palandri

    2009-01-01

    BACKGROUND Acute myocardial infarction is associated with tissue inflammation. Early coronary reperfusion clearly improves the outcome but may help propagate the inflammatory response and enhance tissue damage. Cyclooxygenase-2 is an enzyme that catalyzes the initial step in the formation of inflammatory prostaglandins from arachidonic acid. Cyclooxygenase-2 levels are increased when ischemic cardiac events occur. The overall function of COX-2 in the inflammatory process generated by myocardial ischemic damage has not yet been elucidated. GOAL The objective of this study was to determine whether a selective cyclooxygenase-2 inhibitor (rofecoxib) could alter the evolution of acute myocardial infarction after reperfusion. METHODS AND RESULTS This study was performed with 48 mongrel dogs divided into two groups: controls and those treated with the drug. All animals were prepared for left anterior descending coronary artery occlusion. The dogs then underwent 180 minutes of coronary occlusion, followed by 30 minutes of reperfusion. Blood samples were collected from the venous sinus immediately before coronary occlusion and after 30 minutes of reperfusion for measurements of CPK-MB, CPK-MBm and troponin I. During the experiment we observed the mean blood pressure, heart rate and coronary flow. The coronary flow and heart rate did not change, but in the control group, there was blood pressure instability, in addition to maximal levels of CPK-MB post-infarction. The same results were observed for CPK-MBm and troponin I. CONCLUSION In a canine model of myocardial ischemia-reperfusion, selective inhibition of Cyclooxygenase-2 with rofecoxib was not associated with early detrimental effects on the hemodynamic profile or the gross extent of infarction; in fact, it may be beneficial by limiting cell necrosis. PMID:19330252

  8. Genotoxic Evaluation of Mikania laevigata Extract on DNA Damage Caused by Acute Coal Dust Exposure

    SciTech Connect

    Freitas, T.P.; Heuser, V.D.; Tavares, P.; Leffa, D.D.; da Silva, G.A.; Citadini-Zanette, V.; Romao, P.R.T.; Pinho, R.A.; Streck, E.L.; Andrade,V.M.

    2009-06-15

    We report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100 mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80 mg/kg) and xylazine (20 mg/kg), and gross mineral coal dust (3 mg/0.3 mL saline) (groups 2 and 4) or saline solution (0.3 mL) (groups 1 and 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation.

  9. Novel Lipid Mediators and Resolution Mechanisms in Acute Inflammation

    PubMed Central

    Serhan, Charles N.

    2010-01-01

    Because inflammation is appreciated as a unifying basis of many widely occurring diseases, the mechanisms involved in its natural resolution are of considerable interest. Using contained, self-limited inflammatory exudates and a systems approach, novel lipid-derived mediators and pathways were uncovered in the resolution of inflammatory exudates. These new families of local mediators control both the duration and magnitude of acute inflammation as well as the return of the site to homeostasis in the process of catabasis. This new genus of specialized proresolving mediators (SPM) includes essential fatty acid–derived lipoxins, resolvins, protectins, and, most recently, maresins. These families were named based on their unique structures and potent stereoselective actions. The temporally initiated biosynthesis of SPM and their direct impact on leukocyte trafficking and macrophage-directed clearance mechanisms provide clear evidence that resolution is an active, programmed response at the tissue level. Moreover, SPM that possess anti-inflammatory (ie, limiting PMN infiltration) and proresolving (enhance macrophage uptake and clearance of apoptotic PMN and microbial particles) actions as well as stimulating mucosal antimicrobial responses demonstrate that anti-inflammation and proresolution are different responses of the host and novel defining properties of these molecules. The mapping of new resolution circuits has opened the possibility for understanding mechanisms that lead from acute to chronic inflammation, or to the resolution thereof, as well as to potential, resolution-based immunopharmacological therapies. PMID:20813960

  10. [Mechanisms by which acute orofacial pain becomes chronic].

    PubMed

    Cahana, A; Forster, A

    2006-06-01

    Pain is a complex, multidimensional experience encompassing sensory-discriminative, cognitive, emotional and motivational dimensions. These dimensions in the orofacial region have particular expression since the face and mouth have special biological, emotional and psychological meaning to each individual. Orofacial pain is frequent. Epidemiological studies reveal a high prevalence of severe pain in syndromes such as temporomandibular disorders (TMD), burning mouth syndrome and toothaches, as well as an important role of psychosocial influences, contributing to the persistence of these syndromes. Many of the difficulties experienced by clinicians with the diagnosis and management of acute and chronic orofacial pain stem from a lack of recognition and understanding of these complex conditions, the various intricate bio-psycho-social interactions and the neurobiology behind the chronicisation of acute pain. This text strives to review the important advances and insights into the peripheral processes by which noxious stimuli activates or modulates nociceptive afferent input into the brainstem, the neural pathways in the brainstem and higher levels of the trigeminal (V) somatosensory system and the mechanisms involved in the plasticity of nociceptive transmission. We shall link this knowledge to clinical correlates and suggest a therapeutic approach in acute orofacial pain, in the attempt to avoid the development of chronic pain. PMID:16804482

  11. Impact of mechanical ventilation on the pathophysiology of progressive acute lung injury.

    PubMed

    Nieman, Gary F; Gatto, Louis A; Habashi, Nader M

    2015-12-01

    The earliest description of what is now known as the acute respiratory distress syndrome (ARDS) was a highly lethal double pneumonia. Ashbaugh and colleagues (Ashbaugh DG, Bigelow DB, Petty TL, Levine BE Lancet 2: 319-323, 1967) correctly identified the disease as ARDS in 1967. Their initial study showing the positive effect of mechanical ventilation with positive end-expiratory pressure (PEEP) on ARDS mortality was dampened when it was discovered that improperly used mechanical ventilation can cause a secondary ventilator-induced lung injury (VILI), thereby greatly exacerbating ARDS mortality. This Synthesis Report will review the pathophysiology of ARDS and VILI from a mechanical stress-strain perspective. Although inflammation is also an important component of VILI pathology, it is secondary to the mechanical damage caused by excessive strain. The mechanical breath will be deconstructed to show that multiple parameters that comprise the breath-airway pressure, flows, volumes, and the duration during which they are applied to each breath-are critical to lung injury and protection. Specifically, the mechanisms by which a properly set mechanical breath can reduce the development of excessive fluid flux and pulmonary edema, which are a hallmark of ARDS pathology, are reviewed. Using our knowledge of how multiple parameters in the mechanical breath affect lung physiology, the optimal combination of pressures, volumes, flows, and durations that should offer maximum lung protection are postulated. PMID:26472873

  12. Micro-mechanical modeling of perforating shock damage

    SciTech Connect

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

    1997-11-17

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

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

    SciTech Connect

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

    2002-01-01

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

  14. The Acute Respiratory Distress Syndrome: Mechanisms and Perspective Therapeutic Approaches

    PubMed Central

    Gonzales, JN; Lucas, R; Verin, AD

    2015-01-01

    Acute Respiratory Distress Syndrome (ARDS) is a severe lung inflammatory disorder with a 30–50% mortality. Sepsis and pneumonia are the leading causes of ARDS. On the cellular level there is pulmonary capillary endothelial cell permeability and fluid leakage into the pulmonary parenchyma, followed by neutrophils, cytokines and an acute inflammatory response. When fluid increases in the interstitium then the outward movement continues and protein rich fluid floods the alveolar spaces through the tight junctions of the epithelial cells. Neutrophils play an important role in the development of pulmonary edema associated with acute lung injury or ARDS. Animal studies have shown that endothelial injury appears within minutes to hours after Acute Lung Injury (ALI) initiation with resulting intercellular gaps of the endothelial cells. The Endothelial Cell (EC) gaps allow for permeability of fluid, neutrophils and cytokines into the pulmonary parenchymal space. The neutrophils that infiltrate the lungs and migrate into the airways express pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and contribute to both the endothelial and epithelial integrity disruption of the barriers. Pharmacological treatments have been ineffective. The ARDS Network trial identified low tidal volume mechanical ventilation, positive end expiratory pressure and fluid management guidelines that have improved outcomes for patients with ARDS. Extracorporeal membrane oxygenation is used in specialized centers for severe cases. Prone positioning has recently proven to have significantly decreased ventilator days and days in the intensive care unit. Current investigation includes administration of mesenchymal stem cell therapy, partial fluid ventilation, TIP peptide nebulized administration and the continued examination of pharmacologic drugs. PMID:26973981

  15. Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview

    PubMed Central

    Maléth, József; Hegyi, Péter

    2016-01-01

    Acute pancreatitis (AP) is a leading cause of hospitalization among non-malignant gastrointestinal disorders. The mortality of severe AP can reach 30–50%, which is most probably owing to the lack of specific treatment. Therefore, AP is a major healthcare problem, which urges researchers to identify novel drug targets. Studies from the last decades highlighted that the toxic cellular Ca2+ overload and mitochondrial damage are key pathogenic steps in the disease development affecting both acinar and ductal cell functions. Moreover, recent observations showed that modifying the cellular Ca2+ signalling might be beneficial in AP. The inhibition of Ca2+ release from the endoplasmic reticulum or the activity of plasma membrane Ca2+ influx channels decreased the severity of AP in experimental models. Similarly, inhibition of mitochondrial permeability transition pore (MPTP) opening also seems to improve the outcome of AP in in vivo animal models. At the moment MPTP blockers are under detailed clinical investigation to test whether interventions in MPTP openings and/or Ca2+ homeostasis of the cells can be specific targets in prevention or treatment of cell damage in AP. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377719

  16. Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview.

    PubMed

    Maléth, József; Hegyi, Péter

    2016-08-01

    Acute pancreatitis (AP) is a leading cause of hospitalization among non-malignant gastrointestinal disorders. The mortality of severe AP can reach 30-50%, which is most probably owing to the lack of specific treatment. Therefore, AP is a major healthcare problem, which urges researchers to identify novel drug targets. Studies from the last decades highlighted that the toxic cellular Ca(2+) overload and mitochondrial damage are key pathogenic steps in the disease development affecting both acinar and ductal cell functions. Moreover, recent observations showed that modifying the cellular Ca(2+) signalling might be beneficial in AP. The inhibition of Ca(2+) release from the endoplasmic reticulum or the activity of plasma membrane Ca(2+) influx channels decreased the severity of AP in experimental models. Similarly, inhibition of mitochondrial permeability transition pore (MPTP) opening also seems to improve the outcome of AP in in vivo animal models. At the moment MPTP blockers are under detailed clinical investigation to test whether interventions in MPTP openings and/or Ca(2+) homeostasis of the cells can be specific targets in prevention or treatment of cell damage in AP.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377719

  17. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

    PubMed Central

    Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

    2015-01-01

    The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

  18. Mechanisms of fatigue damage in boron/aluminum composites

    NASA Technical Reports Server (NTRS)

    Johnson, W. S.

    1980-01-01

    Tensile fatigue tests were conducted on several laminates of boron/aluminum (6061-0). In laminates with 0 deg fibers on the outside, an analysis that identifies "shakedown" conditions predicted the stress amplitude below which no fatigue damage accumulated. A fatigue damage accumulation model which relates matrix fatigue cracking and the overall laminate properties is described. A model for the saturation damage stage development is presented, that identical laminates, tested in directions 90 deg apart (such that one layup has 90 deg outer plies and the other 0 deg), have different fatigue behaviors due to the stacking sequence. The 90 deg plies on the surface develop cracks earlier than predicted by shakedown. An attempt was made to explain this stacking sequence effect. Variable load history effects on the fatigue damage response were investigated. Tests reveal that for a given stress ratio the specimen seeks the saturation damage state for the largest stress range to which it is subjected. It was also found that little damage is generated by shifting a given stress range down, whereas significant damage may be created by shifting it upward. The laminate stresses were always tensile.

  19. Acute protease supplementation effects on muscle damage and recovery across consecutive days of cycle racing.

    PubMed

    Shing, Cecilia M; Chong, Suzzen; Driller, Matthew W; Fell, James W

    2016-01-01

    Bromelain, a mixture of proteases obtained from pineapples, has been demonstrated to reduce exercise-induced muscle damage and inflammation, enhancing recovery. This investigation aimed to establish if markers of muscle damage and testosterone were influenced by acute bromelain supplementation in competitive cyclists taking part in a six-day cycle stage race. Fifteen highly trained cyclists [age: 22, [Formula: see text] = 1.2 years, height: 1.79, [Formula: see text] = 0.01 m, body mass: 68.69, [Formula: see text] = 1.97 kg] were supplemented with either bromelain (1000 mg·day(-1)) (n = 8) or a placebo (n = 7) across six days of competitive racing in a randomised, double-blind, placebo-controlled trial. Blood was collected from each cyclist on days one, three and six of racing and analysed for creatine kinase (CK), myoglobin, lactate dehydrogenase (LDH) and testosterone. CK activity (P < 0.001, d = 17.4-18.8), LDH activity (P < 0.004, d = 0.5-2.5) and myoglobin concentration (P < 0.007, d = 3.4-4.8) were elevated from pre-race on days three and six of racing in both groups. Testosterone concentrations were significantly lower on the final day of racing (P = 0.03, d = 1.3) and there was a trend for bromelain to maintain testosterone concentrations across the race period (P = 0.05, d = 1.04-1.70) when compared to placebo. Fatigue rating was lower in the bromelain group on day four of racing (P = 0.01). Consecutive days of competitive cycling were associated with increased markers of muscle damage and a reduction in circulating testosterone across the race period. Bromelain supplementation reduced subjective feelings of fatigue and was associated with a trend to maintain testosterone concentration. PMID:25604346

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

    PubMed Central

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

    2013-01-01

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

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

    SciTech Connect

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

    2013-11-25

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

  2. Mechanisms controlling fatigue damage development in continuous fiber reinforced metal matrix composites

    NASA Technical Reports Server (NTRS)

    Johnson, W. S.

    1989-01-01

    Damage in continuous fiber reinforced metal matrix composite materials can be quite complex since there are a number of different constituents (fiber, matrix, and the fiber/matrix interface) that can fail. Multidirectional lay-ups have an even greater number of possible damage orientations and mechanisms. Based on the simplifying assumption of equivalent constituent strain states in the absence of damage, a strain based failure criteria may be applied to determine when and where initial damage will occur. Based on the relative strain to fatigue failure of the fiber and matrix, the possible damage mechanisms of an MMC can be grouped into three categories: (1) matrix dominated, (2) fiber dominated, and (3) self-similar damage growth. A fourth type of damage development, fiber/matrix interface failure, is dependent on the relative strength of the fiber/matrix interface and the matrix yield strength. These four types of damage are discussed and illustrated by examples.

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

    SciTech Connect

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

    1996-08-01

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

  4. Endothelial microparticles carrying hedgehog-interacting protein induce continuous endothelial damage in the pathogenesis of acute graft-versus-host disease.

    PubMed

    Nie, Di-Min; Wu, Qiu-Ling; Zheng, Peng; Chen, Ping; Zhang, Ran; Li, Bei-Bei; Fang, Jun; Xia, Ling-Hui; Hong, Mei

    2016-05-15

    Accumulating evidence suggests that endothelial microparticles (EMPs), a marker of endothelial damage, are elevated in acute graft-versus-host disease (aGVHD), and that endothelial damage is implicated in the pathogenesis of aGVHD, but the mechanisms remain elusive. In this study, we detected the plasma EMP levels and endothelial damage in patients and mice with aGVHD in vivo and then examined the effects of EMPs derived from injured endothelial cells (ECs) on endothelial damage and the role of hedgehog-interacting protein (HHIP) carried by EMPs in these effects in vitro. Our results showed that EMPs were persistently increased in the early posttransplantation phase in patients and mice with aGVHD. Meanwhile, endothelial damage was continuous in aGVHD mice, but was temporary in non-aGVHD mice after transplantation. In vitro, EMPs induced endothelial damage, including increased EC apoptosis, enhanced reactive oxygen species, decreased nitric oxide production and impaired angiogenic activity. Enhanced expression of HHIP, an antagonist for the Sonic hedgehog (SHH) signaling pathway, was observed in patients and mice with aGVHD and EMPs from injured ECs. The endothelial damage induced by EMPs was reversed when the HHIP incorporated into EMPs was silenced with an HHIP small interfering RNA or inhibited with the SHH pathway agonist, Smoothened agonist. This work supports a feasible vicious cycle in which EMPs generated during endothelial injury, in turn, aggravate endothelial damage by carrying HHIP into target ECs, contributing to the continuously deteriorating endothelial damage in the development of aGVHD. EMPs harboring HHIP would represent a potential therapeutic target for aGVHD. PMID:27009877

  5. Chemo-mechanics of salt damage in stone.

    PubMed

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

    2014-01-01

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

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

    SciTech Connect

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

    2002-05-01

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

  7. Immune mechanisms in acetaminophen-induced acute liver failure.

    PubMed

    Krenkel, Oliver; Mossanen, Jana C; Tacke, Frank

    2014-12-01

    An overdose of acetaminophen (N-acetyl-p-aminophenol, APAP), also termed paracetamol, can cause severe liver damage, ultimately leading to acute liver failure (ALF) with the need of liver transplantation. APAP is rapidly taken up from the intestine and metabolized in hepatocytes. A small fraction of the metabolized APAP forms cytotoxic mitochondrial protein adducts, leading to hepatocyte necrosis. The course of disease is not only critically influenced by dose of APAP and the initial hepatocyte damage, but also by the inflammatory response following acetaminophen-induced liver injury (AILI). As revealed by mouse models of AILI and corresponding translational studies in ALF patients, necrotic hepatocytes release danger-associated-molecular patterns (DAMPs), which are recognized by resident hepatic macrophages, Kupffer cell (KC), and neutrophils, leading to the activation of these cells. Activated hepatic macrophages release various proinflammatory cytokines, such as TNF-α or IL-1β, as well as chemokines (e.g., CCL2) thereby further enhancing inflammation and increasing the influx of immune cells, like bone-marrow derived monocytes and neutrophils. Monocytes are mainly recruited via their receptor CCR2 and aggravate inflammation. Infiltrating monocytes, however, can mature into monocyte-derived macrophages (MoMF), which are, in cooperation with neutrophils, also involved in the resolution of inflammation. Besides macrophages and neutrophils, distinct lymphocyte populations, especially γδ T cells, are also linked to the inflammatory response following an APAP overdose. Natural killer (NK), natural killer T (NKT) and T cells possibly further perpetuate inflammation in AILI. Understanding the complex interplay of immune cell subsets in experimental models and defining their functional involvement in disease progression is essential to identify novel therapeutic targets for human disease. PMID:25568858

  8. Fatigue Damage Mechanisms in Advanced Hybrid Titanium Composite Laminates

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  9. Damage mechanisms avoided or managed for NIF large optics

    DOE PAGESBeta

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

    2016-02-09

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

  10. Mechanical and microstructural changes in tungsten due to irradiation damage

    NASA Astrophysics Data System (ADS)

    Uytdenhouwen, I.; Schwarz-Selinger, T.; Coenen, J. W.; Wirtz, M.

    2016-02-01

    Stress-relieved pure tungsten received three damage levels (0.10, 0.25 and 0.50 dpa) by self-tungsten ion beam irradiation at room temperature. Positron annihilation spectroscopy showed the formation of mono-vacancies and vacancy clusters after ion beam exposure. In the first irradiation step (0-0.10 dpa) some splitting up of large vacancy clusters occurred which became more numerous. For increasing dose to 0.25 dpa, growth of the vacancy clusters was seen. At 0.50 dpa a change in the defect formation seems to occur leading to a saturation in the lifetime signal obtained from the positrons. Nano-indentation on the cross-sections showed a flat damage depth distribution profile. The nano-indentation hardness increased for increasing damage dose without any saturation up to 0.50 dpa. This means that other defects such as dislocation loops and large sized voids seem to contribute.

  11. Fatigue damage mechanisms in boron-aluminium composite laminates

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

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

  12. Quality control mechanisms in cellular and systemic DNA damage responses

    PubMed Central

    Ermolaeva, Maria A.; Dakhovnik, Alexander; Schumacher, Björn

    2016-01-01

    The maintenance of the genome is of pivotal importance for the functional integrity of cells and tissues. The gradual accumulation of DNA damage is thought to contribute to the functional decline of tissues and organs with ageing. Defects in multiple genome maintenance systems cause human disorders characterized by cancer susceptibility, developmental failure, and premature ageing. The complex pathological consequences of genome instability are insufficiently explained by cell-autonomous DNA damage responses (DDR) alone. Quality control pathways play an important role in DNA repair and cellular DDR pathways. Recent years have revealed non-cell autonomous effects of DNA damage that impact the physiological adaptations during ageing. We will discuss the role of quality assurance pathways in cell-autonomous and systemic responses to genome instability. PMID:25560147

  13. DNA damage in organs of mice treated acutely with patulin, a known mycotoxin.

    PubMed

    de Melo, Flávia Terezinha; de Oliveira, Iuri Marques; Greggio, Samuel; Dacosta, Jaderson Costa; Guecheva, Temenouga Nikolova; Saffi, Jenifer; Henriques, João Antonio Pêgas; Rosa, Renato Moreira

    2012-10-01

    Patulin, a known mycotoxin, is considered a significant contaminant in apples, apple-derived products and feeds. This study investigated the genotoxic effects of patulin in multiple organs (brain, kidney, liver and urinary bladder) of mice using an in vivo comet assay. We assessed the mechanism underlying this genotoxicity by measuring the GSH content and the thiobarbituric acid-reactive species (TBARS) level. Male CF-1 mice were given 1.0-3.75 mg/kg patulin intraperitoneally. The effect of patulin was dose-dependent and the highest patulin dose induced DNA strand breaks in the brain (damage index, DI, in hippocampus increased from 36.2 in control animals to 127.5), liver (44.3-138.4) and kidneys (31.5-99); decreased levels of GSH (hippocampus--from 46.9 to 18.4 nmol/mg protein); and an increase in lipid peroxidation (hippocampus--from 5.8 to 20.3 MDA equivalents/mg protein). This finding establishes an interrelationship between the pro-oxidant and genotoxic effects of patulin. Pre-treatment administration of N-acetyl-cysteine reduced patulin-induced DNA damage (hippocampus--DI from 127.5 to 39.8) and lipid peroxidation (hippocampus--20.3 to 12.8 MDA equivalents/mg protein) by restoring cellular GSH levels, reinforcing the positive relationship between patulin-induced GSH depletion and DNA damage caused by systemic administration of this mycotoxin. PMID:22222931

  14. 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.

  15. The genetics and mechanisms of T cell acute lymphoblastic leukaemia.

    PubMed

    Belver, Laura; Ferrando, Adolfo

    2016-07-25

    T cell acute lymphoblastic leukaemia (T-ALL) is an aggressive haematological malignancy derived from early T cell progenitors. In recent years genomic and transcriptomic studies have uncovered major oncogenic and tumour suppressor pathways involved in T-ALL transformation and identified distinct biological groups associated with prognosis. An increased understanding of T-ALL biology has already translated into new prognostic biomarkers and improved animal models of leukaemia and has opened opportunities for the development of targeted therapies for the treatment of this disease. In this Review we examine our current understanding of the molecular mechanisms of T-ALL and recent developments in the translation of these results to the clinic. PMID:27451956

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

    NASA Technical Reports Server (NTRS)

    Cherry, Robert S.; Papoutsakis, E. Terry

    1986-01-01

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

  17. Acute and chronic watercress supplementation attenuates exercise-induced peripheral mononuclear cell DNA damage and lipid peroxidation.

    PubMed

    Fogarty, Mark C; Hughes, Ciara M; Burke, George; Brown, John C; Davison, Gareth W

    2013-01-28

    Pharmacological antioxidant vitamins have previously been investigated for a prophylactic effect against exercise-induced oxidative stress. However, large doses are often required and may lead to a state of pro-oxidation and oxidative damage. Watercress contains an array of nutritional compounds such as β-carotene and α-tocopherol which may increase protection against exercise-induced oxidative stress. The present randomised controlled investigation was designed to test the hypothesis that acute (consumption 2 h before exercise) and chronic (8 weeks consumption) watercress supplementation can attenuate exercise-induced oxidative stress. A total of ten apparently healthy male subjects (age 23 (SD 4) years, stature 179 (SD 10) cm and body mass 74 (SD 15) kg) were recruited to complete the 8-week chronic watercress intervention period (and then 8 weeks of control, with no ingestion) of the experiment before crossing over in order to compete the single-dose acute phase (with control, no ingestion). Blood samples were taken at baseline (pre-supplementation), at rest (pre-exercise) and following exercise. Each subject completed an incremental exercise test to volitional exhaustion following chronic and acute watercress supplementation or control. The main findings show an exercise-induced increase in DNA damage and lipid peroxidation over both acute and chronic control supplementation phases (P< 0.05 v. supplementation), while acute and chronic watercress attenuated DNA damage and lipid peroxidation and decreased H₂O₂ accumulation following exhaustive exercise (P< 0.05 v. control). A marked increase in the main lipid-soluble antioxidants (α-tocopherol, γ-tocopherol and xanthophyll) was observed following watercress supplementation (P< 0.05 v. control) in both experimental phases. These findings suggest that short- and long-term watercress ingestion has potential antioxidant effects against exercise-induced DNA damage and lipid peroxidation. PMID:22475430

  18. Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Introduction: Cerebrovascular Acute Radiation Syndrome (CvARS) is an extremely severe in-jury of Central Nervous System (CNS) and Peripheral Nervous System (PNS). CvARS can be induced by the high doses of neutron, heavy ions, or gamma radiation. The Syndrome clinical picture depends on a type, timing, and the doses of radiation. Four grades of the CvARS were defined: mild, moderate, severe, and extremely severe. Also, four stages of CvARS were developed: prodromal, latent, manifest, outcome -death. Duration of stages depends on the types, doses, and time of radiation. The CvARS clinical symptoms are: respiratory distress, hypotension, cerebral edema, severe disorder of cerebral blood microcirculation, and acute motor weakness. The radiation toxins, Cerebro-Vascular Radiation Neurotoxins (SvARSn), determine development of the acute radiation syndrome. Mechanism of action of the toxins: Though pathogenesis of radiation injury of CNS remains unknown, our concept describes the Cv ARS as a result of Neurotoxicity and Excitotoxicity, cell death through apoptotic necrosis. Neurotoxicity occurs after the high doses radiation exposure, formation of radiation neuro-toxins, possible bioradicals, or group of specific enzymes. Intracerebral hemorrhage can be a consequence of the damage of endothelial cells caused by radiation and the radiation tox-ins. Disruption of blood-brain barrier (BBB)and blood-cerebrospinal fluid barrier (BCFB)is possibly the most significant effect of microcirculation disorder and metabolic insufficiency. NMDA-receptors excitotoxic injury mediated by cerebral ischemia and cerebral hypoxia. Dam-age of the pyramidal cells in layers 3 and 5 and Purkinje cell layer the cerebral cortex , damage of pyramidal cells in the hippocampus occur as a result of cerebral ischemia and intracerebral bleeding. Methods: Radiation Toxins of CV ARS are defined as glycoproteins with the molec-ular weight of RT toxins ranges from 200-250 kDa and with high enzymatic activity

  19. A damage mechanics based approach for developing a quantitative understanding of ductile fracture.

    SciTech Connect

    Thissell, W. R.; Tonks, D. L.; Schwartz, D. S.

    2004-01-01

    A self-consistent damage mechanics approach for describing ductile fracture is introduced. This approach consists of damage quantification of incipiently failed specimens resulting from well-controlled and diagnosed experiments that span a wide parameter space of stress triaxiality, strain rate, and equivalent plastic strain. Numerical simulations are performed of these experiments using damage constitutive models and the simulation predictions are compared with the experimental measurements and post-mortem damage quantification, with the goal of developing, validating, and calibrating the damage constitutive models. New developments are described, such as the coupling between void and deformation bands.

  20. γ-Oryzanol protects against acute cadmium-induced oxidative damage in mice testes.

    PubMed

    Spiazzi, Cristiano C; Manfredini, Vanusa; Barcellos da Silva, Fabiana E; Flores, Erico M M; Izaguirry, Aryele P; Vargas, Laura M; Soares, Melina B; Santos, Francielli W

    2013-05-01

    Cadmium is a non-essential heavy metal that is present at low levels mainly in food and water and also in cigar smoke. The present study evaluated the testicular damage caused by acute cadmium exposure and verified the protective role of γ-oryzanol (ORY). Mice were administrated with a single dose of 2.5mg/kg of CdCl2, and then treated with ORY (50mM in canola oil, 5mL/kg). Testes were removed after 24h and tested for lipid peroxidation (TBARS), protein carbonylation, DNA breakage, ascorbic acid, cadmium and non-proteic thiols contents, and for the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and δ-aminolevulic acid dehydratase (δ-ALA-D). Cadmium presented a significant alteration in all parameters, except GPx and CAT activities. Therapy reduced in a slight degree cadmium concentration in testes (around 23%). ORY restored SOD and GST activities as well as TBARS production to the control levels. Furthermore, ORY partially recovered δ-ALA-D activity inhibited by cadmium. This study provides the first evidence on the therapeutic properties of ORY in protecting against cadmium-induced testicular toxicity. PMID:23395783

  1. Application of damage mechanism-specific NDE methods in support of risk-informed inspections

    SciTech Connect

    Walker, S.M.; Ammirato, F.V.

    1996-12-01

    Risk-informed inservice inspection (RISI) programs effectively concentrate limited and costly examination resources on systems and locations most relevant to plant safety. The thought process used in the selection of nondestructive evaluation (NDE) methods and procedures in a RISI program is expected to change toward integrating NDE into integrity management, with a concentration on understanding failure mechanisms. Identifying which damage mechanisms may be operative in specific locations and applying appropriate NDE methods to detect the presence of these damage mechanisms is fundamental to effective RISI application. Considerable information is already available on inspection for damage mechanisms such as intergranular stress corrosion cracking (IGSCC), thermal fatigue, and erosion-corrosion. Similar procedures are under development for other damage mechanisms that may occur individually or in combination with other mechanisms. Guidance is provided on application of NDE procedures in an RISI framework to facilitate implementation by utility staff (Gosselin, 1996).

  2. Barium cardiotoxicity: Relationship between ultrastructural damage and mechanical effects.

    PubMed

    Delfino, G; Amerini, S; Mugelli, A

    1988-01-01

    The ultrastructural damage in guinea-pig ventricular strips caused by barium was analysed. At a concentration of 1 mmol/litre, barium chloride caused a dramatic increase in the developed tension associated with the onset of automaticity. The ultrastructural analysis demonstrated that barium caused notable and consistent alterations which affected most myocyte components. Various degenerative aspects were observed in mitochondria and in the contractile apparatus. Glycogen deposits were completely depleted. Preparations driven at 4 Hz (i.e. the rate of spontaneous firing of barium-treated preparations) showed moderate ultrastructural alterations, thus demonstrating that the increase in the rate of beating is not the only determinant of the observed damage. These results suggest that the myocardial toxicity of barium is due not only to the well-known modifications in membrane permeability, but possibly also to alterations in cell function. PMID:20702358

  3. Mechanical loading up-regulates early remodeling signals from osteocytes subjected to physical damage.

    PubMed

    Liu, Chao; Zhang, Xiaoqing; Wu, Michael; You, Lidan

    2015-12-16

    In the mineralized bone matrix, mechanical loading causes micrometer-sized cracks. These cracks trigger targeted remodeling along the micro-crack. Physical damage to osteocytes was shown to be involved in the initiation of this remodeling process. However, the role of subsequent mechanical loading osteocyte response to physical damage is unclear. In this study, we have designed and developed an in vitro cell model to study the impact of mechanical loading on osteocytes with physical damage. Specifically, a system was developed to create sub-cellular physical damage on MLO-Y4 osteocytes in vitro. This model re-created the spatial distribution of non-viable cells and VEGF expression around microdamage as reported in vivo. Using this system, the short term (24h) effects of fluid shear stress in regulation of osteocyte response to physical damage were investigated. We have observed that the mechanical stimuli had an additive effect in terms of COX-2, VEGF mRNA expressions, as well as PGE2, VEGF concentrations in the media. Interestingly, other inflammatory signals such as IL-6 and TNF-α did not change with these stimuli, at this time point. Moreover, fluid shear also had a modulating effect in regulation of osteoclast differentiation by osteocyte with physical damage. These results show that (1) subcellular physical damage upregulates remodeling signals in osteocytes at early time point, (2) mechanical loading substantially upregulates these signals for remodeling in osteocytes with physical damage. PMID:26596719

  4. Identification and Elimination of Mechanisms Leading to UV Damage of DKDP

    SciTech Connect

    Burnham, A; Runkel, M; Chase, L; Demos, S; Staggs, M; Siekhaus, W

    2001-03-06

    This LDRD project addressed both bulk and surface damage induced by UV-laser exposure. The primary objectives were (1) to complete our understanding of the factors leading to bulk damage, including growth conditions and orientational direction, and (2) to identify mechanisms of surface damage initiation and growth leading to mitigation methods. Due to the more advanced state of knowledge in bulk damage, a greater portion of that work was completed during the one-year term of this project. Three papers were presented at the 32nd Boulder Damage Symposium on Laser-Induced Damage in Optical Materials, and the three resulting manuscripts submitted to the Proceeding are attached: An important result from this work is that it established a dependence of obscuration from bulk damage on fluence and pulse length, which is shown.

  5. Immune Mechanisms and Novel Pharmacological Therapies of Acute Kidney Injury

    PubMed Central

    Bajwa, Amandeep; Kinsey, Gilbert R.; Okusa, Mark D.

    2010-01-01

    Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and both innate and adaptive immunity contribute to the pathogenesis. Kidney resident cells promote inflammation after IRI by increasing endothelial cell adhesion molecule expression and vascular permeability. Kidney epithelial cells bind complement and express tolllike receptors and resident and infiltrating cells produce cytokines/chemokines. Early activation of kidney dendritic cells (DCs) initiates a cascade of events leading to accumulation of interferon-γ-producing neutrophils, infiltrating macrophages, CD4+ T cells, B cells and invariant natural killer T (NKT) cells. Recent studies from our laboratory now implicate the IL23/IL17 pathway in kidney IRI. Following the initial early phase of inflammation, the late phase involves infiltration of anti-inflammatory cells including regulatory T cells, alternatively activated macrophages and stem cells leading to attenuation of inflammation and initiation of repair. Based upon these immune mechanisms of injury, recent studies hold promise for novel drug therapies. These pharmacological agents have been shown to reduce inflammation or cytotoxicity in rodent models of AKI and some show early promise in clinical trials. This review summarizes recent advances to further our understanding of the immune mechanisms of AKI and potential pharmacological therapies. PMID:19715538

  6. Understanding the Acute Skin Injury Mechanism Caused by Player-Surface Contact During Soccer

    PubMed Central

    van den Eijnde, Wilbert A.J.; Peppelman, Malou; Lamers, Edwin A.D.; van de Kerkhof, Peter C.M.; van Erp, Piet E.J.

    2014-01-01

    Background: Superficial skin injuries are considered minor, and their incidence is probably underestimated. Insight into the incidence and mechanism of acute skin injury can be helpful in developing suitable preventive measures and safer playing surfaces for soccer and other field sports. Purpose: To gain insight into the incidence and severity of skin injuries related to soccer and to describe the skin injury mechanism due to player-surface contact. Study Design: Systematic review; Level of evidence, 4. Methods: The prevention model by van Mechelen et al (1992) combined with the injury causation model of Bahr and Krosshaug (2005) were used as a framework for the survey to describe the skin injury incidence and mechanism caused by player-surface contact. Results: The reviewed literature showed that common injury reporting methods are mainly based on time lost from participation or the need for medical attention. Because skin abrasions seldom lead to absence or medical attention, they are often not reported. When reported, the incidence of abrasion/laceration injuries varies from 0.8 to 6.1 injuries per 1000 player-hours. Wound assessment techniques such as the Skin Damage Area and Severity Index can be a valuable tool to obtain a more accurate estimation of the incidence and severity of acute skin injuries. Conclusion: The use of protective equipment, a skin lubricant, or wet surface conditions has a positive effect on preventing abrasion-type injuries from artificial turf surfaces. The literature also shows that essential biomechanical information of the sliding event is lacking, such as how energy is transferred to the area of contact. From a clinical and histological perspective, there are strong indications that a sliding-induced skin lesion is caused by mechanical rather than thermal injury to the skin. PMID:26535330

  7. Hepatoprotective Effect of Otostegia persica Boiss. Shoot Extract on Carbon Tetrachloride-Induced Acute Liver Damage in Rats

    PubMed Central

    Nasiri Bezenjani, Sedighe; Pouraboli, Iran; Malekpour Afshar, Reza; Mohammadi, Gholamabbas

    2012-01-01

    In this study, the hepatoprotective effect of the methanol extract of aerial parts (shoot) from Otostegia persica Boiss (Golder) was investigated against the carbon tetrachloride (CCl4)-induced acute hepatotoxicity in male rats. Liver damage was induced through the oral administration of 50% CCl4 in liquid paraffin (2.5 mL/Kg bw, per os) 60 min after the administration of the methanol extract of O. persica shoot (in 200, 300, 400 mg/Kg bw doses) and assessed using biochemical parameters (plasma and liver tissue malondialdehyde (MDA), transaminase enzyme levels in plasma [aspartate transaminase (AST), alanine aminotransferase (ALT)] and liver glutathione (GSH) levels). Results show that the methanol extract of O. persica shoot is active at 300 mg/Kg (per os) and it possess remarkable antioxidant and hepatoprotective activities. Additionally, histopathological studies verified the effectiveness of this dose of extract in acute liver damage prevention. PMID:24250558

  8. 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.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2012-07-26

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

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

    NASA Astrophysics Data System (ADS)

    Williams, Kevin Vaughan

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

  12. The influence of acute or chronic nicotine treatment on ethanol-induced gastric mucosal damage in rats.

    PubMed

    Cho, C H; Chen, B W; Hui, W M; Lam, S K

    1990-01-01

    The influences of acute or chronic nicotine pretreatment on ethanol-induced changes on gastric secretion, mucosal blood flow (GMBF), and glandular mucosal damage were studied in anesthetized rats. Ethanol administration decreased gastric acid secretion and GMBF, which were accompanied by a marked increase in gastric mucosal damage. Acute nicotine incubation 2 or 4 mg dose-dependently elevated both the titratable acid in the luminal solution and the gastric secretory volume; it also prevented the depressive action on GMBF and gastric mucosal damage in ethanol-treated animals. Chronic nicotine treatment for 10 days reduced the inhibitory action of ethanol on gastric acid secretion; the higher dose (25 micrograms/ml drinking water) potentiated the decrease of GMBF and the ulcerogenic property of ethanol. However, chronic treatment with the lower dose (5 micrograms/ml drinking water) had the opposite effects; it also markedly increased the gastric secretory volume. It is concluded that acute nicotine pretreatment elevates, whereas chronic nicotine pretreatment differentially affects GMBF. These effects could account for their protective or preventive actions on ethanol ulceration. The increase in nonacid gastric secretory volume by nicotine could partially explain its antiulcer effect. Furthermore, the acid secretory state of the stomach appears unrelated to the ulcerogenic property of ethanol. PMID:2295286

  13. The effects of acute alcohol consumption and eccentric muscle damage on neuromuscular function.

    PubMed

    Barnes, Matthew J; Mündel, Toby; Stannard, Stephen R

    2012-02-01

    Voluntary and electrically stimulated muscular performance was examined to identify the effects of acute alcohol consumption on neuromuscular function in the presence and absence of exercise-induced muscle damage (EIMD). After initial neuromuscular performance measures were made, 12 subjects completed a bout of eccentric exercise (EX) using the quadriceps muscles of 1 leg while the remaining 11 subjects did not exercise (NX). Subjects then consumed either an alcoholic beverage containing 1 g·kg(-1) body weight (ALC) or a nonalcoholic beverage (OJ). On another occasion the contralateral leg of both groups was tested and those in the EX group performed an equivalent bout of eccentric exercise after which the other beverage was consumed. Measurements of neuromuscular function were made pre-exercise and 36 and 60 h post-beverage consumption. Creatine kinase (CK) was measured pre-exercise and at 12, 36, and 60 h. Significantly greater (p < 0.01) decrements in maximal voluntary isometric contraction were observed with EX ALC at 36 and 60 h compared with EX OJ, and no change was seen in the NX group. Significant decreases in voluntary activation were observed at 36 h (p = 0.003) and 60 h (p = 0.01) with EX ALC only. Elevations in CK were observed at all posteccentric exercise time points (all p < 0.05) under both EX OJ and ALC. No change in electromyography or low-frequency fatigue was observed under either treatment in either group. These results suggest that decreased neural drive appears to contribute to alcohol's effect on the magnitude of EIMD-related decrements in voluntary force generation. PMID:22185621

  14. Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats.

    PubMed

    Lee, I-C; Baek, H-S; Kim, S-H; Moon, C; Park, S-H; Kim, S-H; Shin, I-S; Park, S-C; Kim, J-C

    2015-03-01

    This study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic (Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-α and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities. PMID:24972622

  15. Acute Lonomia obliqua caterpillar envenomation-induced physiopathological alterations in rats: evidence of new toxic venom activities and the efficacy of serum therapy to counteract systemic tissue damage.

    PubMed

    Berger, Markus; Beys-da-Silva, Walter Orlando; Santi, Lucélia; de Oliveira, Iuri Marques; Jorge, Patrícia Mendes; Henriques, João Antônio Pêgas; Driemeier, David; Vieira, Maria Aparecida Ribeiro; Guimarães, Jorge Almeida

    2013-11-01

    The clinical manifestations of Lonomia obliqua caterpillar envenomation are systemic hemorrhage and acute kidney injury. In an effort to better understand the physiopathological mechanisms of envenomation, a rat model was established to study systemic tissue damage during L. obliqua envenomation. An array of acute venom effects was characterized, including biochemical, hematological, histopathological, myotoxic and genotoxic alterations. Rapid increases in serum alanine and aspartate transaminases, γ-glutamyl transferase, lactate dehydrogenase, hemoglobin, bilirubin, creatinine, urea and uric acid were observed, indicating that intravascular hemolysis and liver and kidney damage had occurred. Treatment with a specific antivenom (antilonomic serum) for up to 2 h post-venom injection neutralized the biochemical alterations. However, treatment after 6 h post-venom injection failed to normalize all biochemical parameters, despite its efficacy in reversing coagulation dysfunction. The hematological findings were consistent with hemolytic anemia and neutrophilic leukocytosis. The histopathological alterations were mainly related to hemorrhage and inflammation in the subcutaneous tissue, lung, heart and kidneys. Signs of congestion and hemosiderosis were evident in the spleen, and hemoglobin and/or myoglobin casts were also detected in the renal tubules. Increased levels of creatine kinase and creatine kinase-MB were correlated with the myocardial necrosis observed in vivo and confirmed the myotoxicity detected in vitro in isolated extensor digitorum longus muscles. Significant DNA damage was observed in the kidneys, heart, lung, liver and lymphocytes. The majority of the DNA lesions in the kidney were due to oxidative damage. The results presented here will aid in understanding the pathology underlying Lonomia's envenomation. PMID:23994591

  16. Monosodium glutamate-induced oxidative kidney damage and possible mechanisms: a mini-review.

    PubMed

    Sharma, Amod

    2015-01-01

    Animal studies suggest that chronic monosodium glutamate (MSG) intake induces kidney damage by oxidative stress. However, the underlying mechanisms are still unclear, despite the growing evidence and consensus that α-ketoglutarate dehydrogenase, glutamate receptors and cystine-glutamate antiporter play an important role in up-regulation of oxidative stress in MSG-induced renal toxicity. This review summaries evidence from studies into MSG-induced renal oxidative damage, possible mechanisms and their importance from a toxicological viewpoint. PMID:26493866

  17. Mechanisms of interleukin-22's beneficial effects in acute pancreatitis.

    PubMed

    Huan, Chongmin; Kim, Daniel; Ou, Peiqi; Alfonso, Antonio; Stanek, Albert

    2016-02-15

    Acute pancreatitis (AP) is a disorder characterized by parenchymal injury of the pancreas controlled by immune cell-mediated inflammation. AP remains a significant challenge in the clinic due to a lack of specific and effective treatment. Knowledge of the complex mechanisms that regulate the inflammatory response in AP is needed for the development of new approaches to treatment, since immune cell-derived inflammatory cytokines have been recognized to play critical roles in the pathogenesis of the disease. Recent studies have shown that interleukin (IL)-22, a cytokine secreted by leukocytes, when applied in the severe animal models of AP, protects against the inflammation-mediated acinar injury. In contrast, in a mild AP model, endogenous IL-22 has been found to be a predominantly anti-inflammatory mediator that inhibits inflammatory cell infiltration via the induction of Reg3 proteins in acinar cells, but does not protect against acinar injury in the early stage of AP. However, constitutively over-expressed IL-22 can prevent the initial acinar injury caused by excessive autophagy through the induction of the anti-autophagic proteins Bcl-2 and Bcl-XL. Thus IL-22 plays different roles in AP depending on the severity of the AP model. This review focuses on these recently reported findings for the purpose of better understanding IL-22's regulatory roles in AP which could help to develop a novel therapeutic strategy. PMID:26909233

  18. Pathogenic mechanism of acute post-streptococcal glomerulonephritis.

    PubMed

    Nordstrand, A; Norgren, M; Holm, S E

    1999-01-01

    Considerable knowledge has been accumulated regarding the characteristics of acute post-streptococcal glomerulonephritis (APSGN), and many attempts have been made to identify a streptococcal factor or factors responsible for triggering this disease. However, the pathogenic mechanism behind APSGN remains largely unknown. As glomerular deposition of C3 is generally demonstrated before that of IgG in the disease process, it is likely that the inflammatory response is initiated by renal deposition of a streptococcal product, rather than by deposition of antibodies or pre-formed immune complexes. During recent years, a number of streptococcal products have been suggested to be involved in the pathogenic process. In this review, possible roles of these factors are discussed in the context of the clinical and renal findings most often demonstrated in patients with APSGN. Streptokinase was observed to be required in order to induce signs of APSGN in mice, and a number of findings suggest that the initiation of the disease may occur as a result of renal binding by certain nephritis-associated variants of this protein. However, additional factors may be required for the development of the disease. PMID:10680980

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

    PubMed

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

    2008-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

  1. DNA damage by reactive species: Mechanisms, mutation and repair.

    PubMed

    Jena, N R

    2012-07-01

    DNA is continuously attacked by reactive species that can affect its structure and function severely. Structural modifications to DNA mainly arise from modifications in its bases that primarily occur due to their exposure to different reactive species. Apart from this, DNA strand break, inter- and intra-strand crosslinks and DNA-protein crosslinks can also affect the structure of DNA significantly. These structural modifications are involved in mutation, cancer and many other diseases. As it has the least oxidation potential among all the DNA bases, guanine is frequently attacked by reactive species, producing a plethora of lethal lesions. Fortunately, living cells are evolved with intelligent enzymes that continuously protect DNA from such damages. This review provides an overview of different guanine lesions formed due to reactions of guanine with different reactive species. Involvement of these lesions in inter- and intra-strand crosslinks, DNA-protein crosslinks and mutagenesis are discussed. How certain enzymes recognize and repair different guanine lesions in DNA are also presented. PMID:22750987

  2. Site damage from mechanized thinning in southeast Alaska

    SciTech Connect

    Sidle, R.C.; Laurent, T.H.

    1986-01-01

    Soil disturbance and damage to remaining trees were studied in a 0.724 acre, 45 year old second growth western hemlock/Sitka spruce stand on Prince of Wales Island, Alaska, thinned with a Menzi-Muck walking backhoe equipped with hydraulic shears for use as a feller-buncher. The stand was thinned to b.a. 111 square ft/acre and 205 stems/acre. Almost half the roads, which occupied 30% of the total thinned area, received some soil disturbance, though the disturbance was largely within the organic horizon and mineral soil was exposed on only 1.8% of the roaded area. Slight and heavy soil compaction occurred on 23 and 2% of the roads, respectively. Based on the entire thinning unit, 85% of the site was undisturbed and only 0.5% had exposed mineral soil, while 7% was slightly compacted and 0.5% was heavily compacted. Approximately 90% of the remaining trees had some stem or root abrasion. Split or severed roots occurred on 10% of the trees. Only 5% of stem and root scars were greater than 1 square foot, and these were all superficial. 17 references.

  3. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

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

    NASA Technical Reports Server (NTRS)

    Schwottke, G. H.

    1982-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

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

    SciTech Connect

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

    2013-11-15

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

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

    PubMed

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

    2016-03-15

    Damage precursors in the 3ω (351 nm) mirror for a high-power laser system are investigated as well as the relevant damage mechanisms. The precursors are classified into two ensembles according to the different laser resistance and damage features. The former is nano-absorbing precursors, which are sensitive to the standing wave electric field and vulnerable to the laser irradiation. The latter is submicrometer nodular defects, which have higher laser resistance and are sensitive to the adhesion strength between the fluoride coatings and oxide coatings. The damage due to nano-absorbing precursors is efficiently suppressed with the double stack design that screens the electric field in the oxides. Currently, the nodular seed is major originating from the Al2O3/SiO2 stack. Even for the same defect type and mirror, the final damage features are dependent on the local mechanical properties at the irradiation location. The investigations of the damage mechanisms provide a direction to further improve the laser-induced damage threshold of the 3ω mirror. PMID:26977671

  9. Acute and chronic complications of laser angioplasty: vascular wall damage and formation of aneurysms in the atherosclerotic rabbit.

    PubMed

    Lee, G; Ikeda, R M; Theis, J H; Chan, M C; Stobbe, D; Ogata, C; Kumagai, A; Mason, D T

    1984-01-15

    Acute and chronic vascular responses to laser exposure in atherosclerotic rabbits were studied. In 7 rabbits fed an atherogenic diet for 3 to 5 months before the study to induce aortic atherosclerosis, a flexible quartz fiber, 400 micron core diameter, attached to an argon ion laser was passed anterogradely or retrogradely to the atherosclerotic ascending aorta. The laser was turned on using power intensities of 1 to 2 W for 3 seconds. After laser treatment, the aortas were studied acutely in 3 rabbits and chronically in 4 rabbits after recovery for 1 to 14 days. In 2 rabbits studied acutely, the argon laser produced a vaporized crater within the atherosclerotic plaque at the endothelial surface; however, in 1 there was also vascular damage extending deep into the medial layer. In addition, aortic aneurysm with muscular wall damage occurred in 2 of the 4 animals studied chronically. Thus, vascular complications may arise when catheter laser angioplasty is randomly applied without visualizing specific plaque targets or without using safe dose increments of power intensities and durations of exposure. This study suggests caution in the clinical use of intensive phototherapy to cardiovascular lesions and stresses the need for further understanding of laser vascular consequences before application of laser angioplasty in patients. PMID:6695725

  10. The acute cardiorenal syndrome: burden and mechanisms of disease.

    PubMed

    Nijst, Petra; Mullens, Wilfried

    2014-12-01

    Worsening renal function during the treatment of acute decompensated heart failure, so-called acute cardio-renal syndrome, is very common and complicates the treatment course. The underlying pathophysiology of worsening renal function (WRF) involves variable contributions of renal hemodynamics, neurohormonal activity, and oxidative stress. Historically, WRF has been associated with adverse outcomes. However, emerging data support therapeutic strategies that permit WRF while effectively treating congestion as they are associated with improved outcomes. PMID:25135470

  11. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

  12. Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system.

    PubMed

    Aaron, Sanjith; Shyamkumar, N K; Alexander, Sunithi; Babu, P Suresh; Prabhakar, A T; Moses, Vinu; Murthy, T V; Alexander, Mathew

    2016-01-01

    Even though intravenous thrombolysis with tissue plasminogen activator (IV tPA) is the standard of care in acute ischemic stroke, its use in pregnancy is not clearly defined. Mechanical thrombectomy devices can be an option; however, literature on the use of such mechanical devices in stroke in pregnancy is lacking. Here we describe two cases that developed acute embolic stroke during pregnancy who were successfully treated by mechanical clot retrieval using the Penumbra system 28 (Penumbra Inc., Alameda, California, USA). To the best of our knowledge, these are the only case reports on the use of the Penumbra device in pregnant patients with acute ischemic stroke. PMID:27293343

  13. Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system

    PubMed Central

    Aaron, Sanjith; Shyamkumar, N. K.; Alexander, Sunithi; Babu, P. Suresh; Prabhakar, A. T.; Moses, Vinu; Murthy, T. V.; Alexander, Mathew

    2016-01-01

    Even though intravenous thrombolysis with tissue plasminogen activator (IV tPA) is the standard of care in acute ischemic stroke, its use in pregnancy is not clearly defined. Mechanical thrombectomy devices can be an option; however, literature on the use of such mechanical devices in stroke in pregnancy is lacking. Here we describe two cases that developed acute embolic stroke during pregnancy who were successfully treated by mechanical clot retrieval using the Penumbra system 28 (Penumbra Inc., Alameda, California, USA). To the best of our knowledge, these are the only case reports on the use of the Penumbra device in pregnant patients with acute ischemic stroke. PMID:27293343

  14. NRF2 promotes neuronal survival in neurodegeneration and acute nerve damage

    PubMed Central

    Xiong, Wenjun; MacColl Garfinkel, Alexandra E.; Li, Yiqing; Benowitz, Larry I.; Cepko, Constance L.

    2015-01-01

    Oxidative stress contributes to the loss of neurons in many disease conditions as well as during normal aging; however, small-molecule agents that reduce oxidation have not been successful in preventing neurodegeneration. Moreover, even if an efficacious systemic reduction of reactive oxygen and/or nitrogen species (ROS/NOS) could be achieved, detrimental side effects are likely, as these molecules regulate normal physiological processes. A more effective and targeted approach might be to augment the endogenous antioxidant defense mechanism only in the cells that suffer from oxidation. Here, we created several adeno-associated virus (AAV) vectors to deliver genes that combat oxidation. These vectors encode the transcription factors NRF2 and/or PGC1a, which regulate hundreds of genes that combat oxidation and other forms of stress, or enzymes such as superoxide dismutase 2 (SOD2) and catalase, which directly detoxify ROS. We tested the effectiveness of this approach in 3 models of photoreceptor degeneration and in a nerve crush model. AAV-mediated delivery of NRF2 was more effective than SOD2 and catalase, while expression of PGC1a accelerated photoreceptor death. Since the NRF2-mediated neuroprotective effects extended to photoreceptors and retinal ganglion cells, which are 2 very different types of neurons, these results suggest that this targeted approach may be broadly applicable to many diseases in which cells suffer from oxidative damage. PMID:25798616

  15. In Vitro Comparative Assessment of Mechanical Blood Damage Induced by Different Hemodialysis Treatments.

    PubMed

    Sakota, Ranko; Lodi, Carlo Alberto; Sconziano, Sara Antonia; Beck, Werner; Bosch, Juan P

    2015-12-01

    Gradual deterioration of red blood cells (RBCs) due to mechanical stress (chronic hemolysis) is unavoidable during treatments that involve extracorporeal blood circulation, such as hemodialysis (HD). This effect is generally undetectable and does not generate any acute symptoms, but it leads to an increase in plasma free hemoglobin (fHb). There are no absolute safety levels for fHb increase, indicating the need for an empirical evaluation using comparative testing. The increase in fHb levels was investigated in vitro by applying double-needle double-pump HD (HD-DNDP), a new modality in which arterial and venous pumps both run continuously. fHb was measured during typical and worst-case simulated dialysis treatments (double-needle single-pump HD [HD-DNSP], hemodiafiltration [HDF-DN], single-needle double-pump HD [HD-SNDP], and HD-DNDP) performed in vitro using bovine blood for 4 h. Hemolysis-related indices (fHb%; index of hemolysis, IH; and normalized IH) were calculated and used for comparison. The increase in fHb during either HDF-DN or HD-SNDP with Artis and AK200 dialysis machines was similar, while the fHb at the maximum real blood flow rate (Qbreal ) at the completion of the HD-DNDP treatment on Artis was higher than that for HD-DNSP using a Phoenix dialysis machine (fHb% = 1.24 ± 0.13 and 0.92 ± 0.12 for the Artis machine with HD-DNDP at Qbreal  = 450 mL/min and Phoenix with HD-DNSP at Qbreal  = 500 mL/min, respectively). However, the fHb levels increased linearly, and no steep changes were observed. The increases observed during HD-DNDP were the same order of magnitude as those for widely used bloodlines and treatment modes for delivering dialysis treatments. The observed results matched literature findings, and thus the measured fHb trends are not predicted to have clinical side effects. HD-DNDP treatment with Artis does not merit any additional concern regarding mechanical stress to RBCs compared with that observed for

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

    SciTech Connect

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

    1998-11-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  20. Bone marrow mesenchymal stem cell implantation for the treatment of radioactivity‑induced acute skin damage in rats.

    PubMed

    Zheng, Kai; Wu, Weizhen; Yang, Shunliang; Huang, Lianghu; Chen, Jin; Gong, Chungui; Fu, Zhichao; Zhang, Linlin; Tan, Jianming

    2015-11-01

    The present study aimed to observe the role of mesenchymal stem cells (MSCs) in the repair of acute skin damage caused by radiation. Rat bone marrow MSCs (BMSCs) were isolated and cultured in vitro. A rat model of radiation‑induced acute skin damage was established by irradiation of the hind legs of Sprague-Dawley rats using a linear accelerator (45 Gy). After irradiation, rats were randomly divided into two groups: BMSC group and control group. Rats in the BMSC group were treated with a tail vein injection of 2x106 BMSCs (1 ml) immediately after irradiation and a local multipoint injection of 2x106 BMSCs at the injured area two weeks later. Then the wound healing of each rat was observed. The expression of transforming growth factor (TGF)‑β1, stromal cell‑derived factor-1 (SDF‑1) and prostaglandin E2 (PGE2) in the wounded tissues was determined by immunohistochemistry. The results demonstrated that skin damage was milder in the BMSC group than in the control group. Moreover, the speed of healing in the BMSC group was better than that in the control group. In addition, the wound score, it was significantly lower in the BMSC group than in the control group (P<0.05). The expression of PGE2 and TGF‑β1 in the BMSC group was also significantly lower than that in the control group (P<0.05), whereas the SDF‑1 expression was significantly higher in the BMSC group than that in the control group (P<0.05). BMSCs can effectively reduce inflammation and fibrosis in the wounded skin and promote the repair of acute radioactive skin injury. Thus, may be developed as a novel treatment for wound healing. PMID:26323987

  1. Effects of glycerol on human skin damaged by acute sodium lauryl sulphate treatment.

    PubMed

    Atrux-Tallau, Nicolas; Romagny, Céline; Padois, Karine; Denis, Alain; Haftek, Marek; Falson, Françoise; Pirot, Fabrice; Maibach, Howard I

    2010-08-01

    Glycerol, widely used as humectant, is known to protect against irritants and to accelerate recovery of irritated skin. However, most studies were done with topical formulations (i.e. emulsions) containing glycerol in relatively high amounts, preventing drawing conclusions from direct effects. In this study, acute chemical irritations were performed on the forearm with application of a 10% sodium lauryl sulphate (SLS) aqueous solution under occlusion for 3 h. Then, glycerol aqueous solutions from 1 to 10% were applied under occlusion for 3 h. After elimination of moist excess consecutive to occlusive condition, in ambient air for 15 and 30 min, skin barrier function was investigated by dual measurement of skin hydration and transepidermal water loss (TEWL). Treatments with SLS solution under occlusion significantly increased TEWL and decreased skin hydration as assessed by capacitance measurements. The SLS irritant property was raised by the occlusion and the water barrier function as well as water content appeared impaired. Recovery with glycerol at low doses was remarkable through a mechanism that implies its hygroscopic properties and which is saturable. This precocious effect acts through skin rehydration by enhancing water-holding capacity of stratum corneum that would facilitate the late physiological repair of impaired skin barrier. Thus, glycerol appears to substitute for natural moisturizing factors that have been washed out by the detergent action of SLS, enhancing skin hydration but without restoring skin barrier function as depicted by TEWL values that remained high. Thus, irritant contact dermatitis treated with glycerol application compensate for skin dehydration, favouring physiological process to restore water barrier function of the impaired skin. Empirical use of glycerol added topical formulations onto detergent altered skin was substantiated in the present physicochemical approach. PMID:20043170

  2. Forming Prediction of Magnesium Alloy Sheets using a Continuum Damage Mechanics Multistep Inverse Approach

    SciTech Connect

    Bapanapalli, Satish K.; Nguyen, Ba Nghiep

    2008-06-30

    This paper applies multistep inverse approach using a new method to generate the intermediate configurations to analyze the press forming of magnesium alloys. The developed approach considers a final configuration to be formed from a flat blank sheet. It accounts for a series of intermediate configurations that are estimated based on the initial and final configurations as well as tooling conditions using optimization techniques. The approach is based on the concept of minimization of the surface area of the sheet metal subject to the constraints that the punch and die surfaces are not penetrated. Due to the limited formability of magnesium alloys, it is important to realistically estimate the intermediate configurations so that a damage mechanics approach can be explored to predict damage accumulations that can cause rupture of the sheet during forming. Elastic-plastic constitutive laws are used with the modified Hill’s criterion and deformation theory of plasticity to describe the behavior of AZ31 magnesium alloys. Damage is captured by a damage variable that governs the equivalent stress. A damage-plasticity coupled approach is employed for the integration of the constitutive equations. The computed strain increment from two consecutive intermediate configurations is used to predict the resulting damage accumulations during forming. The continuum damage mechanics multistep inverse approach is applied to predict forming of AZ31 magnesium alloys.

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

    PubMed

    Ma, Songyun; Scheider, Ingo; Bargmann, Swantje

    2016-09-01

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

  4. Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury

    PubMed Central

    2010-01-01

    Introduction Recruitment maneuvers (RMs) seem to be more effective in extrapulmonary acute lung injury (ALI), caused mainly by sepsis, than in pulmonary ALI. Nevertheless, the maintenance of adequate volemic status is particularly challenging in sepsis. Since the interaction between volemic status and RMs is not well established, we investigated the effects of RMs on lung and distal organs in the presence of hypovolemia, normovolemia, and hypervolemia in a model of extrapulmonary lung injury induced by sepsis. Methods ALI was induced by cecal ligation and puncture surgery in 66 Wistar rats. After 48 h, animals were anesthetized, mechanically ventilated and randomly assigned to 3 volemic status (n = 22/group): 1) hypovolemia induced by blood drainage at mean arterial pressure (MAP)≈70 mmHg; 2) normovolemia (MAP≈100 mmHg), and 3) hypervolemia with colloid administration to achieve a MAP≈130 mmHg. In each group, animals were further randomized to be recruited (CPAP = 40 cm H2O for 40 s) or not (NR) (n = 11/group), followed by 1 h of protective mechanical ventilation. Echocardiography, arterial blood gases, static lung elastance (Est,L), histology (light and electron microscopy), lung wet-to-dry (W/D) ratio, interleukin (IL)-6, IL-1β, caspase-3, type III procollagen (PCIII), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) mRNA expressions in lung tissue, as well as lung and distal organ epithelial cell apoptosis were analyzed. Results We observed that: 1) hypervolemia increased lung W/D ratio with impairment of oxygenation and Est,L, and was associated with alveolar and endothelial cell damage and increased IL-6, VCAM-1, and ICAM-1 mRNA expressions; and 2) RM reduced alveolar collapse independent of volemic status. In hypervolemic animals, RM improved oxygenation above the levels observed with the use of positive-end expiratory pressure (PEEP), but increased lung injury and led to higher inflammatory and fibrogenetic

  5. Mechanisms of damage to corals exposed to sedimentation.

    PubMed

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

    2012-06-12

    We investigated the mechanisms leading to rapid death of corals when exposed to runoff and resuspended sediments, postulating that the killing was microbially mediated. Microsensor measurements were conducted in mesocosm experiments and in naturally accumulated sediment on corals. In organic-rich, but not in organic-poor sediment, pH and oxygen started to decrease as soon as the sediment accumulated on the coral. Organic-rich sediments caused tissue degradation within 1 d, whereas organic-poor sediments had no effect after 6 d. In the harmful organic-rich sediment, hydrogen sulfide concentrations were low initially but increased progressively because of the degradation of coral mucus and dead tissue. Dark incubations of corals showed that separate exposures to darkness, anoxia, and low pH did not cause mortality within 4 d. However, the combination of anoxia and low pH led to colony death within 24 h. When hydrogen sulfide was added after 12 h of anoxia and low pH, colonies died after an additional 3 h. We suggest that sedimentation kills corals through microbial processes triggered by the organic matter in the sediments, namely respiration and presumably fermentation and desulfurylation of products from tissue degradation. First, increased microbial respiration results in reduced O(2) and pH, initiating tissue degradation. Subsequently, the hydrogen sulfide formed by bacterial decomposition of coral tissue and mucus diffuses to the neighboring tissues, accelerating the spread of colony mortality. Our data suggest that the organic enrichment of coastal sediments is a key process in the degradation of coral reefs exposed to terrestrial runoff. PMID:22615403

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

    NASA Astrophysics Data System (ADS)

    Misra, Santanu; Ellis, Susan; Mandal, Nibir

    2015-08-01

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

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

    NASA Technical Reports Server (NTRS)

    Coats, Timothy William

    1994-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-01-01

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

  9. Pharmacological Inhibition of Transforming Growth Factor β Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas' Disease▿

    PubMed Central

    Waghabi, Mariana C.; de Souza, Elen M.; de Oliveira, Gabriel M.; Keramidas, Michelle; Feige, Jean-Jacques; Araújo-Jorge, Tania C.; Bailly, Sabine

    2009-01-01

    Chagas' disease induced by Trypanosoma cruzi infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. We previously reported that transforming growth factor β (TGF-β) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. This prompted us to evaluate the therapeutic action of an inhibitor of TGF-β signaling (SB-431542) administered during the acute phase of experimental Chagas' disease. Male Swiss mice were infected intraperitoneally with 104 trypomastigotes of T. cruzi (Y strain) and evaluated clinically for the following 30 days. SB-431542 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that SB-431542 treatment was effective in protecting the cardiac conduction system. By 14 day postinfection, enzymatic biomarkers of tissue damage indicated that muscle injury was decreased by SB-431542 treatment, with significantly lower blood levels of aspartate aminotransferase and creatine kinase. In conclusion, inhibition of TGF-β signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic agent for acute and chronic Chagas' disease that warrants further clinical exploration. PMID:19738024

  10. Inhibition of pancreatic oxidative damage by stilbene derivative dihydro-resveratrol: implication for treatment of acute pancreatitis

    PubMed Central

    Tsang, Siu Wai; Guan, Yi-Fu; Wang, Juan; Bian, Zhao-Xiang; Zhang, Hong-Jie

    2016-01-01

    Trans-resveratrol is a natural stilbenoid possessing multifarious pharmacological benefits; however, when orally consumed, it is rapidly metabolised by colonic microflora and converted to dihydro-resveratrol. Thus, this microbial metabolite is of great therapeutic relevance. In the present study, upon the oral administration of dihydro-resveratrol (10–50 mg/kg), the severity of acute pancreatitis in the cerulein-treated rats was significantly ameliorated as evidenced by decreased α-amylase activities in the plasma and lessened oedema formation in the pancreatic parenchyma. In addition, the generation of intracellular reactive oxidative products, including malondialdehyde and protein carbonyls, was accordingly reduced, so as the production of pro-inflammatory cytokines. While inhibiting the activities of NADPH oxidase and myeloperoxidase, the depletion of glutathione was considerably restored. Importantly, the attenuation of pancreatic oxidative damage by dihydro-resveratrol was associated with a down-regulation of the nuclear factor-kappaB and phosphatidylinositol 3′-kinase-serine/threonine kinase signalling pathways. Furthermore, we demonstrated that the solubility of dihydro-resveratrol was at least 5 times higher than trans-resveratrol whilst exhibiting a much lower cytotoxicity. Collectively, the current findings accentuate new mechanistic insight of dihydro-resveratrol in pancreatic oxidative damage, and advocate its therapeutic potential for the management of acute pancreatitis, particularly for patients unresponsive to trans-resveratrol due to the lack of proper microbial strains. PMID:26971398

  11. Inhibition of pancreatic oxidative damage by stilbene derivative dihydro-resveratrol: implication for treatment of acute pancreatitis.

    PubMed

    Tsang, Siu Wai; Guan, Yi-Fu; Wang, Juan; Bian, Zhao-Xiang; Zhang, Hong-Jie

    2016-01-01

    Trans-resveratrol is a natural stilbenoid possessing multifarious pharmacological benefits; however, when orally consumed, it is rapidly metabolised by colonic microflora and converted to dihydro-resveratrol. Thus, this microbial metabolite is of great therapeutic relevance. In the present study, upon the oral administration of dihydro-resveratrol (10-50 mg/kg), the severity of acute pancreatitis in the cerulein-treated rats was significantly ameliorated as evidenced by decreased α-amylase activities in the plasma and lessened oedema formation in the pancreatic parenchyma. In addition, the generation of intracellular reactive oxidative products, including malondialdehyde and protein carbonyls, was accordingly reduced, so as the production of pro-inflammatory cytokines. While inhibiting the activities of NADPH oxidase and myeloperoxidase, the depletion of glutathione was considerably restored. Importantly, the attenuation of pancreatic oxidative damage by dihydro-resveratrol was associated with a down-regulation of the nuclear factor-kappaB and phosphatidylinositol 3'-kinase-serine/threonine kinase signalling pathways. Furthermore, we demonstrated that the solubility of dihydro-resveratrol was at least 5 times higher than trans-resveratrol whilst exhibiting a much lower cytotoxicity. Collectively, the current findings accentuate new mechanistic insight of dihydro-resveratrol in pancreatic oxidative damage, and advocate its therapeutic potential for the management of acute pancreatitis, particularly for patients unresponsive to trans-resveratrol due to the lack of proper microbial strains. PMID:26971398

  12. 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.

  13. Septic acute kidney injury: molecular mechanisms and the importance of stratification and targeting therapy.

    PubMed

    Morrell, Eric D; Kellum, John A; Pastor-Soler, Núria M; Hallows, Kenneth R

    2014-01-01

    The most common cause of acute kidney injury (AKI) in hospitalized patients is sepsis. However, the molecular pathways and mechanisms that mediate septic AKI are not well defined. Experiments performed over the past 20 years suggest that there are profound differences in the pathogenesis between septic and ischemic AKI. Septic AKI often occurs independently of hypoperfusion, and is mediated by a concomitant pro- and anti-inflammatory state that is activated in response to various pathogen-associated molecular patterns, such as endotoxin, as well as damage-associated molecular patterns. These molecular patterns are recognized by Toll-like receptors (TLRs) found in the kidney, and effectuate downstream inflammatory pathways. Additionally, apoptosis has been proposed to play a role in the pathogenesis of septic AKI. However, targeted therapies designed to mitigate the above aspects of the inflammatory state, TLR-related pathways, and apoptosis have failed to show significant clinical benefit. This failure is likely due to the protean nature of septic AKI, whereby different patients present at different points along the immunologic spectrum. While one patient may benefit from targeted therapy at one end of the spectrum, another patient at the other end may be harmed by the same therapy. We propose that a next important step in septic AKI research will be to identify where patients lie on the immunologic spectrum in order to appropriately target therapies at the inflammatory cascade, TLRs, and possibly apoptosis. PMID:25575158

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

    SciTech Connect

    Du Yongfeng; Li Hui

    2008-07-08

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

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

    NASA Technical Reports Server (NTRS)

    Poe, C. C., Jr.

    1985-01-01

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

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

    PubMed

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

    2016-05-01

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

  17. Theory of inception mechanism and growth of defect-induced damage in polyethylene cable insulation

    NASA Astrophysics Data System (ADS)

    Serra, S.; Montanari, G. C.; Mazzanti, G.

    2005-08-01

    We have investigated theoretically the inception mechanism and growth of the damage inside the insulation system of a polymeric cable under working conditions. We focused, in particular, our attention on damage originating from microscopic defects such as voids. In order to clarify the implications of these defects for cable failure, we have developed a theoretical model based on the theory of electrical avalanche solving numerically its basic equations. Calculations of the ionization rates of atmospheric gas filling the voids are done as a function of the applied electric stress and void dimensions. Estimates of the energy release and local damage in polyethylene produced by the resulting hot-electron discharge are given. The developed physical model of damage growth compares reasonably well with known experimental data.

  18. Modeling of combined high-temperature creep and cyclic plasticity in components using continuum damage mechanics

    NASA Astrophysics Data System (ADS)

    Dunne, F. P. E.; Hayhurst, D. R.

    1992-06-01

    A computer-based finite-element viscoplastic damage solver is presented to analyze structural components subject to combined cyclic thermal and mechanical loading. The solver is capable of predicting the combined evolution of creep and cyclic plasticity damage by solution of the combined boundary-initial value problem. The solver has been used to predict the high-temperature behavior of a slag tap component subjected to cyclic thermal loading generated by infrared heaters and water cooling ducts. It is found that the initiation of damage and microcracking occur early in the lifetime at about 3000 cycles adjacent to the cooling duct. The propagation of failure zones stabilizes at 60,000 cycles after which no further damage evolution occurs.

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

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

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

  20. Microstructural coarsening effects on redox instability and mechanical damage in solid oxide fuel cell anodes

    NASA Astrophysics Data System (ADS)

    Abdeljawad, F.; Haataja, M.

    2013-11-01

    In state-of-the-art high temperature solid oxide fuel cells (SOFCs), a porous composite of nickel and yttria stabilized zirconia (Ni/YSZ) is employed as the anode. The rapid oxidation of Ni into NiO is regarded as the main cause of the so-called reduction-oxidation (redox) instability in Ni/YSZ anodes, due to the presence of extensive bulk volume changes associated with this reaction. As a consequence, the development of internal stresses can lead to performance degradation and/or structural failure. In this study, we employ a recently developed continuum formalism to quantify the mechanical deformation behavior and evolution of internal stresses in Ni/YSZ porous anodes due to re-oxidation. In our approach, a local failure criterion is coupled to the continuum framework in order to account for the heterogeneous damage accumulation in the YSZ phase. The hallmark of our approach is the ability to track the spatial evolution of mechanical damage and capture the interaction of YSZ damaged regions with the local microstructure. Simulation results highlight the importance of the microstructure characterized by Ni to YSZ particle size ratio on the redox behavior and damage accumulation in as-synthesized SOFC anode systems. Moreover, a redox-strain-to-failure criterion is developed to quantify the degree by which coarsened anode microstructures become more susceptible to mechanical damage during re-oxidation.

  1. Damage patterns of retinal nerve fiber layer in acute and chronic intraocular pressure elevation in primary angle closure glaucoma

    PubMed Central

    Liu, Xing; Li, Mei; Zhong, Yi-Min; Xiao, Hui; Huang, Jing-Jing; Kong, Xiang-Yun

    2010-01-01

    AIM To observe the differences of damage patterns of retinal nerve fiber layer (RNFL) between acute and chronic intraocular pressure (IOP) elevation in primary angle closure glaucoma (PACG) using optical coherence tomography (OCT). METHODS Twenty-four patients (48 eyes) with unilateral acute PACG (APACG) attack in the 6 months after admission and 36 patients (64 eyes) with chronic PACG (CPACG) were included in this prospective study. For all cases, IOP has been controlled under 21mmHg after treatment. Using stratus OCT, the RNFL thickness was assessed in eyes with PACG within 3 days, 2 weeks, 1, 3 and 6 months after IOP was controlled. Repeated measures ANOVA was used to examine the changes of RNFL thickness at different time after IOP being controlled in both acute attack eyes and unaffected fellow eyes of APACG and eyes with CPACG. RESULTS The mean RNFL thickness for the APACG-attacked eyes increased significantly within 3 days (121.49±23.84)µm after acute onset and then became thinner along with time [(107.22±24.72)µm at 2 weeks,(93.58±18.37)µm at 1 month, (84.10±19.89)µm at 3 months and (78.98±19.17)µm at 6 months]. In APACG-attacked eyes, there were significant differences of average RNFL thickness at 5 different times after IOP was controlled (P<0.001). In the APACG unaffected fellow eyes and CPACG eyes, there were no significant differences in mean RNFL thickness at 5 different times(F=0.450, P=0.104 in APACG unaffected fellow eyes and F=1.558, P=0.200 in CPACG eyes). There was significant difference for interaction between time periods and groups (F=1.912, P=0.003). CONCLUSION RNFL damage patterns are different under different IOP elevated courses. In APACG, RNFL was found to be swollen and thickening right after acute attack and then becomes thinning and atrophy along with the time, while RNFL was found to be diffused thinness in CPACG. PMID:22553541

  2. 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

  3. A Novel Therapy to Attenuate Acute Kidney Injury and Ischemic Allograft Damage after Allogenic Kidney Transplantation in Mice

    PubMed Central

    Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann

    2015-01-01

    Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20–50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells. PMID:25617900

  4. Deformation and damage mechanisms of zinc coatings on hot-dip galvanized steel sheets: Part II. Damage modes

    NASA Astrophysics Data System (ADS)

    Parisot, Rodolphe; Forest, Samuel; Pineau, André; Grillon, François; Demonet, Xavier; Mataigne, Jean-Michel

    2004-03-01

    Zinc-based coatings are widely used for protection against corrosion of steel-sheet products in the automotive industry. The objective of the present article is to investigate the damage modes at work in three different microstructures of a zinc coating on an interstitial-free steel substrate under tension, planestrain tension, and expansion loading. Plastic-deformation mechanisms are addressed in the companion article. Two main fracture mechanisms, namely, intergranular cracking and transgranular cleavage fracture, were identified in an untempered cold-rolled coating, a tempered cold-rolled coating, and a recrystallized coating. No fracture at the interface between the steel and zinc coating was observed that could lead to spalling, in the studied zinc alloy. A complex network of cleavage cracks and their interaction with deformation twinning is shown to develop in the material. An extensive quantitative analysis based on systematic image analysis provides the number and cumulative length of cleavage cracks at different strain levels for the three investigated microstructures and three loading conditions. Grain refinement by recrystallization is shown to lead to an improved cracking resistance of the coating. A model for crystallographic cleavage combining the stress component normal to the basal plane and the amount of plastic slip on the basal slip systems is proposed and identified from equibiaxial tension tests and electron backscattered diffraction (EBSD) analysis of the cracked grains. This analysis requires the computation of the nonlinear stress-strain response of each grain using a crystal-plasticity constitutive model. The model is then applied successfully to other loading conditions and is shown to account for the preferred orientations of damaged grains observed in the case of plane-strain tension.

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

    PubMed

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

    2014-05-01

    The increasing presence of pharmaceutical drugs in nature is cause of concern due to the occurrence of oxidative stress in non-target species. Acetaminophen is widely used in human medicine as an analgesic and antipyretic drug, and it is one of the most sold non-prescription drugs. The present study aimed to assess the toxic effects of acetaminophen (APAP) in Oncorhynchus mykiss following acute and chronic exposures in realistic levels. In order to evaluate the APAP effects in the rainbow trout, gills and liver were analyzed with biochemical biomarkers, such as catalase (CAT), total and selenium-dependent glutathione peroxidase (GPx), glutathione reductase (GRed) and glutathione-S-transferases (GSTs) activity and also lipid peroxidation levels (TBARS). The results obtained in all tests indicate that a significant response of oxidative stress was established, along with the increase of APAP concentrations. The establishment of an oxidative stress scenario occurred with the involvement of all tested biomarkers, sustaining a generalized set of pro-oxidative effects elicited by APAP. Additionally, the occurrence of oxidative damage strongly suggests the impairment of the antioxidant defense mechanism of O. mykiss. It is important to note that the occurrence of oxidative deleterious effects and peroxidative damages occurred for concentrations similar to those already reported for several freshwater ecosystems. The importance of these assumptions is further discussed under the scope of ecological relevance of the assessment of effects caused by pharmaceuticals in non-target organisms. PMID:24816177

  6. Accumulation of oxidatively generated DNA damage in the brain: a mechanism of neurotoxicity.

    PubMed

    Chen, Liuji; Lee, Heung M; Greeley, George H; Englander, Ella W

    2007-02-01

    Unrepaired or erroneously repaired DNA lesions drive genomic instability and contribute to cellular and organ decline. Since delayed neuropathologies are common in survivors of smoke inhalation injuries, we asked whether the integrity of brain DNA might be compromised by acute exposure to combustion smoke. Although many studies demonstrate that the brain is equipped to repair oxidatively damaged DNA, to date, the capacity for accurate DNA repair under conditions of disrupted oxygenation and oxidative stress has not been defined. We show that DNA adducts detectable by their ability to block PCR amplification form in the rat hippocampus after acute exposure to smoke. To identify the different types of adducts and to dissect their temporal formation and repair profiles in vivo in the brain, we used DNA-modifying enzymes to convert specific adducts into strand breaks prior to PCR amplification. Using this strategy, we detected formation of oxidative DNA adducts early on after smoke inhalation, while mismatched bases emerged at the later recovery times, potentially due to an erroneous DNA repair process. Erroneous repair can be mutagenic and because the initial smoke-induced oxidative damage to DNA is extensive, compromised fidelity of DNA repair may underlie neurotoxicity and contribute to delayed death of hippocampal neurons. PMID:17210451

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    EPA Science Inventory

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

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

  9. Acute hydrodynamic damage induced by SPLITT fractionation and centrifugation in red blood cells.

    PubMed

    Urbina, Adriana; Godoy-Silva, Ruben; Hoyos, Mauricio; Camacho, Marcela

    2016-05-01

    Though blood bank processing traditionally employs centrifugation, new separation techniques may be appealing for large scale processes. Split-flow fractionation (SPLITT) is a family of techniques that separates in absence of labelling and uses very low flow rates and force fields, and is therefore expected to minimize cell damage. However, the hydrodynamic stress and possible consequent damaging effects of SPLITT fractionation have not been yet examined. The aim of this study was to investigate the hydrodynamic damage of SPLITT fractionation to human red blood cells, and to compare these effects with those induced by centrifugation. Peripheral whole blood samples were collected from healthy volunteers. Samples were diluted in a buffered saline solution, and were exposed to SPLITT fractionation (flow rates 1-10ml/min) or centrifugation (100-1500g) for 10min. Cell viability, shape, diameter, mean corpuscular hemoglobin, and membrane potential were measured. Under the operating conditions employed, both SPLITT and centrifugation maintained cell viability above 98%, but resulted in significant sublethal damage, including echinocyte formation, decreased cell diameter, decreased mean corpuscular hemoglobin, and membrane hyperpolarization which was inhibited by EGTA. Wall shear stress and maximum energy dissipation rate showed significant correlation with lethal and sublethal damage. Our data do not support the assumption that SPLITT fractionation induces very low shear stress and is innocuous to cell function. Some changes in SPLITT channel design are suggested to minimize cell damage. Measurement of membrane potential and cell diameter could provide a new, reliable and convenient basis for evaluation of hydrodynamic effects on different cell models, allowing identification of optimal operating conditions on different scales. PMID:27023157

  10. Hemodynamics of Acute Right Heart Failure in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome.

    PubMed

    McLean, Barbara

    2015-12-01

    In critically ill patients with circulatory shock, the role of the left ventricle has long been appreciated and the object of measurement and therapeutic targeting. The right ventricle is often under appreciated and dysfunction may be overlooked. Generally, the right ventricle operates passively to support the ejection of the left ventricular diastolic volume. A loss of right ventricular wall compliance secondary to pulmonary pressures may result in an alteration in the normal pressure-volume relationship, ultimately affecting the stroke volume and cardiac output. Traditional right heart filling indices may increase because of decreasing compliance, further complicating the picture. The pathophysiology of pulmonary vascular dysfunction in acute respiratory distress syndrome combined with the effects of a mean airway pressure strategy may create an acute cor pulmonale. PMID:26567491

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

    PubMed Central

    Callegari, A. John; Kelly, Thomas J.

    2016-01-01

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

  12. Effect of technique and timing of tracheostomy in patients with acute traumatic spinal cord injury undergoing mechanical ventilation

    PubMed Central

    Ganuza, Javier Romero; Forcada, Angel Garcia; Gambarrutta, Claudia; De La Lastra Buigues, Elena Diez; Gonzalez, Victoria Eugenia Merlo; Fuentes, Fátima Paz; Luciani, Alejandro A.

    2011-01-01

    Objective To assess the effect of timing and techniques of tracheostomy on morbidity, mortality, and the burden of resources in patients with acute traumatic spinal cord injuries (SCIs) undergoing mechanical ventilation. Design Review of a prospectively collected database. Setting Intensive and intermediate care units of a monographic hospital for the treatment of SCI. Participants Consecutive patients admitted to the intensive care unit (ICU) during their first inpatient rehabilitation for cervical and thoracic traumatic SCI. A total of 323 patients were included: 297 required mechanical ventilation and 215 underwent tracheostomy. Outcome measures Demographic data, data relevant to the patients’ neurological injuries (level and grade of spinal cord damage), tracheostomy technique and timing, duration of mechanical ventilation, length of stay at ICU, incidence of pneumonia, incidence of perioperative and early postoperative complications, and mortality. Results Early tracheostomy (<7 days after orotracheal intubation) tracheostomy was performed in 101 patients (47%) and late (≥7 days) in 114 (53%). Surgical tracheostomy was employed in 119 cases (55%) and percutaneous tracheostomy in 96 (45%). There were 61 complications in 53 patients related to all tracheostomy procedures. Two were qualified as serious (tracheoesophageal fistula and mediastinal abscess). Other complications were mild. Bleeding was moderate in one case (late, percutaneous tracheostomy). Postoperative infection rate was low. Mortality of all causes was also low. Conclusion Early tracheostomy may have favorable effects in patients with acute traumatic SC. Both techniques, percutaneous and surgical tracheostomy, can be performed safely in the ICU. PMID:21528630

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Pattabiraman, Sundararaghavan; Kaganovich, Daniel

    2014-01-01

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

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

    PubMed

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

    2014-01-01

    Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It damages normal tissue and causes side effects including dermatitis and mucositis. Here we use the feather follicle as a model to investigate the mechanism of IR-induced tissue damage, because any perturbation of feather growth will be clearly recorded in its regular yet complex morphology. We find that IR induces defects in feather formation in a dose-dependent manner. No abnormality was observed at 5 Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy, leading to defects in the feather structure. This perturbation became irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation, DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR also induces patterning defects in feather formation, with disrupted branching morphogenesis. This perturbation is mediated by cytokine production and Stat1 activation, as manipulation of cytokine levels or ectopic Stat1 over-expression also led to irregular feather branching. Furthermore, AG-490, a chemical inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our results suggest that the feather follicle could serve as a useful model to address the in vivo impact of the many mechanisms of IR-induced tissue damage. PMID:24586618

  16. Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using ...

  17. Dexrazoxane Diminishes Doxorubicin-Induced Acute Ovarian Damage and Preserves Ovarian Function and Fecundity in Mice

    PubMed Central

    Ringelstetter, Ashley; Khatib, Hasan; Abbott, David H.; Salih, Sana M.

    2015-01-01

    Advances in cancer treatment utilizing multiple chemotherapies have dramatically increased cancer survivorship. Female cancer survivors treated with doxorubicin (DXR) chemotherapy often suffer from an acute impairment of ovarian function, which can persist as long-term, permanent ovarian insufficiency. Dexrazoxane (Dexra) pretreatment reduces DXR-induced insult in the heart, and protects in vitro cultured murine and non-human primate ovaries, demonstrating a drug-based shield to prevent DXR insult. The present study tested the ability of Dexra pretreatment to mitigate acute DXR chemotherapy ovarian toxicity in mice through the first 24 hours post-treatment, and improve subsequent long-term fertility throughout the reproductive lifespan. Adolescent CD-1 mice were treated with Dexra 1 hour prior to DXR treatment in a 1:1 mg or 10:1 mg Dexra:DXR ratio. During the acute injury period (2–24 hours post-injection), Dexra pretreatment at a 1:1 mg ratio decreased the extent of double strand DNA breaks, diminished γH2FAX activation, and reduced subsequent follicular cellular demise caused by DXR. In fertility and fecundity studies, dams pretreated with either Dexra:DXR dose ratio exhibited litter sizes larger than DXR-treated dams, and mice treated with a 1:1 mg Dexra:DXR ratio delivered pups with birth weights greater than DXR-treated females. While DXR significantly increased the “infertility index” (quantifying the percentage of dams failing to achieve pregnancy) through 6 gestations following treatment, Dexra pretreatment significantly reduced the infertility index following DXR treatment, improving fecundity. Low dose Dexra not only protected the ovaries, but also bestowed a considerable survival advantage following exposure to DXR chemotherapy. Mouse survivorship increased from 25% post-DXR treatment to over 80% with Dexra pretreatment. These data demonstrate that Dexra provides acute ovarian protection from DXR toxicity, improving reproductive health in a mouse

  18. Evolution of blood-brain barrier damage associated with changes in brain metabolites following acute ischemia.

    PubMed

    Yan, Gen; Xuan, Yinghua; Dai, Zhuozhi; Zhang, Guishan; Xu, Haiyun; Mikulis, David; Wu, Renhua

    2015-11-11

    Stroke is a serious medical condition that requires emergency care. In the case of ischemic stroke, ischemia may lead to damage to the blood-brain barrier (BBB); the damage in turn may exacerbate the condition. Therefore, noninvasive detection of BBB damage represents a challenge for experimental and clinical researchers. In this study, we assessed the onset of BBB disruption by means of T1-weighted images with administration of the contrast enhancement agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and related BBB breakdown to brain metabolite changes in proton magnetic resonance spectrum (H-MRS) in the infarcted site following middle cerebral artery occlusion (MCAO) in rats. It was shown that MCAO for 30 min and 1.5 h caused no Gd-DTPA signal change in the T1-weighted images, whereas MCAO for 1 h significantly altered some of H-MRS brain metabolites, suggesting that brain metabolite changes occurred earlier than BBB damage after ischemic stroke. MCAO for 2 h caused BBB breakdown, which was related to changes in the levels of some brain metabolites detected by H-MRS. Between the second and the third hour after MCAO, brain metabolite changes continued as the result of BBB breakdown and the concurrent overperfusion to the infarcted site, which may ameliorate the metabolite changes, thus compensating for the functional failures of the brain after stroke. PMID:26366833

  19. 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

  20. Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage

    PubMed Central

    Johnsen, Marc; Späth, Martin Richard; Denzel, Martin S.; Göbel, Heike; Kubacki, Torsten; Hoyer, Karla Johanna Ruth; Hinze, Yvonne; Benzing, Thomas; Schermer, Bernhard; Antebi, Adam; Burst, Volker; Müller, Roman-Ulrich

    2016-01-01

    Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney. PMID:27557097

  1. Acute formation of lumbar discal cyst: what is the mechanism?

    PubMed

    Aydin, S; Kucukyuruk, B; Yildirim, H; Abuzayed, B; Bozkus, H; Vural, M

    2010-12-01

    Lumbar discal cysts are extremely rare pathologies, with only few reports describing these lesions in the literature. Moreover, their definite pathogenesis is still unknown, with proposed theories based on radialogic and histologic findings. In this report, the authors present an acute formation of a discal cyst, which is reported for the first time. Also, we center our case on the discussion of the possible pathogenesis. Also, this is the first case of discal cyst reported in Turkey. A 67-year-old woman, whose complaints, and clinical and radiological findings demonstrated lumbar disc herniation with acute Modic 1 degererative changes of the adjacent end plates of L3-4 level. After medical and physical therapies, follow-up lumbar MRI has been taken to demonstrate a discal cyst formation on the adjacent intervertebral disc, showed cranially migrated cyst superior posterior on herniated disc, in 2 weeks period. The patient was treated by microsurgical resection of the cyst, and her complaints resolved completely. PMID:21423085

  2. Origin and magma pathways for intraplate volcanism: a new damage mechanics model

    NASA Astrophysics Data System (ADS)

    Regenauer-Lieb, K.; Rosenbaum, G.; Weinberg, R. F.; Lyakhovsky, V.; Segev, A.; Weinstein, Y.

    2013-12-01

    We address the question of melting at the base of the lithosphere and the opening of pathways capable of transferring melt to the surface in an intraplate setting of an extending continental lithosphere. We study the initial stage of melting and the onset of the melting instability. The aim of this study thus is to understand: (i) the ubiquitous appearance of alkali-basaltic volcanic provinces that appear without identifiable heat source in intraplate settings; (ii) the apparent relation between melting and localization of deformation under such extremely low intraplate strain rates; (iii) the challenge of generating efficient pathways for the propagation of melt to the surface; (iv) the generation of melt at the base of a lithosphere with low regional heat flow in a thermodynamically consistent model; (iv) as a minor aspect, we also investigate the effect of a pre-existing structure at the surface of the lithosphere. We use a novel method for calculating the effect of melt on lithosphere deformation, which includes damage mechanics and feedback effects between melt generation and rock deformation. We show that it is possible to nucleate melt damage shear bands at the bottom of initially cold lithosphere in slow extensional setting. We conducted numerical models for common continental lithosphere with 50mW/m2 heat flow and a slow asymmetric extension velocity of 1 mm/y, and allowed three different damage mechanisms: (1) classical brittle damage with a Drucker-Prager type rheology; (2) creep damage with a crustal fluid assisted diffusional/dislocation mechanism; and (3) melt damage with a melt-supported diffusional/ dislocation mechanism. The melt conditions were calculated with a Gibbs energy minimization method (Melts; http://melts.ofm-research.org/), and the energy equation solved self-consistently for latent heat and shear heating effects. Our results show that within a short timeframe (~2 Ma), melt damage can propagate from the bottom of the lithosphere upwards

  3. [Structural mechanisms and mathematical modeling of the bone tissue damage caused by hyper-speed impact].

    PubMed

    Ishchenko, A N; Belov, N N; Gaĭdash, A A; Iugov, N T; Bashirov, R S; Afanas'eva, S A; Sinitsa, L N

    2011-03-01

    Method of computer modeling of behavior of cylindrical and lamellar bones under the hypervelocity impact is suggested. This method allows in the frame of mechanics of continuous medium to calculate the stress strain behavior and damage in bone tissues under the shock wave impact. The processes of shock correlation of steel fragments of different shape with diaphysis of cylindrical bones and flat bone of calvaria under the impact 500 m/s are studied. The given method can be used for the evaluation of damage area of bone tissue of shock wave osteoporosis under the gunshot wound. PMID:21770310

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

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

  5. The rodent endovascular puncture model of subarachnoid hemorrhage: mechanisms of brain damage and therapeutic strategies

    PubMed Central

    2014-01-01

    Subarachnoid hemorrhage (SAH) represents a considerable health problem. To date, limited therapeutic options are available. In order to develop effective therapeutic strategies for SAH, the mechanisms involved in SAH brain damage should be fully explored. Here we review the mechanisms of SAH brain damage induced by the experimental endovascular puncture model. We have included a description of similarities and distinctions between experimental SAH in animals and human SAH pathology. Moreover, several novel treatment options to diminish SAH brain damage are discussed. SAH is accompanied by cerebral inflammation as demonstrated by an influx of inflammatory cells into the cerebral parenchyma, upregulation of inflammatory transcriptional pathways and increased expression of cytokines and chemokines. Additionally, various cell death pathways including cerebral apoptosis, necrosis, necroptosis and autophagy are involved in neuronal damage caused by SAH. Treatment strategies aiming at inhibition of inflammatory or cell death pathways demonstrate the importance of these mechanisms for survival after experimental SAH. Moreover, neuroregenerative therapies using stem cells are discussed as a possible strategy to repair the brain after SAH since this therapy may extend the window of treatment considerably. We propose the endovascular puncture model as a suitable animal model which resembles the human pathology of SAH and which could be applied to investigate novel therapeutic therapies to combat this debilitating insult. PMID:24386932

  6. Selenium Pretreatment for Mitigation of Ischemia/Reperfusion Injury in Cardiovascular Surgery: Influence on Acute Organ Damage and Inflammatory Response.

    PubMed

    Steinbrenner, Holger; Bilgic, Esra; Pinto, Antonio; Engels, Melanie; Wollschläger, Lena; Döhrn, Laura; Kellermann, Kristine; Boeken, Udo; Akhyari, Payam; Lichtenberg, Artur

    2016-08-01

    Ischemia/reperfusion injury (IRI) contributes to morbidity and mortality after cardiovascular surgery requiring cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Multi-organ damage is associated with substantial decreases of blood selenium (Se) levels in patients undergoing cardiac surgery with CPB. We compared the influence of a dietary surplus of Se and pretreatment with ebselen, a mimic of the selenoenzyme glutathione peroxidase, on IRI-induced tissue damage and inflammation. Male Wistar rats were fed either a Se-adequate diet containing 0.3 ppm Se or supplemented with 1 ppm Se (as sodium selenite) for 5 weeks. Two other groups of Se-adequate rats received intraperitoneal injection of ebselen (30 mg/kg) or DMSO (solvent control) before surgery. The animals were connected to a heart-lung-machine and underwent 45 min of global ischemia during circulatory arrest at 16 °C, followed by re-warming and reperfusion. Selenite and ebselen suppressed IRI-induced leukocytosis and the increase in plasma levels of tissue damage markers (AST, ALT, LDH, troponin) during surgery but did not prevent the induction of proinflammatory cytokines (IL-6, TNF-α). Both Se compounds affected phosphorylation and expression of proteins related to stress response and inflammation: Ebselen increased phosphorylation of STAT3 transcription factor in the heart and decreased phosphorylation of ERK1/2 MAP kinases in the lungs. Selenite decreased ERK1/2 phosphorylation and HSP-70 expression in the heart. Pretreatment with selenite or ebselen protected against acute IRI-induced tissue damage during CPB and DHCA. Potential implications of their different actions with regard to molecular stress markers on the recovery after surgery represent promising targets for further investigation. PMID:27192987

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  8. Mechanisms of Neurovascular Dysfunction in Acute Ischemic Brain

    PubMed Central

    Terasaki, Y.; Liu, Y.; Hayakawa, K.; Pham, L.D.; Lo, E.H.; Ji, X.; Arai, K.

    2014-01-01

    The neurovascular unit is now well accepted as a conceptual framework for investigating the mechanisms of ischemic stroke. From a molecular and cellular perspective, three broad mechanisms may underlie stroke pathophysiology – excitotoxicity, oxidative stress and inflammation. To date, however, most investigations of these basic mechanisms have focused on neuronal responses. In this mini-review, we ask whether these mechanisms of excitotoxicity, oxidative stress and inflammation can also be examined in terms of non-neuronal interactions in the neurovascular unit, including the release of extracellular vesicles for cell-cell signaling. PMID:24372202

  9. Chemical Mechanical Polishing with Nanocolloidal Ceria Slurry for Low-Damage Planarization of Dielectric Films

    NASA Astrophysics Data System (ADS)

    Ryuzaki, Daisuke; Hoshi, Yosuke; Machii, Yoichi; Koyama, Naoyuki; Sakurai, Haruaki; Ashizawa, Toranosuke

    2012-03-01

    New chemical mechanical polishing processes using nanocolloidal ceria slurry are proposed for high-precision and low-damage planarization of silicon-dioxide-based dielectric films. In the polishing process of a shallow trench isolation structure, a hard pad and a cationic polymer additive are used in combination with the slurry. The new process is effective in improving the planarity and reducing the microscratch count in comparison with a conventional polishing process with calcined ceria slurry and a standard pad. In the polishing process of an interconnect structure with ultralow-k interlayer dielectrics (ULK-ILDs), the standard pad should be used since the ULK-ILDs are easily damaged. By employing a spin-on-type ULK-ILD having a self-planarizing effect, a high planarity is obtained when using the nanocolloidal ceria slurry with the standard pad. The electrical measurement of the interconnect structure indicates that dielectric damage due to the process is successfully suppressed.

  10. A nonlocal continuum damage mechanics approach to simulation of creep fracture in ice sheets

    NASA Astrophysics Data System (ADS)

    Duddu, Ravindra; Waisman, Haim

    2013-06-01

    We present a Lagrangian finite element formulation aimed at modeling creep fracture in ice-sheets using nonlocal continuum damage mechanics. The proposed formulation is based on a thermo-viscoelastic constitutive model and a creep damage model for polycrystalline ice with different behavior in tension and compression. In this paper, mainly, we detail the nonlocal numerical implementation of the constitutive damage model into commercial finite element codes (e.g. Abaqus), wherein a procedure to handle the abrupt failure (rupture) of ice under tension is proposed. Then, we present numerical examples of creep fracture under four-point bending, uniaxial tension, and biaxial tension in order to illustrate the viability of the current approach. Finally, we present simulations of creep crack propagation in idealized rectangular ice slabs so as to estimate calving rates at low deformation rates. The examples presented demonstrate the mesh size and mesh directionality independence of the proposed nonlocal implementation.

  11. Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia

    PubMed Central

    Park, Eugene; Papaemmanuil, Elli; Ford, Anthony; Kweon, Soo-Mi; Trageser, Daniel; Hasselfeld, Brian; Henke, Nadine; Mooster, Jana; Geng, Huimin; Schwarz, Klaus; Kogan, Scott C.; Casellas, Rafael; Schatz, David G.; Lieber, Michael R; Greaves, Mel F.; Müschen, Markus

    2015-01-01

    Childhood acute lymphoblastic leukemia can often be retraced to a pre-leukemic clone carrying a prenatal genetic lesion. Postnatally acquired mutations then drive clonal evolution towards overt leukemia. RAG1-RAG2 and AID enzymes, the diversifiers of immunoglobulin genes, are strictly segregated to early and late stages of B-lymphopoiesis, respectively. Here, we identified small pre-BII cells as a natural subset of increased genetic vulnerability owing to concurrent activation of these enzymes. Consistent with epidemiological findings on childhood ALL etiology, susceptibility to genetic lesions during B-lymphopoiesis at the large to small pre-BII transition is exacerbated by abnormal cytokine signaling and repetitive inflammatory stimuli. We demonstrate that AID and RAG1-RAG2 drive leukemic clonal evolution with repeated exposure to inflammatory stimuli, paralleling chronic infections in childhood. PMID:25985233

  12. Acute fatty liver of pregnancy: an update on mechanisms

    PubMed Central

    Natarajan, Sathish Kumar; Thangaraj, Kavitha R; Goel, Ashish; Eapen, C E; Balasubramanian, K A; Ramachandran, Anup

    2011-01-01

    Acute fatty liver of pregnancy (AFLP), characterized by hepatic microvesicular steatosis, is a sudden catastrophic illness occurring almost exclusively in the third trimester of pregnancy. Defective fatty acid oxidation in the fetus has been shown to be associated with this disease. Since the placenta has the same genetic makeup as the fetus and as AFLP patients generally recover following delivery, we hypothesized that the placenta might be involved in pathogenesis of this disease. In an animal model of hepatic microvesicular steatosis (using sodium valproate), we found that microvesicular steatosis results in mitochondrial structural alterations and oxidative stress in subcellular organelles of the liver. In placentas from patients with AFLP, we observed placental mitochondrial dysfunction and oxidative stress in subcellular organelles. In addition, defective placental fatty acid oxidation results in accumulation of toxic mediators such as arachidonic acid. Escape of these mediators into the maternal circulation might affect the maternal liver resulting in microvesicular steatosis.

  13. Lycopene protects against acute zearalenone-induced oxidative, endocrine, inflammatory and reproductive damages in male mice.

    PubMed

    Boeira, Silvana Peterini; Funck, Vinícius Rafael; Borges Filho, Carlos; Del'Fabbro, Lucian; de Gomes, Marcelo Gomes; Donato, Franciele; Royes, Luiz Fernando Freire; Oliveira, Mauro Schneider; Jesse, Cristiano Ricardo; Furian, Ana Flávia

    2015-03-25

    Male mice received lycopene for 10 days before a single oral administration of zearalenone (ZEA). After 48 h testes and blood were collected. Mice treated with lycopene/ZEA exhibited amelioration of the hematological changes. Lycopene prevented the reduction in the number and motility of spermatozoa and testosterone levels, indicating a protective effect in the testicular damage induced by ZEA. Lycopene was also effective in protecting against the decrease in glutathione-S-transferase, glutathione peroxidase, glutathione reductase and δ-aminolevulinic acid dehydratase activities caused by ZEA in the testes. Exposure of animals to ZEA induced modification of antioxidant and inflammatory status with increase of reduced glutathione (GSH) levels and increase of the oxidized glutathione, interleukins 1β, 2, 6, 10, tumor necrosis factor-α and bilirubin levels. Lycopene prevented ZEA-induced changes in GSH levels and inhibited the processes of inflammation, reducing the damage induced by ZEA. Altogether, our results indicate that lycopene was able to prevent ZEA-induced damage in the mice. PMID:25682699

  14. Hepatoprotective effect of the natural fruit juice from Aronia melanocarpa on carbon tetrachloride-induced acute liver damage in rats.

    PubMed

    Valcheva-Kuzmanova, S; Borisova, P; Galunska, B; Krasnaliev, I; Belcheva, A

    2004-12-01

    The fruits of Aronia melanocarpa are rich in anthocyanins--plant pigments with anti-inflammatory and antioxidant activity. We studied the effect of the natural fruit juice from A. melanocarpa (NFJAM) on carbon tetrachloride (CCl4)-induced acute liver damage in rats. Histopathological changes such as necrosis, fatty change, ballooning degeneration and inflammatory infiltration of lymphocytes around the central veins occurred in rats following acute exposure to CCl4 (0.2 ml kg(-1), 2 days). The administration of CCl4 increased plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities, induced lipid peroxidation (as measured by malondialdehyde (MDA) content in rat liver and plasma) and caused a depletion of liver reduced glutathione (GSH). NFJAM (5, 10 and 20 ml kg(-1), 4 days) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities, induced by CCl4 (0.2ml kg(-1), 3rd and 4th days). NFJAM also prevented the CCl4-induced elevation of MDA formation and depletion of GSH content in rat liver. PMID:15625789

  15. Protecting the heritable genome: DNA damage response mechanisms in spermatogonial stem cells.

    PubMed

    Rübe, Claudia E; Zhang, Sheng; Miebach, Nadine; Fricke, Andreas; Rübe, Christian

    2011-02-01

    Spermatogonial stem cells (SSCs) must maintain the integrity of their genome to prevent reproduction failure and limit the hereditary risk associated with transmission to the progeny. SSCs must therefore have robust response mechanisms to counteract the potentially deleterious effects of DNA damage, with DNA double-strand breaks (DSBs) representing the greatest threat to genomic integrity. Through in vivo analysis of the DNA damage response of SSCs within their physiological tissue context, we aimed to gain insights into the mechanisms by which SSCs preserve genome integrity. After whole-body irradiation of repair-proficient and repair-deficient (DNA-PK- and ATM-deficient) mice, the formation and rejoining of DSBs was analyzed in SSCs of testis compared with somatic cells of other tissues by enumerating γH2AX-, MDC1-, and 53BP1-foci. Caspase-3 and PARP-1 were used as markers for apoptotic cell death. Our results show that DNA damage response mechanisms in SSCs characterized by unique chromatin compositions are markedly different from those of somatic cells. In SSCs lacking compact heterochromatin, histone-associated signaling components of the DNA repair machinery are completely absent and radiation-induced DSBs are rejoined predominantly by DNA-PK-independent pathways, suggesting the existence of alternative repair mechanisms. As a complimentary mechanism characterized by low thresholds for ATM-dependent checkpoint activation, the differentiating progeny, but not the SSCs themselves, promote apoptosis in response to low levels of DNA damage. By evaluating SSCs within their stem cell niche, we show that DNA repair, cell-cycle checkpoints, and apoptosis function together to maintain the integrity of the heritable genome. PMID:21123119

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

    NASA Astrophysics Data System (ADS)

    Izvekov, Oleg

    2014-05-01

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

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

    NASA Technical Reports Server (NTRS)

    Arnold, S. M.; Kruch, S.

    1991-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Yun, Brian; Aidun, Cyrus; Yoganathan, Ajit

    2012-11-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  20. Reversible and Irreversible Mechanical Damaging of Large Double-Stranded DNA upon Electrospraying.

    PubMed

    Shlyapnikov, Yuri M; Shlyapnikova, Elena A; Morozov, Victor N

    2016-07-19

    Electrohydrodynamic spraying (or electrospaying, ES) of DNA solutions is an attractive technique for applications in mass spectrometry, in microarray fabrication, and in generation of DNA nanoaerosols. Here we report how ES affects DNA structure and evaluate possible ways to reduce DNA damage upon ES. It is shown that under any ES conditions, linear λ-phage DNA is subjected to intensive rupture producing a mixture of fragments. In addition to such fragmentation, notable reversible changes in the DNA structure were revealed by a slight increase in DNA electrophoretic mobility. The degree of fragmentation was shown to decrease with decreased DNA length and with increased flow rate through the ES capillary. Fragments shorter than 5 kbp did not show any notable damage upon ES. Both experimental data and theoretical estimations of the forces acting on DNA during ES indicate that DNA is damaged by mechanical forces, and the damage takes place in the vicinity of the Taylor cone tip, presumably due to the high shear stress or/and viscous drag forces operating there. Condensation of λ-DNA with hexamminecobalt(III) ions completely protected it from any damage upon ES. PMID:27306261

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

    PubMed

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

    2016-06-15

    After many decades of improvements in mechanical circulatory assist devices (CADs), blood damage remains a serious problem during support contributing to variety of adverse events, and consequently affecting patient survival and quality of life. The mechanisms of cumulative cell damage in continuous-flow blood pumps are still not fully understood despite numerous in vitro, in vivo, and in silico studies of blood trauma. Previous investigations have almost exclusively focused on lethal blood damage, namely hemolysis, which is typically negligible during normal operation of current generation CADs. The measurement of plasma free hemoglobin (plfHb) concentration to characterize hemolysis is straightforward, however sublethal trauma is more difficult to detect and quantify since no simple direct test exists. Similarly, while multiple studies have focused on thrombosis within blood pumps and accessories, sublethal blood trauma and its sequelae have yet to be adequately documented or characterized. This review summarizes the current understanding of sublethal trauma to red blood cells (RBCs) produced by exposure of blood to flow parameters and conditions similar to those within CADs. It also suggests potential strategies to reduce and/or prevent RBC sublethal damage in a clinically-relevant context, and encourages new research into this relatively uncharted territory. PMID:27034320

  2. Acute Oxidative Effect and Muscle Damage after a Maximum 4 Min Test in High Performance Athletes

    PubMed Central

    Fernandes Filho, José; Fernandes, Luiz Cláudio

    2016-01-01

    The purpose of this investigation was to determine lipid peroxidation markers, physiological stress and muscle damage in elite kayakers in response to a maximum 4-min kayak ergometer test (KE test), and possible correlations with individual 1000m kayaking performances. The sample consisted of twenty-three adult male and nine adult female elite kayakers, with more than three years’ experience in international events, who voluntarily took part in this study. The subjects performed a 10-min warm-up, followed by a 2-min passive interval, before starting the test itself, which consisted of a maximum 4-min work paddling on an ergometer; right after the end of the test, an 8 ml blood sample was collected for analysis. 72 hours after the test, all athletes took part in an official race, when then it was possible to check their performance in the on site K1 1000m test (P1000m). The results showed that all lipoproteins and hematological parameters tested presented a significant difference (p≤0.05) after exercise for both genders. In addition, parameters related to muscle damage such as lactate dehydrogenase (LDH) and creatine kinase (CK) presented significant differences after stress. Uric acid presented an inverse correlation with the performance (r = -0.76), while CK presented a positive correlation (r = 0.46) with it. Based on these results, it was possible to verify muscle damage and the level of oxidative stress caused by indoor training with specific ergometers for speed kayaking, highlighting the importance of analyzing and getting to know the physiological responses to this type of training, in order to provide information to coaches and optimize athletic performance. PMID:27111088

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

    SciTech Connect

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

    1995-12-31

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

  4. Propagation of damage in brain tissue: coupling the mechanics of oedema and oxygen delivery.

    PubMed

    Lang, Georgina E; Vella, Dominic; Waters, Sarah L; Goriely, Alain

    2015-11-01

    Brain tissue swelling, or oedema, is a dangerous consequence of traumatic brain injury and stroke. In particular, a locally swollen region can cause the injury to propagate further through the brain: swelling causes mechanical compression of the vasculature in the surrounding tissue and so can cut off that tissue's oxygen supply. We use a triphasic mathematical model to investigate this propagation, and couple tissue mechanics with oxygen delivery. Starting from a fully coupled, finite elasticity, model, we show that simplifications can be made that allow us to express the volume of the propagating region of damage analytically in terms of key parameters. Our results show that performing a craniectomy, to alleviate pressure in the brain and allow the tissue to swell outwards, reduces the propagation of damage; this finding agrees with experimental observations. PMID:25822263

  5. Exercise-induced muscle damage and potential mechanisms for the repeated bout effect.

    PubMed

    McHugh, M P; Connolly, D A; Eston, R G; Gleim, G W

    1999-03-01

    Unfamiliar, predominantly eccentric exercise, frequently results in muscle damage. A repeated bout of similar eccentric exercise results in less damage and is referred to as the 'repeated bout effect'. Despite numerous studies that have clearly demonstrated the repeated bout effect, there is little consensus as to the actual mechanism. In general, the adaptation has been attributed to neural, connective tissue or cellular adaptations. Other possible mechanisms include, adaptation in excitation-contraction coupling or adaptation in the inflammatory response. The 'neural theory' predicts that the initial damage is a result of high stress on a relatively small number of active fast-twitch fibres. For the repeated bout, an increase in motor unit activation and/or a shift to slow-twitch fibre activation distributes the contractile stress over a larger number of active fibres. Although eccentric training results in marked increases in motor unit activation, specific adaptations to a single bout of eccentric exercise have not been examined. The 'connective tissue theory' predicts that muscle damage occurs when the noncontractile connective tissue elements are disrupted and myofibrillar integrity is lost. Indirect evidence suggests that remodelling of the intermediate filaments and/or increased intramuscular connective tissue are responsible for the repeated bout effect. The 'cellular theory' predicts that muscle damage is the result of irreversible sarcomere strain during eccentric contractions. Sarcomere lengths are thought to be highly non-uniform during eccentric contractions, with some sarcomeres stretched beyond myofilament overlap. Loss of contractile integrity results in sarcomere strain and is seen as the initial stage of damage. Some data suggest that an increase in the number of sarcomeres connected in series, following an initial bout, reduces sarcomere strain during a repeated bout and limits the subsequent damage. It is unlikely that one theory can explain

  6. MECHANISMS OF SYNERGISTIC ANTILEUKEMIC INTERACTIONS BETWEEN VALPROIC ACID AND CYTARABINE IN PEDIATRIC ACUTE MYELOID LEUKEMIA

    PubMed Central

    Xie, Chengzhi; Edwards, Holly; Xu, Xuelian; Zhou, Hui; Buck, Steven A.; Stout, Mark L.; Yu, Qun; Rubnitz, Jeffrey E.; Matherly, Larry H.; Taub, Jeffrey W.; Ge, Yubin

    2010-01-01

    Purpose To determine the possibility of synergistic anti-leukemic activity and the underlying molecular mechanisms associated with cytarabine combined with valproic acid (VPA) [a histone deacetylase inhibitor (HDACI) and an FDA-licensed drug for treating both children and adults with epilepsy] in pediatric acute myeloid leukemia (AML). Experimental Design The type and extent of anti-leukemic interactions between cytarabine and VPA in clinically relevant pediatric AML cell lines and diagnostic blasts from children with AML were determined by MTT assays and standard isobologram analyses. The effects of cytarabine and VPA on apoptosis and cell cycle distributions were determined by flow cytometry analysis and caspase enzymatic assays. The effects of the two agents on DNA damage and Bcl-2 family proteins were determined by Western blotting. Results We demonstrated synergistic antileukemic activities between cytarabine and VPA in 4 pediatric AML cell lines and 9 diagnostic AML blast samples. t(8;21) AML blasts were significantly more sensitive to VPA and showed far greater sensitivities to combined cytarabine and VPA than non-t(8;21) AML cases. Cytarabine and VPA cooperatively induced DNA double strand breaks, reflected in induction of γH2AX and apoptosis, accompanied by activation of caspases 9 and 3. Further, VPA induced Bim expression and shRNA knockdown of Bim resulted in significantly decreased apoptosis induced by cytarabine, and by cytarabine plus VPA. Conclusions Our results establish global synergistic antileukemic activity of combined VPA and cytarabine in pediatric AML and provide compelling evidence to support the use of VPA in the treatment of children with this deadly disease. PMID:20889917

  7. Protracted Oxidative Alterations in the Mechanism of Hematopoietic Acute Radiation Syndrome.

    PubMed

    Gorbunov, Nikolai V; Sharma, Pushpa

    2015-01-01

    The biological effects of high-dose total body ionizing irradiation [(thereafter, irradiation (IR)] are attributed to primary oxidative breakage of biomolecule targets, mitotic, apoptotic and necrotic cell death in the dose-limiting tissues, clastogenic and epigenetic effects, and cascades of functional and reactive responses leading to radiation sickness defined as the acute radiation syndrome (ARS). The range of remaining and protracted injuries at any given radiation dose as well as the dynamics of post-IR alterations is tissue-specific. Therefore, functional integrity of the homeostatic tissue barriers may decline gradually within weeks in the post-IR period culminating with sepsis and failure of organs and systems. Multiple organ failure (MOF) leading to moribundity is a common sequela of the hemotapoietic form of ARS (hARS). Onset of MOF in hARS can be presented as "two-hit phenomenon" where the "first hit" is the underlying consequences of the IR-induced radiolysis in cells and biofluids, non-septic inflammation, metabolic up-regulation of pro-oxidative metabolic reactions, suppression of the radiosensitive hematopoietic and lymphoid tissues and the damage to gut mucosa and vascular endothelium. While the "second hit" derives from bacterial translocation and spread of the bacterial pathogens and inflammagens through the vascular system leading to septic inflammatory, metabolic responses and a cascade of redox pro-oxidative and adaptive reactions. This sequence of events can create a ground for development of prolonged metabolic, inflammatory, oxidative, nitrative, and carbonyl, electrophilic stress in crucial tissues and thus exacerbate the hARS outcomes. With this perspective, the redox mechanisms, which can mediate the IR-induced protracted oxidative post-translational modification of proteins, oxidation of lipids and carbohydrates and their countermeasures in hARS are subjects of the current review. Potential role of ubiquitous, radioresistant mesenchymal

  8. Protracted Oxidative Alterations in the Mechanism of Hematopoietic Acute Radiation Syndrome

    PubMed Central

    Gorbunov, Nikolai V.; Sharma, Pushpa

    2015-01-01

    The biological effects of high-dose total body ionizing irradiation [(thereafter, irradiation (IR)] are attributed to primary oxidative breakage of biomolecule targets, mitotic, apoptotic and necrotic cell death in the dose-limiting tissues, clastogenic and epigenetic effects, and cascades of functional and reactive responses leading to radiation sickness defined as the acute radiation syndrome (ARS). The range of remaining and protracted injuries at any given radiation dose as well as the dynamics of post-IR alterations is tissue-specific. Therefore, functional integrity of the homeostatic tissue barriers may decline gradually within weeks in the post-IR period culminating with sepsis and failure of organs and systems. Multiple organ failure (MOF) leading to moribundity is a common sequela of the hemotapoietic form of ARS (hARS). Onset of MOF in hARS can be presented as “two-hit phenomenon” where the “first hit” is the underlying consequences of the IR-induced radiolysis in cells and biofluids, non-septic inflammation, metabolic up-regulation of pro-oxidative metabolic reactions, suppression of the radiosensitive hematopoietic and lymphoid tissues and the damage to gut mucosa and vascular endothelium. While the “second hit” derives from bacterial translocation and spread of the bacterial pathogens and inflammagens through the vascular system leading to septic inflammatory, metabolic responses and a cascade of redox pro-oxidative and adaptive reactions. This sequence of events can create a ground for development of prolonged metabolic, inflammatory, oxidative, nitrative, and carbonyl, electrophilic stress in crucial tissues and thus exacerbate the hARS outcomes. With this perspective, the redox mechanisms, which can mediate the IR-induced protracted oxidative post-translational modification of proteins, oxidation of lipids and carbohydrates and their countermeasures in hARS are subjects of the current review. Potential role of ubiquitous, radioresistant

  9. The Insect Peptide Coprisin Prevents Clostridium difficile-Mediated Acute Inflammation and Mucosal Damage through Selective Antimicrobial Activity▿

    PubMed Central

    Kang, Jin Ku; Hwang, Jae Sam; Nam, Hyo Jung; Ahn, Keun Jae; Seok, Heon; Kim, Sung-Kuk; Yun, Eun Young; Pothoulakis, Charalabos; Lamont, John Thomas; Kim, Ho

    2011-01-01

    Clostridium difficile-associated diarrhea and pseudomembranous colitis are typically treated with vancomycin or metronidazole, but recent increases in relapse incidence and the emergence of drug-resistant strains of C. difficile indicate the need for new antibiotics. We previously isolated coprisin, an antibacterial peptide from Copris tripartitus, a Korean dung beetle, and identified a nine-amino-acid peptide in the α-helical region of it (LLCIALRKK) that had antimicrobial activity (J.-S. Hwang et al., Int. J. Pept., 2009, doi:10.1155/2009/136284). Here, we examined whether treatment with a coprisin analogue (a disulfide dimer of the nine peptides) prevented inflammation and mucosal damage in a mouse model of acute gut inflammation established by administration of antibiotics followed by C. difficile infection. In this model, coprisin treatment significantly ameliorated body weight decreases, improved the survival rate, and decreased mucosal damage and proinflammatory cytokine production. In contrast, the coprisin analogue had no apparent antibiotic activity against commensal bacteria, including Lactobacillus and Bifidobacterium, which are known to inhibit the colonization of C. difficile. The exposure of C. difficile to the coprisin analogue caused a marked increase in nuclear propidium iodide (PI) staining, indicating membrane damage; the staining levels were similar to those seen with bacteria treated with a positive control for membrane disruption (EDTA). In contrast, coprisin analogue treatment did not trigger increases in the nuclear PI staining of Bifidobacterium thermophilum. This observation suggests that the antibiotic activity of the coprisin analogue may occur through specific membrane disruption of C. difficile. Thus, these results indicate that the coprisin analogue may prove useful as a therapeutic agent for C. difficile infection-associated inflammatory diarrhea and pseudomembranous colitis. PMID:21807975

  10. Protective Role of Nuclear Factor E2-Related Factor 2 against Acute Oxidative Stress-Induced Pancreatic β -Cell Damage.

    PubMed

    Fu, Jingqi; Zheng, Hongzhi; Wang, Huihui; Yang, Bei; Zhao, Rui; Lu, Chunwei; Liu, Zhiyuan; Hou, Yongyong; Xu, Yuanyuan; Zhang, Qiang; Qu, Weidong; Pi, Jingbo

    2015-01-01

    Oxidative stress is implicated in the pathogenesis of pancreatic β-cell dysfunction that occurs in both type 1 and type 2 diabetes. Nuclear factor E2-related factor 2 (NRF2) is a master regulator in the cellular adaptive response to oxidative stress. The present study found that MIN6 β-cells with stable knockdown of Nrf2 (Nrf2-KD) and islets isolated from Nrf2-knockout mice expressed substantially reduced levels of antioxidant enzymes in response to a variety of stressors. In scramble MIN6 cells or wild-type islets, acute exposure to oxidative stressors, including hydrogen peroxide (H2O2) and S-nitroso-N-acetylpenicillamine, resulted in cell damage as determined by decrease in cell viability, reduced ATP content, morphology changes of islets, and/or alterations of apoptotic biomarkers in a concentration- and/or time-dependent manner. In contrast, silencing of Nrf2 sensitized MIN6 cells or islets to the damage. In addition, pretreatment of MIN6 β-cells with NRF2 activators, including CDDO-Im, dimethyl fumarate (DMF), and tert-butylhydroquinone (tBHQ), protected the cells from high levels of H2O2-induced cell damage. Given that reactive oxygen species (ROS) are involved in regulating glucose-stimulated insulin secretion (GSIS) and persistent activation of NRF2 blunts glucose-triggered ROS signaling and GSIS, the present study highlights the distinct roles that NRF2 may play in pancreatic β-cell dysfunction that occurs in different stages of diabetes. PMID:25949772

  11. Comparative study of the damage produced by acute ethanol and acetaldehyde treatment in a human fetal hepatic cell line.

    PubMed

    Olivares, I P; Bucio, L; Souza, V; Cárabez, A; Gutiérrez-Ruiz, M C

    1997-06-27

    The effects of acute ethanol and acetaldehyde treatment on cell proliferation, cell adhesion capacity, neutral red incorporation into lysosomes, glutathione content, protein sulfhydryl compounds, lipid peroxidation, inner mitochondrial membrane integrity (MTT test), lactate dehydrogenase activity (LDH) and ultrastructural alterations were investigated in a human fetal hepatic cell line (WRL-68 cells). WRL-68 cells were used, due to the fact that, although this cell line expresses some hepatic characteristics, it does not express alcohol dehydrogenase or cytochrome P450 activity, so it could be a good model to study the effect of the toxic agents per se. Cells were exposed during 120 min with 200 mM ethanol or 10 mM acetaldehyde. Under these conditions, cells presented 100% viability and no morphological alteration was observed by light microscopy. Acetaldehyde-treated cells reduced their proliferative capacity drastically while the ethanol-treated ones presented no difference with control cells. Cell adhesion to substrate, measured as time required to adhere to the substrate and time required to detach from the substrate, was diminished in acetaldehyde WRL-68-treated cells. Cytotoxicity measures as neutral red and MTT test showed that acetaldehyde-treated cells presented more damage than ethanol-treated ones. Cellular respiratory capacity was compromised by acetaldehyde treatment due to 40% less oxygen consumption than control cells. Lipid peroxidation values, measured as malondialdehyde production, were higher in ethanol-treated WRL-68 cells (127%) than in acetaldehyde-treated ones (60%) to control cell values. Lactate dehydrogenase activity (LDH) in extracellular media of ethanol-treated cells presented the highest values. GSH content was reduced 95% and thiol protein content was diminished severely in acetaldehyde-treated cells. Transmission electron microscopy showed more ultrastructural alterations in cells treated with acetaldehyde. The results indicate that

  12. Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

    PubMed

    Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2014-06-01

    Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration. PMID:24338618

  13. Acute systemic DNA damage in youth does not impair immune defense with aging.

    PubMed

    Pugh, Jason L; Foster, Sarah A; Sukhina, Alona S; Petravic, Janka; Uhrlaub, Jennifer L; Padilla-Torres, Jose; Hayashi, Tomonori; Nakachi, Kei; Smithey, Megan J; Nikolich-Žugich, Janko

    2016-08-01

    Aging-related decline in immunity is believed to be the main driver behind decreased vaccine efficacy and reduced resistance to infections in older adults. Unrepaired DNA damage is known to precipitate cellular senescence, which was hypothesized to be the underlying cause of certain age-related phenotypes. Consistent with this, some hallmarks of immune aging were more prevalent in individuals exposed to whole-body irradiation (WBI), which leaves no anatomical repository of undamaged hematopoietic cells. To decisively test whether and to what extent WBI in youth will leave a mark on the immune system as it ages, we exposed young male C57BL/6 mice to sublethal WBI (0.5-4 Gy), mimicking human survivor exposure during nuclear catastrophe. We followed lymphocyte homeostasis thorough the lifespan, response to vaccination, and ability to resist lethal viral challenge in the old age. None of the irradiated groups showed significant differences compared with mock-irradiated (0 Gy) animals for the parameters measured. Even the mice that received the highest dose of sublethal WBI in youth (4 Gy) exhibited equilibrated lymphocyte homeostasis, robust T- and B-cell responses to live attenuated West Nile virus (WNV) vaccine and full survival following vaccination upon lethal WNV challenge. Therefore, a single dose of nonlethal WBI in youth, resulting in widespread DNA damage and repopulation stress in hematopoietic cells, leaves no significant trace of increased immune aging in a lethal vaccine challenge model. PMID:27072188

  14. Acute LVOT Obstruction with a Carbomedics Mechanical Valve Prosthesis.

    PubMed

    Alsidawi, Said; Joyce, David L; Malouf, Joseph F; Nkomo, Vuyisile T

    2016-06-01

    A 62-year-old female with severe symptomatic rheumatic mitral stenosis was referred for mitral valve replacement. A 27-mm Carbomedics mechanical mitral valve was placed using everting sutures. As the patient was weaned off cardiopulmonary bypass, she became hemodynamically unstable. Intraoperative transesophageal echocardiogram revealed a significant drop in left ventricular function along with severe LVOT obstruction. The Carbomedics prosthesis was replaced by a 27-mm St. Jude mechanical valve using noneverting sutures which relieved the LVOT obstruction. doi: 10.1111/jocs.12749 (J Card Surg 2016;31:376-379). PMID:27087635

  15. Mechanisms of surface-tension-induced epithelial cell damage in a model of pulmonary airway reopening.

    PubMed

    Bilek, Anastacia M; Dee, Kay C; Gaver, Donald P

    2003-02-01

    Airway collapse and reopening due to mechanical ventilation exerts mechanical stress on airway walls and injures surfactant-compromised lungs. The reopening of a collapsed airway was modeled experimentally and computationally by the progression of a semi-infinite bubble in a narrow fluid-occluded channel. The extent of injury caused by bubble progression to pulmonary epithelial cells lining the channel was evaluated. Counterintuitively, cell damage increased with decreasing opening velocity. The presence of pulmonary surfactant, Infasurf, completely abated the injury. These results support the hypotheses that mechanical stresses associated with airway reopening injure pulmonary epithelial cells and that pulmonary surfactant protects the epithelium from this injury. Computational simulations identified the magnitudes of components of the stress cycle associated with airway reopening (shear stress, pressure, shear stress gradient, or pressure gradient) that may be injurious to the epithelial cells. By comparing these magnitudes to the observed damage, we conclude that the steep pressure gradient near the bubble front was the most likely cause of the observed cellular damage. PMID:12433851

  16. 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.

  17. Second-generation locking mechanisms and ethylene oxide sterilization reduce tibial insert backside damage in total knee arthroplasty.

    PubMed

    Azzam, Michael G; Roy, Marcel E; Whiteside, Leo A

    2011-06-01

    This study evaluated the effects of polyethylene quality and locking mechanism on damage to the nonarticulating (backside) surface of retrieved tibial inserts in total knee arthroplasty. Inserts with peripheral capture (PC) locking mechanisms and ethylene oxide (EtO)-sterilized polyethylene were hypothesized to prevent major backside damage. A total of 156 inserts were sorted by locking mechanism and sterilization method and analyzed by damage scoring methods. Ninety-seven specimens exhibited burnishing. Significant positive linear correlations were observed between damage score and age in vivo for all combinations, but damage occurred at a significantly lower rate for second-generation PC implants with EtO sterilization. Most specimens in this group were undamaged (46/72), with others exhibiting only burnishing. Sex, body mass index, and weight did not influence backside damage. PMID:20541356

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

    NASA Astrophysics Data System (ADS)

    Güney, D.; Aydin, E.; Öztürk, B.

    2015-07-01

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

  19. Mechanisms of Focused Ion Beam Implantation Damage and Recovery in Si

    NASA Astrophysics Data System (ADS)

    Balasubramanian, G. P. S.; Hull, R.

    2016-06-01

    The ion current density in focused ion beam (FIB) systems, 0.1-10 A cm-2, is at least three orders of magnitude greater than that in commercial broad ion beam implanters. This large difference in ion current density is expected to strongly affect the damage recovery dynamics. In this work, we study the ion implantation damage and recovery of Si(100) substrates implanted with 1 × 1012-5 × 1015 Si cm-2 fluences of 60-keV Si2+ at normal incidence in a mass-selecting FIB. Additionally, damage and recovery in different broad ion beam implants of 60-keV Si+ were studied for a comparison. For recovering implantation damage, specimens were annealed for different times at 730-900°C in an ultra-high purity nitrogen ambient, and for characterizing damage and recovery, Raman spectroscopy at wavelengths 405 nm and 514 nm was carried out. Raman measurements comprised of measurements of crystalline Si (c-Si) peak height of the peak at 520 cm-1, and the peak shift relative to that of un-implanted reference Si. Our measurements of structural damage—calculated from the attenuation in the c-Si peak heights for the implants relative to that of unimplanted Si(100)—indicates that the FIB implantations lead to a greater as-implanted damage but also typically lead to a better recovery than that for the commercial broad-area implants. The underlying mechanisms for these observations are discussed.

  20. The relationships between RBE and LET for different types of lethal damage in mammalian cells: Biophysical and molecular mechanisms

    SciTech Connect

    Barendsen, G.W.

    1994-09-01

    The relative biological effective (RBE) of radiations as a function of linear energy transfer (LET) is analyzed for different types of damage causing reproductive death of mammalian cells. Survival curves are evaluated assuming a linear-quadratic dose dependence of the induction of reproductive death of cells. The linear term represents damage from single particle tracks and the quadratic term represents damage due to interaction of lesions from independent tracks. Differences and similarities are discussed of the LET dependence of single-track lethal damage, sublethal damage, potentially lethal damage and DNA double-strand breaks. The RBE-LET relationships are correlated with local energy deposition in small regions of the cells. The analysis shows that single-track lethal damage is composed in part of a type of damage that is not repaired by delayed plating and is very strongly dependent on LET with maximum RBE values up to 20, while another component consists of potentially lethal damage that is weakly dependent on LET with maximum RBE values less than 3. Potentially lethal damage and sublethal damage depend similarly on LET as DNA double-strand breaks. The sector of single-track damage which is not repaired by delayed plating is hypothesized to be caused through a repair-exchange mechanism involving two double-strand breaks induced close together. The identification of these different components of damage leads to an interpretation of differences in radiosensitivity and in RBE-LET relationships among various types of cells. 68 refs., 4 figs., 1 tab.

  1. The cardiac surgery-associated neutrophil gelatinase-associated lipocalin (CSA-NGAL) score: A potential tool to monitor acute tubular damage.

    PubMed

    de Geus, Hilde R H; Ronco, Claudio; Haase, Michael; Jacob, Laurent; Lewington, Andrew; Vincent, Jean-Louis

    2016-06-01

    Acute kidney injury (AKI), defined as a rise in serum creatinine (functional AKI), is a frequent complication after cardiac surgery. The expression pattern of acute tubular damage biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) has been shown to precede functional AKI and, therefore, may be useful to identify very early tubular damage. The term subclinical AKI represents acute tubular damage in the absence of functional AKI (biomarker positivity without a rise in serum creatinine) and affects hard outcome measures. This potentiates an tubular-damage-based identification of renal injury, which may guide clinical management, allowing for very early preventive-protective strategies. The aim of this paper was to review the current available evidence on NGAL applicability in adult cardiac surgery patients and combine this knowledge with the expert consensus of the authors to generate an NGAL based tubular damage score: The cardiac surgery-associated NGAL Score (CSA-NGAL score). The CSA-NGAL score might be the tool needed to improve awareness and enable interventions to possibly modify these detrimental outcomes. In boldly doing so, it is intended to introduce a different approach in study designs, which will undoubtedly expand our knowledge and will hopefully move the AKI biomarker field forward. PMID:26952930

  2. Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF.

    PubMed

    Adibzadeh, F; van Rhoon, G C; Verduijn, G M; Naus-Postema, N C; Paulides, M M

    2016-01-21

    The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg(-1)) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients' feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R (2) =  0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature simulations as a

  3. Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF

    NASA Astrophysics Data System (ADS)

    Adibzadeh, F.; van Rhoon, G. C.; Verduijn, G. M.; Naus-Postema, N. C.; Paulides, M. M.

    2016-01-01

    The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg-1) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients’ feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R 2  =  0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature

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

    NASA Astrophysics Data System (ADS)

    Shao, Junfeng; Guo, Jin; Wang, Tingfeng

    2013-09-01

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

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

    PubMed

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

    2016-05-01

    A great deal of literature is available regarding the environmental and ecological effects of rare earth element pollution on plants. These studies have shown that excess lanthanum (La) (III) in the environment can inhibit plant growth and even cause plant death. Moreover, inhibition of plant photosynthesis is known to be one of the physiological bases of these damages. However, the mechanism responsible for these effects is still unclear. In this study, the mechanism of La(III)-induced damage to plant photosynthesis was clarified from the viewpoint of the chloroplast ultrastructure, the contents of chloroplast mineral elements and chlorophyll, the transcription of chloroplast ATPase subunits and chloroplast Mg(2+)-ATPase activity, in which rice was selected as a study object. Following treatment with low level of La(III), the chloroplast ultrastructure of rice was not changed, and the contents of chloroplast mineral elements (Mg, P, K, Ca, Mn, Fe, Ni, Cu, and Zn) increased, but the chlorophyll content did not change significantly. Moreover, the transcription of chloroplast ATPase subunits, chloroplast Mg(2+)-ATPase activity, the net photosynthetic rate and growth indices increased. Following treatment with high levels of La(III), the chloroplast ultrastructure was damaged, chloroplast mineral elements (except Cu and Zn) and chlorophyll contents decreased, and the transcription of chloroplast ATPase subunits, chloroplast Mg(2+)-ATPase activity, the net photosynthetic rate and growth indices decreased. Based on these results, a possible mechanism of La(III)-induced damage to plant photosynthesis was proposed to provide a reference for scientific evaluation of the potential ecological risk of rare earth elements in the environment. PMID:26802561

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

    PubMed

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

    2014-01-01

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

  7. Thermomigration: An experimental damage mechanics study on nanoelectronic lead free solder alloys

    NASA Astrophysics Data System (ADS)

    Abdul Hamid, Mohd Foad

    This dissertation focuses on experimental study of thermomigration in lead-free solder alloys. Thermomigration in microelectronic solder joints was not a concern until significant miniaturization of electronics devices required to run high current densities with smaller solder joint sizes. High current density induces electromigration and Joule heating at the same time. The imbalance of Joule heating generated at top and bottom of solder joint causes a temperature gradient which is large enough to induce thermomigration damage. In the literature, most studies report electromigration induced damage without considering the influence of thermomigration, thus the effect of electromigration and thermomigration can not be individually identified. This dissertation studies the experimental damage mechanics of thermomigration without electromigration by studying formation and destruction of intermetallic compound, and vacancy migration due to diffusion driving forces. Microstructural degradation and hardness testing were used to quantify thermomigration induced damage. After studying material science and physics behind the thermomigration process, using test vehicles, the combined effects of electromigration and thermomigration were studied experimentally. The studies were repeated at a subzero temperatures to see the effect of low temperature on thermomigration and electromigration, and reliability of nanoelectronic solder joints. A new time to failure equation is proposed to show a threshold temperature below which diffusion slows down significantly. By ensuring the solder operating temperature is well kept below the threshold value by proper thermal management, the solder joint life can be extended.

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

    PubMed

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

    2016-10-01

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

  9. Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema.

    PubMed

    Desai, Ketaki V; Laine, Glen A; Stewart, Randolph H; Cox, Charles S; Quick, Christopher M; Allen, Steven J; Fischer, Uwe M

    2008-06-01

    Myocardial interstitial edema forms as a result of several disease states and clinical interventions. Acute myocardial interstitial edema is associated with compromised systolic and diastolic cardiac function and increased stiffness of the left ventricular chamber. Formation of chronic myocardial interstitial edema results in deposition of interstitial collagen, which causes interstitial fibrosis. To assess the effect of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. Acute myocardial edema was generated by coronary sinus pressure elevation, while chronic myocardial edema was generated by chronic pulmonary artery banding. The pressure-volume relationships of the left ventricular myocardial interstitium and left ventricular chamber for control animals were compared with acutely and chronically edematous animals. Collagen content of nonedematous and chronically edematous animals was also compared. Generating acute myocardial interstitial edema resulted in decreased left ventricular chamber compliance compared with nonedematous animals. With chronic edema, the primary form of collagen changed from type I to III. Left ventricular chamber compliance in animals made chronically edematous was significantly higher than nonedematous animals. The change in primary collagen type secondary to chronic left ventricular myocardial interstitial edema provides direct evidence for structural remodeling. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus preserving cardiac function over a wide range of interstitial fluid pressures. PMID:18375722

  10. Acute dissection of a Contegra conduit: a rare mechanism of failure.

    PubMed

    Kavarana, Minoo N; Dorfman, Adam L; Agarwal, Prachi P; Bove, Edward L

    2010-09-01

    The Contegra (Medtronic Inc, Minneapolis, MN) bovine jugular vein conduit has been used with increasing frequency in congenital heart disease for the reconstruction of the right ventricular outflow tract. In this report, we describe a mechanism for conduit failure secondary to an acute dissection of the inner neointimal peel from the conduit wall. PMID:20732536

  11. “Missing clot” during mechanical thrombectomy in acute stroke using Solitaire stent retrieval system

    PubMed Central

    Huded, Vikram; Nambiar, Vivek; De Souza, Romnesh; Bohra, Vikram; Ramankutty, Ritesh

    2016-01-01

    Stent retrieval system is an established treatment modality in acute ischemic stroke with large vessel occlusion. Here, we describe a complication which occurred during mechanical thrombectomy in three cases where the clot dislodged during retrieval. There was a possibility of the clot getting reinjected into the artery with possible dire consequences. PMID:27293350

  12. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    SciTech Connect

    Qu, Wei Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

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

    PubMed

    Smith, Lincoln; Beck, John J

    2015-09-01

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

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

    NASA Technical Reports Server (NTRS)

    Norman, Timothy L.; Anglin, Colin

    1995-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Franck, Christian; Estrada, Jonathan

    2015-11-01

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

  16. Modifications of lung clearance mechanisms by acute influenza A infection

    SciTech Connect

    Levandowski, R.A.; Gerrity, T.R.; Garrard, C.S.

    1985-10-01

    Four volunteers with naturally acquired, culture-proved influenza A infection inhaled a radiolabeled aerosol to permit investigation of lung mucociliary clearance mechanisms during and after symptomatic illness. Mucus transport in the trachea was undetectable when monitored with an external multidetector probe within 48 hours of the onset of the illness, but was found at a normal velocity by 1 week in three of the four subjects. In two volunteers who coughed 23 to 48 times during the 4.5-hour observation period, whole lung clearance was as fast within the first 48 hours of illness as during health 3 months later in spite of the absence of measurable tracheal mucus transport. Conversely, in spite of the return 1 week later of mucus transport at velocities expected in the trachea, whole lung clearance for the 4.5-hour period was slowed in two volunteers who coughed less than once an hour. The data offer evidence that cough is important in maintaining lung clearance for at least several days after symptomatic influenza A infection when other mechanisms that depend on ciliary function are severely deficient.

  17. Surgical treatment of early acute thrombosis of mechanical mitral prosthesis.

    PubMed

    Jiang, Shengli; Zhang, Tao; Ren, Chonglei; Wang, Yao

    2010-10-01

    Prosthetic valve thrombosis is a rare but life threatening complication of mechanical heart valve prosthesis. A 44-year-old woman diagnosed with rheumatic heart disease with severe mitral valve stenosis, moderate tricuspid valve insufficiency, and atrial fibrillation underwent transseptal mitral valve replacement and tricuspid valvuloplasty in our department. Heparin and warfarin were routinely used postoperatively. Although the international normalized ratio (INR), activated partial thromboplastin time ratio, and platelet count were satisfactory, the patient presented with severe dyspnea suddenly 10 days after discharge; echocardiogram showed that the prosthetic posterior leaflet was immobile. The patient suffered cardiac arrest suddenly during the examination and cardiopulmonary resuscitation was carried out successfully. Emergent surgery was performed, confirming the prosthetic valve thrombosis. The prosthetic valve was replaced with another mechanical prosthesis. The patient recovered smoothly and was discharged 14 days later with atrial fibrillation. During the 12-months follow-up period, her prosthetic valve and heart function were normal with INR around 3.0. This case highlights the need for awareness among clinicians for the possibility of valve thrombosis in the early postoperative period. PMID:20961833

  18. Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism.

    PubMed

    Chousterman, Benjamin G; Boissonnas, Alexandre; Poupel, Lucie; Baudesson de Chanville, Camille; Adam, Julien; Tabibzadeh, Nahid; Licata, Fabrice; Lukaszewicz, Anne-Claire; Lombès, Amélie; Deterre, Philippe; Payen, Didier; Combadière, Christophe

    2016-03-01

    Monocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6C(high) monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro-adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis. PMID:26160897

  19. Improved clinicopathologic assessments of acute liver damage due to trauma in Indian ring-necked parakeets (Psittacula krameri manillensis).

    PubMed

    Williams, Susan M; Holthaus, Lisa; Barron, Heather Wilson; Divers, Stephen J; McBride, Michael; Almy, Frederic; Bush, Sharon; Latimer, Kenneth S

    2012-06-01

    Increased activities of certain biochemical enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], alkaline phosphatase [ALP]) have been associated with blunt liver injury in many species. To evaluate changes in plasma hepatic biochemical parameters in acute avian liver disease caused by trauma and to compare biochemical changes with histologic lesions in hepatic parenchyma, 30 healthy fasted Indian ring-necked parakeets (Psittacula krameri manillensis) were divided into 2 groups, and traumatic liver injury was caused by endoscopic liver biopsy (group 1) or by liver biopsy and crushing injury to the hepatic parenchyma with endoscopic forceps (group 2) in anesthetized birds. Blood samples were collected at baseline and at 12, 24, 36, 48, 60, 72, 84, 96, 108, and 120 hours in alternate groups to compare analyte values after injury with those at baseline. Results showed consistently decreased plasma ALP activity (excluding 1 time point) throughout the study, which was thought to be associated with isoflurane administration. Plasma glutamate dehydrogenase activity initially increased but rapidly declined thereafter and was attributed to acute focal hepatocellular injury. In both groups, increases in plasma AST, ALT, and LDH activities was most likely caused by muscle injury because creatine kinase activity was concurrently increased. Compared with baseline values, bile acid concentration and y-glutamyl transferase activity were not affected by liver biopsy or crush injury. Plasma sorbitol dehydrogenase activity was the most specific indicator of liver injury in both groups. Histologic changes correlated poorly with biochemical results, possibly because the small area of hepatic parenchyma that was damaged did not affect enzyme values substantially. PMID:22872978

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

    PubMed Central

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

    2013-01-01

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

  1. Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair.

    PubMed

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

    2016-01-28

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

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

    PubMed

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

    2015-11-01

    Synaptic spine loss is one of the major preceding consequences of stroke damages, but its underlying molecular mechanisms remain unknown. Here, we report that a direct interaction of DAPK1 with Tau causes spine loss and subsequently neuronal death in a mouse model with stroke. We found that DAPK1 phosphorylates Tau protein at Ser262 (pS(262)) in cortical neurons of stroke mice. Either genetic deletion of DAPK1 kinase domain (KD) in mice (DAPK1-KD(-/-)) or blocking DAPK1-Tau interaction by systematic application of a membrane permeable peptide protects spine damages and improves neurological functions against stroke insults. Thus, disruption of DAPK1-Tau interaction is a promising strategy in clinical management of stroke. PMID:25995053

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

    PubMed Central

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

    2015-01-01

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

  4. Global Sensitivity Analysis of a Mathematical Model of Acute Inflammation Identifies Nonlinear Dependence of Cumulative Tissue Damage on Host Interleukin-6 Responses

    PubMed Central

    Mathew, Shibin; Bartels, John; Banerjee, Ipsita; Vodovotz, Yoram

    2014-01-01

    The precise inflammatory role of the cytokine interleukin (IL)-6 and its utility as a biomarker or therapeutic target have been the source of much debate, presumably due to the complex pro- and anti-inflammatory effects of this cytokine. We previously developed a nonlinear ordinary differential equation (ODE) model to explain the dynamics of endotoxin (lipopolysaccharide; LPS)-induced acute inflammation and associated whole-animal damage/dysfunction (a proxy for the health of the organism), along with the inflammatory mediators tumor necrosis factor (TNF)-α, IL-6, IL-10, and nitric oxide (NO). The model was partially calibrated using data from endotoxemic C57Bl/6 mice. Herein, we investigated the sensitivity of the area under the damage curve (AUCD) to the 51 rate parameters of the ODE model for different levels of simulated LPS challenges using a global sensitivity approach called Random Sampling High Dimensional Model Representation (RS-HDMR). We explored sufficient parametric Monte Carlo samples to generate the variance-based Sobol' global sensitivity indices, and found that inflammatory damage was highly sensitive to the parameters affecting the activity of IL-6 during the different stages of acute inflammation. The AUCIL6 showed a bimodal distribution, with the lower peak representing healthy response and the higher peak representing sustained inflammation. Damage was minimal at low AUCIL6, giving rise to a healthy response. In contrast, intermediate levels of AUCIL6 resulted in high damage, and this was due to the insufficiency of damage recovery driven by anti-inflammatory responses and the activation of positive feedback sustained by IL-6. At high AUCIL6, damage recovery was interestingly restored in some population of simulated animals due to the NO-mediated anti-inflammatory responses. These observations suggest that the host's health status during acute inflammation depends in a nonlinear fashion on the magnitude of the inflammatory stimulus, on the

  5. The serpentine path to a novel mechanism-based inhibitor of acute inflammatory lung injury

    PubMed Central

    2014-01-01

    The Comroe lecture on which this review is based described my research path during the past 45 years, beginning with studies of oxidant stress (hyperoxia) and eventuating in the discovery of a synthetic inhibitor of phospholipase A2 activity (called MJ33) that prevents acute lung injury in mice exposed to lipopolysaccharide. In between were studies of lung ischemia, lung surfactant metabolism, the protein peroxiredoxin 6 and its phospholipase A2 activity, and mechanisms for NADPH oxidase activation. These seemingly unrelated research activities provided the nexus for identification of a novel target and a potentially novel therapeutic agent for prevention or treatment of acute lung injury. PMID:24744383

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  9. Acoustic emission data clustering for analyzing damage mechanisms in glass/polyester composites under mode I delamination

    NASA Astrophysics Data System (ADS)

    Oskouei, Amir Refahi; Khamedi, Ramin; Heidary, Hossein; Farajpur, Mehdi

    2012-05-01

    In using acoustic emissions (AE) for mechanical diagnostics, one major problem is the discrimination of events due to different types of damage occurring during loading of composite materials. In the present work, a procedure for the investigation of local damage in composite materials based on the analysis of the signals of Acoustic Emission (AE) is presented. One of the remaining problems is the analysis of the AE signals in order to identify the most critical damage mechanisms. In this work, unsupervised pattern recognition analyses (fuzzyc-means clustering) associated with a principal component analysis are the tools that are used for the classification of the monitored AE events. A cluster analysis of AE data is achieved and the resulting clusters are correlated to the damage mechanisms of the material under investigation. Time domain methods are used to determine new relevant descriptors to be introduced in the classification process in order to improve the characterization and the discrimination of the damage mechanisms. The results show that there is a good fitness between clustering groups and damage mechanisms. Also, AE with clustering procedure are as effective tools that provide a better discrimination of damage mechanisms in glass/polyester composite materials.

  10. Feedback inhibition of ENaC: Acute and chronic mechanisms

    PubMed Central

    Patel, Ankit B; Yang, Lei; Deng, Su; Palmer, Lawrence G

    2014-01-01

    Intracellular [Na+] ([Na+]i) modulates the activity of the epithelial Na channel (ENaC) to help prevent cell swelling and regulate epithelial Na+ transport, but the underlying mechanisms remain unclear. We show here that short-term (60–80 min) incubation of ENaC-expressing oocytes in high Na+ results in a 75% decrease in channel activity. When the β subunit was truncated, corresponding to a gain-of-function mutation found in Liddle's syndrome, the same maneuver reduced activity by 45% despite a larger increase in [Na+]i. In both cases the inhibition occurred with little to no change in cell-surface expression of γENaC. Long-term incubation (18 hours) in high Na+ reduced activity by 92% and 75% in wild-type channels and Liddle's mutant, respectively, with concomitant 70% and 52% decreases in cell-surface γENaC. In the presence of Brefeldin A to inhibit forward protein trafficking, high-Na+ incubation decreased wt ENaC activity by 52% and 88% after 4 and 8 hour incubations, respectively. Cleaved γENaC at the cell surface had lifetimes at the surface of 6 hrs in low Na+ and 4 hrs in high Na+, suggesting that [Na+]i increased the rate of retrieval of cleaved γ ENaC by 50%. This implies that enhanced retrieval of ENaC channels at the cell surface accounts for part, but not all, of the downregulation of ENaC activity shown with chronic increases in [Na+]i. PMID:25483587

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

    SciTech Connect

    Fok, Alex

    2013-10-30

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

  12. Effects of Tissue Mechanical Properties on Susceptibility to Histotripsy-induced Tissue Damage

    PubMed Central

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

    2014-01-01

    Histotripsy is a non-invasive tissue ablation method capable of fractionating tissue by controlling acoustic cavitation. To determine the fractionation susceptibility of various tissues, we investigated histotripsy-induced damage on tissue phantoms and ex vivo tissues with different mechanical strengths. A histotripsy bubble cloud was formed at tissue phantom surfaces using 5-cycle long ultrasound pulses with peak negative pressure of 18 MPa and PRFs of 10, 100, and 1000 Hz. Results showed significantly smaller lesions were generated in tissue phantoms of higher mechanical strength. Histotripsy was also applied to 43 different ex vivo porcine tissues with a wide range of mechanical properties. Gross morphology demonstrated stronger tissues with higher ultimate stress, higher density, and lower water content were more resistant to histotripsy damage in comparison to weaker tissues. Based on these results, a self-limiting vessel-sparing treatment strategy was developed in an attempt to preserve major vessels while fractionating the surrounding target tissue. This strategy was tested in porcine liver in vivo. After treatment, major hepatic blood vessels and bile ducts remained intact within a completely fractionated liver volume. These results identify varying susceptibilities of tissues to histotripsy therapy and provide a rational basis to optimize histotripsy parameters for treatment of specific tissues. PMID:24351722

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  18. Mechanical thrombectomy in pediatric acute ischemic stroke: Clinical outcomes and literature review.

    PubMed

    Madaelil, Thomas P; Kansagra, Akash P; Cross, DeWitte T; Moran, Christopher J; Derdeyn, Colin P

    2016-08-01

    There are limited data on outcomes of mechanical thrombectomy for pediatric stroke using modern devices. In this study, we report two cases of pediatric acute ischemic stroke treated with mechanical thrombectomy, both with good angiographic result (TICI 3) and clinical outcome (no neurological deficits at 90 days). In addition, we conducted a literature review of all previously reported cases describing the use of modern thrombectomy devices. Including our two cases, the aggregate rate of partial or complete vessel recanalization was 100% (22/22), and the aggregate rate of favorable clinical outcome was 91% (20/22). This preliminary evidence suggests that mechanical thrombectomy with modern devices may be a safe and effective treatment option in pediatric patients with acute ischemic stroke. PMID:26945589

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

    PubMed

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

    2015-10-01

    The increased incidence of solar ultraviolet B (UVB) radiation has been proposed as an environmental stressor, which may help to explain the enigmatic decline of amphibian populations worldwide. Despite growing knowledge regarding the UV-induced biological effects in several amphibian models, little is known about the efficacy of DNA repair pathways. In addition, little attention has been given to the interplay between these molecular mechanisms with other physiological strategies that avoid the damage induced by sunlight. Here, DNA lesions induced by environmental doses of solar UVB and UVA radiation were detected in genomic DNA samples of treefrog tadpoles (Hypsiboas pulchellus) and their DNA repair activity was evaluated. These data were complemented by monitoring the induction of apoptosis in blood cells and tadpole survival. Furthermore, the tadpoles' ability to perceive and escape from UV wavelengths was evaluated as an additional strategy of photoprotection. The results show that tadpoles are very sensitive to UVB light, which could be explained by the slow DNA repair rates for both cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6,4) pyrimidone photoproducts (6,4PPs). However, they were resistant to UVA, probably as a result of the activation of photolyases during UVA irradiation. Surprisingly, a sensory mechanism that triggers their escape from UVB and UVA light avoids the generation of DNA damage and helps to maintain the genomic integrity. This work demonstrates the genotoxic impact of both UVB and UVA radiation on tadpoles and emphasizes the importance of the interplay between molecular and sensory mechanisms to minimize the damage caused by sunlight. PMID:26447197

  20. Pro-oxidant Induced DNA Damage in Human Lymphoblastoid Cells: Homeostatic Mechanisms of Genotoxic Tolerance

    PubMed Central

    Seager, Anna L.

    2012-01-01

    Oxidative stress contributes to many disease etiologies including ageing, neurodegeneration, and cancer, partly through DNA damage induction (genotoxicity). Understanding the i nteractions of free radicals with DNA is fundamental to discern mutation risks. In genetic toxicology, regulatory authorities consider that most genotoxins exhibit a linear relationship between dose and mutagenic response. Yet, homeostatic mechanisms, including DNA repair, that allow cells to tolerate low levels of genotoxic exposure exist. Acceptance of thresholds for genotoxicity has widespread consequences in terms of understanding cancer risk and regulating human exposure to chemicals/drugs. Three pro-oxidant chemicals, hydrogen peroxide (H2O2), potassium bromate (KBrO3), and menadione, were examined for low dose-response curves in human lymphoblastoid cells. DNA repair and antioxidant capacity were assessed as possible threshold mechanisms. H2O2 and KBrO3, but not menadione, exhibited thresholded responses, containing a range of nongenotoxic low doses. Levels of the DNA glycosylase 8-oxoguanine glycosylase were unchanged in response to pro- oxidant stress. DNA repair–focused gene expression arrays reported changes in ATM and BRCA1, involved in double-strand break repair, in response to low-dose pro-oxidant exposure; however, these alterations were not substantiated at the protein level. Determination of oxidatively induced DNA damage in H2O2-treated AHH-1 cells reported accumulation of thymine glycol above the genotoxic threshold. Further, the H2O2 dose-response curve was shifted by modulating the antioxidant glutathione. Hence, observed pro- oxidant thresholds were due to protective capacities of base excision repair enzymes and antioxidants against DNA damage, highlighting the importance of homeostatic mechanisms in “genotoxic tolerance.” PMID:22539617

  1. Flaxseed Mitigates Acute Oxidative Lung Damage in a Mouse Model of Repeated Radiation and Hyperoxia Exposure Associated with Space Exploration

    PubMed Central

    Pietrofesa, Ralph A.; Solomides, Charalambos C.; Christofidou-Solomidou, Melpo

    2015-01-01

    Background Spaceflight missions may require crewmembers to conduct extravehicular activities (EVA). Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours and be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health. We have developed a mouse model of total body radiation and hyperoxia exposure and identified acute damage of lung tissues. In the current study we evaluated the usefulness of dietary flaxseed (FS) as a countermeasure agent for such double-hit exposures. Methods We evaluated lung tissue changes 2 weeks post-initiation of exposure challenges. Mouse cohorts (n=5/group) were pre-fed diets containing either 0% FS or 10% FS for 3 weeks and exposed to: a) normoxia (Untreated); b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) 3 times per week for 2 consecutive weeks, where 8-hour hyperoxia treatments were spanned by normoxic intervals. Results At 2 weeks post challenge, while control-diet fed mice developed significant lung injury and inflammation across all challenges, FS protected lung tissues by decreasing bronchoalveolar lavage fluid (BALF) neutrophils (p<0.003) and protein levels, oxidative tissue damage, as determined by levels of malondialdehyde (MDA) (p<0.008) and nitrosative stress as determined by nitrite levels. Lung hydroxyproline levels, a measure of lung fibrosis, were significantly elevated in mice fed 0% FS (p<0.01) and exposed to hyperoxia/radiation or the combination treatment, but not in FS-fed mice. FS also decreased levels of a pro-inflammatory, pro-fibrogenic cytokine (TGF-β1) gene expression levels in lung. Conclusion Flaxseed mitigated adverse effects in lung of repeat exposures to radiation/hyperoxia. This data will provide useful information in the design of countermeasures to early

  2. [Non-invasive mechanical ventilation in the treatment of acute heart failure].

    PubMed

    Alfonso Megido, Joaquín; González Franco, Alvaro

    2014-03-01

    When acute heart failure progresses and there is acute cardiogenic pulmonary edema, routine therapeutic measures should be accompanied by other measures that help to correct oxygenation of the patient. The final and most drastic step is mechanical ventilation. Non-invasive ventilation has been developed in the last few years as a method that attempts to improve oxygenation without the need for intubation, thus, in theory, reducing morbidity and mortality in these patients. The present article describes the controversies surrounding the results of this technique and discusses its indications. The article also discusses how to start non-invasive ventilation in patients with acute pulmonary edema from a practical point of view. PMID:24930085

  3. TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis.

    PubMed

    Xu, Chang; Chang, Anthony; Hack, Bradley K; Eadon, Michael T; Alper, Seth L; Cunningham, Patrick N

    2014-01-01

    Severe sepsis is often accompanied by acute kidney injury (AKI) and albuminuria. Here we studied whether the AKI and albuminuria associated with lipopolysaccharide (LPS) treatment in mice reflects impairment of the glomerular endothelium with its associated endothelial surface layer. LPS treatment decreased the abundance of endothelial surface layer heparan sulfate proteoglycans and sialic acid, and led to albuminuria likely reflecting altered glomerular filtration permselectivity. LPS treatment decreased the glomerular filtration rate (GFR), while also causing significant ultrastructural alterations in the glomerular endothelium. The density of glomerular endothelial cell fenestrae was 5-fold lower, whereas the average fenestrae diameter was 3-fold higher in LPS-treated than in control mice. The effects of LPS on the glomerular endothelial surface layer, endothelial cell fenestrae, GFR, and albuminuria were diminished in TNF receptor 1 (TNFR1) knockout mice, suggesting that these LPS effects are mediated by TNF-α activation of TNFR1. Indeed, intravenous administration of TNF decreased GFR and led to loss of glomerular endothelial cell fenestrae, increased fenestrae diameter, and damage to the glomerular endothelial surface layer. LPS treatment decreased kidney expression of vascular endothelial growth factor (VEGF). Thus, our findings confirm the important role of glomerular endothelial injury, possibly by a decreased VEGF level, in the development and progression of AKI and albuminuria in the LPS model of sepsis in the mouse. PMID:23903370

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

    NASA Astrophysics Data System (ADS)

    Chen, Ming

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

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

    PubMed

    Ponomarenko, O V

    2015-07-01

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

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

    NASA Astrophysics Data System (ADS)

    Ryu, Jaejoong

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

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

    SciTech Connect

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

    2009-01-23

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  9. Molecular mechanisms of DNA damage recognition for mammalian nucleotide excision repair.

    PubMed

    Sugasawa, Kaoru

    2016-08-01

    For faithful DNA repair, it is crucial for cells to locate lesions precisely within the vast genome. In the mammalian global genomic nucleotide excision repair (NER) pathway, this difficult task is accomplished through multiple steps, in which the xeroderma pigmentosum group C (XPC) protein complex plays a central role. XPC senses the presence of oscillating 'normal' bases in the DNA duplex, and its binding properties contribute to the extremely broad substrate specificity of NER. Unlike XPC, which acts as a versatile sensor of DNA helical distortion, the UV-damaged DNA-binding protein (UV-DDB) is more specialized, recognizing UV-induced photolesions and facilitating recruitment of XPC. Recent single-molecule analyses and structural studies have advanced our understanding of how UV-DDB finds its targets, particularly in the context of chromatin. After XPC binds DNA, it is necessary to verify the presence of damage in order to avoid potentially deleterious incisions at damage-free sites. Accumulating evidence suggests that XPA and the helicase activity of transcription factor IIH (TFIIH) cooperate to verify abnormalities in DNA chemistry. This chapter reviews recent findings about the mechanisms underlying the efficiency, versatility, and accuracy of NER. PMID:27264556

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    PubMed

    Beutel, Bryan G; Kennedy, Oran D

    2015-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  13. Electron irradiation-induced change of structure and damage mechanisms in multi-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Yang, Jian-Qun; Li, Xing-Ji; Liu, Chao-Ming; Ma, Guo-Liang; Gao, Feng

    2015-11-01

    Owing to their unique structure and excellent electrical property, carbon nanotubes (CNTs) as an ideal candidate for making future electronic components have great application potentiality. In order to meet the requirements for space application in electronic components, it is necessary to study structural changes and damage mechanisms of multi-walled carbon nanotubes (MWCNTs), caused by the irradiations of 70 and 110 keV electrons. In the paper, the changes of structure and damage mechanisms in the irradiated MWCNTs, induced by the irradiations of 70 and 110 keV electrons, are investigated. The changes in surface morphology and structure of the irradiated MWCNT film are characterized using scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS), Raman spectroscopy, x-ray diffraction analysis (XRD), and electron paramagnetic resonance (EPR) spectroscopy. It is found that the MWCNTs show different behaviors in structural changes after 70 and 110 keV electron irradiation due to different damage mechanisms. SEM results reveal that the irradiation of 70 keV electrons does not change surface morphology of the MWCNT film, while the irradiation of 110 keV electrons with a high fluence of 5 × 1015 cm-2 leads to evident morphological changes, such as the formation of a rough surface, the entanglement of nanotubes and the shrinkage of nanotubes. Based on Raman spectroscopy, XPS, and XRD analyses, it is confirmed that the irradiation of 70 keV electrons increases the interlayer spacing of the MWCNTs and disorders their structure through electronic excitations and ionization effects, while the irradiation of 110 keV electrons obviously reduces the interlayer spacing of the MWCNTs and improves their graphitic order through knock-on atom displacements. The improvement of the irradiated MWCNTs by 110 keV electrons is attributed to the restructuring of defect sites induced by knock-on atom displacements. EPR spectroscopic analyses reveal that the MWCNTs exposed

  14. Effect of Temperature on Damage Evolution of Cr25Ni35Nb Alloy Subjected to Combined Mechanical and Environmental Degradation

    NASA Astrophysics Data System (ADS)

    Shen, Limin; Liu, Huansheng; Gong, Jianming; Geng, Luyang

    2015-07-01

    Due to combined mechanical and environmental degradation, i.e. coupled creep and carburization, Cr25Ni35Nb alloy often fails prior to the expected design life. In the present paper, based on the continuum damage mechanics, the constitutive model of coupled multi-damage factors for computing the damage evolution of Cr25Ni35Nb alloy was proposed. The damage prediction was carried out by using finite element method based on ABAQUS code. And then damage evolution processes at different operating temperatures (950 °C and 1050 °C) were simulated and the effect of service temperature on the damage evolution was discussed. The results showed that the rate of damage increased obviously with operating temperature increasing. The location with maximum damage is along the inner surface of tube, which implies that fracture begins along the inner surface of tube under the action of coupled creep and carburization damage and this is coincident with the actual observation of the failure of furnace tube.

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

    PubMed

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

    2016-05-11

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

  16. A damage mechanics model for power-law creep and earthquake aftershock and foreshock sequences

    NASA Astrophysics Data System (ADS)

    Main, Ian G.

    2000-07-01

    It is common practice to refer to three independent stages of creep under static loading conditions in the laboratory: namely transient, steady-state, and accelerating. Here we suggest a simple damage mechanics model for the apparently trimodal behaviour of the strain and event rate dependence, by invoking two local mechanisms of positive and negative feedback applied to constitutive rules for time-dependent subcritical crack growth. In both phases, the individual constitutive rule for measured strain ɛ takes the form ɛ(t)=ɛ0[1+t/mτ]m, where τ is the ratio of initial crack length to rupture velocity. For a local hardening mechanism (negative feedback), we find that transient creep dominates, with 0mechanism (positive feedback), m<0, and crack growth is unstable and accelerating. In this case a quasi-static instability criterion ɛ->∞ can be defined at a finite failure time, resulting in the localization of damage and the formation of a throughgoing fracture. In the hybrid model, transient creep dominates in the early stages of damage and accelerating creep in the latter stages. At intermediate times the linear superposition of the two mechanisms spontaneously produces an apparent steady-state phase of relatively constant strain rate, with a power-law rheology, as observed in laboratory creep test data. The predicted acoustic emission event rates in the transient and accelerating phases are identical to the modified Omori laws for aftershocks and foreshocks, respectively, and provide a physical meaning for the empirical constants measured. At intermediate times, the event rate tends to a relatively constant background rate. The requirement for a finite event rate at the time of the main shock can be satisfied by modifying the instability criterion to having a finite crack velocity at the dynamic failure time, dx/dt->VR, where VR is the dynamic rupture velocity. The same hybrid

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

    PubMed

    Lindahl, Tomas; Modrich, Paul; Sancar, Aziz

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

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

    NASA Astrophysics Data System (ADS)

    Han, Fei; Lubineau, Gilles; Azdoud, Yan

    2016-09-01

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

  20. A Tissue Phantom for Evaluation of Mechanical Damage Caused by Cavitation

    NASA Astrophysics Data System (ADS)

    Maxwell, Adam; Wang, Tzu-Yin; Yuan, Lingqian; Duryea, Alex; Xu, Zhen; Cain, Charles

    2010-03-01

    We have developed a phantom which acts as an indicator of mechanical tissue damage caused by cavitation in therapeutic ultrasound such as histotripsy. The phantom is an optically-transparent gel, allowing real-time visualization of cavitation. Lesions are visible as a change in transparency, giving immediate feedback of the damage. The phantom was formed in 3 layers of agarose gel, with the center layer containing 5% porcine red blood cells. It was found that the acoustic and mechanical properties are similar to tissue. To compare lesions induced in the phantom and tissue, phantoms and ex-vivo kidney were treated using a focused 1-MHz transducer applying 15 cycle pulses at a rate of 100 Hz and peak negative pressure of 14 MPa. Cavitation caused lysis of red blood cells, which changed the affected area from translucent red to transparent. Lesion morphology of the phantom was similar to tissue, with no cellular structures remaining inside the lesion and sharp boundaries between the transparent and translucent zones. Lesions in the phantom produced a hypoechoic appearance in the phantom on a B-Mode ultrasound image, as previously observed with histotripsy lesions generated in tissue. High-speed imaging was used to correlate cavitation activity with the formation of lesions spatially. During ultrasound exposure, cavitation clouds were observed in the phantom by high-speed optical imaging. Lesions in the gel only formed when and where cavitation was observed. The tissue phantom allows immediate visualization of cavitation and cavitational tissue damage providing a useful research tool for cavitational ultrasound therapy studies such as testing acoustic parameters or scanning algorithms.

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

    SciTech Connect

    Kazi, Haseeb; Kelber, Jeffry A.

    2014-03-15

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

  2. Mechanisms of oxidative damage of low density lipoprotein in human atherosclerosis.

    PubMed

    Heinecke, J W

    1997-10-01

    Oxidatively damaged LDL may play a critical role in the pathogenesis of atherosclerotic vascular disease. Several pathways promote LDL oxidation in vitro but the physiologically relevant mechanisms have proven difficult to identify. Detection of stable compounds that result from specific reaction pathways has provided the first insights into the mechanism of oxidative damage in the human artery wall. Mass spectrometric analysis of protein oxidation products isolated from atherosclerotic tissue implicate tyrosyl radical, reactive nitrogen intermediates and hypochlorous acid in LDL oxidation and lesion formation in vivo. Hypochlorous acid is only generated by the phagocytic enzyme myeloperoxidase, which can also generate tyrosyl radical and reactive nitrogen intermediates. Chiral phase high-pressure liquid chromatography analysis of lipid oxidation products suggests that cellular lipoxygenases may also play a role at certain stages. In contrast, LDL isolated from atherosclerotic tissue is not enriched in protein oxidation products characteristic of free metal ions, which are the most widely studied in vitro model of LDL oxidation. These observations provide the first direct chemical evidence for reaction pathways that promote LDL oxidation in human atherosclerosis. PMID:9335950

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

    PubMed

    Amis, James

    2016-01-01

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

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

    PubMed Central

    Amis, James

    2016-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  6. Damage to pancreatic acinar cells and preservation of islets of Langerhans in a rat model of acute pancreatitis induced by Karwinskia humboldtiana (buckthorn).

    PubMed

    Carcano-Diaz, Katya; Garcia-Garcia, Aracely; Segoviano-Ramirez, Juan Carlos; Rodriguez-Rocha, Humberto; Loera-Arias, Maria de Jesus; Garcia-Juarez, Jaime

    2016-09-01

    Karwinskia humboldtiana (Kh) is a poisonous plant that grows in some regions of the American continent. Consuming large amounts of Kh fruit results in acute intoxication leading to respiratory failure, culminating in death within days. There is evidence of histological damage to the lungs, liver, and kidneys following accidental and experimental Kh intoxication. To date, the microscopic effect of Kh consumption on the pancreas has not been described. We examined the early effects of Kh fruit on pancreatic tissue at different stages of acute intoxication in the Wistar rat. We found progressive damage confined to the exocrine pancreas, starting with a reduction in the number of zymogen granules, loss of acinar architecture, the presence of autophagy-like vesicles, apoptosis and inflammatory infiltrate. The pancreatic pathology culminated in damaged acini characterized by necrosis and edema, with a complete loss of lobular architecture. Interestingly, the morphology of the islets of Langerhans was conserved throughout our evaluations. Taken together, our results indicate the damage induced by a high dose of Kh fruit in the Wistar rat is consistent with an early acute necrotizing pancreatitis that exclusively affects the exocrine pancreas. Therefore, this system might be useful as an animal model to study the treatment of pancreatic diseases. More importantly, as the islets of Langerhans were preserved, the active compounds of Kh fruit could be utilized for the treatment of acinar pancreatic cancer. Further studies might provide insight into the severity of acute Kh intoxication in humans and influence the design of treatments for pancreatic diseases and acinar pancreatic cancer. PMID:26877198

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

    NASA Technical Reports Server (NTRS)

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

    2008-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Chen, Chun-Zhang

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

  9. Bayesian inference of the lung alveolar spatial model for the identification of alveolar mechanics associated with acute respiratory distress syndrome

    NASA Astrophysics Data System (ADS)

    Christley, Scott; Emr, Bryanna; Ghosh, Auyon; Satalin, Josh; Gatto, Louis; Vodovotz, Yoram; Nieman, Gary F.; An, Gary

    2013-06-01

    Acute respiratory distress syndrome (ARDS) is acute lung failure secondary to severe systemic inflammation, resulting in a derangement of alveolar mechanics (i.e. the dynamic change in alveolar size and shape during tidal ventilation), leading to alveolar instability that can cause further damage to the pulmonary parenchyma. Mechanical ventilation is a mainstay in the treatment of ARDS, but may induce mechano-physical stresses on unstable alveoli, which can paradoxically propagate the cellular and molecular processes exacerbating ARDS pathology. This phenomenon is called ventilator induced lung injury (VILI), and plays a significant role in morbidity and mortality associated with ARDS. In order to identify optimal ventilation strategies to limit VILI and treat ARDS, it is necessary to understand the complex interplay between biological and physical mechanisms of VILI, first at the alveolar level, and then in aggregate at the whole-lung level. Since there is no current consensus about the underlying dynamics of alveolar mechanics, as an initial step we investigate the ventilatory dynamics of an alveolar sac (AS) with the lung alveolar spatial model (LASM), a 3D spatial biomechanical representation of the AS and its interaction with airflow pressure and the surface tension effects of pulmonary surfactant. We use the LASM to identify the mechanical ramifications of alveolar dynamics associated with ARDS. Using graphical processing unit parallel algorithms, we perform Bayesian inference on the model parameters using experimental data from rat lung under control and Tween-induced ARDS conditions. Our results provide two plausible models that recapitulate two fundamental hypotheses about volume change at the alveolar level: (1) increase in alveolar size through isotropic volume change, or (2) minimal change in AS radius with primary expansion of the mouth of the AS, with the implication that the majority of change in lung volume during the respiratory cycle occurs in the

  10. Bayesian inference of the lung alveolar spatial model for the identification of alveolar mechanics associated with acute respiratory distress syndrome.

    PubMed

    Christley, Scott; Emr, Bryanna; Ghosh, Auyon; Satalin, Josh; Gatto, Louis; Vodovotz, Yoram; Nieman, Gary F; An, Gary

    2013-06-01

    Acute respiratory distress syndrome (ARDS) is acute lung failure secondary to severe systemic inflammation, resulting in a derangement of alveolar mechanics (i.e. the dynamic change in alveolar size and shape during tidal ventilation), leading to alveolar instability that can cause further damage to the pulmonary parenchyma. Mechanical ventilation is a mainstay in the treatment of ARDS, but may induce mechano-physical stresses on unstable alveoli, which can paradoxically propagate the cellular and molecular processes exacerbating ARDS pathology. This phenomenon is called ventilator induced lung injury (VILI), and plays a significant role in morbidity and mortality associated with ARDS. In order to identify optimal ventilation strategies to limit VILI and treat ARDS, it is necessary to understand the complex interplay between biological and physical mechanisms of VILI, first at the alveolar level, and then in aggregate at the whole-lung level. Since there is no current consensus about the underlying dynamics of alveolar mechanics, as an initial step we investigate the ventilatory dynamics of an alveolar sac (AS) with the lung alveolar spatial model (LASM), a 3D spatial biomechanical representation of the AS and its interaction with airflow pressure and the surface tension effects of pulmonary surfactant. We use the LASM to identify the mechanical ramifications of alveolar dynamics associated with ARDS. Using graphical processing unit parallel algorithms, we perform Bayesian inference on the model parameters using experimental data from rat lung under control and Tween-induced ARDS conditions. Our results provide two plausible models that recapitulate two fundamental hypotheses about volume change at the alveolar level: (1) increase in alveolar size through isotropic volume change, or (2) minimal change in AS radius with primary expansion of the mouth of the AS, with the implication that the majority of change in lung volume during the respiratory cycle occurs in the

  11. DNA damage drives accelerated bone aging via an NF-κB-dependent mechanism

    PubMed Central

    Chen, Qian; Liu, Kai; Robinson, Andria R.; Clauson, Cheryl L.; Blair, Harry C.; Robbins, Paul D.; Niedernhofer, Laura J.; Ouyang, Hongjiao

    2013-01-01

    Advanced age is one of the most important risk factors for osteoporosis. Accumulation of oxidative DNA damage has been proposed to contribute to age-related deregulation of osteoblastic and osteoclastic cells. ERCC1 (Excision Repair Cross Complementary group 1)-XPF (Xeroderma Pigmentosum Group F) is an evolutionarily conserved structure-specific endonuclease that is required for multiple DNA repair pathways. Inherited mutations affecting expression of ERCC1-XPF cause a severe progeroid syndrome in humans, including early onset of osteopenia and osteoporosis, or anomalies in skeletal development. Herein, we used progeroid ERCC1-XPF deficient mice, including Ercc1-null (Ercc1−/−) and hypomorphic (Ercc1−/Δ) mice, to investigate the mechanism by which DNA damage leads to accelerated bone aging. Compared to their wild-type littermates, both Ercc1−/− and Ercc1−/Δ mice display severe, progressive osteoporosis caused by reduced bone formation and enhanced osteoclastogenesis. ERCC1 deficiency leads to atrophy of osteoblastic progenitors in the bone marrow stromal cell (BMSC) population. There is increased cellular senescence of BMSCs and osteoblastic cells, as characterized by reduced proliferation, accumulation of DNA damage and a senescence-associated secretory phenotype (SASP). This leads to enhanced secretion of inflammatory cytokines known to drive osteoclastogenesis, such as IL-6, TNFα, and RANKL and thereby induces an inflammatory bone microenvironment favoring osteoclastogenesis. Furthermore, we found that the transcription factor NF-κB is activated in osteoblastic and osteoclastic cells of the Ercc1 mutant mice. Importantly, we demonstrated that haploinsufficiency of the p65 NF-κB subunit partially rescued the osteoporosis phenotype of Ercc1−/Δ mice. Finally, pharmacological inhibition of the NF-κB signaling via an IKK inhibitor reversed cellular senescence and SASP in Ercc1−/Δ BMSCs. These results demonstrate that DNA damage drives

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

    DOE PAGESBeta

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

    2016-06-02

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

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

    PubMed Central

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

    2007-01-01

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

  14. Free radical damage to protein and DNA: mechanisms involved and relevant observations on brain undergoing oxidative stress.

    PubMed

    Floyd, R A; Carney, J M

    1992-01-01

    Iron mediates damage to proteins and DNA. The mechanisms of damage not only involve iron but also oxygen free radical intermediates. Oxidative damage to DNA causes not only strand breaks, but also formation of specific base adducts, such as 8-hydroxy-2'-deoxyguanosine. Oxidative damage also inactivates certain enzymes such as glutamine synthetase. Novel methods of assessing oxidative damage to tissue, including quantitation of salicylate hydroxylation as an index of hydroxyl free radical flux as well as specific lesions to proteins and DNA, have yielded results that clearly show that ischemia/reperfusion injury to mongolian gerbil brain involves oxidatively damaging events. Aging in gerbil as well as human brain is also associated with increased oxidative damage. Recent novel observations have shown that the spin-trapping agent phenyl alpha-tert-butylnitrone (PBN) offers protection in gerbil brain during ischemia/reperfusion injury. We also show that oxidative damage to brain during aging is decreased by chronic administration of PBN. The mechanism of action of PBN may be related to its trapping of specific free radicals, which triggers a cascade of oxidative events that eventually lead to tissue injury. PMID:1510377

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

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

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

  16. Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving.

    PubMed

    Shiels, H A; Galli, G L J; Block, B A

    2015-02-01

    Understanding the physiology of vertebrate thermal tolerance is critical for predicting how animals respond to climate change. Pacific bluefin tuna experience a wide range of ambient sea temperatures and occupy the largest geographical niche of all tunas. Their capacity to endure thermal challenge is due in part to enhanced expression and activity of key proteins involved in cardiac excitation-contraction coupling, which improve cardiomyocyte function and whole animal performance during temperature change. To define the cellular mechanisms that enable bluefin tuna hearts to function during acute temperature change, we investigated the performance of freshly isolated ventricular myocytes using confocal microscopy and electrophysiology. We demonstrate that acute cooling and warming (between 8 and 28°C) modulates the excitability of the cardiomyocyte by altering the action potential (AP) duration and the amplitude and kinetics of the cellular Ca(2+) transient. We then explored the interactions between temperature, adrenergic stimulation and contraction frequency, and show that when these stressors are combined in a physiologically relevant way, they alter AP characteristics to stabilize excitation-contraction coupling across an acute 20°C temperature range. This allows the tuna heart to maintain consistent contraction and relaxation cycles during acute thermal challenges. We hypothesize that this cardiac capacity plays a key role in the bluefin tunas' niche expansion across a broad thermal and geographical range. PMID:25540278

  17. Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving

    PubMed Central

    Shiels, H. A.; Galli, G. L. J.; Block, B. A.

    2015-01-01

    Understanding the physiology of vertebrate thermal tolerance is critical for predicting how animals respond to climate change. Pacific bluefin tuna experience a wide range of ambient sea temperatures and occupy the largest geographical niche of all tunas. Their capacity to endure thermal challenge is due in part to enhanced expression and activity of key proteins involved in cardiac excitation–contraction coupling, which improve cardiomyocyte function and whole animal performance during temperature change. To define the cellular mechanisms that enable bluefin tuna hearts to function during acute temperature change, we investigated the performance of freshly isolated ventricular myocytes using confocal microscopy and electrophysiology. We demonstrate that acute cooling and warming (between 8 and 28°C) modulates the excitability of the cardiomyocyte by altering the action potential (AP) duration and the amplitude and kinetics of the cellular Ca2+ transient. We then explored the interactions between temperature, adrenergic stimulation and contraction frequency, and show that when these stressors are combined in a physiologically relevant way, they alter AP characteristics to stabilize excitation–contraction coupling across an acute 20°C temperature range. This allows the tuna heart to maintain consistent contraction and relaxation cycles during acute thermal challenges. We hypothesize that this cardiac capacity plays a key role in the bluefin tunas' niche expansion across a broad thermal and geographical range. PMID:25540278

  18. Acute Pancreatitis after Percutaneous Mechanical Thrombectomy: Case Report and Review of the Literature

    SciTech Connect

    Hershberger, Richard C. Bornak, Arash; Aulivola, Bernadette; Mannava, Krishna

    2011-02-15

    Purpose: We describe a case of severe acute pancreatitis after percutaneous mechanical thrombectomy (PMT) and review the literature for the occurrence of this complication. Materials and Methods: A 53-year-old man with a history of bilateral external iliac artery stent placement sought care for acute onset of lifestyle-limiting left claudication. Angiography confirmed left external iliac stent occlusion, and PMT with the AngioJet Xpeedior catheter (Possis Medical, Minneapolis MN) was performed. Results: After PMT of the occluded external iliac artery, a residual in-stent stenosis required the placement of a second iliac stent. The procedure was complicated by severe acute pancreatitis. Other causes of pancreatitis were eliminated during the patient's hospital stay. A literature review revealed nine cases of acute pancreatitis after PMT. Conclusion: Although rare, pancreatitis can be a devastating complication of PMT. The development of pancreatitis seems to be related to the products of extensive hemolysis triggering an inflammatory process. To prevent this complication, we recommend that close attention be paid to the duration and extent of PMT, thereby avoiding extensive hemolysis and subsequent complications.

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    NASA Astrophysics Data System (ADS)

    Moll, Jericho L.

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

  1. Metal uptake and acute toxicity in zebrafish: common mechanisms across multiple metals.

    PubMed

    Alsop, Derek; Wood, Chris M

    2011-10-01

    Zebrafish larvae (Danio rerio) were used to examine the mechanisms of action and acute toxicities of metals. Larvae had similar physiological responses and sensitivities to waterborne metals as adults. While cadmium and zinc have previously been shown to reduce Ca(2+) uptake, copper and nickel also decreased Ca(2+) uptake, suggesting that the epithelial transport of all these metals is through Ca(2+) pathways. However, exposure to cadmium, copper or nickel for up to 48 h had little or no effect on total whole body Ca(2+) levels, indicating that the reduction of Ca(2+) uptake is not the acute toxic mechanism of these metals. Instead, mortalities were effectively related to whole body Na(+), which decreased up to 39% after 48 h exposures to different metals around their respective 96 h LC50s. Decreases in whole body K(+) were also observed, although they were not as pronounced or frequent as Na(+) losses. None of the metals tested inhibited Na(+) uptake in zebrafish (Na(+) uptake was in fact increased with exposure) and the observed losses of Na(+), K(+), Ca(2+) and Mg(2+) were proportional to the ionic gradients between the plasma and water, indicating diffusive ion loss with metal exposure. This study has shown that there is a common pathway for metal uptake and a common mechanism of acute toxicity across groups of metals in zebrafish. The disruption of ion uptake accompanying metal exposure does not appear to be responsible for the acute toxicity of metals, as has been previously suggested, but rather the toxicity is instead due to total ion loss (predominantly Na(+)). PMID:21820385

  2. Modeling of Stone-impact Resistance of Monolithic Glass Ply Using Continuum Damage Mechanics

    SciTech Connect

    Sun, Xin; Khaleel, Mohammad A.; Davies, Richard W.

    2005-04-01

    We study the stone-impact resistance of a monolithic glass ply using a combined experimental and computational approach. Instrumented stone impact tests were first carried out in controlled environment. Explicit finite element analyses were then used to simulate the interactions of the indentor and the glass layer during the impact event, and a continuum damage mechanics (CDM) model was used to describe the constitutive behavior of glass. The experimentally measured strain histories for low velocity impact served as validation of the modeling procedures. Next, stair-stepping impact experiments were performed with two indentor sizes on two glass ply thickness, and the test results were used to calibrate the critical stress parameters used in the CDM constitutive model. The purpose of this study is to establish the modeling procedures and the CDM critical stress parameters under impact loading conditions. The modeling procedures and the CDM model will be used in our future studies to predict through-thickness damage evolution patterns for different laminated windshield designs in automotive applications.

  3. Extended Kalman filtering for the detection of damage in linear mechanical structures

    NASA Astrophysics Data System (ADS)

    Liu, X.; Escamilla-Ambrosio, P. J.; Lieven, N. A. J.

    2009-09-01

    This paper addresses the problem of assessing the location and extent of damage in a vibrating structure by means of vibration measurements. Frequency domain identification methods (e.g. finite element model updating) have been widely used in this area while time domain methods such as the extended Kalman filter (EKF) method, are more sparsely represented. The difficulty of applying EKF in mechanical system damage identification and localisation lies in: the high computational cost, the dependence of estimation results on the initial estimation error covariance matrix P(0), the initial value of parameters to be estimated, and on the statistics of measurement noise R and process noise Q. To resolve these problems in the EKF, a multiple model adaptive estimator consisting of a bank of EKF in modal domain was designed, each filter in the bank is based on different P(0). The algorithm was iterated by using the weighted global iteration method. A fuzzy logic model was incorporated in each filter to estimate the variance of the measurement noise R. The application of the method is illustrated by simulated and real examples.

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    The micromechanical damage mechanics formulated by Ashby and Sammis, 1990 and generalized by Deshpande and Evans 2008 has been extended to allow for a more generalized stress state and to incorporate an experimentally motivated new crack growth (damage evolution) law that is valid over a wide range of loading rates. This law is sensitive to both the crack tip stress field and its time derivative. Incorporating this feature produces additional strain-rate sensitivity in the constitutive response. The model is also experimentally verified by predicting the failure strength of Dionysus-Pentelicon marble over a wide range of strain rates. Model parameters determined from quasi-static experiments were used to predict the failure strength at higher loading rates. Agreement with experimental results was excellent. After this verification step the constitutive law was incorporated into a Finite Element Code focused on simulating dynamic earthquake ruptures with specific focus on the ends of the fault (fault tip process zone) and the resulting strong ground motion radiation was studied.

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

    NASA Astrophysics Data System (ADS)

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

    2010-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  7. 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.

  8. Mechanism of chronic dietary iron overload-induced liver damage in mice.

    PubMed

    Liu, Dan; He, Huan; Yin, Dong; Que, Ailing; Tang, Lei; Liao, Zhangping; Huang, Qiren; He, Ming

    2013-04-01

    Chronic iron overload may result in hepatic fibrosis and even neoplastic transformation due to a burst of reactive oxygen species (ROS). Mitochondria have been proposed to be important in the production of ROS. The purpose of this study was to investigate the role of the mitochondrial permeability transition pore (mPTP) in the burst of ROS, and to clarify the mechanism whereby ROS induced by iron overload results in hepatic damage. It has been demonstrated that when ferrocene-induced iron-overloaded mice were fed the cyclosporin A (CsA), a specific inhibitor of the mPTP, diet (10 mg/kg/day) for 50 days, liver-to-body weight ratio, serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), ROS production, mitochondrial swelling, loss of mitochondrial membrane potential (Δψ) and hepatocyte apoptosis decreased. However, the total antioxidant status, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase activities, increased. The protective effect of CsA on the liver of iron-overloaded mice may be due to inhibition of the ROS burst and a successive antioxidant effect. To the best of our knowledge, these data provide the first support for the theory that ROS-induced ROS release (RIRR) may be involved in the burst of ROS in the liver and greatly contribute to the hepatic damage initiated by iron overload. PMID:23404080

  9. DNA Repair Gene Polymorphisms and Their Relation With DNA Damage, DNA Repair, and Total Antioxidant Capacity in Childhood Acute Lymphoblastic Leukemia Survivors.

    PubMed

    Dincer, Yildiz; Yüksel, Selin; Batar, Bahadir; Güven, Mehmet; Onaran, Ilhan; Celkan, Tiraje

    2015-07-01

    Oxidative stress and defective DNA repair are major contributory factors in the initiation and progression of carcinogenesis. Chemotherapy and radiotherapy cause oxidative DNA damage, consume antioxidant capacity, and impair DNA repair activity. These effects of chemotherapy and radiotherapy may be contributory factors in the development of secondary malignancy in cancer survivors. Basal, H2O2-induced, and postrepair DNA damage; urinary 8-hydroxydeoxyguanosine level as a marker of oxidatively damaged DNA; and serum total antioxidant capacity were measured; XPD Lys751Gln, XRCC1 Arg399Gln, and XRCC1 Arg194Trp polymorphisms were analyzed in childhood acute lymphoblastic leukemia (ALL) survivors. Basal and H2O2-induced DNA damage were found to be higher in the ALL survivor group versus the control group, however, there was no significant difference between the other parameters. No association was found between the examined parameters and polymorphisms of XPD 751 and XRCC1 399 and both the groups. XRCC1 194Trp allele was found to be associated with a low level of postrepair DNA damage in the ALL survivors. In conclusion, basal DNA damage and susceptibility to oxidation are high in childhood ALL survivors. This situation which may easily lead to occurrence of a secondary cancer does not seem to be a result of deficient DNA repair. PMID:24577548

  10. Mechanical thrombectomy in patients with acute ischemic stroke: a cost-utility analysis

    PubMed Central

    Xie, Xuanqian; Lambrinos, Anna; Chan, Brian; Dhalla, Irfan A.; Krings, Timo; Casaubon, Leanne K.; Lum, Cheemun; Sikich, Nancy; Bharatha, Aditya; Pereira, Vitor Mendes; Stotts, Grant; Saposnik, Gustavo; O'Callaghan, Christina; Kelloway, Linda; Hill, Michael D.

    2016-01-01

    Background: The beneficial effects of endovascular treatment with new-generation mechanical thrombectomy devices compared with intravenous thrombolysis alone to treat acute large-artery ischemic stroke have been shown in randomized controlled trials (RCTs). This study aimed to estimate the cost utility of mechanical thrombectomy compared with the established standard of care. Methods: We developed a Markov decision process analytic model to assess the cost-effectiveness of treatment with mechanical thrombectomy plus intravenous thrombolysis versus treatment with intravenous thrombolysis alone from the public payer perspective in Canada. We conducted comprehensive literature searches to populate model inputs. We estimated the efficacy of mechanical thrombectomy plus intravenous thrombolysis from a meta-analysis of 5 RCTs, and we used data from the Oxford Vascular Study to model long-term clinical outcomes. We calculated incremental cost-effectiveness ratios (ICER) using a 5-year time horizon. Results: The base case analysis showed the cost and effectiveness of treatment with mechanical thrombectomy plus intravenous thrombolysis to be $126 939 and 1.484 quality-adjusted life-years (QALYs), respectively, and the cost and effectiveness of treatment with intravenous thrombolysis alone to be $124 419 and 1.273 QALYs, respectively. The mechanical thrombectomy plus intravenous thrombolysis strategy was associated with an ICER of $11 990 per QALY gained. Probabilistic sensitivity analysis showed that the probability of treatment with mechanical thrombectomy plus intravenous thrombolysis being cost-effective was 57.5%, 89.7% and 99.6% at thresholds of $20 000, $50 000 and $100 000 per QALY gained, respectively. The main factors influencing the ICER were time horizon, extra cost of mechanical thrombectomy treatment and age of the patient. Interpretation: Mechanical thrombectomy as an adjunct therapy to intravenous thrombolysis is cost-effective compared with

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

    SciTech Connect

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

    2004-12-01

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

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

    NASA Astrophysics Data System (ADS)

    Peng, Yajing; Jiang, Yanxue; Yang, Yanqiang

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Duffy, Stephen F.; Gyekenyesi, John P.

    1989-01-01

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

  14. [Postural therapy during mechanical pulmonary ventilation with PEEP in patients with unilateral lung damage].

    PubMed

    Neverin, V K; Vlasenko, A V; Mitrokhin, A A; Galushka, S V; Ostapchenko, D V; Shishkina, E V

    2000-01-01

    Mechanical ventilation of the lungs (MVL) with positive end expiratory pressure (PEEP) is difficult in patients with unilateral lung damage because of uneven distribution of volumes and pressures in the involved and intact lungs. Harmful effects are easier manifested under such conditions. Selective MVL with selective PEEP is widely used abroad for optimizing MVL, but this method is rather expensive and is not devoid of shortcomings. Our study carried out in 32 patients with unilateral lung involvement showed that traditional MVL with general PEEP can effectively (in 75% cases) regulate gaseous exchange and decrease its untoward effects if MVL is performed with the patient lying on the healthy side and not supine. MVL in patients with unilateral lung injury lying on the healthy side can be a simpler and cheaper alternative to selective MVL with selective PEEP. PMID:10833838

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

    NASA Astrophysics Data System (ADS)

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

    2010-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1993-09-01

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

  17. Radiation damage mechanisms for luminescence in Eu-doped GaN

    SciTech Connect

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

    2007-03-01

    Thin films of Eu-doped GaN were irradiated with 500 keV He{sup +} ions to understand radiation damage mechanisms and to quantify luminescence efficiency. The dependence of ion-beam-induced luminescence intensity on ion fluence was consistent with the simultaneous creation of nonradiative defects and the destruction of luminescent centers associated with 4f-4f core-level transitions in Eu{sup 3+}. This model contrasts with a previous description which takes into account only nonradiative defect generation in GaN:Eu. Based on light from a BaF{sub 2} scintillator standard, the luminescent energy generation efficiency of GaN:Eu films doped to {approx}3x10{sup 18} cm{sup -3} Eu is estimated to be {approx}0.1%.

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. Damage mechanisms in thin film solar cells during sputtering deposition of transparent conductive coatings

    SciTech Connect

    Fan Qihua; Liao Xianbo; Deng, Michael; Deng Xunming

    2009-02-01

    Amorphous silicon (a-Si) based thin film solar cell grown on flexible stainless steel substrate is one of the most promising energy conversion devices in the future. This type of solar cell uses a transparent conductive oxide (TCO) film as top electrode. It has been a widely accepted opinion that the radio frequency sputtering deposition of the TCO film produces a higher yield than direct current sputtering, and the reason is not clear. Here we show that the damage to the solar cell during the sputtering process is caused by a reverse bias applied to the n-i-p junction. This reverse bias is related to the characteristics of plasma discharge. The mechanism we reveal may significantly affect the solar cell process.

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

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

    DOE PAGESBeta

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

    2015-01-06

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

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

    SciTech Connect

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

    2015-01-06

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

  7. Iron Oxide Nanoparticles Induce Autophagosome Accumulation through Multiple Mechanisms: Lysosome Impairment, Mitochondrial Damage, and ER Stress.

    PubMed

    Zhang, Xudong; Zhang, Hongqiu; Liang, Xin; Zhang, Jinxie; Tao, Wei; Zhu, Xianbing; Chang, Danfeng; Zeng, Xiaowei; Liu, Gan; Mei, Lin

    2016-07-01

    Magnetite (iron oxide, Fe3O4) nanoparticles have been widely used for drug delivery and magnetic resonance imaging (MRI). Previous studies have shown that many metal-based nanoparticles including Fe3O4 nanoparticles can induce autophagosome accumulation in treated cells. However, the underlying mechanism is still not clear. To investigate the biosafety of Fe3O4 and PLGA-coated Fe3O4 nanoparticles, some experiments related to the mechanism of autophagy induction by these nanoparticles have been investigated. In this study, the results showed that Fe3O4, PLGA-coated Fe3O4, and PLGA nanoparticles could be taken up by the cells through cellular endocytosis. Fe3O4 nanoparticles extensively impair lysosomes and lead to the accumulation of LC3-positive autophagosomes, while PLGA-coated Fe3O4 nanoparticles reduce this destructive effect on lysosomes. Moreover, Fe3O4 nanoparticles could also cause mitochondrial damage and ER and Golgi body stresses, which induce autophagy, while PLGA-coated Fe3O4 nanoparticles reduce the destructive effect on these organelles. Thus, the Fe3O4 nanoparticle-induced autophagosome accumulation may be caused by multiple mechanisms. The autophagosome accumulation induced by Fe3O4 was also investigated. The Fe3O4, PLGA-coated Fe3O4, and PLGA nanoparticle-treated mice were sacrificed to evaluate the toxicity of these nanoparticles on the mice. The data showed that Fe3O4 nanoparticle treated mice would lead to the extensive accumulation of autophagosomes in the kidney and spleen in comparison to the PLGA-coated Fe3O4 and PLGA nanoparticles. Our data clarifies the mechanism by which Fe3O4 induces autophagosome accumulation and the mechanism of its toxicity on cell organelles and mice organs. These findings may have an important impact on the clinical application of Fe3O4 based nanoparticles. PMID:27287467

  8. Pathophysiological Basis of Acute Respiratory Failure on Non-Invasive Mechanical Ventilation

    PubMed Central

    Romero-Dapueto, C; Budini, H; Cerpa, F; Caceres, D; Hidalgo, V; Gutiérrez, T; Keymer, J; Pérez, R; Molina, J; Giugliano-Jaramillo, C

    2015-01-01

    Noninvasive mechanical ventilation (NIMV) was created for patients who needed noninvasive ventilator support, this procedure decreases the complications associated with the use of endotracheal intubation (ETT). The application of NIMV has acquired major relevance in the last few years in the management of acute respiratory failure (ARF), in patients with hypoxemic and hypercapnic failure. The main advantage of NIMV as compared to invasive mechanical ventilation (IMV) is that it can be used earlier outside intensive care units (ICUs). The evidence strongly supports its use in patients with COPD exacerbation, support in weaning process in chronic obstructive pulmonary disease (COPD) patients, patients with acute cardiogenic pulmonary edema (ACPE), and Immunosuppressed patients. On the other hand, there is poor evidence that supports the use of NIMV in other pathologies such as pneumonia, acute respiratory distress syndrome (ARDS), and during procedures as bronchoscopy, where its use is still controversial because the results of these studies are inconclusive against the decrease in the rate of intubation or mortality. PMID:26312101

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

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

    PubMed

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

    2012-07-01

    Cavitation was investigated as a possible damage mechanism for war-related traumatic brain injury (TBI) due to an improvised explosive device (IED) blast. When a frontal blast wave encounters the head, a shock wave is transmitted through the skull, cerebrospinal fluid (CSF), and tissue, causing negative pressure at the contrecoup that may result in cavitation. Numerical simulations and shock tube experiments were conducted to determine the possibility of cranial cavitation from realistic IED non-impact blast loading. Simplified surrogate models of the head consisted of a transparent polycarbonate ellipsoid. The first series of tests in the 18-inch-diameter shock tube were conducted on an ellipsoid filled with degassed water to simulate CSF and tissue. In the second series, Sylgard gel, surrounded by a layer of degassed water, was used to represent the tissue and CSF, respectively. Simulated blast overpressure in the shock tube tests ranged from a nominal 10-25 pounds per square inch gauge (psig; 69-170 kPa). Pressure in the simulated CSF was determined by Kulite thin line pressure sensors at the coup, center, and contrecoup positions. Using video taken at 10,000 frames/sec, we verified the presence of cavitation bubbles at the contrecoup in both ellipsoid models. In all tests, cavitation at the contrecoup was observed to coincide temporally with periods of negative pressure. Collapse of the cavitation bubbles caused by the surrounding pressure and elastic rebound of the skull resulted in significant pressure spikes in the simulated CSF. Numerical simulations using the DYSMAS hydrocode to predict onset of cavitation and pressure spikes during cavity collapse were in good agreement with the tests. The numerical simulations and experiments indicate that skull deformation is a significant factor causing cavitation. These results suggest that cavitation may be a damage mechanism contributing to TBI that requires future study. PMID:22489674

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  12. Investigating Fault Zone Damage Processes Using Waveform Relocated Seismicity and High Precision Focal Mechanisms

    NASA Astrophysics Data System (ADS)

    Hauksson, E.; Yang, W.

    2011-12-01

    We analyze waveform relocated seismicity and focal mechanisms located near the principal slip zones (PSZs) of the late Quaternary fault zones in southern California to address questions such as: 1) Do mainshocks, aftershocks, and interseismic seismicity occur in the same place? 2) Is there evidence for fault normal compression along strike-slip faults? 3) Does seismicity in the near-field (±2km) of PSZs respond strongly to stress changes from nearby large earthquakes? 4) Is there other evidence for weak faults? We show that major earthquakes that can slip more than several meters, aftershocks, and near-fault relocated background seismicity mostly rupture different surfaces within late Quaternary fault zones. Major earthquakes rupture along the mapped traces of the late Quaternary faults, called the PSZs. Aftershocks illuminate damage zones in the immediate vicinity of the PSZs, typically ±2 km wide. In contrast, the near-fault background seismicity is mostly accommodated on a secondary heterogeneous network of small slip surfaces, and forms spatially decaying distributions extending out to distances of ±10 km away from the PSZs. As part of our efforts to address these questions, we have completed waveform relocations of more than 500,000 earthquakes. We have also determined a new focal mechanism catalog of more than 150,000 events, applying the latest techniques that include using S/P amplitude ratios for additional constraints, and taking advantage of the new waveform based relocations. We use the data set of focal mechanisms to analyze the style of faulting and the stress field next to PSZs of major faults. For detailed analysis we select all the events located within ±10 km of major PSZs as defined in the SCEC Community Fault Model. There is a difference in the depth distribution as well as in the rake distribution on each side of the PSZs. The events may be deeper on one side of the PSZ as compared to the other. Further, the focal mechanisms often have a

  13. Effects of DHA-rich fish oil supplementation on the lipid profile, markers of muscle damage, and neutrophil function in wheelchair basketball athletes before and after acute exercise.

    PubMed

    Marques, Camila Garcia; Santos, Vinicius Coneglian; Levada-Pires, Adriana Cristina; Jacintho, Thiago Manzoni; Gorjão, Renata; Pithon-Curi, Tânia Cristina; Cury-Boaventura, Maria Fernanda

    2015-06-01

    We investigated the effects of docosahexaenoic acid (DHA)-rich fish oil (FO) supplementation on the lipid profile, levels of plasma inflammatory mediators, markers of muscle damage, and neutrophil function in wheelchair basketball players before and after acute exercise. We evaluated 8 male basketball wheelchair athletes before and after acute exercise both prior to (S0) and following (S1) FO supplementation. The subjects were supplemented with 3 g of FO daily for 30 days. The following components were measured: the plasma lipid profile (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), plasma inflammatory mediators (C-reactive protein, interleukin (IL)-1β, IL-1ra, IL-4, IL-6, IL-8, and tumor necrosis factor-α), markers of muscle damage (creatine kinase and lactate dehydrogenase (LDH)), and neutrophil function (cytokine production, phagocytic capacity, loss of membrane integrity, mitochondrial membrane potential, neutral lipid accumulation, phosphatidylserine externalization, DNA fragmentation, and production of reactive oxygen species (ROS)). Acute exercise increased the plasma levels of total cholesterol, LDH, IL1ra, and IL-6, led to the loss of membrane integrity, ROS production, and a high mitochondrial membrane potential in neutrophils, and reduced the phagocytic capacity and IL-6 production by the neutrophils (S0). However, supplementation prevented the increases in the plasma levels of LDH and IL-6, the loss of membrane integrity, and the alterations in ROS production and mitochondrial membrane potential in the neutrophils that were induced by exercise (S1). In conclusion, DHA-rich FO supplementation reduces the markers of muscle damage, inflammatory disturbances, and neutrophil death induced by acute exercise in wheelchair athletes. PMID:25942100

  14. Different mechanisms for the photoinduced production of oxidative DNA damage by fluoroquinolones differing in photostability.

    PubMed

    Spratt, T E; Schultz, S S; Levy, D E; Chen, D; Schlüter, G; Williams, G M

    1999-09-01

    Several fluoroquinolone antibacterial agents exhibit an adverse phototoxic effect in humans and are photo-cocarcinogenic in mice. The UV-induced production of reactive oxygen species plays a role in the toxicity and may be involved in carcinogenicity. Four fluoroquinolones were examined for the ability to photochemically produce oxidative damage in naked DNA. The major structural difference in the fluoroquinolones that would have an effect on their photostability is the functionality at the 8-position. At this position, 1-cyclopropyl-7-(2,8-diazbicyclo[4.3.0]non-8-yl)-6, 8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (BAY y3118) contains a chlorine atom, lomefloxacin a fluorine atom, ciprofloxacin a proton, and moxifloxacin a methoxy group. The formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in calf thymus DNA was assessed by HPLC with electrochemical detection, and strand breaks were measured in pBR322 with agarose gel electrophoresis. The relative photolability of the fluoroquinolones correlated to the extent of production of 8-oxodGuo and strand breaks, with both UVA and UVB irradiation, in the following order: BAY y3118 approximately lomefloxacin > ciprofloxacin > moxifloxacin. Experiments were performed to determine whether the mechanism of damage was due to a type I (radical) or type II (singlet oxygen) pathway. Nitrogen depletion of oxygen resulted in a decrease in the extent of formation of 8-oxodGuo, suggesting that oxygen was involved. The use of selective radical or singlet oxygen inhibitors was inconclusive with respect to which pathway was involved. The use of D(2)O as a solvent, which would extend the lifetime of singlet oxygen, suggested that this species is involved in the formation of 8-oxodGuo by moxifloxacin and ciprofloxacin, but not by lomefloxacin and BAY y3118. Similarly, it was found that singlet oxygen was not involved in strand break formation. Thus, the evidence suggests that fluoroquinolones can photochemically

  15. Identification of volatile compounds emitted by Artemisia ordosica (Artemisia, Asteraceae) and changes due to mechanical damage and weevil infestation.

    PubMed

    Zhang, Hui; Zhou, Dayong; Luo, Youqing; Wang, Jinlin; Zong, Shixiang

    2013-01-01

    Volatiles emitted by healthy, mechanically damaged, and weevil-infested Artemisia ordosica (Asteraceae) were obtained through a dynamic headspace method and analysed by automatic thermal desorption/gas chromatography/mass spectrometry (ATD/GC/MS). Twenty-eight compounds in all were identified, and the qualitative as well as quantitative differences were compared. The green leaf volatiles 2-hexenal, (Z)-3-hexen-1-ol, 2-hexen-1-ol, 1-hexanol, and (Z)-3-hexen-1-ol acetate were present in all of the damaged plants, but in relatively lower portions when plants were infested by the weevil Adosopius sp., while the terpenoids alpha-copaene, beta-cedrene, and (E,E)-alpha-farnesene and the ester methyl salicylate were only present in weevil-damaged plants. The volatiles from healthy and weevil-infested leaves were dominated by D-limonene, whereas mechanically damaged leaves emitted beta-pinene as the dominant compound. PMID:24066517

  16. Noninvasive mechanical ventilation in chronic obstructive pulmonary disease and in acute cardiogenic pulmonary edema.

    PubMed

    Rialp Cervera, G; del Castillo Blanco, A; Pérez Aizcorreta, O; Parra Morais, L

    2014-03-01

    Noninvasive ventilation (NIV) with conventional therapy improves the outcome of patients with acute respiratory failure due to hypercapnic decompensation of chronic obstructive pulmonary disease (COPD) or acute cardiogenic pulmonary edema (ACPE). This review summarizes the main effects of NIV in these pathologies. In COPD, NIV improves gas exchange and symptoms, reducing the need for endotracheal intubation, hospital mortality and hospital stay compared with conventional oxygen therapy. NIV may also avoid reintubation and may decrease the length of invasive mechanical ventilation. In ACPE, NIV accelerates the remission of symptoms and the normalization of blood gas parameters, reduces the need for endotracheal intubation, and is associated with a trend towards lesser mortality, without increasing the incidence of myocardial infarction. The ventilation modality used in ACPE does not affect the patient prognosis. PMID:23158869

  17. Clinical review: mechanical circulatory support for cardiogenic shock complicating acute myocardial infarction

    PubMed Central

    2010-01-01

    Acute myocardial infarction is one of the 10 leading reasons for admission to adult critical care units. In-hospital mortality for this condition has remained static in recent years, and this is related primarily to the development of cardiogenic shock. Recent advances in reperfusion therapies have had little impact on the mortality of cardiogenic shock. This may be attributable to the underutilization of life support technology that may assist or completely supplant the patient's own cardiac output until adequate myocardial recovery is established or long-term therapy can be initiated. Clinicians working in the intensive care environment are increasingly likely to be exposed to these technologies. The purpose of this review is to outline the various techniques of mechanical circulatory support and discuss the latest evidence for their use in cardiogenic shock complicating acute myocardial infarction. PMID:21067535

  18. Iron Oxide Nanoparticles Induce Dopaminergic Damage: In vitro Pathways and In Vivo Imaging Reveals Mechanism of Neuronal Damage.

    PubMed

    Imam, Syed Z; Lantz-McPeak, Susan M; Cuevas, Elvis; Rosas-Hernandez, Hector; Liachenko, Serguei; Zhang, Yongbin; Sarkar, Sumit; Ramu, Jaivijay; Robinson, Bonnie L; Jones, Yvonne; Gough, Bobby; Paule, Merle G; Ali, Syed F; Binienda, Zbigniew K

    2015-10-01

    Various iron-oxide nanoparticles have been in use for a long time as therapeutic and imaging agents and for supplemental delivery in cases of iron-deficiency. While all of these products have a specified size range of ∼ 40 nm and above, efforts are underway to produce smaller particles, down to ∼ 1 nm. Here, we show that after a 24-h exposure of SHSY-5Y human neuroblastoma cells to 10 μg/ml of 10 and 30 nm ferric oxide nanoparticles (Fe-NPs), cellular dopamine content was depleted by 68 and 52 %, respectively. Increases in activated tyrosine kinase c-Abl, a molecular switch induced by oxidative stress, and neuronal α-synuclein expression, a protein marker associated with neuronal injury, were also observed (55 and 38 % percent increases, respectively). Inhibition of cell-proliferation, significant reductions in the number of active mitochondria, and a dose-dependent increase in reactive oxygen species (ROS) were observed in neuronal cells. Additionally, using a rat in vitro blood-brain barrier (BBB) model, a dose-dependent increase in ROS accompanied by increased fluorescein efflux demonstrated compromised BBB integrity. To assess translational implications, in vivo Fe-NP-induced neurotoxicity was determined using in vivo MRI and post-mortem neurochemical and neuropathological correlates in adult male rats after exposure to 50 mg/kg of 10 nm Fe-NPs. Significant decrease in T 2 values was observed. Dynamic observations suggested transfer and retention of Fe-NPs from brain vasculature into brain ventricles. A significant decrease in striatal dopamine and its metabolites was also observed, and neuropathological correlates provided additional evidence of significant nerve cell body and dopaminergic terminal damage as well as damage to neuronal vasculature after exposure to 10 nm Fe-NPs. These data demonstrate a neurotoxic potential of very small size iron nanoparticles and suggest that use of these ferric oxide nanoparticles may result in neurotoxicity, thereby

  19. A comparison between acute pressure block of the sciatic nerve and acupressure: methodology, analgesia, and mechanism involved

    PubMed Central

    Luo, Danping; Wang, Xiaolin; He, Jiman

    2013-01-01

    Acupressure is an alternative medicine methodology that originated in ancient China. Treatment effects are achieved by stimulating acupuncture points using acute pressure. Acute pressure block of the sciatic nerve is a newly reported analgesic method based on a current neuroscience concept: stimulation of the peripheral nerves increases the pain threshold. Both methods use pressure as an intervention method. Herein, we compare the methodology and mechanism of these two methods, which exhibit several similarities and differences. Acupressure entails variation in the duration of manipulation, and the analgesic effect achieved can be short-or long-term. The acute effect attained with acupressure presents a scope that is very different from that of the chronic effect attained after long-term treatment. This acute effect appears to have some similarities to that achieved with acute pressure block of the sciatic nerve, both in methodology and mechanism. More evidence is needed to determine whether there is a relationship between the two methods. PMID:23983488

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

    SciTech Connect

    Phillpot, Simon; Tulenko, James

    2011-09-08

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2004-01-01

    The hepatoprotective effects of the extract of Terminalia catappa L. leaves (TCE) against D-Galactosamine (D-GalN)-induced liver injury and the mechanisms underlying its protection were studied. In acute hepatic injury test, it was found that serum ALT activity was remarkably increased (3.35-fold) after injection of D-GalN in mice. But with oral pretreatment of TCE (20, 50 and 100 mg/kg/d) for 7days, change in serum ALT was notably reversed. In primary cultured hepatocytes from fetal mice, it was found that cell viability was decreased by 45.0% after addition of D-GalN, while incubation with TCE (0.1, 0.5 and 1.0 mg/ml) for 36 hours could prevent the decrease in a dose-dependent manner. Meanwhile, D-GalN-induced both the increase of AST level (1.9-fold) and the decrease of SOD activity (48.0%) in supernatant of primary cultured hepatocytes could also be inhibited by pretreatment with TCE. In order to study the possible mechanisms underlying its hepatoprotective effects, one effective component separated from TCE, 2alpha, 3beta, 23-trihydroxyursane-12-en-28-oic acid (DHUA), was used to determine anti-mitochondrial swelling activity and superoxide radicals scavenging activity in vitro. It was found that at the concentration range of 50-500 micromol/L DHUA, Ca2+ -induced mitochondrial swelling was dose-dependently inhibited, and superoxide radicals scavenging activity was also shown in a dose-dependent manner. It was concluded that TCE has hepatoprotective activity and the mechanisms underlying its protective effects may be related to the direct mitochondrion protection and strong scavenging activity on reactive oxygen species (ROS). PMID:15481641

  3. Neuroendocrine, metabolic, and immune functions during the acute phase response of inflammatory stress in monosodium L-glutamate-damaged, hyperadipose male rat.

    PubMed

    Castrogiovanni, Daniel; Gaillard, Rolf C; Giovambattista, Andrés; Spinedi, Eduardo

    2008-01-01

    In rats, neonatal treatment with monosodium L-glutamate (MSG) induces several metabolic and neuroendocrine abnormalities, which result in hyperadiposity. No data exist, however, regarding neuroendocrine, immune and metabolic responses to acute endotoxemia in the MSG-damaged rat. We studied the consequences of MSG treatment during the acute phase response of inflammatory stress. Neonatal male rats were treated with MSG or vehicle (controls, CTR) and studied at age 90 days. Pituitary, adrenal, adipo-insular axis, immune, metabolic and gonadal functions were explored before and up to 5 h after single sub-lethal i.p. injection of bacterial lipopolysaccharide (LPS; 150 microg/kg). Our results showed that, during the acute phase response of inflammatory stress in MSG rats: (1) the corticotrope-adrenal, leptin, insulin and triglyceride responses were higher than in CTR rats, (2) pro-inflammatory (TNFalpha) cytokine response was impaired and anti-inflammatory (IL-10) cytokine response was normal, and (3) changes in peripheral estradiol and testosterone levels after LPS varied as in CTR rats. These data indicate that metabolic and neroendocrine-immune functions are altered in MSG-damaged rats. Our study also suggests that the enhanced corticotrope-corticoadrenal activity in MSG animals could be responsible, at least in part, for the immune and metabolic derangements characterizing hypothalamic obesity. PMID:18382067

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

    PubMed

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

    2016-07-01

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

  5. Trans-Differentiation of Neural Stem Cells: A Therapeutic Mechanism Against the Radiation Induced Brain Damage

    PubMed Central

    Kang, Bong Gu; Lee, Se Jeong; Kim, Kang Ho; Yang, Heekyoung; Lee, Young-Ae; Cho, Yu Jin; Im, Yong-Seok; Lee, Dong-Sup; Lim, Do-Hoon; Kim, Dong Hyun; Um, Hong-Duck; Lee, Sang-Hun; Lee, Jung-II; Nam, Do-Hyun

    2012-01-01

    Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases. PMID:22347993

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

    PubMed Central

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

    2014-01-01

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

  7. Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

    PubMed Central

    Hou, Shuai; Shen, Ping-Ping; Zhao, Ming-Ming; Liu, Xiu-Ping; Xie, Hong-Yan; Deng, Fang; Feng, Jia-Chun

    2016-01-01

    We observed mitochondrial connexin43 (mtCx43) expression under cerebral ischemia-reperfusion (I/R) injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO). Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. MtCx43, p-mtCx43, protein kinase C (PKC), and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX) and diazoxide (DZX) groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD) groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA) reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists. PMID:27164087

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

    SciTech Connect

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

    2005-11-28

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

  9. Creep in Thermally Cracked Granite: Physical, Mechanical and Damage Properties Evolution

    NASA Astrophysics Data System (ADS)

    Wang, X.; Schubnel, A. J.; Fortin, J.; Gueguen, Y.; Ge, H.

    2011-12-01

    We investigate the effects of pervasive crack damage on the rupture processes of a fine-grained granite, under triaxial stress, in wet (H20) and dry (argon gas) saturated conditions, at room temperature. Eight samples of La Peyratte granite (a granodiorite with an average grain size of 200 microns) were cored with an initial porosity of <1%. Damage was introduced by heating four samples up to 700°C. These were then compared to the intact granite specimens. 4 samples were deformed at a constant strain rate of 2x10-6/s until brittle failure occurred. 4 other samples were deformed in creep conditions. During these 8 experiments, at each step, we recorded strains, elastic wave velocities and Acoustic Emissions (AE). Our main results are: 1. The brittle strength of the sample remained unchanged (approx. 500MPa deviatoric stress at 30MPa effective pressure), whether the sample was heat-treated or not. We did not observe any significant water weakening as well. However, the onset of dilatancy was observed at lower deviatoric stress in the heat-treated specimen than for the intact ones. 2. Acoustic emissions revealed useful in order to image the rupture processes. Indeed, AE locations and Focal mechanism were in good agreement with the post mortem analysis of sample. In intact specimen, failure occurred after a larger premonitory AE activity, while heat-treated specimen had a longer aftershocks activity. In creep conditions, we show that extreme damage localization is already initiated during the primary and secondary creep phases. 3. However, in all our experiments, we observed the development of an elastic fabric well before the onset of rupture. To be more precise, measuring the P wave velocities along two different horizontal travel paths - one perpendicular and one parallel to the eventual rupture plane, away from the nucleation zone - we showed that that both started to diverge as early as at 70% of the final rupture strength. This shows that quite early on during

  10. Mechanisms of Acute Kidney Injury Induced by Experimental Lonomia obliqua Envenomation

    PubMed Central

    Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O.; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R.; Ribeiro, Maria Aparecida; Guimarães, Jorge Almeida

    2015-01-01

    Background Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. Methods To characterize L. obliqua venom effects we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. Results L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman’s space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increases expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. Conclusions Mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia’s envenomation. PMID:24798088

  11. Mechanisms of acute kidney injury induced by experimental Lonomia obliqua envenomation.

    PubMed

    Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R; Vieira, Maria Aparecida Ribeiro; Guimarães, Jorge Almeida

    2015-03-01

    Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. To characterize L. obliqua venom effects, we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery-based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman's space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increase the expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. In conclusion, the mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia's envenomation. PMID:24798088

  12. Sites and Mechanisms of Localization of Technetium-99m Phosphorus Radiopharmaceuticals in Acute Myocardial Infarcts and other Tissues

    PubMed Central

    Buja, L. Maximilian; Tofe, Andrew J.; Kulkarni, Padmakar V.; Mukherjee, Amal; Parkey, Robert W.; Francis, Marion D.; Bonte, Frederick J.; Willerson, James T.

    1977-01-01

    This study was performed to elucidate the localization at the cellular level of technetium-99m phosphorus (99mTc-P) radiopharmaceuticals in acute myocardial infarcts and the mechanisms responsible for 99mTc-P uptake in acute myocardial infarcts and other tissues. In 20 dogs with proximal left anterior descending coronary arterial ligation for 1-3 days, elevated calcium levels were measured at all sites of increased 99mTc-P uptake (acute myocardial infarcts, necrotic thoracotomy muscle, lactating breast, and normal bone); however, a consistent linear relationship between 99mTc-P and calcium levels was not observed. A strong correlation (r = 0.95 and 0.99, n = 2 dogs) was demonstrated between levels of 3H-diphosphonate and 99mTc-P in infarcted myocardium. Autoradiographic studies with 3H-diphosphonate revealed extensive labeling in the infarct periphery which contained necrotic muscle cells with features of severe calcium overloading, including widespread hypercontraction as well as more selective formation of mitochondrial calcific deposits. Autoradiography also demonstrated labeling of a small population of damaged border zone muscle cells which exhibited prominent accumulation of lipid droplets and focal, early mitochondrial calcification. Cell fractionation studies revealed major localization of both 99mTc-P and calcium in the soluble supernate and membrane-debris fractions of infarcted myocardium and less than 2% of total 99mTc-P and calcium in the mitochondrial fractions; however, electron microscopic examination showed that mitochondria with calcific deposits were not preserved in the mitochondrial fractions. In vitro studies evaluating the role of serum protein binding on tissue uptake of 99mTc-P agents demonstrated that, in spite of significant complexing with serum proteins, serum 99mTc-P activity retained the ability to adsorp to calcium hydroxyapatite and amorphous calcium phosphate. In vivo studies showed that concentration of human serum albumin

  13. Cytoskeletal mechanisms regulating vascular endothelial barrier function in response to acute lung injury.

    PubMed

    Kása, Anita; Csortos, Csilla; Verin, Alexander D

    2015-01-01

    Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased vascular permeability. It is widely accepted that EC barrier integrity is critically dependent upon intact cytoskeletal structure and cell junctions. Edemagenic agonists, like thrombin or endotoxin lipopolysaccharide (LPS), induced cytoskeletal rearrangement, and EC contractile responses leading to disruption of intercellular contacts and EC permeability increase. The highly clinically-relevant cytoskeletal mechanisms of EC barrier dysfunction are currently under intense investigation and will be described and discussed in the current review. PMID:25838980

  14. Cytoskeletal mechanisms regulating vascular endothelial barrier function in response to acute lung injury

    PubMed Central

    Kása, Anita; Csortos, Csilla; Verin, Alexander D

    2014-01-01

    Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased vascular permeability. It is widely accepted that EC barrier integrity is critically dependent upon intact cytoskeletal structure and cell junctions. Edemagenic agonists, like thrombin or endotoxin lipopolysaccharide (LPS), induced cytoskeletal rearrangement, and EC contractile responses leading to disruption of intercellular contacts and EC permeability increase. The highly clinically-relevant cytoskeletal mechanisms of EC barrier dysfunction are currently under intense investigation and will be described and discussed in the current review. PMID:25838980

  15. Mechanism of action of lung damage caused by a nanofilm spray product.

    PubMed

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

    2014-08-01

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

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

    PubMed Central

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

    2014-01-01

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

  17. A Phenomenological Model for Mechanically Mediated Growth, Remodeling, Damage, and Plasticity of Gel-Derived Tissue Engineered Blood Vessels

    PubMed Central

    Raykin, Julia; Rachev, Alexander I.

    2011-01-01

    Mechanical stimulation has been shown to dramatically improve mechanical and functional properties of gel-derived tissue engineered blood vessels (TEBVs). Adjusting factors such as cell source, type of extracellular matrix, cross-linking, magnitude, frequency, and time course of mechanical stimuli (among many other factors) make interpretation of experimental results challenging. Interpretation of data from such multifactor experiments requires modeling. We present a modeling framework and simulations for mechanically mediated growth, remodeling, plasticity, and damage of gel-derived TEBVs that merge ideas from classical plasticity, volumetric growth, and continuum damage mechanics. Our results are compared with published data and suggest that this model framework can predict the evolution of geometry and material behavior under common experimental loading scenarios. PMID:19831486

  18. Impact Damage Detection in Composite Plates using a Self-diagnostic Electro-Mechanical Impedance-based Structural Health Monitoring System

    NASA Astrophysics Data System (ADS)

    Sharif-Khodaei, Z.; Ghajari, M.; Aliabadi, M. H.

    2015-03-01

    In this work, application of the electro-mechanical impedance (EMI) method in structural health monitoring as a damage detection technique has been investigated. A damage metric based on the real and imaginary parts of the impedance measures is introduced. Numerical and experimental tests are carried out to investigate the applicability of the method for various types of damage, such as debonding between the transducers and the plate, faulty sensors and impact damage in composite plates. The effect of several parameters, such as environmental effects, frequency sweep, severity of damage, location of damage, etc., on the damage metric has been reported.

  19. Mechanical Thrombectomy in Patients With Acute Ischemic Stroke: A Health Technology Assessment

    PubMed Central

    2016-01-01

    Background In Ontario, current treatment for eligible patients who have an acute ischemic stroke is intravenous thrombolysis (IVT). However, there are some limitations and contraindications to IVT, and outcomes may not be favourable for patients with stroke caused by a proximal intracranial occlusion. An alternative is mechanical thrombectomy with newer devices, and a number of recent studies have suggested that this treatment is more effective for improving functional independence and clinical outcomes. The objective of this health technology assessment was to evaluate the clinical effectiveness and cost-effectiveness of new-generation mechanical thrombectomy devices (with or without IVT) compared to IVT alone (if eligible) in patients with acute ischemic stroke. Methods We conducted a systematic review of the literature, limited to randomized controlled trials that examined the effectiveness of mechanical thrombectomy using stent retrievers and thromboaspiration devices for patients with acute ischemic stroke. We assessed the quality of the evidence using the GRADE approach. We developed a Markov decision-analytic model to assess the cost-effectiveness of mechanical thrombectomy (with or without IVT) versus IVT alone (if eligible), calculated incremental cost-effectiveness ratios using a 5-year time horizon, and conducted sensitivity analyses to examine the robustness of the estimates. Results There was a substantial, statistically significant difference in rate of functional independence (GRADE: high quality) between those who received mechanical thrombectomy (with or without IVT) and IVT alone (odds ratio [OR] 2.39, 95% confidence interval [CI] 1.88–3.04). We did not observe a difference in mortality (GRADE: moderate quality) (OR 0.80, 95% CI 0.60–1.07) or symptomatic intracerebral hemorrhage (GRADE: moderate quality) (OR 1.11, 95% CI 0.66–1.87). In the base-case cost-utility analysis, which had a 5 year time horizon, the costs and effectiveness for

  20. Brittle, creep and melt damage mechanics of the lithosphere: is slow creep deformation a key to intraplate volcanic provinces?

    NASA Astrophysics Data System (ADS)

    Liu, J.; Regenauer-Lieb, K.; Karrech, A.; Rosenbaum, G.; Lyakhovsky, V.

    2014-12-01

    We investigate the problem of intraplate melt generation with the aim of understanding spatial and temporal relationships between magmatism and extremely slow intraplate deformation. We present numerical models that consider feedback between melt generation and lithospheric deformation and incorporate three different damage mechanisms: brittle damage, creep damage, and melt damage. Melt conditions are calculated with a Gibbs energy minimization method, and the energy equation solved self-consistently for latent heat and shear heating effects. We use an extremely slowly lithosphere extension model (1-1.5 mm/y) to investigate the mechanics leading to intraplate volcanism in a cold lithosphere (~50mW/m2) such as the Harrat Ash-Shaam volcanic field in NW Arabia. We find that the extremely slow extension is a key to a very potent melt transfer mechanism through the lithosphere. The mechanism relies on multiple feedback mechanisms active in the accommodation of strain in the presence of fluids. These are capable of generating melts in the lithosphere/asthenosphere even in regions of relatively low heat flux. Once low degrees of partial melts are generated, the triple feedback between brittle-creep and melt damage leads to high porosity lithospheric-scale shear zones capable of transferring melts and fluids to the surface. Efficient localization in the weaker ductile domains implies that the final pattern of strain distribution is controlled by slow creep from below rather than by brittle deformation from above. Our model provides an explanation for intraplate volcanic provinces, which appear to rely on slowly deforming lithospheres. A significant finding is that slow extension, rather than fast extension, can localize melt damage more effectively in the deeper creeping section of the lithosphere. This finding may have profound implications to the fundamental dynamic control on intraplate volcanism.

  1. Mechanical Revascularization for Acute Ischemic Stroke: A Single-Center, Retrospective Analysis

    SciTech Connect

    Jeromel, Miran Milosevic, Z. V. Kocijancic, I. J. Lovric, D.; Svigelj, V. Zvan, B.

    2013-04-15

    BackgroundEndovascular mechanical revascularization (thrombectomy) is an increasingly used method for intracranial large vessel recanalization in acute stroke. The purpose of the study was to analyze the recanalization rate, clinical outcome, and complication rate in our stroke patients treated with mechanical revascularization. A total of 57 patients with large vessel stroke (within 3 h for anterior and 12 h for posterior circulation) were treated with mechanical revascularization at a single center during 24 months. The primary goal of endovascular treatment using different mechanical devices was recanalization of the occluded vessel. Recanalization rate (reported as thrombolysis in cerebral infarction [TICI] score), clinical outcome (reported as National Institutes of Health Stroke Scale [NIHSS] score and modified Rankin scale [mRS] score), as well as periprocedural complications were analyzed. The mean age of the patients was 63.1 {+-} 12.9 years, with baseline median NIHSS score of 14 (interquartile range, 9.5-19). Successful recanalization (TICI 2b or 3) was achieved in 41 (72 %) patients. Twenty patients (35 %) presented with favorable outcome (mRS {<=}2) 30 days after stroke. Overall, significant neurological improvement ({>=}4 NIHSS point reduction) occurred in 36 (63 %) patients. A clinically significant procedure-related adverse events (vessel disruption, peri/postprocedural intracranial bleeding) defined with decline in NIHSS of {>=}4 or death occurred in three (5 %) patients. The study showed a high recanalization rate with improved clinical outcome and a low rate of periprocedural complications in our stroke patients treated with mechanical revascularization. Therefore, we could conclude that endovascular revascularization (primary or in combination with a bridging thrombolysis) was an effective and safe procedure for intracranial large vessel recanalization in acute stroke.

  2. Mechanism-anchored profiling derived from epigenetic networks predicts outcome in acute lymphoblastic leukemia

    PubMed Central

    Yang, Xinan; Huang, Yong; Chen, James L; Xie, Jianming; Sun, Xiao; Lussier, Yves A

    2009-01-01

    Background Current outcome predictors based on "molecular profiling" rely on gene lists selected without consideration for their molecular mechanisms. This study was designed to demonstrate that we could learn about genes related to a specific mechanism and further use this knowledge to predict outcome in patients – a paradigm shift towards accurate "mechanism-anchored profiling". We propose a novel algorithm, PGnet, which predicts a tripartite mechanism-anchored network associated to epigenetic regulation consisting of phenotypes, genes and mechanisms. Genes termed as GEMs in this network meet all of the following criteria: (i) they are co-expressed with genes known to be involved in the biological mechanism of interest, (ii) they are also differentially expressed between distinct phenotypes relevant to the study, and (iii) as a biomodule, genes correlate with both the mechanism and the phenotype. Results This proof-of-concept study, which focuses on epigenetic mechanisms, was conducted in a well-studied set of 132 acute lymphoblastic leukemia (ALL) microarrays annotated with nine distinct phenotypes and three measures of response to therapy. We used established parametric and non parametric statistics to derive the PGnet tripartite network that consisted of 10 phenotypes and 33 significant clusters of GEMs comprising 535 distinct genes. The significance of PGnet was estimated from empirical p-values, and a robust subnetwork derived from ALL outcome data was produced by repeated random sampling. The evaluation of derived robust network to predict outcome (relapse of ALL) was significant (p = 3%), using one hundred three-fold cross-validations and the shrunken centroids classifier. Conclusion To our knowledge, this is the first method predicting co-expression networks of genes associated with epigenetic mechanisms and to demonstrate its inherent capability to predict therapeutic outcome. This PGnet approach can be applied to any regulatory mechanisms including

  3. Mechanism for the acute effects of organophosphate pesticides on the adult 5-HT system.

    PubMed

    Judge, Sarah J; Savy, Claire Y; Campbell, Matthew; Dodds, Rebecca; Gomes, Larissa Kruger; Laws, Grace; Watson, Anna; Blain, Peter G; Morris, Christopher M; Gartside, Sarah E

    2016-02-01

    The neurotransmitter serotonin (5-HT) is involved in mood disorder aetiology and it has been reported that (organophosphate) OP exposure affects 5-HT turnover. The aim of this study was to elucidate the mechanism underlying OP effects on the adult 5-HT system. First, acute in vivo administration of the OP diazinon (0, 1.3, 13 or 39 mg/kg i.p.) to male Hooded Lister rats inhibited the activity of the cholinergic enzyme acetylcholinesterase in blood and in the hippocampus, dorsal raphe nucleus (DRN), striatum and prefrontal cortex. Diazinon-induced cholinesterase inhibition was greatest in the DRN, the brain's major source of 5-HT neurones. Second, acute in vivo diazinon exposure (0 or 39 mg/kg i.p.) increased the basal firing rate of DRN neurones measured ex vivo in brain slices. The excitatory responses of DRN neurones to α1-adrenoceptor or AMPA/kainate receptor activation were not affected by in vivo diazinon exposure but the inhibitory response to 5-HT was attenuated, indicating 5-HT1A autoreceptor down-regulation. Finally, direct application of the diazinon metabolite diazinon oxon to naive rat brain slices increased the firing rate of DRN 5-HT neurones, as did chlorpyrifos-oxon, indicating the effect was not unique to diazinon. The oxon-induced augmentation of firing was blocked by the nicotinic acetylcholine receptor antagonist mecamylamine and the AMPA/kainate glutamate receptor antagonist DNQX. Together these data indicate that 1) acute OP exposure inhibits DRN cholinesterase, leading to acetylcholine accumulation, 2) the acetylcholine activates nicotinic receptors on 5-HT neurones and also on glutamatergic neurones, thus releasing glutamate and activating 5-HT neuronal AMPA/kainate receptors 3) the increase in 5-HT neuronal activity, and resulting 5-HT release, may lead to 5-HT1A autoreceptor down-regulation. This mechanism may be involved in the reported increase in risk of developing anxiety and depression following occupational OP exposure. PMID

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

    NASA Astrophysics Data System (ADS)

    Mita, Akira; Takhira, Shinpei

    2003-04-01

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

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

    PubMed Central

    Meier, Bettina; Gartner, Anton

    2014-01-01

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

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

    PubMed

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

    2016-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    PubMed Central

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

    2013-01-01

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

  9. Mechanisms of Hg species induced toxicity in cultured human astrocytes: genotoxicity and DNA-damage response.

    PubMed

    Pieper, Imke; Wehe, Christoph A; Bornhorst, Julia; Ebert, Franziska; Leffers, Larissa; Holtkamp, Michael; Höseler, Pia; Weber, Till; Mangerich, Aswin; Bürkle, Alexander; Karst, Uwe; Schwerdtle, Tanja

    2014-03-01

    The toxicologically most relevant mercury (Hg) species for human exposure is methylmercury (MeHg). Thiomersal is a common preservative used in some vaccine formulations. The aim of this study is to get further mechanistic insight into the yet not fully understood neurotoxic modes of action of organic Hg species. Mercury species investigated include MeHgCl and thiomersal. Additionally HgCl2 was studied, since in the brain mercuric Hg can be formed by dealkylation of the organic species. As a cellular system astrocytes were used. In vivo astrocytes provide the environment necessary for neuronal function. In the present study, cytotoxic effects of the respective mercuricals increased with rising alkylation level and correlated with their cellular bioavailability. Further experiments revealed for all species at subcytotoxic concentrations no induction of DNA strand breaks, whereas all species massively increased H2O2-induced DNA strand breaks. This co-genotoxic effect is likely due to a disturbance of the cellular DNA damage response. Thus, at nanomolar, sub-cytotoxic concentrations, all three mercury species strongly disturbed poly(ADP-ribosyl)ation, a signalling reaction induced by DNA strand breaks. Interestingly, the molecular mechanism behind this inhibition seems to be different for the species. Since chronic PARP-1 inhibition is also discussed to sacrifice neurogenesis and learning abilities, further experiments on neurons and in vivo studies could be helpful to clarify whether the inhibition of poly(ADP-ribosyl)ation contributes to organic Hg induced neurotoxicity. PMID:24549367

  10. Ultimate tensile strength of dentin: Evidence for a damage mechanics approach to dentin failure.

    PubMed

    Staninec, Michal; Marshall, Grayson W; Hilton, Joan F; Pashley, David H; Gansky, Stuart A; Marshall, Sally J; Kinney, John H

    2002-01-01

    Dentin structure and properties are known to vary with orientation and location. The present study explored the variation in the ultimate tensile strength (UTS) of dentin with location in the tooth. Hourglass specimens were prepared from dentin located in the center, under cusps, and in the cervical regions of human molar teeth. These were tested in tension at various distances from the pulp. Median tensile strengths ranged from 44.4 MPa in the inner dentin near the pulp, to 97.8 MPa near the dentino-enamel junction (DEJ). This increase in the median UTS with distance from the pulp to the DEJ was statistically significant (P <.001). Of particular importance was the observation that the UTS measurements followed a Weibull probability distribution, with a Weibull modulus of about 4.5. The Weibull behavior of the UTS data strongly suggests that the large variances in fracture strength data result from a distribution of preexisting defects in the dentin. These findings justify a damage-mechanics approach to studies of dentin failure. PMID:12115767

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

    NASA Astrophysics Data System (ADS)

    Narayanan, Arun; Subramaniam, Kolluru V. L.

    2016-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  14. Usefulness of the Pain Tracking Technique in Acute Mechanical Low Back Pain

    PubMed Central

    Bravo Acosta, Tania; Martín Cordero, Jorge E.; Hernández Tápanes, Solangel; Pedroso Morales, Isis; Fernández Cuesta, José Ignacio; Leyva Serrano, Maritza

    2015-01-01

    Objective. To evaluate the usefulness of the pain tracking technique in acute mechanical low back pain. Method. We performed an experimental prospective (longitudinal) explanatory study between January 2011 and September 2012. The sample was randomly divided into two groups. Patients were assessed at the start and end of the treatment using the visual analogue scale and the Waddell test. Treatment consisted in applying the pain tracking technique to the study group and interferential current therapy to the control group. At the end of treatment, cryotherapy was applied for 10 minutes. The Wilcoxon signed-rank test and the Mann Whitney test were used. They were performed with a predetermined significance level of p ≤ 0.05. Results. Pain was triggered by prolonged static posture and intense physical labor and intensified through trunk movements and when sitting and standing. The greatest relief was reported in lateral decubitus position and in William's position. The majority of the patients had contracture. Pain and disability were modified with the rehabilitation treatment in both groups. Conclusions. Both the pain tracking and interferential current techniques combined with cryotherapy are useful treatments for acute mechanical low back pain. The onset of analgesia is faster when using the pain tracking technique. PMID:26240758

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

    NASA Astrophysics Data System (ADS)

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

    2011-05-01

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

  16. Scintillation mechanism and radiation damage in Ce{sub x}La{sub 1-x}F{sub 3} crystals

    SciTech Connect

    Wojtowicz, A.J.; Wisniewski, D. |; Lempicki, A.; Brecher, C.; Bartram, R.H.; Woody, C.; Levy, P.; Stoll, S.; Kierstead, J.; Pedrini, C.

    1994-08-01

    Recent spectroscopic and radiation damage experiments on a series of Ce{sub x}La{sub 1{minus}x}F{sub 3} crystals suggest that the scintillation light output is limited by an unusual quenching mechanism, which also plays a major role in minimizing radiation-induced damage. The intensity of the radiation-induced absorptions is a strong function of the Ce content x, reaching a maximum for x = 0.03 and a minimum for x = 1. This peculiar dependence appears to be due to the influence of deep-lying Ce levels on both scintillation mechanism and radiation damage. The authors suggest that various charge transfer processes can explain many aspects of the performance of Ce{sub x}La{sub 1{minus}x}F{sub 3} scintillators.

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

    SciTech Connect

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

    1995-10-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury*

    PubMed Central

    Zhang, Xi-ping; Wang, Lei; Zhang, Jie

    2007-01-01

    Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death. Its complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression. PMID:17444596

  1. Endovascular Mechanical Recanalisation of Acute Carotid-T Occlusions: A Single-Center Retrospective Analysis

    SciTech Connect

    Fesl, Gunther; Wiesmann, Martin; Patzig, Maximilian; Holtmannspoetter, Markus; Pfefferkorn, Thomas; Dichgans, Martin; Brueckmann, Hartmut

    2011-04-15

    Purpose: Acute carotid-T occlusion generally responds poorly to thrombolysis. Endovascular mechanical thrombectomy (EMT) seems to be a promising alternative. However, there are few data on EMT in carotid-T occlusions. Materials and Methods: We reviewed data of 14 consecutive patients with acute carotid-T occlusions treated with mechanical recanalisation devices. A clot separation/aspiration system was used in 11 patients; different other mechanical retriever devices were used in seven patients; and stents were used in four patients. Modified Rankin Scale scores at 90 days were recorded to assess functional outcome. Results: Six women and eight men were included in the study. Mean patient age was 59.2 years; median National Institute of Health Stroke Scale score on admission was 19; and mean time to treatment was 4.2 h. Successful recanalisation (Thrombolysis in Myocardial Infarction [TIMI] score II and III) was achieved in 11 patients (78.6%). Seven patients (50.0%) were treated with more than one device, leading to successful recanalisation in six of these patients (85.7%). Subarachnoid haemorrhage and large space-occupying bleedings occurred in one (7.1%) and three (21.4%) patients, respectively. At follow-up, three patients (21.4%) were functionally independent, and six (42.9%) had died. Conclusion: When applying different mechanical devices, we found a high recanalisation rate. However, discrepancy between recanalisation and clinical outcome remained. More data are needed to assess the effect of the different methods on the prognoses of stroke patients.

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

    EPA Science Inventory

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

    Inorganic arsenic (iAs, arsenite and arsenate) has been thought to act as a carcinogen without reacting directly with DNA; neither iAs nor the As(...

  3. Ion implantation in Al{sub x}Ga{sub 1-x}As : damage structures and amorphization mechanisms.

    SciTech Connect

    Lagow, B. W.; Turkot, B. A.; Robertson, I. M.; Coleman, J. J.; Roh, S. D.; Forbes, D. V.; Rehn, L. E.; Baldo, P. M.; Materials Science Division; Univ. of Illinois

    1998-07-01

    We review previous research on ion implantation in Al{sub x}Ga{sub 1-x}As-GaAs heterostructures, and include observations from our current work in order to assess the various mechanisms that have been proposed to account for damage accumulation and amorphization in this system. In considering all of the experimental observations, the most consistent description is one where amorphization occurs by a combination of point-defect buildup and direct impact amorphization mechanisms.

  4. Comparison of ex-situ volatile emissions from intact and mechanically damaged walnuts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The codling moth (Cydia pomonella) and navel orangeworm (Amyelois transitella) are insect pests that inflict serious economic damage to California walnuts. Feeding by these larvae causes physical damage, resulting in lower kernel quality, and can lead to fungal contamination by the aflatoxigenic fun...

  5. Common Practice Lightning Strike Protection Characterization Technique to Quantify Damage Mechanisms on Composite Substrates

    NASA Technical Reports Server (NTRS)

    Szatkowski, George N.; Dudley, Kenneth L.; Koppen, Sandra V.; Ely, Jay J.; Nguyen, Truong X.; Ticatch, Larry A.; Mielnik, John J.; Mcneill, Patrick A.

    2013-01-01

    To support FAA certification airworthiness standards, composite substrates are subjected to lightning direct-effect electrical waveforms to determine performance characteristics of the lightning strike protection (LSP) conductive layers used to protect composite substrates. Test results collected from independent LSP studies are often incomparable due to variability in test procedures & applied practices at different organizations, which impairs performance correlations between different LSP data sets. Under a NASA supported contract, The Boeing Company developed technical procedures and documentation as guidance in order to facilitate a test method for conducting universal common practice lightning strike protection test procedures. The procedures obtain conformity in future lightning strike protection evaluations to allow meaningful performance correlations across data sets. This universal common practice guidance provides the manufacturing specifications to fabricate carbon fiber reinforced plastic (CFRP) test panels, including finish, grounding configuration, and acceptable methods for pretest nondestructive inspection (NDI) and posttest destructive inspection. The test operations guidance elaborates on the provisions contained in SAE ARP5416 to address inconsistencies in the generation of damage protection performance data, so as to provide for maximum achievable correlation across capable lab facilities. In addition, the guidance details a direct effects test bed design to aid in quantification of the multi-physical phenomena surrounding a lightning direct attachment supporting validation data requirements for the development of predictive computational modeling. The lightning test bed is designed to accommodate a repeatable installation procedure to secure the test panel and eliminate test installation uncertainty. It also facilitates a means to capture the electrical waveform parameters in 2 dimensions, along with the mechanical displacement and thermal

  6. Blood damage through a bileaflet mechanical heart valve: a quantitative computational study using a multiscale suspension flow solver.

    PubMed

    Min Yun, B; Aidun, Cyrus K; Yoganathan, Ajit P

    2014-10-01

    Bileaflet mechanical heart valves (BMHVs) are among the most popular prostheses to replace defective native valves. However, complex flow phenomena caused by the prosthesis are thought to induce serious thromboembolic complications. This study aims at employing a novel multiscale numerical method that models realistic sized suspended platelets for assessing blood damage potential in flow through BMHVs. A previously validated lattice-Boltzmann method (LBM) is used to simulate pulsatile flow through a 23 mm St. Jude Medical (SJM) Regent™ valve in the aortic position at very high spatiotemporal resolution with the presence of thousands of suspended platelets. Platelet damage is modeled for both the systolic and diastolic phases of the cardiac cycle. No platelets exceed activation thresholds for any of the simulations. Platelet damage is determined to be particularly high for suspended elements trapped in recirculation zones, which suggests a shift of focus in blood damage studies away from instantaneous flow fields and toward high flow mixing regions. In the diastolic phase, leakage flow through the b-datum gap is shown to cause highest damage to platelets. This multiscale numerical method may be used as a generic solver for evaluating blood damage in other cardiovascular flows and devices. PMID:25070372

  7. Assessing the Impact of Mechanical Damage on Full-Thickness Porcine and Human Skin Using an In Vitro Approach

    PubMed Central

    Dabboue, Hinda; Builles, Nicolas; Frouin, Éric; Scott, Dan; Ramos, Jeanne; Marti-Mestres, Gilberte

    2015-01-01

    For most xenobiotics, the rates of percutaneous absorption are limited by diffusion through the horny layer of skin. However, percutaneous absorption of chemicals may seriously increase when the skin is damaged. The aim of this work was to develop an in vitro representative model of mechanically damaged skins. The epidermal barrier was examined following exposure to a razor, a rotating brush, and a microneedle system in comparison to tape-stripping which acted as a reference. Excised full-thickness skins were mounted on a diffusion chamber in order to evaluate the effect of injuries and to mimic physiological conditions. The transepidermal water loss (TEWL) was greatly increased when the barrier function was compromised. Measurements were made for all the damaged biopsies and observed histologically by microscopy. On human and porcine skins, the tape-stripping application (0 to 40 times) showed a proportional increase in TEWL which highlights the destruction of the stratum corneum. Similar results were obtained for all cosmetic instruments. This is reflected in our study by the nonsignificant difference of the mean TEWL scores between 30 strips and mechanical damage. For a specific appreciation, damaged skins were then selected to qualitatively evaluate the absorption of a chlorogenic acid solution using fluorescence microscopy. PMID:26247021

  8. Assessing the Impact of Mechanical Damage on Full-Thickness Porcine and Human Skin Using an In Vitro Approach.

    PubMed

    Dabboue, Hinda; Builles, Nicolas; Frouin, Éric; Scott, Dan; Ramos, Jeanne; Marti-Mestres, Gilberte

    2015-01-01

    For most xenobiotics, the rates of percutaneous absorption are limited by diffusion through the horny layer of skin. However, percutaneous absorption of chemicals may seriously increase when the skin is damaged. The aim of this work was to develop an in vitro representative model of mechanically damaged skins. The epidermal barrier was examined following exposure to a razor, a rotating brush, and a microneedle system in comparison to tape-stripping which acted as a reference. Excised full-thickness skins were mounted on a diffusion chamber in order to evaluate the effect of injuries and to mimic physiological conditions. The transepidermal water loss (TEWL) was greatly increased when the barrier function was compromised. Measurements were made for all the damaged biopsies and observed histologically by microscopy. On human and porcine skins, the tape-stripping application (0 to 40 times) showed a proportional increase in TEWL which highlights the destruction of the stratum corneum. Similar results were obtained for all cosmetic instruments. This is reflected in our study by the nonsignificant difference of the mean TEWL scores between 30 strips and mechanical damage. For a specific appreciation, damaged skins were then selected to qualitatively evaluate the absorption of a chlorogenic acid solution using fluorescence microscopy. PMID:26247021

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

    PubMed

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

    2013-11-01

    Blood vessel is one of the most important targets encountered during focused ultrasound (FU) therapy. The lasting high temperature caused by continuous FU can result in structural modification of small vessel. For the vessel with a diameter larger than 2mm, convective cooling can significantly weaken the thermal effect of FU. Meanwhile, the continued presence of ultrasound will cause repetitive cavitation and acoustic microstreaming, making comprehension of continuous wave induced cavitation effect in large vessels necessary. The Sonoluminescence (SL) method, mechanical damage observation and high-speed camera were used in this study to investigate the combination effect of ultrasound contrast agents (UCAs) and continuous FU in large phantom vessels with a diameter of 10mm without consideration of thermal effect. When the focus was positioned at the proximal wall, cylindrical hole along the acoustic axis opposite the ultrasound wave propagation direction was observed at the input power equal to or greater than 50 W. When the focus was located at the distal wall, only small tunnels can be found. The place where the cylindrical hole formed was corresponding to where bubbles gathered and emitted brilliant light near the wall. Without UCAs neither such bright SL nor cylindrical hole can be found. However, the UCAs concentration had little influence on the SL distribution and the length of cylindrical hole. The SL intensity near the proximal vessel wall and the length of the cylindrical hole both increased with the input power. It is suggested that these findings need to be considered in the large vessel therapy and UCAs usage. PMID:23623758

  10. Modelling and simulations of the chemo-mechanical behaviour of leached cement-based materials: Interactions between damage and leaching

    SciTech Connect

    Stora, E.; Bary, B.; Deville, E.; Montarnal, P.

    2010-08-15

    The assessment of the durability of cement-based materials, which could be employed in underground structures for nuclear waste disposal, requires accounting for deterioration factors, such as chemical attacks and damage, and for the interactions between these phenomena. The objective of the present paper consists in investigating the long-term behaviour of cementitious materials by simulating their response to chemical and mechanical solicitations. In a companion paper (Stora et al., submitted to Cem. Concr. Res. 2008), the implementation of a multi-scale homogenization model into an integration platform has allowed for evaluating the evolution of the mineral composition, diffusive and elastic properties inside a concrete material subjected to leaching. To complete this previous work, an orthotropic micromechanical damage model is presently developed and incorporated in this numerical platform to estimate the mechanical and diffusive properties of damaged cement-based materials. Simulations of the chemo-mechanical behaviour of leached cementitious materials are performed with the tool thus obtained and compared with available experiments. The numerical results are insightful about the interactions between damage and chemical deteriorations.

  11. Interstitial Outburst of Angiogenic Factors During Skeletal Muscle Regeneration After Acute Mechanical Trauma.

    PubMed

    Ceafalan, Laura Cristina; Manole, Emilia; Tanase, Cristiana Pistol; Codrici, Elena; Mihai, Simona; Gonzalez, Aldebarani; Popescu, Bogdan Ovidiu

    2015-11-01

    Angiogenesis is a key event during tissue regeneration, but the intimate mechanisms controlling this process are still largely unclear. Therefore, the cellular and molecular interplay along normal tissue regeneration should be carefully unveiled. To this matter, we investigated by xMAP assay the dynamics of some angiogenic factors known to be involved in tissue repair, such as follistatin (FST), Placental Growth Factor-2 (PLGF-2), epidermal growth factor (EGF), betacellulin (BTC), and amphiregulin (AREG) using an animal model that mimics acute muscle contusion injuries. In situ immunofluorescence was used for the evaluation and tissue distribution of their cellular sources. Tissue levels of explored factors increased significantly during degeneration and inflammatory stage of regeneration, peaking first week postinjury. However, except for PLGF-2 and EGF, their levels remained significantly elevated after the inflammatory process started to fade. Serum levels were significantly increased only after 24 h for AREG and EGF. Though, for all factors except FST, the levels in injured samples did not correlate with serum or contralateral tissue levels, excluding the systemic influence. We found significant correlations between the levels of EGF and AREG, BTC, FST and FST and AREG in injured samples. Interstitial cells expressing these factors were highlighted by in situ immunolabeling and their number correlated with measured levels dynamics. Our study provides evidence of a dynamic level variation along the regeneration process and a potential interplay between selected angiogenic factors. They are synthesized, at least partially, by cell populations residing in skeletal muscle interstitium during regeneration after acute muscle trauma. PMID:26260512

  12. Mutations of Complement Factor I and Potential Mechanisms of Neuroinflammation in Acute Hemorrhagic Leukoencephalitis

    PubMed Central

    Broderick, Lori; Gandhi, Chhavi; Mueller, James L.; Putnam, Christopher D.; Shayan, Katayoon; Giclas, Patricia C.; Peterson, Karin S.; Aceves, Seema S.; Sheets, Robert M.; Peterson, Bradley M.; Newbury, Robert O.; Hoffman, Hal M.; Bastian, John F.

    2012-01-01

    Purpose Acute Hemorrhagic Leukoencephalitis (AHLE) is a rare demyelinating disorder of acute onset, rapid deterioration and significant morbidity and mortality. Most often described as a post-infectious complication of an upper respiratory illness, its precise pathophysiology remains unclear. We describe two pediatric patients with AHLE with partial complement factor I (FI) deficiency whose successful treatment included the interleukin-1 (IL-1) receptor antagonist, anakinra, implicating a role for FI and IL-1 in this disorder. Methods Extensive clinical workup of two patients presenting with AHLE revealed complement abnormalities, specifically related to the alternative pathway and its regulator, FI. Aggressive management with steroids, immunoglobulin, and anakinra ultimately led to improvement of clinical status and near return to neurologic baseline in both patients. Genetic sequencing of the FI coding regions of the patients and their families was performed. In vitro protein expression studies and immunohistochemistry of fixed brain tissue was used to investigate pathogenic mechanisms. Results Two novel mutations in FI were identified in our patients, which result in failure to secrete FI. Immunohistochemical evaluation of brain tissue demonstrated positive staining for C3, membrane attack complex (MAC) and IL-1. Conclusions We propose AHLE is an unreported, rare phenotype for partial FI deficiency. The upregulation of C3, MAC and IL-1 with subsequent demyelination support a pathologic role for complement activation in AHLE, and suggest anakinra as an important adjunctive therapy in this disease. PMID:22926405

  13. Incidence of acute volleyball injuries: a prospective cohort study of injury mechanisms and risk factors.

    PubMed

    Bahr, R; Bahr, I A

    1997-06-01

    The purpose of the study was to examine the incidence and mechanisms of acute volleyball injuries, with particular reference to possible risk factors for ankle injuries. Coaches and players in the top two divisions of the Norwegian Volleyball Federation were asked to keep records of exposure time and all acute volleyball injuries causing a player to miss at least one playing day during one season. We found 89 injuries among 272 players during 51588 player hours, 45837 h of training and 5751 h of match play. The total injury incidence was 1.7 +/- 0.2 per 1000 h of play, 1.5 +/- 0.2 during training and 3.5 +/- 0.8 during match play. The ankle (54%) was the most commonly injured region, followed by the lower back (11%), knee (8%), shoulder (8%) and fingers (7%). Of the ankle injuries, 79% were recurrences, and the relative risk of injury was 3.8 (P < 0.0001) for previously injured ankles (38 of 232) vs. non-injured ankles (10 of the 234). Moreover, a reinjury was observed in 21 of the 50 ankles that had suffered an ankle sprain within the last 6 months (42.0 +/- 7.0%; risk ratio: 9.8 vs. uninjured ankles; P < 0.000001). The data indicate that external supports should be worn for 6-12 months after an ankle sprain and that specific injury prevention programs may be developed for ankle sprains in volleyball. PMID:9200321

  14. Enteric Neuronal Damage, Intramuscular Denervation and Smooth Muscle Phenotype Changes as Mechanisms of Chagasic Megacolon: Evidence from a Long-Term Murine Model of Tripanosoma cruzi Infection

    PubMed Central

    Duz, Ana Luiza Cassin; Cartelle, Christiane Teixeira; Noviello, Maria de Lourdes; Veloso, Vanja Maria; Bahia, Maria Terezinha; Almeida-Leite, Camila Megale; Arantes, Rosa Maria Esteves

    2016-01-01

    We developed a novel murine model of long-term infection with Trypanosoma cruzi with the aim to elucidate the pathogenesis of megacolon and the associated adaptive and neuromuscular intestinal disorders. Our intent was to produce a chronic stage of the disease since the early treatment should avoid 100% mortality of untreated animals at acute phase. Treatment allowed animals to be kept infected and alive in order to develop the chronic phase of infection with low parasitism as in human disease. A group of Swiss mice was infected with the Y strain of T. cruzi. At the 11th day after infection, a sub-group was euthanized (acute-phase group) and another sub-group was treated with benznidazole and euthanized 15 months after infection (chronic-phase group). Whole colon samples were harvested and used for studying the histopathology of the intestinal smooth muscle and the plasticity of the enteric nerves. In the acute phase, all animals presented inflammatory lesions associated with intense and diffuse parasitism of the muscular and submucosa layers, which were enlarged when compared with the controls. The occurrence of intense degenerative inflammatory changes and increased reticular fibers suggests inflammatory-induced necrosis of muscle cells. In the chronic phase, parasitism was insignificant; however, the architecture of Aüerbach plexuses was focally affected in the inflamed areas, and a significant decrease in the number of neurons and in the density of intramuscular nerve bundles was detected. Other changes observed included increased thickness of the colon wall, diffuse muscle cell hypertrophy, and increased collagen deposition, indicating early fibrosis in the damaged areas. Mast cell count significantly increased in the muscular layers. We propose a model for studying the long-term (15 months) pathogenesis of Chagasic megacolon in mice that mimics the human disease, which persists for several years and has not been fully elucidated. We hypothesize that the long

  15. Enteric Neuronal Damage, Intramuscular Denervation and Smooth Muscle Phenotype Changes as Mechanisms of Chagasic Megacolon: Evidence from a Long-Term Murine Model of Tripanosoma cruzi Infection.

    PubMed

    Campos, Camila França; Cangussú, Silvia Dantas; Duz, Ana Luiza Cassin; Cartelle, Christiane Teixeira; Noviello, Maria de Lourdes; Veloso, Vanja Maria; Bahia, Maria Terezinha; Almeida-Leite, Camila Megale; Arantes, Rosa Maria Esteves

    2016-01-01

    We developed a novel murine model of long-term infection with Trypanosoma cruzi with the aim to elucidate the pathogenesis of megacolon and the associated adaptive and neuromuscular intestinal disorders. Our intent was to produce a chronic stage of the disease since the early treatment should avoid 100% mortality of untreated animals at acute phase. Treatment allowed animals to be kept infected and alive in order to develop the chronic phase of infection with low parasitism as in human disease. A group of Swiss mice was infected with the Y strain of T. cruzi. At the 11th day after infection, a sub-group was euthanized (acute-phase group) and another sub-group was treated with benznidazole and euthanized 15 months after infection (chronic-phase group). Whole colon samples were harvested and used for studying the histopathology of the intestinal smooth muscle and the plasticity of the enteric nerves. In the acute phase, all animals presented inflammatory lesions associated with intense and diffuse parasitism of the muscular and submucosa layers, which were enlarged when compared with the controls. The occurrence of intense degenerative inflammatory changes and increased reticular fibers suggests inflammatory-induced necrosis of muscle cells. In the chronic phase, parasitism was insignificant; however, the architecture of Aüerbach plexuses was focally affected in the inflamed areas, and a significant decrease in the number of neurons and in the density of intramuscular nerve bundles was detected. Other changes observed included increased thickness of the colon wall, diffuse muscle cell hypertrophy, and increased collagen deposition, indicating early fibrosis in the damaged areas. Mast cell count significantly increased in the muscular layers. We propose a model for studying the long-term (15 months) pathogenesis of Chagasic megacolon in mice that mimics the human disease, which persists for several years and has not been fully elucidated. We hypothesize that the long

  16. Anti-B7-H3 monoclonal antibody ameliorates the damage of acute experimental pancreatitis by attenuating the inflammatory response.

    PubMed

    Zhuang, Xiaohui; Shen, Jiaqing; Jia, Zhengyu; Wu, Airong; Xu, Ting; Shi, Yuqi; Xu, Chunfang

    2016-06-01

    B7-H3, a recently discovered B7 family member, is documented as a regulator in the inflammatory response as well as T cell-mediated immune responses. In this paper, we find that patients with acute pancreatitis revealed overwhelming levels of serum soluble B7-H3 (sB7-H3) associated with the clinical outcomes. Furthermore, B7-H3 protein was marked increased in l-arginine-induced acute experimental pancreatitis. Anti-B7-H3 monoclonal antibody treatment attenuated the proinflammatory cytokine production, downregulated the activation of the NF-κB signaling pathway, and ameliorated the pancreas disruption in l-arginine-induced pancreatitis. In addition, although l-arginine alone failed to induce the production of proinflammatory cytokine and anti-B7-H3 mAb had no effect on the proinflammatory cytokine production of acinar cells, administration of anti-B7-H3 mAb in the coculture model of acinar cells and macrophages stimulated by l-arginine displayed the similar effects. On the whole, B7-H3 participates in the development of acute pancreatitis, and anti-B7-H3 monoclonal antibody ameliorates severity of acute experimental pancreatitis via attenuation of the inflammatory response. PMID:27003113

  17. Damage mechanisms and transparency changes in CO2-laser-irradiated glass

    NASA Astrophysics Data System (ADS)

    Guignard, Franck; Autric, Michel L.; Baudinaud, Vincent

    1998-04-01

    Transverse excited atmospheric pressure CO2 laser induced damage on BK7 and fused silica has been investigated. Damage processes have been characterized by looking at the transparency changes during irradiation with a helium-neon laser and plasma formation, with a photodiode. Both results are compared with thermal coupling and damage threshold measurements. The two glass qualities show slightly different behavior. BK7 shows surface crazing after irradiation, fused silica shows micro-fractures formation. In both cases, residual tensile stresses induced near the surface on cooling is identified as the most likely cause of cracking. A model was developed to calculate temperature and residual stresses, calculations results gives good agreement with damage thresholds measured.

  18. North American ginseng protects against muscle damage and reduces neutrophil infiltration after an acute bout of downhill running in rats.

    PubMed

    Estaki, Mehrbod; Noble, Earl G

    2015-02-01

    Eccentric muscle contractions such as those experienced during downhill running are associated with inflammation, delayed-onset of muscle soreness, myofiber damage, and various functional deficits. North American ginseng (Panax quinquefolius L.) has been reported to possess anti-inflammatory properties and thus may offset some of this exercise-induced damage. Hence, we tested the hypothesis that intervention with North American ginseng would reduce eccentric exercise-induced muscle damage and inflammation. Male Wistar rats were fed (300 mg/(kg·day)(-1)) of either an alcohol (AL) or aqueous (AQ) extract of North American ginseng for 14 days before a single bout of downhill running and were compared with matching nonexercised (C) groups. Plasma creatine kinase levels were significantly reduced in both ginseng treated groups compared with the C group that received a water placebo (p < 0.002). Further, the AQ but not AL group also showed attenuated morphological signs of damage (hemotoxylin and eosin) as well as reduced levels of infiltrating neutrophils (HIS48) in the soleus muscle (p < 0.001). In summary, supplementation with an AQ but not AL extract of North American ginseng was able to reduce eccentric exercise-induced muscle damage and inflammation. PMID:25531801

  19. [Mucolytics in acute and chronic respiratory tract disorders. I. Pathophysiology and mechanisms of action].

    PubMed

    Kupczyk, Maciej; Kuna, Piotr

    2002-03-01

    Mucus hypersecretion is a cardinal sign of both acute and chronic pulmonary diseases. Normally, mucus protects respiratory tract, but its overproduction leads to airway obstruction and promotes bacterial colonization. In the first part of our review we outlined the possible factors responsible for mucus hypersecretion and clinical consequences of this process. Mucolytic agents such as Ambroxol and N-acetylcysteine are able to alter the secretion of mucus and its physical properties which results in improvement of mucociliary clearance. Mechanisms of action and indications for use of mucolytics are presented. Mucolytics have been shown to have a role in improving lung functions and patients' quality of life. Undoubtedly they are useful as an adjunctive therapy of respiratory tract disorders. PMID:12053600

  20. CYLD Regulates Noscapine Activity in Acute Lymphoblastic Leukemia via a Microtubule-Dependent Mechanism

    PubMed Central

    Yang, Yunfan; Ran, Jie; Sun, Lei; Sun, Xiaodong; Luo, Youguang; Yan, Bing; Tala; Liu, Min; Li, Dengwen; Zhang, Lei; Bao, Gang; Zhou, Jun

    2015-01-01

    Noscapine is an orally administrable drug used worldwide for cough suppression and has recently been demonstrated to disrupt microtubule dynamics and possess anticancer activity. However, the molecular mechanisms regulating noscapine activity remain poorly defined. Here we demonstrate that cylindromatosis (CYLD), a microtubule-associated tumor suppressor protein, modulates the activity of noscapine both in cell lines and in primary cells of acute lymphoblastic leukemia (ALL). Flow cytometry and immunofluorescence microscopy reveal that CYLD increases the ability of noscapine to induce mitotic arrest and apoptosis. Examination of cellular microtubules as well as in vitro assembled microtubules shows that CYLD enhances the effect of noscapine on microtubule polymerization. Microtubule cosedimentation and fluorescence titration assays further reveal that CYLD interacts with microtubule outer surface and promotes noscapine binding to microtubules. These findings thus demonstrate CYLD as a critical regulator of noscapine activity and have important implications for ALL treatment. PMID:25897332

  1. CYLD Regulates Noscapine Activity in Acute Lymphoblastic Leukemia via a Microtubule-Dependent Mechanism.

    PubMed

    Yang, Yunfan; Ran, Jie; Sun, Lei; Sun, Xiaodong; Luo, Youguang; Yan, Bing; Tala; Liu, Min; Li, Dengwen; Zhang, Lei; Bao, Gang; Zhou, Jun

    2015-01-01

    Noscapine is an orally administrable drug used worldwide for cough suppression and has recently been demonstrated to disrupt microtubule dynamics and possess anticancer activity. However, the molecular mechanisms regulating noscapine activity remain poorly defined. Here we demonstrate that cylindromatosis (CYLD), a microtubule-associated tumor suppressor protein, modulates the activity of noscapine both in cell lines and in primary cells of acute lymphoblastic leukemia (ALL). Flow cytometry and immunofluorescence microscopy reveal that CYLD increases the ability of noscapine to induce mitotic arrest and apoptosis. Examination of cellular microtubules as well as in vitro assembled microtubules shows that CYLD enhances the effect of noscapine on microtubule polymerization. Microtubule cosedimentation and fluorescence titration assays further reveal that CYLD interacts with microtubule outer surface and promotes noscapine binding to microtubules. These findings thus demonstrate CYLD as a critical regulator of noscapine activity and have important implications for ALL treatment. PMID:25897332

  2. Scaling Between Fault Length, Damaged Zone Thickness and Width of Secondary Fault Fans Derived from Fracture Mechanics

    NASA Astrophysics Data System (ADS)

    Ampuero, Jean Paul; Mao, Xiaolin

    2016-04-01

    The interaction between earthquakes, fault network geometry and fault zone structure is a key question motivating the integration of dynamic rupture and long-term crustal deformation modeling. Here, we address the scaling between fault structural properties from the perspective of dynamic and quasi-static processes involved in fault system evolution. Faults are surrounded by materials damaged through quasi-static and dynamic processes, forming damaged zones whose thickness and damage intensity may vary as a function of fault maturity and length. In the vicinity (typically less than a few hundred meters) of their principal slip surface, faults develop an "inner damage zone", usually characterized by micro-fracture observations. At a larger scale, faults develop an "outer damage zone" of secondary macroscopic fault branches at their tips, which organize into fans of splay faults. Inner damage zones can significantly affect earthquake ruptures, enhance near-field ground motions and facilitate fluid transport in the crust. Fault zone trapped waves can generate pulse-like rupture and oscillatory rupture speed, facilitate supershear rupture transition and allow for steady rupture propagation at speeds that are unstable or inadmissible in homogeneous media. The effects of a fault damage zone crucially depend on its thickn