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Sample records for analysis reveal damage

  1. 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

  2. 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

  3. Structural Analysis of Shu Proteins Reveals a DNA Binding Role Essential for Resisting Damage*

    PubMed Central

    Tao, Yuyong; Li, Xu; Liu, Yiwei; Ruan, Jianbin; Qi, Shali; Niu, Liwen; Teng, Maikun

    2012-01-01

    The yeast Shu complex, consisting of the proteins Shu1, Shu2, Psy3, and Csm2, maintains genomic stability by coupling post-replication repair to homologous recombination. However, a lack of biochemical and structural information on the Shu proteins precludes revealing their precise roles within the pathway. Here, we report on the 1.9-Å crystal structure of the Psy3-Csm2 complex. The crystal structure shows that Psy3 forms a heterodimer with Csm2 mainly through a hydrophobic core. Unexpectedly, Psy3 and Csm2 share a similar architecture that closely resembles the ATPase core domain of Rad51. The L2 loop present in Psy3 and Csm2 is similar to that of Rad51 and confers the DNA binding activity of the Shu complex. As with Rad51, the Shu complex appears to form a nucleoprotein filament by binding nonspecifically to DNA. Structure-based mutagenesis studies have demonstrated that the DNA binding activity of the Shu complex is essential for repair of the methyl methanesulfonate-induced DNA damage. Our findings provide good foundations for the understanding of the Srs2 regulation by the Shu complex. PMID:22465956

  4. Phosphoproteomic analysis reveals that PP4 dephosphorylates KAP-1 impacting the DNA damage response

    PubMed Central

    Lee, Dong-Hyun; Goodarzi, Aaron A; Adelmant, Guillaume O; Pan, Yunfeng; Jeggo, Penelope A; Marto, Jarrod A; Chowdhury, Dipanjan

    2012-01-01

    Protein phosphatase PP4C has been implicated in the DNA damage response (DDR), but its substrates in DDR remain largely unknown. We devised a novel proteomic strategy for systematic identification of proteins dephosphorylated by PP4C and identified KRAB-domain-associated protein 1 (KAP-1) as a substrate. Ionizing radiation leads to phosphorylation of KAP-1 at S824 (via ATM) and at S473 (via CHK2). A PP4C/R3β complex interacts with KAP-1 and silencing this complex leads to persistence of phospho-S824 and phospho-S473. We identify a new role for KAP-1 in DDR by showing that phosphorylation of S473 impacts the G2/M checkpoint. Depletion of PP4R3β or expression of the phosphomimetic KAP-1 S473 mutant (S473D) leads to a prolonged G2/M checkpoint. Phosphorylation of S824 is necessary for repair of heterochromatic DNA lesions and similar to cells expressing phosphomimetic KAP-1 S824 mutant (S824D), or PP4R3β-silenced cells, display prolonged relaxation of chromatin with release of chromatin remodelling protein CHD3. Our results define a new role for PP4-mediated dephosphorylation in the DDR, including the regulation of a previously undescribed function of KAP-1 in checkpoint response. PMID:22491012

  5. Systems Analysis of the Dynamic Inflammatory Response to Tissue Damage Reveals Spatiotemporal Properties of the Wound Attractant Gradient.

    PubMed

    Weavers, Helen; Liepe, Juliane; Sim, Aaron; Wood, Will; Martin, Paul; Stumpf, Michael P H

    2016-08-01

    In the acute inflammatory phase following tissue damage, cells of the innate immune system are rapidly recruited to sites of injury by pro-inflammatory mediators released at the wound site. Although advances in live imaging allow us to directly visualize this process in vivo, the precise identity and properties of the primary immune damage attractants remain unclear, as it is currently impossible to directly observe and accurately measure these signals in tissues. Here, we demonstrate that detailed information about the attractant signals can be extracted directly from the in vivo behavior of the responding immune cells. By applying inference-based computational approaches to analyze the in vivo dynamics of the Drosophila inflammatory response, we gain new detailed insight into the spatiotemporal properties of the attractant gradient. In particular, we show that the wound attractant is released by wound margin cells, rather than by the wounded tissue per se, and that it diffuses away from this source at rates far slower than those of previously implicated signals such as H2O2 and ATP, ruling out these fast mediators as the primary chemoattractant. We then predict, and experimentally test, how competing attractant signals might interact in space and time to regulate multi-step cell navigation in the complex environment of a healing wound, revealing a period of receptor desensitization after initial exposure to the damage attractant. Extending our analysis to model much larger wounds, we uncover a dynamic behavioral change in the responding immune cells in vivo that is prognostic of whether a wound will subsequently heal or not. VIDEO ABSTRACT. PMID:27426513

  6. Automated Analysis of Cell Cycle Phase-Specific DNA Damage Reveals Phase-Specific Differences in Cell Sensitivity to Etoposide.

    PubMed

    Luzhin, Artem V; Velichko, Artem K; Razin, Sergey V; Kantidze, Omar L

    2016-10-01

    The comet assay is one of the most widely used approaches for detecting DNA damage; generally, it provides information on the cell population-averaged level of DNA damage. Here, we present an automatic technique for easy measurement of standard comet characteristics and an annotation of the cell cycle phase of each comet. The approach includes the modified neutral comet assay and a pipeline for CellProfiler software designed to analyze DNA damage-related characteristics and annotate the cell cycle phase of each comet. Using this technique we have performed cell cycle phase-specific analysis of DNA damage induced by the topoisomerase II poison etoposide and have shown that the sensitivity of cells to this drug dramatically differed according to their cell cycle phase. It became evident from our results that the proposed protocol provides important additional information that often remains hidden in a standard comet analysis of an asynchronous cell population. J. Cell. Biochem. 117: 2209-2214, 2016. © 2016 Wiley Periodicals, Inc. PMID:27240930

  7. Single-molecule analysis reveals human UV-damaged DNA-binding protein (UV-DDB) dimerizes on DNA via multiple kinetic intermediates

    PubMed Central

    Ghodke, Harshad; Wang, Hong; Hsieh, Ching L.; Woldemeskel, Selamawit; Watkins, Simon C.; Rapić-Otrin, Vesna; Van Houten, Bennett

    2014-01-01

    How human DNA repair proteins survey the genome for UV-induced photoproducts remains a poorly understood aspect of the initial damage recognition step in nucleotide excision repair (NER). To understand this process, we performed single-molecule experiments, which revealed that the human UV-damaged DNA-binding protein (UV-DDB) performs a 3D search mechanism and displays a remarkable heterogeneity in the kinetics of damage recognition. Our results indicate that UV-DDB examines sites on DNA in discrete steps before forming long-lived, nonmotile UV-DDB dimers (DDB1-DDB2)2 at sites of damage. Analysis of the rates of dissociation for the transient binding molecules on both undamaged and damaged DNA show multiple dwell times over three orders of magnitude: 0.3–0.8, 8.1, and 113–126 s. These intermediate states are believed to represent discrete UV-DDB conformers on the trajectory to stable damage detection. DNA damage promoted the formation of highly stable dimers lasting for at least 15 min. The xeroderma pigmentosum group E (XP-E) causing K244E mutant of DDB2 found in patient XP82TO, supported UV-DDB dimerization but was found to slide on DNA and failed to stably engage lesions. These findings provide molecular insight into the loss of damage discrimination observed in this XP-E patient. This study proposes that UV-DDB recognizes lesions via multiple kinetic intermediates, through a conformational proofreading mechanism. PMID:24760829

  8. A systematic analysis of factors localized to damaged chromatin reveals PARP-dependent recruitment of transcription factors

    PubMed Central

    Izhar, Lior; Adamson, Britt; Ciccia, Alberto; Lewis, Jedd; Pontano-Vaites, Laura; Leng, Yumei; Liang, Anthony C.; Westbrook, Thomas F.; Harper, J. Wade; Elledge, Stephen J.

    2015-01-01

    Localization to sites of DNA damage is a hallmark of DNA damage response (DDR) proteins. To identify new DDR factors, we screened epitope-tagged proteins for localization to sites of chromatin damaged by UV laser microirradiation and found >120 proteins that localize to damaged chromatin. These include the BAF tumor suppressor complex and the ALS candidate protein TAF15. TAF15 contains multiple domains that bind damaged chromatin in a PARP-dependent manner, suggesting a possible role as glue that tethers multiple PAR chains together. Many positives were transcription factors and >70% of randomly tested transcription factors localized to sites of DNA damage and approximately 90% were PARP-dependent for localization. Mutational analyses showed that localization to damaged chromatin is DNA-binding domain-dependent. By examining Hoechst staining patterns at damage sites, we see evidence of chromatin decompaction that is PARP-dependent. We propose that PARP-regulated chromatin remodeling at sites of damage allows transient accessibility of DNA-binding proteins. PMID:26004182

  9. Structural and functional analysis of the Crb2–BRCT2 domain reveals distinct roles in checkpoint signaling and DNA damage repair

    PubMed Central

    Kilkenny, Mairi L.; Doré, Andrew S.; Roe, S. Mark; Nestoras, Konstantinos; Ho, Jenny C.Y.; Watts, Felicity Z.; Pearl, Laurence H.

    2008-01-01

    Schizosaccharomyces pombe Crb2 is a checkpoint mediator required for the cellular response to DNA damage. Like human 53BP1 and Saccharomyces cerevisiae Rad9 it contains Tudor2 and BRCT2 domains. Crb2-Tudor2 domain interacts with methylated H4K20 and is required for recruitment to DNA dsDNA breaks. The BRCT2 domain is required for dimerization, but its precise role in DNA damage repair and checkpoint signaling is unclear. The crystal structure of the Crb2–BRCT2 domain, alone and in complex with a phosphorylated H2A.1 peptide, reveals the structural basis for dimerization and direct interaction with γ-H2A.1 in ionizing radiation-induced foci (IRIF). Mutational analysis in vitro confirms the functional role of key residues and allows the generation of mutants in which dimerization and phosphopeptide binding are separately disrupted. Phenotypic analysis of these in vivo reveals distinct roles in the DNA damage response. Dimerization mutants are genotoxin sensitive and defective in checkpoint signaling, Chk1 phosphorylation, and Crb2 IRIF formation, while phosphopeptide-binding mutants are only slightly sensitive to IR, have extended checkpoint delays, phosphorylate Chk1, and form Crb2 IRIF. However, disrupting phosphopeptide binding slows formation of ssDNA-binding protein (Rpa1/Rad11) foci and reduces levels of Rad22(Rad52) recombination foci, indicating a DNA repair defect. PMID:18676809

  10. Combined experimental and computational analysis of DNA damage signaling reveals context-dependent roles for Erk in apoptosis and G1/S arrest after genotoxic stress.

    PubMed

    Tentner, Andrea R; Lee, Michael J; Ostheimer, Gerry J; Samson, Leona D; Lauffenburger, Douglas A; Yaffe, Michael B

    2012-01-01

    Following DNA damage, cells display complex multi-pathway signaling dynamics that connect cell-cycle arrest and DNA repair in G1, S, or G2/M phase with phenotypic fate decisions made between survival, cell-cycle re-entry and proliferation, permanent cell-cycle arrest, or cell death. How these phenotypic fate decisions are determined remains poorly understood, but must derive from integrating genotoxic stress signals together with inputs from the local microenvironment. To investigate this in a systematic manner, we undertook a quantitative time-resolved cell signaling and phenotypic response study in U2OS cells receiving doxorubicin-induced DNA damage in the presence or absence of TNFα co-treatment; we measured key nodes in a broad set of DNA damage signal transduction pathways along with apoptotic death and cell-cycle regulatory responses. Two relational modeling approaches were then used to identify network-level relationships between signals and cell phenotypic events: a partial least squares regression approach and a complementary new technique which we term 'time-interval stepwise regression.' Taken together, the results from these analysis methods revealed complex, cytokine-modulated inter-relationships among multiple signaling pathways following DNA damage, and identified an unexpected context-dependent role for Erk in both G1/S arrest and apoptotic cell death following treatment with this commonly used clinical chemotherapeutic drug. PMID:22294094

  11. Silicon-wafer-surface damage revealed by surface photovoltage measurements

    NASA Astrophysics Data System (ADS)

    Goodman, Alvin M.

    1982-11-01

    Anomalous results of surface photovoltage (SPV) measurements on Si wafers are shown to be associated with a damaged region beneath the illuminated surface of the wafer being measured. The anomaly is a concave-upward curvature of the I0(α-1) plot with an r2 value, derived from linear regression analysis, less than the normally observed minimum value (˜0.98). Removal of the damaged region by an appropriate etching procedure allows subsequent SPV measurements whose results are substantially free of the previously observed anomaly. The qualitative character of the anomaly can be reproduced by a simple theoretical model in which only one effect of the damage is considered; this effect is a diminished quantum efficiency for hole-electron pair generation by photon absorption in the damaged region. The results suggest the use of SPV measurements as a test procedure for revealing the presence of surface damage in Si wafers.

  12. Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

    PubMed Central

    van Leeuwen, Elisabeth M; Sabo, Aniko; Bis, Joshua C; Huffman, Jennifer E; Manichaikul, Ani; Smith, Albert V; Feitosa, Mary F; Demissie, Serkalem; Joshi, Peter K; Duan, Qing; Marten, Jonathan; van Klinken, Jan B; Surakka, Ida; Nolte, Ilja M; Zhang, Weihua; Mbarek, Hamdi; Li-Gao, Ruifang; Trompet, Stella; Verweij, Niek; Evangelou, Evangelos; Lyytikäinen, Leo-Pekka; Tayo, Bamidele O; Deelen, Joris; van der Most, Peter J; van der Laan, Sander W; Arking, Dan E; Morrison, Alanna; Dehghan, Abbas; Franco, Oscar H; Hofman, Albert; Rivadeneira, Fernando; Sijbrands, Eric J; Uitterlinden, Andre G; Mychaleckyj, Josyf C; Campbell, Archie; Hocking, Lynne J; Padmanabhan, Sandosh; Brody, Jennifer A; Rice, Kenneth M; White, Charles C; Harris, Tamara; Isaacs, Aaron; Campbell, Harry; Lange, Leslie A; Rudan, Igor; Kolcic, Ivana; Navarro, Pau; Zemunik, Tatijana; Salomaa, Veikko; Kooner, Angad S; Kooner, Jaspal S; Lehne, Benjamin; Scott, William R; Tan, Sian-Tsung; de Geus, Eco J; Milaneschi, Yuri; Penninx, Brenda W J H; Willemsen, Gonneke; de Mutsert, Renée; Ford, Ian; Gansevoort, Ron T; Segura-Lepe, Marcelo P; Raitakari, Olli T; Viikari, Jorma S; Nikus, Kjell; Forrester, Terrence; McKenzie, Colin A; de Craen, Anton J M; de Ruijter, Hester M; Pasterkamp, Gerard; Snieder, Harold; Oldehinkel, Albertine J; Slagboom, P Eline; Cooper, Richard S; Kähönen, Mika; Lehtimäki, Terho; Elliott, Paul; van der Harst, Pim; Jukema, J Wouter; Mook-Kanamori, Dennis O; Boomsma, Dorret I; Chambers, John C; Swertz, Morris; Ripatti, Samuli; Willems van Dijk, Ko; Vitart, Veronique; Polasek, Ozren; Hayward, Caroline; Wilson, James G; Wilson, James F; Gudnason, Vilmundur; Rich, Stephen S; Psaty, Bruce M; Borecki, Ingrid B; Boerwinkle, Eric; Rotter, Jerome I; Cupples, L Adrienne; van Duijn, Cornelia M

    2016-01-01

    Background So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. Methods We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ∼60 000 individuals in the discovery stage and ∼90 000 samples in the replication stage. Results Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene. Conclusions This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels. PMID:27036123

  13. Different precursor populations revealed by microscopic studies of bulk damage in KDP and DKDP crystals

    SciTech Connect

    DeMange, P; Negres, R A; Radousky, H B; Demos, S G

    2005-10-31

    We present experimental results aiming to reveal the relationship between damage initiating defect populations in KDP and DKDP crystals under irradiation at different wavelengths. Our results indicate that there is more than one type of defects leading to damage initiation, each defect acting as damage initiators over a different wavelength range. Results showing disparities in the morphology of damage sites from exposure at different wavelengths provides additional evidence for the presence of multiple types of defects responsible for damage initiation.

  14. Gear Damage Detection Using Oil Debris Analysis

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.

    2001-01-01

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

  15. Femtosecond near-infrared laser microirradiation reveals a crucial role for PARP signaling on factor assemblies at DNA damage sites

    PubMed Central

    Saquilabon Cruz, Gladys Mae; Kong, Xiangduo; Silva, Bárbara Alcaraz; Khatibzadeh, Nima; Thai, Ryan; Berns, Michael W.; Yokomori, Kyoko

    2016-01-01

    Laser microirradiation is a powerful tool for real-time single-cell analysis of the DNA damage response (DDR). It is often found, however, that factor recruitment or modification profiles vary depending on the laser system employed. This is likely due to an incomplete understanding of how laser conditions/dosages affect the amounts and types of damage and the DDR. We compared different irradiation conditions using a femtosecond near-infrared laser and found distinct damage site recruitment thresholds for 53BP1 and TRF2 correlating with the dose-dependent increase of strand breaks and damage complexity. Low input-power microirradiation that induces relatively simple strand breaks led to robust recruitment of 53BP1 but not TRF2. In contrast, increased strand breaks with complex damage including crosslinking and base damage generated by high input-power microirradiation resulted in TRF2 recruitment to damage sites with no 53BP1 clustering. We found that poly(ADP-ribose) polymerase (PARP) activation distinguishes between the two damage states and that PARP activation is essential for rapid TRF2 recruitment while suppressing 53BP1 accumulation at damage sites. Thus, our results reveal that careful titration of laser irradiation conditions allows induction of varying amounts and complexities of DNA damage that are gauged by differential PARP activation regulating protein assembly at the damage site. PMID:26424850

  16. Quantitative Proteomics Reveals That Hsp90 Inhibition Preferentially Targets Kinases and the DNA Damage Response*

    PubMed Central

    Sharma, Kirti; Vabulas, R. Martin; Macek, Boris; Pinkert, Stefan; Cox, Jürgen; Mann, Matthias; Hartl, F. Ulrich

    2012-01-01

    Despite the increasing importance of heat shock protein 90 (Hsp90) inhibitors as chemotherapeutic agents in diseases such as cancer, their global effects on the proteome remain largely unknown. Here we use high resolution, quantitative mass spectrometry to map protein expression changes associated with the application of the Hsp90 inhibitor, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG). In depth data obtained from five replicate SILAC experiments enabled accurate quantification of about 6,000 proteins in HeLa cells. As expected, we observed activation of a heat shock response with induced expression of molecular chaperones, which refold misfolded proteins, and proteases, which degrade irreparably damaged polypeptides. Despite the broad range of known Hsp90 substrates, bioinformatics analysis revealed that particular protein classes were preferentially affected. These prominently included proteins involved in the DNA damage response, as well as protein kinases and especially tyrosine kinases. We followed up on this observation with a quantitative phosphoproteomic analysis of about 4,000 sites, which revealed that Hsp90 inhibition leads to much more down- than up-regulation of the phosphoproteome (34% down versus 6% up). This study defines the cellular response to Hsp90 inhibition at the proteome level and sheds light on the mechanisms by which it can be used to target cancer cells. PMID:22167270

  17. Equivalent damage validation by variable cluster analysis

    NASA Astrophysics Data System (ADS)

    Drago, Carlo; Ferlito, Rachele; Zucconi, Maria

    2016-06-01

    The main aim of this work is to perform a clustering analysis on the damage relieved in the old center of L'Aquila after the earthquake occurred on April 6, 2009 and to validate an Indicator of Equivalent Damage ED that summarizes the information reported on the AeDES card regarding the level of damage and their extension on the surface of the buildings. In particular we used a sample of 13442 masonry buildings located in an area characterized by a Macroseismic Intensity equal to 8 [1]. The aim is to ensure the coherence between the clusters and its hierarchy identified in the data of damage detected and in the data of the ED elaborated.

  18. Profiling DNA damage-induced phosphorylation in budding yeast reveals diverse signaling networks.

    PubMed

    Zhou, Chunshui; Elia, Andrew E H; Naylor, Maria L; Dephoure, Noah; Ballif, Bryan A; Goel, Gautam; Xu, Qikai; Ng, Aylwin; Chou, Danny M; Xavier, Ramnik J; Gygi, Steven P; Elledge, Stephen J

    2016-06-28

    The DNA damage response (DDR) is regulated by a protein kinase signaling cascade that orchestrates DNA repair and other processes. Identifying the substrate effectors of these kinases is critical for understanding the underlying physiology and mechanism of the response. We have used quantitative mass spectrometry to profile DDR-dependent phosphorylation in budding yeast and genetically explored the dependency of these phosphorylation events on the DDR kinases MEC1, RAD53, CHK1, and DUN1. Based on these screens, a database containing many novel DDR-regulated phosphorylation events has been established. Phosphorylation of many of these proteins has been validated by quantitative peptide phospho-immunoprecipitation and examined for functional relevance to the DDR through large-scale analysis of sensitivity to DNA damage in yeast deletion strains. We reveal a link between DDR signaling and the metabolic pathways of inositol phosphate and phosphatidyl inositol synthesis, which are required for resistance to DNA damage. We also uncover links between the DDR and TOR signaling as well as translation regulation. Taken together, these data shed new light on the organization of DDR signaling in budding yeast. PMID:27298372

  19. Damage analysis of a crack layer

    NASA Technical Reports Server (NTRS)

    Botsis, J.

    1989-01-01

    Damage analysis of a crack layer in polystyrene is carried out by employing optical microscopy and principles of quantitative stereology. The results show that, within the quasistatic phase of crack layer propagation, the average crazing density, along the trailing edge of the active zone, is constant. This is consistent with a self-similarity hypothesis of damage evolution employed by the crack layer theory. The average crazing densities within the active zone and along its trailing edge are found to be practically equal. A layer of constant crazing density, adjacent to the crack planes, accompanies the crack during its quasi-static growth. This suggests that: (1) a certain level of crazing density should be reached, around the crack tip, prior to crack advance; (2) the specific energy, associated with this 'core' of damage, could be considered as a Griffith's type energy. The results are in favor of certain hypothesis adopted by the crack layer theory.

  20. Damage detection using multivariate recurrence quantification analysis

    NASA Astrophysics Data System (ADS)

    Nichols, J. M.; Trickey, S. T.; Seaver, M.

    2006-02-01

    Recurrence-quantification analysis (RQA) has emerged as a useful tool for detecting subtle non-stationarities and/or changes in time-series data. Here, we extend the RQA analysis methods to multivariate observations and present a method by which the "length scale" parameter ɛ (the only parameter required for RQA) may be selected. We then apply the technique to the difficult engineering problem of damage detection. The structure considered is a finite element model of a rectangular steel plate where damage is represented as a cut in the plate, starting at one edge and extending from 0% to 25% of the plate width in 5% increments. Time series, recorded at nine separate locations on the structure, are used to reconstruct the phase space of the system's dynamics and subsequently generate the multivariate recurrence (and cross-recurrence) plots. Multivariate RQA is then used to detect damage-induced changes to the structural dynamics. These results are then compared with shifts in the plate's natural frequencies. Two of the RQA-based features are found to be more sensitive to damage than are the plate's frequencies.

  1. Analysis of Boling's laser-damage morphology

    SciTech Connect

    Sparks, M.S.

    1980-08-15

    Boling observed that his total-internal-reflection laser-damage sites in glass closely resembled the scattering cross section for small (ka << 1), perfectly conducting sphere and suggested that a very small plasma formed and grew to a larger size, still with ka << 1 satisfied. Even with ka = 1, for which the cross section is different from that observed, the scattered field still is too small to explain the damage in terms of constructive interference between the incident- and scattered fields. Furthermore, the characteristic shape of the scattering cross section that matches the damage patterns is for circular polarization or unpolarized light, in contrast to the experimental plane polarizations. Extending the ideas to include effects of the scattered field outside the glass, such as plasma formation, and to include the correct field (with interesting polarization, including longitudinal circuler polarization at certain distances from the surface) incident on the sphere may explain the experiments. Additional experiments and analysis would be useful to determine if the extended model is valid and to investigate related materials improvement, nondestructive testing, and the relation between laser damage, plasma initiation, and failure under stress, all initiated at small isolated spots.

  2. iTRAQ-based chromatin proteomic screen reveals CHD4-dependent recruitment of MBD2 to sites of DNA damage.

    PubMed

    Sun, Yazhou; Yang, Yeran; Shen, Hongyan; Huang, Min; Wang, Zhifeng; Liu, Yang; Zhang, Hui; Tang, Tie-Shan; Guo, Caixia

    2016-02-26

    Many DNA repair proteins can be recruited to DNA damage sites upon genotoxic stress. In order to search potential DNA repair proteins involved in cellular response to mitomycin C treatment, we utilized a quantitative proteome to uncover proteins that manifest differentially enrichment in the chromatin fraction after DNA damage. 397 proteins were identified, among which many factors were shown to be involved in chromatin modification and DNA repair by GO analysis. Specifically, methyl-CpG-binding domain protein 2 (MBD2) is revealed to be recruited to DNA damage sites after laser microirradiation, which was mediated through MBD domain and MBD2 C-terminus. Additionally, the recruitment of MBD2 is dependent on poly (ADP-ribose) and chromodomain helicase DNA-binding protein 4 (CHD4). Moreover, knockdown of MBD2 by CRISPR-Cas9 technique results in MMC sensitivity in mammalian cells. PMID:26827827

  3. Recent flood events in Germany - revealing damage influencing factors on residential property

    NASA Astrophysics Data System (ADS)

    Elmer, F.; Pech, I.; Thieken, A. H.; Kreibich, H.

    2009-04-01

    The trend of increasing damages due to floods can only be counteracted with effective flood management, based on reliable flood risk analysis. Better knowledge about the connections between flood losses and damage determining factors is necessary to improve damage estimation models. Thus extensive data about flood losses were collected at affected properties in Germany in the aftermath of floods in August 2002, August 2005 and April 2006. The data set contains more than 2100 residential damage cases. The data for the residential sector include information about building and content damages, evacuation, locations of the objects, people living at the sites and their socioeconomic situation, flood experience, precautionary measures undertaken before and during the event as well as flood information like maximum water level, flood duration, and flow velocity at the affected buildings. As first analyses showed significantly higher average damages caused by the extreme event in 2002 than by the 2005 and 2006 events the data sets were amended by adding site specific information about the recurrence interval of the event. Therefore, an estimation of the flood annuality was done for more than 120 gauges in the affected areas. The results were assigned to each damaged object to be able to analyze the influence of the magnitude on the flood damage. Thus, the data set enables a comparative analysis of multiple events of different severity that occurred over a couple of years in the same regions. Variables that contribute most to the explanation of damages are identified by multi-criteria analyses using data mining techniques and software, namely the WEKA-tool. In applying this routine to subsets (divided by region, by recurrence interval, by event) main differences in the contribution of single factors can be identified. The aim is to use the results for the improvement of existing flood damage estimation models.

  4. Quantitative proteomics reveal ATM kinase-dependent exchange in DNA damage response complexes.

    PubMed

    Choi, Serah; Srivas, Rohith; Fu, Katherine Y; Hood, Brian L; Dost, Banu; Gibson, Gregory A; Watkins, Simon C; Van Houten, Bennett; Bandeira, Nuno; Conrads, Thomas P; Ideker, Trey; Bakkenist, Christopher J

    2012-10-01

    ATM is a protein kinase that initiates a well-characterized signaling cascade in cells exposed to ionizing radiation (IR). However, the role for ATM in coordinating critical protein interactions and subsequent exchanges within DNA damage response (DDR) complexes is unknown. We combined SILAC-based tandem mass spectrometry and a subcellular fractionation protocol to interrogate the proteome of irradiated cells treated with or without the ATM kinase inhibitor KU55933. We developed an integrative network analysis to identify and prioritize proteins that were responsive to KU55933, specifically in chromatin, and that were also enriched for physical interactions with known DNA repair proteins. This analysis identified 53BP1 and annexin A1 (ANXA1) as strong candidates. Using fluorescence recovery after photobleaching, we found that the exchange of GFP-53BP1 in DDR complexes decreased with KU55933. Further, we found that ANXA1 knockdown sensitized cells to IR via a mechanism that was not potentiated by KU55933. Our study reveals a role for ATM kinase activity in the dynamic exchange of proteins in DDR complexes and identifies a role for ANXA1 in cellular radioprotection. PMID:22909323

  5. Dark progression reveals slow timescales for radiation damage between T = 180 and 240 K

    PubMed Central

    Warkentin, Matthew; Badeau, Ryan; Hopkins, Jesse; Thorne, Robert E.

    2011-01-01

    Can radiation damage to protein crystals be ‘outrun’ by collecting a structural data set before damage is manifested? Recent experiments using ultra-intense pulses from a free-electron laser show that the answer is yes. Here, evidence is presented that significant reductions in global damage at temperatures above 200 K may be possible using conventional X-ray sources and current or soon-to-be available detectors. Specifically, ‘dark progression’ (an increase in damage with time after the X-rays have been turned off) was observed at temperatures between 180 and 240 K and on timescales from 200 to 1200 s. This allowed estimation of the temperature-dependent timescale for damage. The rate of dark progression is consistent with an Arrhenius law with an activation energy of 14 kJ mol−1. This is comparable to the activation energy for the solvent-coupled diffusive damage processes responsible for the rapid increase in radiation sensitivity as crystals are warmed above the glass transition near 200 K. Analysis suggests that at T = 300 K data-collection times of the order of 1 s (and longer at lower temperatures) may allow significant reductions in global radiation damage, facilitating structure solution on crystals with liquid solvent. No dark progression was observed below T = 180 K, indicating that no important damage process is slowed through this timescale window in this temperature range. PMID:21904032

  6. Cross-Sectional Nakagami Images in Passive Stretches Reveal Damage of Injured Muscles.

    PubMed

    Lin, Shih-Ping; Lin, Yi-Hsun; Fan, Shih-Chen; Huang, Bu-Miin; Lin, Wei-Yin; Wang, Shyh-Hau; Shung, K Kirk; Su, Fong-Chin; Wu, Chia-Ching

    2016-01-01

    Muscle strain is still awanting a noninvasive quantitatively diagnosis tool. High frequency ultrasound (HFU) improves image resolution for monitoring changes of tissue structures, but the biomechanical factors may influence ultrasonography during injury detection. We aim to illustrate the ultrasonic parameters to present the histological damage of overstretched muscle with the consideration of biomechanical factors. Gastrocnemius muscles from mice were assembled and ex vivo passive stretching was performed before or after injury. After injury, the muscle significantly decreased mechanical strength. Ultrasonic images were obtained by HFU at different deformations to scan in cross and longitudinal orientations of muscle. The ultrasonography was quantified by echogenicity and Nakagami parameters (NP) for structural evaluation and correlated with histological results. The injured muscle at its original length exhibited decreased echogenicity and NP from HFU images. Cross-sectional ultrasonography revealed a loss of correlation between NP and passive muscle stretching that suggested a special scatterer pattern in the cross section of injured muscle. The independence of NP during passive stretching of injured muscle was confirmed by histological findings in ruptured collagen fibers, decreased muscle density, and increased intermuscular fiber space. Thus, HFU analysis of NP in cross section represents muscle injury that may benefit the clinical diagnosis. PMID:27034946

  7. Cross-Sectional Nakagami Images in Passive Stretches Reveal Damage of Injured Muscles

    PubMed Central

    Lin, Shih-Ping; Lin, Yi-Hsun; Fan, Shih-Chen; Huang, Bu-Miin; Lin, Wei-Yin; Wang, Shyh-Hau; Shung, K. Kirk; Su, Fong-Chin; Wu, Chia-Ching

    2016-01-01

    Muscle strain is still awanting a noninvasive quantitatively diagnosis tool. High frequency ultrasound (HFU) improves image resolution for monitoring changes of tissue structures, but the biomechanical factors may influence ultrasonography during injury detection. We aim to illustrate the ultrasonic parameters to present the histological damage of overstretched muscle with the consideration of biomechanical factors. Gastrocnemius muscles from mice were assembled and ex vivo passive stretching was performed before or after injury. After injury, the muscle significantly decreased mechanical strength. Ultrasonic images were obtained by HFU at different deformations to scan in cross and longitudinal orientations of muscle. The ultrasonography was quantified by echogenicity and Nakagami parameters (NP) for structural evaluation and correlated with histological results. The injured muscle at its original length exhibited decreased echogenicity and NP from HFU images. Cross-sectional ultrasonography revealed a loss of correlation between NP and passive muscle stretching that suggested a special scatterer pattern in the cross section of injured muscle. The independence of NP during passive stretching of injured muscle was confirmed by histological findings in ruptured collagen fibers, decreased muscle density, and increased intermuscular fiber space. Thus, HFU analysis of NP in cross section represents muscle injury that may benefit the clinical diagnosis. PMID:27034946

  8. Accurate 3d Scanning of Damaged Ancient Greek Inscriptions for Revealing Weathered Letters

    NASA Astrophysics Data System (ADS)

    Papadaki, A. I.; Agrafiotis, P.; Georgopoulos, A.; Prignitz, S.

    2015-02-01

    In this paper two non-invasive non-destructive alternative techniques to the traditional and invasive technique of squeezes are presented alongside with specialized developed processing methods, aiming to help the epigraphists to reveal and analyse weathered letters in ancient Greek inscriptions carved in masonry or marble. The resulting 3D model would serve as a detailed basis for the epigraphists to try to decipher the inscription. The data were collected by using a Structured Light scanner. The creation of the final accurate three dimensional model is a complicated procedure requiring large computation cost and human effort. It includes the collection of geometric data in limited space and time, the creation of the surface, the noise filtering and the merging of individual surfaces. The use of structured light scanners is time consuming and requires costly hardware and software. Therefore an alternative methodology for collecting 3D data of the inscriptions was also implemented for reasons of comparison. Hence, image sequences from varying distances were collected using a calibrated DSLR camera aiming to reconstruct the 3D scene through SfM techniques in order to evaluate the efficiency and the level of precision and detail of the obtained reconstructed inscriptions. Problems in the acquisition processes as well as difficulties in the alignment step and mesh optimization are also encountered. A meta-processing framework is proposed and analysed. Finally, the results of processing and analysis and the different 3D models are critically inspected and then evaluated by a specialist in terms of accuracy, quality and detail of the model and the capability of revealing damaged and "hidden" letters.

  9. NMR metabolomic profiling reveals new roles of SUMOylation in DNA damage response.

    PubMed

    Cano, Kristin E; Li, Yi-Jia; Chen, Yuan

    2010-10-01

    Post-translational modifications by the Small Ubiquitin-like Modifier (SUMO) family of proteins have been established as critical events in the cellular response to a wide range of DNA damaging reagents and radiation; however, the detailed mechanism of SUMOylation in DNA damage response is not well understood. In this study, we used a nuclear magnetic resonance (NMR) spectroscopy-based metabolomics approach to examine the effect of an inhibitor of SUMO-mediated protein-protein interactions on MCF7 breast cancer cell response to radiation. Metabolomics is sensitive to changes in cellular functions and thus provides complementary information to other biological studies. The peptide inhibitor (SUMO interaction motif mimic, SIM) and a control peptide were stably expressed in MCF-7 cell line. Metabolite profiles of the cell lines before and after radiation were analyzed using solution NMR methods. Various statistical methods were used to isolate significant changes. Differences in the amounts of glutamine, aspartate, malate, alanine, glutamate and NADH between the SIM-expressing and control cells suggest a role for SUMOylation in regulating mitochondrial function. This is also further verified following the metabolism of (13)C-labeled glutamine. The inability of the cells expressing the SIM peptide to increase production of the antioxidants carnosine and glutathione after radiation damage suggests an important role of SUMOylation in regulating the levels of antioxidants that protect cells from free radicals and reactive oxygen species generated by radiation. This study reveals previously unknown roles of SUMOylation in DNA damage response. PMID:20695451

  10. 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

  11. Thermographic analysis of surface damage in teeth

    NASA Astrophysics Data System (ADS)

    Conde-Contreras, M.; Bante-Guerra, J.; Hernandez-Garcia, E.; Hernandez, A. M.; Trujillo, S.; Quintana, P.; Alvarado-Gil, J. J.

    2008-02-01

    The analysis of the surface of teeth is an important field of research and technological development due to the importance of dental pieces in health and aesthetics. The presence of cracks as well as the etching effects on teeth surface, due to different chemical agents, affects not only the appearance of teeth but its integrity. In this work, laser thermography analysis of dental pieces with damage in the form of cracks is presented. The technique consists in the illumination of the surface at the center of the sample, using a 300 mW pulsed solid state laser beam focused with a gradium lens, and monitoring the spatial and temporal distribution of the temperature field. The heating of the sample is monitored using a focal plane array infrared camera, sensitive in the spectral range 7.5-13 μm with a noise equivalent temperature difference of 0.12°C. The data acquisition was performed by the PC firewire port using a PCI-8254R card and a home-made program in Labview 8.0 was used for data acquisition. The images were processed in a home-made linux program to obtain the experimental table values. Our results are compared with position and frequency scans obtained by infrared photothermal radiometry. It is shown that the crack in the tooth appears as an increase in the photothermal signal. In contrast, the thermographic image shows a more detailed structure in which close to the crack the temperature increases, but at the crack the signal falls.

  12. Structural Damage Prediction and Analysis for Hypervelocity Impacts: Handbook

    NASA Technical Reports Server (NTRS)

    Elfer, N. C.

    1996-01-01

    This handbook reviews the analysis of structural damage on spacecraft due to hypervelocity impacts by meteoroid and space debris. These impacts can potentially cause structural damage to a Space Station module wall. This damage ranges from craters, bulges, minor penetrations, and spall to critical damage associated with a large hole, or even rupture. The analysis of damage depends on a variety of assumptions and the area of most concern is at a velocity beyond well controlled laboratory capability. In the analysis of critical damage, one of the key questions is how much momentum can actually be transfered to the pressure vessel wall. When penetration occurs without maximum bulging at high velocity and obliquities (if less momentum is deposited in the rear wall), then large tears and rupture may be avoided. In analysis of rupture effects of cylindrical geometry, biaxial loading, bending of the crack, a central hole strain rate and R-curve effects are discussed.

  13. Nonlinear damage analysis: Postulate and evaluation

    NASA Technical Reports Server (NTRS)

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

    1983-01-01

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

  14. 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

  15. Analysis of optics damage growth at the National Ignition Facility

    NASA Astrophysics Data System (ADS)

    Liao, Z. M.; Nostrand, M.; Whitman, P.; Bude, J.

    2015-11-01

    Optics damage growth modeling and analysis at the National Ignition Facility (NIF) has been performed on fused silica. We will show the results of single shot growth comparisons, damage site lifetime comparisons as well as growth metrics for each individual NIF beamline. These results help validate the consistency of the damage growth models and allow us to have confidence in our strategic planning in regards to projected optic usage.

  16. Multiscale models of skeletal muscle reveal the complex effects of muscular dystrophy on tissue mechanics and damage susceptibility

    PubMed Central

    Virgilio, Kelley M.; Martin, Kyle S.; Peirce, Shayn M.; Blemker, Silvia S.

    2015-01-01

    Computational models have been increasingly used to study the tissue-level constitutive properties of muscle microstructure; however, these models were not created to study or incorporate the influence of disease-associated modifications in muscle. The purpose of this paper was to develop a novel multiscale muscle modelling framework to elucidate the relationship between microstructural disease adaptations and modifications in both mechanical properties of muscle and strain in the cell membrane. We used an agent-based model to randomly generate new muscle fibre geometries and mapped them into a finite-element model representing a cross section of a muscle fascicle. The framework enabled us to explore variability in the shape and arrangement of fibres, as well as to incorporate disease-related changes. We applied this method to reveal the trade-offs between mechanical properties and damage susceptibility in Duchenne muscular dystrophy (DMD). DMD is a fatal genetic disease caused by a lack of the transmembrane protein dystrophin, leading to muscle wasting and death due to cardiac or pulmonary complications. The most prevalent microstructural variations in DMD include: lack of transmembrane proteins, fibrosis, fatty infiltration and variation in fibre cross-sectional area. A parameter analysis of these variations and case study of DMD revealed that the nature of fibrosis and density of transmembrane proteins strongly affected the stiffness of the muscle and susceptibility to membrane damage. PMID:25844152

  17. Progressive Damage Analysis of Bonded Composite Joints

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  18. Double Linear Damage Rule for Fatigue Analysis

    NASA Technical Reports Server (NTRS)

    Halford, G.; Manson, S.

    1985-01-01

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

  19. Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling

    PubMed Central

    Li, Renfeng; Pinto, Sneha M.; Shaw, Patrick G.; Huang, Tai-Chung; Wan, Jun; Qian, Jiang; Gowda, Harsha; Wu, Xinyan; Lv, Dong-Wen; Zhang, Kun; Manda, Srikanth S.; Pandey, Akhilesh; Hayward, S. Diane

    2015-01-01

    Epstein-Barr virus (EBV) is etiologically linked to infectious mononucleosis and several human cancers. EBV encodes a conserved protein kinase BGLF4 that plays a key role in the viral life cycle. To provide new insight into the host proteins regulated by BGLF4, we utilized stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics to compare site-specific phosphorylation in BGLF4-expressing Akata B cells. Our analysis revealed BGLF4-mediated hyperphosphorylation of 3,046 unique sites corresponding to 1,328 proteins. Frequency analysis of these phosphosites revealed a proline-rich motif signature downstream of BGLF4, indicating a broader substrate recognition for BGLF4 than its cellular ortholog cyclin-dependent kinase 1 (CDK1). Further, motif analysis of the hyperphosphorylated sites revealed enrichment in ATM, ATR and Aurora kinase substrates while functional analyses revealed significant enrichment of pathways related to the DNA damage response (DDR), mitosis and cell cycle. Phosphorylation of proteins associated with the mitotic spindle assembly checkpoint (SAC) indicated checkpoint activation, an event that inactivates the anaphase promoting complex/cyclosome, APC/C. Furthermore, we demonstrated that BGLF4 binds to and directly phosphorylates the key cellular proteins PP1, MPS1 and CDC20 that lie upstream of SAC activation and APC/C inhibition. Consistent with APC/C inactivation, we found that BGLF4 stabilizes the expression of many known APC/C substrates. We also noted hyperphosphorylation of 22 proteins associated the nuclear pore complex, which may contribute to nuclear pore disassembly and SAC activation. A drug that inhibits mitotic checkpoint activation also suppressed the accumulation of extracellular EBV virus. Taken together, our data reveal that, in addition to the DDR, manipulation of mitotic kinase signaling and SAC activation are mechanisms associated with lytic EBV replication. All MS data have been deposited in

  20. Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling.

    PubMed

    Li, Renfeng; Liao, Gangling; Nirujogi, Raja Sekhar; Pinto, Sneha M; Shaw, Patrick G; Huang, Tai-Chung; Wan, Jun; Qian, Jiang; Gowda, Harsha; Wu, Xinyan; Lv, Dong-Wen; Zhang, Kun; Manda, Srikanth S; Pandey, Akhilesh; Hayward, S Diane

    2015-12-01

    Epstein-Barr virus (EBV) is etiologically linked to infectious mononucleosis and several human cancers. EBV encodes a conserved protein kinase BGLF4 that plays a key role in the viral life cycle. To provide new insight into the host proteins regulated by BGLF4, we utilized stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics to compare site-specific phosphorylation in BGLF4-expressing Akata B cells. Our analysis revealed BGLF4-mediated hyperphosphorylation of 3,046 unique sites corresponding to 1,328 proteins. Frequency analysis of these phosphosites revealed a proline-rich motif signature downstream of BGLF4, indicating a broader substrate recognition for BGLF4 than its cellular ortholog cyclin-dependent kinase 1 (CDK1). Further, motif analysis of the hyperphosphorylated sites revealed enrichment in ATM, ATR and Aurora kinase substrates while functional analyses revealed significant enrichment of pathways related to the DNA damage response (DDR), mitosis and cell cycle. Phosphorylation of proteins associated with the mitotic spindle assembly checkpoint (SAC) indicated checkpoint activation, an event that inactivates the anaphase promoting complex/cyclosome, APC/C. Furthermore, we demonstrated that BGLF4 binds to and directly phosphorylates the key cellular proteins PP1, MPS1 and CDC20 that lie upstream of SAC activation and APC/C inhibition. Consistent with APC/C inactivation, we found that BGLF4 stabilizes the expression of many known APC/C substrates. We also noted hyperphosphorylation of 22 proteins associated the nuclear pore complex, which may contribute to nuclear pore disassembly and SAC activation. A drug that inhibits mitotic checkpoint activation also suppressed the accumulation of extracellular EBV virus. Taken together, our data reveal that, in addition to the DDR, manipulation of mitotic kinase signaling and SAC activation are mechanisms associated with lytic EBV replication. All MS data have been deposited in

  1. Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability.

    PubMed

    Kim, Jeongkyu; Sturgill, David; Tran, Andy D; Sinclair, David A; Oberdoerffer, Philipp

    2016-04-20

    DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. As a result, DSBs have been proposed to promote transcriptional and, ultimately, physiological dysfunction via both cell-intrinsic and cell-non-autonomous pathways. Studying the consequences of DSBs in higher organisms has, however, been hindered by a scarcity of tools for controlled DSB induction. Here, we describe a mouse model that allows for both tissue-specific and temporally controlled DSB formation at ∼140 defined genomic loci. Using this model, we show that DSBs promote a DNA damage signaling-dependent decrease in gene expression in primary cells specifically at break-bearing genes, which is reversed upon DSB repair. Importantly, we demonstrate that restoration of gene expression can occur independently of cell cycle progression, underlining its relevance for normal tissue maintenance. Consistent with this, we observe no evidence for persistent transcriptional repression in response to a multi-day course of continuous DSB formation and repair in mouse lymphocytesin vivo Together, our findings reveal an unexpected capacity of primary cells to maintain transcriptome integrity in response to DSBs, pointing to a limited role for DNA damage as a mediator of cell-autonomous epigenetic dysfunction. PMID:26687720

  2. Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability

    PubMed Central

    Kim, Jeongkyu; Sturgill, David; Tran, Andy D.; Sinclair, David A.; Oberdoerffer, Philipp

    2016-01-01

    DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. As a result, DSBs have been proposed to promote transcriptional and, ultimately, physiological dysfunction via both cell-intrinsic and cell-non-autonomous pathways. Studying the consequences of DSBs in higher organisms has, however, been hindered by a scarcity of tools for controlled DSB induction. Here, we describe a mouse model that allows for both tissue-specific and temporally controlled DSB formation at ∼140 defined genomic loci. Using this model, we show that DSBs promote a DNA damage signaling-dependent decrease in gene expression in primary cells specifically at break-bearing genes, which is reversed upon DSB repair. Importantly, we demonstrate that restoration of gene expression can occur independently of cell cycle progression, underlining its relevance for normal tissue maintenance. Consistent with this, we observe no evidence for persistent transcriptional repression in response to a multi-day course of continuous DSB formation and repair in mouse lymphocytes in vivo. Together, our findings reveal an unexpected capacity of primary cells to maintain transcriptome integrity in response to DSBs, pointing to a limited role for DNA damage as a mediator of cell-autonomous epigenetic dysfunction. PMID:26687720

  3. Damage functions for climate-related hazards: unification and uncertainty analysis

    NASA Astrophysics Data System (ADS)

    Prahl, Boris F.; Rybski, Diego; Boettle, Markus; Kropp, Jürgen P.

    2016-05-01

    Most climate change impacts manifest in the form of natural hazards. Damage assessment typically relies on damage functions that translate the magnitude of extreme events to a quantifiable damage. In practice, the availability of damage functions is limited due to a lack of data sources and a lack of understanding of damage processes. The study of the characteristics of damage functions for different hazards could strengthen the theoretical foundation of damage functions and support their development and validation. Accordingly, we investigate analogies of damage functions for coastal flooding and for wind storms and identify a unified approach. This approach has general applicability for granular portfolios and may also be applied, for example, to heat-related mortality. Moreover, the unification enables the transfer of methodology between hazards and a consistent treatment of uncertainty. This is demonstrated by a sensitivity analysis on the basis of two simple case studies (for coastal flood and storm damage). The analysis reveals the relevance of the various uncertainty sources at varying hazard magnitude and on both the microscale and the macroscale level. Main findings are the dominance of uncertainty from the hazard magnitude and the persistent behaviour of intrinsic uncertainties on both scale levels. Our results shed light on the general role of uncertainties and provide useful insight for the application of the unified approach.

  4. Damage identification techniques via modal curvature analysis: Overview and comparison

    NASA Astrophysics Data System (ADS)

    Dessi, Daniele; Camerlengo, Gabriele

    2015-02-01

    This paper aims to compare several damage identification methods based on the analysis of modal curvature and related quantities (natural frequencies and modal strain energy) by evaluating their performances on the same test case, a damaged Euler-Bernoulli beam. Damage is modelled as a localized and uniform reduction of stiffness so that closed-form expressions of the mode-shape curvatures can be analytically computed and data accuracy, which affects final results, can be controlled. The selected techniques belong to two categories: one includes several methods that need reference data for detecting structural modifications due to damage, the second group, including the modified Laplacian operator and the fractal dimension, avoids the knowledge of the undamaged behavior for issuing a damage diagnosis. To explain better the different performances of the methods, the mathematical formulation has been revised in some cases so as to fit into a common framework where the underlying hypotheses are clearly stated. Because the various damage indexes are calculated on 'exact' data, a sensitivity analysis has been carried out with respect to the number of points where curvature information is available, to the position of damage between adjacent points, to the modes involved in the index computation. In this way, this analysis intends to point out comparatively the capability of locating and estimating damage of each method along with some critical issues already present with noiseless data.

  5. Identification of S-phase DNA damage-response targets in fission yeast reveals conservation of damage-response networks.

    PubMed

    Willis, Nicholas A; Zhou, Chunshui; Elia, Andrew E H; Murray, Johanne M; Carr, Antony M; Elledge, Stephen J; Rhind, Nicholas

    2016-06-28

    The cellular response to DNA damage during S-phase regulates a complicated network of processes, including cell-cycle progression, gene expression, DNA replication kinetics, and DNA repair. In fission yeast, this S-phase DNA damage response (DDR) is coordinated by two protein kinases: Rad3, the ortholog of mammalian ATR, and Cds1, the ortholog of mammalian Chk2. Although several critical downstream targets of Rad3 and Cds1 have been identified, most of their presumed targets are unknown, including the targets responsible for regulating replication kinetics and coordinating replication and repair. To characterize targets of the S-phase DDR, we identified proteins phosphorylated in response to methyl methanesulfonate (MMS)-induced S-phase DNA damage in wild-type, rad3∆, and cds1∆ cells by proteome-wide mass spectrometry. We found a broad range of S-phase-specific DDR targets involved in gene expression, stress response, regulation of mitosis and cytokinesis, and DNA replication and repair. These targets are highly enriched for proteins required for viability in response to MMS, indicating their biological significance. Furthermore, the regulation of these proteins is similar in fission and budding yeast, across 300 My of evolution, demonstrating a deep conservation of S-phase DDR targets and suggesting that these targets may be critical for maintaining genome stability in response to S-phase DNA damage across eukaryotes. PMID:27298342

  6. Study on an auto-correlation-function-based damage index: Sensitivity analysis and structural damage detection

    NASA Astrophysics Data System (ADS)

    Zhang, Muyu; Schmidt, Rüdiger

    2015-12-01

    The damage index based on the auto correlation function to detect the damage of the structure under white noise excitation is studied in detail in this paper. The maximum values of the auto correlation function of the vibration response signals (displacement, velocity and acceleration) from different measurement points of the structure are collected and formulated as a vector called Auto Correlation Function at Maximum Point Value Vector (AMV), which is expressed as a weighted combination of the Hadamard product of two mode shapes. AMV is normalized by its root mean square value so that the influence of the excitation can be eliminated. Sensitivity analysis for the different parts of the normalized AMV shows that the sensitivity of the normalized AMV to the local stiffness is dependent most on the sensitivity of the Hadamard product of the two lower order mode shapes to the local stiffness, which has a sudden change of the value around the local stiffness change position. The sensitivity of the normalized AMV has the similar shape and same trend that shows it is a very good damage indicator even for the very small damage. The relative change of the normalized AMV before and after damage occurs in the structure is adopted as the damage index to show the damage location. Several examples of the stiffness reduction detection of a 12-story shear frame structure are utilized to validate the results in sensitivity analysis, illustrate the effectiveness and anti-noise ability of the AMV-based damage detection method and compare the effect of the response type on the detectability of the normalized AMV.

  7. Structure of crystal defects in damaged RDX as revealed by an AFM

    SciTech Connect

    Sharma, J.; Hoover, S. M.; Coffey, C. S.; Tompa, A. S.; Sandusky, H. W.; Armstrong, R. W.; Elban, W. L.

    1998-07-10

    An atomic force microscope (AFM) was employed to reveal the structure of defects produced in single crystals of cyclotrimethylenetrinitramine (RDX), damaged either by indentation, heat or underwater shock. In general, all of these stimuli produced dislocation pits, cracks, fissures and mosaics, however, the details were different. Indentation generated a large number of triangular dislocation pits, which in their turn produced fissures, cracks and holes by coalescing. Heat produced fine parallel cracks. Slivers as thin as sixty molecules across were observed. Shock caused the crystal to become a three-dimensional mosaic structure, 100-500 nm in size, produced by intensive cleavage and delamination. In all cases very fine particles, 20-500 nm in size, were ejected onto the surface as debris from the formation of defects. The AFM has revealed for the first time un-etched dislocation pits in their pristine condition, so that their internal structure could be investigated. A dislocation density of 10{sup 6} cm{sup -2} has been observed. RDX is found to behave like a very fragile crystal in which numerous imperfections show up at a level of the stimuli, far below that necessary for the start of chemical reaction.

  8. Numerical analysis of impact-damaged sandwich composites

    NASA Astrophysics Data System (ADS)

    Hwang, Youngkeun

    Sandwich structures are used in a wide variety of structural applications due to their relative advantages over other conventional structural materials in terms of improved stability, weight savings, and ease of manufacture and repair. Foreign object impact damage in sandwich composites can result in localized damage to the facings, core, and core-facing interface. Such damage may result in drastic reductions in composite strength, elastic moduli, and durability and damage tolerance characteristics. In this study, physically-motivated numerical models have been developed for predicting the residual strength of impact-damaged sandwich composites comprised of woven-fabric graphite-epoxy facesheets and Nomex honeycomb cores subjected to compression-after-impact loading. Results from non-destructive inspection and destructive sectioning of damaged sandwich panels were used to establish initial conditions for damage (residual facesheet indentation, core crush dimension, etc.) in the numerical analysis. Honeycomb core crush test results were used to establish the nonlinear constitutive behavior for the Nomex core. The influence of initial facesheet property degradation and progressive loss of facesheet structural integrity on the residual strength of impact-damaged sandwich panels was examined. The influence of damage of various types and sizes, specimen geometry, support boundary conditions, and variable material properties on the estimated residual strength is discussed. Facesheet strains from material and geometric nonlinear finite element analyses correlated relatively well with experimentally determined values. Moreover, numerical predictions of residual strength are consistent with experimental observations. Using a methodology similar to that presented in this work, it may be possible to develop robust residual strength estimates for complex sandwich composite structural components with varying levels of in-service damage. Such studies may facilitate sandwich

  9. Photoinduced Oxidative DNA Damage Revealed by an Agarose Gel Nicking Assay: A Biophysical Chemistry Laboratory Experiment

    NASA Astrophysics Data System (ADS)

    Shafirovich, Vladimir; Singh, Carolyn; Geacintov, Nicholas E.

    2003-11-01

    Oxidative damage of DNA molecules associated with electron-transfer reactions is an important phenomenon in living cells, which can lead to mutations and contribute to carcinogenesis and the aging processes. This article describes the design of several simple experiments to explore DNA damage initiated by photoinduced electron-transfer reactions sensitized by the acridine derivative, proflavine (PF). A supercoiled DNA agarose gel nicking assay is employed as a sensitive probe of DNA strand cleavage. A low-cost experimental and computer-interfaced imaging apparatus is described allowing for the digital recording and analysis of the gel electrophoresis results. The first experiment describes the formation of direct strand breaks in double-stranded DNA induced by photoexcitation of the intercalated PF molecules. The second experiment demonstrates that the addition of the well-known electron acceptor, methylviologen, gives rise to a significant enhancement of the photochemical DNA strand cleavage effect. This occurs by an electron transfer step to methylviologen that renders the inital photoinduced charge separation between photoexcited PF and DNA irreversible. The third experiment demonstrates that the action spectrum of the DNA photocleavage matches the absorption spectrum of DNA-bound, intercalated PF molecules, which differs from that of free PF molecules. This result demonstrates that the photoinduced DNA strand cleavage is initiated by intercalated rather than free PF molecules.

  10. Simultaneous Tomography and Diffraction Analysis of Creep Damage

    NASA Astrophysics Data System (ADS)

    Pyzalla, A.; Camin, B.; Buslaps, T.; Di Michiel, M.; Kaminski, H.; Kottar, A.; Pernack, A.; Reimers, W.

    2005-04-01

    Creep damage by void nucleation and growth limits the lifetime of components subjected to loading at high temperatures. We report a combined tomography and diffraction experiment using high-energy synchrotron radiation that permitted us to follow in situ void growth and microstructure development in bulk samples. The results reveal that void growth versus time follows an exponential growth law. The formation of large void volumes coincides with texture evolution and dislocation density, reaching a steady state. Creep damage during a large proportion of sample creep life is homogeneous before damage localization occurs, which leads to rapid failure. The in situ determination of void evolution in bulk samples should allow for the assessment of creep damage in metallic materials and subsequently for lifetime predictions about samples and components that are subject to high-temperature loading.

  11. Adhesive Characterization and Progressive Damage Analysis of Bonded Composite Joints

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  12. Damage Detection and Analysis in CFRPs Using Acoustic Emission Technique

    NASA Astrophysics Data System (ADS)

    Whitlow, Travis Laron

    Real time monitoring of damage is an important aspect of life management of critical structures. Acoustic emission (AE) techniques allow for measurement and assessment of damage in real time. Acoustic emission parameters such as signal amplitude and duration were monitored during the loading sequences. Criteria that can indicate the onset of critical damage to the structure were developed. Tracking the damage as it happens gives a better analysis of the failure evolution that will allow for a more accurate determination of structural life. The main challenge is distinguishing between legitimate damage signals and "false positives" which are unrelated to damage growth. Such false positives can be related to electrical noise, friction, or mechanical vibrations. This research focuses on monitoring signals of damage growth in carbon fiber reinforced polymers (CFRPs) and separating the relevant signals from the false ones. In this Dissertation, acoustic emission signals from CFRP specimens were experimentally recorded and analyzed. The objectives of this work are: (1) perform static and fatigue loading of CFRP composite specimens and measure the associated AE signals, (2) accurately determine the AE parameters (energy, frequency, duration, etc.) of signals generated during failure of such specimens, (3) use fiber optic sensors to monitor the strain distribution of the damage zone and relate these changes in strain measurements to AE data.

  13. Damage functions for climate-related hazards: unification and uncertainty analysis

    NASA Astrophysics Data System (ADS)

    Prahl, B. F.; Rybski, D.; Boettle, M.; Kropp, J. P.

    2015-11-01

    Most climate change impacts manifest in the form of natural hazards. For example, sea-level rise and changes in storm climatology are expected to increase the frequency and magnitude of flooding events. In practice there is a need for comprehensive damage assessment at an intermediate level of complexity. Answering this need, we reveal the common grounds of macroscale damage functions employed in storm damage, coastal-flood damage, and heat mortality assessment. The universal approach offers both bottom-up and top-down damage evaluation, employing either an explicit or an implicit portfolio description. Putting emphasis on the treatment of data uncertainties, we perform a sensitivity analysis across different scales. We find that the behaviour of intrinsic uncertainties on the microscale level (i.e. single item) does still persist on the macroscale level (i.e. portfolio). Furthermore, the analysis of uncertainties can reveal their specific relevance, allowing for simplification of the modelling chain. Our results shed light on the role of uncertainties and provide useful insight for the application of a unified damage function.

  14. Application Of Shakedown Analysis To Cyclic Creep Damage Limits

    SciTech Connect

    Carter, Peter; Jetter, Robert I; Sham, Sam

    2012-01-01

    Shakedown analysis may be used to provide a conservative estimate of local rupture and hence cyclic creep damage for use in a creep-fatigue assessment. The shakedown analysis is based on an elastic-perfectly plastic material with a temperature-dependent pseudo yield stress defined to guarantee that a shakedown solution exists which does not exceed rupture stress and temperature for a defined life. The ratio of design life to the estimated maximum cyclic life is the shakedown creep damage. The methodology does not require stress classification and is also applicable to cycles over the full range of temperature above and below the creep regime. Full cyclic creep and damage analysis is the alternative when shakedown analysis appears to be excessively conservative.

  15. Analysis of nonlinear deformations and damage in CFRP textile laminates

    NASA Astrophysics Data System (ADS)

    Ullah, H.; Harland, A. R.; Lucas, T.; Price, D.; Silberschmidt, V. V.

    2011-07-01

    Carbon fibre-reinforced polymer (CFRP) textile composites are widely used in aerospace, automotive and construction components and structures thanks to their relatively low production costs, higher delamination and impact strength. They can also be used in various products in sports industry. These products are usually exposed to different in-service conditions such as large bending deformation and multiple impacts. Composite materials usually demonstrate multiple modes of damage and fracture due to their heterogeneity and microstructure, in contrast to more traditional homogeneous structural materials like metals and alloys. Damage evolution affects both their in-service properties and performance that can deteriorate with time. These damage modes need adequate means of analysis and investigation, the major approaches being experimental characterisation, numerical simulations and microtomography analysis. This research deals with a deformation behaviour and damage in composite laminates linked to their quasi-static bending. Experimental tests are carried out to characterise the behaviour of woven CFRP material under large-deflection bending. Two-dimensional finite element (FE) models are implemented in the commercial code Abaqus/Explicit to study the deformation behaviour and damage in woven CFRP laminates. Multiple layers of bilinear cohesive-zone elements are employed to model the onset and progression of inter-ply delamination process. X-ray Micro-Computed Tomography (MicroCT) analysis is carried out to investigate internal damage mechanisms such as cracking and delaminations. The obtained results of simulations are in agreement with experimental data and MicroCT scans.

  16. 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

  17. Nonlocal damage approach to analysis of the fracture process zone

    NASA Astrophysics Data System (ADS)

    Xia, S.; Takezono, S.; Tao, K.

    1994-05-01

    A two-zone fracture process model with a crack-bridging zone (CBZ) and a microcracking zone (MCZ) is proposed to describe the fracture process around the tip of a macrocrack. A nonlocal damage approach based on previous work is used to determined the size of the fracture process zone (FPZ). The experimental analysis given by Horii and Ichinomiya (1991) supports the proposal that the existence of the crack bridging effect brings out an increase in load-carrying capacity of materials, whereas microcracking leads to the deterioration of the capacity. Based on the above and utilizing Westergaard's complex function, the distribution functions of stress and damage in the FPZ are given. Applying these to the concrete-like material mortar, we can determine the distribution functions of stress and damage in the FPZ if load and crack opening displacement (COD) at a point are given. Additionally, a nonlocal damage failure criterion is proposed to judge the propagation of the macrocrack.

  18. Spiral Bevel Gear Damage Detection Using Decision Fusion Analysis

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.; Handschuh, Robert F.; Afjeh, Abdollah A.

    2002-01-01

    A diagnostic tool for detecting damage to spiral bevel gears was developed. Two different monitoring technologies, oil debris analysis and vibration, were integrated using data fusion into a health monitoring system for detecting surface fatigue pitting damage on gears. This integrated system showed improved detection and decision-making capabilities as compared to using individual monitoring technologies. This diagnostic tool was evaluated by collecting vibration and oil debris data from fatigue tests performed in the NASA Glenn Spiral Bevel Gear Fatigue Rigs. Data was collected during experiments performed in this test rig when pitting damage occurred. Results show that combining the vibration and oil debris measurement technologies improves the detection of pitting damage on spiral bevel gears.

  19. Online Nanoflow RP-RP-MS Reveals Dynamics of Multi-component Ku Complex in Response to DNA Damage

    PubMed Central

    Zhou, Feng; Cardoza, Job D.; Ficarro, Scott B.; Adelmant, Guillaume O.; Lazaro, Jean-Bernard; Marto, Jarrod A.

    2010-01-01

    Tandem affinity purification (TAP) coupled with mass spectrometry has become the technique of choice for characterization of multi-component protein complexes. While current TAP protocols routinely provide high yield and specificity for proteins expressed under physiologically relevant conditions, analytical figures of merit required for efficient and in-depth LC-MS analysis remain unresolved. Here we implement a multidimensional chromatography platform, based on two stages of reversed-phase separation operated at high and low pH, respectively. We compare performance metrics for RP-RP and SCX-RP for the analysis of complex peptide mixtures derived from cell lysate, as well as protein complexes purified via TAP. Our data reveal that RP-RP fractionation outperforms SCX-RP primarily due to increased peak capacity in the first dimension separation. We integrate this system with miniaturized LC assemblies to achieve true online fractionation at low (≤5nL/min) effluent flow rates. Stable isotope labeling is used to monitor the dynamics of the multi-component Ku protein complex in response to DNA damage induced by gamma radiation. PMID:20873769

  20. Nonlinear damage detection in composite structures using bispectral analysis

    NASA Astrophysics Data System (ADS)

    Ciampa, Francesco; Pickering, Simon; Scarselli, Gennaro; Meo, Michele

    2014-03-01

    Literature offers a quantitative number of diagnostic methods that can continuously provide detailed information of the material defects and damages in aerospace and civil engineering applications. Indeed, low velocity impact damages can considerably degrade the integrity of structural components and, if not detected, they can result in catastrophic failure conditions. This paper presents a nonlinear Structural Health Monitoring (SHM) method, based on ultrasonic guided waves (GW), for the detection of the nonlinear signature in a damaged composite structure. The proposed technique, based on a bispectral analysis of ultrasonic input waveforms, allows for the evaluation of the nonlinear response due to the presence of cracks and delaminations. Indeed, such a methodology was used to characterize the nonlinear behaviour of the structure, by exploiting the frequency mixing of the original waveform acquired from a sparse array of sensors. The robustness of bispectral analysis was experimentally demonstrated on a damaged carbon fibre reinforce plastic (CFRP) composite panel, and the nonlinear source was retrieved with a high level of accuracy. Unlike other linear and nonlinear ultrasonic methods for damage detection, this methodology does not require any baseline with the undamaged structure for the evaluation of the nonlinear source, nor a priori knowledge of the mechanical properties of the specimen. Moreover, bispectral analysis can be considered as a nonlinear elastic wave spectroscopy (NEWS) technique for materials showing either classical or non-classical nonlinear behaviour.

  1. Thermomechanical analysis of a damaged thermal protection system

    NASA Astrophysics Data System (ADS)

    Ng, Wei Heok

    Research on the effects of damage on the thermomechanical performance and structural integrity of thermal protection systems (TPS) has been limited. The objective of this research is to address this need by conducting experiments and finite element (FE) analysis on damaged TPS. The TPS selected for study is the High-Temperature Reusable Insulation (HRSI) tiles that are used extensively on NASA's Space Shuttle Orbiter. The TPS considered, which consists of a LI-900 tile, the strain isolator pad and the underlying structure, is subjected to the thermal loading and re-entry static pressure of the Access to Space reference vehicle. The damage to the TPS emulates hypervelocity-impact-type damage, which is approximated in the current research by a cylindrical hole ending with a spherical cap. Preliminary FE analysis using several simplifying assumptions, was conducted to determine the accuracy of using an approximate axisymmetric model compared to a complete three-dimensional model for both heat transfer and thermal stress analyses. Temperature results from the two models were found to be reasonable close; however, thermal stress results displayed significant differences. The sensitivity of the FE results to the various simplifying assumptions was also examined and it was concluded that for reliable results, the simplifying assumptions were not acceptable. Subsequently, an exact three-dimensional model was developed and validated by comparison with experimental data. Re-entry static pressures and temperatures were simulated using a high-temperature experimental facility that consists of a quartz radiant heater and a vacuum chamber with appropriate instrumentation. This facility was developed during the course of this dissertation. Temperatures on the top and bottom surfaces of the TPS specimen as well as strains in the underlying structure were recorded for FE model validation. The validated FE model was then combined with improved thermal loads based on the interactions

  2. Structural Damage Prediction and Analysis for Hypervelocity Impact: Consulting

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A portion of the contract NAS8-38856, 'Structural Damage Prediction and Analysis for Hypervelocity Impacts,' from NASA Marshall Space Flight Center (MSFC), included consulting which was to be documented in the final report. This attachment to the final report contains memos produced as part of that consulting.

  3. DETECTION OF DNA DAMAGE USING MELTING ANALYSIS TECHNIQUES

    EPA Science Inventory

    A rapid and simple fluorescence screening assay for UV radiation-, chemical-, and enzyme-induced DNA damage is reported. This assay is based on a melting/annealing analysis technique and has been used with both calf thymus DNA and plasmid DNA (puc 19 plasmid from E. coli). DN...

  4. Analysis of tank damage during the 1994 Northridge earthquake

    SciTech Connect

    Haroun, M.A.; Bhatia, H.

    1995-12-31

    The damage sustained by cylindrical liquid storage tanks during the 1994 Northridge earthquake is summarized. It included elephant foot buckling, anchor failure and roof-shell connection separation. A few of the important lessons learned, in particular, as related to the accuracy of code computations in predicting the actual behavior of these structures are outlined. A detailed case study is presented to illustrate the application of current seismic design standards to a damaged unanchored tank and to demonstrate the use of a state-of-the-art finite element analysis in assessing the seismic safety of the same tank.

  5. The Effects of Revealed Information on Catastrophe Loss Projection Models' Characterization of Risk: Damage Vulnerability Evidence from Florida.

    PubMed

    Karl, J Bradley; Medders, Lorilee A; Maroney, Patrick F

    2016-06-01

    We examine whether the risk characterization estimated by catastrophic loss projection models is sensitive to the revelation of new information regarding risk type. We use commercial loss projection models from two widely employed modeling firms to estimate the expected hurricane losses of Florida Atlantic University's building stock, both including and excluding secondary information regarding hurricane mitigation features that influence damage vulnerability. We then compare the results of the models without and with this revealed information and find that the revelation of additional, secondary information influences modeled losses for the windstorm-exposed university building stock, primarily evidenced by meaningful percent differences in the loss exceedance output indicated after secondary modifiers are incorporated in the analysis. Secondary risk characteristics for the data set studied appear to have substantially greater impact on probable maximum loss estimates than on average annual loss estimates. While it may be intuitively expected for catastrophe models to indicate that secondary risk characteristics hold value for reducing modeled losses, the finding that the primary value of secondary risk characteristics is in reduction of losses in the "tail" (low probability, high severity) events is less intuitive, and therefore especially interesting. Further, we address the benefit-cost tradeoffs that commercial entities must consider when deciding whether to undergo the data collection necessary to include secondary information in modeling. Although we assert the long-term benefit-cost tradeoff is positive for virtually every entity, we acknowledge short-term disincentives to such an effort. PMID:26720056

  6. Development of synthetic flood damage curve by explicit costs analysis

    NASA Astrophysics Data System (ADS)

    Martina, Mario; Molinari, Daniela; Dottori, Francesco; Scorzini, Annarita

    2015-04-01

    characteristics. Such functions were developed using a what-if analysis using data collected after the 2012 flood in the Umbria Region in Central Italy, as well as authors' experience, as reference to understand damage mechanisms. Observed damage data were also used to calibrate the functions.

  7. Transmission Bearing Damage Detection Using Decision Fusion Analysis

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.; Lewicki, David G.; Decker, Harry J.

    2004-01-01

    A diagnostic tool was developed for detecting fatigue damage to rolling element bearings in an OH-58 main rotor transmission. Two different monitoring technologies, oil debris analysis and vibration, were integrated using data fusion into a health monitoring system for detecting bearing surface fatigue pitting damage. This integrated system showed improved detection and decision-making capabilities as compared to using individual monitoring technologies. This diagnostic tool was evaluated by collecting vibration and oil debris data from tests performed in the NASA Glenn 500 hp Helicopter Transmission Test Stand. Data was collected during experiments performed in this test rig when two unanticipated bearing failures occurred. Results show that combining the vibration and oil debris measurement technologies improves the detection of pitting damage on spiral bevel gears duplex ball bearings and spiral bevel pinion triplex ball bearings in a main rotor transmission.

  8. Building protypes of damaged systems from analysis simulations

    SciTech Connect

    Tsai, C.S.; Dolin, R.M.; Hefele, J.

    1996-12-31

    Our rapid prototype of damaged systems project seeks to provide a technology for allowing engineers to build demonstration prototypes of damaged products from analysis post-processing data. Most commercial finite element programs do not have a capability to construct deformed geometry at the conclusion of an analysis simulation. It is therefore not presently possible to build prototypes of predicted states of a product as the result of being subjected to simulated adverse environments. Our approach is to reverse engineer a description of a deformed finite element mesh into a stereolithography format for prototyping using a Selective Laser Sintering (SLS) machine. This stereolithography file can be generated from deformed surface node information as well as from a reconstructed surface defined by inspection data. We are developing software to allow users to represent a part or assembly in a deformed condition. The damaged part can then be manufactured using the SLS process for visualization and assessment purposes. The resulting representation can also be used to create simulated X-rays of a damaged or deformed configuration for comparison with experimental test results or field data. This allows engineers to benchmark their analysis methods and provide increased understanding of analysis results through enhanced visualization. The process of reverse engineering `in-use` or damaged products allows for a more refined inspection and comparison of imperfect parts. It addresses the issue of whether or not a part will still work when subjected to certain environments or scenarios. Answers to this question can be found using our model reconstruction technique that represents an `as- built` engineering model configuration. An additional feature of this reverse engineering process is product benchmarking and closer engineer/manufacturer interactions.

  9. Tapered Roller Bearing Damage Detection Using Decision Fusion Analysis

    NASA Technical Reports Server (NTRS)

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

    2006-01-01

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

  10. Quantitative interactome analysis reveals a chemoresistant edgotype

    PubMed Central

    Chavez, Juan D.; Schweppe, Devin K.; Eng, Jimmy K.; Zheng, Chunxiang; Taipale, Alex; Zhang, Yiyi; Takara, Kohji; Bruce, James E.

    2015-01-01

    Chemoresistance is a common mode of therapy failure for many cancers. Tumours develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. Here, chemical crosslinking and mass spectrometry were employed to quantify changes in protein structures and interactions in multidrug-resistant human carcinoma cells. Quantitative analysis of the largest crosslinking-derived, protein interaction network comprising 1,391 crosslinked peptides allows for ‘edgotype' analysis in a cell model of chemoresistance. We detect consistent changes to protein interactions and structures, including those involving cytokeratins, topoisomerase-2-alpha, and post-translationally modified histones, which correlate with a chemoresistant phenotype. PMID:26235782

  11. Quantitative interactome analysis reveals a chemoresistant edgotype.

    PubMed

    Chavez, Juan D; Schweppe, Devin K; Eng, Jimmy K; Zheng, Chunxiang; Taipale, Alex; Zhang, Yiyi; Takara, Kohji; Bruce, James E

    2015-01-01

    Chemoresistance is a common mode of therapy failure for many cancers. Tumours develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. Here, chemical crosslinking and mass spectrometry were employed to quantify changes in protein structures and interactions in multidrug-resistant human carcinoma cells. Quantitative analysis of the largest crosslinking-derived, protein interaction network comprising 1,391 crosslinked peptides allows for 'edgotype' analysis in a cell model of chemoresistance. We detect consistent changes to protein interactions and structures, including those involving cytokeratins, topoisomerase-2-alpha, and post-translationally modified histones, which correlate with a chemoresistant phenotype. PMID:26235782

  12. Analysis Methods for Progressive Damage of Composite Structures

    NASA Technical Reports Server (NTRS)

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

    2013-01-01

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

  13. Lightning Strike Ablation Damage Characteristic Analysis for Carbon Fiber/Epoxy Composite Laminate with Fastener

    NASA Astrophysics Data System (ADS)

    Yin, J. J.; Li, S. L.; Yao, X. L.; Chang, F.; Li, L. K.; Zhang, X. H.

    2016-08-01

    In order to analyze the lightning strike ablation damage characteristic of composite laminate with fastener, based on the energy-balance relationship in lightning strike, mathematical analysis model of ablation damage of composite laminate with fastener was constructed. According to the model, an effective three dimensional thermal-electrical coupling analysis finite element model of composite laminate with fastener suffered from lightning current was established based on ABAQUS, and lightning strike ablation damage characteristic was analyzed. Analytical results reveal that lightning current could conduct through the thickness direction of the laminate due to the existence of metallic fastener, and then distribute to all layers, finally conducted in-the-plane of each layer, conductive ability of different layup orientations depend on potential distribution and in-the-plane electrical conductivity along potential gradient declining direction; different potential boundaries correspond to different potential distribution in each layer, and result in conductive ability of different layup orientations was changed, then caused different lightning strike ablation damage distribution. According to the investigation in this paper, we can recognize the lightning strike ablation damage characteristic of composite laminate with fastener qualitatively.

  14. Lightning Strike Ablation Damage Characteristic Analysis for Carbon Fiber/Epoxy Composite Laminate with Fastener

    NASA Astrophysics Data System (ADS)

    Yin, J. J.; Li, S. L.; Yao, X. L.; Chang, F.; Li, L. K.; Zhang, X. H.

    2016-04-01

    In order to analyze the lightning strike ablation damage characteristic of composite laminate with fastener, based on the energy-balance relationship in lightning strike, mathematical analysis model of ablation damage of composite laminate with fastener was constructed. According to the model, an effective three dimensional thermal-electrical coupling analysis finite element model of composite laminate with fastener suffered from lightning current was established based on ABAQUS, and lightning strike ablation damage characteristic was analyzed. Analytical results reveal that lightning current could conduct through the thickness direction of the laminate due to the existence of metallic fastener, and then distribute to all layers, finally conducted in-the-plane of each layer, conductive ability of different layup orientations depend on potential distribution and in-the-plane electrical conductivity along potential gradient declining direction; different potential boundaries correspond to different potential distribution in each layer, and result in conductive ability of different layup orientations was changed, then caused different lightning strike ablation damage distribution. According to the investigation in this paper, we can recognize the lightning strike ablation damage characteristic of composite laminate with fastener qualitatively.

  15. Building prototypes of damaged systems from analysis simulations

    NASA Astrophysics Data System (ADS)

    Tsai, Cynthia S.; Dolin, Ronald M.; Hefele, Jill

    1997-01-01

    Our rapid prototype of damaged systems project seeks to provide a technology for allowing engineers to build demonstration prototypes of damaged products from analysis post-processing data. Most commercial finite element programs do not have a capability to construct deformed geometry at conclusion of an analysis simulation. It is therefore not presently possible to build prototypes of predicted states of a product as the result of being subjected to simulated adverse environments. Our approach is to reverse engineer a description of a deformed finite element mesh into a stereolithography format for prototyping using a selective laser sintering (SLS) machine. This stereolithography file can be generated from deformed surface node information as well as from a reconstructed surface defined by inspection data. We are developing software to allow users to represent a part or assembly in a deformed condition. The resulting representation can also be used to create simulated x-rays of a damaged or deformed configuration for comparison with experimental test results or field data. This allows engineers to benchmark their analysis methods and provide increased understanding of analysis results through enhanced visualization. The process of reverse engineering 'in-use' or damaged products allows for a more refined inspection and comparison of imperfect parts. It addresses the issue of whether or not a part will still work when subjected to certain environments or scenarios. Answers to this question can be found using our model reconstruction technique that represents an 'as-built' engineering model configuration. An additional feature of this reverse engineering process is product benchmarking and closer engineer/manufacturer interactions.

  16. Image Science and Analysis Group Spacecraft Damage Detection/Characterization

    NASA Technical Reports Server (NTRS)

    Wheaton, Ira M., Jr.

    2010-01-01

    This project consisted of several tasks that could be served by an intern to assist the ISAG in detecting damage to spacecrafts during missions. First, this project focused on supporting the Micrometeoroid Orbital Debris (MMOD) damage detection and assessment for the Hubble Space Telescope (HST) using imagery from the last two HST Shuttle servicing missions. In this project, we used coordinates of two windows on the Shuttle Aft flight deck from where images were taken and the coordinates of three ID points in order to calculate the distance from each window to the three points. Then, using the specifications from the camera used, we calculated the image scale in pixels per inch for planes parallel to and planes in the z-direction to the image plane (shown in Table 1). This will help in the future for calculating measurements of objects in the images. Next, tabulation and statistical analysis were conducted for screening results (shown in Table 2) of imagery with Orion Thermal Protection System (TPS) damage. Using the Microsoft Excel CRITBINOM function and Goal Seek, the probabilities of detection of damage to different shuttle tiles were calculated as shown in Table 3. Using developed measuring tools, volume and area measurements will be created from 3D models of Orion TPS damage. Last, mathematical expertise was provided to the Photogrammetry Team. These mathematical tasks consisted of developing elegant image space error equations for observations along 3D lines, circles, planes, etc. and checking proofs for minimal sets of sufficient multi-linear constraints. Some of the processes and resulting equations are displayed in Figure 1.

  17. Identification and analysis of damaged or porous hair.

    PubMed

    Hill, Virginia; Loni, Elvan; Cairns, Thomas; Sommer, Jonathan; Schaffer, Michael

    2014-06-01

    Cosmetic hair treatments have been referred to as 'the pitfall' of hair analysis. However, most cosmetic treatments, when applied to the hair as instructed by the product vendors, do not interfere with analysis, provided such treatments can be identified by the laboratory and the samples analyzed and reported appropriately for the condition of the hair. This paper provides methods for identifying damaged or porous hair samples using digestion rates of hair in dithiothreitol with and without proteinase K, as well as a protein measurement method applied to dithiothreitol-digested samples. Extremely damaged samples may be unsuitable for analysis. Aggressive and extended aqueous washing of hair samples is a proven method for removing or identifying externally derived drug contamination of hair. In addition to this wash procedure, we have developed an alternative wash procedure using 90% ethanol for washing damaged or porous hair. The procedure, like the aqueous wash procedure, requires analysis of the last of five washes to evaluate the effectiveness of the washing procedure. This evaluation, termed the Wash Criterion, is derived from studies of the kinetics of washing of hair samples that have been experimentally contaminated and of hair from drug users. To study decontamination methods, in vitro contaminated drug-negative hair samples were washed by both the aqueous buffer method and a 90% ethanol method. Analysis of cocaine and methamphetamine was by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Porous hair samples from drug users, when washed in 90% ethanol, pass the wash criterion although they may fail the aqueous wash criterion. Those samples that fail both the ethanolic and aqueous wash criterion are not reported as positive for ingestion. Similar ratios of the metabolite amphetamine relative to methamphetamine in the last wash and the hair is an additional criterion for assessing contamination vs. ingestion of methamphetamine. PMID:24817048

  18. Brain damages in ketamine addicts as revealed by magnetic resonance imaging

    PubMed Central

    Wang, Chunmei; Zheng, Dong; Xu, Jie; Lam, Waiping; Yew, D. T.

    2013-01-01

    Ketamine, a known antagonist of N-methyl-D-aspartic (NMDA) glutamate receptors, had been used as an anesthetic particularly for pediatric or for cardiac patients. Unfortunately, ketamine has become an abusive drug in many parts of the world while chronic and prolonged usage led to damages of many organs including the brain. However, no studies on possible damages in the brains induced by chronic ketamine abuse have been documented in the human via neuroimaging. This paper described for the first time via employing magnetic resonance imaging (MRI) the changes in ketamine addicts of 0.5–12 years and illustrated the possible brain regions susceptible to ketamine abuse. Twenty-one ketamine addicts were recruited and the results showed that the lesions in the brains of ketamine addicts were located in many regions which appeared 2–4 years after ketamine addiction. Cortical atrophy was usually evident in the frontal, parietal or occipital cortices of addicts. Such study confirmed that many brain regions in the human were susceptible to chronic ketamine injury and presented a diffuse effect of ketamine on the brain which might differ from other central nervous system (CNS) drugs, such as cocaine, heroin, and methamphetamine. PMID:23882190

  19. Finite element stress analysis of idealized composite damage zones

    NASA Technical Reports Server (NTRS)

    Obrien, D.; Herakovich, C. T.

    1978-01-01

    A quasi three dimensional finite element stress analysis of idealized damage zones in composite laminates is presented. The damage zones consist of a long centered groove or cutout extending one or two layers in depth from both top and bottom surfaces of a thin composite laminate. Elastic results are presented for compressive loading of four and eight layer laminates. It is shown that a boundary layer exists near the cutout edge similar to that previously shown to exist along free edges. The cutout is shown to produce significant interlaminar stresses in the interior of the laminate away from free cutout edges. The interlaminar stresses are also shown to contribute to failure which is defined using the Tsai-Wu failure criteria.

  20. Spiral-Bevel-Gear Damage Detected Using Decision Fusion Analysis

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.; Handschuh, Robert F.

    2003-01-01

    Helicopter transmission integrity is critical to helicopter safety because helicopters depend on the power train for propulsion, lift, and flight maneuvering. To detect impending transmission failures, the ideal diagnostic tools used in the health-monitoring system would provide real-time health monitoring of the transmission, demonstrate a high level of reliable detection to minimize false alarms, and provide end users with clear information on the health of the system without requiring them to interpret large amounts of sensor data. A diagnostic tool for detecting damage to spiral bevel gears was developed. (Spiral bevel gears are used in helicopter transmissions to transfer power between nonparallel intersecting shafts.) Data fusion was used to integrate two different monitoring technologies, oil debris analysis and vibration, into a health-monitoring system for detecting surface fatigue pitting damage on the gears.

  1. Quantitative phase imaging applied to laser damage detection and analysis.

    PubMed

    Douti, Dam-Bé L; Chrayteh, Mhamad; Aknoun, Sherazade; Doualle, Thomas; Hecquet, Christophe; Monneret, Serge; Gallais, Laurent

    2015-10-01

    We investigate phase imaging as a measurement method for laser damage detection and analysis of laser-induced modification of optical materials. Experiments have been conducted with a wavefront sensor based on lateral shearing interferometry associated with a high-magnification optical microscope. The system has been used for the in-line observation of optical thin films and bulk samples, laser irradiated in two different conditions: 500 fs pulses at 343 and 1030 nm, and millisecond to second irradiation with a CO2 laser at 10.6 μm. We investigate the measurement of the laser-induced damage threshold of optical material by detection and phase changes and show that the technique realizes high sensitivity with different optical path measurements lower than 1 nm. Additionally, the quantitative information on the refractive index or surface modification of the samples under test that is provided by the system has been compared to classical metrology instruments used for laser damage or laser ablation characterization (an atomic force microscope, a differential interference contrast microscope, and an optical surface profiler). An accurate in-line measurement of the morphology of laser-ablated sites, from few nanometers to hundred microns in depth, is shown. PMID:26479612

  2. Diagnosis of Lung Cancer by Fractal Analysis of Damaged DNA.

    PubMed

    Namazi, Hamidreza; Kiminezhadmalaie, Mona

    2015-01-01

    Cancer starts when cells in a part of the body start to grow out of control. In fact cells become cancer cells because of DNA damage. A DNA walk of a genome represents how the frequency of each nucleotide of a pairing nucleotide couple changes locally. In this research in order to study the cancer genes, DNA walk plots of genomes of patients with lung cancer were generated using a program written in MATLAB language. The data so obtained was checked for fractal property by computing the fractal dimension using a program written in MATLAB. Also, the correlation of damaged DNA was studied using the Hurst exponent measure. We have found that the damaged DNA sequences are exhibiting higher degree of fractality and less correlation compared with normal DNA sequences. So we confirmed this method can be used for early detection of lung cancer. The method introduced in this research not only is useful for diagnosis of lung cancer but also can be applied for detection and growth analysis of different types of cancers. PMID:26539245

  3. Diagnosis of Lung Cancer by Fractal Analysis of Damaged DNA

    PubMed Central

    Namazi, Hamidreza; Kiminezhadmalaie, Mona

    2015-01-01

    Cancer starts when cells in a part of the body start to grow out of control. In fact cells become cancer cells because of DNA damage. A DNA walk of a genome represents how the frequency of each nucleotide of a pairing nucleotide couple changes locally. In this research in order to study the cancer genes, DNA walk plots of genomes of patients with lung cancer were generated using a program written in MATLAB language. The data so obtained was checked for fractal property by computing the fractal dimension using a program written in MATLAB. Also, the correlation of damaged DNA was studied using the Hurst exponent measure. We have found that the damaged DNA sequences are exhibiting higher degree of fractality and less correlation compared with normal DNA sequences. So we confirmed this method can be used for early detection of lung cancer. The method introduced in this research not only is useful for diagnosis of lung cancer but also can be applied for detection and growth analysis of different types of cancers. PMID:26539245

  4. Fatigue Crack Growth Database for Damage Tolerance Analysis

    NASA Technical Reports Server (NTRS)

    Forman, R. G.; Shivakumar, V.; Cardinal, J. W.; Williams, L. C.; McKeighan, P. C.

    2005-01-01

    The objective of this project was to begin the process of developing a fatigue crack growth database (FCGD) of metallic materials for use in damage tolerance analysis of aircraft structure. For this initial effort, crack growth rate data in the NASGRO (Registered trademark) database, the United States Air Force Damage Tolerant Design Handbook, and other publicly available sources were examined and used to develop a database that characterizes crack growth behavior for specific applications (materials). The focus of this effort was on materials for general commercial aircraft applications, including large transport airplanes, small transport commuter airplanes, general aviation airplanes, and rotorcraft. The end products of this project are the FCGD software and this report. The specific goal of this effort was to present fatigue crack growth data in three usable formats: (1) NASGRO equation parameters, (2) Walker equation parameters, and (3) tabular data points. The development of this FCGD will begin the process of developing a consistent set of standard fatigue crack growth material properties. It is envisioned that the end product of the process will be a general repository for credible and well-documented fracture properties that may be used as a default standard in damage tolerance analyses.

  5. Analysis of progressive damage in fibrous composite laminates

    SciTech Connect

    Kaveh-Ahangar, A.

    1990-01-01

    A model of a cracked laminate which consisted of three layers of fibrous composite materials where the middle layer is a 90 degree ply and contains an infinite row of equally spaced transverse cracks and the outer layers have arbitrary fiber orientations was proposed to study the progressive transverse cracking phenomena in multi-layered laminates. It was assumed that a microcrack which resembles a slit crack exists in the ply undergoing cracking. The constructed admissible stress field in the tiplet at dilute crack density was utilized to calculate the energy release rate of the microcrack. The thickness of the ply undergoing cracking, fiber orientation, and thickness of its adjacent plies were included in the analysis. Then, linear elastic fracture mechanics was used to predict the strength of a typical ply. The residual thermal stresses were also included in the analysis. The classical laminated plate theory was used to calculate the complementary energy of the cracked triplet in terms of its unknown effective thermoelastic properties and those of its damaged middle layer. The complementary energy of the triplet was also calculated in terms of the local properties of each layer of the triplet, from the constructed admissible stress fields. After calculating the thermoelastic properties of the damaged triplet, the thermoelastic properties of the damaged middle layer of the triplet were extracted from the relations between them which was obtained through the classical laminated plate theory. The energy release rate of a microcrack in the ligament between two existing cracks was calculated based on the constructed admissible stress fields. The effect of the crack density in the ply undergoing progressive cracking, the location of the microcrack, and fiber orientation of the adjacent plies were included in the analysis.

  6. Promoter hijack reveals pericentrin functions in mitosis and the DNA damage response

    PubMed Central

    Wang, Yifan; Dantas, Tiago J.; Lalor, Pierce; Dockery, Peter; Morrison, Ciaran G.

    2013-01-01

    Centrosomes, the principal microtubule-organizing centers of animal somatic cells, consist of two centrioles embedded in the pericentriolar material (PCM). Pericentrin is a large PCM protein that is required for normal PCM assembly. Mutations in PCNT cause primordial dwarfism. Pericentrin has also been implicated in the control of DNA damage responses. To test how pericentrin is involved in cell cycle control after genotoxic stress, we disrupted the Pcnt locus in chicken DT40 cells. Pericentrin-deficient cells proceeded through mitosis more slowly, with a high level of monopolar spindles, and were more sensitive to spindle poisons than controls. Centriole structures appeared normal by light and electron microscopy, but the PCM did not recruit γ-tubulin efficiently. Cell cycle delays after ionizing radiation (IR) treatment were normal in pericentrin-deficient cells. However, pericentrin disruption in Mcph1−/− cells abrogated centrosome hyperamplification after IR. We conclude that pericentrin controls genomic stability by both ensuring appropriate mitotic spindle activity and centrosome regulation. PMID:23324397

  7. Deep rock damage in the San Andreas Fault revealed by P- and S-type fault-zone-guided waves

    USGS Publications Warehouse

    Ellsworth, William L.; Malin, Peter E.

    2011-01-01

    Damage to fault-zone rocks during fault slip results in the formation of a channel of low seismic-wave velocities. Within such channels guided seismic waves, denoted by Fg, can propagate. Here we show with core samples, well logs and Fg-waves that such a channel is crossed by the SAFOD (San Andreas Fault Observatory at Depth) borehole at a depth of 2.7 km near Parkfield, California, USA. This laterally extensive channel extends downwards to at least half way through the seismogenic crust, more than about 7 km. The channel supports not only the previously recognized Love-type- (FL) and Rayleigh-type- (FR) guided waves, but also a new fault-guided wave, which we name FF. As recorded 2.7 km underground, FF is normally dispersed, ends in an Airy phase, and arrives between the P- and S-waves. Modelling shows that FF travels as a leaky mode within the core of the fault zone. Combined with the drill core samples, well logs and the two other types of guided waves, FF at SAFOD reveals a zone of profound, deep, rock damage. Originating from damage accumulated over the recent history of fault movement, we suggest it is maintained either by fracturing near the slip surface of earthquakes, such as the 1857 Fort Tejon M 7.9, or is an unexplained part of the fault-creep process known to be active at this site.

  8. Chromosome Model reveals Dynamic Redistribution of DNA Damage into Nuclear Sub-domains

    NASA Technical Reports Server (NTRS)

    Costes, Sylvain V.; Ponomarev, Artem; Chen, James L.; Cucinotta, Francis A.; Barcellos-Hoff, Helen

    2007-01-01

    Several proteins involved in the response to DNA double strand breaks (DSB) form microscopically visible nuclear domains, or foci, after exposure to ionizing radiation. Radiation-induced foci (RIF) are believed to be located where DNA damage is induced. To test this assumption, we analyzed the spatial distribution of 53BP1, phosphorylated ATM and gammaH2AX RIF in cells irradiated with high linear energy transfer (LET) radiation. Since energy is randomly deposited along high-LET particle paths, RIF along these paths should also be randomly distributed. The probability to induce DSB can be derived from DNA fragment data measured experimentally by pulsed-field gel electrophoresis. We used this probability in Monte Carlo simulations to predict DSB locations in synthetic nuclei geometrically described by a complete set of human chromosomes, taking into account microscope optics from real experiments. As expected, simulations produced DNA-weighted random (Poisson) distributions. In contrast, the distributions of RIF obtained as early as 5 min after exposure to high LET (1 GeV/amu Fe) were non-random. This deviation from the expected DNA-weighted random pattern can be further characterized by relative DNA image measurements. This novel imaging approach shows that RIF were located preferentially at the interface between high and low DNA density regions, and were more frequent in regions with lower density DNA than predicted. This deviation from random behavior was more pronounced within the first 5 min following irradiation for phosphorylated ATM RIF, while gammaH2AX and 53BP1 RIF showed very pronounced deviation up to 30 min after exposure. These data suggest the existence of repair centers in mammalian epithelial cells. These centers would be nuclear sub-domains where DNA lesions would be collected for more efficient repair.

  9. Sensitivity analysis of an auto-correlation-function-based damage index and its application in structural damage detection

    NASA Astrophysics Data System (ADS)

    Zhang, Muyu; Schmidt, Rüdiger

    2014-12-01

    Structural damage detection using time domain vibration responses has advantages such as simplicity in calculation and no requirement of a finite element model, which attracts more and more researchers in recent years. In present paper, a new approach to detect the damage based on the auto correlation function is proposed. The maximum values of the auto correlation function of the vibration response signals from different measurement points are formulated as a vector called Auto Correlation Function at Maximum Point Value Vector, AMV for short. The relative change of the normalized AMV before and after damage is used as the damage index to locate the damage. Sensitivity analysis of the normalized AMV with respect to the local stiffness shows that the normalized AMV has a sharp change around the local stiffness change location, which means the normalized AMV is a good indicator to detect the damage even when the damage is very small. Stiffness reduction detection of a 12-story frame structure is provided to illustrate the validity, effectiveness and the anti-noise ability of the proposed method. Comparison of the normalized AMV and the other correlation-function-based damage detection method shows the normalized AMV has a better detectability.

  10. Impact damage analysis of balsawood sandwich composite materials

    NASA Astrophysics Data System (ADS)

    Abdalslam, Suof Omran

    In this study, a new composite sandwich structure with a balsa wood core (end grain and regular balsa) in conjunction with E-glass/epoxy face sheets was proposed, fabricated, impact tested, and modeled. The behavior of the sandwich structure under low velocity impact and compression after impact was investigated. Low velocity impact tests were carried out by drop-weight impact tower at different energy levels (8J-35J) to evaluate the impact response of the sandwich structure. Visual inspection, destructive and non destructive evaluation methods have been conducted. For the sandwich plate with end grain core, the damage was very clear and can be visually detected. However, the damage in regular balsa core was not clearly visible and destructive evaluation method was used. Compression testing was done after subjecting the specimens to impact testing. Impact test results; load-time, load-deflection history and energy absorption for sandwich composites with two different cores, end grain and regular balsa were compared and they were investigated at three different impact energies. The results show that the sandwich structures with end grain core are able to withstand impact loading better than the regular balsa core because the higher stiffness of end grain core informs of sustaining higher load and higher overall energy. The results obtained from compression after impact testing show that the strengths of sandwich composites with end grain and regular balsa cores were reduced about 40% and 52%, respectively, after impact. These results were presented in terms of stress-strain curves for both damaged and undamaged specimens. Finite element analysis was conducted on the sandwich composite structure using LS-DYNA code to simulate impact test. A 3- D finite element model was developed and appropriate material properties were given to each component. The computational model was developed to predict the response of sandwich composite under dynamic loading. The experimental

  11. Genomic assay reveals tolerance of DNA damage by both translesion DNA synthesis and homology-dependent repair in mammalian cells.

    PubMed

    Izhar, Lior; Ziv, Omer; Cohen, Isadora S; Geacintov, Nicholas E; Livneh, Zvi

    2013-04-16

    DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategies are translesion DNA synthesis (TLS), in which low-fidelity DNA polymerases bypass the blocking lesion, and homology-dependent repair (HDR; postreplication repair), which is based on the homologous sister chromatid. Here we describe a unique high-resolution method for the simultaneous analysis of TLS and HDR across defined DNA lesions in mammalian genomes. The method is based on insertion of plasmids carrying defined site-specific DNA lesions into mammalian chromosomes, using phage integrase-mediated integration. Using this method we show that mammalian cells use HDR to tolerate DNA damage in their genome. Moreover, analysis of the tolerance of the UV light-induced 6-4 photoproduct, the tobacco smoke-induced benzo[a]pyrene-guanine adduct, and an artificial trimethylene insert shows that each of these three lesions is tolerated by both TLS and HDR. We also determined the specificity of nucleotide insertion opposite these lesions during TLS in human genomes. This unique method will be useful in elucidating the mechanism of DNA damage tolerance in mammalian chromosomes and their connection to pathological processes such as carcinogenesis. PMID:23530190

  12. Finite Element Analysis of 2.5D Woven Composites, Part II: Damage Behavior Simulation and Strength Prediction

    NASA Astrophysics Data System (ADS)

    Song, Jian; Wen, Weidong; Cui, Haitao; Zhang, Hongjian; Xu, Ying

    2016-02-01

    In the first part of the work, a new 2.5D woven composites finite element model (2.5D WCFEM) which took into consideration the impact of face structures and can accurately predict the main elastic performances has been established. In this part, the stress-strain behavior and the damage characteristic of this material under uniaxial tension are simulated using nonlinear progressive damage analysis based on damage mechanics. Meanwhile, experimental investigation and fracture analysis are conducted to evaluate the validity of the proposed method. Finally, the influence of woven parameters on the mechanical behavior is discussed. Compared with the test results, a good agreement between the computational and experimental results has been obtained. The progressive damage characteristic and main failure modes are also revealed.

  13. Nanoscale histone localization in live cells reveals reduced chromatin mobility in response to DNA damage

    PubMed Central

    Liu, Jing; Vidi, Pierre-Alexandre; Lelièvre, Sophie A.; Irudayaraj, Joseph M. K.

    2015-01-01

    ABSTRACT Nuclear functions including gene expression, DNA replication and genome maintenance intimately rely on dynamic changes in chromatin organization. The movements of chromatin fibers might play important roles in the regulation of these fundamental processes, yet the mechanisms controlling chromatin mobility are poorly understood owing to methodological limitations for the assessment of chromatin movements. Here, we present a facile and quantitative technique that relies on photoactivation of GFP-tagged histones and paired-particle tracking to measure chromatin mobility in live cells. We validate the method by comparing live cells to ATP-depleted cells and show that chromatin movements in mammalian cells are predominantly energy dependent. We also find that chromatin diffusion decreases in response to DNA breaks induced by a genotoxic drug or by the ISceI meganuclease. Timecourse analysis after cell exposure to ionizing radiation indicates that the decrease in chromatin mobility is transient and precedes subsequent increased mobility. Future applications of the method in the DNA repair field and beyond are discussed. PMID:25501817

  14. Radiation Damage and Racemic Protein Crystallography Reveal the Unique Structure of the GASA/Snakin Protein Superfamily.

    PubMed

    Yeung, Ho; Squire, Christopher J; Yosaatmadja, Yuliana; Panjikar, Santosh; López, Gemma; Molina, Antonio; Baker, Edward N; Harris, Paul W R; Brimble, Margaret A

    2016-07-01

    Proteins from the GASA/snakin superfamily are common in plant proteomes and have diverse functions, including hormonal crosstalk, development, and defense. One 63-residue member of this family, snakin-1, an antimicrobial protein from potatoes, has previously been chemically synthesized in a fully active form. Herein the 1.5 Å structure of snakin-1, determined by a novel combination of racemic protein crystallization and radiation-damage-induced phasing (RIP), is reported. Racemic crystals of snakin-1 and quasi-racemic crystals incorporating an unnatural 4-iodophenylalanine residue were prepared from chemically synthesized d- and l-proteins. Breakage of the C-I bonds in the quasi-racemic crystals facilitated structure determination by RIP. The crystal structure reveals a unique protein fold with six disulfide crosslinks, presenting a distinct electrostatic surface that may target the protein to microbial cell surfaces. PMID:27145301

  15. DAMAGE DETECTION IN PLATE STRUCTURES USING MODAL POWER FLOW ANALYSIS

    SciTech Connect

    Liu, X.; Wong, W. O.; Cheng, L.

    2010-05-28

    The power flow and energy distribution of a vibration mode of a damaged plate is studied experimentally. Variation of the modal reactive power distribution of a damaged plate is experimentally evaluated with a scanning LDV and compared to the theoretical predictions. Large variation of local reactive power flow in or around the damage region of a plate under resonant vibration is found to be related to the change of strain and kinetic energies in the damage region. Feasibility of damage identification based on the detection of this local variation of modal reactive power flow in a structure is studied.

  16. PCR-Based Analysis of Mitochondrial DNA Copy Number, Mitochondrial DNA Damage, and Nuclear DNA Damage.

    PubMed

    Gonzalez-Hunt, Claudia P; Rooney, John P; Ryde, Ian T; Anbalagan, Charumathi; Joglekar, Rashmi; Meyer, Joel N

    2016-01-01

    Because of the role that DNA damage and depletion play in human disease, it is important to develop and improve tools to assess these endpoints. This unit describes PCR-based methods to measure nuclear and mitochondrial DNA damage and copy number. Long amplicon quantitative polymerase chain reaction (LA-QPCR) is used to detect DNA damage by measuring the number of polymerase-inhibiting lesions present based on the amount of PCR amplification; real-time PCR (RT-PCR) is used to calculate genome content. In this unit, we provide step-by-step instructions to perform these assays in Homo sapiens, Mus musculus, Rattus norvegicus, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Oryzias latipes, Fundulus grandis, and Fundulus heteroclitus, and discuss the advantages and disadvantages of these assays. PMID:26828332

  17. PCR-based analysis of mitochondrial DNA copy number, mitochondrial DNA damage, and nuclear DNA damage

    PubMed Central

    Gonzalez-Hunt, Claudia P.; Rooney, John P.; Ryde, Ian T.; Anbalagan, Charumathi; Joglekar, Rashmi

    2016-01-01

    Because of the role DNA damage and depletion play in human disease, it is important to develop and improve tools to assess these endpoints. This unit describes PCR-based methods to measure nuclear and mitochondrial DNA damage and copy number. Long amplicon quantitative polymerase chain reaction (LA-QPCR) is used to detect DNA damage by measuring the number of polymerase-inhibiting lesions present based on the amount of PCR amplification; real-time PCR (RT-PCR) is used to calculate genome content. In this unit we provide step-by-step instructions to perform these assays in Homo sapiens, Mus musculus, Rattus norvegicus, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Oryzias latipes, Fundulus grandis, and Fundulus heteroclitus, and discuss the advantages and disadvantages of these assays. PMID:26828332

  18. Non-Harmonic Fourier Analysis for bladed wheels damage detection

    NASA Astrophysics Data System (ADS)

    Neri, P.; Peeters, B.

    2015-11-01

    The interaction between bladed wheels and the fluid distributed by the stator vanes results in cyclic loading of the rotating components. Compressors and turbines wheels are subject to vibration and fatigue issues, especially when resonance conditions are excited. Even if resonance conditions can be often predicted and avoided, high cycle fatigue failures can occur, causing safety issues and economic loss. Rigorous maintenance programs are then needed, forcing the system to expensive shut-down. Blade crack detection methods are beneficial for condition-based maintenance. While contact measurement systems are not always usable in exercise conditions (e.g. high temperature), non-contact methods can be more suitable. One (or more) stator-fixed sensor can measure all the blades as they pass by, in order to detect the damaged ones. The main drawback in this situation is the short acquisition time available for each blade, which is shortened by the high rotational speed of the components. A traditional Discrete Fourier Transform (DFT) analysis would result in a poor frequency resolution. A Non-Harmonic Fourier Analysis (NHFA) can be executed with an arbitrary frequency resolution instead, allowing to obtain frequency information even with short-time data samples. This paper shows an analytical investigation of the NHFA method. A data processing algorithm is then proposed to obtain frequency shift information from short time samples. The performances of this algorithm are then studied by experimental and numerical tests.

  19. Structural Damage Prediction and Analysis for Hypervelocity Impact

    NASA Technical Reports Server (NTRS)

    Elfer, Norman

    1995-01-01

    It is necessary to integrate a wide variety of technical disciplines to provide an analysis of structural damage to a spacecraft due to hypervelocity impact. There are many uncertainties, and more detailed investigation is warranted, in each technical discipline. However, a total picture of the debris and meteoroid hazard is required to support manned spaceflight in general, and the international Space Station in particular. In the performance of this contract, besides producing a handbook, research and development was conducted in several different areas. The contract was broken into six separate tasks. Each task objectives and accomplishments will be reviewed in the following sections. The Handbook and separate task reports are contained as attachments to the final report. The final section summarizes all of the recommendations coming out of this study. The analyses and comments are general design guidelines and not necessarily applicable to final Space Station designs since several configuration and detailed design changes were being made during the course of this contract. Rather, the analyses and comments may indicate either a point-in-time concept analysis, available test data, or desirable protection goals, not hindered by the design and operation constraints faced by Space Station designers.

  20. Lightning damage to a general aviation aircraft: Description and analysis

    NASA Technical Reports Server (NTRS)

    Hacker, P. T.

    1974-01-01

    The damage sustained by a Beechcraft King Air Model B90 aircraft by a single lightning discharge is presented and analyzed. The incident occurred during landing approach at Jackson, Michigan, on Feb. 19, 1971. In addition to the usual melted-metal damage at the lightning attachment points, there was severe implosion-type damage over a large area on the lower right side of the aircraft and impact- and crushing-type damage on the upper and lower surfaces on the left wingtip near the trailing edge. Analyses indicate that the implosion-type damage was probably caused by lightning-generated shock waves, that the impact-and crushing-type damage was caused by magnetic forces, and that the lightning discharge was a multiple strike with at least 11 strokes separated in time by about 4.5 milliseconds. The evidence indicates that the lightning discharge was rather different from the average in character severity.

  1. Damage Analysis of Rectangular Section Composite Beam under Pure Bending

    NASA Astrophysics Data System (ADS)

    Liu, Yiping; Xiao, Fan; Liu, Zejia; Tang, Liqun; Fang, Daining

    2013-02-01

    Laminated composite beams are commonly used in engineering applications involving macro to nano structures. Based on the assumption that plain sections remain plain after deformation, this paper analyzes stress distributions in cross-ply laminated composite beams with rectangular cross-sections, and formulates the basic damage equations through Kachanov's damage definition and Janson's failure criterion. The location of the neutral axis and the ultimate bending moment are obtained for pure bending cases. The effect of the elastic modulus of the two layers on the damage evolution is analyzed; a reasonable damage composite beam model is proposed to predict the ultimate bending moment.

  2. Mechanistic Analysis of Rock Damage Anisotropy and Rotation Around Circular Cavities

    NASA Astrophysics Data System (ADS)

    Xu, Hao; Arson, Chloé

    2015-11-01

    We used the differential stress-induced damage (DSID) model to predict anisotropic crack propagation under tensile and shear stress. The damage variable is similar to a crack density tensor. The damage function and the damage potential are expressed as functions of the energy release rate, defined as the thermodynamic force that is work-conjugate to damage. Contrary to the previous damage models, flow rules are obtained by deriving dissipation functions by the energy release rate, and thermodynamic consistency is ensured. The damage criterion is adapted from the Drucker-Prager yield function. Simulations of biaxial stress tests showed that: (1) three-dimensional states of damage can be obtained for three-dimensional states of stress; (2) no damage propagates under isotropic compression; (3) crack planes propagate in the direction parallel to major compression stress; (4) damage propagation hardens the material; (5) stiffness and deformation anisotropy result from the anisotropy of damage. There is no one-to-one relationship between stress and damage. We demonstrated the effect of the loading sequence in a two-step simulation (a shear loading phase and a compression loading phase): the current state of stress and damage can be used to track the effect of stress history on damage rotation. We finally conducted a sensitivity analysis with the finite element method, to explore the stress conditions in which damage is expected to rotate around a circular cavity subject to pressurization or depressurization. Simulation results showed that: (1) before damage initiation, the DSID model matches the analytical solution of stress distribution obtained with the theory of elasticity; (2) the DSID model can predict the extent of the tensile damage zone at the crown, and that of the compressive damage zone at the sidewalls; (3) damage generated during a vertical far-field compression followed by a depressurization of the cavity is more intense than that generated during a

  3. A comet assay study reveals that aluminium induces DNA damage and inhibits the repair of radiation-induced lesions in human peripheral blood lymphocytes.

    PubMed

    Lankoff, Anna; Banasik, Anna; Duma, Anna; Ochniak, Edyta; Lisowska, Halina; Kuszewski, Tomasz; Góźdź, Stanisław; Wojcik, Andrzej

    2006-02-01

    Although it is known that many metals induce DNA damage and inhibit DNA repair, information regarding aluminium (Al) is scarce. The aim of this study was to analyze the level of DNA damage in human peripheral blood lymphocytes treated with Al and the impact of Al on the repair of DNA damage induced by ionizing radiation. Cells were treated with different doses of aluminium chloride (1, 2, 5, 10 and 25 microg/ml AlCl(3)) for 72 h. The level of DNA damage and of apoptosis was determined by the comet assay. The level of oxidative damage was determined by the application of endonuclease III and formamidopyrimidine DNA glycosylase. The results on apoptosis were confirmed by flow cytometry. Based on the fluorescence intensity, cells were divided into cohorts of different relative DNA content that corresponds to G(1), S and G(2) phases of the cell cycle. Our results revealed that Al induces DNA damage in a dose-dependent manner, however, at the dose of 25 microg/ml the level of damage declined. This decline was accompanied by a high level of apoptosis indicating selective elimination of damaged cells. Cells pre-treated with Al showed a decreased repair capacity indicating that Al inhibits DNA repair. The possible mechanisms by which Al induces DNA damage and inhibits the repair are discussed. PMID:16139969

  4. Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells

    PubMed Central

    FANG, YI; ZHANG, QIAN; WANG, XIN; YANG, XUE; WANG, XIANGYU; HUANG, ZHEN; JIAO, YUCHEN; WANG, JING

    2016-01-01

    Around one sixth of breast cancer cases are classified as triple-negative breast cancer (TNBC), named after the absence of the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2); however, patients with TNBC suffer from poor clinical outcome and shortage of targeted therapy. Genistein, an estrogenic soy isoflavone, shows anticancer effects in TNBC cells such as inducing G2/M cell cycle arrest and apoptosis. However, the underlying mechanism of its anticancer effects is poorly understood and its elucidation can help the development of novel therapeutic strategies for TNBC. In this study, by combining isobaric tag-based TMT labeling with titanium dioxide-based phosphopeptide enrichment, we quantitated 5,445 phosphorylation sites on 2,008 phosphoproteins in the TNBC cell line MDA-MB-231, upon genistein treatment. Our analysis revealed 332 genistein-regulated phosphorylation sites on 226 proteins. Our data show that genistein can regulate several biological processes during the cell cycle, including DNA replication, cohesin complex cleavage, and kinetochore formation. Furthermore, genistein can also activate DNA damage response, including activation of ATR and BRCA1 complex. Overall, our study presents evidence at a phosphoproteomic level that genistein is able to inhibit TNBC cell growth by regulating the cell cycle and DNA damage response in a more complex manner. Our findings help elucidate the mechanisms through which genistein exerts its anticancer effects in TNBC cells. PMID:26783066

  5. Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells.

    PubMed

    Fang, Yi; Zhang, Qian; Wang, Xin; Yang, Xue; Wang, Xiangyu; Huang, Zhen; Jiao, Yuchen; Wang, Jing

    2016-03-01

    Around one sixth of breast cancer cases are classified as triple-negative breast cancer (TNBC), named after the absence of the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2); however, patients with TNBC suffer from poor clinical outcome and shortage of targeted therapy. Genistein, an estrogenic soy isoflavone, shows anticancer effects in TNBC cells such as inducing G2/M cell cycle arrest and apoptosis. However, the underlying mechanism of its anticancer effects is poorly understood and its elucidation can help the development of novel therapeutic strategies for TNBC. In this study, by combining isobaric tag-based TMT labeling with titanium dioxide-based phosphopeptide enrichment, we quantitated 5,445 phosphorylation sites on 2,008 phosphoproteins in the TNBC cell line MDA-MB-231, upon genistein treatment. Our analysis revealed 332 genistein-regulated phosphorylation sites on 226 proteins. Our data show that genistein can regulate several biological processes during the cell cycle, including DNA replication, cohesin complex cleavage, and kinetochore formation. Furthermore, genistein can also activate DNA damage response, including activation of ATR and BRCA1 complex. Overall, our study presents evidence at a phosphoproteomic level that genistein is able to inhibit TNBC cell growth by regulating the cell cycle and DNA damage response in a more complex manner. Our findings help elucidate the mechanisms through which genistein exerts its anticancer effects in TNBC cells. PMID:26783066

  6. Damage Tolerance Analysis of a Pressurized Liquid Oxygen Tank

    NASA Technical Reports Server (NTRS)

    Forth, Scott C.; Harvin, Stephen F.; Gregory, Peyton B.; Mason, Brian H.; Thompson, Joe E.; Hoffman, Eric K.

    2006-01-01

    A damage tolerance assessment was conducted of an 8,000 gallon pressurized Liquid Oxygen (LOX) tank. The LOX tank is constructed of a stainless steel pressure vessel enclosed by a thermal-insulating vacuum jacket. The vessel is pressurized to 2,250 psi with gaseous nitrogen resulting in both thermal and pressure stresses on the tank wall. Finite element analyses were performed on the tank to characterize the stresses from operation. Engineering material data was found from both the construction of the tank and the technical literature. An initial damage state was assumed based on records of a nondestructive inspection performed on the tank. The damage tolerance analyses were conducted using the NASGRO computer code. This paper contains the assumptions, and justifications, made for the input parameters to the damage tolerance analyses and the results of the damage tolerance analyses with a discussion on the operational safety of the LOX tank.

  7. Analysis of 1w Bulk Laser Damage in KDP

    SciTech Connect

    Cross, D A; Carr, C W

    2011-04-11

    The influence of laser parameters on laser-induced damage in the bulk of KDP is difficult to determine because the damage manifests as discrete sites a few microns in diameter distributed throughout a relatively large volume of material. Here, they present a method to directly measure the size and location of many thousands of such sites and correlate them to the laser conditions which produced them. This technique is used to characterize the effects of pulse duration on damage initiated by 1053 nm light in the bulk of KDP crystals. They find that the density of damage sites produced by 1053 nm light is less sensitive to pulse duration than was previously reported for 526 nm and 351 nm light. In addition, the effect of pulse duration on the size of the damage sites produced appears insensitive to wavelength.

  8. On damage detection in wind turbine gearboxes using outlier analysis

    NASA Astrophysics Data System (ADS)

    Antoniadou, Ifigeneia; Manson, Graeme; Dervilis, Nikolaos; Staszewski, Wieslaw J.; Worden, Keith

    2012-04-01

    The proportion of worldwide installed wind power in power systems increases over the years as a result of the steadily growing interest in renewable energy sources. Still, the advantages offered by the use of wind power are overshadowed by the high operational and maintenance costs, resulting in the low competitiveness of wind power in the energy market. In order to reduce the costs of corrective maintenance, the application of condition monitoring to gearboxes becomes highly important, since gearboxes are among the wind turbine components with the most frequent failure observations. While condition monitoring of gearboxes in general is common practice, with various methods having been developed over the last few decades, wind turbine gearbox condition monitoring faces a major challenge: the detection of faults under the time-varying load conditions prevailing in wind turbine systems. Classical time and frequency domain methods fail to detect faults under variable load conditions, due to the temporary effect that these faults have on vibration signals. This paper uses the statistical discipline of outlier analysis for the damage detection of gearbox tooth faults. A simplified two-degree-of-freedom gearbox model considering nonlinear backlash, time-periodic mesh stiffness and static transmission error, simulates the vibration signals to be analysed. Local stiffness reduction is used for the simulation of tooth faults and statistical processes determine the existence of intermittencies. The lowest level of fault detection, the threshold value, is considered and the Mahalanobis squared-distance is calculated for the novelty detection problem.

  9. Analysis of shape memory alloy sensory particles for damage detection via substructure and continuum damage modeling

    NASA Astrophysics Data System (ADS)

    Bielefeldt, Brent R.; Benzerga, A. Amine; Hartl, Darren J.

    2016-04-01

    The ability to monitor and predict the structural health of an aircraft is of growing importance to the aerospace industry. Currently, structural inspections and maintenance are based upon experiences with similar aircraft operating in similar conditions. While effective, these methods are time-intensive and unnecessary if the aircraft is not in danger of structural failure. It is imagined that future aircraft will utilize non-destructive evaluation methods, allowing for the near real-time monitoring of structural health. A particularly interesting method involves utilizing the unique transformation response of shape memory alloy (SMA) particles embedded in an aircraft structure. By detecting changes in the mechanical and/or electromagnetic responses of embedded particles, operators could detect the formation or propagation of fatigue cracks in the vicinity of these particles. This work focuses on a finite element model of SMA particles embedded in an aircraft wing using a substructure modeling approach in which degrees of freedom are retained only at specified points of connection to other parts or the application of boundary conditions, greatly reducing computational cost. Previous work evaluated isolated particle response to a static crack to numerically demonstrate and validate this damage detection method. This paper presents the implementation of a damage model to account for crack propagation and examine for the first time the effect of particle configuration and/or relative placement with respect to the ability to detect damage.

  10. Multi-frequency local wavenumber analysis and ply correlation of delamination damage.

    PubMed

    Juarez, Peter D; Leckey, Cara A C

    2015-09-01

    Wavenumber domain analysis through use of scanning laser Doppler vibrometry has been shown to be effective for non-contact inspection of damage in composites. Qualitative and semi-quantitative local wavenumber analysis of realistic delamination damage and quantitative analysis of idealized damage scenarios (Teflon inserts) have been performed previously in the literature. This paper presents a new methodology based on multi-frequency local wavenumber analysis for quantitative assessment of multi-ply delamination damage in carbon fiber reinforced polymer (CFRP) composite specimens. The methodology is presented and applied to a real world damage scenario (impact damage in an aerospace CFRP composite). The methodology yields delamination size and also correlates local wavenumber results from multiple excitation frequencies to theoretical dispersion curves in order to robustly determine the delamination ply depth. Results from the wavenumber based technique are validated against a traditional nondestructive evaluation method. PMID:25980617

  11. Damage Identification in Cable-Stayed Bridge Based on Modal Analysis and Neural Networks

    NASA Astrophysics Data System (ADS)

    Zhang, Xiedong; Zhang, Zhiguo; Li, Xiaofan; Zhan, Hao

    2007-03-01

    A damage-detection-oriented finite element model of a cable-stayed highway bridge is established and the modal analysis is then carried out. Modal frequency, displacement modal shape and curvature modal shape are included in BP neural network input vector. BP neural network models are established for bridge damage detection. The result indicates that the method based on vibration modal analysis theory and BP neural networks can detect both the position and degree of the damage.

  12. Experimental damage analysis of steels after exploitation loading

    NASA Astrophysics Data System (ADS)

    Kowalewski, Z.; Szelä Żek, J.; Mackiewicz, S.; Augustyniak, B.

    2010-06-01

    Development of creep damage at elevated temperatures and structural degradation due to plastic deformation at room temperature were assessed using destructive and non-destructive methods in steels commonly applied in power plants (40HNMA, 13HMF and P91). As destructive methods the standard tension tests were carried out after every kind of prestraining. Subsequently, an evolution of the selected tension parameters was taken into account for damage identification. In order to assess a damage development during the creep and plastic deformation the tests for the steels were interrupted for a range of the selected strain magnitudes. The ultrasonic and magnetic techniques were used as the non-destructive methods for damage evaluation. The experimental programme also contained microscopic observations.

  13. Damage Analysis for Hypervelocity Impact Experiments on Spaceship Windows Glass

    NASA Astrophysics Data System (ADS)

    Jiyun, Y.; Jidong, Z.; Zizheng, G.; Hewei, P.

    2010-06-01

    The hypervelocity impact characteristics in fused silica glass, which is used for the outermost pane of the windshield as the critical part of the thermal protection system of spacecraft, were studied by 37 impact experiments with different millimeter diameter projectiles up to the velocity of 7 km/s launched by two stage light-gas-gun facility. The empirical damage equations were obtained from experiment data by the least square method and they were compared with NASA damage equations.

  14. TSS tether cable meteoroid/orbital debris damage analysis

    NASA Technical Reports Server (NTRS)

    Hayashida, K. B.; Robinson, J. H.

    1993-01-01

    This report summarizes the damage analyses performed on the tether cable used for the tethered satellite system (TSS), for the damage that could be caused by meteoroid or orbital debris impacts. The TSS consists of a tethered satellite deployer and a tethered satellite. The analytical studies were performed at Marshall Space Flight Center (MSFC) with the results from the following tests: (1) hypervelocity impact tests to determine the 'critical' meteoroid particle diameter, i.e., the maximum size of a meteoroid particle which can impact the tether cable without causing 'failure'; (2) electrical resistance tests on the damaged and undamaged tether cable to determine if degradation of current flow occurred through the damaged tether cables; and (3) tensile load tests to verify the load carrying capability of the damaged tether cables. Finally, the HULL hydrodynamic computer code was used to simulate the hypervelocity impact of the tether cable by particles at velocities higher than can be tested, to determine the extent of the expected tether damage.

  15. Seismic Damage Analysis of Aged Concrete Gravity Dams

    NASA Astrophysics Data System (ADS)

    Nayak, Parsuram; Maity, Damodar

    2013-08-01

    The design of a concrete gravity dam must provide the ability to withstand the seismic forces for which nonlinear behavior is expected. The nonlinear seismic response of the dam may be different due to aging, as the concrete gets degraded because of environmental factors and mechanical loadings. The present study investigates the evolution of tensile damages in aged concrete gravity dams, which is necessary to estimate the safety of existing dams towards future earthquake forces. The degraded material properties of the concrete with age, subjected to environmental factors and mechanical loadings, are determined introducing an isotropic degradation index. A concrete damaged plasticity model, which assumes both the compressive and tensile damage, is used to evaluate the nonlinear seismic response of the dam. Results show that the peak maximum principal stresses reduced at the neck due to aging effects in the concrete. It is observed that the neck region is the most vulnerable region to initiate damage for all cases of aged dams. The results show that there are severe damages to the structure at higher ages under seismic loadings. The proposed method can ensure the safety of dams during their entire design life considering the environmental factors and mechanical loadings affecting the materials as they age.

  16. Analysis of chromatin integrity and DNA damage of buffalo spermatozoa.

    PubMed

    Mahmoud, K Gh M; El-Sokary, A A E; Abdel-Ghaffar, A E; Abou El-Roos, M E A; Ahmed, Y F

    2015-01-01

    This study was conducted to determine chromatin integrity and DNA damage by DNA electrophoresis and comet assays of buffalo fresh and frozen semen. Semen samples were collected from four buffalo bulls and evaluated after freezing for semen motility, viability, sperm abnormalities, chromatin integrity and DNA damage. A significant variation was found in semen parameters after thawing. Highly significant differences (P<0.001) in chromatin integrity were observed between fresh and frozen semen. For the fresh semen, there was no significant difference between the bulls for chromatin integrity; however, a significant variation (P<0.05) was detected in their frozen semen. No DNA fragmentation was observed by agarose gel electrophoresis. The percentage of sperm with damaged DNA detected by comet assay differed significantly between fresh and frozen semen. A significant negative correlation was recorded between motility and DNA damage (r=-0.68, P<0.05). Sperm abnormalities and DNA fragmentation were significantly positively correlated (r=0.59, P<0.05). In conclusion, DNA damage evaluation can provide reassurance about genomic normalcy and guide the development of improved methods of selecting spermatozoa with intact DNA to be used in artificial insemination. PMID:27175169

  17. Analysis of chromatin integrity and DNA damage of buffalo spermatozoa

    PubMed Central

    Mahmoud, K. Gh. M.; El-Sokary, A. A. E.; Abdel-Ghaffar, A. E.; Abou El-Roos, M. E. A.; Ahmed, Y. F.

    2015-01-01

    This study was conducted to determine chromatin integrity and DNA damage by DNA electrophoresis and comet assays of buffalo fresh and frozen semen. Semen samples were collected from four buffalo bulls and evaluated after freezing for semen motility, viability, sperm abnormalities, chromatin integrity and DNA damage. A significant variation was found in semen parameters after thawing. Highly significant differences (P<0.001) in chromatin integrity were observed between fresh and frozen semen. For the fresh semen, there was no significant difference between the bulls for chromatin integrity; however, a significant variation (P<0.05) was detected in their frozen semen. No DNA fragmentation was observed by agarose gel electrophoresis. The percentage of sperm with damaged DNA detected by comet assay differed significantly between fresh and frozen semen. A significant negative correlation was recorded between motility and DNA damage (r=-0.68, P<0.05). Sperm abnormalities and DNA fragmentation were significantly positively correlated (r=0.59, P<0.05). In conclusion, DNA damage evaluation can provide reassurance about genomic normalcy and guide the development of improved methods of selecting spermatozoa with intact DNA to be used in artificial insemination. PMID:27175169

  18. Damage Characterization in Copper Deformed Under Hydrostatic Stress - Experimental Analysis

    NASA Astrophysics Data System (ADS)

    Flater, Philip; de Angelis, Robert; House, Joel

    2005-07-01

    This paper presents an experimental investigation to characterize the effect of damage created by hydrostatic tensile loading on the properties of copper. Three metallurgical conditions were investigated: half-hard OFHC copper in the as worked, annealed 2hr at 400°C (˜40 micron grain diameter), and annealed 2hr at 800^ oC (˜80 micron grain diameter). Quasi-static testing of each condition included uniaxial tension and compression, round notched bar tension, and flat tapered bar tension. Dynamic properties under uniaxial tension and compression were tested using a split-Hopkinson pressure bar. Damaged structures were created employing Taylor impact tests and rod-on-rod impact experiments. The resulting damage was characterized employing optical and scanning electron microscopy. Quasi-static compression samples machined from recovered samples were tested to determine the influence of damage on deformation behavior and elastic modulus. The compression experimental results will be discussed in relationship to the starting microstructure and subsequent damaged material.

  19. Thermomechanics of damageable materials under diffusion: modelling and analysis

    NASA Astrophysics Data System (ADS)

    Roubíček, Tomáš; Tomassetti, Giuseppe

    2015-12-01

    We propose a thermodynamically consistent general-purpose model describing diffusion of a solute or a fluid in a solid undergoing possible phase transformations and damage, beside possible visco-inelastic processes. Also heat generation/consumption/transfer is considered. Damage is modelled as rate-independent. The applications include metal-hydrogen systems with metal/hydride phase transformation, poroelastic rocks, structural and ferro/para-magnetic phase transformation, water and heat transport in concrete, and if diffusion is neglected, plasticity with damage and viscoelasticity, etc. For the ensuing system of partial differential equations and inclusions, we prove existence of solutions by a carefully devised semi-implicit approximation scheme of the fractional-step type.

  20. Analysis of bending properties for damaged laminated pipes

    SciTech Connect

    Yokoyama, A.; Nishiwaki, T.; Nakai, A.; Hamada, H.

    1996-12-01

    Various composite cylinders, such as braided cylinders, could be fabricated with a high volume fabrication method, using thermoplastic composites and so on. If so, usage of composite cylinder would be extended. In this paper, a new analytical model named Quasi-Three-Dimensional model was proposed and applied to a two-layered composite cylinder. Under various service environments, a damaged cylinder with interlaminar fracture often appeared. The calculated elastic modulus was decreased with an increase of the damaged area. From deformation states and stress distribution of interlaminae, some coupling effects were recognized, even if the analytical cylinder without any damage never showed any coupling effects. This result showed the usefulness of the Quasi-Three-Dimensional model.

  1. Analysis of Raster Scanning Damage and Conditioning Experiments

    SciTech Connect

    Feit, M D; Rubenchik, A M

    2002-10-11

    The raster scan technique is used for large optics damage tests and laser conditioning. We show that the ''effective area'' concept enables the possibility to compare various scanning schemes and to use raster scan experiments for NIF optics damage prediction. It is shown that the hexagonal lattice of laser beam imprints yields optimal use of each shot for most of the typically used parameters. The effects of beam fluence fluctuations and pointing inaccuracies on experiments are evaluated. To analyze raster scan conditioning experiments, we introduce the concept of ''effective dose'', i.e. total dose averaged over a unit cell of the scan lattice. This allows various scanning schemes to be compared quantitatively.

  2. Surface crack analysis applied to impact damage in a thick graphite-epoxy composite

    NASA Technical Reports Server (NTRS)

    Poe, C. C., Jr.; Harris, C. E.; Morris, D. H.

    1988-01-01

    The residual tensile strength of a thick graphite/epoxy composite with impact damage was predicted using surface crack analysis. The damage was localized to a region directly beneath the impact site and extended only part way through the laminate. The damaged region contained broken fibers, and the locus of breaks in each layer resembled a crack perpendicular to the direction of the fibers. In some cases, the impacts broke fibers without making a visible crater. The impact damage was represented as a semi-elliptical surface crack with length and depth equal to that of the impact damage. The maximum length and depth of the damage were predicted with a stress analysis and a maximum shear stress criterion. The predictions and measurements of strength were in good agreement.

  3. Surface crack analysis applied to impact damage in a thick graphite/epoxy composite

    NASA Technical Reports Server (NTRS)

    Poe, Clarence C., Jr.; Harris, Charles E.; Morris, Don H.

    1990-01-01

    The residual tensile strength of a thick graphite/epoxy composite with impact damage was predicted using surface crack analysis. The damage was localized to a region directly beneath the impact site and extended only part way through the laminate. The damaged region contained broken fibers, and the locus of breaks in each layer resembled a crack perpendicular to the direction of the fibers. In some cases, the impacts broke fibers without making a visible crater. The impact damage was represented as a semi-elliptical surface crack with length and depth equal to that of the impact damage. The maximum length and depth of the damage were predicted with a stress analysis and a maximum shear stress criterion. The predictions and measurements of strength were in good agreement.

  4. ANALYSIS FOR HOUSE DAMAGE PROPERTY OF 2007 MID-NIIGATA PREFECTURE OFFSHORE EARTHQUAKE

    NASA Astrophysics Data System (ADS)

    Ochiai, Hirokazu; Yamada, Kento; Ohtsuka, Satoru; Isobe, Koichi

    This paper reports the result of correlation analysis for house damage in 2007 Mid-piigata prefecture offshore earthquake by focusing geomorphological land classification and other factors as landform and ground properties with organizing the house damage data of disaster victim certificate conducted by public administrations. In former part of the paper, the features of house damage at 2007 Mid-Niigata prefecture offshore earthquake were analyzed for various influencing factors. The authors discussed the affrecting factors to houses at earthquake. In latter part, the features of house damage at 2007 Mid-Niigata prefecture offshore earthquake was discussed with that at 2004 Mid-Niigata prefecture earthquake. The house damage function of distance from the epicenter was proposed based on the analysis on house damage ratio recorded in two earthquakes.

  5. Estimation of crack and damage progression in concrete by quantitative acoustic emission analysis

    SciTech Connect

    Ohtsu, Masayasu

    1999-05-01

    The kinematics of cracking can be represented by the moment tensor. To distinguish moment tensor components from acoustic emission waveforms, the SiGMA (simplified Green`s functions for moment tensor analysis) procedure was developed. By applying the procedure to bending tests of notched beams, cracks in the fracture process zone of cementitious materials can be identified by kinematic means. In addition to cracks, estimation of the damage level in structural concrete is also conducted, based on acoustic emission activity of a concrete sample under compression. Depending on the damage resulting from existing microcracks, acoustic emission generated behavior is quantitatively estimated by the rate process analysis. The damage mechanics are introduced to quantify the degree of damage. Determining the current damage level using acoustic emission without information on undamaged concrete is attempted by correlating the damage value with the rate process.

  6. FRP/steel composite damage acoustic emission monitoring and analysis

    NASA Astrophysics Data System (ADS)

    Li, Dongsheng; Chen, Zhi

    2015-04-01

    FRP is a new material with good mechanical properties, such as high strength of extension, low density, good corrosion resistance and anti-fatigue. FRP and steel composite has gotten a wide range of applications in civil engineering because of its good performance. As the FRP/steel composite get more and more widely used, the monitor of its damage is also getting more important. To monitor this composite, acoustic emission (AE) is a good choice. In this study, we prepare four identical specimens to conduct our test. During the testing process, the AE character parameters and mechanics properties were obtained. Damaged properties of FRP/steel composite were analyzed through acoustic emission (AE) signals. By the growing trend of AE accumulated energy, the severity of the damage made on FRP/steel composite was estimated. The AE sentry function has been successfully used to study damage progression and fracture emerge release rate of composite laminates. This technique combines the cumulative AE energy with strain energy of the material rather than analyzes the AE information and mechanical separately.

  7. Mathematical Analysis of Biomolecular Network Reveals Connections Between Diseases

    NASA Astrophysics Data System (ADS)

    Wang, Guanyu

    2012-02-01

    Connections between cancer and metabolic diseases may consist in the complex network of interactions among a common set of biomolecules. By applying singularity and bifurcation analysis, the phenotypes constrained by the AKT signaling pathway are identified and mapped onto the parameter space, which include cancer and certain metabolic diseases. By considering physiologic properties (sensitivity, robustness and adaptivity) the AKT pathway must possess in order to efficiently sense growth factors and nutrients, the region of normal responses is located. The analysis illuminates the parameter space and reveals system-level mechanisms in regulating biological functions (cell growth, survival, proliferation and metabolism) and how their deregulation may lead to the development of diseases. The analytical expressions summarize the synergistic interactions among many molecules, which provides valuable insights into therapeutic interventions.

  8. Proteomic analysis of mismatch repair-mediated alkylating agent-induced DNA damage response

    PubMed Central

    2013-01-01

    Background Mediating DNA damage-induced apoptosis is an important genome-maintenance function of the mismatch repair (MMR) system. Defects in MMR not only cause carcinogenesis, but also render cancer cells highly resistant to chemotherapeutics, including alkylating agents. To understand the mechanisms of MMR-mediated apoptosis and MMR-deficiency-caused drug resistance, we analyze a model alkylating agent (N-methyl-N’-nitro-N-nitrosoguanidine, MNNG)-induced changes in protein phosphorylation and abundance in two cell lines, the MMR-proficient TK6 and its derivative MMR-deficient MT1. Results Under an experimental condition that MNNG-induced apoptosis was only observed in MutSα-proficient (TK6), but not in MutSα-deficient (MT1) cells, quantitative analysis of the proteomic data revealed differential expression and phosphorylation of numerous individual proteins and clusters of protein kinase substrates, as well differential activation of response pathways/networks in MNNG-treated TK6 and MT1 cells. Many alterations in TK6 cells are in favor of turning on the apoptotic machinery, while many of those in MT1 cells are to promote cell proliferation and anti-apoptosis. Conclusions Our work provides novel molecular insights into the mechanism of MMR-mediated DNA damage-induced apoptosis. PMID:24330662

  9. Geometric morphometric analysis reveals sexual dimorphism in the distal femur.

    PubMed

    Cavaignac, Etienne; Savall, Frederic; Faruch, Marie; Reina, Nicolas; Chiron, Philippe; Telmon, Norbert

    2016-02-01

    An individual's sex can be determined by the shape of their distal femur. The goal of this study was to show that differences in distal femur shape related to sexual dimorphism could be identified, visualized, and quantified using 3D geometric morphometric analysis. Geometric morphometric analysis was carried out on CT scans of the distal femur of 256 subjects living in the south of France. Ten landmarks were defined on 3D reconstructions of the distal femur. Both traditional metric and geometric morphometric analyses were carried out on these bone reconstructions; these analyses identified trends in bone shape in sex-based subgroups. Sex-related differences in shape were statistically significant. The subject's sex was correctly assigned in 77.3% of cases using geometric morphometric analysis. This study has shown that geometric morphometric analysis of the distal femur is feasible and has revealed sexual dimorphism differences in this bone segment. This reliable, accurate method could be used for virtual autopsy and be used to perform diachronic and interethnic comparisons. Moreover, this study provides updated morphometric data for a modern population in the south of France. PMID:26743712

  10. Analysis of distribution of critical current of bent-damaged Bi2223 composite tape

    NASA Astrophysics Data System (ADS)

    Ochiai, S.; Okuda, H.; Sugano, M.; Hojo, M.; Osamura, K.; Kuroda, T.; Kumakura, H.; Kitaguchi, H.; Itoh, K.; Wada, H.

    2011-10-01

    Distributions of critical current of damaged Bi2223 tape specimens bent by 0.6, 0.8 and 1.0% were investigated analytically with a modelling approach based on the correlation of damage evolution to distribution of critical current. It was revealed that the distribution of critical current is described by three parameter Weibull distribution function through the distribution of the tensile damage strain of Bi2223 filaments that determines the damage front in bent-composite tape. Also it was shown that the measured distribution of critical current values can be reproduced successfully by a Monte Carlo simulation using the distributions of tensile damage strain of filaments and original critical current.

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

    NASA Technical Reports Server (NTRS)

    Humphreys, E. A.

    1981-01-01

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

  12. 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

  13. Application of outlier analysis for baseline-free damage diagnosis

    NASA Astrophysics Data System (ADS)

    Kim, Seung Dae; In, Chi Won; Cronin, Kelly E.; Sohn, Hoon; Harries, Kent

    2006-03-01

    As carbon fiber-reinforced polymer (CFRP) laminates have been widely accepted as valuable materials for retrofitting civil infrastructure systems, an appropriate assessment of bonding conditions between host structures and CFRP laminates becomes a critical issue to guarantee the performance of CFRP strengthened structures. This study attempts to develop a continuous performance monitoring system for CFRP strengthened structures by autonomously inspecting the bonding conditions between the CFRP layers and the host structure. The uniqueness of this study is to develop a new concept and theoretical framework of nondestructive testing (NDT), in which debonding is detected "without using past baseline data." The proposed baseline-free damage diagnosis is achieved in two stages. In the first step, features sensitive to debonding of the CFPR layers but insensitive to loading conditions are extracted based on a concept referred to as a time reversal process. This time reversal process allows extracting damage-sensitive features without direct comparison with past baseline data. Then, a statistical damage classifier will be developed in the second step to make a decision regarding the bonding condition of the CFRP layers. The threshold necessary for decision making will be adaptively determined without predetermined threshold values. Monotonic and fatigue load tests of full-scale CFRP strengthened RC beams are conducted to demonstrate the potential of the proposed reference-free debonding monitoring system.

  14. Rate process analysis of thermal damage in cartilage

    NASA Astrophysics Data System (ADS)

    Díaz, Sergio H.; Nelson, J. Stuart; Wong, Brian J. F.

    2003-01-01

    Cartilage laser thermoforming (CLT) is a new surgical procedure that allows in situ treatment of deformities in the head and neck with less morbidity than traditional approaches. While some animal and human studies have shown promising results, the clinical feasibility of CLT depends on preservation of chondrocyte viability, which has not been extensively studied. The present paper characterizes cellular damage due to heat in rabbit nasal cartilage. Damage was modelled as a first order rate process for which two experimentally derived coefficients, A = 1.2 × 1070 s-1 and Ea = 4.5 × 105 J mole-1, were determined by quantifying the decrease in concentration of healthy chondrocytes in tissue samples as a function of exposure time to constant-temperature water baths. After immersion, chondrocytes were enzymatically isolated from the matrix and stained with a two-component fluorescent dye. The dye binds nuclear DNA differentially depending upon chondrocyte viability. A flow cytometer was used to detect differential cell fluorescence to determine the percentage of live and dead cells in each sample. As a result, a damage kinetic model was obtained that can be used to predict the onset, extent and severity of cellular injury to thermal exposure.

  15. Analysis of hail damages and temperature series for peninsular Spain

    NASA Astrophysics Data System (ADS)

    Saa Requejo, A.; García Moreno, R.; Díaz Alvarez, M. C.; Burgaz, F.; Tarquis, M.

    2011-12-01

    Hail is a serious concern for agriculture on the Iberian Peninsula. Hailstorms affect crop yield and/or quality to a degree that depends on the crop species and the phenological time. In Europe, Spain is one of the countries that experience relatively high agricultural losses related to hailstorms. It is of high interest to study models that can support calculations of the probabilities of economic losses due to hail damage and of the tendency over time for such losses. Some studies developed in France and the Netherdlands show that the summer mean temperature was highly correlated with a yearly hail severity index developed from hail-related parameters obtained for insurance purposes. Meanwhile, other studies in the USA point out that a highly significant correlation between both is not possible to find due to high climatic variability. The aim of this work is to test the correlation between average minimum temperatures and hail damage intensity over the Spanish Iberian Peninsula. With this purpose, correlation analyses on both variables were performed for the 47 Spanish provinces (as individuals and single set) and for all crops and four individual crops: grapes, wheat, barley and winter grains. Suitable crop insurance data are available from 1981 until 2007 and based on this period, temperature data were obtained. This study does not confirm the results previously obtained for France and the Netherlands that relate observed hail damage to the average minimum temperature. The reason for this difference and the nature of the cases observed are discussed.

  16. A damage identification technique based on embedded sensitivity analysis and optimization processes

    NASA Astrophysics Data System (ADS)

    Yang, Chulho; Adams, Douglas E.

    2014-07-01

    A vibration based structural damage identification method, using embedded sensitivity functions and optimization algorithms, is discussed in this work. The embedded sensitivity technique requires only measured or calculated frequency response functions to obtain the sensitivity of system responses to each component parameter. Therefore, this sensitivity analysis technique can be effectively used for the damage identification process. Optimization techniques are used to minimize the difference between the measured frequency response functions of the damaged structure and those calculated from the baseline system using embedded sensitivity functions. The amount of damage can be quantified directly in engineering units as changes in stiffness, damping, or mass. Various factors in the optimization process and structural dynamics are studied to enhance the performance and robustness of the damage identification process. This study shows that the proposed technique can improve the accuracy of damage identification with less than 2 percent error of estimation.

  17. A damage analysis for brittle materials using stochastic micro-structural information

    NASA Astrophysics Data System (ADS)

    Lin, Shih-Po; Chen, Jiun-Shyan; Liang, Shixue

    2016-03-01

    In this work, a micro-crack informed stochastic damage analysis is performed to consider the failures of material with stochastic microstructure. The derivation of the damage evolution law is based on the Helmholtz free energy equivalence between cracked microstructure and homogenized continuum. The damage model is constructed under the stochastic representative volume element (SRVE) framework. The characteristics of SRVE used in the construction of the stochastic damage model have been investigated based on the principle of the minimum potential energy. The mesh dependency issue has been addressed by introducing a scaling law into the damage evolution equation. The proposed methods are then validated through the comparison between numerical simulations and experimental observations of a high strength concrete. It is observed that the standard deviation of porosity in the microstructures has stronger effect on the damage states and the peak stresses than its effect on the Young's and shear moduli in the macro-scale responses.

  18. Aging and DNA damage in humans: a meta-analysis study

    PubMed Central

    Soares, Jorge Pinto; Cortinhas, António; Bento, Teresa; Leitão, José Carlos; Collins, Andrew R.; Gaivã, Isabel; Mota, Maria Paula

    2014-01-01

    Age-related DNA damage is regarded as one of the possible explanations of aging. Although a generalized idea about the accumulation of DNA damage with age exists, results found in the literature are inconsistent. To better understand the question of age-related DNA damage in humans and to identify possible moderator variables, a meta-analysis was conducted. Electronic databases and bibliographies for studies published since 2004 were searched. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for age-related DNA damage were calculated in a random-effects model. A total of 76 correlations from 36 studies with 4676 participants were included. Based on our analysis, a correlation between age and DNA damage was found (r = 0.230, p = 0.000; 95% confidence interval = 0.111 - 0.342). The test for heterogeneity of variance indicates that the study´s results are significantly high (Q (75) = 1754.831, p = 0.000). Moderator variables such as smoking habits, technique used, and the tissue/sample analyzed, are shown to influence age-related DNA damage (p=0.026; p=0.000; p=0.000, respectively). Nevertheless, sex did not show any influence on this relation (p=0.114). In conclusion, this meta-analysis showed an association between age and DNA damage in humans. It was also found that smoking habits, the technique used, and tissue/sample analyzed, are important moderator variables in age-related DNA damage. PMID:25140379

  19. Genomic analysis of primordial dwarfism reveals novel disease genes.

    PubMed

    Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S

    2014-02-01

    Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis. PMID:24389050

  20. Interactome Analysis Reveals Ezrin Can Adopt Multiple Conformational States*

    PubMed Central

    Viswanatha, Raghuvir; Wayt, Jessica; Ohouo, Patrice Y.; Smolka, Marcus B.; Bretscher, Anthony

    2013-01-01

    Ezrin, a member of the ezrin-radixin-moesin family (ERM), is an essential regulator of the structure of microvilli on the apical aspect of epithelial cells. Ezrin provides a linkage between membrane-associated proteins and F-actin, oscillating between active/open and inactive/closed states, and is regulated in part by phosphorylation of a C-terminal threonine. In the open state, ezrin can bind a number of ligands, but in the closed state the ligand-binding sites are inaccessible. In vitro analysis has proposed that there may be a third hyperactivated form of ezrin. To gain a better understanding of ezrin, we conducted an unbiased proteomic analysis of ezrin-binding proteins in an epithelial cell line, Jeg-3. We refined our list of interactors by comparing the interactomes using quantitative mass spectrometry between wild-type ezrin, closed ezrin, open ezrin, and hyperactivated ezrin. The analysis reveals several novel interactors confirmed by their localization to microvilli, as well as a significant class of proteins that bind closed ezrin. Taken together, the data indicate that ezrin can exist in three different conformational states, and different ligands “perceive” ezrin conformational states differently. PMID:24151071

  1. Graph analysis of cortical networks reveals complex anatomical communication substrate

    NASA Astrophysics Data System (ADS)

    Zamora-López, Gorka; Zhou, Changsong; Kurths, Jürgen

    2009-03-01

    Sensory information entering the nervous system follows independent paths of processing such that specific features are individually detected. However, sensory perception, awareness, and cognition emerge from the combination of information. Here we have analyzed the corticocortical network of the cat, looking for the anatomical substrate which permits the simultaneous segregation and integration of information in the brain. We find that cortical communications are mainly governed by three topological factors of the underlying network: (i) a large density of connections, (ii) segregation of cortical areas into clusters, and (iii) the presence of highly connected hubs aiding the multisensory processing and integration. Statistical analysis of the shortest paths reveals that, while information is highly accessible to all cortical areas, the complexity of cortical information processing may arise from the rich and intricate alternative paths in which areas can influence each other.

  2. Thermal analysis of induced damage to the healthy cell during RFA of breast tumor.

    PubMed

    Singh, Sundeep; Bhowmik, Arka; Repaka, Ramjee

    2016-05-01

    Effective pre-clinical computational modeling strategies have been demonstrated in this article to enable risk free clinical application of radiofrequency ablation (RFA) of breast tumor. The present study (a) determines various optimal regulating parameters required for RFA of tumor and (b) introduces an essential clinical monitoring scheme to minimize the extent of damage to the healthy cell during RFA of tumor. The therapeutic capabilities offered by RFA of breast tumor, viz., the rise in local temperature and induced thermal damage have been predicted by integrating the bioheat transfer model, the electric field distribution model and the thermal damage model. The mathematical model has been validated with the experimental results available in the literature. The results revealed that, the effective damage of tumor volume sparing healthy tissue essentially depends on the voltage, the exposure time, the local heat distribution, the tumor stage and the electrode geometric configuration. It has been confirmed that, the assessment of damage front can accurately determine the extent of damage as compared to the thermal front. The study further evaluates the damaged healthy and tumor volumes due to RFA of different stages of breast cancer. The assessment of cell survival and damage fractions discloses the propensity of reappearance/healing of tumor cells after treatment. PMID:27157337

  3. Single cell transcriptional analysis reveals novel innate immune cell types.

    PubMed

    Kippner, Linda E; Kim, Jinhee; Gibson, Greg; Kemp, Melissa L

    2014-01-01

    Single-cell analysis has the potential to provide us with a host of new knowledge about biological systems, but it comes with the challenge of correctly interpreting the biological information. While emerging techniques have made it possible to measure inter-cellular variability at the transcriptome level, no consensus yet exists on the most appropriate method of data analysis of such single cell data. Methods for analysis of transcriptional data at the population level are well established but are not well suited to single cell analysis due to their dependence on population averages. In order to address this question, we have systematically tested combinations of methods for primary data analysis on single cell transcription data generated from two types of primary immune cells, neutrophils and T lymphocytes. Cells were obtained from healthy individuals, and single cell transcript expression data was obtained by a combination of single cell sorting and nanoscale quantitative real time PCR (qRT-PCR) for markers of cell type, intracellular signaling, and immune functionality. Gene expression analysis was focused on hierarchical clustering to determine the existence of cellular subgroups within the populations. Nine combinations of criteria for data exclusion and normalization were tested and evaluated. Bimodality in gene expression indicated the presence of cellular subgroups which were also revealed by data clustering. We observed evidence for two clearly defined cellular subtypes in the neutrophil populations and at least two in the T lymphocyte populations. When normalizing the data by different methods, we observed varying outcomes with corresponding interpretations of the biological characteristics of the cell populations. Normalization of the data by linear standardization taking into account technical effects such as plate effects, resulted in interpretations that most closely matched biological expectations. Single cell transcription profiling provides

  4. Neonatal `Brain Damage'—An Analysis of 250 Claims

    PubMed Central

    Cornblath, Marvin; Clark, Russell L.

    1984-01-01

    Advances in perinatal care have resulted in decreased neonatal mortality. Increasingly, damage in survivors has been attributed to alleged negligence. We analyzed the 250 claims (1957 to 1982) from one major insurance company for factors to characterize high-risk pregnancies and then to distinguish preventable from nonpreventable causes within the group. Using predetermined criteria, 77 (31%) were classified preventable, 105 (42%) nonpreventable and 68 (27%) indeterminate. Preventable actions could be attributed to family members as well as health care providers. Twenty risk factors were significantly increased in the study group compared with those in a general population and included maternal, gestational, delivery and postdelivery risks. Furthermore, 13 of 25 factors differed significantly between preventable and nonpreventable cases. Those with significantly higher prevalence in preventable cases included prolonged gestation, the use of mid or high forceps, cesarean sections, meconium staining, low one- and five-minute Apgar scores, birth weight exceeding 4.5 kg (10 lb), poor tone, seizures and transfers to neonatal intensive care units. Increased in prevalence in the nonpreventable cases were congenital infections and malformations and the late onset of neurologic abnormalities. These findings suggest preventive measures to reduce unwarranted litigation and certain cases of neonatal brain damage. PMID:6730485

  5. Equivalent Plate Analysis of Aircraft Wing with Discrete Source Damage

    NASA Technical Reports Server (NTRS)

    Krishnamurthy, T.; Mason, Brian H.

    2006-01-01

    An equivalent plate procedure is developed to provide a computationally efficient means of matching the stiffness and frequencies of flight vehicle wing structures for prescribed loading conditions. First, the equivalent plate is used to match the stiffness of a stiffened panel without damage and the stiffness of a stiffened panel with damage. For both stiffened panels, the equivalent plate models reproduce the deformation of a corresponding detailed model exactly for the given loading conditions. Once the stiffness was matched, the equivalent plate models were then used to predict the frequencies of the panels. Two analytical procedures using the lumped-mass matrix were used to match the first five frequencies of the corresponding detailed model. In both the procedures, the lumped-mass matrix for the equivalent plate is constructed by multiplying the diagonal terms of the consistent-mass matrix by a proportionality constant. In the first procedure, the proportionality constant is selected such that the total mass of the equivalent plate is equal to that of the detailed model. In the second method, the proportionality constant is selected to minimize the sum of the squares of the errors in a set of pre-selected frequencies between the equivalent plate model and the detailed model. The equivalent plate models reproduced the fundamental first frequency accurately in both the methods. It is observed that changing only the mass distribution in the equivalent plate model did not provide enough flexibility to match all of the frequencies.

  6. A probabilistic fatigue analysis of multiple site damage

    NASA Technical Reports Server (NTRS)

    Rohrbaugh, S. M.; Ruff, D.; Hillberry, B. M.; Mccabe, G.; Grandt, A. F., Jr.

    1994-01-01

    The variability in initial crack size and fatigue crack growth is incorporated in a probabilistic model that is used to predict the fatigue lives for unstiffened aluminum alloy panels containing multiple site damage (MSD). The uncertainty of the damage in the MSD panel is represented by a distribution of fatigue crack lengths that are analytically derived from equivalent initial flaw sizes. The variability in fatigue crack growth rate is characterized by stochastic descriptions of crack growth parameters for a modified Paris crack growth law. A Monte-Carlo simulation explicitly describes the MSD panel by randomly selecting values from the stochastic variables and then grows the MSD cracks with a deterministic fatigue model until the panel fails. Different simulations investigate the influences of the fatigue variability on the distributions of remaining fatigue lives. Six cases that consider fixed and variable conditions of initial crack size and fatigue crack growth rate are examined. The crack size distribution exhibited a dominant effect on the remaining fatigue life distribution, and the variable crack growth rate exhibited a lesser effect on the distribution. In addition, the probabilistic model predicted that only a small percentage of the life remains after a lead crack develops in the MSD panel.

  7. Transcriptome meta-analysis reveals dysregulated pathways in nasopharyngeal carcinoma.

    PubMed

    Tulalamba, Warut; Larbcharoensub, Noppadol; Sirachainan, Ekaphop; Tantiwetrueangdet, Aunchalee; Janvilisri, Tavan

    2015-08-01

    Nasopharyngeal carcinoma (NPC) is a malignant cancer arising from the epithelial surface of the nasopharynx that mostly appears in advanced stages of the disease, leading to a poor prognosis. To date, a number of mRNA profiling investigations on NPC have been reported in order to identify suitable biomarkers for early detection. However, the results may be specific to each study with distinct sample types. In this study, an integrative meta-analysis of NPC transcriptome data was performed to determine dysregulated pathways, potentially leading to identification of molecular markers. Ten independent NPC gene expression profiling microarray datasets, including 135 samples from NPC cell lines, primary cell lines, and tissues were assimilated into a meta-analysis and cross-validation to identify a cohort of genes that were significantly dysregulated in NPC. Bioinformatics analyses of these genes revealed the significant pathways and individual players involving in cellular metabolism, cell cycle regulation, DNA repair, as well as ErbB pathway. Altogether, we propose that dysregulation of these molecular pathways in NPC might play a role in the NPC pathogenesis, providing clues, which could eventually translate into diagnostic and therapeutic approaches. PMID:25724187

  8. Revealing oxidative damage to enzymes of carbohydrate metabolism in yeast: An integration of 2D DIGE, quantitative proteomics, and bioinformatics.

    PubMed

    Boone, Cory H T; Grove, Ryan A; Adamcova, Dana; Braga, Camila P; Adamec, Jiri

    2016-07-01

    Clinical usage of lidocaine, a pro-oxidant has been linked with severe, mostly neurological complications. The mechanism(s) causing these complications is independent of the blockade of voltage-gated sodium channels. The budding yeast Saccharomyces cerevisiae lacks voltage-gated sodium channels, thus provides an ideal system to investigate lidocaine-induced protein and pathway alterations. Whole-proteome alterations leading to these complications have not been identified. To address this, S. cerevisiae was grown to stationary phase and exposed to an LC50 dose of lidocaine. The differential proteomes of lidocaine treatment and control were resolved 6 h post exposure using 2D DIGE. Amine reactive dyes and carbonyl reactive dyes were used to assess protein abundance and protein oxidation, respectively. Quantitative analysis of these dyes (⩾ 1.5-fold alteration, p ⩽ 0.05) revealed a total of 33 proteoforms identified by MS differing in abundance and/or oxidation upon lidocaine exposure. Network analysis showed enrichment of apoptotic proteins and cell wall maintenance proteins, while the abundance of proteins central to carbohydrate metabolism, such as triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase, and redox proteins superoxide dismutase and peroxiredoxin were significantly decreased. Enzymes of carbohydrate metabolism, such as phosphoglycerate kinase and enolase, the TCA cycle enzyme aconitase, and multiple ATP synthase subunits were found to be oxidatively modified. Also, the activity of aconitase was found to be decreased. Overall, these data suggest that toxic doses of lidocaine induce significant disruption of glycolytic pathways, energy production, and redox balance, potentially leading to cell malfunction and death. PMID:27193513

  9. FUNCTIONAL DEFICITS PRODUCED BY 3-METHYLINDOLE-INDUCED OLFACTORY MUCOSAL DAMAGE REVEALED BY A SIMPLE OLFACTORY LEARNING TASK

    EPA Science Inventory

    Methods for assessing functional consequences of olfactory mucosal damage were examined in rats exposed to 3-methylindole (3-MI). Treatment with 3-MI (400 mg/kg) induced severe degeneration of olfactory sensory epithelium followed by regeneration, fibrous adhesions and osseous re...

  10. Far Forward Anesthesia and Massive Blood Transfusion: Two Cases Revealing the Challenge of Damage Control Resuscitation in an Austere Environment.

    PubMed

    Gaskin, David; Kroll, Nicholas A; Ochs, Alyson A; Schreiber, Martin A; Pandalai, Prakash K

    2015-10-01

    Since the beginning of Operation Enduring Freedom and Operation Iraqi Freedom, the US military has treated more than 51,000 casualties and sustained more than 6,600 deaths. The past decade of conflict has solidified major advances in the use of blood component therapy and the liberal use of fresh whole blood during damage control resuscitation. This resuscitation strategy, combined with far forward damage control surgery, rapid aeromedical evacuation, and major improvements in critical care air transportation and personal protective equipment has led to a 90% to 92% survival rate in US casualties. We describe 2 cases treated by a Forward Surgical Team serving in Afghanistan during Operation Enduring Freedom in 2014. Both patients suffered severe trauma and required massive blood transfusion and damage control surgery. In describing these 2 cases, we wish to share our experience with damage control, resuscitation in an austere environment, as well as advocate for the critical role of the Certified Registered Nurse Anesthetist in advancing the knowledge and execution of this lifesaving strategy in both military and civilian trauma centers. In addition, we suggest alternatives to the current transfusion strategy, which will mitigate limitations currently encountered. PMID:26638455

  11. Proteomics Analysis Reveals Overlapping Functions of Clustered Protocadherins*

    PubMed Central

    Han, Meng-Hsuan; Lin, Chengyi; Meng, Shuxia; Wang, Xiaozhong

    2010-01-01

    The three tandem-arrayed protocadherin (Pcdh) gene clusters, namely Pcdh-α, Pcdh-β, and Pcdh-γ, play important roles in the development of the vertebrate central nervous system. To gain insight into the molecular action of PCDHs, we performed a systematic proteomics analysis of PCDH-γ-associated protein complexes. We identified a list of 154 non-redundant proteins in the PCDH-γ complexes. This list includes nearly 30 members of clustered Pcdh-α, -β, and -γ families as core components of the complexes and additionally over 120 putative PCDH-associated proteins. We validated a selected subset of PCDH-γ-associated proteins using specific antibodies. Analysis of the identities of PCDH-associated proteins showed that the majority of them overlap with the proteomic profile of postsynaptic density preparations. Further analysis of membrane protein complexes revealed that several validated PCDH-γ-associated proteins exhibit reduced levels in Pcdh-γ-deficient brain tissues. Therefore, PCDH-γs are required for the integrity of the complexes. However, the size of the overall complexes and the abundance of many other proteins remained unchanged, raising a possibility that PCDH-αs and PCDH-βs might compensate for PCDH-γ function in complex formation. As a test of this idea, RNA interference knockdown of both PCDH-αs and PCDH-γs showed that PCDHs have redundant functions in regulating neuronal survival in the chicken spinal cord. Taken together, our data provide evidence that clustered PCDHs coexist in large protein complexes and have overlapping functions during vertebrate neural development. PMID:19843561

  12. Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth.

    PubMed

    Cuomo, Christina A; Desjardins, Christopher A; Bakowski, Malina A; Goldberg, Jonathan; Ma, Amy T; Becnel, James J; Didier, Elizabeth S; Fan, Lin; Heiman, David I; Levin, Joshua Z; Young, Sarah; Zeng, Qiandong; Troemel, Emily R

    2012-12-01

    Microsporidia comprise a large phylum of obligate intracellular eukaryotes that are fungal-related parasites responsible for widespread disease, and here we address questions about microsporidia biology and evolution. We sequenced three microsporidian genomes from two species, Nematocida parisii and Nematocida sp1, which are natural pathogens of Caenorhabditis nematodes and provide model systems for studying microsporidian pathogenesis. We performed deep sequencing of transcripts from a time course of N. parisii infection. Examination of pathogen gene expression revealed compact transcripts and a dramatic takeover of host cells by Nematocida. We also performed phylogenomic analyses of Nematocida and other microsporidian genomes to refine microsporidian phylogeny and identify evolutionary events of gene loss, acquisition, and modification. In particular, we found that all microsporidia lost the tumor-suppressor gene retinoblastoma, which we speculate could accelerate the parasite cell cycle and increase the mutation rate. We also found that microsporidia acquired transporters that could import nucleosides to fuel rapid growth. In addition, microsporidian hexokinases gained secretion signal sequences, and in a functional assay these were sufficient to export proteins out of the cell; thus hexokinase may be targeted into the host cell to reprogram it toward biosynthesis. Similar molecular changes appear during formation of cancer cells and may be evolutionary strategies adopted independently by microsporidia to proliferate rapidly within host cells. Finally, analysis of genome polymorphisms revealed evidence for a sexual cycle that may provide genetic diversity to alleviate problems caused by clonal growth. Together these events may explain the emergence and success of these diverse intracellular parasites. PMID:22813931

  13. Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth

    PubMed Central

    Cuomo, Christina A.; Desjardins, Christopher A.; Bakowski, Malina A.; Goldberg, Jonathan; Ma, Amy T.; Becnel, James J.; Didier, Elizabeth S.; Fan, Lin; Heiman, David I.; Levin, Joshua Z.; Young, Sarah; Zeng, Qiandong; Troemel, Emily R.

    2012-01-01

    Microsporidia comprise a large phylum of obligate intracellular eukaryotes that are fungal-related parasites responsible for widespread disease, and here we address questions about microsporidia biology and evolution. We sequenced three microsporidian genomes from two species, Nematocida parisii and Nematocida sp1, which are natural pathogens of Caenorhabditis nematodes and provide model systems for studying microsporidian pathogenesis. We performed deep sequencing of transcripts from a time course of N. parisii infection. Examination of pathogen gene expression revealed compact transcripts and a dramatic takeover of host cells by Nematocida. We also performed phylogenomic analyses of Nematocida and other microsporidian genomes to refine microsporidian phylogeny and identify evolutionary events of gene loss, acquisition, and modification. In particular, we found that all microsporidia lost the tumor-suppressor gene retinoblastoma, which we speculate could accelerate the parasite cell cycle and increase the mutation rate. We also found that microsporidia acquired transporters that could import nucleosides to fuel rapid growth. In addition, microsporidian hexokinases gained secretion signal sequences, and in a functional assay these were sufficient to export proteins out of the cell; thus hexokinase may be targeted into the host cell to reprogram it toward biosynthesis. Similar molecular changes appear during formation of cancer cells and may be evolutionary strategies adopted independently by microsporidia to proliferate rapidly within host cells. Finally, analysis of genome polymorphisms revealed evidence for a sexual cycle that may provide genetic diversity to alleviate problems caused by clonal growth. Together these events may explain the emergence and success of these diverse intracellular parasites. PMID:22813931

  14. GENETIC AND MOLECULAR ANALYSIS OF DNA DAMAGE REPAIR AND TOLERANCE PATHWAYS.

    SciTech Connect

    SUTHERLAND, B.M.

    2001-07-26

    Radiation can damage cellular components, including DNA. Organisms have developed a panoply of means of dealing with DNA damage. Some repair paths have rather narrow substrate specificity (e.g. photolyases), which act on specific pyrimidine photoproducts in a specific type (e.g., DNA) and conformation (double-stranded B conformation) of nucleic acid. Others, for example, nucleotide excision repair, deal with larger classes of damages, in this case bulky adducts in DNA. A detailed discussion of DNA repair mechanisms is beyond the scope of this article, but one can be found in the excellent book of Friedberg et al. [1] for further detail. However, some DNA damages and paths for repair of those damages important for photobiology will be outlined below as a basis for the specific examples of genetic and molecular analysis that will be presented below.

  15. Damage classification and estimation in experimental structures using time series analysis and pattern recognition

    NASA Astrophysics Data System (ADS)

    de Lautour, Oliver R.; Omenzetter, Piotr

    2010-07-01

    Developed for studying long sequences of regularly sampled data, time series analysis methods are being increasingly investigated for the use of Structural Health Monitoring (SHM). In this research, Autoregressive (AR) models were used to fit the acceleration time histories obtained from two experimental structures: a 3-storey bookshelf structure and the ASCE Phase II Experimental SHM Benchmark Structure, in undamaged and limited number of damaged states. The coefficients of the AR models were considered to be damage-sensitive features and used as input into an Artificial Neural Network (ANN). The ANN was trained to classify damage cases or estimate remaining structural stiffness. The results showed that the combination of AR models and ANNs are efficient tools for damage classification and estimation, and perform well using small number of damage-sensitive features and limited sensors.

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

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

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

  17. Structure of BRCA1-BRCT/Abraxas Complex Reveals Phosphorylation-Dependent BRCT Dimerization at DNA Damage Sites

    PubMed Central

    Wu, Qian; Paul, Atanu; Su, Dan; Mehmood, Shahid; Foo, Tzeh Keong; Ochi, Takashi; Bunting, Emma L.; Xia, Bing; Robinson, Carol V.; Wang, Bin; Blundell, Tom L.

    2016-01-01

    Summary BRCA1 accumulation at DNA damage sites is an important step for its function in the DNA damage response and in DNA repair. BRCA1-BRCT domains bind to proteins containing the phosphorylated serine-proline-x-phenylalanine (pSPxF) motif including Abraxas, Bach1/FancJ, and CtIP. In this study, we demonstrate that ionizing radiation (IR)-induces ATM-dependent phosphorylation of serine 404 (S404) next to the pSPxF motif. Crystal structures of BRCT/Abraxas show that phosphorylation of S404 is important for extensive interactions through the N-terminal sequence outside the pSPxF motif and leads to formation of a stable dimer. Mutation of S404 leads to deficiency in BRCA1 accumulation at DNA damage sites and cellular sensitivity to IR. In addition, two germline mutations of BRCA1 are found to disrupt the dimer interface and dimer formation. Thus, we demonstrate a mechanism involving IR-induced phosphorylation and dimerization of the BRCT/Abraxas complex for regulating Abraxas-mediated recruitment of BRCA1 in response to IR. PMID:26778126

  18. A registry analysis of damage to the deceased donor pancreas during procurement.

    PubMed

    Ausania, F; Drage, M; Manas, D; Callaghan, C J

    2015-11-01

    Surgical injury to the pancreas is thought to occur commonly during procurement. The UK Transplant Registry was analyzed to determine the frequency of pancreatic injuries, identify factors associated with damage, and assess the impact of injuries on graft survival. Twelve hundred ninety-six pancreata were procured from donation after brain death donors, with 314 (19.5%) from donation after circulatory death donors. More than 50% of recovered pancreata had at least one injury, most commonly a short portal vein (21.5%). Liver donation, procurement team origin, hepatic artery (HA) arising from the superior mesenteric artery (SMA), and increasing donor BMI were associated with increased rates of pancreas damage on univariate analyses; on multivariate analysis only the presence of an HA from the SMA remained significant (p = 0.02). Six hundred forty solid organ pancreas transplants were performed; 238 had some form of damage. Overall, there was no difference in graft survival between damaged and undamaged organs (p = 0.28); however, graft loss was significantly more frequent in pancreata with arterial damage (p = 0.04) and in those with parenchymal damage (p = 0.05). Damage to the pancreas during organ recovery is more common than other organs, and meticulous surgical technique and awareness of damage risk factors are essential to reduce rates of procurement-related injuries. PMID:26484838

  19. Ionizing radiation, antioxidant response and oxidative damage: A meta-analysis.

    PubMed

    Einor, D; Bonisoli-Alquati, A; Costantini, D; Mousseau, T A; Møller, A P

    2016-04-01

    One mechanism proposed as a link between exposure to ionizing radiation and detrimental effects on organisms is oxidative damage. To test this hypothesis, we surveyed the scientific literature on the effects of chronic low-dose ionizing radiation (LDIR) on antioxidant responses and oxidative damage. We found 40 publications and 212 effect sizes for antioxidant responses and 288 effect sizes for effects of oxidative damage. We performed a meta-analysis of signed and unsigned effect sizes. We found large unsigned effects for both categories (0.918 for oxidative damage; 0.973 for antioxidant response). Mean signed effect size weighted by sample size was 0.276 for oxidative damage and -0.350 for antioxidant defenses, with significant heterogeneity among effects for both categories, implying that ionizing radiation caused small to intermediate increases in oxidative damage and small to intermediate decreases in antioxidant defenses. Our estimates are robust, as shown by very high fail-safe numbers. Species, biological matrix (tissue, blood, sperm) and age predicted the magnitude of effects for oxidative damage as well as antioxidant response. Meta-regression models showed that effect sizes for oxidative damage varied among species and age classes, while effect sizes for antioxidant responses varied among species and biological matrices. Our results are consistent with the description of mechanisms underlying pathological effects of chronic exposure to LDIR. Our results also highlight the importance of resistance to oxidative stress as one possible mechanism associated with variation in species responses to LDIR-contaminated areas. PMID:26851726

  20. Structural damage localization by outlier analysis of signal-processed mode shapes - Analytical and experimental validation

    NASA Astrophysics Data System (ADS)

    Ulriksen, M. D.; Damkilde, L.

    2016-02-01

    Contrary to global modal parameters such as eigenfrequencies, mode shapes inherently provide structural information on a local level. Therefore, this particular modal parameter and its derivatives are utilized extensively for damage identification. Typically, more or less advanced mathematical methods are employed to identify damage-induced discontinuities in the spatial mode shape signals, hereby, potentially, facilitating damage detection and/or localization. However, by being based on distinguishing damage-induced discontinuities from other signal irregularities, an intrinsic deficiency in these methods is the high sensitivity towards measurement noise. In the present paper, a damage localization method which, compared to the conventional mode shape-based methods, has greatly enhanced robustness towards measurement noise is proposed. The method is based on signal processing of a spatial mode shape by means of continuous wavelet transformation (CWT) and subsequent application of a generalized discrete Teager-Kaiser energy operator (GDTKEO) to identify damage-induced mode shape discontinuities. In order to evaluate whether the identified discontinuities are in fact damage-induced, outlier analysis is conducted by applying the Mahalanobis metric to major principal scores of the sensor-located bands of the signal-processed mode shape. The method is tested analytically and benchmarked with other mode shape-based damage localization approaches on the basis of a free-vibrating beam and validated experimentally in the context of a residential-sized wind turbine blade subjected to an impulse load.

  1. Phosphoproteomic analysis reveals regulatory mechanisms at the kidney filtration barrier.

    PubMed

    Rinschen, Markus M; Wu, Xiongwu; König, Tim; Pisitkun, Trairak; Hagmann, Henning; Pahmeyer, Caroline; Lamkemeyer, Tobias; Kohli, Priyanka; Schnell, Nicole; Schermer, Bernhard; Dryer, Stuart; Brooks, Bernard R; Beltrao, Pedro; Krueger, Marcus; Brinkkoetter, Paul T; Benzing, Thomas

    2014-07-01

    Diseases of the kidney filtration barrier are a leading cause of ESRD. Most disorders affect the podocytes, polarized cells with a limited capacity for self-renewal that require tightly controlled signaling to maintain their integrity, viability, and function. Here, we provide an atlas of in vivo phosphorylated, glomerulus-expressed proteins, including podocyte-specific gene products, identified in an unbiased tandem mass spectrometry-based approach. We discovered 2449 phosphorylated proteins corresponding to 4079 identified high-confidence phosphorylated residues and performed a systematic bioinformatics analysis of this dataset. We discovered 146 phosphorylation sites on proteins abundantly expressed in podocytes. The prohibitin homology domain of the slit diaphragm protein podocin contained one such site, threonine 234 (T234), located within a phosphorylation motif that is mutated in human genetic forms of proteinuria. The T234 site resides at the interface of podocin dimers. Free energy calculation through molecular dynamic simulations revealed a role for T234 in regulating podocin dimerization. We show that phosphorylation critically regulates formation of high molecular weight complexes and that this may represent a general principle for the assembly of proteins containing prohibitin homology domains. PMID:24511133

  2. Lipidome analysis reveals antifungal polyphenol curcumin affects membrane lipid homeostasis.

    PubMed

    Sharma, Monika; Dhamgaye, Sanjiveeni; Singh, Ashutosh; Prasad, Rajendra

    2012-01-01

    This study shows that antifungal curcumin (CUR), significantly depletes ergosterol levels in Candida albicans. CUR while displaying synergy with fluconazole (FLC) lowers ergosterol. However, CUR alone at its synergistic concentration (lower than MIC50), could not affect ergosterol contents. For deeper insight of CUR effects on lipids, we performed high throughput mass spectroscopy (MS) based lipid profiling of C. albicans cells. The lipidome analysis revealed that there were no major changes in phosphoglycerides (PGLs) composition following CUR treatment of Candida, however, significant differences in molecular species of PGLs were detected. Among major SPLs, CUR treatment resulted in the reduction of ceramide and accumulation of IPCs levels. The lipidome of CUR treated cells confirmed a dramatic drop in the ergosterol levels with a simultaneous accumulation of its biosynthetic precursors. This was further supported by the fact that the mutants defective in ergosterol biosynthesis (ERG2 and ERG11) and those lacking the transcription factor regulating ergosterol biosynthesis, UPC2, were highly susceptible to CUR. Our study first time shows that CUR, for its antifungal activity, targets and down regulates delta 5, 6 desaturase (ERG3) resulting in depletion of ergosterol. This results in parallel accumulation of ergosterol biosynthetic precursors, generation of reactive oxygen species (ROS) and cell death. PMID:22201946

  3. Point-of-gaze analysis reveals visual search strategies

    NASA Astrophysics Data System (ADS)

    Rajashekar, Umesh; Cormack, Lawrence K.; Bovik, Alan C.

    2004-06-01

    Seemingly complex tasks like visual search can be analyzed using a cognition-free, bottom-up framework. We sought to reveal strategies used by observers in visual search tasks using accurate eye tracking and image analysis at point of gaze. Observers were instructed to search for simple geometric targets embedded in 1/f noise. By analyzing the stimulus at the point of gaze using the classification image (CI) paradigm, we discovered CI templates that indeed resembled the target. No such structure emerged for a random-searcher. We demonstrate, qualitatively and quantitatively, that these CI templates are useful in predicting stimulus regions that draw human fixations in search tasks. Filtering a 1/f noise stimulus with a CI results in a 'fixation prediction map'. A qualitative evaluation of the prediction was obtained by overlaying k-means clusters of observers' fixations on the prediction map. The fixations clustered around the local maxima in the prediction map. To obtain a quantitative comparison, we computed the Kullback-Leibler distance between the recorded fixations and the prediction. Using random-searcher CIs in Monte Carlo simulations, a distribution of this distance was obtained. The z-scores for the human CIs and the original target were -9.70 and -9.37 respectively indicating that even in noisy stimuli, observers deploy their fixations efficiently to likely targets rather than casting them randomly hoping to fortuitously find the target.

  4. Sequential analysis of the numerical Stroop effect reveals response suppression.

    PubMed

    Cohen Kadosh, Roi; Gevers, Wim; Notebaert, Wim

    2011-09-01

    Automatic processing of irrelevant stimulus dimensions has been demonstrated in a variety of tasks. Previous studies have shown that conflict between relevant and irrelevant dimensions can be reduced when a feature of the irrelevant dimension is repeated. The specific level at which the automatic process is suppressed (e.g., perceptual repetition, response repetition), however, is less understood. In the current experiment we used the numerical Stroop paradigm, in which the processing of irrelevant numerical values of 2 digits interferes with the processing of their physical size, to pinpoint the precise level of the suppression. Using a sequential analysis, we dissociated perceptual repetition from response repetition of the relevant and irrelevant dimension. Our analyses of reaction times, error rates, and diffusion modeling revealed that the congruity effect is significantly reduced or even absent when the response sequence of the irrelevant dimension, rather than the numerical value or the physical size, is repeated. These results suggest that automatic activation of the irrelevant dimension is suppressed at the response level. The current results shed light on the level of interaction between numerical magnitude and physical size as well as the effect of variability of responses and stimuli on automatic processing. PMID:21500951

  5. Stereology-based fabric analysis of microcracks in damaged granite

    NASA Astrophysics Data System (ADS)

    Takemura, Takato; Oda, Masanobu

    2004-08-01

    Crack-related fabric analyses were carried out in terms of crack tensors using Inada granite deformed inelastically in a triaxial vessel up to post-failure, focusing on the fabric changes during brittle failure. Complementarily, numerical simulation tests were conducted to determine the representative volume element (RVE) required for crack surveying. Numerical simulation tests show that the window size for crack surveying should be at least six times the mean trace length in order to obtain a statistically meaningful crack tensor. A larger window is needed to estimate the distribution of crack radii. In quartz, cracks grow preferentially parallel to the major loading axis. Crack tensors in quartz can provide a measure of damage reflecting inelastic deformation under differential stress in past geological events. During the first stage of inelastic deformation, the number density of cracks decreases with a rather sharp increase in crack diameters. This happens because pre-existing cracks in intact rock join together to make longer cracks. However, the density remains almost constant during the second stage of loading from 90% to 100% of the peak stress. The crack diameter gradually increases due to the stable propagation of cracks. When granite is further deformed beyond the peak stress, the number density decreases again while sharp increases in crack diameters appear as a result of the forking and coalescence of cracks. It is also suggested that load-normal grain boundary cracks are generated as a result of the rolling and sliding of disintegrated blocks in the post-failure stage.

  6. Acoustic Emission Analysis of Damage Progression in Thermal Barrier Coatings Under Thermal Cyclic Conditions

    NASA Technical Reports Server (NTRS)

    Appleby, Matthew; Zhu, Dongming; Morscher, Gregory

    2015-01-01

    Damage evolution of electron beam-physical vapor deposited (EBVD-PVD) ZrO2-7 wt.% Y2O3 thermal barrier coatings (TBCs) under thermal cyclic conditions was monitored using an acoustic emission (AE) technique. The coatings were heated using a laser heat flux technique that yields a high reproducibility in thermal loading. Along with AE, real-time thermal conductivity measurements were also taken using infrared thermography. Tests were performed on samples with induced stress concentrations, as well as calcium-magnesium-alumino-silicate (CMAS) exposure, for comparison of damage mechanisms and AE response to the baseline (as-produced) coating. Analysis of acoustic waveforms was used to investigate damage development by comparing when events occurred, AE event frequency, energy content and location. The test results have shown that AE accumulation correlates well with thermal conductivity changes and that AE waveform analysis could be a valuable tool for monitoring coating degradation and provide insight on specific damage mechanisms.

  7. Full-length high-temperature severe fuel damage test No. 2. Final safety analysis

    SciTech Connect

    Hesson, G.M.; Lombardo, N.J.; Pilger, J.P.; Rausch, W.N.; King, L.L.; Hurley, D.E.; Parchen, L.J.; Panisko, F.E.

    1993-09-01

    Hazardous conditions associated with performing the Full-Length High- Temperature (FLHT). Severe Fuel Damage Test No. 2 experiment have been analyzed. Major hazards that could cause harm or damage are (1) radioactive fission products, (2) radiation fields, (3) reactivity changes, (4) hydrogen generation, (5) materials at high temperature, (6) steam explosion, and (7) steam pressure pulse. As a result of this analysis, it is concluded that with proper precautions the FLHT- 2 test can be safely conducted.

  8. Electromyographic analysis of exercise resulting in symptoms of muscle damage.

    PubMed

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

    2000-03-01

    Surface electromyographic (EMG) signals were recorded from the hamstring muscles during six sets of submaximal isokinetic (2.6 rad x s(-1)) eccentric (11 men, 9 women) or concentric (6 men, 4 women) contractions. The EMG per unit torque increased during eccentric (P < 0.01) but not during concentric exercise. Similarly, the median frequency increased during eccentric (P < 0.01) but not during concentric exercise. The EMG per unit torque was lower for submaximal eccentric than maximum isometric contractions (P < 0.001), and lower for submaximal concentric than maximum isometric contractions (P < 0.01). The EMG per unit torque was lower for eccentric than concentric contractions (P < 0.05). The median frequency was higher for submaximal eccentric than maximum isometric contractions (P < 0.001); it was similar, however, between submaximal concentric and maximum isometric contractions (P = 0.07). Eccentric exercise resulted in significant isometric strength loss (P < 0.01), pain (P < 0.01) and muscle tenderness (P < 0.05). The greatest strength loss was seen 1 day after eccentric exercise, while the most severe pain and muscle tenderness occurred 2 days after eccentric exercise. A lower EMG per unit torque is consistent with the selective recruitment of a small number of motor units during eccentric exercise. A higher median frequency during eccentric contractions may be explained by selective recruitment of fast-twitch motor units. The present results are consistent with the theory that muscle damage results from excessive stress on a small number of active fibres during eccentric contractions. PMID:10737267

  9. Quantitative flux analysis reveals folate-dependent NADPH production

    NASA Astrophysics Data System (ADS)

    Fan, Jing; Ye, Jiangbin; Kamphorst, Jurre J.; Shlomi, Tomer; Thompson, Craig B.; Rabinowitz, Joshua D.

    2014-06-01

    ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis. The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important. Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography-mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway. Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP+ to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP+ and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress. Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power.

  10. Isotope Analysis Reveals Foraging Area Dichotomy for Atlantic Leatherback Turtles

    PubMed Central

    Angulo, Elena; Das, Krishna; Girondot, Marc

    2008-01-01

    Background The leatherback turtle (Dermochelys coriacea) has undergone a dramatic decline over the last 25 years, and this is believed to be primarily the result of mortality associated with fisheries bycatch followed by egg and nesting female harvest. Atlantic leatherback turtles undertake long migrations across ocean basins from subtropical and tropical nesting beaches to productive frontal areas. Migration between two nesting seasons can last 2 or 3 years, a time period termed the remigration interval (RI). Recent satellite transmitter data revealed that Atlantic leatherbacks follow two major dispersion patterns after nesting season, through the North Gulf Stream area or more eastward across the North Equatorial Current. However, information on the whole RI is lacking, precluding the accurate identification of feeding areas where conservation measures may need to be applied. Methodology/Principal Findings Using stable isotopes as dietary tracers we determined the characteristics of feeding grounds of leatherback females nesting in French Guiana. During migration, 3-year RI females differed from 2-year RI females in their isotope values, implying differences in their choice of feeding habitats (offshore vs. more coastal) and foraging latitude (North Atlantic vs. West African coasts, respectively). Egg-yolk and blood isotope values are correlated in nesting females, indicating that egg analysis is a useful tool for assessing isotope values in these turtles, including adults when not available. Conclusions/Significance Our results complement previous data on turtle movements during the first year following the nesting season, integrating the diet consumed during the year before nesting. We suggest that the French Guiana leatherback population segregates into two distinct isotopic groupings, and highlight the urgent need to determine the feeding habitats of the turtle in the Atlantic in order to protect this species from incidental take by commercial fisheries. Our

  11. Genetic heterogeneity in rhabdomyosarcoma revealed by SNP array analysis.

    PubMed

    Walther, Charles; Mayrhofer, Markus; Nilsson, Jenny; Hofvander, Jakob; Jonson, Tord; Mandahl, Nils; Øra, Ingrid; Gisselsson, David; Mertens, Fredrik

    2016-01-01

    Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Alveolar (ARMS) and embryonal (ERMS) histologies predominate, but rare cases are classified as spindle cell/sclerosing (SRMS). For treatment stratification, RMS is further subclassified as fusion-positive (FP-RMS) or fusion-negative (FN-RMS), depending on whether a gene fusion involving PAX3 or PAX7 is present or not. We investigated 19 cases of pediatric RMS using high resolution single-nucleotide polymorphism (SNP) array. FP-ARMS displayed, on average, more structural rearrangements than ERMS; the single FN-ARMS had a genomic profile similar to ERMS. Apart from previously known amplification (e.g., MYCN, CDK4, and MIR17HG) and deletion (e.g., NF1, CDKN2A, and CDKN2B) targets, amplification of ERBB2 and homozygous loss of ASCC3 or ODZ3 were seen. Combining SNP array with cytogenetic data revealed that most cases were polyploid, with at least one case having started as a near-haploid tumor. Further bioinformatic analysis of the SNP array data disclosed genetic heterogeneity, in the form of subclonal chromosomal imbalances, in five tumors. The outcome was worse for patients with FP-ARMS than ERMS or FN-ARMS (6/8 vs. 1/9 dead of disease), and the only children with ERMS showing intratumor diversity or with MYOD1 mutation-positive SRMS also died of disease. High resolution SNP array can be useful in evaluating genomic imbalances in pediatric RMS. PMID:26482321

  12. Towards a Fuzzy Bayesian Network Based Approach for Safety Risk Analysis of Tunnel-Induced Pipeline Damage.

    PubMed

    Zhang, Limao; Wu, Xianguo; Qin, Yawei; Skibniewski, Miroslaw J; Liu, Wenli

    2016-02-01

    Tunneling excavation is bound to produce significant disturbances to surrounding environments, and the tunnel-induced damage to adjacent underground buried pipelines is of considerable importance for geotechnical practice. A fuzzy Bayesian networks (FBNs) based approach for safety risk analysis is developed in this article with detailed step-by-step procedures, consisting of risk mechanism analysis, the FBN model establishment, fuzzification, FBN-based inference, defuzzification, and decision making. In accordance with the failure mechanism analysis, a tunnel-induced pipeline damage model is proposed to reveal the cause-effect relationships between the pipeline damage and its influential variables. In terms of the fuzzification process, an expert confidence indicator is proposed to reveal the reliability of the data when determining the fuzzy probability of occurrence of basic events, with both the judgment ability level and the subjectivity reliability level taken into account. By means of the fuzzy Bayesian inference, the approach proposed in this article is capable of calculating the probability distribution of potential safety risks and identifying the most likely potential causes of accidents under both prior knowledge and given evidence circumstances. A case concerning the safety analysis of underground buried pipelines adjacent to the construction of the Wuhan Yangtze River Tunnel is presented. The results demonstrate the feasibility of the proposed FBN approach and its application potential. The proposed approach can be used as a decision tool to provide support for safety assurance and management in tunnel construction, and thus increase the likelihood of a successful project in a complex project environment. PMID:26224125

  13. Applying robust variant of Principal Component Analysis as a damage detector in the presence of outliers

    NASA Astrophysics Data System (ADS)

    Gharibnezhad, Fahit; Mujica, Luis E.; Rodellar, José

    2015-01-01

    Using Principal Component Analysis (PCA) for Structural Health Monitoring (SHM) has received considerable attention over the past few years. PCA has been used not only as a direct method to identify, classify and localize damages but also as a significant primary step for other methods. Despite several positive specifications that PCA conveys, it is very sensitive to outliers. Outliers are anomalous observations that can affect the variance and the covariance as vital parts of PCA method. Therefore, the results based on PCA in the presence of outliers are not fully satisfactory. As a main contribution, this work suggests the use of robust variant of PCA not sensitive to outliers, as an effective way to deal with this problem in SHM field. In addition, the robust PCA is compared with the classical PCA in the sense of detecting probable damages. The comparison between the results shows that robust PCA can distinguish the damages much better than using classical one, and even in many cases allows the detection where classic PCA is not able to discern between damaged and non-damaged structures. Moreover, different types of robust PCA are compared with each other as well as with classical counterpart in the term of damage detection. All the results are obtained through experiments with an aircraft turbine blade using piezoelectric transducers as sensors and actuators and adding simulated damages.

  14. Detection of bearing damage by statistic vibration analysis

    NASA Astrophysics Data System (ADS)

    Sikora, E. A.

    2016-04-01

    The condition of bearings, which are essential components in mechanisms, is crucial to safety. The analysis of the bearing vibration signal, which is always contaminated by certain types of noise, is a very important standard for mechanical condition diagnosis of the bearing and mechanical failure phenomenon. In this paper the method of rolling bearing fault detection by statistical analysis of vibration is proposed to filter out Gaussian noise contained in a raw vibration signal. The results of experiments show that the vibration signal can be significantly enhanced by application of the proposed method. Besides, the proposed method is used to analyse real acoustic signals of a bearing with inner race and outer race faults, respectively. The values of attributes are determined according to the degree of the fault. The results confirm that the periods between the transients, which represent bearing fault characteristics, can be successfully detected.

  15. Duplication and analysis of meteoroid damage on LDEF and advanced spacecraft materials

    NASA Technical Reports Server (NTRS)

    Hill, David C.; Rose, M. Frank

    1995-01-01

    The analysis of exposed surfaces on LDEF since its retrieval in 1990 has revealed a wide range of meteoroid and debris (M&D) impact features in the sub-micron to millimeter size range, ranging from quasi-infinite target cratering in LDEF metallic structural members (e.g. inter-costals, tray clamps, etc.) to non-marginal perforations in metallic experimental surfaces (e.g. thin foil detectors, etc.). Approximately 34,000 impact features are estimated to exist on the exposed surfaces of LDEF. The vast majority of impact craters in metal substrates exhibit circular footprints, with approximately 50 percent retaining impactor residues in varying states of shock processing. The fundamental goals of this project were to duplicate and analyze meteoroid impact damage on spacecraft metallic materials with a view to quantifying the residue retention and oblique impact morphology characteristics. Using the hypervelocity impact test facility established at Auburn University a series of impact tests (normal and oblique incidence) were executed producing consistently high (11-12 km/s) peak impact velocities, the results of which were subsequently analyzed using Scanning Electron Microscope (SEM) and Energy Dispersive X-ray Spectroscopy (EDXS) facilities at Auburn University.

  16. Fatigue analysis of multiple site damage at a row of holes in a wide panel

    NASA Astrophysics Data System (ADS)

    Buhler, Kimberley; Grandt, Alten F., Jr.; Moukawsher, E. J.

    1994-09-01

    This paper is concerned with predicting the fatigue life of unstiffened panels which contain multiple site damage (MSD). The initial damage consists of through-the-thickness cracks emanating from a row of holes in the center of a finite width panel. A fracture mechanics analysis has been developed to predict the growth, interaction, and coalescence of the various cracks which propagate in the panel. A strain-life analysis incorporating Neuber's rule for notches, and Miner's rule for cumulative damage, is also employed to predict crack initiation for holes without initial cracking. This analysis is compared with the results of a series of fatigue tests on 2024-T3 aluminum panels, and is shown to do an excellent job of predicting the influence of MSD on the fatigue life of nine inch wide specimens. Having established confidence in the ability to analyze the influence of MSD on fatigue life, a parametric study is conducted to examine the influence of various MSD scenarios in an unstiffened panel. The numerical study considered 135 cases in all, with the parametric variables being the applied cyclic stress level, the lead crack geometry, and the number and location of MSD cracks. The numerical analysis provides details for the manner in which lead cracks and MSD cracks grow and coalesce leading to final failure. The results indicate that MSD located adjacent to lead cracks is the most damaging configuration, while for cases without lead cracks, MSD clusters which are not separated by uncracked holes are most damaging.

  17. Fatigue analysis of multiple site damage at a row of holes in a wide panel

    NASA Technical Reports Server (NTRS)

    Buhler, Kimberley; Grandt, Alten F., Jr.; Moukawsher, E. J.

    1994-01-01

    This paper is concerned with predicting the fatigue life of unstiffened panels which contain multiple site damage (MSD). The initial damage consists of through-the-thickness cracks emanating from a row of holes in the center of a finite width panel. A fracture mechanics analysis has been developed to predict the growth, interaction, and coalescence of the various cracks which propagate in the panel. A strain-life analysis incorporating Neuber's rule for notches, and Miner's rule for cumulative damage, is also employed to predict crack initiation for holes without initial cracking. This analysis is compared with the results of a series of fatigue tests on 2024-T3 aluminum panels, and is shown to do an excellent job of predicting the influence of MSD on the fatigue life of nine inch wide specimens. Having established confidence in the ability to analyze the influence of MSD on fatigue life, a parametric study is conducted to examine the influence of various MSD scenarios in an unstiffened panel. The numerical study considered 135 cases in all, with the parametric variables being the applied cyclic stress level, the lead crack geometry, and the number and location of MSD cracks. The numerical analysis provides details for the manner in which lead cracks and MSD cracks grow and coalesce leading to final failure. The results indicate that MSD located adjacent to lead cracks is the most damaging configuration, while for cases without lead cracks, MSD clusters which are not separated by uncracked holes are most damaging.

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

    NASA Technical Reports Server (NTRS)

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

    2006-01-01

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

  19. Analysis about factors affecting the degree of damage of buildings in earthquake

    NASA Astrophysics Data System (ADS)

    Jia, Jing; Yan, Jinghong

    2015-07-01

    Earthquakes have been affecting human's safety through human's history. Previous studies on earthquake, mostly, focused on the performance of buildings or evaluating damages. This paper, however, compares different factors that have influence on the damage of buildings with a case study in Wenchuan earthquake, using multiple linear regression methodology, so as to identify to what extend this factors influence the buildings’ damages, then give the rank of importance of these factors. In this process, authors take the type of structure as a dummy variable to compare the degree of damages caused by different types of structure, which were barely studied before. Besides, Factor Analysis Methodology(FA) will be adapted to classify factors, the results of which will simplify later study. The outcome of this study would make a big difference in optimizing the seismic design and improving residential seismic quality.

  20. 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.

  1. The severity of alpha-particle-induced DNA damage is revealed by exposure to cell-free extracts

    SciTech Connect

    Hodgkins, P.S.; O`Neill, P.; Stevens, D.; Fairman, M.P.

    1996-12-01

    The rejoining of single-strand breaks induced by {alpha}-particle and {gamma} irradiation in plasmid DNA under two scavenging conditions has been compared. At the two scavenger conditions has been compared. At the two scavenger capacities used of 1.5 {times} 10{sup 7} and 3 {times} 10{sup 8}s{sup {minus}1} using Tris-HCl as the scavenger, the ratio of single- to double-strand breaks for {alpha} particles is fivefold less than the corresponding ratios for {gamma} irradiation. The repair of such radiation-induced single-strand breaks has been examined using a cell-free system derived from human whole-cell extracts. We show that the rejoining of single-strand breaks for both {alpha}-particle- and {gamma}-irradiated plasmid is dependent upon the scavenging capacity and that the efficiency of rejoining of {alpha}-particle-induced single-strand breaks is significantly less than that observed for {gamma}-ray-induced breaks. In addition, for DNA that had been irradiated under conditions that mimic the cellular environment with respect to the radical scavenging capacity, 50 of {alpha}-particle-induced single-strand breaks are converted to double-strand breaks, in contrast with only {approximately}12% conversion of {gamma}-ray-induced single-strand breaks, indicating that the initial damage caused by {alpha} particles is more severe. These studies provide experimental evidence for increased clustering of damage which may have important implications for the induction of cancer by low-level {alpha}-particle sources such as domestic radon. 37 refs., 5 figs., 1 tab.

  2. Fatigue damage evaluation of plain woven carbon fiber reinforced plastic (CFRP) modified with MFC (micro-fibrillated cellulose) by thermo-elastic damage analysis (TDA)

    NASA Astrophysics Data System (ADS)

    Aoyama, Ryohei; Okubo, Kazuya; Fujii, Toru

    2013-04-01

    The aim of this study is to investigate characteristics of fatigue damage of CFRP modified with MFC by TDA under tensile cyclic loading. In this paper, fatigue life of CFRP modified with MFC was investigated under cyclic loading. Characteristics of fatigue damage of CFRP modified with MFC were evaluated by thermo-elastic damage analysis. Maximum improvement in fatigue life was also obtained under cyclic loading when epoxy matrix was enhanced with 0.3wt% of MFC as well as under static loading. Result of TDA showed same tendency as the result of fatigue test, and the result of TDA well expressed the fatigue damage behavior of plain woven CFRP plate. Eventually, TDA was effective for clear understanding the degree of fatigue damage progression of CFRP modified with MFC.

  3. Analysis of damage and failure in metal matrix composites

    SciTech Connect

    Brust, F.W.; Majumdar, B.S.; Newaz, G.M.

    1995-12-31

    This paper presents the results of the analysis of the constitutive response of a model Metal Matrix Composite (MMC) system. The model is described first, followed by some direct comparison of predicted response to corresponding experimental data. An important result discussed here is that when model verification is made, it is important to compare load direction response to the experimental data, but also, comparisons to the out of load direction response must be made, or the model may not be performing as desired. Some discussion of failure predictions using simple models is also made here.

  4. Evaluation of Progressive Failure Analysis and Modeling of Impact Damage in Composite Pressure Vessels

    NASA Technical Reports Server (NTRS)

    Sanchez, Christopher M.

    2011-01-01

    NASA White Sands Test Facility (WSTF) is leading an evaluation effort in advanced destructive and nondestructive testing of composite pressure vessels and structures. WSTF is using progressive finite element analysis methods for test design and for confirmation of composite pressure vessel performance. Using composite finite element analysis models and failure theories tested in the World-Wide Failure Exercise, WSTF is able to estimate the static strength of composite pressure vessels. Additionally, test and evaluation on composites that have been impact damaged is in progress so that models can be developed to estimate damage tolerance and the degradation in static strength.

  5. Applications of a damage tolerance analysis methodology in aircraft design and production

    NASA Technical Reports Server (NTRS)

    Woodward, M. R.; Owens, S. D.; Law, G. E.; Mignery, L. A.

    1992-01-01

    Objectives of customer mandated aircraft structural integrity initiatives in design are to guide material selection, to incorporate fracture resistant concepts in the design, to utilize damage tolerance based allowables and planned inspection procedures necessary to enhance the safety and reliability of manned flight vehicles. However, validated fracture analysis tools for composite structures are needed to accomplish these objectives in a timely and economical manner. This paper briefly describes the development, validation, and application of a damage tolerance methodology for composite airframe structures. A closed-form analysis code, entitled SUBLAM was developed to predict the critical biaxial strain state necessary to cause sublaminate buckling-induced delamination extension in an impact damaged composite laminate. An embedded elliptical delamination separating a thin sublaminate from a thick parent laminate is modelled. Predicted failure strains were correlated against a variety of experimental data that included results from compression after impact coupon and element tests. An integrated analysis package was developed to predict damage tolerance based margin-of-safety (MS) using NASTRAN generated loads and element information. Damage tolerance aspects of new concepts are quickly and cost-effectively determined without the need for excessive testing.

  6. Pre-2014 mudslides at Oso revealed by InSAR and multi-source DEM analysis

    NASA Astrophysics Data System (ADS)

    Kim, J. W.; Lu, Z.; QU, F.

    2014-12-01

    The landslide is a process that results in the downward and outward movement of slope-reshaping materials including rocks and soils and annually causes the loss of approximately $3.5 billion and tens of casualties in the United States. The 2014 Oso mudslide was an extreme event costing nearly 40 deaths and damaging civilian properties. Landslides are often unpredictable, but in many cases, catastrophic events are repetitive. Historic record in the Oso mudslide site indicates that there have been serial events in decades, though the extent of sliding events varied from time to time. In our study, the combination of multi-source DEMs, InSAR, and time-series InSAR analysis has enabled to characterize the Oso mudslide. InSAR results from ALOS PALSAR show that there was no significant deformation between mid-2006 and 2011. The combination of time-series InSAR analysis and old-dated DEM indicated revealed topographic changes associated the 2006 sliding event, which is confirmed by the difference of multiple LiDAR DEMs. Precipitation and discharge measurements before the 2006 and 2014 landslide events did not exhibit extremely anomalous records, suggesting the precipitation is not the controlling factor in determining the sliding events at Oso. The lack of surface deformation during 2006-2011 and weak correlation between the precipitation and the sliding event, suggest other factors (such as porosity) might play a critical role on the run-away events at this Oso and other similar landslides.

  7. Independent component analysis of DTI data reveals white matter covariances in Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Ouyang, Xin; Sun, Xiaoyu; Guo, Ting; Sun, Qiaoyue; Chen, Kewei; Yao, Li; Wu, Xia; Guo, Xiaojuan

    2014-03-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease with the clinical symptom of the continuous deterioration of cognitive and memory functions. Multiple diffusion tensor imaging (DTI) indices such as fractional anisotropy (FA) and mean diffusivity (MD) can successfully explain the white matter damages in AD patients. However, most studies focused on the univariate measures (voxel-based analysis) to examine the differences between AD patients and normal controls (NCs). In this investigation, we applied a multivariate independent component analysis (ICA) to investigate the white matter covariances based on FA measurement from DTI data in 35 AD patients and 45 NCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We found that six independent components (ICs) showed significant FA reductions in white matter covariances in AD compared with NC, including the genu and splenium of corpus callosum (IC-1 and IC-2), middle temporal gyral of temporal lobe (IC-3), sub-gyral of frontal lobe (IC-4 and IC-5) and sub-gyral of parietal lobe (IC-6). Our findings revealed covariant white matter loss in AD patients and suggest that the unsupervised data-driven ICA method is effective to explore the changes of FA in AD. This study assists us in understanding the mechanism of white matter covariant reductions in the development of AD.

  8. Gene expression studies reveal that DNA damage, vascular perturbation, and inflammation contribute to the pathogenesis of carbonyl sulfide neurotoxicity.

    PubMed

    Morrison, James P; Ton, Thai-Vu; Collins, Jennifer B; Switzer, Robert C; Little, Peter B; Morgan, Daniel L; Sills, Robert C

    2009-06-01

    Carbonyl sulfide (COS) is an odorless gas that produces highly reproducible lesions in the central nervous system. In the present study, the time course for the development of the neurotoxicological lesions was defined and the gene expression changes occurring in the posterior colliculus upon exposure to COS were characterized. Fischer 344 rats were exposed to 0 or 500 ppm COS for one, two, three, four, five, eight, or ten days, six hours per day. On days 1 and 2, no morphological changes were detected; on day 3, 10/10 (100%) rats had necrosis in the posterior colliculi; and on day 4 and later, necrosis was observed in numerous areas of the brain. Important gene expression changes occurring in the posterior colliculi after one or two days of COS exposure that were predictive of the subsequent morphological findings included up-regulation of genes associated with DNA damage and G1/S checkpoint regulation (KLF4, BTG2, GADD45g), apoptosis (TGM2, GADD45g, RIPK3), and vascular mediators (ADAMTS, CTGF, CYR61, VEGFC). Proinflammatory mediators (CCL2, CEBPD) were up-regulated prior to increases in expression of the astrocytic marker GFAP and macrophage marker CSF2rb1. These gene expression findings were predictive of later CNS lesions caused by COS exposure and serve as a model for future investigations into the mechanisms of disease in the central nervous system. PMID:19395590

  9. Quantitative Phosphoproteomics Reveals Crosstalk Between Phosphorylation and O-GlcNAc in the DNA Damage Response Pathway

    PubMed Central

    Zhong, Jun; Martinez, Marissa; Sengupta, Srona; Lee, Albert; Wu, Xinyan; Chaerkady, Raghothama; Chatterjee, Aditi; O’Meally, Robert N.; Cole, Robert N.; Pandey, Akhilesh; Zachara, Natasha E.

    2015-01-01

    The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification of metazoans. The addition and removal of O-GlcNAc is catalyzed by the O-GlcNAc transferase (OGT) and O-GlcNAcase, respectively. One mechanism by which O-GlcNAc is thought to mediate proteins is by regulating phosphorylation. To provide insight into the pathways regulated by O-GlcNAc, we have utilized stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative proteomics to carry out comparisons of site-specific phosphorylation in OGT wild-type (WT) and Null cells. Quantitation of the phosphoproteome demonstrated that out of 5,529 phosphoserine, phosphothreonine and phosphotyrosine sites, 232 phosphosites were upregulated and 133 downregulated in the absence of O-GlcNAc. Collectively, these data suggest that deletion of OGT has a profound effect on the phosphorylation of cell cycle and DNA damage response proteins. Key events were confirmed by biochemical analyses and demonstrate a increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM’s downstream targets p53, H2AX and Chk2. Together, these data support widespread changes in the phosphoproteome upon removal of O-GlcNAc, suggesting that O-GlcNAc regulates processes such as the cell cycle, genomic stability, and lysosomal biogenesis. PMID:25263469

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

    PubMed

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

    2014-08-01

    Many populations of threatened mammals persist outside formally protected areas, and their survival depends on the willingness of communities to coexist with them. An understanding of the attitudes, and specifically the tolerance, of individuals and communities and the factors that determine these is therefore fundamental to designing strategies to alleviate human-wildlife conflict. We conducted a meta-analysis to identify factors that affected attitudes toward 4 groups of terrestrial mammals. Elephants (65%) elicited the most positive attitudes, followed by primates (55%), ungulates (53%), and carnivores (44%). Urban residents presented the most positive attitudes (80%), followed by commercial farmers (51%) and communal farmers (26%). A tolerance to damage index showed that human tolerance of ungulates and primates was proportional to the probability of experiencing damage while elephants elicited tolerance levels higher than anticipated and carnivores elicited tolerance levels lower than anticipated. Contrary to conventional wisdom, experiencing damage was not always the dominant factor determining attitudes. Communal farmers had a lower probability of being positive toward carnivores irrespective of probability of experiencing damage, while commercial farmers and urban residents were more likely to be positive toward carnivores irrespective of damage. Urban residents were more likely to be positive toward ungulates, elephants, and primates when probability of damage was low, but not when it was high. Commercial and communal farmers had a higher probability of being positive toward ungulates, primates, and elephants irrespective of probability of experiencing damage. Taxonomic bias may therefore be important. Identifying the distinct factors explaining these attitudes and the specific contexts in which they operate, inclusive of the species causing damage, will be essential for prioritizing conservation investments. PMID:24661270

  11. A new hand-held microfluidic cytometer for evaluating irradiation damage by analysis of the damaged cells distribution

    PubMed Central

    Wang, Junsheng; Fan, Zhiqiang; Zhao, Yile; Song, Younan; Chu, Hui; Song, Wendong; Song, Yongxin; Pan, Xinxiang; Sun, Yeqing; Li, Dongqing

    2016-01-01

    Space radiation brings uneven damages to cells. The detection of the distribution of cell damage plays a very important role in radiation medicine and the related research. In this paper, a new hand-held microfluidic flow cytometer was developed to evaluate the degree of radiation damage of cells. The device we propose overcomes the shortcomings (e.g., large volume and high cost) of commercial flow cytometers and can evaluate the radiation damage of cells accurately and quickly with potential for onsite applications. The distribution of radiation-damaged cells is analyzed by a simultaneous detection of immunofluorescence intensity of γ-H2AX and resistance pulse sensor (RPS) signal. The γ-H2AX fluorescence intensity provides information of the degree of radiation damage in cells. The ratio of the number of cells with γ-H2AX fluorescence signals to the total numbers of cells detected by RPS indicates the percentage of the cells that are damaged by radiation. The comparison experiment between the developed hand-held microfluidic flow cytometer and a commercial confocal microscope indicates a consistent and comparable detection performance. PMID:26983800

  12. A new hand-held microfluidic cytometer for evaluating irradiation damage by analysis of the damaged cells distribution.

    PubMed

    Wang, Junsheng; Fan, Zhiqiang; Zhao, Yile; Song, Younan; Chu, Hui; Song, Wendong; Song, Yongxin; Pan, Xinxiang; Sun, Yeqing; Li, Dongqing

    2016-01-01

    Space radiation brings uneven damages to cells. The detection of the distribution of cell damage plays a very important role in radiation medicine and the related research. In this paper, a new hand-held microfluidic flow cytometer was developed to evaluate the degree of radiation damage of cells. The device we propose overcomes the shortcomings (e.g., large volume and high cost) of commercial flow cytometers and can evaluate the radiation damage of cells accurately and quickly with potential for onsite applications. The distribution of radiation-damaged cells is analyzed by a simultaneous detection of immunofluorescence intensity of γ-H2AX and resistance pulse sensor (RPS) signal. The γ-H2AX fluorescence intensity provides information of the degree of radiation damage in cells. The ratio of the number of cells with γ-H2AX fluorescence signals to the total numbers of cells detected by RPS indicates the percentage of the cells that are damaged by radiation. The comparison experiment between the developed hand-held microfluidic flow cytometer and a commercial confocal microscope indicates a consistent and comparable detection performance. PMID:26983800

  13. A new hand-held microfluidic cytometer for evaluating irradiation damage by analysis of the damaged cells distribution

    NASA Astrophysics Data System (ADS)

    Wang, Junsheng; Fan, Zhiqiang; Zhao, Yile; Song, Younan; Chu, Hui; Song, Wendong; Song, Yongxin; Pan, Xinxiang; Sun, Yeqing; Li, Dongqing

    2016-03-01

    Space radiation brings uneven damages to cells. The detection of the distribution of cell damage plays a very important role in radiation medicine and the related research. In this paper, a new hand-held microfluidic flow cytometer was developed to evaluate the degree of radiation damage of cells. The device we propose overcomes the shortcomings (e.g., large volume and high cost) of commercial flow cytometers and can evaluate the radiation damage of cells accurately and quickly with potential for onsite applications. The distribution of radiation-damaged cells is analyzed by a simultaneous detection of immunofluorescence intensity of γ-H2AX and resistance pulse sensor (RPS) signal. The γ-H2AX fluorescence intensity provides information of the degree of radiation damage in cells. The ratio of the number of cells with γ-H2AX fluorescence signals to the total numbers of cells detected by RPS indicates the percentage of the cells that are damaged by radiation. The comparison experiment between the developed hand-held microfluidic flow cytometer and a commercial confocal microscope indicates a consistent and comparable detection performance.

  14. Damage analysis and fundamental studies. Quarterly progress report, October-December 1980

    SciTech Connect

    Not Available

    1981-02-01

    This report is the twelfth in a series of Quarterly Technical Progress Reports on Damage Analysis and Fundamental Studies (DAFS) which is one element of the Fusion Reactor Materials Program, conducted in support of the Magnetic Fusion Energy Program of the US Department of Energy. The first eight reports in this series were numbered DOE/ET-0065/1 through 8.

  15. [Chlorophyll fluorescence spectrum analysis of greenhouse cucumber disease and insect damage].

    PubMed

    Sui, Yuan-yuan; Yu, Hai-ye; Zhang, Lei; Luo, Han; Ren, Shun; Zhao, Guo-gang

    2012-05-01

    The present paper is based on chlorophyll fluorescence spectrum analysis. The wavelength 685 nm was determined as the primary characteristic point for the analysis of healthy or disease and insect damaged leaf by spectrum configuration. Dimensionality reduction of the spectrum was achieved by combining simple intercorrelation bands selection and principal component analysis (PCA). The principal component factor was reduced from 10 to 5 while the spectrum information was kept reaching 99.999%. By comparing and analysing three modeling methods, namely the partial least square regression (PLSR), BP neural network (BP) and least square support vector machine regression (LSSVMR), regarding correlation coefficient of true value and predicted value as evaluation criterion, eventually, LSSVMR was confirmed as the appropriate method for modeling of greenhouse cucumber disease and insect damage chlorophyll fluorescence spectrum analysis. PMID:22827075

  16. A Finite Element Analysis for Predicting the Residual Compressive Strength of Impact-Damaged Sandwich Panels

    NASA Technical Reports Server (NTRS)

    Ratcliffe, James G.; Jackson, Wade C.

    2008-01-01

    A simple analysis method has been developed for predicting the residual compressive strength of impact-damaged sandwich panels. The method is tailored for honeycomb core-based sandwich specimens that exhibit an indentation growth failure mode under axial compressive loading, which is driven largely by the crushing behavior of the core material. The analysis method is in the form of a finite element model, where the impact-damaged facesheet is represented using shell elements and the core material is represented using spring elements, aligned in the thickness direction of the core. The nonlinear crush response of the core material used in the analysis is based on data from flatwise compression tests. A comparison with a previous analysis method and some experimental data shows good agreement with results from this new approach.

  17. A Finite Element Analysis for Predicting the Residual Compression Strength of Impact-Damaged Sandwich Panels

    NASA Technical Reports Server (NTRS)

    Ratcliffe, James G.; Jackson, Wade C.

    2008-01-01

    A simple analysis method has been developed for predicting the residual compression strength of impact-damaged sandwich panels. The method is tailored for honeycomb core-based sandwich specimens that exhibit an indentation growth failure mode under axial compression loading, which is driven largely by the crushing behavior of the core material. The analysis method is in the form of a finite element model, where the impact-damaged facesheet is represented using shell elements and the core material is represented using spring elements, aligned in the thickness direction of the core. The nonlinear crush response of the core material used in the analysis is based on data from flatwise compression tests. A comparison with a previous analysis method and some experimental data shows good agreement with results from this new approach.

  18. Damage Detection in a Composite Plate Using Modal Analysis and Artificial Intelligence

    NASA Astrophysics Data System (ADS)

    Nasiri, M. R.; Mahjoob, M. J.; Aghakasiri, A.

    2011-12-01

    The use of composite materials has vastly increased in recent years. Great interest is therefore developed in the damage detection of composites using non-destructive test methods. Several approaches have been applied to obtain information about the existence, location and growth of the faults. The main goal in this paper is to use the vibration response of a composite plate to detect and localize delamination defect based on the frequency response and modal analysis. The features extracted are used as the input data in an artificial intelligence scheme to identify the severity of the damages. Experiments are then conducted to validate the developed model.

  19. Tornado risk analysis at Savannah River Plant using windspeed damage thresholds and single building strike frequencies

    SciTech Connect

    Taylor, D.H.; McDonald, J.R.; Twisdale, L.A.

    1985-01-01

    In order to evaluate the safety of existing structures and properly design new structures, an analysis of tornado resistance was conducted on each process building at SRP and other buildings by type. Damage estimates were cataloged for each Fujita class windspeed interval and windspeeds were cataloged as a function of increased levels of damage. The probability, for any structure, of a tornado exceeding each windspeed threshold was calculated using the TORRISK computer code which was developed for calculating the probability of a tornado strike on nuclear power generating plants.

  20. Analysis of damaging effects of laser-plasma accelerated shrapnels on protecting glass shield

    NASA Astrophysics Data System (ADS)

    Martinkova, Michaela; Kalal, Milan; Shmatov, Mikhail L.

    2013-11-01

    Analysis of the damage caused by laser plasma accelerated fragments of metal target was performed. Measured as well as calculated parameters of craters and shrapnel found in BK7 glass blastshield are presented. Method applied for the measurement of parameters of craters is described. Potential damage of optical elements by the so-called striking cores (high-velocity stable objects arising due to collapse of cones or some other target parts toward their axes) that can be generated in IFE related experiments is evaluated.

  1. Quantitative analysis of damage clustering and void linking for spallation modeling in tantalum

    SciTech Connect

    Tonks, D.L.; Zurek, A.K.; Thissell, W.R.; Hixson, R.

    1997-05-01

    In a companion paper in this volume by Zurek et al, micrographs of incipient spallation damage in rolled tantalum were numerically analyzed using image analysis techniques. Void sizes, locations, and overall porosity were measured and tabulated. In this paper, we extend this analysis to include void clusters and examine the correlation between cluster size and the ranges of local instabilities between voids visible in the micrographs. The implications for spallation modeling will be given.

  2. Shear Correction Factors in Creep-Damage Analysis of Beams, Plates and Shells

    NASA Astrophysics Data System (ADS)

    Altenbach, Holm; Naumenko, Konstantin

    Modern design rules for thin-walled structures which operate at elevated temperatures are based on the demand that the creep and may be the damage behaviour should be taken into account. In the last four decades various models including the scalar or tensor valued hardening and damage variables are established. These models reflect the influence of the deformation or the damage induced anisotropy on the creep response. One problem in creep analysis of thin-walled structures is the selection of the structural mechanics model which has to be adequate to the choice of the constitutive equations. Considering complex loading conditions the structural mechanics model has to reflect for instance the different constitutive behaviour in tension and compression. Below the applicability of classical engineering models for beams, plates and shells to the creep-damage analysis is discussed. It will be shown that a first improvement of the classical approach can be given within the assumptions of the first order shear deformation theory. Based on the beam equations we demonstrate that the shear correction factors have to be modified within the time-step analysis.

  3. Decision-tree analysis of factors influencing rainfall-related building structure and content damage

    NASA Astrophysics Data System (ADS)

    Spekkers, M. H.; Kok, M.; Clemens, F. H. L. R.; ten Veldhuis, J. A. E.

    2014-09-01

    Flood-damage prediction models are essential building blocks in flood risk assessments. So far, little research has been dedicated to damage from small-scale urban floods caused by heavy rainfall, while there is a need for reliable damage models for this flood type among insurers and water authorities. The aim of this paper is to investigate a wide range of damage-influencing factors and their relationships with rainfall-related damage, using decision-tree analysis. For this, district-aggregated claim data from private property insurance companies in the Netherlands were analysed, for the period 1998-2011. The databases include claims of water-related damage (for example, damages related to rainwater intrusion through roofs and pluvial flood water entering buildings at ground floor). Response variables being modelled are average claim size and claim frequency, per district, per day. The set of predictors include rainfall-related variables derived from weather radar images, topographic variables from a digital terrain model, building-related variables and socioeconomic indicators of households. Analyses were made separately for property and content damage claim data. Results of decision-tree analysis show that claim frequency is most strongly associated with maximum hourly rainfall intensity, followed by real estate value, ground floor area, household income, season (property data only), buildings age (property data only), a fraction of homeowners (content data only), a and fraction of low-rise buildings (content data only). It was not possible to develop statistically acceptable trees for average claim size. It is recommended to investigate explanations for the failure to derive models. These require the inclusion of other explanatory factors that were not used in the present study, an investigation of the variability in average claim size at different spatial scales, and the collection of more detailed insurance data that allows one to distinguish between the

  4. Evaluation of liver tissue damage and grasp stability using finite element analysis.

    PubMed

    Cheng, Lei; Hannaford, Blake

    2016-01-01

    Minimizing tissue damage and maintaining grasp stability are essential considerations in surgical grasper design. Most past and current research analyzing graspers used for tissue manipulation in minimally invasive surgery is based on in vitro experiments. Most previous work assessed tissue injury and grasp security by visual inspection; only a few studies have quantified it. The goal of the present work is to develop a methodology with which to compute tissue damage magnitude and grasp quality that is appropriate for a wide range of grasper-tissue interaction. Using finite element analysis (FEA), four graspers with varying radii of curvature and four graspers with different tooth sizes were analyzed while squeezing and pulling liver tissue. All graspers were treated as surgical steel with linear elastic material properties. Nonlinear material properties of tissue used in the FEA as well as damage evaluation were derived from previously reported in vivo experiments. Computed peak stress, integrated stress, and tissue damage were compared. Applied displacement is vertical and then horizontal to the tissue surface to represent grasp and retraction. A close examination of the contact status of each node within the grasper-tissue interaction surface was carried out to investigate grasp stability. The results indicate less tissue damage with increasing radius of curvature. A smooth wave pattern reduced tissue damage at the cost of inducing higher percentage of slipping area. This methodology may be useful for researchers to develop and test various designs of graspers. Also it could improve surgical simulator performance by reflecting more realistic tissue material properties and predicting tissue damage for the student. PMID:25408249

  5. A padding method to reduce edge effects for enhanced damage identification using wavelet analysis

    NASA Astrophysics Data System (ADS)

    Montanari, Lorenzo; Basu, Biswajit; Spagnoli, Andrea; Broderick, Brian M.

    2015-02-01

    Vibration response based structural damage identification by spatial wavelet analysis is widely considered a powerful tool in Structural Health Monitoring (SHM). This work deals with the issue of border distortions in wavelet transform that can mask tiny damages close to the boundary of a structure. Since traditional padding methods (e.g., zero-padding, symmetric padding, linear padding) are often not satisfactory, a simple and computationally inexpensive signal extension method, based on fitting polynomial functions and continuity conditions at the extrema, is proposed. The method is applied to analyze noisy mode shapes and static deflection of cracked cantilever and simply supported beams. The effectiveness and the versatility of the method in localizing tiny damages close to clamped, free or hinged beam boundaries is demonstrated. Furthermore, an extensive comparison with the linear padding method and Messina's isomorphism methods is carried out.

  6. Mathematical models for estimating earthquake casualties and damage cost through regression analysis using matrices

    NASA Astrophysics Data System (ADS)

    Urrutia, J. D.; Bautista, L. A.; Baccay, E. B.

    2014-04-01

    The aim of this study was to develop mathematical models for estimating earthquake casualties such as death, number of injured persons, affected families and total cost of damage. To quantify the direct damages from earthquakes to human beings and properties given the magnitude, intensity, depth of focus, location of epicentre and time duration, the regression models were made. The researchers formulated models through regression analysis using matrices and used α = 0.01. The study considered thirty destructive earthquakes that hit the Philippines from the inclusive years 1968 to 2012. Relevant data about these said earthquakes were obtained from Philippine Institute of Volcanology and Seismology. Data on damages and casualties were gathered from the records of National Disaster Risk Reduction and Management Council. The mathematical models made are as follows: This study will be of great value in emergency planning, initiating and updating programs for earthquake hazard reductionin the Philippines, which is an earthquake-prone country.

  7. Damage and Failure Analysis of AZ31 Alloy Sheet in Warm Stamping Processes

    NASA Astrophysics Data System (ADS)

    Zhao, P. J.; Chen, Z. H.; Dong, C. F.

    2016-07-01

    In this study, a combined experimental-numerical investigation on the failure of AZ31 Mg alloy sheet in the warm stamping process was carried out based on modified GTN damage model which integrated Yld2000 anisotropic yield criterion. The constitutive equations of material were implemented into a VUMAT subroutine for solver ABAQUS/Explicit and applied to the formability analysis of mobile phone shell. The morphology near the crack area was observed using SEM, and the anisotropic damage evolution at various temperatures was simulated. The distributions of plastic strain, damage evolution, thickness, and fracture initiation obtained from FE simulation were analyzed. The corresponding forming limit diagrams were worked out, and the comparison with the experimental data showed a good agreement.

  8. Damage and Failure Analysis of AZ31 Alloy Sheet in Warm Stamping Processes

    NASA Astrophysics Data System (ADS)

    Zhao, P. J.; Chen, Z. H.; Dong, C. F.

    2016-06-01

    In this study, a combined experimental-numerical investigation on the failure of AZ31 Mg alloy sheet in the warm stamping process was carried out based on modified GTN damage model which integrated Yld2000 anisotropic yield criterion. The constitutive equations of material were implemented into a VUMAT subroutine for solver ABAQUS/Explicit and applied to the formability analysis of mobile phone shell. The morphology near the crack area was observed using SEM, and the anisotropic damage evolution at various temperatures was simulated. The distributions of plastic strain, damage evolution, thickness, and fracture initiation obtained from FE simulation were analyzed. The corresponding forming limit diagrams were worked out, and the comparison with the experimental data showed a good agreement.

  9. Global phospholipidomics analysis reveals selective pulmonary peroxidation profiles upon inhalation of single-walled carbon nanotubes.

    PubMed

    Tyurina, Yulia Y; Kisin, Elena R; Murray, Ashley; Tyurin, Vladimir A; Kapralova, Valentina I; Sparvero, Louis J; Amoscato, Andrew A; Samhan-Arias, Alejandro K; Swedin, Linda; Lahesmaa, Riitta; Fadeel, Bengt; Shvedova, Anna A; Kagan, Valerian E

    2011-09-27

    It is commonly believed that nanomaterials cause nonspecific oxidative damage. Our mass spectrometry-based oxidative lipidomics analysis of all major phospholipid classes revealed highly selective patterns of pulmonary peroxidation after inhalation exposure of mice to single-walled carbon nanotubes. No oxidized molecular species were found in the two most abundant phospholipid classes: phosphatidylcholine and phosphatidylethanolamine. Peroxidation products were identified in three relatively minor classes of anionic phospholipids, cardiolipin, phosphatidylserine, and phosphatidylinositol, whereby oxygenation of polyunsaturated fatty acid residues also showed unusual substrate specificity. This nonrandom peroxidation coincided with the accumulation of apoptotic cells in the lung. A similar selective phospholipid peroxidation profile was detected upon incubation of a mixture of total lung lipids with H(2)O(2)/cytochrome c known to catalyze cardiolipin and phosphatidylserine peroxidation in apoptotic cells. The characterized specific phospholipid peroxidation signaling pathways indicate new approaches to the development of mitochondria-targeted regulators of cardiolipin peroxidation to protect against deleterious effects of pro-apoptotic effects of single-walled carbon nanotubes in the lung. PMID:21800898

  10. Global Phospholipidomics Analysis Reveals Selective Pulmonary Peroxidation Profiles Upon Inhalation of Single Walled Carbon Nanotubes

    PubMed Central

    Tyurina, Yulia Y.; Kisin, Elena R.; Murray, Ashley; Tyurin, Vladimir A.; Kapralova, Valentina I.; Sparvero, Louis J.; Amoscato, Andrew A.; Samhan-Arias, Alejandro K.; Swedin, Linda; Lahesmaa, Riitta; Fadeel, Bengt; Shvedova, Anna A.; Kagan, Valerian E.

    2011-01-01

    It is commonly believed that nanomaterials cause non-specific oxidative damage. Our mass spectrometry-based oxidative lipidomics analysis of all major phospholipid classes revealed highly selective patterns of pulmonary peroxidation after inhalation exposure of mice to single-walled carbon nanotubes. No oxidized molecular species were found in two most abundant phospholipid classes – phosphatidylcholine and phosphatidylethanolamine. Peroxidation products were identified in three relatively minor classes of anionic phospholipids, cardiolipin, phosphatidylserine and phosphatidylinositol whereby oxygenation of polyunsaturated fatty acid residues also showed unusual substrate specificity. This non-random peroxidation coincided with the accumulation of apoptotic cells in the lung. A similar selective phospholipid peroxidation profile was detected upon incubation of a mixture of total lung lipids with H2O2/cytochrome c known to catalyze cardiolipin and phosphatidylserine peroxidation in apoptotic cells. The characterized specific phospholipid peroxidation signaling pathways indicate new approaches to the development of mitochondria targeted regulators of cardiolipin peroxidation to protect against deleterious effects of pro-apoptotic effects of single-walled carbon nanotubes in the lung. PMID:21800898

  11. Damage behavior analysis of smart composites with embedded pre-strained SMA foils

    NASA Astrophysics Data System (ADS)

    Ogisu, Toshimichi; Shimanuki, Masakazu; Kiyoshima, Satoshi; Takaki, Junji; Taketa, Ichiro; Takeda, Nobuo

    2006-02-01

    This paper presents the results of experimental and analytical studies with respect to the damage onset/growth suppression behavior using quasi-isotropic CFRP laminates with embedded pre-strained SMA foils under quasi-static uniaxial tension load. In our previous studies, we conducted some preliminary quasi-static load-unload tests using CFRP laminates with embedded pre-strained SMA foils (smart composites). The results confirmed that these smart composites had excellent effects on damage onset/growth suppression, in comparison with the conventional CFRP laminates. In this study, systematic load-unload tests are conducted for quasi-isotropic laminates, with and without SMA foils and adhesive layers. Following this, a detailed observation of the damage onset/growth suppression behavior is conducted. This observation verified that the microcracks, which originated at the -45/90 interface, generally grow into transverse cracks in a 90° ply of the quasi-isotropic CFRP laminates ([45/0/-45/90]s). It has also been experimentally confirmed that the damage onset/growth suppression effects of smart composites are obtained by the suppression of crack opening displacement. Furthermore, the stress and strain distributions of all the composite systems with microcracks are calculated by FEM analysis at room temperature (RT) and at 80 °C for conventional composites ([45/0/-45/90]s) and smart composites ([45/0/-45/90/Ad/SMA/Ad/90/-45/0/45]), respectively. From the results of the FEM analysis, the strain energy release rate is calculated using the 'crack closure method' for the evaluation of the damage onset/growth suppression effect. It is confirmed that the damage onset/growth suppression effects of the CFRP laminates with embedded pre-strained SMA foils are obtained by the suppression of crack opening displacement in 90° layers, which is generated by the suppression of the strain energy release rate for smart composites by the recovery stress of SMA.

  12. Subfield profitability analysis reveals an economic case for cropland diversification

    NASA Astrophysics Data System (ADS)

    Brandes, E.; McNunn, G. S.; Schulte, L. A.; Bonner, I. J.; Muth, D. J.; Babcock, B. A.; Sharma, B.; Heaton, E. A.

    2016-01-01

    Public agencies and private enterprises increasingly desire to achieve ecosystem service outcomes in agricultural systems, but are limited by perceived conflicts between economic and ecosystem service goals and a lack of tools enabling effective operational management. Here we use Iowa—an agriculturally homogeneous state representative of the Maize Belt—to demonstrate an economic rationale for cropland diversification at the subfield scale. We used a novel computational framework that integrates disparate but publicly available data to map ˜3.3 million unique potential management polygons (9.3 Mha) and reveal subfield opportunities to increase overall field profitability. We analyzed subfield profitability for maize/soybean fields during 2010-2013—four of the most profitable years in recent history—and projected results for 2015. While cropland operating at a loss of US 250 ha-1 or more was negligible between 2010 and 2013 at 18 000-190 000 ha (<2% of row-crop land), the extent of highly unprofitable land increased to 2.5 Mha, or 27% of row-crop land, in the 2015 projection. Aggregation of these areas to the township level revealed ‘hotspots’ for potential management change in Western, Central, and Northeast Iowa. In these least profitable areas, incorporating conservation management that breaks even (e.g., planting low-input perennials), into low-yielding portions of fields could increase overall cropland profitability by 80%. This approach is applicable to the broader region and differs substantially from the status quo of ‘top-down’ land management for conservation by harnessing private interest to align profitability with the production of ecosystem services.

  13. Analysis of copy number variations reveals differences among cattle breeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in the modern domesticated cattle using array comparative genomic hybridization (array CGH) and quanti...

  14. Trophic hierarchies revealed via amino acid isotopic analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite the potential of isotopic methods to illuminate trophic function, accurate estimates of lifetime feeding tendencies have remained elusive. A relatively new approach—referred to as compound-specific isotopic analysis (CSIA)—has emerged, centering on the measurement of 15N:14N ratios in amino ...

  15. Advanced Damage Tolerance Analysis of International Space Station Pressure Wall Welds

    NASA Technical Reports Server (NTRS)

    Allen, Phillip A.

    2006-01-01

    EM20/MSFC has sponsored technology in the area of advanced damage tolerance analysis tools used to analyze the International Space Station (ISS) pressure wall welds. The ISS European modules did not receive non-destructive evaluation (NDE) inspection after proof test. In final assembly configuration, most welds could only be inspected from one side, and some welds were uninspectible. Therefore, advanced damage tolerance analysis was required to determine the critical initial flaw sizes and predicted safe life for the pressure wall welds. EM20 sponsored the development of a new finite element tools using FEA-Crack and WARP3D to solve the problem. This presentation gives a brief overview of the new analytical tools and the analysis results.

  16. Molecular Analysis of Sarcoidosis Granulomas Reveals Antimicrobial Targets.

    PubMed

    Rotsinger, Joseph E; Celada, Lindsay J; Polosukhin, Vasiliy V; Atkinson, James B; Drake, Wonder P

    2016-07-01

    Sarcoidosis is a granulomatous disease of unknown cause. Prior molecular and immunologic studies have confirmed the presence of mycobacterial virulence factors, such as catalase peroxidase and superoxide dismutase A, within sarcoidosis granulomas. Molecular analysis of granulomas can identify targets of known antibiotics classes. Currently, major antibiotics are directed against DNA synthesis, protein synthesis, and cell wall formation. We conducted molecular analysis of 40 sarcoidosis diagnostic specimens and compared them with 33 disease control specimens for the presence of mycobacterial genes that encode antibiotic targets. We assessed for genes involved in DNA synthesis (DNA gyrase A [gyrA] and DNA gyrase B), protein synthesis (RNA polymerase subunit β), cell wall synthesis (embCAB operon and enoyl reductase), and catalase peroxidase. Immunohistochemical analysis was conducted to investigate the locale of mycobacterial genes such as gyrA within 12 sarcoidosis specimens and 12 disease controls. Mycobacterial DNA was detected in 33 of 39 sarcoidosis specimens by quantitative real-time polymerase chain reaction compared with 2 of 30 disease control specimens (P < 0.001, two-tailed Fisher's test). Twenty of 39 were positive for three or more mycobacterial genes, compared with 1 of 30 control specimens (P < 0.001, two-tailed Fisher's test). Immunohistochemistry analysis localized mycobacterial gyrA nucleic acids to sites of granuloma formation in 9 of 12 sarcoidosis specimens compared with 1 of 12 disease controls (P < 0.01). Microbial genes encoding enzymes that can be targeted by currently available antimycobacterial antibiotics are present in sarcoidosis specimens and localize to sites of granulomatous inflammation. Use of antimicrobials directed against target enzymes may be an innovative treatment alternative. PMID:26807608

  17. Fractal analysis reveals reduced complexity of retinal vessels in CADASIL.

    PubMed

    Cavallari, Michele; Falco, Teresa; Frontali, Marina; Romano, Silvia; Bagnato, Francesca; Orzi, Francesco

    2011-01-01

    The Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) affects mainly small cerebral arteries and leads to disability and dementia. The relationship between clinical expression of the disease and progression of the microvessel pathology is, however, uncertain as we lack tools for imaging brain vessels in vivo. Ophthalmoscopy is regarded as a window into the cerebral microcirculation. In this study we carried out an ophthalmoscopic examination in subjects with CADASIL. Specifically, we performed fractal analysis of digital retinal photographs. Data are expressed as mean fractal dimension (mean-D), a parameter that reflects complexity of the retinal vessel branching. Ten subjects with genetically confirmed diagnosis of CADASIL and 10 sex and age-matched control subjects were enrolled. Fractal analysis of retinal digital images was performed by means of a computer-based program, and the data expressed as mean-D. Brain MRI lesion volume in FLAIR and T1-weighted images was assessed using MIPAV software. Paired t-test was used to disclose differences in mean-D between CADASIL and control groups. Spearman rank analysis was performed to evaluate potential associations between mean-D values and both disease duration and disease severity, the latter expressed as brain MRI lesion volumes, in the subjects with CADASIL. The results showed that mean-D value of patients (1.42±0.05; mean±SD) was lower than control (1.50±0.04; p = 0.002). Mean-D did not correlate with disease duration nor with MRI lesion volumes of the subjects with CADASIL. The findings suggest that fractal analysis is a sensitive tool to assess changes of retinal vessel branching, likely reflecting early brain microvessel alterations, in CADASIL patients. PMID:21556373

  18. Analysis of core damage frequency from internal events: Peach Bottom, Unit 2

    SciTech Connect

    Kolaczkowski, A.M.; Lambright, J.A.; Ferrell, W.L.; Cathey, N.G.; Najafi, B.; Harper, F.T.

    1986-10-01

    This document contains the internal event initiated accident sequence analyses for Peach Bottom, Unit 2; one of the reference plants being examined as part of the NUREG-1150 effort by the Nuclear Regulatory Commission. NUREG-1150 will document the risk of a selected group of nuclear power plants. As part of that work, this report contains the overall core damage frequency estimate for Peach Bottom, Unit 2, and the accompanying plant damage state frequencies. Sensitivity and uncertainty analyses provided additional insights regarding the dominant contributors to the Peach Bottom core damage frequency estimate. The mean core damage frequency at Peach Bottom was calculated to be 8.2E-6. Station blackout type accidents (loss of all ac power) were found to dominate the overall results. Anticipated Transient Without Scram accidents were also found to be non-negligible contributors. The numerical results are largely driven by common mode failure probability estimates and to some extent, human error. Because of significant data and analysis uncertainties in these two areas (important, for instance, to the most dominant scenario in this study), it is recommended that the results of the uncertainty and sensitivity analyses be considered before any actions are taken based on this analysis.

  19. Dipeptidylpeptidase-IV Activity and Expression Reveal Decreased Damage to the Intrahepatic Biliary Tree in Fatty Livers Submitted to Subnormothermic Machine-Perfusion Respect to Conventional Cold Storage

    PubMed Central

    Tarantola, E.; Bertone, V.; Milanesi, G.; Gruppi, C.; Ferrigno, A.; Vairetti, M.; Barni, S.

    2014-01-01

    Graft steatosis is a risk factor for poor initial function after liver transplantation. Biliary complications are frequent even after normal liver transplantation. A subnormothermic machine perfusion (MP20) preservation procedure was developed by our group with high potential for reducing injury to hepatocytes and sinusoidal cells of lean and fatty livers respect to conventional cold storage (CS). We report the response of the biliary tree to CS or MP20, in lean and obese Zucker rat liver. Dipeptidylpeptidase-IV (DPP-IV), crucial for the inactivation of incretins and neuropeptides, was used as a marker. Liver morphology and canalicular network of lean livers were similar after CS/reperfusion or MP20/reperfusion. CS preservation of fatty livers induced serious damage to the parenchyma and to the canalicular activity/ expression of DPP-IV, whereas with MP20 the morphology and canalicular network were similar to those of untreated lean liver. CS and MP20 had similar effects on DPP-IV activity and expression in the upper segments of the intrahepatic biliary tree of fatty livers. DPP-IV expression was significantly increased after MP20 respect to CS or to the controls, both for lean and obese animals. Our data support the superiority of MP20 over CS for preserving fatty livers. Dipeptidylpeptidase-IV activity and expression reveal decreased damage to the intrahepatic biliary tree in fatty livers submitted to subnormothermic machine-perfusion respect to conventional cold storage. PMID:25308846

  20. Decision tree analysis of factors influencing rainfall-related building damage

    NASA Astrophysics Data System (ADS)

    Spekkers, M. H.; Kok, M.; Clemens, F. H. L. R.; ten Veldhuis, J. A. E.

    2014-04-01

    Flood damage prediction models are essential building blocks in flood risk assessments. Little research has been dedicated so far to damage of small-scale urban floods caused by heavy rainfall, while there is a need for reliable damage models for this flood type among insurers and water authorities. The aim of this paper is to investigate a wide range of damage-influencing factors and their relationships with rainfall-related damage, using decision tree analysis. For this, district-aggregated claim data from private property insurance companies in the Netherlands were analysed, for the period of 1998-2011. The databases include claims of water-related damage, for example, damages related to rainwater intrusion through roofs and pluvial flood water entering buildings at ground floor. Response variables being modelled are average claim size and claim frequency, per district per day. The set of predictors include rainfall-related variables derived from weather radar images, topographic variables from a digital terrain model, building-related variables and socioeconomic indicators of households. Analyses were made separately for property and content damage claim data. Results of decision tree analysis show that claim frequency is most strongly associated with maximum hourly rainfall intensity, followed by real estate value, ground floor area, household income, season (property data only), buildings age (property data only), ownership structure (content data only) and fraction of low-rise buildings (content data only). It was not possible to develop statistically acceptable trees for average claim size, which suggest that variability in average claim size is related to explanatory variables that cannot be defined at the district scale. Cross-validation results show that decision trees were able to predict 22-26% of variance in claim frequency, which is considerably better compared to results from global multiple regression models (11-18% of variance explained). Still, a

  1. Tremor patches in Cascadia revealed by seismic array analysis

    NASA Astrophysics Data System (ADS)

    Ghosh, Abhijit; Vidale, John E.; Sweet, Justin R.; Creager, Kenneth C.; Wech, Aaron G.

    2009-09-01

    Episodic tremor and slip (ETS) events in Cascadia have recently been observed, illuminating the general area that radiates seismic energy in the form of non-volcanic tremor (NVT). However, the picture of the ETS zone remains fuzzy because of difficulties in tremor detection and location. To observe the intimate details of tremor, we deployed a dense 84-element small-aperture seismic array on the Olympic Peninsula, Washington, above the tremor migration path. It recorded the main ETS event in May 2008, as well as a weaker tremor episode two months earlier. Using a beamforming technique, we are able to capture and track tremor activity with an unprecedented resolution from southern Puget Sound to the Strait of Juan de Fuca. The array technique reveals up to four times more duration of tremor compared to the conventional envelope cross-correlation method. Our findings suggest that NVT is not uniformly distributed on the subduction interface, and unveils several distinct patches that release much of the tremor moment. The patches appear to be devoid of ordinary earthquakes, and may indicate the heterogeneity in fault strength that affects the modes of stress release within the ETS zone.

  2. Multiple etiologies for Alzheimer disease are revealed by segregation analysis

    SciTech Connect

    Rao, V.S.; Connor-Lacke, L.; Cupplies, L.A.; Growdon, J.H.; Farrer, L.A.; Duijn, C.M. van

    1994-11-01

    We have evaluated several transmission models for Alzheimer disease (AD), using the logistic regressive approach in 401 nuclear families of consecutively ascertained and rigorously diagnosed probands. Models postulating no major gene effect, random environmental transmission, recessive inheritance, and sporadic occurrence were rejected under varied assumptions regarding the associations among sex, age, and major gene susceptibility. Transmission of the disorder was not fully explained by a single Mendelian model for all families. Stratification of families as early- and late-onset by using the median of family mean onset ages showed that, regardless of the model studied, two groups of families fit better than a single group. AD in early-onset families is transmitted as an autosomal dominant trait with full penetrance in both sexes and has a gene frequency of 1.5%. Dominant inheritance also gave the best fit of the data in late-onset families, but this hypothesis was rejected, suggesting the presence of heterogeneity within this subset. Our study also revealed that genetically nonsusceptible males and females develop AD, indicating the presence of phenocopies within early-onset and late-onset groups. Moreover, our results suggest that the higher risk to females is not solely due to their increased longevity. 50 refs., 5 tabs.

  3. Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus

    PubMed Central

    Ray, Ann; Kinch, Lisa N.; de Souza Santos, Marcela; Grishin, Nick V.

    2016-01-01

    ABSTRACT Members of the genus Vibrio include many pathogens of humans and marine animals that share genetic information via horizontal gene transfer. Hence, the Vibrio pan-genome carries the potential to establish new pathogenic strains by sharing virulence determinants, many of which have yet to be characterized. Here, we investigated the virulence properties of Vibrio proteolyticus, a Gram-negative marine bacterium previously identified as part of the Vibrio consortium isolated from diseased corals. We found that V. proteolyticus causes actin cytoskeleton rearrangements followed by cell lysis in HeLa cells in a contact-independent manner. In search of the responsible virulence factor involved, we determined the V. proteolyticus secretome. This proteomics approach revealed various putative virulence factors, including active type VI secretion systems and effectors with virulence toxin domains; however, these type VI secretion systems were not responsible for the observed cytotoxic effects. Further examination of the V. proteolyticus secretome led us to hypothesize and subsequently demonstrate that a secreted hemolysin, belonging to a previously uncharacterized clan of the leukocidin superfamily, was the toxin responsible for the V. proteolyticus-mediated cytotoxicity in both HeLa cells and macrophages. Clearly, there remains an armory of yet-to-be-discovered virulence factors in the Vibrio pan-genome that will undoubtedly provide a wealth of knowledge on how a pathogen can manipulate host cells. PMID:27460800

  4. Proteomics Analysis Reveals Novel RASSF2 Interaction Partners.

    PubMed

    Barnoud, Thibaut; Wilkey, Daniel W; Merchant, Michael L; Clark, Jennifer A; Donninger, Howard

    2016-01-01

    RASSF2 is a tumor suppressor that shares homology with other Ras-association domain (RASSF) family members. It is a powerful pro-apoptotic K-Ras effector that is frequently inactivated in many human tumors. The exact mechanism by which RASSF2 functions is not clearly defined, but it likely acts as a scaffolding protein, modulating the activity of other pro-apoptotic effectors, thereby regulating and integrating tumor suppressor pathways. However, only a limited number of RASSF2 interacting partners have been identified to date. We used a proteomics based approach to identify additional RASSF2 interactions, and thereby gain a better insight into the mechanism of action of RASSF2. We identified several proteins, including C1QBP, Vimentin, Protein phosphatase 1G and Ribonuclease inhibitor that function in diverse biological processes, including protein post-translational modifications, epithelial-mesenchymal transition, cell migration and redox homeostasis, which have not previously been reported to interact with RASSF2. We independently validated two of these novel interactions, C1QBP and Vimentin and found that the interaction with C1QBP was enhanced by K-Ras whereas, interestingly, the Vimentin interaction was reduced by K-Ras. Additionally, RASSF2/K-Ras regulated the acetylation of Vimentin. Our data thus reveal novel mechanisms by which RASSF2 may exert its functions, several of which may be Ras-regulated. PMID:26999212

  5. Proteomics Analysis Reveals Novel RASSF2 Interaction Partners

    PubMed Central

    Barnoud, Thibaut; Wilkey, Daniel W.; Merchant, Michael L.; Clark, Jennifer A.; Donninger, Howard

    2016-01-01

    RASSF2 is a tumor suppressor that shares homology with other Ras-association domain (RASSF) family members. It is a powerful pro-apoptotic K-Ras effector that is frequently inactivated in many human tumors. The exact mechanism by which RASSF2 functions is not clearly defined, but it likely acts as a scaffolding protein, modulating the activity of other pro-apoptotic effectors, thereby regulating and integrating tumor suppressor pathways. However, only a limited number of RASSF2 interacting partners have been identified to date. We used a proteomics based approach to identify additional RASSF2 interactions, and thereby gain a better insight into the mechanism of action of RASSF2. We identified several proteins, including C1QBP, Vimentin, Protein phosphatase 1G and Ribonuclease inhibitor that function in diverse biological processes, including protein post-translational modifications, epithelial-mesenchymal transition, cell migration and redox homeostasis, which have not previously been reported to interact with RASSF2. We independently validated two of these novel interactions, C1QBP and Vimentin and found that the interaction with C1QBP was enhanced by K-Ras whereas, interestingly, the Vimentin interaction was reduced by K-Ras. Additionally, RASSF2/K-Ras regulated the acetylation of Vimentin. Our data thus reveal novel mechanisms by which RASSF2 may exert its functions, several of which may be Ras-regulated. PMID:26999212

  6. Molecular analysis of Baylisascaris columnaris revealed mitochondrial and nuclear polymorphisms

    PubMed Central

    2013-01-01

    Background Baylisascaris species are intestinal nematodes of skunks, raccoons, badgers, and bears belonging to the genus Ascarididae. Oral uptake of embryonated Baylisascaris sp. eggs by a wide variety of mammals and birds can lead to visceral, ocular and neurological larva migrans. B. procyonis, the raccoon roundworm, is known to cause severe illness in intermediate hosts and in humans, whereas the skunk roundworm B. columnaris is probably less pathogenic. Skunks and raccoons are kept as pets in Europe, sometimes together with cats and dogs, living in close contact with humans. B. procyonis and B. columnaris are difficult to differentiate based on morphological criteria and molecular and phylogenetic information concerning B. columnaris is missing. This is the first study on the genetic characterisation of B. columnaris, based on mitochondrial and nuclear molecular markers. Methods B. columnaris worms were isolated from pet skunks, and used for molecular analysis. PCR primers targeted at mitochondrial cytochrome c oxidase 1 and 2 (CO1 and CO2), ribosomal ITS1-5.8S-ITS2 and ribosomal 28S genes were used. DNA sequences from B. columnaris, B. procyonis and B. transfuga from bears were analysed by cluster analysis. Results Four different multi-locus genotypes were found in B. columnaris, based on 14 single nucleotide polymorphisms (SNPs) and two insertions / deletions in CO1, CO2, ITS1-5.8S-ITS2 and 28S. Conclusions The genetic characteristics of B. columnaris show close resemblance to those of B. procyonis, but in contrast to B. procyonis, show several polymorphisms in both mitochondrial and nuclear markers. These polymorphisms could be used as a tool to differentiate B. columnaris from B. procyonis in molecular diagnostic assays, and to identify B. columnaris by PCR, in addition to or replacing morphometric analysis. This might lead to more insight into the zoonotic relevance of B. columnaris in humans. PMID:23627901

  7. Clostridium clariflavum: Key Cellulosome Players Are Revealed by Proteomic Analysis

    PubMed Central

    Artzi, Lior; Morag, Ely; Barak, Yoav; Lamed, Raphael

    2015-01-01

    ABSTRACT Clostridium clariflavum is an anaerobic, cellulosome-forming thermophile, containing in its genome genes for a large number of cellulosomal enzyme and a complex scaffoldin system. Previously, we described the major cohesin-dockerin interactions of the cellulosome components, and on this basis a model of diverse cellulosome assemblies was derived. In this work, we cultivated C. clariflavum on cellobiose-, microcrystalline cellulose-, and switchgrass-containing media and isolated cell-free cellulosome complexes from each culture. Gel filtration separation of the cellulosome samples revealed two major fractions, which were analyzed by label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to identify the key players of the cellulosome assemblies therein. From the 13 scaffoldins present in the C. clariflavum genome, 11 were identified, and a variety of enzymes from different glycoside hydrolase and carbohydrate esterase families were identified, including the glycoside hydrolase families GH48, GH9, GH5, GH30, GH11, and GH10. The expression level of the cellulosomal proteins varied as a function of the carbon source used for cultivation of the bacterium. In addition, the catalytic activity of each cellulosome was examined on different cellulosic substrates, xylan and switchgrass. The cellulosome isolated from the microcrystalline cellulose-containing medium was the most active of all the cellulosomes that were tested. The results suggest that the expression of the cellulosome proteins is regulated by the type of substrate in the growth medium. Moreover, both cell-free and cell-bound cellulosome complexes were produced which together may degrade the substrate in a synergistic manner. These observations are compatible with our previously published model of cellulosome assemblies in this bacterium. PMID:25991683

  8. Large-scale transient sensitivity analysis of a radiation damaged bipolar junction transistor.

    SciTech Connect

    Hoekstra, Robert John; Gay, David M.; Bartlett, Roscoe Ainsworth; Phipps, Eric Todd

    2007-11-01

    Automatic differentiation (AD) is useful in transient sensitivity analysis of a computational simulation of a bipolar junction transistor subject to radiation damage. We used forward-mode AD, implemented in a new Trilinos package called Sacado, to compute analytic derivatives for implicit time integration and forward sensitivity analysis. Sacado addresses element-based simulation codes written in C++ and works well with forward sensitivity analysis as implemented in the Trilinos time-integration package Rythmos. The forward sensitivity calculation is significantly more efficient and robust than finite differencing.

  9. Extensive exometabolome analysis reveals extended overflow metabolism in various microorganisms

    PubMed Central

    2012-01-01

    Overflow metabolism is well known for yeast, bacteria and mammalian cells. It typically occurs under glucose excess conditions and is characterized by excretions of by-products such as ethanol, acetate or lactate. This phenomenon, also denoted the short-term Crabtree effect, has been extensively studied over the past few decades, however, its basic regulatory mechanism and functional role in metabolism is still unknown. Here we present a comprehensive quantitative and time-dependent analysis of the exometabolome of Escherichia coli, Corynebacterium glutamicum, Bacillus licheniformis, and Saccharomyces cerevisiae during well-controlled bioreactor cultivations. Most surprisingly, in all cases a great diversity of central metabolic intermediates and amino acids is found in the culture medium with extracellular concentrations varying in the micromolar range. Different hypotheses for these observations are formulated and experimentally tested. As a result, the intermediates in the culture medium during batch growth must originate from passive or active transportation due to a new phenomenon termed “extended” overflow metabolism. Moreover, we provide broad evidence that this could be a common feature of all microorganism species when cultivated under conditions of carbon excess and non-inhibited carbon uptake. In turn, this finding has consequences for metabolite balancing and, particularly, for intracellular metabolite quantification and 13C-metabolic flux analysis. PMID:22963408

  10. Lipidomic analysis of Toxoplasma gondii reveals unusual polar lipids†

    PubMed Central

    Welti, Ruth; Mui, Ernie; Sparks, Alexis; Wernimont, Sarah; Isaac, Giorgis; Kirisits, Michael; Roth, Mary; Roberts, Craig W.; Botté, Cyrille; Maréchal, Eric; McLeod, Rima

    2008-01-01

    Analysis of the polar lipids of Toxoplasma gondii by electrospray ionization tandem mass spectrometry provides a detailed picture of the lipid molecular species of this parasitic protozoan. Most notably, T. gondii contains a relatively high level, estimated to about 2% of the total polar lipid, of ceramide phosphoethanolamine. The ceramide phosphoethanolamine has a fatty amide profile with only 16- and 18-carbon species. Compared with the host fibroblasts in which it was grown, T. gondii also has higher levels of phosphatidylcholine, but lower levels of sphingomyelin and phosphatidylserine. Analysis at the molecular species level indicated that T. gondii has greater amounts of shorter-chain fatty acid in its polar lipid molecular species than the host fibroblasts. Shorter-chain fatty acids with a combined total of 30 or fewer acyl carbons make up 21% of Toxoplasma’s, but only 3% of the host’s, diacyl phosphatidylcholine. Furthermore, diacyl phosphatidylcholine with two saturated acyl chains with 12, 14, or 16 carbons make up over 11% of parasite phosphatidylcholine, but less than 3% of the host phosphatidylcholine molecular species. The distinctive T. gondii tachyzoite lipid profile may be particularly suited to the function of parasitic membranes and the interaction of the parasite with the host cell and the host’s immune system. Combined with T. gondii genomic data, these lipidomic data will assist in elucidation of metabolic pathways for lipid biosynthesis in this important human pathogen. PMID:17988103

  11. Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes.

    PubMed

    Keerthikumar, Shivakumar; Gangoda, Lahiru; Liem, Michael; Fonseka, Pamali; Atukorala, Ishara; Ozcitti, Cemil; Mechler, Adam; Adda, Christopher G; Ang, Ching-Seng; Mathivanan, Suresh

    2015-06-20

    Extracellular vesicles (EVs) include the exosomes (30-100 nm) that are produced through the endocytic pathway via the multivesicular bodies and the ectosomes (100-1000 nm) that are released through the budding of the plasma membrane. Despite the differences in the mode of biogenesis and size, reliable markers that can distinguish between exosomes and ectosomes are non-existent. Moreover, the precise functional differences between exosomes and ectosomes remains poorly characterised. Here, using label-free quantitative proteomics, we highlight proteins that could be exploited as markers to discriminate between exosomes and ectosomes. For the first time, a global proteogenomics analysis unveiled the secretion of mutant proteins that are implicated in cancer progression through tumor-derived EVs. Follow up integrated bioinformatics analysis highlighted the enrichment of oncogenic cargo in exosomes and ectosomes. Interestingly, exosomes induced significant cell proliferation and migration in recipient cells compared to ectosomes confirming the oncogenic nature of exosomes. These findings ascertain that cancer cells facilitate oncogenesis by the secretion of mutant and oncoproteins into the tumor microenvironment via exosomes and ectosomes. The integrative proteogenomics approach utilized in this study has the potential to identify disease biomarker candidates which can be later assayed in liquid biopsies obtained from cancer patients. PMID:25944692

  12. Network analysis reveals potential markers for pediatric adrenocortical carcinoma

    PubMed Central

    Kulshrestha, Anurag; Suman, Shikha; Ranjan, Rakesh

    2016-01-01

    Pediatric adrenocortical carcinoma (ACC) is a rare malignancy with a poor outcome. Molecular mechanisms of pediatric ACC oncogenesis and advancement are not well understood. Accurate and timely diagnosis of the disease requires identification of new markers for pediatric ACC. Differentially expressed genes (DEGs) were identified from the gene expression profile of pediatric ACC and obtained from Gene Expression Omnibus. Gene Ontology functional and pathway enrichment analysis was implemented to recognize the functions of DEGs. A protein–protein interaction (PPI) and gene–gene functional interaction (GGI) network of DEGs was constructed. Hub gene detection and enrichment analysis of functional modules were performed. Furthermore, a gene regulatory network incorporating DEGs–microRNAs–transcription factors was constructed and analyzed. A total of 431 DEGs including 228 upregulated and 203 downregulated DEGs were screened. These genes were largely involved in cell cycle, steroid biosynthesis, and p53 signaling pathways. Upregulated genes, CDK1, CCNB1, CDC20, and BUB1B, were identified as the common hubs of PPI and GGI networks. All the four common hub genes were also part of modules of the PPI network. Moreover, all the four genes were also present in the largest module of GGI network. A gene regulatory network consisting of 82 microRNAs and 100 transcription factors was also constructed. CDK1, CCNB1, CDC20, and BUB1B may serve as potential biomarker of pediatric ACC and as potential targets for therapeutic approach, although experimental studies are required to authenticate our findings. PMID:27555782

  13. Genomic analysis of regulatory network dynamics reveals large topological changes

    NASA Astrophysics Data System (ADS)

    Luscombe, Nicholas M.; Madan Babu, M.; Yu, Haiyuan; Snyder, Michael; Teichmann, Sarah A.; Gerstein, Mark

    2004-09-01

    Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information and gene-expression data for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. We uncover large changes in underlying network architecture that are unexpected given current viewpoints and random simulations. In response to diverse stimuli, transcription factors alter their interactions to varying degrees, thereby rewiring the network. A few transcription factors serve as permanent hubs, but most act transiently only during certain conditions. By studying sub-network structures, we show that environmental responses facilitate fast signal propagation (for example, with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (for example, with highly inter-connected transcription factors). Indeed, to drive the latter processes forward, phase-specific transcription factors inter-regulate serially, and ubiquitously active transcription factors layer above them in a two-tiered hierarchy. We anticipate that many of the concepts presented here-particularly the large-scale topological changes and hub transience-will apply to other biological networks, including complex sub-systems in higher eukaryotes.

  14. Time-temperature analysis of damage initiation and growth in composite laminates

    SciTech Connect

    Negesh, S.

    1992-01-01

    Polymer-based composites are used in aerospace structures due to their high strength to weight ratio. However polymers also exhibit time-dependent behavior and this behavior may in turn be affected by high temperature and humid environments. Long-term effects manifest themselves in the form of loss of stiffness and/or strength. And, in this regard, the contributing factors could stem from the time-dependent material behavior as well as the accumulation of damages in time. Clearly, generic methodology is needed which addresses the fundamental issues caused by both of the contributing factors. The objective of the present study is to investigate the time-dependent damage initiation and growth behavior associated with the various sublaminate damage modes in polymer-based composites. A quasi-three dimensional finite element procedure is first developed based on the linear theory of viscoelasticity for simulating sublaminate damages in composite laminates. Specifically the unidirectional plies of the laminate are represented by a set of linear anisotropic, viscoelastic constitutive relations. Damage modes in the forms of transverse cracks, delamination of fiber-wise splitting are incorporated in the analysis by means of appropriately evolving local boundary conditions. Calculation of the stress fields and fracture parameters such as the strain energy release rates (G) and the stress intensity factors (K) associated with the different modes of damage and a different stages of evolution are also made a part of the routine. Numerical solutions are obtained by a convolution as well as a quasi-elastic technique. To illustrate the applicability of the numerical routine, the problem of fiber-wise splitting is chosen. Since fiber-wise splitting is a mixed-mode type of failure, an appropriate mixed-mode fracture criterion is needed for predicting its onset and growth.

  15. Time-Frequency Analysis Reveals Pairwise Interactions in Insect Swarms

    NASA Astrophysics Data System (ADS)

    Puckett, James G.; Ni, Rui; Ouellette, Nicholas T.

    2015-06-01

    The macroscopic emergent behavior of social animal groups is a classic example of dynamical self-organization, and is thought to arise from the local interactions between individuals. Determining these interactions from empirical data sets of real animal groups, however, is challenging. Using multicamera imaging and tracking, we studied the motion of individual flying midges in laboratory mating swarms. By performing a time-frequency analysis of the midge trajectories, we show that the midge behavior can be segmented into two distinct modes: one that is independent and composed of low-frequency maneuvers, and one that consists of higher-frequency nearly harmonic oscillations conducted in synchrony with another midge. We characterize these pairwise interactions, and make a hypothesis as to their biological function.

  16. Time-Frequency Analysis Reveals Pairwise Interactions in Insect Swarms.

    PubMed

    Puckett, James G; Ni, Rui; Ouellette, Nicholas T

    2015-06-26

    The macroscopic emergent behavior of social animal groups is a classic example of dynamical self-organization, and is thought to arise from the local interactions between individuals. Determining these interactions from empirical data sets of real animal groups, however, is challenging. Using multicamera imaging and tracking, we studied the motion of individual flying midges in laboratory mating swarms. By performing a time-frequency analysis of the midge trajectories, we show that the midge behavior can be segmented into two distinct modes: one that is independent and composed of low-frequency maneuvers, and one that consists of higher-frequency nearly harmonic oscillations conducted in synchrony with another midge. We characterize these pairwise interactions, and make a hypothesis as to their biological function. PMID:26197145

  17. Genome analysis of the platypus reveals unique signatures of evolution.

    PubMed

    Warren, Wesley C; Hillier, LaDeana W; Marshall Graves, Jennifer A; Birney, Ewan; Ponting, Chris P; Grützner, Frank; Belov, Katherine; Miller, Webb; Clarke, Laura; Chinwalla, Asif T; Yang, Shiaw-Pyng; Heger, Andreas; Locke, Devin P; Miethke, Pat; Waters, Paul D; Veyrunes, Frédéric; Fulton, Lucinda; Fulton, Bob; Graves, Tina; Wallis, John; Puente, Xose S; López-Otín, Carlos; Ordóñez, Gonzalo R; Eichler, Evan E; Chen, Lin; Cheng, Ze; Deakin, Janine E; Alsop, Amber; Thompson, Katherine; Kirby, Patrick; Papenfuss, Anthony T; Wakefield, Matthew J; Olender, Tsviya; Lancet, Doron; Huttley, Gavin A; Smit, Arian F A; Pask, Andrew; Temple-Smith, Peter; Batzer, Mark A; Walker, Jerilyn A; Konkel, Miriam K; Harris, Robert S; Whittington, Camilla M; Wong, Emily S W; Gemmell, Neil J; Buschiazzo, Emmanuel; Vargas Jentzsch, Iris M; Merkel, Angelika; Schmitz, Juergen; Zemann, Anja; Churakov, Gennady; Kriegs, Jan Ole; Brosius, Juergen; Murchison, Elizabeth P; Sachidanandam, Ravi; Smith, Carly; Hannon, Gregory J; Tsend-Ayush, Enkhjargal; McMillan, Daniel; Attenborough, Rosalind; Rens, Willem; Ferguson-Smith, Malcolm; Lefèvre, Christophe M; Sharp, Julie A; Nicholas, Kevin R; Ray, David A; Kube, Michael; Reinhardt, Richard; Pringle, Thomas H; Taylor, James; Jones, Russell C; Nixon, Brett; Dacheux, Jean-Louis; Niwa, Hitoshi; Sekita, Yoko; Huang, Xiaoqiu; Stark, Alexander; Kheradpour, Pouya; Kellis, Manolis; Flicek, Paul; Chen, Yuan; Webber, Caleb; Hardison, Ross; Nelson, Joanne; Hallsworth-Pepin, Kym; Delehaunty, Kim; Markovic, Chris; Minx, Pat; Feng, Yucheng; Kremitzki, Colin; Mitreva, Makedonka; Glasscock, Jarret; Wylie, Todd; Wohldmann, Patricia; Thiru, Prathapan; Nhan, Michael N; Pohl, Craig S; Smith, Scott M; Hou, Shunfeng; Nefedov, Mikhail; de Jong, Pieter J; Renfree, Marilyn B; Mardis, Elaine R; Wilson, Richard K

    2008-05-01

    We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation. PMID:18464734

  18. Genome analysis of the platypus reveals unique signatures of evolution

    PubMed Central

    Warren, Wesley C.; Hillier, LaDeana W.; Marshall Graves, Jennifer A.; Birney, Ewan; Ponting, Chris P.; Grützner, Frank; Belov, Katherine; Miller, Webb; Clarke, Laura; Chinwalla, Asif T.; Yang, Shiaw-Pyng; Heger, Andreas; Locke, Devin P.; Miethke, Pat; Waters, Paul D.; Veyrunes, Frédéric; Fulton, Lucinda; Fulton, Bob; Graves, Tina; Wallis, John; Puente, Xose S.; López-Otín, Carlos; Ordóñez, Gonzalo R.; Eichler, Evan E.; Chen, Lin; Cheng, Ze; Deakin, Janine E.; Alsop, Amber; Thompson, Katherine; Kirby, Patrick; Papenfuss, Anthony T.; Wakefield, Matthew J.; Olender, Tsviya; Lancet, Doron; Huttley, Gavin A.; Smit, Arian F. A.; Pask, Andrew; Temple-Smith, Peter; Batzer, Mark A.; Walker, Jerilyn A.; Konkel, Miriam K.; Harris, Robert S.; Whittington, Camilla M.; Wong, Emily S. W.; Gemmell, Neil J.; Buschiazzo, Emmanuel; Vargas Jentzsch, Iris M.; Merkel, Angelika; Schmitz, Juergen; Zemann, Anja; Churakov, Gennady; Kriegs, Jan Ole; Brosius, Juergen; Murchison, Elizabeth P.; Sachidanandam, Ravi; Smith, Carly; Hannon, Gregory J.; Tsend-Ayush, Enkhjargal; McMillan, Daniel; Attenborough, Rosalind; Rens, Willem; Ferguson-Smith, Malcolm; Lefèvre, Christophe M.; Sharp, Julie A.; Nicholas, Kevin R.; Ray, David A.; Kube, Michael; Reinhardt, Richard; Pringle, Thomas H.; Taylor, James; Jones, Russell C.; Nixon, Brett; Dacheux, Jean-Louis; Niwa, Hitoshi; Sekita, Yoko; Huang, Xiaoqiu; Stark, Alexander; Kheradpour, Pouya; Kellis, Manolis; Flicek, Paul; Chen, Yuan; Webber, Caleb; Hardison, Ross; Nelson, Joanne; Hallsworth-Pepin, Kym; Delehaunty, Kim; Markovic, Chris; Minx, Pat; Feng, Yucheng; Kremitzki, Colin; Mitreva, Makedonka; Glasscock, Jarret; Wylie, Todd; Wohldmann, Patricia; Thiru, Prathapan; Nhan, Michael N.; Pohl, Craig S.; Smith, Scott M.; Hou, Shunfeng; Renfree, Marilyn B.; Mardis, Elaine R.; Wilson, Richard K.

    2009-01-01

    We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation. PMID:18464734

  19. Image analysis of weaverbird nests reveals signature weave textures.

    PubMed

    Bailey, Ida E; Backes, André; Walsh, Patrick T; Morgan, Kate V; Meddle, Simone L; Healy, Susan D

    2015-06-01

    In nature, many animals build structures that can be readily measured at the scale of their gross morphology (e.g. length, volume and weight). Capturing individuality as can be done with the structures designed and built by human architects or artists, however, is more challenging. Here, we tested whether computer-aided image texture classification approaches can be used to describe textural variation in the nests of weaverbirds (Ploceus species) in order to attribute nests to the individual weaverbird that built them. We found that a computer-aided texture analysis approach does allow the assignment of a signature to weaverbirds' nests. We suggest that this approach will be a useful tool with which to examine individual variation across a range of animal constructions, not just for nests. PMID:26543586

  20. Image analysis of weaverbird nests reveals signature weave textures

    PubMed Central

    Bailey, Ida E.; Backes, André; Walsh, Patrick T.; Morgan, Kate V.; Meddle, Simone L.; Healy, Susan D.

    2015-01-01

    In nature, many animals build structures that can be readily measured at the scale of their gross morphology (e.g. length, volume and weight). Capturing individuality as can be done with the structures designed and built by human architects or artists, however, is more challenging. Here, we tested whether computer-aided image texture classification approaches can be used to describe textural variation in the nests of weaverbirds (Ploceus species) in order to attribute nests to the individual weaverbird that built them. We found that a computer-aided texture analysis approach does allow the assignment of a signature to weaverbirds' nests. We suggest that this approach will be a useful tool with which to examine individual variation across a range of animal constructions, not just for nests. PMID:26543586

  1. Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis

    PubMed Central

    Irie, Naoki; Kuratani, Shigeru

    2011-01-01

    One of the central issues in evolutionary developmental biology is how we can formulate the relationships between evolutionary and developmental processes. Two major models have been proposed: the 'funnel-like' model, in which the earliest embryo shows the most conserved morphological pattern, followed by diversifying later stages, and the 'hourglass' model, in which constraints are imposed to conserve organogenesis stages, which is called the phylotypic period. Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent. These results allow us to predict approximate developmental timetables between different species, and indicate that pharyngula embryos have the most conserved gene expression profiles, which may be the source of the basic body plan of vertebrates. PMID:21427719

  2. Integrated analysis considered mitigation cost, damage cost and adaptation cost in Northeast Asia

    NASA Astrophysics Data System (ADS)

    Park, J. H.; Lee, D. K.; Kim, H. G.; Sung, S.; Jung, T. Y.

    2015-12-01

    Various studies show that raising the temperature as well as storms, cold snap, raining and drought caused by climate change. And variety disasters have had a damage to mankind. The world risk report(2012, The Nature Conservancy) and UNU-EHS (the United Nations University Institute for Environment and Human Security) reported that more and more people are exposed to abnormal weather such as floods, drought, earthquakes, typhoons and hurricanes over the world. In particular, the case of Korea, we influenced by various pollutants which are occurred in Northeast Asian countries, China and Japan, due to geographical meteorological characteristics. These contaminants have had a significant impact on air quality with the pollutants generated in Korea. Recently, around the world continued their effort to reduce greenhouse gas and to improve air quality in conjunction with the national or regional development goals priority. China is also working on various efforts in accordance with the international flows to cope with climate change and air pollution. In the future, effect of climate change and air quality in Korea and Northeast Asia will be change greatly according to China's growth and mitigation policies. The purpose of this study is to minimize the damage caused by climate change on the Korean peninsula through an integrated approach taking into account the mitigation and adaptation plan. This study will suggest a climate change strategy at the national level by means of a comprehensive economic analysis of the impacts and mitigation of climate change. In order to quantify the impact and damage cost caused by climate change scenarios in a regional scale, it should be priority variables selected in accordance with impact assessment of climate change. The sectoral impact assessment was carried out on the basis of selected variables and through this, to derive the methodology how to estimate damage cost and adaptation cost. And then, the methodology was applied in Korea

  3. Differential network analysis reveals dysfunctional regulatory networks in gastric carcinogenesis.

    PubMed

    Cao, Mu-Shui; Liu, Bing-Ya; Dai, Wen-Tao; Zhou, Wei-Xin; Li, Yi-Xue; Li, Yuan-Yuan

    2015-01-01

    Gastric Carcinoma is one of the most common cancers in the world. A large number of differentially expressed genes have been identified as being associated with gastric cancer progression, however, little is known about the underlying regulatory mechanisms. To address this problem, we developed a differential networking approach that is characterized by including a nascent methodology, differential coexpression analysis (DCEA), and two novel quantitative methods for differential regulation analysis. We first applied DCEA to a gene expression dataset of gastric normal mucosa, adenoma and carcinoma samples to identify gene interconnection changes during cancer progression, based on which we inferred normal, adenoma, and carcinoma-specific gene regulation networks by using linear regression model. It was observed that cancer genes and drug targets were enriched in each network. To investigate the dynamic changes of gene regulation during carcinogenesis, we then designed two quantitative methods to prioritize differentially regulated genes (DRGs) and gene pairs or links (DRLs) between adjacent stages. It was found that known cancer genes and drug targets are significantly higher ranked. The top 4% normal vs. adenoma DRGs (36 genes) and top 6% adenoma vs. carcinoma DRGs (56 genes) proved to be worthy of further investigation to explore their association with gastric cancer. Out of the 16 DRGs involved in two top-10 DRG lists of normal vs. adenoma and adenoma vs. carcinoma comparisons, 15 have been reported to be gastric cancer or cancer related. Based on our inferred differential networking information and known signaling pathways, we generated testable hypotheses on the roles of GATA6, ESRRG and their signaling pathways in gastric carcinogenesis. Compared with established approaches which build genome-scale GRNs, or sub-networks around differentially expressed genes, the present one proved to be better at enriching cancer genes and drug targets, and prioritizing

  4. Differential network analysis reveals dysfunctional regulatory networks in gastric carcinogenesis

    PubMed Central

    Cao, Mu-Shui; Liu, Bing-Ya; Dai, Wen-Tao; Zhou, Wei-Xin; Li, Yi-Xue; Li, Yuan-Yuan

    2015-01-01

    Gastric Carcinoma is one of the most common cancers in the world. A large number of differentially expressed genes have been identified as being associated with gastric cancer progression, however, little is known about the underlying regulatory mechanisms. To address this problem, we developed a differential networking approach that is characterized by including a nascent methodology, differential coexpression analysis (DCEA), and two novel quantitative methods for differential regulation analysis. We first applied DCEA to a gene expression dataset of gastric normal mucosa, adenoma and carcinoma samples to identify gene interconnection changes during cancer progression, based on which we inferred normal, adenoma, and carcinoma-specific gene regulation networks by using linear regression model. It was observed that cancer genes and drug targets were enriched in each network. To investigate the dynamic changes of gene regulation during carcinogenesis, we then designed two quantitative methods to prioritize differentially regulated genes (DRGs) and gene pairs or links (DRLs) between adjacent stages. It was found that known cancer genes and drug targets are significantly higher ranked. The top 4% normal vs. adenoma DRGs (36 genes) and top 6% adenoma vs. carcinoma DRGs (56 genes) proved to be worthy of further investigation to explore their association with gastric cancer. Out of the 16 DRGs involved in two top-10 DRG lists of normal vs. adenoma and adenoma vs. carcinoma comparisons, 15 have been reported to be gastric cancer or cancer related. Based on our inferred differential networking information and known signaling pathways, we generated testable hypotheses on the roles of GATA6, ESRRG and their signaling pathways in gastric carcinogenesis. Compared with established approaches which build genome-scale GRNs, or sub-networks around differentially expressed genes, the present one proved to be better at enriching cancer genes and drug targets, and prioritizing

  5. Flood damage maps: ranking sources of uncertainty with variance-based sensitivity analysis

    NASA Astrophysics Data System (ADS)

    Saint-Geours, N.; Grelot, F.; Bailly, J.-S.; Lavergne, C.

    2012-04-01

    In order to increase the reliability of flood damage assessment, we need to question the uncertainty associated with the whole flood risk modeling chain. Using a case study on the basin of the Orb River, France, we demonstrate how variance-based sensitivity analysis can be used to quantify uncertainty in flood damage maps at different spatial scales and to identify the sources of uncertainty which should be reduced first. Flood risk mapping is recognized as an effective tool in flood risk management and the elaboration of flood risk maps is now required for all major river basins in the European Union (European directive 2007/60/EC). Flood risk maps can be based on the computation of the Mean Annual Damages indicator (MAD). In this approach, potential damages due to different flood events are estimated for each individual stake over the study area, then averaged over time - using the return period of each flood event - and finally mapped. The issue of uncertainty associated with these flood damage maps should be carefully scrutinized, as they are used to inform the relevant stakeholders or to design flood mitigation measures. Maps of the MAD indicator are based on the combination of hydrological, hydraulic, geographic and economic modeling efforts: as a result, numerous sources of uncertainty arise in their elaboration. Many recent studies describe these various sources of uncertainty (Koivumäki 2010, Bales 2009). Some authors propagate these uncertainties through the flood risk modeling chain and estimate confidence bounds around the resulting flood damage estimates (de Moel 2010). It would now be of great interest to go a step further and to identify which sources of uncertainty account for most of the variability in Mean Annual Damages estimates. We demonstrate the use of variance-based sensitivity analysis to rank sources of uncertainty in flood damage mapping and to quantify their influence on the accuracy of flood damage estimates. We use a quasi

  6. Phylogenetic analysis reveals a scattered distribution of autumn colours

    PubMed Central

    Archetti, Marco

    2009-01-01

    Background and Aims Leaf colour in autumn is rarely considered informative for taxonomy, but there is now growing interest in the evolution of autumn colours and different hypotheses are debated. Research efforts are hindered by the lack of basic information: the phylogenetic distribution of autumn colours. It is not known when and how autumn colours evolved. Methods Data are reported on the autumn colours of 2368 tree species belonging to 400 genera of the temperate regions of the world, and an analysis is made of their phylogenetic relationships in order to reconstruct the evolutionary origin of red and yellow in autumn leaves. Key Results Red autumn colours are present in at least 290 species (70 genera), and evolved independently at least 25 times. Yellow is present independently from red in at least 378 species (97 genera) and evolved at least 28 times. Conclusions The phylogenetic reconstruction suggests that autumn colours have been acquired and lost many times during evolution. This scattered distribution could be explained by hypotheses involving some kind of coevolutionary interaction or by hypotheses that rely on the need for photoprotection. PMID:19126636

  7. Layered Social Network Analysis Reveals Complex Relationships in Kindergarteners.

    PubMed

    Golemiec, Mireille; Schneider, Jonathan; Boyce, W Thomas; Bush, Nicole R; Adler, Nancy; Levine, Joel D

    2016-01-01

    The interplay between individuals forms building blocks for social structure. Here, we examine the structure of behavioral interactions among kindergarten classroom with a hierarchy-neutral approach to examine all possible underlying patterns in the formation of layered networks of "reciprocal" interactions. To understand how these layers are coordinated, we used a layered motif approach. Our dual layered motif analysis can therefore be thought of as the dynamics of smaller groups that tile to create the group structure, or alternatively they provide information on what the average child would do in a given local social environment. When we examine the regulated motifs in layered networks, we find that transitivity is at least partially involved in the formation of these layered network structures. We also found complex combinations of the expected reciprocal interactions. The mechanisms used to understand social networks of kindergarten children here are also applicable on a more general scale to any group of individuals where interactions and identities can be readily observed and scored. PMID:26973572

  8. Layered Social Network Analysis Reveals Complex Relationships in Kindergarteners

    PubMed Central

    Golemiec, Mireille; Schneider, Jonathan; Boyce, W. Thomas; Bush, Nicole R.; Adler, Nancy; Levine, Joel D.

    2016-01-01

    The interplay between individuals forms building blocks for social structure. Here, we examine the structure of behavioral interactions among kindergarten classroom with a hierarchy-neutral approach to examine all possible underlying patterns in the formation of layered networks of “reciprocal” interactions. To understand how these layers are coordinated, we used a layered motif approach. Our dual layered motif analysis can therefore be thought of as the dynamics of smaller groups that tile to create the group structure, or alternatively they provide information on what the average child would do in a given local social environment. When we examine the regulated motifs in layered networks, we find that transitivity is at least partially involved in the formation of these layered network structures. We also found complex combinations of the expected reciprocal interactions. The mechanisms used to understand social networks of kindergarten children here are also applicable on a more general scale to any group of individuals where interactions and identities can be readily observed and scored. PMID:26973572

  9. Bioimage analysis of Shigella infection reveals targeting of colonic crypts.

    PubMed

    Arena, Ellen T; Campbell-Valois, Francois-Xavier; Tinevez, Jean-Yves; Nigro, Giulia; Sachse, Martin; Moya-Nilges, Maryse; Nothelfer, Katharina; Marteyn, Benoit; Shorte, Spencer L; Sansonetti, Philippe J

    2015-06-23

    Few studies within the pathogenic field have used advanced imaging and analytical tools to quantitatively measure pathogenicity in vivo. In this work, we present a novel approach for the investigation of host-pathogen processes based on medium-throughput 3D fluorescence imaging. The guinea pig model for Shigella flexneri invasion of the colonic mucosa was used to monitor the infectious process over time with GFP-expressing S. flexneri. A precise quantitative imaging protocol was devised to follow individual S. flexneri in a large tissue volume. An extensive dataset of confocal images was obtained and processed to extract specific quantitative information regarding the progression of S. flexneri infection in an unbiased and exhaustive manner. Specific parameters included the analysis of S. flexneri positions relative to the epithelial surface, S. flexneri density within the tissue, and volume of tissue destruction. In particular, at early time points, there was a clear association of S. flexneri with crypts, key morphological features of the colonic mucosa. Numerical simulations based on random bacterial entry confirmed the bias of experimentally measured S. flexneri for early crypt targeting. The application of a correlative light and electron microscopy technique adapted for thick tissue samples further confirmed the location of S. flexneri within colonocytes at the mouth of crypts. This quantitative imaging approach is a novel means to examine host-pathogen systems in a tailored and robust manner, inclusive of the infectious agent. PMID:26056271

  10. Bioimage analysis of Shigella infection reveals targeting of colonic crypts

    PubMed Central

    Arena, Ellen T.; Campbell-Valois, Francois-Xavier; Tinevez, Jean-Yves; Nigro, Giulia; Sachse, Martin; Moya-Nilges, Maryse; Nothelfer, Katharina; Marteyn, Benoit; Shorte, Spencer L.; Sansonetti, Philippe J.

    2015-01-01

    Few studies within the pathogenic field have used advanced imaging and analytical tools to quantitatively measure pathogenicity in vivo. In this work, we present a novel approach for the investigation of host–pathogen processes based on medium-throughput 3D fluorescence imaging. The guinea pig model for Shigella flexneri invasion of the colonic mucosa was used to monitor the infectious process over time with GFP-expressing S. flexneri. A precise quantitative imaging protocol was devised to follow individual S. flexneri in a large tissue volume. An extensive dataset of confocal images was obtained and processed to extract specific quantitative information regarding the progression of S. flexneri infection in an unbiased and exhaustive manner. Specific parameters included the analysis of S. flexneri positions relative to the epithelial surface, S. flexneri density within the tissue, and volume of tissue destruction. In particular, at early time points, there was a clear association of S. flexneri with crypts, key morphological features of the colonic mucosa. Numerical simulations based on random bacterial entry confirmed the bias of experimentally measured S. flexneri for early crypt targeting. The application of a correlative light and electron microscopy technique adapted for thick tissue samples further confirmed the location of S. flexneri within colonocytes at the mouth of crypts. This quantitative imaging approach is a novel means to examine host–pathogen systems in a tailored and robust manner, inclusive of the infectious agent. PMID:26056271