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Sample records for internal cellular damage

  1. Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Yasuda, Takeshi [Radiation Emergency Medicine Research Program, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Fujita, Mayumi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Asada, Masahiro [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Meineke, Viktor [Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich (Germany); Imamura, Toru [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan)

    2014-02-01

    Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation with γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can protect the

  2. Programmed cellular response to ionizing radiation damage

    International Nuclear Information System (INIS)

    Crompton, N.E.A.

    1998-01-01

    Three forms of radiation response were investigated to evaluate the hypothesis that cellular radiation response is the result of active molecular signaling and not simply a passive physicochemical process. The decision whether or not a cell should respond to radiation-induced damage either by induction of rescue systems, e.g. mobilization of repair proteins, or induction of suicide mechanisms, e.g. programmed cell death, appears to be the expression of intricate cellular biochemistry. A cell must recognize damage in its genetic material and then activate the appropriate responses. Cell type is important; the response of a fibroblast to radiation damage is both quantitatively and qualitatively different form that of a lymphocyte. The programmed component of radiation response is significant in radiation oncology and predicted to create unique opportunities for enhanced treatment success. (orig.)

  3. Cellular responses to environmental DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    1994-08-01

    This volume contains the proceedings of the conference entitled Cellular Responses to Environmental DNA Damage held in Banff,Alberta December 1--6, 1991. The conference addresses various aspects of DNA repair in sessions titled DNA repair; Basic Mechanisms; Lesions; Systems; Inducible Responses; Mutagenesis; Human Population Response Heterogeneity; Intragenomic DNA Repair Heterogeneity; DNA Repair Gene Cloning; Aging; Human Genetic Disease; and Carcinogenesis. Individual papers are represented as abstracts of about one page in length.

  4. DNA damage and decrease of cellular oxidase activity in piglet ...

    African Journals Online (AJOL)

    DNA damage and decrease of cellular oxidase activity in piglet sertoli cells exposed to gossypol. Ming Zhang, Hui Yuan, Zuping He, Liyun Yuan, Jine Yi, Sijun Deng, Li Zhu, Chengzhi Guo, Yin Lu, Jing Wu, Lixin Wen, Qiang Wei, Liqun Xue ...

  5. Cellular radiosensitivity and DNA damage in primary human fibroblasts

    International Nuclear Information System (INIS)

    Wurm, R.; Burnet, N.G.; Duggal, N.

    1994-01-01

    To evaluate the relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts to decide whether the initial or residual DNA damage levels are more predictive of normal tissue cellular radiosensitivity. Five primary human nonsyndromic and two primary ataxia telangiectasia fibroblast strains grown in monolayer were studied. Cell survival was assessed by clonogenic assay. Irradiation was given at high dose rate (HDR) 1-2 Gy/min. DNA damage was measured in stationary phase cells and expressed as fraction released from the well by pulsed-field gel electrophoresis (PFGE). For initial damage, cells were embedded in agarose and irradiated at HDR on ice. Residual DNA damage was measured in monolayer by allowing a 4-h repair period after HDR irradiation. Following HDR irradiation, cell survival varied between SF 2 0.025 to 0.23. Measurement of initial DNA damage demonstrated linear induction up to 30 Gy, with small differences in the slope of the dose-response curve between strains. No correlation between cell survival and initial damage was found. Residual damage increased linearly up to 80 Gy with a variation in slope by a factor of 3.2. Cell survival correlated with the slope of the dose-response curves for residual damage of the different strains (p = 0.003). The relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts of differing radiosensitivity is closest with the amount of DNA damage remaining after repair. If assays of DNA damage are to be used as predictors of normal tissue response to radiation, residual DNA damage provides the most likely correlation with cell survival. 52 refs., 5 figs., 2 tabs

  6. HSV-I and the cellular DNA damage response.

    Science.gov (United States)

    Smith, Samantha; Weller, Sandra K

    2015-04-01

    Peter Wildy first observed genetic recombination between strains of HSV in 1955. At the time, knowledge of DNA repair mechanisms was limited, and it has only been in the last decade that particular DNA damage response (DDR) pathways have been examined in the context of viral infections. One of the first reports addressing the interaction between a cellular DDR protein and HSV-1 was the observation by Lees-Miller et al . that DNA-dependent protein kinase catalytic subunit levels were depleted in an ICP0-dependent manner during Herpes simplex virus 1 infection. Since then, there have been numerous reports describing the interactions between HSV infection and cellular DDR pathways. Due to space limitations, this review will focus predominantly on the most recent observations regarding how HSV navigates a potentially hostile environment to replicate its genome.

  7. Cellular responses of Saccharomyces cerevisiae to DNA damage

    International Nuclear Information System (INIS)

    Ciesla, Z.; Sledziewska-Gojska, E.; Nowicka, A.; Mieczkowski, P.; Fikus, M.U.; Koprowski, P.

    1998-01-01

    Full text. Several experimental strategies have been used to study responses of S. cerevisiae cells to DNA damage. One approach was based on the isolation of novel genes, the expression of which is induced by lesions in DNA. One of these genes, DIN7, was cloned and partially characterized previously. The product of DIN7 belongs to a large family of proteins involved in DNA repair and mutagenesis. This family includes Rad2, Rad27 and ExoI proteins of S. cerevisiae and their respective human homologues, all of which are endowed with DNA nuclease activity. To study cellular function of Din7 we constructed the pPK3 plasmid carrying DIN7 fused to the GAL1 promoter. Effects of DIN7 overproduction on the phenotypes of wild-type cells and of rad27 and exoI mutants were examined. Overproduction of Din7 does not seem to affect the proficiency of wild-type S. cerevisiae cells in recombination and mutagenesis. Also, overexpression of DIN7 does not suppress the deficiency of the EXOI gene product, the closest homologue of Din7, both in recombination and in controlling the fidelity of DNA replication. Unexpectedly, we found that elevated levels of Din7 result in a very high frequency of mitochondrial rho - mutants. A high frequency of production of rho - mutants wa s also observed in strains defective in the functioning of the Dun1 protein kinase involved in signal transmission in cells exposed to DNA damaging agents. Interestingly, deficiency of Dun1 results also in a significant derepression of the DIN7 gene. Experiments are under way to distinguish whether a high cellular level of Din7 specifically decreases stability of mitochondrial DNA or affects stability of chromosomal DNA as well. Analysis of previously constructed S. cerevisiae strains carrying random geno mic fusions with reporter lacZ gene, allowed us to identify the reading frame YBR173c, on chromosome II as a novel damage inducible gene - DIN8. We have shown that DIN8-lacZ fusion is induced in yeast cells treated

  8. Ultraviolet radiation-mediated damage to cellular DNA

    International Nuclear Information System (INIS)

    Cadet, Jean; Sage, Evelyne; Douki, Thierry

    2005-01-01

    Emphasis is placed in this review article on recent aspects of the photochemistry of cellular DNA in which both the UVB and UVA components of solar radiation are implicated individually or synergistically. Interestingly, further mechanistic insights into the UV-induced formation of DNA photoproducts were gained from the application of new accurate and sensitive chromatographic and enzymic assays aimed at measuring base damage. Thus, each of the twelve possible dimeric photoproducts that are produced at the four main bipyrimidine sites can now be singled out as dinucleoside monophosphates that are enzymatically released from UV-irradiated DNA. This was achieved using a recently developed high-performance liquid chromatography-tandem mass spectrometry assay (HPLC-MS/MS) assay after DNA extraction and appropriate enzymic digestion. Interestingly, a similar photoproduct distribution pattern is observed in both isolated and cellular DNA upon exposure to low doses of either UVC or UVB radiation. This applies more specifically to the DNA of rodent and human cells, the cis-syn cyclobutadithymine being predominant over the two other main photolesions, namely thymine-cytosine pyrimidine (6-4) pyrimidone adduct and the related cyclobutyl dimer. UVA-irradiation was found to generate cyclobutane dimers at TT and to a lower extent at TC sites as a likely result of energy transfer mechanism involving still unknown photoexcited chromophore(s). Oxidative damage to DNA is also induced although less efficiently by UVA-mediated photosensitization processes that mostly involved 1 O 2 together with a smaller contribution of hydroxyl radical-mediated reactions through initially generated superoxide radicals

  9. Cellular Response to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Wong, Michael; Stodieck, Louis; Karouia, Fathi; Wu, Honglu

    2015-01-01

    Outside the protection of the geomagnetic field, astronauts and other living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. Whether spaceflight factors, microgravity in particular, have effects on cellular responses to DNA damage induced by exposure to radiation or cytotoxic chemicals is still unknown, as is their impact on the radiation risks for astronauts and on the mutation rate in microorganisms. Although possible synergistic effects of space radiation and other spaceflight factors have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on cellular responses to DNA damages, human fibroblast cells flown to the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induced DNA damages including double-strand breaks (DSB) similar to the ionizing radiation. Damages in the DNA were measured by the phosphorylation of a histone protein H2AX (g-H2AX), which showed slightly more foci in the cells on ISS than in the ground control. The expression of genes involved in DNA damage response was also analyzed using the PCR array. Although a number of the genes, including CDKN1A and PCNA, were significantly altered in the cells after bleomycin treatment, no significant difference in the expression profile of DNA damage response genes was found between the flight and ground samples. At the time of the bleomycin treatment, the cells on the ISS were found to be proliferating faster than the ground control as measured by the percentage of cells containing positive Ki-67 signals. Our results suggested that the difference in g-H2AX focus counts between flight and ground was due to the faster growth rate of the cells in space, but spaceflight did not affect initial transcriptional responses of the DNA damage response genes to

  10. Ozone effects on radish (Raphanus sativus L. cv. Cherry Belle): morphological and cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Athanassious, R.; Klyne, M.A.; Phan, C.T.

    1978-01-01

    Morphological symptoms of ozone damage were related to cellular alterations. The different degrees of damage reflected by the severity of plasmolysis, membrane destruction and coagulation were shown at different levels of microscopy.

  11. DNA damage induced by radionuclide internal irradiation

    International Nuclear Information System (INIS)

    Cui Fengmei; Zhao Jingyong; Hong Chengjiao; Lao Qinhua; Wang Liuyi; Yang Shuqin

    2004-01-01

    Objective: To study the DNA damage of peripheral blood mononuclear cell (PBMC) in rats exposed to radionuclide internal irradiation. Methods: The radionuclides were injected into the rats and single cell get electrophoresis (SCGE) was performed to detect the length of DNA migration in the rat PBMC. Results: DNA migration in the rat PBMC increased with accumulative dose or dose-rate. It showed good relationship of dose vs. response and of dose-rate vs. response, both relationship could be described as linear models. Conclusion: Radionuclide internal irradiation could cause DNA damage in rat PBMC. (authors)

  12. Liability for nuclear damage. An international perspective

    International Nuclear Information System (INIS)

    Lopuski, J.

    1993-01-01

    The book deals with some of the complex issues of liability and compensation for nuclear damage which have been considered in the course of the work of the IAEA concerning the revision of the Vienna Convention on nuclear liability. It presents, in an orderly way, personal reflections of its author based on this experience gathered in years 1989-1992 when participating in this work. Necessarily it contains in some of its parts references to documents of the IAEA Standing Committee on Nuclear Liability; these documents because of their length could not be reproduced. Consequently these parts may be fully intelligible for those who have not participated in or closely followed in Committee's work. The IAEA work on liability for nuclear damage was initiated in the wake of the impact made on the world's public opinion by the Chernobyl incident and its transboundary effects; issues of international state liability and full compensation have been raised. But humanitarian ideas have quickly been confronted with cold calculations of the cost of financial protection for victims and an open unwillingness of some nuclear states the engage their liability; conflict of interests between nuclear and non-nuclear states has been manifested. After three years of discussion no wide consensus could be reached on some basic issues, such as: relationship between international state and civil liability regimes, structures of international legislation, concept of nuclear damage, limits of compensation, role of public funds or jurisdiction. The author presents his approach to these controversial issues, trying to provide at the same time a theoretical outline for the future international legislation on nuclear liability. (author)

  13. Cellular Responses to Cisplatin-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Alakananda Basu

    2010-01-01

    Full Text Available Cisplatin is one of the most effective anticancer agents widely used in the treatment of solid tumors. It is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis. How cells respond to cisplatin-induced DNA damage plays a critical role in deciding cisplatin sensitivity. Cisplatin-induced DNA damage activates various signaling pathways to prevent or promote cell death. This paper summarizes our current understandings regarding the mechanisms by which cisplatin induces cell death and the bases of cisplatin resistance. We have discussed various steps, including the entry of cisplatin inside cells, DNA repair, drug detoxification, DNA damage response, and regulation of cisplatin-induced apoptosis by protein kinases. An understanding of how various signaling pathways regulate cisplatin-induced cell death should aid in the development of more effective therapeutic strategies for the treatment of cancer.

  14. Reconstitution of the cellular response to DNA damage in vitro using damage-activated extracts from mammalian cells

    International Nuclear Information System (INIS)

    Roper, Katherine; Coverley, Dawn

    2012-01-01

    In proliferating mammalian cells, DNA damage is detected by sensors that elicit a cellular response which arrests the cell cycle and repairs the damage. As part of the DNA damage response, DNA replication is inhibited and, within seconds, histone H2AX is phosphorylated. Here we describe a cell-free system that reconstitutes the cellular response to DNA double strand breaks using damage-activated cell extracts and naïve nuclei. Using this system the effect of damage signalling on nuclei that do not contain DNA lesions can be studied, thereby uncoupling signalling and repair. Soluble extracts from G1/S phase cells that were treated with etoposide before isolation, or pre-incubated with nuclei from etoposide-treated cells during an in vitro activation reaction, restrain both initiation and elongation of DNA replication in naïve nuclei. At the same time, H2AX is phosphorylated in naïve nuclei in a manner that is dependent upon the phosphatidylinositol 3-kinase-like protein kinases. Notably, phosphorylated H2AX is not focal in naïve nuclei, but is evident throughout the nucleus suggesting that in the absence of DNA lesions the signal is not amplified such that discrete foci can be detected. This system offers a novel screening approach for inhibitors of DNA damage response kinases, which we demonstrate using the inhibitors wortmannin and LY294002. -- Highlights: ► A cell free system that reconstitutes the response to DNA damage in the absence of DNA lesions. ► Damage-activated extracts impose the cellular response to DNA damage on naïve nuclei. ► PIKK-dependent response impacts positively and negatively on two separate fluorescent outputs. ► Can be used to screen for inhibitors that impact on the response to damage but not on DNA repair. ► LY294002 and wortmannin demonstrate the system's potential as a pathway focused screening approach.

  15. Sub-cellular damage by copper in the cnidarian Zoanthus robustus.

    Science.gov (United States)

    Grant, A; Trompf, K; Seung, D; Nivison-Smith, L; Bowcock, H; Kresse, H; Holmes, S; Radford, J; Morrow, P

    2010-09-01

    Sessile organisms may experience chronic exposure to copper that is released into the marine environment from antifoulants and stormwater runoff. We have identified the site of damage caused by copper to the symbiotic cnidarian, Zoanthus robustus (Anthozoa, Hexacorallia). External changes to the zoanthids were apparent when compared with controls. The normally flexible bodies contracted and became rigid. Histological examination of the zoanthid tissue revealed that copper had caused sub-cellular changes to proteins within the extracellular matrix (ECM) of the tubular body. Collagen in the ECM and the internal septa increased in thickness to five and seven times that of controls respectively. The epithelium, which stained for elastin, was also twice as thick and tough to cut, but exposure to copper did not change the total amount of desmosine which is found only in elastin. We conclude that copper stimulated collagen synthesis in the ECM and also caused cross-linking of existing proteins. However, there was no expulsion of the symbiotic algae (Symbiodinium sp.) and no effect on algal pigments or respiration (44, 66 and 110 microg Cu L(-1)). A decrease in net photosynthesis was observed only at the highest copper concentration (156 microg Cu L(-1)). These results show that cnidarians may be more susceptible to damage by copper than their symbiotic algae. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  16. 1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling

    Directory of Open Access Journals (Sweden)

    Lars-Oliver Klotz

    2014-09-01

    Full Text Available Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others to cellular and inter-cellular signaling processes are discussed: (i naphthoquinone-induced Nrf2-dependent modulation of gene expression and its potentially beneficial outcome; (ii the modulation of receptor tyrosine kinases, such as the epidermal growth factor receptor by naphthoquinones, resulting in altered gap junctional intercellular communication. Generation of reactive oxygen species and modulation of redox signaling are properties of naphthoquinones that render them interesting leads for the development of novel compounds of potential use in various therapeutic settings.

  17. Radiation-induced DNA damage and cellular lethality

    International Nuclear Information System (INIS)

    Sakai, K.; Okada, S.

    1984-01-01

    Radiation-induced DNA scissions and their repair were investigated in mammalian cells using an alkaline separation method. DNA breaks in mouse L5178Y cells and Chinese hamster V79 cells were grouped into three in terms of their repair profile; fast-reparable breaks (FRBs; T1/2 = 5 min), slow-reparable breaks (SRBs; T1/2 = 70 min) and non-reparable breaks (NRBs). The three types of DNA lesions were studied under conditions where cellular radiosensitivity was modified. The authors obtained the following results: 1. Cell cycle fluctuation: L5178Y showed maximum sensitivity at M and G/sub 1/-S boundary, and minimum sensitivity at G/sub 1/ and late S. Cycle dependency was not found for FRBs or SRBs, but NRBs showed bimodal fluctuation with peaks at M and G/sub 1/-S, and with bottoms at G/sub 1/ and late S. 2. Different sensitivity of L5178Y and V79: L5178Y cells were more sensitive to X-rays (D/sub ο/ = 0.9 Gy) than V79 (D/sub ο/ = 1.8 Gy). The amount of FRBs or SRBs was identical in the two cell lines. However, the amount of NRBs in L5178Y was greater than that in V79. 3. Split dose irradiation: The time interval between two doses resulted in a gradual decrease of NRBs. The time course of the decrease was similar to the split dose recovery in terms of cell death. The parallel relationship between NRBs and cell killing implies that NRBs could play an important role in radiation-induced cell death

  18. Radiation damage on sub-cellular scales: beyond DNA

    International Nuclear Information System (INIS)

    Byrne, H L; McNamara, A L; Domanova, W; Kuncic, Z; Guatelli, S

    2013-01-01

    This study investigates a model cell as a target for low-dose radiation using Monte Carlo simulations. Mono-energetic electrons and photons are used with initial energies between 10 and 50 keV, relevant to out-of-field radiotherapy scenarios where modern treatment modalities expose relatively large amounts of healthy tissue to low-dose radiation, and also to microbeam cell irradiation studies which show the importance of the cytoplasm as a radiation target. The relative proportions of number of ionizations and total energy deposit in the nucleus and cytoplasm are calculated. We show that for a macroscopic dose of no more than 1 Gy only a few hundred ionizations occur in the nucleus volume whereas the number of ionizations in the cytoplasm is over a magnitude larger. We find that the cell geometry can have an appreciable effect on the energy deposit in the cell and can cause a nonlinear increase in energy deposit with cytoplasm density. We also show that changing the nucleus volume has negligible effect on the total energy deposit but alters the relative proportion deposited in the nucleus and cytoplasm; the nucleus volume must increase to approximately the same volume as the cytoplasm before the energy deposit in the nucleus matches that in the cytoplasm. Additionally we find that energy deposited by electrons is generally insensitive to spatial variations in chemical composition, which can be attributed to negligible differences in electron stopping power for cytoplasm and nucleus materials. On the other hand, we find that chemical composition can affect energy deposited by photons due to non-negligible differences in attenuation coefficients. These results are of relevance in considering radiation effects in healthy cells, which tend to have smaller nuclei. Our results further show that the cytoplasm and organelles residing therein can be important targets for low-dose radiation damage in healthy cells and warrant investigation as much as the conventional focus

  19. In vitro studies of cellular response to DNA damage induced by boron neutron capture therapy

    International Nuclear Information System (INIS)

    Perona, M.; Pontiggia, O.; Carpano, M.; Thomasz, L.; Thorp, S.; Pozzi, E.; Simian, M.; Kahl, S.; Juvenal, G.; Pisarev, M.; Dagrosa, A.

    2011-01-01

    The aim of these studies was to evaluate the mechanisms of cellular response to DNA damage induced by BNCT. Thyroid carcinoma cells were incubated with 10 BPA or 10 BOPP and irradiated with thermal neutrons. The surviving fraction, the cell cycle distribution and the expression of p53 and Ku70 were analyzed. Different cellular responses were observed for each irradiated group. The decrease of Ku70 in the neutrons +BOPP group could play a role in the increase of sensitization to radiation.

  20. Scavenging capacity of medicinal plants against free radical-induced cellular damage by radiation and photoactivation

    Energy Technology Data Exchange (ETDEWEB)

    Gadkar, Shalaka [Ruia College, Mumbai (India); Mohan, H [Chemistry Group, Bhabha Atomic Research Centre, Mumbai (India); Kamat, J P [Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai (India)

    2004-01-01

    The scavenging capacity of medicinal plants. Andrographis paniculata (Ap) and Swertia chirata (Sc) was examined against cellular damage, induced by radiation and photo-activation in sub-cellular membranes. The results demonstrated significant radical scavenging capacity of the extracts. The rate constants as evaluated by deoxyribose degradation studies and the pulse radiolysis studies carried in presence of ABTS radical well supported the antioxidant properties of the extracts. (author)

  1. Asymmetric segregation of damaged cellular components in spatially structured multicellular organisms.

    Directory of Open Access Journals (Sweden)

    Charlotte Strandkvist

    Full Text Available The asymmetric distribution of damaged cellular components has been observed in species ranging from fission yeast to humans. To study the potential advantages of damage segregation, we have developed a mathematical model describing ageing mammalian tissue, that is, a multicellular system of somatic cells that do not rejuvenate at cell division. To illustrate the applicability of the model, we specifically consider damage incurred by mutations to mitochondrial DNA, which are thought to be implicated in the mammalian ageing process. We show analytically that the asymmetric distribution of damaged cellular components reduces the overall damage level and increases the longevity of the cell population. Motivated by the experimental reports of damage segregation in human embryonic stem cells, dividing symmetrically with respect to cell-fate, we extend the model to consider spatially structured systems of cells. Imposing spatial structure reduces, but does not eliminate, the advantage of asymmetric division over symmetric division. The results suggest that damage partitioning could be a common strategy for reducing the accumulation of damage in a wider range of cell types than previously thought.

  2. Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

    Science.gov (United States)

    Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

    2011-01-01

    It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

  3. Symposium cellular response to DNA damage the role of poly(ADP-ribose) poly(ADP-ribose) in the cellular response to DNA damage

    International Nuclear Information System (INIS)

    Berger, N.A.

    1985-01-01

    Poly(ADP-ribose) polymerase is a chromatin-bound enzyme which, on activation by DNA strand breaks, catalyzes the successive transfer of ADP-ribose units from NAD to nuclear proteins. Poly(ADP-ribose) synthesis is stimulated by DNA strand breaks, and the polymer may alter the structure and/or function of chromosomal proteins to facilitate the DNA repair process. Inhibitors of Poly(ADP-ribose) polymerase or deficiencies of the substrate, NAD, lead to retardation of the DNA repair process. When DNA strand breaks are extensive or when breaks fail to be repaired, the stimulus for activation of Poly(ADP-ribose) persists and the activated enzyme is capable of totaly consuming cellular pools of NAD. Depletion of NAD and consequent lowering of cellular ATP pools, due to activation of Poly(ADP-ribose) polymerase, may account for rapid cell death before DNA repair takes place and before the genetic effects of DNA damage become manifest

  4. The usefulness of the nuclear cardiology in the cellular implant in patients with severe myocardial damage

    International Nuclear Information System (INIS)

    Omelas A, M.; Arguero S, R.; Garrido G, M.H.; Rodriguez C, A.; Careaga, G.; Castano G, R.; Nambo, M.J.; Pascual P, J.; Ortega R, A.; Gaxiola A, A.; Magana S, J.A.; Estrada A, H.; Equipo de Tecnicos en Medicina Nuclear

    2005-01-01

    The recent therapeutic advances as the cellular implant as well as those different protocols of image acquisition in the field of the Nuclear Cardiology its have allowed that the patient with severe myocardial damage and without some possibility of revascularization is benefited with these advances. Doubtless the Tl-201 par excellence has an important paper for standardize the more appropriate therapeutic behavior for the heart attack patient; reason by this investigation protocol was developed. The objective of the study was to identify the heart attack regions without viable tissue with SPECT in patient with important myocardial damage without some possibility of traditional revascularization; for the 'Stem cell' cellular implantation therapy. The methodology it was carried out by a study of myocardial perfusion in 10 patients with important myocardial damage previous cellular implants, with PICANUC/ SPECT methodology and using a software (Emory Tool Box) for the image processing validated by the University of Emory Atlanta GA; and using as tracer the Tl - 201 to identify the heart attack regions without presence of viable tissue with an analysis model of 17 segments standardized for the left ventricle; qualifying this way the myocardial perfusion in: 0 (normal), 1 (light), 2 (moderate), 3 (severe), 4 (absent) and x (bad technique). The conclusions were that the SPECT study with PICANUC methodology with Tl-201 is safe and effective for the precise localization for the cellular implantation via direct intra myocardial. (Author)

  5. Cellular characterization of compression induced-damage in live biological samples

    Science.gov (United States)

    Bo, Chiara; Balzer, Jens; Hahnel, Mark; Rankin, Sara M.; Brown, Katherine A.; Proud, William G.

    2011-06-01

    Understanding the dysfunctions that high-intensity compression waves induce in human tissues is critical to impact on acute-phase treatments and requires the development of experimental models of traumatic damage in biological samples. In this study we have developed an experimental system to directly assess the impact of dynamic loading conditions on cellular function at the molecular level. Here we present a confinement chamber designed to subject live cell cultures in liquid environment to compression waves in the range of tens of MPa using a split Hopkinson pressure bars system. Recording the loading history and collecting the samples post-impact without external contamination allow the definition of parameters such as pressure and duration of the stimulus that can be related to the cellular damage. The compression experiments are conducted on Mesenchymal Stem Cells from BALB/c mice and the damage analysis are compared to two control groups. Changes in Stem cell viability, phenotype and function are assessed flow cytometry and with in vitro bioassays at two different time points. Identifying the cellular and molecular mechanisms underlying the damage caused by dynamic loading in live biological samples could enable the development of new treatments for traumatic injuries.

  6. Furfural induces reactive oxygen species accumulation and cellular damage in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Slininger Patricia J

    2010-01-01

    Full Text Available Abstract Background Biofuels offer a viable alternative to petroleum-based fuel. However, current methods are not sufficient and the technology required in order to use lignocellulosic biomass as a fermentation substrate faces several challenges. One challenge is the need for a robust fermentative microorganism that can tolerate the inhibitors present during lignocellulosic fermentation. These inhibitors include the furan aldehyde, furfural, which is released as a byproduct of pentose dehydration during the weak acid pretreatment of lignocellulose. In order to survive in the presence of furfural, yeast cells need not only to reduce furfural to the less toxic furan methanol, but also to protect themselves and repair any damage caused by the furfural. Since furfural tolerance in yeast requires a functional pentose phosphate pathway (PPP, and the PPP is associated with reactive oxygen species (ROS tolerance, we decided to investigate whether or not furfural induces ROS and its related cellular damage in yeast. Results We demonstrated that furfural induces the accumulation of ROS in Saccharomyces cerevisiae. In addition, furfural was shown to cause cellular damage that is consistent with ROS accumulation in cells which includes damage to mitochondria and vacuole membranes, the actin cytoskeleton and nuclear chromatin. The furfural-induced damage is less severe when yeast are grown in a furfural concentration (25 mM that allows for eventual growth after an extended lag compared to a concentration of furfural (50 mM that prevents growth. Conclusion These data suggest that when yeast cells encounter the inhibitor furfural, they not only need to reduce furfural into furan methanol but also to protect themselves from the cellular effects of furfural and repair any damage caused. The reduced cellular damage seen at 25 mM furfural compared to 50 mM furfural may be linked to the observation that at 25 mM furfural yeast were able to exit the furfural

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

    Science.gov (United States)

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

    2013-01-01

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

  8. Fructose-1,6-bisphosphatase mediates cellular responses to DNA damage and aging in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Kitanovic, Ana; Woelfl, Stefan

    2006-01-01

    Response to DNA damage, lack of nutrients and other stress conditions is an essential property of living systems. The coordinate response includes DNA damage repair, activation of alternate biochemical pathways, adjustment of cellular proliferation and cell cycle progression as well as drastic measures like cellular suicide which prevents proliferation of severely damaged cells. Investigating the transcriptional response of Saccharomyces cerevisiae to low doses of the alkylating agent methylmethane sulfonate (MMS) we observed induction of genes involved in glucose metabolism. RT-PCR analysis showed that the expression of the key enzyme in gluconeogenesis fructose-1,6-bisphosphatase (FBP1) was clearly up-regulated by MMS in glucose-rich medium. Interestingly, deletion of FBP1 led to reduced sensitivity to MMS, but not to other DNA-damaging agents, such as 4-NQO or phleomycin. Reintroduction of FBP1 in the knockout restored the wild-type phenotype while overexpression increased MMS sensitivity of wild-type, shortened life span and increased induction of RNR2 after treatment with MMS. Deletion of FBP1 reduced production of reactive oxygen species (ROS) in response to MMS treatment and in untreated aged cells, and increased the amount of cells able to propagate and to form colonies, but had no influence on the genotoxic effect of MMS. Our results indicate that FBP1 influences the connection between DNA damage, aging and oxidative stress through either direct signalling or an intricate adaptation in energy metabolism

  9. Fructose-1,6-bisphosphatase mediates cellular responses to DNA damage and aging in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Kitanovic, Ana [Institut fuer Pharmazie und Molekulare Biotechnologie, Ruprecht-Karls-Universitaet Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg (Germany); Woelfl, Stefan [Institut fuer Pharmazie und Molekulare Biotechnologie, Ruprecht-Karls-Universitaet Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg (Germany)]. E-mail: wolfl@uni-hd.de

    2006-02-22

    Response to DNA damage, lack of nutrients and other stress conditions is an essential property of living systems. The coordinate response includes DNA damage repair, activation of alternate biochemical pathways, adjustment of cellular proliferation and cell cycle progression as well as drastic measures like cellular suicide which prevents proliferation of severely damaged cells. Investigating the transcriptional response of Saccharomyces cerevisiae to low doses of the alkylating agent methylmethane sulfonate (MMS) we observed induction of genes involved in glucose metabolism. RT-PCR analysis showed that the expression of the key enzyme in gluconeogenesis fructose-1,6-bisphosphatase (FBP1) was clearly up-regulated by MMS in glucose-rich medium. Interestingly, deletion of FBP1 led to reduced sensitivity to MMS, but not to other DNA-damaging agents, such as 4-NQO or phleomycin. Reintroduction of FBP1 in the knockout restored the wild-type phenotype while overexpression increased MMS sensitivity of wild-type, shortened life span and increased induction of RNR2 after treatment with MMS. Deletion of FBP1 reduced production of reactive oxygen species (ROS) in response to MMS treatment and in untreated aged cells, and increased the amount of cells able to propagate and to form colonies, but had no influence on the genotoxic effect of MMS. Our results indicate that FBP1 influences the connection between DNA damage, aging and oxidative stress through either direct signalling or an intricate adaptation in energy metabolism.0.

  10. Molecular biophysics: detection and characterization of damage in molecular, cellular, and physiological systems

    International Nuclear Information System (INIS)

    Danyluk, S.S.

    1979-01-01

    This section contains summaries of research on the detection and characterization of damage in molecular, cellular, and physiological systems. Projects under investigation in this section include: chemical synthesis of nucleic acid derivatives; structural and conformational properties of biological molecules in solution; crystallographic and chemical studies of immunoglobulin structure; instrument design and development for x-ray and neutron scattering studies of biological molecules; and chromobiology and circadian regulation

  11. Bacterial intoxication evokes cellular senescence with persistent DNA damage and cytokine signalling

    Czech Academy of Sciences Publication Activity Database

    Blažková, Hana; Krejčíková, Kateřina; Moudrý, Pavel; Frisan, T.; Hodný, Zdeněk; Bartek, Jiří

    2009-01-01

    Roč. 14, 1-2 (2009), s. 357-367 ISSN 1582-1838 R&D Projects: GA AV ČR IAA500390501; GA ČR GA204/08/1418; GA ČR GA301/08/0353 Institutional research plan: CEZ:AV0Z50520514 Keywords : cellular senescence * DNA damage response * bacterial toxins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.228, year: 2009

  12. Cellular defense against singlet oxygen-induced oxidative damage by cytosolic NADP+-dependent isocitrate dehydrogenase.

    Science.gov (United States)

    Kim, Sun Yee; Park, Jeen-Woo

    2003-03-01

    Singlet oxygen (1O2) is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules. Recently, we have shown that NADP+-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study, we investigated the role of cytosolic form of NADP+-dependent isocitrate dehydrogenase (IDPc) against singlet oxygen-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to singlet oxygen generated from photoactivated dye, the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against singlet oxygen, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against singlet oxygen-induced oxidative injury.

  13. Participation of ATM in cellular response to DNA damage induced by ionizing radiation

    International Nuclear Information System (INIS)

    Meng Xiangbing; Song Yi; Mao Jianping; Gong Bo; Dong Yan; Liu Bin; Sun Zhixian

    2000-01-01

    Objective: To clone ATM full length cDNA and cDNA fragments containing some functional domains and to identify proteins that interact with ATM and mediate DNA damage signal transduction in cellular response to DNA damage. Methods: ATM cDNA was amplified from MarthomTM-Ready cDNA kit of human leukocytes by LD-PCR. ATM-interacting proteins were screened by yeast two hybrid system. Results: ATM full-length cDNA and cDNA fragments containing PI3K kinase domain, leucine zipper and proline rich region were amplified from human cDNAs. Several candidate clones that interacted with ATM PI3K domain were identified. Conclusion: ATM mediates DNA damage signal transduction by interacting with many proteins

  14. Coupling mechanisms between nucleosome assembly and the cellular response to DNA damage

    International Nuclear Information System (INIS)

    Lautrette, Aurelie

    2006-01-01

    Cells are continuously exposed to genotoxic stresses that induce a variety of DNA lesions. To protect their genome, cells have specific pathways that orchestrate the detection, signaling and repair of DNA damages. This work is dedicated to the characterization of such pathways that couple the DNA damage response to the assembly of chromatin, a complex that protects and regulates DNA accessibility. We have focused our study on two multifunctional proteins: Rad53, a central checkpoint kinase in the cellular response to DNA damage and Asf1, a histone chaperone involved in chromatin assembly. We have characterized in vitro the binding mode of Asf1 with Rad53 and Asfl with histones. This study is associated with the functional analysis of the role of these interactions in vivo in yeast cells. (author) [fr

  15. Quantification and localization of internal pipe damage

    NARCIS (Netherlands)

    Vogelaar, B.B.S.A.; Golombok, M.

    2016-01-01

    Internal pipeline defects are detectable and locatable from guided acoustic wave reflections using sensors mounted on the outer wall of a pipe. We demonstrate pipeline integrity monitoring with only two single acoustic sensors. Multi-mode dispersion imaging of shear displacement shows that the pure

  16. Translational Cellular Research on the International Space Station

    Science.gov (United States)

    Love, John; Cooley, Vic

    2016-01-01

    The emerging field of Translational Research aims to coalesce interdisciplinary findings from basic science for biomedical applications. To complement spaceflight research using human subjects, translational studies can be designed to address aspects of space-related human health risks and help develop countermeasures to prevent or mitigate them, with therapeutical benefits for analogous conditions experienced on Earth. Translational research with cells and model organisms is being conducted onboard the International Space Station (ISS) in connection with various human systems impacted by spaceflight, such as the cardiovascular, musculoskeletal, and immune systems. Examples of recent cell-based translational investigations on the ISS include the following. The JAXA investigation Cell Mechanosensing seeks to identify gravity sensors in skeletal muscle cells to develop muscle atrophy countermeasures by analyzing tension fluctuations in the plasma membrane, which changes the expression of key proteins and genes. Earth applications of this study include therapeutic approaches for some forms of muscular dystrophy, which appear to parallel aspects of muscle wasting in space. Spheroids is an ESA investigation examining the system of endothelial cells lining the inner surface of all blood vessels in terms of vessel formation, cellular proliferation, and programmed cell death, because injury to the endothelium has been implicated as underpinning various cardiovascular and musculoskeletal problems arising during spaceflight. Since endothelial cells are involved in the functional integrity of the vascular wall, this research has applications to Earth diseases such as atherosclerosis, diabetes, and hypertension. The goal of the T-Cell Activation in Aging NASA investigation is to understand human immune system depression in microgravity by identifying gene expression patterns of candidate molecular regulators, which will provide further insight into factors that may play a

  17. Lycopene: An antioxidant and radioprotector against γ-radiation-induced cellular damages in cultured human lymphocytes

    International Nuclear Information System (INIS)

    Srinivasan, M.; Devipriya, N.; Kalpana, K.B.; Menon, Venugopal P.

    2009-01-01

    The present study aimed to evaluate the radioprotective effect of lycopene, a naturally occurring dietary carotenoid on γ-radiation-induced toxicity. The cellular changes were estimated by using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), hydroperoxides (HP), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH). The DNA damage was analyzed by cytokinesis blocked micronucleus assay (CBMN), dicentric aberration (DC) and translocation frequency. The γ-radiation at different doses (1, 2 and 4 Gy) resulted in a significant increase in the number of micronuclei (MN), DC, translocation frequency, TBARS and HP level, whereas the levels of GSH and antioxidant enzymes were significantly decreased when compared with normal control. The maximum damage to lymphocytes was observed at 4 Gy irradiation. Lycopene pretreatment (1, 5 and 10 μg/ml) significantly decreased the frequency of MN, DC and translocation when compared with γ-radiation control. The levels of TBARS, HP were also decreased and activities of SOD, CAT and GPx were significantly increased along with GSH levels when compared with γ-radiation control. The dose of 5 μg/ml of lycopene was found to be more effective than the other two doses. Thus, our result shows that pretreatment with lycopene offers protection to normal lymphocytes against γ-radiation-induced cellular damage.

  18. Initial events in the cellular effects of ionizing radiations: clustered damage in DNA

    International Nuclear Information System (INIS)

    Goodhead, D.T.

    1994-01-01

    Ionizing radiations produce many hundreds of different simple chemical products in DNA and also multitudes of possible clustered combinations. The simple products, including single-strand breaks, tend to correlate poorly with biological effectiveness. Even for initial double-strand breaks, as a broad class, there is apparently little or no increase in yield with increasing ionization density, in contrast with the large rise in relative biological effectiveness for cellular effects. Track structure analysis has revealed that clustered DNA damage of severity greater than simple double-strand breaks is likely to occur at biologically relevant frequencies with all ionizing radiations. Studies are in progress to describe in more detail the chemical nature of these clustered lesions and to consider the implications for cellular repair. (author)

  19. Chemical radiosensitization and quality of cellular damage in bacteria exposed to gamma rays

    International Nuclear Information System (INIS)

    Nair, C.K.K.; Pradhan, D.S.; Sreenivasan, A.

    1976-01-01

    Iodoacetic acid (IAA) and N-ethylmaleimide (NEM) when present during exposure of Streptococcus faecalis cells to gamma radiation enhance radiation-induced lethality under both anoxic and aerated conditions. The changes brought about by this radiosensitization in cellular functions have been studied with a view to elucidating the mechanism responsible for the increased loss of viability. The quality of cellular damage in chemical radiosensitization was investigated by correlating survival and the biosynthetic capacity of an irradiated cell population. The relationship between surviving fraction and extent of incorporation of 3 H-thymidine into DNA was found to be unaffected regardless of whether the sensitizers (IAA or NEM) were present or absent during irradiation under anoxia. However, under the oxic condition of irradiation the survival--DNA-labeling relationship was completely different in the presence and in the absence of the sensitizers

  20. MECHANISMS OF DAMAGING EFFECT OF MANGENESE IN TOXIC CONCENTRATIONS ON CELLULAR AND SUBCELLULAR LEVELS

    Directory of Open Access Journals (Sweden)

    Goncharenko A. V.

    2012-11-01

    Full Text Available Influence of subtoxic concentration of manganese chloride in dose equal to LD 50 on condition of plasmatic membranes (model: erythrocytes and functional activity of cell power (model: the isolated liver mitochondrion of rats was studied. It was established that manganese chloride in fixed concentration caused authentic augmentation of sorption capacity of erythrocytes towards alcian blue, influenced increasing of their spontaneous haemolysis and activation of peroxide oxidation of lipids. In experiment on the isolated mitochondrion it was proved that manganese chloride caused dissociation of an oxidizing phosphorusling and complete inhibition of respiration in concentrations of 3 and 4,5mM. These dependences testify that subtoxic concentration of manganese can damage the cell energy. Thus, this pilot research indicated damaging effect of manganese on cellular (erythrocytes and subcellular (mitochondrion levels which are realized through external functioning of membrane structures and deprived them from restoration.

  1. TRANSBOUNDARY DAMAGE IN THE LIGHT OF INTERNATIONAL ENVIRONMENTAL LAW

    Directory of Open Access Journals (Sweden)

    Oana Maria HANCIU

    2014-05-01

    Full Text Available Some activities that are useful for economic and social development of a State even if are not prohibited by national or international law can cause transboundary damages to other countries. This kind of transboundary damages have given rise to theories of State responsibility and a worldwide demand for increased environmental protection. "Under the principles of international law...no State has the right to use or permit the use of its territory in such a manner as to cause [environmental] injury ... in or to the territory of another or the properties of persons therein, when the case is of serious consequence and the injury is established by clear and convincing evidence." (Stockholm Principle 21 The paper analyses the impact of transboundary damage in the light of international environmental law and the increasing concern among States for environmental protection.

  2. Multiple repair pathways mediate cellular tolerance to resveratrol-induced DNA damage.

    Science.gov (United States)

    Liu, Ying; Wu, Xiaohua; Hu, Xiaoqing; Chen, Ziyuan; Liu, Hao; Takeda, Shunichi; Qing, Yong

    2017-08-01

    Resveratrol (RSV) has been reported to exert health benefits for the prevention and treatment of many diseases, including cancer. The anticancer mechanisms of RSV seem to be complex and may be associated with genotoxic potential. To better understand the genotoxic mechanisms, we used wild-type (WT) and a panel of isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects and molecular mechanisms of cellular tolerance to RSV. Our results showed that RSV induced significant formation of γ-H2AX foci and chromosome aberrations (CAs) in WT cells, suggesting direct DNA damage effects. Comparing the survival of WT with isogenic DNA-repair deficient DT40 cell lines demonstrated that single strand break repair (SSBR) deficient cell lines of Parp1 -/- , base excision repair (BER) deficient cell lines of Polβ -/- , homologous recombination (HR) mutants of Brca1 -/- and Brca2 -/- and translesion DNA synthesis (TLS) mutants of Rev3 -/- and Rad18 -/- were more sensitive to RSV. The sensitivities of cells were associated with enhanced DNA damage comparing the accumulation of γ-H2AX foci and number of CAs of isogenic DNA-repair deficient DT40 cell lines with WT cells. These results clearly demonstrated that RSV-induced DNA damage in DT40 cells, and multiple repair pathways including BER, SSBR, HR and TLS, play critical roles in response to RSV- induced genotoxicity. Copyright © 2017. Published by Elsevier Ltd.

  3. Cellular and molecular mechanisms of cigarette smoke-induced lung damage and prevention by vitamin C

    Directory of Open Access Journals (Sweden)

    Roy Siddhartha

    2008-11-01

    Full Text Available Abstract Background Cigarette smoke-induced cellular and molecular mechanisms of lung injury are not clear. Cigarette smoke is a complex mixture containing long-lived radicals, including p-benzosemiquinone that causes oxidative damage. Earlier we had reported that oxidative protein damage is an initial event in smoke-induced lung injury. Considering that p-benzosemiquinone may be a causative factor of lung injury, we have isolated p-benzosemiquinone and compared its pathophysiological effects with cigarette smoke. Since vitamin C is a strong antioxidant, we have also determined the modulatory effect of vitamin C for preventing the pathophysiological events. Methods Vitamin C-restricted guinea pigs were exposed to cigarette smoke (5 cigarettes/day; 2 puffs/cigarette for 21 days with and without supplementation of 15 mg vitamin C/guinea pig/day. Oxidative damage, apoptosis and lung injury were assessed in vitro, ex vivo in A549 cells as well as in vivo in guinea pigs. Inflammation was measured by neutrophilia in BALF. p-Benzosemiquinone was isolated from freshly prepared aqueous extract of cigarette smoke and characterized by various physico-chemical methods, including mass, NMR and ESR spectroscopy. p-Benzosemiquinone-induced lung damage was examined by intratracheal instillation in guinea pigs. Lung damage was measured by increased air spaces, as evidenced by histology and morphometric analysis. Oxidative protein damage, MMPs, VEGF and VEGFR2 were measured by western blot analysis, and formation of Michael adducts using MALDI-TOF-MS. Apoptosis was evidenced by TUNEL assay, activation of caspase 3, degradation of PARP and increased Bax/Bcl-2 ratio using immunoblot analysis and confocal microscopy. Results Exposure of guinea pigs to cigarette smoke resulted in progressive protein damage, inflammation, apoptosis and lung injury up to 21 days of the experimental period. Administration of 15 mg of vitamin C/guinea pig/day prevented all these

  4. Various irrigation fluids affect postoperative brain edema and cellular damage during experimental neurosurgery in rats.

    Science.gov (United States)

    Doi, Kazuhisa; Kawano, Takeshi; Morioka, Yujiro; Fujita, Yasutaka; Nishimura, Masuhiro

    2006-12-01

    This study was conducted to investigate how various irrigation fluids used during neurosurgical procedures affect the degree of postoperative brain edema and cellular damage during experimental neurosurgery in rats. The cerebral cortex was exposed and incised crosswise with a surgical knife under irrigation with an artificial CSF, lactated Ringer's solution, or normal saline. Four hours after injury, irrigation was stopped and brain tissue samples were obtained from injured and uninjured sites. Specific gravity, cerebrovascular permeability, and TTC staining of the samples were evaluated. Incision and irrigation of the brain were not performed on the control group. At the injured site, specific gravities of the samples in the normal saline group and the lactated Ringer's solution group were significantly lower than the specific gravity in the artificial CSF group. The EB concentration was significantly higher in the lactated Ringer's solution group and relatively high in the normal saline group as compared with the artificial CSF group. TTC staining did not differ significantly between the artificial CSF group and the control group. It was significantly lower in the lactated Ringer's solution group and the normal saline group than in the control group and the artificial CSF group. As compared with normal saline and lactated Ringer's solution, artificial CSF reduced postoperative brain edema, cerebrovascular permeability, and cellular damage in sites injured by experimental neurosurgery in rats.

  5. Fungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway

    Directory of Open Access Journals (Sweden)

    Peter Belenky

    2013-02-01

    Full Text Available Amphotericin, miconazole, and ciclopirox are antifungal agents from three different drug classes that can effectively kill planktonic yeast, yet their complete fungicidal mechanisms are not fully understood. Here, we employ a systems biology approach to identify a common oxidative-damage cellular death pathway triggered by these representative fungicides in Candida albicans and Saccharomyces cerevisiae. This mechanism utilizes a signaling cascade involving the GTPases Ras1 and Ras2 and protein kinase A, and it culminates in death through the production of toxic reactive oxygen species in a tricarboxylic-acid-cycle- and respiratory-chain-dependent manner. We also show that the metabolome of C. albicans is altered by antifungal drug treatment, exhibiting a shift from fermentation to respiration, a jump in the AMP/ATP ratio, and elevated production of sugars; this coincides with elevated mitochondrial activity. Lastly, we demonstrate that DNA damage plays a critical role in antifungal-induced cellular death and that blocking DNA-repair mechanisms potentiates fungicidal activity.

  6. The cellular environment in computer simulations of radiation-induced damage to DNA

    International Nuclear Information System (INIS)

    Moiseenko, V.V.; Hamm, R.N.; Waker, A.J.; Prestwich, W.V.

    1988-01-01

    Radiation-induced DNA single- and double-strand breaks were modeled for 660 keV photon radiation and scavenger capacity mimicking the cellular environment. Atomistic representation of DNA in B form with a first hydration shell was utilized to model direct and indirect damage. Monte Carlo generated electron tracks were used to model energy deposition in matter and to derive initial spatial distributions of species which appear in the medium following radiolysis. Diffusion of species was followed with time, and their reactions with DNA and each other were modeled in an encounter-controlled manner. Three methods to account for hydroxyl radical diffusion in cellular environment were tested: assumed exponential survival, time-limited modeling and modeling of reactions between hydroxyl radicals and scavengers in an encounter-controlled manner. Although the method based on modeling scavenging in an encounter-controlled manner is more precise, it requires substantially more computer resources than either the exponential or time-limiting method. Scavenger concentrations of 0.5 and 0.15 M were considered using exponential and encounter-controlled methods with reaction rate set at 3x10 9 dm 3 mol -1 s-1. Diffusion length and strand break yields, predicted by these two methods for the same scavenger molarity, were different by 20%-30%. The method based on limiting time of chemistry follow-up to 10 -9 s leads to DNA damage and radical diffusion estimates similar to 0.5 M scavenger concentration in the other two methods. The difference observed in predictions made by the methods considered could be tolerated in computer simulations of DNA damage. (author)

  7. The cellular environment in computer simulations of radiation-induced damage to DNA

    International Nuclear Information System (INIS)

    Moiseenko, V.V.; Waker, A.J.; Prestwich, W.V.

    1998-01-01

    Radiation-induced DNA single- and double-strand breaks were modeled for 660 keV photon radiation and scavenger capacity mimicking the cellular environment. Atomistic representation of DNA in B form with a first hydration shell was utilized to model direct and indirect damage. Monte Carlo generated electron tracks were used to model energy deposition in matter and to derive initial spatial distributions of species which appear in the medium following radiolysis. Diffusion of species was followed with time, and their reactions with DNA and each other were modeled in an encounter-controlled manner. Three methods to account for hydroxyl radical diffusion in a cellular environment were tested: assumed exponential survival, time-limited modeling and modeling of reactions between hydroxyl radicals and scavengers in an encounter-controlled manner. Although the method based on modeling scavenging in an encounter-controlled manner is more precise, it requires substantially more computer resources than either the exponential or time-limiting method. Scavenger concentrations of 0.5 and 0.15 M were considered using exponential and encounter-controlled methods with reaction rate set at 3 x 10 9 dm 3 mol -1 s -1 . Diffusion length and strand break yields, predicted by these two methods for the same scavenger molarity, were different by 20%-30%. The method based on limiting time of chemistry follow-up to 10 -9 s leads to DNA damage and radical diffusion estimates similar to 0.5 M scavenger concentration in the other two methods. The difference observed in predictions made by the methods considered could be tolerated in computer simulations of DNA damage. (orig.)

  8. Characterization of non-dimer DNA lesions and cellular damages caused by ultraviolet light

    International Nuclear Information System (INIS)

    Nakao, Kumi

    1989-01-01

    To understand the mechanisms of carcinogenicity and cytotoxicity induced by ultraviolet (UV) light, non-dimer DNA damages produced by near UV light (wave-length: 290∼320 nm) were examined by alkaline elution using Chinese hamster V-79 cells. UV exposure produced a dose-dependent induction of DNA single strand breaks and DNA-protein crosslinks. However, neither of these DNA lesions were repaired within a 24 hr incubation of the cells following UV exposure. Rather the number of these lesions increased. Also, UV exposure inhibited DNA and RNA synthesis. In addition, UV induced both cytotoxicity and chromosomal aberration. Electron spin resornance (ESR) studies showed that the exposure of cells to UV light resulted in the appearance of an ESR signal at -120degC. The roles of glutathione, vitamin E and vitamin B 2 , which were celluar antioxidant, on the induction of cytotoxicity by UV exposure were also examined. Pretreatment with vitamin E reduced the cytotoxicty caused by UV, whereas neither preteatment with vitamin B 2 nor the alteration of cellular gluthaione content affected the cytotoxicity. These results suggest that non-dimer DNA damages, such as DNA single strand breaks and DNA-protein crosslinks play an important role in inducing UV-carcinogenicity and UV-cytotoxicity, and that the mechanisms of these damages may be associated with the generation of free radicals. (author)

  9. UV-B component of sunlight causes measurable damage in field-grown maize (Zea mays L.): developmental and cellular heterogeneity of damage and repair

    International Nuclear Information System (INIS)

    Stapleton, A.E.; Thornber, C.S.; Walbot, V.

    1997-01-01

    Ultraviolet radiation has diverse morphogenetic and damaging effects on plants. The end point of damage is reduced plant growth, but in the short term UV radiation damages specific cellular components. We measured cyclobutane pyrimidine dimers in maize DNA from plants grown in natural solar radiation. Green maize tissues had detectable DNA damage, roots had less damage, and anthers had much more damage than green leaves. This heterogeneity in damage levels may reflect differences in dose received or in damage repair. The architecture of green tissues had no measurable effects on DNA damage levels, as leaf sheath and leaf blade were equivalent. We observed a slight increase in damage levels in plants sampled at the end of the day, but there was no accumulation of damage over the growing season. We measured photoreactivation, and found substantial levels of this light-dependent repair in both the epidermis and inner cell layers of leaves, and in all organelles that contain DNA – the nucleus, chloroplasts and mitochondria. We conclude that maize has efficient mechanisms for photo repair of daily UV-induced DNA damage that prevent accumulation

  10. Purine receptor P2Y_6 mediates cellular response to γ-ray-induced DNA damage

    International Nuclear Information System (INIS)

    Ide, Shunta; Nishimaki, Naoko; Tsukimoto, Mitsutoshi; Kojima, Shuji

    2014-01-01

    We previously showed that nucleotide P2 receptor agonists such as ATP and UTP amplify γ-ray-induced focus formation of phosphorylated histone H2A variant H2AX (γH2AX), which is considered to be an indicator of DNA damage so far, by activating purine P2Y_6 and P2Y_1_2 receptors. Therefore, we hypothesized that these P2 receptors play a role in inducing the repair response to γ-ray-induced DNA damage. In the present study, we tested this idea by using human lung cancer A549 cells. First, reverse-transcription polymerase chain reaction (RT-PCR) showed that P2Y_6 receptor is highly expressed in A549 cells, but P2Y_1_2 receptor is only weakly expressed. Next, colony formation assay revealed that P2Y_6 receptor antagonist MRS2578 markedly reduced the survival rate of γ-ray-exposed A549 cells. The survival rate was also significantly reduced in P2Y_6-knock-down cells, compared with scramble siRNA-transfected cells. Since it has reported that phosphorylation of ERK1/2 after activation of EGFR via P2Y_6 and P2Y_1_2 receptors is involved in the repair response to γ-ray-induced DNA damage, we next examined whether γ-ray-induced phosphorylation of ERK1/2 was also inhibited by MRS2578 in A549 cells. We found that it was. Taken together, these findings indicate that purinergic signaling through P2Y_6 receptor, followed by ERK1/2 activation, promotes the cellular repair response to γ-ray-induced DNA damage. (author)

  11. Dental pulp stem cells promote regeneration of damaged neuron cells on the cellular model of Alzheimer's disease.

    Science.gov (United States)

    Wang, Feixiang; Jia, Yali; Liu, Jiajing; Zhai, Jinglei; Cao, Ning; Yue, Wen; He, Huixia; Pei, Xuetao

    2017-06-01

    Alzheimer's disease (AD) is an incurable neurodegenerative disease and many types of stem cells have been used in AD therapy with some favorable effects. In this study, we investigated the potential therapeutical effects of human dental pulp stem cells (hDPSCs) on AD cellular model which established by okadaic acid (OA)-induced damage to human neuroblastoma cell line, SH-SY5Y, in vitro for 24 h. After confirmed the AD cellular model, the cells were co-culture with hDPSCs by transwell co-culture system till 24 h for treatment. Then the cytomorphology of the hDPSCs-treated cells were found to restore gradually with re-elongation of retracted dendrites. Meanwhile, Cell Counting Kit-8 assay and Hoechst 33258 staining showed that hDPSCs caused significant increase in the viability and decrease in apoptosis of the model cells, respectively. Observation of DiI labeling also exhibited the prolongation dendrites in hDPSCs-treated cells which were obviously different from the retraction dendrites in AD model cells. Furthermore, specific staining of α-tubulin and F-actin demonstrated that the hDPSCs-treated cells had the morphology of restored neurons, with elongated dendrites, densely arranged microfilaments, and thickened microtubular fibrils. In addition, results from western blotting revealed that phosphorylation at Ser 396 of Tau protein was significantly suppressed by adding of hDPSCs. These results indicate that hDPSCs may promote regeneration of damaged neuron cells in vitro model of AD and may serve as a useful cell source for treatment of AD. © 2017 International Federation for Cell Biology.

  12. Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

    Science.gov (United States)

    Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

    1991-01-01

    The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

  13. Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

    International Nuclear Information System (INIS)

    Cucinotta, F.A.; Katz, R.; Wilson, J.W.; Townsend, L.W.; Nealy, J.E.; Shinn, J.L.

    1991-02-01

    The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space

  14. Gymnemagenin-a triterpene saponin prevents γ-radiation induced cellular DNA damage

    International Nuclear Information System (INIS)

    Arunachalam, Kantha Deivi; Arun, Lilly Baptista; Annamalai, Sathesh Kumar; Hari, Shanmugasundaram

    2014-01-01

    Gymnema sylvestre an ethno-medicinally important plant was investigated for its protecting activity against radiation induced DNA damage. The major bioactive component present in Gymnema sylvestre such as gymnemic acid and gymnemagenin a triterpene saponin, were tested for its radioprotective effects against 60 Co irradiation induced DNA damage in fish model using fresh water fish Pangasius sutchi. Fishes subjected to a dose of 133 Gy of gamma radiation and observed for eight days. The genotoxic assessment by micronucleus assay showed us that that the plant extract helped in reducing the frequency of micronucleated and binucleated erythrocytes compared to the irradiated control group. The genotoxic assessment by alkaline comet assay by single gel electrophoresis shows that pretreatment with the plant extract appreciably decreased the percentage of tail DNA towards the levels close to those of normal control group. The gradual increase in the level of the antioxidant enzymes: superoxide dismutase (SOD) and catalase (CAT) during the course of the experiment indicates that the antioxidant enzyme activities play an important role in protecting organisms against gamma radiation-induced cellular oxidative stress. In conclusion the leaf extracts of Gymnema sylvstre exerts its radio protective potential by suppressing the toxic assault of ROS generated by the ionizing radiation through its ability to boost the levels of antioxidant enzymes (CAT and SOD) due to the presence of its phytochemicals like gymnemgenenin- a Triterpene Saponin. (author)

  15. Correlation of binding efficacies of DNA to flavonoids and their induced cellular damage.

    Science.gov (United States)

    Das, Asmita; Majumder, Debashis; Saha, Chabita

    2017-05-01

    Flavonoids are dietary intakes which are bestowed with several health benefits. The most studied property of flavonoids is their antioxidant efficacy. Among the chosen flavonoids Quercetin, Kaempferol and Myricetin is catagorized as flavonols whereas Apigenin and Luteolin belong to the flavone group. In the present study anti-cancer properties of flavonoids are investigated on the basis of their binding efficacy to ct-DNA and their ability to induce cytotoxicity in K562 leukaemic cells. The binding affinities of the flavonoids with calf thymus DNA (ct-DNA) are in the order Quercetin>Myricetin>Luteolin>Kaempferol>Apigenin. Quercetin with fewer OH than myricetin has higher affinity towards DNA suggesting that the number and position of OH influence the binding efficacies of flavonoids to ct-DNA. CD spectra and EtBr displacement studies evidence myricetin and apigenin to be stronger intercalators of DNA compared to quercetin. From comet assay results it is observed that quercetin and myricetin when used in combination induce higher DNA damage in K562 leukemic cells than when tested individually. Higher binding efficacy has been recorded for quercetin to DNA at lower pH, which is the micro environment of cancerous cells, and hence quercetin can act as a potential anti-cancer agent. Presence of Cu also increases cellular damage as recorded by comet assay. Copyright © 2017. Published by Elsevier B.V.

  16. Influence of radiation damage on internal friction background

    International Nuclear Information System (INIS)

    Burbelo, R.M.; Grinik, Eh.U.; Paliokha, M.I.; Orlinskij, A.B.

    1984-01-01

    Influence of radiation damage on internal friction background in samples of polycrystalline nickel and iron irradiated by a fast neutron flux approximately 10 14 neutr/(cm 2 xs) at 350 deg C has been studied using the low-frequency unit of the reverse torsion pendulum type. It has been established experimentally that a high-temperature background of internal friction of iron and nickel samples decreases as accumulating radiation defects occurring under neutron irradiation. Assumptions on a possible mechanism of the effect have been proposed. Simple expression for the background magnitude evaluation has been suggested

  17. 7th International Workshop on Microbeam Probes of Cellular Radiation Response

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, David J.

    2009-07-21

    The extended abstracts that follow present a summary of the Proceedings of the 7th International Workshop: Microbeam Probes of Cellular Radiation Response, held at Columbia University’s Kellogg Center in New York City on March 15–17, 2006. These International Workshops on Microbeam Probes of Cellular Radiation Response have been held regularly since 1993 (1–5). Since the first workshop, there has been a rapid growth (see Fig. 1) in the number of centers developing microbeams for radiobiological research, and worldwide there are currently about 30 microbeams in operation or under development. Single-cell/single-particle microbeam systems can deliver beams of different ionizing radiations with a spatial resolution of a few micrometers down to a few tenths of a micrometer. Microbeams can be used to addressquestions relating to the effects of low doses of radiation (a single radiation track traversing a cell or group of cells), to probe subcellular targets (e.g. nucleus or cytoplasm), and to address questions regarding the propagation of information about DNA damage (for example, the radiation-induced bystander effect). Much of the recent research using microbeams has been to study low-dose effects and ‘‘non-targeted’’ responses such as bystander effects, genomic instability and adaptive responses. This Workshop provided a forum to assess the current state of microbeam technology and current biological applications and to discuss future directions for development, both technological and biological. Over 100 participants reviewed the current state of microbeam research worldwide and reported on new technological developments in the fields of both physics and biology.

  18. Cellular internalization, transcellular transport, and cellular effects of silver nanoparticles in polarized Caco-2 cells following apical or basolateral exposure

    International Nuclear Information System (INIS)

    Imai, Shunji; Morishita, Yuki; Hata, Tomoyuki; Kondoh, Masuo; Yagi, Kiyohito; Gao, Jian-Qing; Nagano, Kazuya; Higashisaka, Kazuma; Yoshioka, Yasuo; Tsutsumi, Yasuo

    2017-01-01

    When considering the safety of ingested nanomaterials, it is important to quantitate their transfer across intestinal cells; however, little information exists about the effects of nanomaterial size or exposure side (apical versus basolateral epithelial surface) on nanomaterial transfer. Here, we examined cellular internalization and transcellular transport, and the effects of nanomaterials on Caco-2 monolayers after apical or basolateral exposure to Ag or Au nanoparticles with various sizes. After apical treatment, both internalization and transfer to the basolateral side of the monolayers were greater for smaller Ag nanoparticles than for larger Ag nanoparticles. In contrast, after basolateral treatment, larger Ag nanoparticles were more internalized than smaller Ag nanoparticles, but the transfer to the apical side was greater for smaller Ag nanoparticles. Au nanoparticles showed different rules of internalization and transcellular transport compared with Ag nanoparticles. Furthermore, the paracellular permeability of the Caco-2 monolayers was temporarily increased by Ag nanoparticles (5 μg/mL; diameters, ≤10 nm) following basolateral but not apical exposure. We conclude that the internalization, transfer, and effects of nanomaterials in epithelial cell monolayers depend on the size and composition of nanomaterials, and the exposure side. - Highlights: • Ag and Au nanoparticles can transfer across Caco-2 monolayers. • Cellular uptake of nanoparticles change between apical and basolateral exposure. • Basolateral Ag nanoparticle exposure increases the permeability of Caco-2 monolayers.

  19. Detection, characterization and measure of a new radiation-induced damage in isolated and cellular DNA

    International Nuclear Information System (INIS)

    Regulus, P.

    2006-10-01

    Deoxyribonucleic acid (DNA) contains the genetic information and chemical injury to this macromolecule may have severe biological consequences. We report here the detection of 4 new radiation-induced DNA lesions by using a high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) approach. For that purpose, the characteristic fragmentation of most 2'-deoxy-ribo nucleosides, the loss of 116 Da corresponding to the loss of the 2-deoxyribose moiety, was used in the so-called neutral loss mode of the HPLC-MS/MS. One of the newly detected lesions, named dCyd341 because it is a 2'-deoxycytidine modification exhibiting a molecular weight of 341 Da, was also detected in cellular DNA. Characterization of this modified nucleoside was performed using NMR and exact mass determination of the product obtained by chemical synthesis. A mechanism of formation was then proposed, in which the first event is the H-abstraction at the C4 position of a 2-deoxyribose moiety. Then, the sugar modification produced exhibits a reactive aldehyde that, through reaction with a vicinal cytosine base, gives rise to dCyd341. dCyd341 could be considered as a complex damage since its formation involves a DNA strand break and a cross-link between a damaged sugar residue and a vicinal cytosine base located most probably on the complementary DNA strand. In addition to its characterization, preliminary biological studies revealed that cells are able to remove the lesion from DNA. Repair studies have revealed the ability of cells to excise the lesion. Identification of the repair systems involved could represent an interesting challenge. (author)

  20. Analysis of core damage frequency: Surry, Unit 1 internal events

    International Nuclear Information System (INIS)

    Bertucio, R.C.; Julius, J.A.; Cramond, W.R.

    1990-04-01

    This document contains the accident sequence analysis of internally initiated events for the Surry Nuclear Station, Unit 1. This is one of the five plant analyses conducted as part of the NUREG-1150 effort by the Nuclear Regulatory Commission. NUREG-1150 documents the risk of a selected group of nuclear power plants. The work performed and described here is an extensive of that published in November 1986 as NUREG/CR-4450, Volume 3. It addresses comments form numerous reviewers and significant changes to the plant systems and procedures made since the first report. The uncertainty analysis and presentation of results are also much improved. The context and detail of this report are directed toward PRA practitioners who need to know how the work was performed and the details for use in further studies. The mean core damage frequency at Surry was calculated to be 4.05-E-5 per year, with a 95% upper bound of 1.34E-4 and 5% lower bound of 6.8E-6 per year. Station blackout type accidents (loss of all AC power) were the largest contributors to the core damage frequency, accounting for approximately 68% of the total. The next type of dominant contributors were Loss of Coolant Accidents (LOCAs). These sequences account for 15% of core damage frequency. No other type of sequence accounts for more than 10% of core damage frequency. 49 refs., 52 figs., 70 tabs

  1. Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Shinotsuka, Takanori; Yasui, Masato; Nuriya, Mutsuo, E-mail: mnuriya@z2.keio.jp

    2014-02-07

    Highlights: • Astrocytes exhibit characteristic changes in [Ca{sup 2+}]{sub i} under OGD. • Astrocytic [Ca{sup 2+}]{sub i} increase is synchronized with a neuronal anoxic depolarization. • Gap junctional couplings protect neurons as well as astrocytes during OGD. - Abstract: Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca{sup 2+}]{sub i}) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca{sup 2+}]{sub i} oscillations followed by larger and sustained [Ca{sup 2+}]{sub i} increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca{sup 2+}]{sub i} increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca{sup 2+}]{sub i} increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca{sup 2+}]{sub i} increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage

  2. Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

    International Nuclear Information System (INIS)

    Shinotsuka, Takanori; Yasui, Masato; Nuriya, Mutsuo

    2014-01-01

    Highlights: • Astrocytes exhibit characteristic changes in [Ca 2+ ] i under OGD. • Astrocytic [Ca 2+ ] i increase is synchronized with a neuronal anoxic depolarization. • Gap junctional couplings protect neurons as well as astrocytes during OGD. - Abstract: Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca 2+ ] i ) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca 2+ ] i oscillations followed by larger and sustained [Ca 2+ ] i increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca 2+ ] i increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca 2+ ] i increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca 2+ ] i increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage during the acute phase of ischemia

  3. Hierarchical Targeting Strategy for Enhanced Tumor Tissue Accumulation/Retention and Cellular Internalization.

    Science.gov (United States)

    Wang, Sheng; Huang, Peng; Chen, Xiaoyuan

    2016-09-01

    Targeted delivery of therapeutic agents is an important way to improve the therapeutic index and reduce side effects. To design nanoparticles for targeted delivery, both enhanced tumor tissue accumulation/retention and enhanced cellular internalization should be considered simultaneously. So far, there have been very few nanoparticles with immutable structures that can achieve this goal efficiently. Hierarchical targeting, a novel targeting strategy based on stimuli responsiveness, shows good potential to enhance both tumor tissue accumulation/retention and cellular internalization. Here, the recent design and development of hierarchical targeting nanoplatforms, based on changeable particle sizes, switchable surface charges and activatable surface ligands, will be introduced. In general, the targeting moieties in these nanoplatforms are not activated during blood circulation for efficient tumor tissue accumulation, but re-activated by certain internal or external stimuli in the tumor microenvironment for enhanced cellular internalization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

    Energy Technology Data Exchange (ETDEWEB)

    Kiran, Shashi; Oddi, Vineesha [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Laboratory of Cancer Cell Biology, Department of Research, Institute of Liver and Biliary Sciences, Delhi 110070 (India)

    2015-02-01

    Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose of doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT

  5. Aluminium-induced excessive ROS causes cellular damage and metabolic shifts in black gram Vigna mungo (L.) Hepper.

    Science.gov (United States)

    Chowra, Umakanta; Yanase, Emiko; Koyama, Hiroyuki; Panda, Sanjib Kumar

    2017-01-01

    Aluminium-induced oxidative damage caused by excessive ROS production was evaluated in black gram pulse crop. Black gram plants were treated with different aluminium (Al 3+ ) concentrations (10, 50 and 100 μM with pH 4.7) and further the effects of Al 3+ were characterised by means of root growth inhibition, histochemical assay, ROS content analysis, protein carbonylation quantification and 1 H-NMR analysis. The results showed that aluminium induces excessive ROS production which leads to cellular damage, root injury, stunt root growth and other metabolic shifts. In black gram, Al 3+ induces cellular damage at the earliest stage of stress which was characterised from histochemical analysis. From this study, it was observed that prolonged stress can activate certain aluminium detoxification defence mechanism. Probably excessive ROS triggers such defence mechanism in black gram. Al 3+ can induce excessive ROS initially in the root region then transported to other parts of the plant. As much as the Al 3+ concentration increases, the rate of cellular injury and ROS production also increases. But after 72 h of stress, plants showed a lowered ROS level and cellular damage which indicates the upregulation of defensive mechanisms. Metabolic shift analysis also showed that the black gram plant under stress has less metabolic content after 24 h of treatment, but gradually, it was increased after 72 h of treatment. It was assumed that ROS played the most important role as a signalling molecule for aluminium stress in black gram.

  6. Cellular and molecular repair of X-ray-induced damage: dependence on oxygen tension and nutritional status

    International Nuclear Information System (INIS)

    Spiro, I.J.; Kennedy, K.A.; Stickler, R.; Ling, C.C.

    1985-01-01

    Cellular and molecular repair was studied at 23 0 C using split-dose recovery and alkaline elution techniques, respectively, as a function of cellular oxygen and nutrient conditions. Hypoxic cells in full medium showed a partial reduction in the level of sublethal damage (SLD) repair relative to aerated cells; the respective repair kinetics were similar with a common repair half-time of 30 min. Similarly, hypoxic cells showed a slight reduction in strand break rejoining capacity compared to aerated cells. Under nutrient deprivation, anoxic cells displayed no SLD repair or strand break repair, while aerated cells exhibited the same level of SLD and strand break repair as for well-fed cells. In addition, nutrient deprived cells at low O 2 levels displayed normal SLD and strand break repair capability. These results indicate that both nutrient and O 2 deprivation are necessary for complete inhibition of cellular and molecular repair, and low levels of O 2 can effectively reverse this inhibition

  7. Probing the cellular damage in bacteria induced by GaN nanoparticles using confocal laser Raman spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Sahoo, Prasana, E-mail: prasanasahoo@gmail.com [Indira Gandhi Center for Atomic Research, Surface and Nanoscience Division (India); Murthy, P. Sriyutha [Bhabha Atomic Research Centre, Biofouling and Biofilm Processes Section, Water and Steam Chemistry Division (India); Dhara, S., E-mail: dhara@igcar.gov.in [Indira Gandhi Center for Atomic Research, Surface and Nanoscience Division (India); Venugopalan, V. P. [Bhabha Atomic Research Centre, Biofouling and Biofilm Processes Section, Water and Steam Chemistry Division (India); Das, A.; Tyagi, A. K. [Indira Gandhi Center for Atomic Research, Surface and Nanoscience Division (India)

    2013-08-15

    Understanding the mechanism of nanoparticle (NP) induced toxicity in microbes is of potential importance to a variety of disciplines including disease diagnostics, biomedical implants, and environmental analysis. In this context, toxicity to bacterial cells and inhibition of biofilm formation by GaN NPs and their functional derivatives have been investigated against gram positive and gram negative bacterial species down to single cellular level. High levels of inhibition of biofilm formation (>80 %) was observed on treatments with GaN NPs at sub-micro molar concentrations. These results were substantiated with morphological features investigated with field emission scanning electron microscope, and the observed changes in vibrational modes of microbial cells using Raman spectroscopy. Raman spectra provided molecular interpretation of cell damage by registering signatures of molecular vibrations of individual living microbial cells and mapping the interplay of proteins at the cell membrane. As compared to the untreated cells, Raman spectra of NP-treated cells showed an increase in the intensities of characteristic protein bands, which confirmed membrane damage and subsequent release of cellular contents outside the cells. Raman spectral mapping at single cellular level can facilitate understanding of the mechanistic aspect of toxicity of GaN NPs. The effect may be correlated to passive diffusion causing mechanical damage to the membrane or ingress of Ga{sup 3+} (ionic radius {approx}0.076 nm) which can potentially interfere with bacterial metabolism, as it resembles Fe{sup 2+} (ionic radius {approx}0.077 nm), which is essential for energy metabolism.

  8. Probing the cellular damage in bacteria induced by GaN nanoparticles using confocal laser Raman spectroscopy

    International Nuclear Information System (INIS)

    Sahoo, Prasana; Murthy, P. Sriyutha; Dhara, S.; Venugopalan, V. P.; Das, A.; Tyagi, A. K.

    2013-01-01

    Understanding the mechanism of nanoparticle (NP) induced toxicity in microbes is of potential importance to a variety of disciplines including disease diagnostics, biomedical implants, and environmental analysis. In this context, toxicity to bacterial cells and inhibition of biofilm formation by GaN NPs and their functional derivatives have been investigated against gram positive and gram negative bacterial species down to single cellular level. High levels of inhibition of biofilm formation (>80 %) was observed on treatments with GaN NPs at sub-micro molar concentrations. These results were substantiated with morphological features investigated with field emission scanning electron microscope, and the observed changes in vibrational modes of microbial cells using Raman spectroscopy. Raman spectra provided molecular interpretation of cell damage by registering signatures of molecular vibrations of individual living microbial cells and mapping the interplay of proteins at the cell membrane. As compared to the untreated cells, Raman spectra of NP-treated cells showed an increase in the intensities of characteristic protein bands, which confirmed membrane damage and subsequent release of cellular contents outside the cells. Raman spectral mapping at single cellular level can facilitate understanding of the mechanistic aspect of toxicity of GaN NPs. The effect may be correlated to passive diffusion causing mechanical damage to the membrane or ingress of Ga 3+ (ionic radius ∼0.076 nm) which can potentially interfere with bacterial metabolism, as it resembles Fe 2+ (ionic radius ∼0.077 nm), which is essential for energy metabolism

  9. Adhesion and internalization differences of COM nanocrystals on Vero cells before and after cell damage

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Qiong-Zhi; Sun, Xin-Yuan; Ouyang, Jian-Ming, E-mail: toyjm@jnu.edu.cn

    2016-02-01

    The adhesion and internalization between African green monkey kidney epithelial (Vero) cells (before and after oxidative damage by hydrogen peroxide) and calcium oxalate monohydrate (COM) nanocrystals (97 ± 35 nm) were investigated so as to discuss the molecular and cellular mechanism of kidney stone formation. Scanning electron microscope (SEM) was used to observe the Vero–COM nanocrystal adhesion; the nanocrystal-cell adhesion was evaluated by measuring the content of malonaldehyde (MDA), the activity of superoxide dismutase (SOD), the expression level of cell surface osteopontin (OPN) and the change of Zeta potential. Confocal microscopy and flow cytometry were used for the observation and quantitative analysis of crystal internalization. In the process of adhesion, the cell viability and the SOD activity declined, the MDA content, Zeta potential, and the OPN expression level increased. The adhesive capacity of injured Vero was obviously stronger than normal cells; in addition the injured cells promoted the aggregation of COM nanocrystals. The capacity of normal cells to internalize crystals was obviously stronger than that of injured cells. Cell injury increased adhesive sites on cell surface, thereby facilitating the aggregation of COM nanocrystals and their attachment, which results in enhanced risk of calcium oxalate stone formation. - Graphical abstract: The adhesion and internalization differences between Vero cells before and after oxidative damage and calcium oxalate monohydrate nanocrystals were comparatively studied. - Highlights: • Adhesion capacity of injured Vero cells was stronger than normal cells. • Internalization capacity of injured Vero cells was weaker than normal cells. • Injured cells promoted the aggregation of COM nanocrystals. • COM adhesion could aggravate cell injury in both normal and injured cells.

  10. Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures

    Directory of Open Access Journals (Sweden)

    Murugan K

    2015-03-01

    Full Text Available Karmani Murugan, Yahya E Choonara, Pradeep Kumar, Divya Bijukumar, Lisa C du Toit, Viness Pillay Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Abstract: Cellular internalization and trans-barrier transport of nanoparticles can be manipulated on the basis of the physicochemical and mechanical characteristics of nanoparticles. Research has shown that these factors significantly influence the uptake of nanoparticles. Dictating these characteristics allows for the control of the rate and extent of cellular uptake, as well as delivering the drug-loaded nanosystem intra-cellularly, which is imperative for drugs that require a specific cellular level to exert their effects. Additionally, physicochemical characteristics of the nanoparticles should be optimal for the nanosystem to bypass the natural restricting phenomena of the body and act therapeutically at the targeted site. The factors at the focal point of emerging smart nanomedicines include nanoparticle size, surface charge, shape, hydrophobicity, surface chemistry, and even protein and ligand conjugates. Hence, this review discusses the mechanism of internalization of nanoparticles and ideal nanoparticle characteristics that allow them to evade the biological barriers in order to achieve optimal cellular uptake in different organ systems. Identifying these parameters assists with the progression of nanomedicine as an outstanding vector of pharmaceuticals. Keywords: nanoparticles, transport mechanisms, cellular uptake, size, shape, charge

  11. DNA damage and cellular death in oral mucosa cells of children who have undergone panoramic dental radiography

    International Nuclear Information System (INIS)

    Angelieri, Fernanda; Oliveira, Gabriela R. de; Sannomiya, Eduardo K.; Ribeiro, Daniel A.

    2007-01-01

    Despite wide use as a diagnostic tool in medical and dental practice, radiography can induce cytotoxic effects and genetic damage. To evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated buccal mucosa cells taken from healthy children following exposure to radiation during dental radiography. A total of 17 children who had undergone panoramic dental radiography were included. We found no statistically significant differences (P > 0.05) between micronucleated oral mucosa cells in children before and after exposure to radiation. On the other hand, radiation did cause other nuclear alterations closely related to cytotoxicity including karyorrhexis, pyknosis and karyolysis. Taken together, these results indicate that panoramic dental radiography might not induce chromosomal damage, but may be cytotoxic. Overall, the results reinforce the importance of evaluating the health side effects of radiography and contribute to the micronucleus database, which will improve our understanding and practice of this methodology in children. (orig.)

  12. DNA damage and cellular death in oral mucosa cells of children who have undergone panoramic dental radiography

    Energy Technology Data Exchange (ETDEWEB)

    Angelieri, Fernanda; Oliveira, Gabriela R. de [Sao Paulo Metodista University (UMESP), Department of Orthodontics, Sao Bernardo do Campo, Sao Paulo (Brazil); Sannomiya, Eduardo K. [Sao Paulo Metodista University (UMESP), Department of Dento-Maxillofacial Radiology, Sao Bernardo do Campo, Sao Paulo (Brazil); Ribeiro, Daniel A. [Federal University of Sao Paulo (UNIFESP), Department of Health Sciences, Santos, Sao Paulo (Brazil); Universidade Federal de Sao Paulo (UNIFESP), Departamento de Ciencias da Saude, Santos, Sao Paulo (Brazil)

    2007-06-15

    Despite wide use as a diagnostic tool in medical and dental practice, radiography can induce cytotoxic effects and genetic damage. To evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated buccal mucosa cells taken from healthy children following exposure to radiation during dental radiography. A total of 17 children who had undergone panoramic dental radiography were included. We found no statistically significant differences (P > 0.05) between micronucleated oral mucosa cells in children before and after exposure to radiation. On the other hand, radiation did cause other nuclear alterations closely related to cytotoxicity including karyorrhexis, pyknosis and karyolysis. Taken together, these results indicate that panoramic dental radiography might not induce chromosomal damage, but may be cytotoxic. Overall, the results reinforce the importance of evaluating the health side effects of radiography and contribute to the micronucleus database, which will improve our understanding and practice of this methodology in children. (orig.)

  13. Studies of cellular damage induced by X-rays and visible light

    International Nuclear Information System (INIS)

    Christensen, T.; Kinn, G.; Reitan, J.B.

    1989-01-01

    DNA-damage in cells has been studied by use of spectrophotometry and fluorometry. The method is based on the differential fluorescence quantum yield of the fluorochrome Hoechst 33258 when bound to single and double stranded DNA, respectively. DNA-damage by doses of X-rays below 2 Gy was clearly detectable. Blue light from phototherapy lamps induced DNA-damage in human TMG-1 glioblastoma, but no significant effect could be observed after irradiation with green lamps. In the presence of bilirubin the amount of DNA-damage was increased, notably at high bilirubin concentration and by blue light. 9 refs; 12 figs

  14. Tissue repair in myxobacteria: A cooperative strategy to heal cellular damage.

    Science.gov (United States)

    Vassallo, Christopher N; Wall, Daniel

    2016-04-01

    Damage repair is a fundamental requirement of all life as organisms find themselves in challenging and fluctuating environments. In particular, damage to the barrier between an organism and its environment (e.g. skin, plasma membrane, bacterial cell envelope) is frequent because these organs/organelles directly interact with the external world. Here, we discuss the general strategies that bacteria use to cope with damage to their cell envelope and their repair limits. We then describe a novel damage-coping mechanism used by multicellular myxobacteria. We propose that cell-cell transfer of membrane material within a population serves as a wound-healing strategy and provide evidence for its utility. We suggest that--similar to how tissues in eukaryotes have evolved cooperative methods of damage repair--so too have some bacteria that live a multicellular lifestyle. © 2016 WILEY Periodicals, Inc.

  15. Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

    International Nuclear Information System (INIS)

    Renis, M.; Malfa, G.; Tomasello, B.; Borghesi, M.; Schettino, G.; Favetta, M.; Romano, F.; Cirrone, G. A. P.; Manti, L.

    2013-01-01

    Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/μm on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately

  16. Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

    Energy Technology Data Exchange (ETDEWEB)

    Renis, M.; Malfa, G.; Tomasello, B. [Drug Sciences Department, University of Catania, Catania (Italy); Borghesi, M.; Schettino, G. [Queen' s University Belfast, Northern Ireland (United Kingdom); Favetta, M.; Romano, F.; Cirrone, G. A. P. [National Institute for Nuclear Physics (INFN-LNS), Catania (Italy); Manti, L. [Physics Science Department, University of Naples Federico II, Naples, and National Institute for Nuclear Physics (INFN), Naples (Italy)

    2013-07-26

    Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/μm on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately

  17. Selected materials of the international workshop on radiation risk and its origin at molecular and cellular level

    International Nuclear Information System (INIS)

    Pinak, Miroslav

    2003-11-01

    The workshop ''International Workshop on Radiation Risk and its Origin at Molecular and Cellular Level'' was held at The Tokai Research Establishment, Japan Atomic Energy Research Institute, on the 6th and 7th of February 2003. The Laboratory of Radiation Risk Analysis of JAERI organized it. This international workshop attracted scientists from several different scientific areas, including radiation physics, radiation biology, molecular biology, crystallography of biomolecules, modeling and bio-informatics. Several foreign and domestic keynote speakers addresses the very fundamental areas of radiation risk and tried to establish a link between the fundamental studies at the molecular and cellular level and radiation damages at the organism. The symposium consisted of 13 oral lectures, 10 poster presentations and panel discussion. The 108 participants attended the workshop. This publication comprises of proceedings of oral and poster presentations where available. For the rest of contributions the abstracts or/and selections of presentation materials are shown instead. The 5 papers are indexed individually. (J.P.N.)

  18. Retinal Damage Induced by Internal Limiting Membrane Removal

    Directory of Open Access Journals (Sweden)

    Rachel Gelman

    2015-01-01

    Full Text Available The internal limiting membrane (ILM, the basement membrane of the Müller cells, serves as the interface between the vitreous body and the retinal nerve fiber layer. It has a fundamental role in the development, structure, and function of the retina, although it also is a pathologic component in the various vitreoretinal disorders, most notably in macular holes. It was not until understanding of the evolution of idiopathic macular holes and the advent of idiopathic macular hole surgery that the idea of adjuvant ILM peeling in the treatment of tractional maculopathies was explored. Today intentional ILM peeling is a commonly applied surgical technique among vitreoretinal surgeons as it has been found to increase the rate of successful macular hole closure and improve surgical outcomes in other vitreoretinal diseases. Though ILM peeling has refined surgery for tractional maculopathies, like all surgical procedures it is not immune to perioperative risk. The essential role of the ILM to the integrity of the retina and risk of trauma to retinal tissue spurs suspicion with regard to its routine removal. Several authors have investigated the retinal damage induced by ILM peeling and these complications have been manifested across many different diagnostic studies.

  19. Quantitative measurement of ultraviolet-induced damage in cellular DNA by an enzyme immunodot assay

    International Nuclear Information System (INIS)

    Wakizaka, A.; Nishizawa, Y.; Aiba, N.; Okuhara, E.; Takahashi, S.

    1989-01-01

    A simple enzyme immunoassay procedure was developed for the quantitative determination of 254-nm uv-induced DNA damage in cells. With the use of specific antibodies to uv-irradiated DNA and horseradish peroxidase-conjugated antibody to rabbit IgG, the extent of damaged DNA in uv-irradiated rat spleen mononuclear cells was quantitatively measurable. Through the use of this method, the amount of damaged DNA present in 2 X 10(5) cells irradiated at a dose of 75 J/m2 was estimated to be 7 ng equivalents of the standard uv-irradiated DNA. In addition, when the cells, irradiated at 750 J/m2, were incubated for 1 h, the antigenic activity of DNA decreased by 40%, suggesting that a repair of the damaged sites in DNA had proceeded to some extent in the cells

  20. Bacterial Intoxication Evokes Cellular Senescence with Persistent DNA Damage and Cytokine Signaling

    DEFF Research Database (Denmark)

    Blazkova, Hana; Krejcikova, Katerina; Moudry, Pavel

    2009-01-01

    to such intoxication are mechanistically incompletely understood. Here we show that both normal and cancer cells (BJ, IMR-90 and WI-38 fibroblasts, HeLa and U2-OS cell lines) that survive the acute phase of intoxication by Haemophilus ducreyi CDT possess the hallmarks of cellular senescence. This characteristic...... mechanistically underlie the 'distended' morphology evoked by CDTs. Finally, the activation of the two anti-cancer barriers, apoptosis and cellular senescence, together with evidence of chromosomal aberrations (micronucleation) reported here, support the emerging genotoxic and potentially oncogenic effects...

  1. Cellular response to DNA damage. Link between p53 and DNA-PK

    International Nuclear Information System (INIS)

    Salles-Passador, I.; Fotedar, R.; Fotedar, A.

    1999-01-01

    Cells which lack DNA-activated protein kinase (DNA-PK) are very susceptible to ionizing radiation and display an inability to repair double-strand DNA breaks. DNA-PK is a member of a protein kinase family that includes ATR and ATM which have strong homology in their carboxy-terminal kinase domain with Pl-3 kinase. ATM has been proposed to act upstream of p53 in cellular response to ionizing radiation. DNA-PK may similarly interact with p53 in cellular growth control and in mediation of the response to ionizing radiation. (author)

  2. Public international law and civil law liability for compensation for damages by virtue of international environmental law

    International Nuclear Information System (INIS)

    Rest, A.

    1982-01-01

    The author analyses the current provisions in international law and international private law for their suitability to establish liability for damages due to transfrontier pollution, also taking into account damage occurred through the operation of nuclear power plants. As a result the author suggests that the national goverments should jointly set up standards and catalogues of environmentally detrimental effects and impacts, and of the seriousness thereof, and to make these form part of international conventions and agreements which also should unambigiously state liability for compensation for damages. For activities involving special hazards, liability for risks should be introduced in such a body of international regulations. (CB) [de

  3. Cellular irradiation during phase S: a study of induced chromosomic damage and its transmission

    International Nuclear Information System (INIS)

    Antoine, J.L.

    1986-01-01

    The author examines the effects of ionizing radiation on the chromosomes during phase S (synthesis) in which DNA progressively duplicates itself. He analyses disturbances in the cellular cycle of human lymphocytes caused by the type and number of radiologically induced lesions on the chromosomes [fr

  4. Epigenetic and genetic factors in the cellular response to radiations and DNA-damaging chemicals

    International Nuclear Information System (INIS)

    Williams, J.R.; D'Arpa, P.

    1981-01-01

    DNA-damaging agents are widely used as therapeutic tools for a variety of disease states. Many such agents are considered to produce detrimental side effects. Thus, it is important to evaluate both therapeutic efficacy and potential risk. DNA-damaging agents can be so evaluated by comparison to agents whose therapeutic benefit and potential hazards are better known. We propose a framework for such comparison, demonstrating that a simple transformation of cytotoxicity-dose response patterns permits a facile comparison of variation between cells exposed to a single DNA-damaging agent or to different cytotoxic agents. Further, by transforming data from experiments which compare responses of 2 cell populations to an effects ratio, different patterns for the changes in cytotoxicity produced by epigenetic and genetic factors were compared. Using these transformations, we found that there is a wide variation (a factor of 4) between laboratories for a single agent (UVC) and only a slightly larger variation (factor of 6) between normal cell response for different types of DNA-damaging agents (x-ray, UVC, alkylating agents, crosslinking agents). Epigenetic factors such as repair and recovery appear to be a factor only at higher dose levels. Comparison in the cytotoxic effect of a spectrum of DNA-damaging agents in xeroderma pigmentosum, ataxia telangiectasia, and Fanconi's anemia cells indicates significantly different patterns, implying that the effect, and perhaps the nature, of these genetic conditions are quite different

  5. Cellular Internalization of Therapeutic Oligonucleotides by Peptide Amphiphile Nanofibers and Nanospheres.

    Science.gov (United States)

    Mumcuoglu, Didem; Sardan Ekiz, Melis; Gunay, Gokhan; Tekinay, Turgay; Tekinay, Ayse B; Guler, Mustafa O

    2016-05-11

    Oligonucleotides are promising drug candidates due to the exceptionally high specificity they exhibit toward their target DNA and RNA sequences. However, their poor pharmacokinetic and pharmacodynamic properties, in conjunction with problems associated with their internalization by cells, necessitates their delivery through specialized carrier systems for efficient therapy. Here, we investigate the effects of carrier morphology on the cellular internalization mechanisms of oligonucleotides by using self-assembled fibrous or spherical peptide nanostructures. Size and geometry were both found to be important parameters for the oligonucleotide internalization process; direct penetration was determined to be the major mechanism for the internalization of nanosphere carriers, whereas nanofibers were internalized by clathrin- and dynamin-dependent endocytosis pathways. We further showed that glucose conjugation to carrier nanosystems improved cellular internalization in cancer cells due to the enhanced glucose metabolism associated with oncogenesis, and the internalization of the glucose-conjugated peptide/oligonucleotide complexes was found to be dependent on glucose transporters present on the surface of the cell membrane.

  6. Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage

    DEFF Research Database (Denmark)

    Gibbs-Seymour, Ian; Markiewicz, Ewa; Bekker-Jensen, Simon

    2015-01-01

    Lamins A/C have been implicated in DNA damage response pathways. We show that the DNA repair protein 53BP1 is a lamin A/C binding protein. In undamaged human dermal fibroblasts (HDF), 53BP1 is a nucleoskeleton protein. 53BP1 binds to lamins A/C via its Tudor domain, and this is abrogated by DNA...... damage. Lamins A/C regulate 53BP1 levels and consequently lamin A/C-null HDF display a 53BP1 null-like phenotype. Our data favour a model in which lamins A/C maintain a nucleoplasmic pool of 53BP1 in order to facilitate its rapid recruitment to sites of DNA damage and could explain why an absence...

  7. Damage to cellular and isolated DNA induced by a metabolite of aspirin

    Energy Technology Data Exchange (ETDEWEB)

    Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan)], E-mail: s-oikawa@doc.medic.mie-u.ac.jp; Kobayashi, Hatasu; Tada-Oikawa, Saeko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); JSPS Research Fellow (Japan); Isono, Yoshiaki [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Kawanishi, Shosuke [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 (Japan)

    2009-02-10

    Aspirin has been proposed as a possible chemopreventive agent. On the other hand, a recent cohort study showed that aspirin may increase the risk for pancreatic cancer. To clarify whether aspirin is potentially carcinogenic, we investigated the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is correlated with the incidence of cancer, in cultured cells treated with 2,3-dihydroxybenzoic acid (2,3-DHBA), a metabolite of aspirin. 2,3-DHBA induced 8-oxodG formation in the PANC-1 human pancreatic cancer cell line. 2,3-DHBA-induced DNA single-strand breaks were also revealed by comet assay using PANC-1 cells. Flow cytometric analyses showed that 2,3-DHBA increased the levels of intracellular reactive oxygen species (ROS) in PANC-1 cells. The 8-oxodG formation and ROS generation were also observed in the HL-60 leukemia cell line, but not in the hydrogen peroxide (H{sub 2}O{sub 2})-resistant clone HP100 cells, suggesting the involvement of H{sub 2}O{sub 2}. In addition, an hprt mutation assay supported the mutagenicity of 2,3-DHBA. We investigated the mechanism underlying the 2,3-DHBA-induced DNA damage using {sup 32}P-labeled DNA fragments of human tumor suppressor genes. 2,3-DHBA induced DNA damage in the presence of Cu(II) and NADH. DNA damage induced by 2,3-DHBA was enhanced by the addition of histone peptide-6 [AKRHRK]. Interestingly, 2,3-DHBA and histone peptide-6 caused base damage in the 5'-ACG-3' and 5'-CCG-3' sequences, hotspots of the p53 gene. Bathocuproine, a Cu(I) chelator, and catalase inhibited the DNA damage. Typical hydroxyl radical scavengers did not inhibit the DNA damage. These results suggest that ROS derived from the reaction of H{sub 2}O{sub 2} with Cu(I) participate in the DNA damage. In conclusion, 2,3-DHBA induces oxidative DNA damage and mutations, which may result in carcinogenesis.

  8. Damage to cellular and isolated DNA induced by a metabolite of aspirin

    International Nuclear Information System (INIS)

    Oikawa, Shinji; Kobayashi, Hatasu; Tada-Oikawa, Saeko; Isono, Yoshiaki; Kawanishi, Shosuke

    2009-01-01

    Aspirin has been proposed as a possible chemopreventive agent. On the other hand, a recent cohort study showed that aspirin may increase the risk for pancreatic cancer. To clarify whether aspirin is potentially carcinogenic, we investigated the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is correlated with the incidence of cancer, in cultured cells treated with 2,3-dihydroxybenzoic acid (2,3-DHBA), a metabolite of aspirin. 2,3-DHBA induced 8-oxodG formation in the PANC-1 human pancreatic cancer cell line. 2,3-DHBA-induced DNA single-strand breaks were also revealed by comet assay using PANC-1 cells. Flow cytometric analyses showed that 2,3-DHBA increased the levels of intracellular reactive oxygen species (ROS) in PANC-1 cells. The 8-oxodG formation and ROS generation were also observed in the HL-60 leukemia cell line, but not in the hydrogen peroxide (H 2 O 2 )-resistant clone HP100 cells, suggesting the involvement of H 2 O 2 . In addition, an hprt mutation assay supported the mutagenicity of 2,3-DHBA. We investigated the mechanism underlying the 2,3-DHBA-induced DNA damage using 32 P-labeled DNA fragments of human tumor suppressor genes. 2,3-DHBA induced DNA damage in the presence of Cu(II) and NADH. DNA damage induced by 2,3-DHBA was enhanced by the addition of histone peptide-6 [AKRHRK]. Interestingly, 2,3-DHBA and histone peptide-6 caused base damage in the 5'-ACG-3' and 5'-CCG-3' sequences, hotspots of the p53 gene. Bathocuproine, a Cu(I) chelator, and catalase inhibited the DNA damage. Typical hydroxyl radical scavengers did not inhibit the DNA damage. These results suggest that ROS derived from the reaction of H 2 O 2 with Cu(I) participate in the DNA damage. In conclusion, 2,3-DHBA induces oxidative DNA damage and mutations, which may result in carcinogenesis

  9. Monoacylated Cellular Prion Proteins Reduce Amyloid-β-Induced Activation of Cytoplasmic Phospholipase A2 and Synapse Damage

    Directory of Open Access Journals (Sweden)

    Ewan West

    2015-06-01

    Full Text Available Alzheimer’s disease (AD is a progressive neurodegenerative disease characterized by the accumulation of amyloid-β (Aβ and the loss of synapses. Aggregation of the cellular prion protein (PrPC by Aβ oligomers induced synapse damage in cultured neurons. PrPC is attached to membranes via a glycosylphosphatidylinositol (GPI anchor, the composition of which affects protein targeting and cell signaling. Monoacylated PrPC incorporated into neurons bound “natural Aβ”, sequestering Aβ outside lipid rafts and preventing its accumulation at synapses. The presence of monoacylated PrPC reduced the Aβ-induced activation of cytoplasmic phospholipase A2 (cPLA2 and Aβ-induced synapse damage. This protective effect was stimulus specific, as treated neurons remained sensitive to α-synuclein, a protein associated with synapse damage in Parkinson’s disease. In synaptosomes, the aggregation of PrPC by Aβ oligomers triggered the formation of a signaling complex containing the cPLA2.a process, disrupted by monoacylated PrPC. We propose that monoacylated PrPC acts as a molecular sponge, binding Aβ oligomers at the neuronal perikarya without activating cPLA2 or triggering synapse damage.

  10. Deficiency of methionine sulfoxide reductase A causes cellular dysfunction and mitochondrial damage in cardiac myocytes under physical and oxidative stresses

    International Nuclear Information System (INIS)

    Nan, Changlong; Li, Yuejin; Jean-Charles, Pierre-Yves; Chen, Guozhen; Kreymerman, Alexander; Prentice, Howard; Weissbach, Herbert; Huang, Xupei

    2010-01-01

    Research highlights: → Deficiency of MsrA in the heart renders myocardial cells more sensitive to oxidative stress. → Mitochondrial damage happens in the heart lacking MsrA. → More protein oxidation in myocardial cells lacking MsrA. → MsrA protects the heart against oxidative stress. -- Abstract: Methionine sulfoxide reductase A (MsrA) is an enzyme that reverses oxidation of methionine in proteins. Using a MsrA gene knockout (MsrA -/- ) mouse model, we have investigated the role of MsrA in the heart. Our data indicate that cellular contractility and cardiac function are not significantly changed in MsrA -/- mice if the hearts are not stressed. However, the cellular contractility, when stressed using a higher stimulation frequency (2 Hz), is significantly reduced in MsrA -/- cardiac myocytes. MsrA -/- cardiac myocytes also show a significant decrease in contractility after oxidative stress using H 2 O 2 . Corresponding changes in Ca 2+ transients are observed in MsrA -/- cardiomyocytes treated with 2 Hz stimulation or with H 2 O 2 . Electron microscope analyses reveal a dramatic morphological change of mitochondria in MsrA -/- mouse hearts. Further biochemical measurements indicate that protein oxidation levels in MsrA -/- mouse hearts are significantly higher than those in wild type controls. Our study demonstrates that the lack of MsrA in cardiac myocytes reduces myocardial cell's capability against stress stimulations resulting in a cellular dysfunction in the heart.

  11. Preparation of Well-Dispersed Chitosan/Alginate Hollow Multilayered Microcapsules for Enhanced Cellular Internalization

    Directory of Open Access Journals (Sweden)

    Carla Ribeiro

    2018-03-01

    Full Text Available Hollow multilayered capsules have shown massive potential for being used in the biomedical and biotechnology fields, in applications such as cellular internalization, intracellular trafficking, drug delivery, or tissue engineering. In particular, hollow microcapsules, developed by resorting to porous calcium carbonate sacrificial templates, natural-origin building blocks and the prominent Layer-by-Layer (LbL technology, have attracted increasing attention owing to their key features. However, these microcapsules revealed a great tendency to aggregate, which represents a major hurdle when aiming for cellular internalization and intracellular therapeutics delivery. Herein, we report the preparation of well-dispersed polysaccharide-based hollow multilayered microcapsules by combining the LbL technique with an optimized purification process. Cationic chitosan (CHT and anionic alginate (ALG were chosen as the marine origin polysaccharides due to their biocompatibility and structural similarity to the extracellular matrices of living tissues. Moreover, the inexpensive and highly versatile LbL technology was used to fabricate core-shell microparticles and hollow multilayered microcapsules, with precise control over their composition and physicochemical properties, by repeating the alternate deposition of both materials. The microcapsules’ synthesis procedure was optimized to extensively reduce their natural aggregation tendency, as shown by the morphological analysis monitored by advanced microscopy techniques. The well-dispersed microcapsules showed an enhanced uptake by fibroblasts, opening new perspectives for cellular internalization.

  12. Understanding radiation damage on sub-cellular scale using RADAMOL simulation tool

    Czech Academy of Sciences Publication Activity Database

    Štěpán, Václav; Davídková, Marie

    2016-01-01

    Roč. 128, NOV (2016), s. 11-17 ISSN 0969-806X R&D Projects: GA ČR(CZ) GBP108/12/G108; GA MŠk LD12008 Grant - others:GA MŠk(CZ) LM2010005 Institutional support: RVO:61389005 Keywords : charged particles * DNA * proteins * radiation damage * radical attack * water radiolysis Subject RIV: BO - Biophysics Impact factor: 1.315, year: 2016

  13. Aging-associated oxidized albumin promotes cellular senescence and endothelial damage

    Directory of Open Access Journals (Sweden)

    Luna C

    2016-02-01

    Full Text Available Carlos Luna,1,* Matilde Alique,2,* Estefanía Navalmoral,2 Maria-Victoria Noci,3 Lourdes Bohorquez-Magro,2 Julia Carracedo,1 Rafael Ramírez2 1Nephrology Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC, Reina Sofía University Hospital, Córdoba, Spain; 2Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Madrid, Spain; 3Anesthesia Unit, Reina sofía University Hospital, Córdoba, Spain*These authors contributed equally to this work Abstract: Increased levels of oxidized proteins with aging have been considered a cardiovascular risk factor. However, it is unclear whether oxidized albumin, which is the most abundant serum protein, induces endothelial damage. The results of this study indicated that with aging processes, the levels of oxidized proteins as well as endothelial microparticles release increased, a novel marker of endothelial damage. Among these, oxidized albumin seems to play a principal role. Through in vitro studies, endothelial cells cultured with oxidized albumin exhibited an increment of endothelial damage markers such as adhesion molecules and apoptosis levels. In addition, albumin oxidation increased the amount of endothelial microparticles that were released. Moreover, endothelial cells with increased oxidative stress undergo senescence. In addition, endothelial cells cultured with oxidized albumin shown a reduction in endothelial cell migration measured by wound healing. As a result, we provide the first evidence that oxidized albumin induces endothelial injury which then contributes to the increase of cardiovascular disease in the elderly subjects.Keywords: elderly, oxidative stress, microparticles, vascular damage

  14. HTLV-1 Tax Oncoprotein Subverts the Cellular DNA Damage Response via Binding to DNA-dependent Protein Kinase*S⃞

    Science.gov (United States)

    Durkin, Sarah S.; Guo, Xin; Fryrear, Kimberly A.; Mihaylova, Valia T.; Gupta, Saurabh K.; Belgnaoui, S. Mehdi; Haoudi, Abdelali; Kupfer, Gary M.; Semmes, O. John

    2008-01-01

    Human T-cell leukemia virus type-1 is the causative agent for adult T-cell leukemia. Previous research has established that the viral oncoprotein Tax mediates the transformation process by impairing cell cycle control and cellular response to DNA damage. We showed previously that Tax sequesters huChk2 within chromatin and impairs the response to ionizing radiation. Here we demonstrate that DNA-dependent protein kinase (DNA-PK) is a member of the Tax·Chk2 nuclear complex. The catalytic subunit, DNA-PKcs, and the regulatory subunit, Ku70, were present. Tax-containing nuclear extracts showed increased DNA-PK activity, and specific inhibition of DNA-PK prevented Tax-induced activation of Chk2 kinase activity. Expression of Tax induced foci formation and phosphorylation of H2AX. However, Tax-induced constitutive signaling of the DNA-PK pathway impaired cellular response to new damage, as reflected in suppression of ionizing radiation-induced DNA-PK phosphorylation and γH2AX stabilization. Tax co-localized with phospho-DNA-PK into nuclear speckles and a nuclear excluded Tax mutant sequestered endogenous phospho-DNA-PK into the cytoplasm, suggesting that Tax interaction with DNA-PK is an initiating event. We also describe a novel interaction between DNA-PK and Chk2 that requires Tax. We propose that Tax binds to and stabilizes a protein complex with DNA-PK and Chk2, resulting in a saturation of DNA-PK-mediated damage repair response. PMID:18957425

  15. Dancing on damaged chromatin. Functions of ATM and the RAD50/MRE11/NBS1 complex in cellular responses to DNA damage

    International Nuclear Information System (INIS)

    Iijima, Kenta; Ohara, Maki; Seki, Ryota; Tauchi, Hiroshi

    2008-01-01

    In order to preserve and protect genetic information, eukaryotic cells have developed a signaling or communications network to help the cell respond to DNA damage, and ATM and NBS1 are key players in this network. ATM is a protein kinase which is activated immediately after a DNA double strand break (DSB) is formed, and the resulting signal cascade generated in response to cellular DSBs is regulated by post-translational protein modifications such as phosphorylation and acetylation. In addition, to ensure the efficient functioning of DNA repair and cell cycle checkpoints, the highly ordered structure of eukaryotic chromatin must be appropriately altered to permit access of repair-related factors to DNA. These alterations are termed chromatin remodeling, and are executed by a specific remodeling complex in conjunction with histone modifications. Current advances in the molecular analysis of DNA damage responses have shown that the auto-phosphorylation of ATM and the interaction between ATM and NBS1 are key steps for ATM activation, and that the association of ATM and NBS1 is involved in chromatin remodeling. Identification of novel factors which function in ubiquitination (RNF8, Ubc13, Rap80, etc.) has also enabled us to understand more details of the early stages in DNA repair pathways which respond to DSBs. In this review, the focus is on the role of ATM and the RAD50/MRE11/NBS1 complex in DSB response pathways, and their role in DSB repair and in the regulation of chromatin remodeling. (author)

  16. Downregulation of Wip1 phosphatase modulates the cellular threshold of DNA damage signaling in mitosis

    Science.gov (United States)

    Macurek, Libor; Benada, Jan; Müllers, Erik; Halim, Vincentius A.; Krejčíková, Kateřina; Burdová, Kamila; Pecháčková, Sona; Hodný, Zdeněk; Lindqvist, Arne; Medema, René H.; Bartek, Jiri

    2013-01-01

    Cells are constantly challenged by DNA damage and protect their genome integrity by activation of an evolutionary conserved DNA damage response pathway (DDR). A central core of DDR is composed of a spatiotemporally ordered net of post-translational modifications, among which protein phosphorylation plays a major role. Activation of checkpoint kinases ATM/ATR and Chk1/2 leads to a temporal arrest in cell cycle progression (checkpoint) and allows time for DNA repair. Following DNA repair, cells re-enter the cell cycle by checkpoint recovery. Wip1 phosphatase (also called PPM1D) dephosphorylates multiple proteins involved in DDR and is essential for timely termination of the DDR. Here we have investigated how Wip1 is regulated in the context of the cell cycle. We found that Wip1 activity is downregulated by several mechanisms during mitosis. Wip1 protein abundance increases from G1 phase to G2 and declines in mitosis. Decreased abundance of Wip1 during mitosis is caused by proteasomal degradation. In addition, Wip1 is phosphorylated at multiple residues during mitosis, and this leads to inhibition of its enzymatic activity. Importantly, ectopic expression of Wip1 reduced γH2AX staining in mitotic cells and decreased the number of 53BP1 nuclear bodies in G1 cells. We propose that the combined decrease and inhibition of Wip1 in mitosis decreases the threshold necessary for DDR activation and enables cells to react adequately even to modest levels of DNA damage encountered during unperturbed mitotic progression. PMID:23255129

  17. Myocardial perfusion alterations observed months after radiotherapy are related to the cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Dogan, I.; Sonmez, B. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Nuclear Medicine; Sezen, O.; Zengin, A.Y.; Bahat, Z. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Radiation Oncology; Yenilmez, E.; Yulug, E. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Histology and Embryology; Abidin, I. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Biophysics

    2010-07-01

    Myocardial perfusion scintigraphy (MPS) is one of the widely used tools to follow developing radiation-induced heart disease (RIHD). But the clinical significance of MPS defects has not been fully understood. We have investigated the biodistribution alterations related to perfusion defects following radiotherapy (RT) and showed coexisting morphological changes. Animals, methods: A total of 18 Wistar rats were divided into three groups (1 control and 2 irradiated groups). A single cardiac 20 Gy radiation dose was used to induce long term cardiac defects. Biodistribution studies with technetium ({sup 99m}Tc) sestamibi and histological evaluations were performed 4 and 6 months after irradiation. The percent radioactivity (%ID/g) was calculated for each heart. For determination of the myocardial damage, positive apoptotic cardiomyocytes, myocardial cell degeneration, myocardial fibrosis, vascular damage and ultrastructural structures were evaluated. Results: Six months after treatment, a significant drop of myocardial uptake was observed (p < 0.05). Irradiation-induced apoptosis rose within the first 4 months after radiation treatment and were stayed elevated until the end of the observation period (p < 0.05). Also, the irradiation has induced myocardial degeneration, perivascular and interstitial fibrosis in the heart at the end of six and four months (p < 0.01). The severity and extent of myocardial injury has became more evident at the end of six month (p < 0.05). At ultrastructural level, prominent changes have been observed in the capillary endothelial and myocardial cells. Conclusion: Our findings suggest that the reduced rest myocardial perfusion, occuring months after the radiation, indicates a serious myocard tissue damage which is characterized by myocardial degeneration and fibrosis. (orig.)

  18. Myocardial perfusion alterations observed months after radiotherapy are related to the cellular damage

    International Nuclear Information System (INIS)

    Dogan, I.; Sonmez, B.; Sezen, O.; Zengin, A.Y.; Bahat, Z.; Yenilmez, E.; Yulug, E.; Abidin, I.

    2010-01-01

    Myocardial perfusion scintigraphy (MPS) is one of the widely used tools to follow developing radiation-induced heart disease (RIHD). But the clinical significance of MPS defects has not been fully understood. We have investigated the biodistribution alterations related to perfusion defects following radiotherapy (RT) and showed coexisting morphological changes. Animals, methods: A total of 18 Wistar rats were divided into three groups (1 control and 2 irradiated groups). A single cardiac 20 Gy radiation dose was used to induce long term cardiac defects. Biodistribution studies with technetium ( 99m Tc) sestamibi and histological evaluations were performed 4 and 6 months after irradiation. The percent radioactivity (%ID/g) was calculated for each heart. For determination of the myocardial damage, positive apoptotic cardiomyocytes, myocardial cell degeneration, myocardial fibrosis, vascular damage and ultrastructural structures were evaluated. Results: Six months after treatment, a significant drop of myocardial uptake was observed (p < 0.05). Irradiation-induced apoptosis rose within the first 4 months after radiation treatment and were stayed elevated until the end of the observation period (p < 0.05). Also, the irradiation has induced myocardial degeneration, perivascular and interstitial fibrosis in the heart at the end of six and four months (p < 0.01). The severity and extent of myocardial injury has became more evident at the end of six month (p < 0.05). At ultrastructural level, prominent changes have been observed in the capillary endothelial and myocardial cells. Conclusion: Our findings suggest that the reduced rest myocardial perfusion, occuring months after the radiation, indicates a serious myocard tissue damage which is characterized by myocardial degeneration and fibrosis. (orig.)

  19. Downregulation of Wip1 phosphatase modulates the cellular threshold of DNA damage signaling in mitosis

    Czech Academy of Sciences Publication Activity Database

    Macůrek, Libor; Benada, Jan; Müllers, E.; Halim, V.A.; Krejčíková, Kateřina; Burdová, Kamila; Pecháčková, Soňa; Hodný, Zdeněk; Lindqvist, A.; Medema, R.H.; Bartek, Jiří

    2013-01-01

    Roč. 12, č. 2 (2013), s. 251-262 ISSN 1538-4101 R&D Projects: GA ČR GPP305/10/P420; GA ČR GAP301/10/1525 Grant - others:Netherlands Genomic Initiative of NWO(NL) CGC; EK(XE) 259893 Institutional support: RVO:68378050 Keywords : DNA damage response * Wip1 phosphatase * cell cycle * mitotic progression * γH2AX Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.006, year: 2013

  20. Ubiquitin-activating enzyme UBA1 is required for cellular response to DNA damage

    Czech Academy of Sciences Publication Activity Database

    Moudrý, Pavel; Lukas, C.; Macůrek, Libor; Hanzlíková, Hana; Hodný, Zdeněk; Lukas, J.; Bartek, Jiří

    2012-01-01

    Roč. 11, č. 8 (2012), s. 1573-1582 ISSN 1538-4101 R&D Projects: GA ČR GA301/08/0353; GA ČR GAP301/10/1525 Grant - others:7.RP EU(XE) CZ.1.05/2.1.00/01.0030 Institutional research plan: CEZ:AV0Z50520514 Keywords : 53BP1 * DNA damage response * UBA1 * UBA6 * ubiquitylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.243, year: 2012

  1. IRESPred: Web Server for Prediction of Cellular and Viral Internal Ribosome Entry Site (IRES)

    Science.gov (United States)

    Kolekar, Pandurang; Pataskar, Abhijeet; Kulkarni-Kale, Urmila; Pal, Jayanta; Kulkarni, Abhijeet

    2016-01-01

    Cellular mRNAs are predominantly translated in a cap-dependent manner. However, some viral and a subset of cellular mRNAs initiate their translation in a cap-independent manner. This requires presence of a structured RNA element, known as, Internal Ribosome Entry Site (IRES) in their 5′ untranslated regions (UTRs). Experimental demonstration of IRES in UTR remains a challenging task. Computational prediction of IRES merely based on sequence and structure conservation is also difficult, particularly for cellular IRES. A web server, IRESPred is developed for prediction of both viral and cellular IRES using Support Vector Machine (SVM). The predictive model was built using 35 features that are based on sequence and structural properties of UTRs and the probabilities of interactions between UTR and small subunit ribosomal proteins (SSRPs). The model was found to have 75.51% accuracy, 75.75% sensitivity, 75.25% specificity, 75.75% precision and Matthews Correlation Coefficient (MCC) of 0.51 in blind testing. IRESPred was found to perform better than the only available viral IRES prediction server, VIPS. The IRESPred server is freely available at http://bioinfo.net.in/IRESPred/. PMID:27264539

  2. HPLC-MS/MS measurement of radiation and photo-induced damage in cellular DNA and human skin

    International Nuclear Information System (INIS)

    Cadet, Jean; Douki, Thierry; Ravanat, Jean-Luc

    2010-01-01

    Full text: The measurement of damage induced in cellular DNA by ionizing and solar radiations is of major importance to assess the molecular mode of action and the biological role (mutagenesis, DNA repair) of these genotoxic agents. For this purpose several analytical approaches including immunodetection, post-labeling and chromatographic assays have been designed. However most of them have been shown to suffer from a lack of specificity, sensitivity or quantitative response. It may be noted that the gas-chromatography method in its basal version has been found to lead to overestimated yields of oxidatively generated base lesions by two to three order of magnitude due to the occurrence of artifactual oxidation of the overwhelming purine and pyrimidine bases during the derivatization step of the assay. The advent of HPLC coupled to tandem mass spectrometry operating in the electrospray ionization mode has allowed overcoming most of these drawbacks. Thus, accurate determination of 11 oxidized bases and nucleosides has been achieved in cellular DNA upon exposure to radiation-induced hydroxyl radical and one-electron oxidation agents. This has involved quantitative enzymatic release of lesions from extracted DNA and their accurate detection at the output of the HPLC column using the highly quantitative isotopic dilution technique. Evidence was also provided for the generation of five clustered lesions that all involve a base modification and an altered 2-deoxyribose residue as the result of only one initial radical oxidation hit. These consist of (5'R)-5',8-cyclo-2'-deoxyadenosine and cytosinealdehyde adducts that arise from .OH-mediated hydrogen abstraction at C5 and C4 of the sugar moiety of cellular DNA respectively. The damaging effects of UVA radiation on cellular DNA and human skin were rationalized in terms of predominant 1 O 2 -mediated formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine. Other relevant types of DNA modifications consist in bipyrimidine

  3. Exposure to environmental polycyclic aromatic hydrocarbons: Influences on cellular susceptibility to DNA damage (sampling Kosice and Sofia)

    Energy Technology Data Exchange (ETDEWEB)

    Cebulska-Wasilewska, Antonina [Department of Radiation and Environmental Biology, Henryk Niewodniczanski Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Cracow (Poland) and Chair of the Epidemiology and Preventive Medicine, CM UJ, Cracow (Poland)]. E-mail: b7wasile@cyf-kr.edu.pl; Pawlyk, Igor [Department of Radiation and Environmental Biology, Henryk Niewodniczanski Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Cracow (Poland); Panek, Agnieszka [Department of Radiation and Environmental Biology, Henryk Niewodniczanski Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Cracow (Poland); Wiechec, Anna [Department of Radiation and Environmental Biology, Henryk Niewodniczanski Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Cracow (Poland); Kalina, Ivan [Department of Molecular Biology of the P.J.Safarik University, Kosice (Slovakia); Popov, Todor [Department of Toxicology, National Centre of Public Health Protection, Sofia (Bulgaria); Georgieva, Tzveta [Department of Toxicology, National Centre of Public Health Protection, Sofia (Bulgaria); Farmer, Peter B. [Cancer Biomarkers and Prevention Group, University of Leicester (United Kingdom)

    2007-07-01

    The aim of this study was to investigate a possible influence of occupational exposure to carcinogenic environmental polycyclic aromatic hydrocarbons (c-PAHs) on cellular susceptibility to the induction of the DNA damage. Monitoring was performed and blood samples were collected from two groups of male subjects: occupationally exposed and matched controls. The group exposed to c-PAHs (average age of 35.1 years) consisted of 52 policemen from Kosice and 26 policemen and 25 bus drivers (51 altogether) from Sofia. The control group (average age of 36.4 years) consisted of 54 unexposed subjects from Kosice and 24 from Sofia. In the investigated groups 52.5% of exposed subjects and 45.3% of control were current smokers. A challenging dose of X-rays (3 Gy) and an alkaline version of the single cell gel electrophoresis (SCGE) assay, known as Comet assay, were used to evaluate levels of induced DNA damage and repair kinetics in isolated human blood lymphocytes. DNA damage detected in lymphocytes prior to or after irradiation did not differ significantly between exposed and unexposed subjects. A significant decrease in repair efficiency due to exposure to PAHs was observed in the exposed individuals from Kosice and Sofia, when analysed separately or together. A negative influence of tobacco smoking on the efficiency of DNA repair was observed. Statistically significant differences were found between subgroups stratified according to education level in Sofia: the half times for DNA repair declined with the increasing level of education. These results confirm that environmental exposure to c-PAHs can alter the ability of blood lymphocytes to repair DNA damage and, as a result could potentially lead to effects that are hazardous to human health.

  4. Histamine protects bone marrow against cellular damage induced by Ionizing radiation

    International Nuclear Information System (INIS)

    Medina, Vanina; Sambuco, Lorena; Massari, Noelia; Cricco, Graciela; Martin, Gabriela; Bergoc, Rosa; Rivera, Elena S.

    2008-01-01

    After surgery, radiotherapy is arguably one of the most important treatments for cancer, especially for localized disease that has not spread. However, ionizing radiation is toxic not only to tumor cells but also to healthy tissues causing serious adverse effects to patients. We have recently reported that histamine prevents ionizing radiation-induced toxicity on mouse small intestine. The aim of the present work was to determine whether histamine is able to protect bone marrow cells against ionizing radiation damage. For that purpose 56 mice were divided into 4 groups. Histamine and Histamine-10Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 20 hours before irradiation and continued till the end of experimental period; untreated group received saline. Histamine-10Gy and untreated-10Gy groups were irradiated with a single dose on whole-body using Cesium-137 source (7 Gy/min) and were sacrificed 3 days after irradiation. Bone marrow was removed, fixed and stained with hematoxylin and eosin. The number of megacariocytes per 40x field, bone marrow tropism, edema, vascular damage, and other histological characteristics of bone marrow cells were evaluated. We further determined by immunohistochemistry the expression of proliferating cell nuclear antigen (PCNA) and cells in the S phase of the cell cycle were identified by immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Results indicate that histamine treatment substantially reduced the grade of aplasia, the edema and the vascular damage induced by ionizing radiation on bone marrow. Additionally, histamine preserved medullar components increasing significantly the number of megacariocytes per field (5.4 ± 0.4 vs. 2.8 ± 0.4 in Control-10 Gy, P<0.01). This effect was associated with an increased proliferation rate determined by the augmented PCNA expression and BrdU incorporation of bone marrow cells. On the basis of these results, we conclude that histamine

  5. Cells, bilirubin and light: formation of bilirubin photoproducts and cellular damage at defined wavelengths

    International Nuclear Information System (INIS)

    Christensen, T.; Kinn, G.; Granli, T.; Amundsen, I.

    1994-01-01

    Cultured cells from one human and one murine cell line were treated with bilirubin and irradiated with visible light of different wavelengths, either from phototherapy lamps or from a Xenon/Mercury lamp equipped with a monochromator. Bilirubin bound to human serum albumin was also irradiated with light. After irradiation, the bilirubin and its photoisomers were extracted with High Pressure Liquid Chromatography. The formation of single strand breaks in the DNA of treated cells was studied using a fluorescence marker. Cytotoxicity in the mouse skin cell line was measured by loss of the ability to form visible colonies in vitro. Green light exposure favours the production of lumirubin, while blue light causes more DNA damage and cytotoxicity. Green light may be more efficient and safer than shorter wavelength exposure when treating jaundiced newborns with phototherapy. 27 refs., 6 figs

  6. DOE contractors' workshop: Cellular and molecular aspects of radiation induced DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    For four decades the US Department of Energy and its predecessors have been the lead federal agency in supporting radiation biology research. Over the years emphasis in this program has gradually shifted from dose-effect studies on animals to research on the effects of radiations of various qualities on cells and molecules. Mechanistic studies on the action of radiation at the subcellular level are few in number and there is a need for more research in this area if we are to gain a better understanding of how radiation affects living cells. The intent of this workshop was to bring together DOE contractors and grantees who are investigating the effects of radiation at the cellular and molecular levels. The aims were to foster the exchange of information on research projects and experimental results, promote collaborative research efforts, and obtain an overview of research currently supported by the Health Effects Research Division of the Office of Health and Environmental Research. The latter is needed by the Office for program planning purposes. This report on the workshop which took place in Albuquerque, New Mexico on March 10-11, 1987, includes an overview with future research recommendations, extended abstracts of the plenary presentations, shorter abstracts of each poster presentation, a workshop agenda and the names and addresses of the attendees.

  7. DOE contractors' workshop: Cellular and molecular aspects of radiation induced DNA damage and repair

    International Nuclear Information System (INIS)

    1987-01-01

    For four decades the US Department of Energy and its predecessors have been the lead federal agency in supporting radiation biology research. Over the years emphasis in this program has gradually shifted from dose-effect studies on animals to research on the effects of radiations of various qualities on cells and molecules. Mechanistic studies on the action of radiation at the subcellular level are few in number and there is a need for more research in this area if we are to gain a better understanding of how radiation affects living cells. The intent of this workshop was to bring together DOE contractors and grantees who are investigating the effects of radiation at the cellular and molecular levels. The aims were to foster the exchange of information on research projects and experimental results, promote collaborative research efforts, and obtain an overview of research currently supported by the Health Effects Research Division of the Office of Health and Environmental Research. The latter is needed by the Office for program planning purposes. This report on the workshop which took place in Albuquerque, New Mexico on March 10-11, 1987, includes an overview with future research recommendations, extended abstracts of the plenary presentations, shorter abstracts of each poster presentation, a workshop agenda and the names and addresses of the attendees

  8. Cell damage from radiation-induced bystander effects for different cell densities simulated by a mathematical model via cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Meireles, Sincler P. de; Santos, Adriano M.; Grynberg, Suely Epsztein, E-mail: spm@cdtn.b, E-mail: amsantos@cdtn.b, E-mail: seg@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Nunes, Maria Eugenia S., E-mail: mariaeugenia@iceb.ufop.b [Universidade Federal de Ouro Preto (UFOP), MG (Brazil)

    2011-07-01

    During recent years, there has been a shift from an approach focused entirely on DNA as the main target of ionizing radiation to a vision that considers complex signaling pathways in cells and among cells within tissues. Several newly recognized responses were classified as the so-called non-target responses in which the biological effects are not directly related to the amount of energy deposited in the DNA of cells that were traversed by radiation. In 1992 the bystander effect was described referring to a series of responses such as death, chromosomal instability or other abnormalities that occur in non-irradiated cells that came into contact with irradiated cells or medium from irradiated cells. In this work, we have developed a mathematical model via cellular automata, to quantify cell death induced by the bystander effect. The model is based on experiments with irradiated cells conditioned medium which suggests that irradiated cells secrete molecules in the medium that are capable of damaging other cells. The computational model consists of two-dimensional cellular automata which is able to simulate the transmission of bystander signals via extrinsic route and via Gap junctions. The model has been validated by experimental results in the literature. The time evolution of the effect and the dose-response curves were obtained in good accordance to them. Simulations were conducted for different values of bystander and irradiated cell densities with constant dose. From this work, we have obtained a relationship between cell density and effect. (author)

  9. Cell damage from radiation-induced bystander effects for different cell densities simulated by a mathematical model via cellular automata

    International Nuclear Information System (INIS)

    Meireles, Sincler P. de; Santos, Adriano M.; Grynberg, Suely Epsztein; Nunes, Maria Eugenia S.

    2011-01-01

    During recent years, there has been a shift from an approach focused entirely on DNA as the main target of ionizing radiation to a vision that considers complex signaling pathways in cells and among cells within tissues. Several newly recognized responses were classified as the so-called non-target responses in which the biological effects are not directly related to the amount of energy deposited in the DNA of cells that were traversed by radiation. In 1992 the bystander effect was described referring to a series of responses such as death, chromosomal instability or other abnormalities that occur in non-irradiated cells that came into contact with irradiated cells or medium from irradiated cells. In this work, we have developed a mathematical model via cellular automata, to quantify cell death induced by the bystander effect. The model is based on experiments with irradiated cells conditioned medium which suggests that irradiated cells secrete molecules in the medium that are capable of damaging other cells. The computational model consists of two-dimensional cellular automata which is able to simulate the transmission of bystander signals via extrinsic route and via Gap junctions. The model has been validated by experimental results in the literature. The time evolution of the effect and the dose-response curves were obtained in good accordance to them. Simulations were conducted for different values of bystander and irradiated cell densities with constant dose. From this work, we have obtained a relationship between cell density and effect. (author)

  10. Algorithm for repairing the damaged images of grain structures obtained from the cellular automata and measurement of grain size

    Science.gov (United States)

    Ramírez-López, A.; Romero-Romo, M. A.; Muñoz-Negron, D.; López-Ramírez, S.; Escarela-Pérez, R.; Duran-Valencia, C.

    2012-10-01

    Computational models are developed to create grain structures using mathematical algorithms based on the chaos theory such as cellular automaton, geometrical models, fractals, and stochastic methods. Because of the chaotic nature of grain structures, some of the most popular routines are based on the Monte Carlo method, statistical distributions, and random walk methods, which can be easily programmed and included in nested loops. Nevertheless, grain structures are not well defined as the results of computational errors and numerical inconsistencies on mathematical methods. Due to the finite definition of numbers or the numerical restrictions during the simulation of solidification, damaged images appear on the screen. These images must be repaired to obtain a good measurement of grain geometrical properties. Some mathematical algorithms were developed to repair, measure, and characterize grain structures obtained from cellular automata in the present work. An appropriate measurement of grain size and the corrected identification of interfaces and length are very important topics in materials science because they are the representation and validation of mathematical models with real samples. As a result, the developed algorithms are tested and proved to be appropriate and efficient to eliminate the errors and characterize the grain structures.

  11. Final Report - Modeling the Physics of Damage Cluster Formation in a Cellular Environment

    International Nuclear Information System (INIS)

    L.H. Toburen, Principal Investigator; J.L. Shinpaugh; M. Dingfelder; and G. Lapicki; Co-Investigators

    2007-01-01

    Modern tools of radiobiology are leading to many new discoveries regarding how cells and tissues respond to radiation exposure. We can now irradiate single cells and observe responses in adjacent cells. We can also measure clusters of radiation damage produced in DNA. Our primary objective has been to understand the underling physics associated with these new biological responses. The primary tools available to describe the initial spatial pattern of damage formed by the absorption of ionizing radiation are based on Monte Carlo simulation of the structure of charged particle tracks. Although many Monte Carlo codes exist and considerable progress is being made in the incorporation of detailed macromolecular target structures into these codes, much of the interaction physics is still based on gas phase measurements and/or untested theoretical calculations that focus on water as the transport medium. Our objectives were threefold, (1) to expand the applicability of Monte Carlo track structure simulation to tissue-like material beyond the current focus on water, (2) to incorporate the most recent experimental information on electron interactions in biologically relevant material, and (3) to compare recent measurements of electron emissions induced by charged particles in thin foils with Monte Carlo predictions. We addressed these research objectives in three ways. First we applied theoretical techniques, similar to those used to derive data for water, to obtain cross sections for other condensed phase materials. This served two purposes. One was to provide testability of the theoretical technique by comparison to existing experimental data for electron transport (similar data does not exist for water), and the other was to expand the target database for use in modeling tissue. Second, we carefully reviewed published data, and ongoing experiments, for electron interaction cross-sections in biologically relevant condensed phase material. Results for low-energy electron

  12. An experimental study of radioprotective effect of ginseng alkaloid fraction on cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seong Yul; Cho, Chul Koo; Kim, Mi Sook; Yoo, Hyung Jun; Kim, Seong Ho; Kim, Tae Hwan [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1997-09-01

    This paper is to assess the effect of Adaptagen as a radioprotector in which main component is alkaloid fraction of ginseng. Evaluation was made in vitro and in vivo study with NIGP(S) mouse by the measurement of regeneration of jejunal crypt cell and micronucleus assay to analyze radioprotective effect of ginseng alkaloid fraction in comparison with that of water fraction after whole body irradiation. The results were as follows, 1. The degree of radiation damage of mouse jejunal crypt cell was diminished in both of alkaloid and water fraction groups compared to control group but more in alkaloid fraction group than water fraction group. 2. Regeneration of mouse jejunal crypt cell was higher both in alkaloid and water fraction groups than control group. 3. In vitro study, frequency of micronucleus was diminished in tendency for the treated groups than control group but statistically insignificant. 4. In vitro study, frequency of micronucleus was diminished in both alkaloid and water fraction groups compared to control group but more in alkaloid fraction group than water fraction group.

  13. A possible mechanism for transpupillary thermotherapy: nitric-oxide-related cellular damage.

    Science.gov (United States)

    Ozdek, Sengul; Urgancioglu, Berrak; Turkcu, Ummuhani Ozel; Bilgihan, Ayse

    2007-08-01

    To determine the oxidative stress markers on rabbit vitreous following transpupillary thermotherapy (TTT) application. The pigmented rabbit eyes were divided into 3 groups, each containing 6 eyes. Group 1 was used as a control group. Twelve eyes underwent TTT with a power of 250 mW (group 2) and 800 mW (group 3), with a diameter of 3000 microm and duration of 60 s; 24 h after laser application, vitreous samples were collected. Nitric oxide (NO) and malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities were determined in all groups. NO levels were statistically significantly higher in all groups when compared with the control group (p 0.05). Our results support the hypothesis that TTT application induces NO synthesis, which may lead to occlusion at choroidal neovessels. Because of the nonsignificantly increased levels of MDA and decrease of SOD activities there maybe only a weak relation between lipid peroxidation induced by free oxygen radicals and TTT-induced vascular damage.

  14. Cellular Internalization and Biocompatibility of Periodic Mesoporous Organosilica Nanoparticles with Tunable Morphologies: From Nanospheres to Nanowires

    KAUST Repository

    Fatieiev, Yevhen

    2017-01-10

    This work describes the sol-gel syntheses of para-substituted phenylene-bridged periodic mesoporous organosilica (PMO) nanoparticles (NPs) with tunable morphologies ranging from nanowires to nanospheres. The findings show the key role of the addition of organic co-solvents in the aqueous templates on the final morphologies of PMO NPs. Other factors such as the temperature, the stirring speed, and the amount of organic solvents also influence the shape of PMO NPs. The tuning of the shape of the PMO nanomaterials made it possible to study the influence of the particle morphology on the cellular internalization and biocompatibility.

  15. Damage invariant and high security acquisition of the internal fingerprint using optical coherence tomography

    CSIR Research Space (South Africa)

    Darlow, Luke N

    2016-11-01

    Full Text Available representation they offer. Using an emerging fingerprint acquisition technology – optical coherence tomography – to access an internal fingerprint under the skin surface, this paper serves to address two limitations of conventional scanners: fingertip skin damage...

  16. Radiation induced microvascular damage in the rat spinal cord: cellular and secretory factors

    International Nuclear Information System (INIS)

    Pfeffer, M. Raphael; Siegal, Tali; Meltzer, A; Shezen, E; Ovadia, Haim

    1996-01-01

    Purpose/Objective: To investigate the short and long-term effect of radiation on micro vessel permeability, endothelin and nitric oxide production, and cellular profile in the spinal cord of rats and to evaluate the influence of recombinant human manganese superoxide dismutase (r-hMnSOD) on these effects. Materials and Methods: The thoracolumbar spinal cord of Fischer rats was irradiated to a dose of 15 Gy. At various times afterwards the rats were killed and the spinal cord was excised. Endothelin and nitric oxide synthase (NOS) activity and microvascular permeability were assayed quantitatively. Astrocytes, microglia, vascular basal membrane and neuro filaments were immunohistochemically evaluated. Results: None of the rats developed signs of neurological dysfunction. Endothelin concentrations in the spinal cord were significantly reduced 18 hours after irradiation and continued to decrease until after 10 days (p=<0.007). After 56 days endothelin concentration returned to normal and then rose to markedly elevated levels at 120 and 180 days (p=<0.002). NOS activity was reduced soon after irradiation and remained very low throughout the period of observation despite the changes in endothelin. Vascular permeability was markedly increased after 18 hours and again after 120 and 180 days. Treatment with r-hMnSOD had no effect on normal vascular permeability but abolished the increase in vascular permeability seen after irradiation. Standard microscopic examination revealed no changes in the irradiated spinal cord. Immunohistochemical stains showed a progressive increase in the number of microglial cells per field after 120 and 180 days (p=<0.0003). An increase in astrocytic cells was seen after 180 days with an earlier short lasting peak after 14 days. No abnormalities were found in blood vessel configuration, density and diameter. Vascular basal membrane and neuro filaments were unchanged throughout the study. Conclusions: Following radiation to the spinal cord there

  17. Live Imaging of Cellular Internalization of Single Colloidal Particle by Combined Label-Free and Fluorescence Total Internal Reflection Microscopy.

    Science.gov (United States)

    Byrne, Gerard D; Vllasaliu, Driton; Falcone, Franco H; Somekh, Michael G; Stolnik, Snjezana

    2015-11-02

    In this work we utilize the combination of label-free total internal reflection microscopy and total internal reflectance fluorescence (TIRM/TIRF) microscopy to achieve a simultaneous, live imaging of single, label-free colloidal particle endocytosis by individual cells. The TIRM arm of the microscope enables label free imaging of the colloid and cell membrane features, while the TIRF arm images the dynamics of fluorescent-labeled clathrin (protein involved in endocytosis via clathrin pathway), expressed in transfected 3T3 fibroblasts cells. Using a model polymeric colloid and cells with a fluorescently tagged clathrin endocytosis pathway, we demonstrate that wide field TIRM/TIRF coimaging enables live visualization of the process of colloidal particle interaction with the labeled cell structure, which is valuable for discerning the membrane events and route of colloid internalization by the cell. We further show that 500 nm in diameter model polystyrene colloid associates with clathrin, prior to and during its cellular internalization. This association is not apparent with larger, 1 μm in diameter colloids, indicating an upper particle size limit for clathrin-mediated endocytosis.

  18. Internal Disequilibria and Phenotypic Diversification during Replication of Hepatitis C Virus in a Noncoevolving Cellular Environment.

    Science.gov (United States)

    Moreno, Elena; Gallego, Isabel; Gregori, Josep; Lucía-Sanz, Adriana; Soria, María Eugenia; Castro, Victoria; Beach, Nathan M; Manrubia, Susanna; Quer, Josep; Esteban, Juan Ignacio; Rice, Charles M; Gómez, Jordi; Gastaminza, Pablo; Domingo, Esteban; Perales, Celia

    2017-05-15

    Viral quasispecies evolution upon long-term virus replication in a noncoevolving cellular environment raises relevant general issues, such as the attainment of population equilibrium, compliance with the molecular-clock hypothesis, or stability of the phenotypic profile. Here, we evaluate the adaptation, mutant spectrum dynamics, and phenotypic diversification of hepatitis C virus (HCV) in the course of 200 passages in human hepatoma cells in an experimental design that precluded coevolution of the cells with the virus. Adaptation to the cells was evidenced by increase in progeny production. The rate of accumulation of mutations in the genomic consensus sequence deviated slightly from linearity, and mutant spectrum analyses revealed a complex dynamic of mutational waves, which was sustained beyond passage 100. The virus underwent several phenotypic changes, some of which impacted the virus-host relationship, such as enhanced cell killing, a shift toward higher virion density, and increased shutoff of host cell protein synthesis. Fluctuations in progeny production and failure to reach population equilibrium at the genomic level suggest internal instabilities that anticipate an unpredictable HCV evolution in the complex liver environment. IMPORTANCE Long-term virus evolution in an unperturbed cellular environment can reveal features of virus evolution that cannot be explained by comparing natural viral isolates. In the present study, we investigate genetic and phenotypic changes that occur upon prolonged passage of hepatitis C virus (HCV) in human hepatoma cells in an experimental design in which host cell evolutionary change is prevented. Despite replication in a noncoevolving cellular environment, the virus exhibited internal population disequilibria that did not decline with increased adaptation to the host cells. The diversification of phenotypic traits suggests that disequilibria inherent to viral populations may provide a selective advantage to viruses that can

  19. Damaged Self-Esteem is Associated with Internalizing Problems.

    Science.gov (United States)

    Creemers, Daan H M; Scholte, Ron H J; Engels, Rutger C M E; Prinstein, Mitchell J; Wiers, Reinout W

    2013-01-01

    Implicit and explicit self-esteem are assumed to be important factors in understanding the onset and maintenance of psychological problems. The current study aims to examine the association between implicit and explicit self-esteem and their interaction with depressive symptoms, suicidal ideation, and loneliness. Specifically, the relationship between the size and the direction of the discrepancy between implicit and explicit self-esteem with depressive symptoms, suicidal ideation, and loneliness were examined. Participants were 95 young female adults (M = 21.2 years, SD = 1.88) enrolled in higher education. We administered the IAT to assess implicit self-esteem, and the Rosenberg self-esteem scale to measure explicit self-esteem while psychological problems were assessed through self-reports. Results showed that discrepancies between implicit and explicit self-esteem were positively associated with depressive symptoms, suicidal ideation, and loneliness. In addition, the direction of the discrepancy was specifically relevant: damaged self-esteem (i.e., high implicit self-esteem and low explicit self-esteem) was consistently associated with increased levels of depressive symptoms, suicidal ideation, and loneliness. In contrast, defensive or fragile self-esteem (i.e., low implicit and high explicit self-esteem) was solely associated with loneliness. These findings provide further support that specifically damaged self-esteem is an important vulnerability marker for depressive symptoms, suicidal ideation, and loneliness.

  20. Damaged Self-Esteem is Associated with Internalizing Problems

    Science.gov (United States)

    Creemers, Daan H. M.; Scholte, Ron H. J.; Engels, Rutger C. M. E.; Prinstein, Mitchell J.; Wiers, Reinout W.

    2013-01-01

    Implicit and explicit self-esteem are assumed to be important factors in understanding the onset and maintenance of psychological problems. The current study aims to examine the association between implicit and explicit self-esteem and their interaction with depressive symptoms, suicidal ideation, and loneliness. Specifically, the relationship between the size and the direction of the discrepancy between implicit and explicit self-esteem with depressive symptoms, suicidal ideation, and loneliness were examined. Participants were 95 young female adults (M = 21.2 years, SD = 1.88) enrolled in higher education. We administered the IAT to assess implicit self-esteem, and the Rosenberg self-esteem scale to measure explicit self-esteem while psychological problems were assessed through self-reports. Results showed that discrepancies between implicit and explicit self-esteem were positively associated with depressive symptoms, suicidal ideation, and loneliness. In addition, the direction of the discrepancy was specifically relevant: damaged self-esteem (i.e., high implicit self-esteem and low explicit self-esteem) was consistently associated with increased levels of depressive symptoms, suicidal ideation, and loneliness. In contrast, defensive or fragile self-esteem (i.e., low implicit and high explicit self-esteem) was solely associated with loneliness. These findings provide further support that specifically damaged self-esteem is an important vulnerability marker for depressive symptoms, suicidal ideation, and loneliness. PMID:23565101

  1. Damaged Self-Esteem is Associated with Internalizing Problems

    Directory of Open Access Journals (Sweden)

    Daan eCreemers

    2013-04-01

    Full Text Available Implicit and explicit self-esteem are assumed to be important factors in understanding the onset and maintenance of psychological problems. The current study aims to examine the association between implicit and explicit self-esteem and their interaction with depressive symptoms, suicidal ideation and loneliness. Specifically, the relationship between the size and the direction of the discrepancy between implicit and explicit self-esteem with depressive symptoms, suicidal ideation and loneliness were examined. Participants were 95 young female adults (M= 21.2 years, SD = 1.88 enrolled in higher education. We administered the IAT to assess implicit self-esteem, and the Rosenberg self-esteem scale to measure explicit self-esteem while psychological problems were assessed through self-reports. Results showed that discrepancies between implicit and explicit self-esteem were positively associated with depressive symptoms, suicidal ideation, and loneliness. In addition, the direction of the discrepancy was specifically relevant: damaged self-esteem (i.e., high implicit self-esteem and low explicit self-esteem was consistently associated with increased levels of depressive symptoms, suicidal ideation, and loneliness. In contrast, defensive or fragile self-esteem (i.e., low implicit and high explicit self-esteem was solely associated with loneliness. These findings provide further support that specifically damaged self-esteem is an important vulnerability marker for depressive symptoms, suicidal ideation, and loneliness.

  2. A theory of viscoplasticity accounting for internal damage

    Science.gov (United States)

    Freed, A. D.; Robinson, D. N.

    1988-01-01

    A constitutive theory for use in structural and durability analyses of high temperature isotropic alloys is presented. Constitutive equations based upon a potential function are determined from conditions of stability and physical considerations. The theory is self-consistent; terms are not added in an ad hoc manner. It extends a proven viscoplastic model by introducing the Kachanov-Rabotnov concept of net stress. Material degradation and inelastic deformation are unified; they evolve simultaneously and interactively. Both isotropic hardening and material degradation evolve with dissipated work which is the sum of inelastic work and internal work. Internal work is a continuum measure of the stored free energy resulting from inelastic deformation.

  3. Effects of wearing bio-active material coated fabric against γ-irradiation-induced cellular damaged in Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Kang, Jung Ae; Kim, Hye Rim; Yoon, Sun Hye; Nam, Sang Hyun; Park, Sang Hyun; Jang, Beom Su; Go, Kyung Chan; Yang, Gwang Wung; Rho, Young Hwan; Park, Hyo Suk

    2016-01-01

    Ionizing radiation causes cellular damage and death through the direct damage and/or indirectly the production of ROS, which induces oxidative stress. This study was designed to evaluate the in vivo radioprotective effects of a bio-active material coated fabric (BMCF) against γ-irradiation-induced cellular damage in Sprague-Dawley (SD) rats. Healthy male SD rats wore bio-active material coated (concentrations in 10% and 30%) fabric for 7 days after 3 Gy of γ-irradiation. Radioprotective effects were evaluated by performing various biochemical assays including spleen and thymus index, WBC count, hepatic damage marker enzymes [aspartate transaminase (AST) and alanine transaminase (ALT)] in plasma, liver antioxidant enzymes, and mitochondrial activity in muscle. Exposure to γ-irradiation resulted in hepatocellular and immune systemic damage. Gamma-irradiation induced decreases in antioxidant enzymes. However, wearing the BMCF-30% decreased significantly AST and ALT activities in plasma. Furthermore, wearing the BMCF-30% increased SOD (superoxide dismutase) and mitochondrial activity. These results suggest that wearing BMCF offers effective radioprotection against γ-irradiation-induced cellular damage in SD rats

  4. Effects of wearing bio-active material coated fabric against γ-irradiation-induced cellular damaged in Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Jung Ae; Kim, Hye Rim; Yoon, Sun Hye; Nam, Sang Hyun; Park, Sang Hyun; Jang, Beom Su [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Go, Kyung Chan; Yang, Gwang Wung; Rho, Young Hwan; Park, Hyo Suk [Research and Development Center, VENTEX Co. Ltd., Seoul (Korea, Republic of)

    2016-09-15

    Ionizing radiation causes cellular damage and death through the direct damage and/or indirectly the production of ROS, which induces oxidative stress. This study was designed to evaluate the in vivo radioprotective effects of a bio-active material coated fabric (BMCF) against γ-irradiation-induced cellular damage in Sprague-Dawley (SD) rats. Healthy male SD rats wore bio-active material coated (concentrations in 10% and 30%) fabric for 7 days after 3 Gy of γ-irradiation. Radioprotective effects were evaluated by performing various biochemical assays including spleen and thymus index, WBC count, hepatic damage marker enzymes [aspartate transaminase (AST) and alanine transaminase (ALT)] in plasma, liver antioxidant enzymes, and mitochondrial activity in muscle. Exposure to γ-irradiation resulted in hepatocellular and immune systemic damage. Gamma-irradiation induced decreases in antioxidant enzymes. However, wearing the BMCF-30% decreased significantly AST and ALT activities in plasma. Furthermore, wearing the BMCF-30% increased SOD (superoxide dismutase) and mitochondrial activity. These results suggest that wearing BMCF offers effective radioprotection against γ-irradiation-induced cellular damage in SD rats.

  5. Proceedings of 6th International Microbeam Workshop/12th L.H. Gray Workshop Microbeam Probes of Cellular Radiation Response

    International Nuclear Information System (INIS)

    Prise, Kevin M.

    2004-01-01

    The extended abstracts which are submitted here present a summary of the proceedings of the 6th International Workshop/12th LH Gray Workshop: Microbeam Probes of Cellular Radiation Response, held at St. Catherine's College, University of Oxford, UK on March, 29th-31st, 2003. In 1993 the 4th LH Gray Workshop entitled ''Microbeam Probes of Cellular Radiation Response'' was held at the Gray Cancer Institute in Northwood. This was organized by Prof BD Michael, Dr M. Folkard and Dr KM Prise and brought together 40 participants interested in developing and applying new microbeam technology to problems in radiation biology (1). The workshop was an undoubted success and has spawned a series of subsequent workshops every two years. In the past, these workshops have been highly successful in bringing together groups interested in developing and applying micro-irradiation techniques to the study of cell and tissue damage by ionizing radiations. Following the first microbeam workshop, there has been a rapid growth in the number of centres developing radiobiology microbeams, or planning to do so and there are currently 15-20 worldwide. Much of the recent research using microbeams has used them to study low-dose effects and ''non-targeted'' responses such bystander effects, genomic instability and adaptive responses. The goal of the 6th workshop was to build on our knowledge of the development of microbeam approaches and the application to radiation biology in the future with the meeting stretching over a 3 day period. Over 80 participants reviewed the current state of radiobiology microbeam research worldwide and reported on new technological developments both in the fields of physics and biology

  6. Lactobacillus plantarum (VR1 isolated from an Ayurvedic medicine (Kutajarista ameliorates in vitro cellular damage caused by Aeromonas veronii

    Directory of Open Access Journals (Sweden)

    Patole Milind S

    2011-06-01

    Full Text Available Abstract Background Lactobacillus plantarum is considered as a safe and effective probiotic microorganism. Among various sources of isolation, traditionally fermented foods are considered to be rich in Lactobacillus spp., which can be exploited for their probiotic attribute. Antibacterial property of L. plantarum has been demonstrated against various enteric pathogens in both in vitro and in vivo systems. This study was aimed at characterizing L. plantarum isolated from Kutajarista, an ayurvedic fermented biomedicine, and assessing its antagonistic property against a common enteropathogen Aeromonas veronii. Results We report the isolation of L. plantarum (VR1 from Kutajarista, and efficacy of its cell free supernatant (CFS in amelioration of cytotoxicity caused by Aeromonas veronii. On the part of probiotic attributes, VR1 was tolerant to pH 2, 0.3% bile salts and simulated gastric juice. Additionally, VR1 also exhibited adhesive property to human intestinal HT-29 cell line. Furthermore, CFS of VR1 was antibacterial to enteric pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Aeromonas veronii and clinical isolates of P. aeruginosa and E. coli. Detailed study regarding the effect of VR1 CFS on A. veronii cytotoxicity showed a significant decrease in vacuole formation and detrimental cellular changes in Vero cells. On the other hand, A. veronii CFS caused disruption of tight junction proteins ZO-1 and actin in MDCK cell line, which was prevented by pre-incubation with CFS of VR1. Conclusions This is the first study to report isolation of L. plantarum (VR1 from Kutajarista and characterisation for its probiotic attributes. Our study demonstrates the antagonistic property of VR1 to A. veronii and effect of VR1 CFS in reduction of cellular damage caused by A. veronii in both Vero and MDCK cell lines.

  7. Use of X - Rays for the evaluation of internal damages provoked by corn seed drying and the effect of those damages upon the seeds quality

    International Nuclear Information System (INIS)

    Obando Flor, Ebert Pepe; Moreira de Carvalho, Maria Laene

    2002-01-01

    The work was conducted in the seed analysis laboratory of the department of agriculture and forest sciences of the Universidade Federal de Lavras (Federal University of Lavras. MG), over the period 1999 - 2000. Aiming to evaluate the efficiency of utilization of X - rays in the identification of the several types of internal damages provoked by corn seed drying to high temperatures as well as the effect of those damages upon the physiological quality of stored seeds, lots of the cultivars AG1143 and BR 106 were submitted to drying at the temperature of 50 degrades Celsius. The lots were divided into two categories according to the presence or not of internal damages visible with the naked eye submitted to the X - ray test (for 45 at 25 Kvp of radiation intensity) afterwards. They were separated into three sub lots. CDVCDRX (with visual damages and detected by X - ray) SDVSDRX (without visual damages and with damages detected by X ray). The sub lots were evaluated in their physiological quality by viability and vigor tests. The results showed the efficiency of X ray in detecting internal damages of drying not observed by visual analysis. The vigor of corn seeds with internal drying damages is affected in several manners, depending on the cultivars, evaluation time and sort of damage internal damages of drying detected by the radiographical analysis in spite of not affecting early viability, when they occurs in the two directions horizontal and vertical (Double damage) decrease the vigor of seeds after storage

  8. Nonlinear Ultrasonic Techniques to Monitor Radiation Damage in RPV and Internal Components

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Laurence [Georgia Inst. of Technology, Atlanta, GA (United States); Kim, Jin-Yeon [Georgia Inst. of Technology, Atlanta, GA (United States); Qu, Jisnmin [Northwestern Univ., Evanston, IL (United States); Ramuhalli, Pradeep [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wall, Joe [Electric Power Research Inst. (EPRI), Knoxville, TN (United States)

    2015-11-02

    The objective of this research is to demonstrate that nonlinear ultrasonics (NLU) can be used to directly and quantitatively measure the remaining life in radiation damaged reactor pressure vessel (RPV) and internal components. Specific damage types to be monitored are irradiation embrittlement and irradiation assisted stress corrosion cracking (IASCC). Our vision is to develop a technique that allows operators to assess damage by making a limited number of NLU measurements in strategically selected critical reactor components during regularly scheduled outages. This measured data can then be used to determine the current condition of these key components, from which remaining useful life can be predicted. Methods to unambiguously characterize radiation related damage in reactor internals and RPVs remain elusive. NLU technology has demonstrated great potential to be used as a material sensor – a sensor that can continuously monitor a material’s damage state. The physical effect being monitored by NLU is the generation of higher harmonic frequencies in an initially monochromatic ultrasonic wave. The degree of nonlinearity is quantified with the acoustic nonlinearity parameter, β, which is an absolute, measurable material constant. Recent research has demonstrated that nonlinear ultrasound can be used to characterize material state and changes in microscale characteristics such as internal stress states, precipitate formation and dislocation densities. Radiation damage reduces the fracture toughness of RPV steels and internals, and can leave them susceptible to IASCC, which may in turn limit the lifetimes of some operating reactors. The ability to characterize radiation damage in the RPV and internals will enable nuclear operators to set operation time thresholds for vessels and prescribe and schedule replacement activities for core internals. Such a capability will allow a more clear definition of reactor safety margins. The research consists of three tasks: (1

  9. Nonlinear Ultrasonic Techniques to Monitor Radiation Damage in RPV and Internal Components

    International Nuclear Information System (INIS)

    Jacobs, Laurence; Kim, Jin-Yeon; Qu, Jisnmin; Ramuhalli, Pradeep; Wall, Joe

    2015-01-01

    The objective of this research is to demonstrate that nonlinear ultrasonics (NLU) can be used to directly and quantitatively measure the remaining life in radiation damaged reactor pressure vessel (RPV) and internal components. Specific damage types to be monitored are irradiation embrittlement and irradiation assisted stress corrosion cracking (IASCC). Our vision is to develop a technique that allows operators to assess damage by making a limited number of NLU measurements in strategically selected critical reactor components during regularly scheduled outages. This measured data can then be used to determine the current condition of these key components, from which remaining useful life can be predicted. Methods to unambiguously characterize radiation related damage in reactor internals and RPVs remain elusive. NLU technology has demonstrated great potential to be used as a material sensor - a sensor that can continuously monitor a material's damage state. The physical effect being monitored by NLU is the generation of higher harmonic frequencies in an initially monochromatic ultrasonic wave. The degree of nonlinearity is quantified with the acoustic nonlinearity parameter, β, which is an absolute, measurable material constant. Recent research has demonstrated that nonlinear ultrasound can be used to characterize material state and changes in microscale characteristics such as internal stress states, precipitate formation and dislocation densities. Radiation damage reduces the fracture toughness of RPV steels and internals, and can leave them susceptible to IASCC, which may in turn limit the lifetimes of some operating reactors. The ability to characterize radiation damage in the RPV and internals will enable nuclear operators to set operation time thresholds for vessels and prescribe and schedule replacement activities for core internals. Such a capability will allow a more clear definition of reactor safety margins. The research consists of three tasks

  10. Summary of core damage frequency from internal initiators: Peach Bottom

    International Nuclear Information System (INIS)

    Kolaczkowski, A.M.; Lambright, J.A.; Cathey, N.

    1986-01-01

    Probabilistic risk assessments (PRA) based on internal initiators are being conducted on a number of reference plants in order to provide the Nuclear Regulatory Commission (NRC) with updated information about light water reactor risk. The results of these analyses will be used by the NRC to prepare NUREG-1150 which will examine the NRC's current perception of risk. Peach Bottom has been chosen as one of the reference plants

  11. Comparative kinetics of damage to the plasma and mitochondrial membranes by intra-cellularly synthesized and externally-provided photosensitizers using multi-color FACS.

    Science.gov (United States)

    Haupt, Sara; Malik, Zvi; Ehrenberg, Benjamin

    2014-01-01

    Photodynamic therapy (PDT) of cancer involves inflicting lethal damage to the cells of malignant tumors, primarily by singlet oxygen that is generated following light-absorption in a photosensitizer molecule. Dysfunction of cells is manifested in many ways, including peroxidation of cellular components, membrane rupture, depolarization of electric potentials, termination of mitochondrial activity, onset of apoptosis and necrosis and eventually cell lysis. These events do not necessarily occur in linear fashion and different types of damage to cell components occur, most probably, in parallel. In this report we measured the relative rates of damage to two cellular membranes: the plasma membrane and the mitochondrial membrane. We employed photosensitizers of diverse hydrophobicities and used different incubation procedures, which lead to their different intra-cellular localizations. We monitored the damage that was inflicted on these membranes, by employing optical probes of membrane integrity, in a multi-color FACS experiment. The potentiometric indicator JC-1 monitored the electric cross-membrane potential of the mitochondria and the fluorometric indicator Draq7 monitored the rupture of the plasma membrane. We show that the electric depolarization of the mitochondrial membrane and the damage to the enveloping plasma membrane proceed with different kinetics that reflect the molecular character and intracellular location of the sensitizer: PpIX that is synthesized in the cells from ALA causes rapid mitochondrial damage and very slow damage to the plasma membrane, while externally added PpIX has an opposite effect. The hydrophilic sensitizer HypS4 can be taken up by the cells by different incubation conditions, and these affect its intracellular location, and as a consequence either the plasma membrane or the mitochondria is damaged first. A similar correlation was found for additional extracellularly-provided photosensitizers HP and PpIX.

  12. Toxicity evaluation of e-juice and its soluble aerosols generated by electronic cigarettes using recombinant bioluminescent bacteria responsive to specific cellular damages.

    Science.gov (United States)

    Bharadwaj, Shiv; Mitchell, Robert J; Qureshi, Anjum; Niazi, Javed H

    2017-04-15

    Electronic-cigarettes (e-cigarette) are widely used as an alternative to traditional cigarettes but their safety is not well established. Herein, we demonstrate and validate an analytical method to discriminate the deleterious effects of e-cigarette refills (e-juice) and soluble e-juice aerosol (SEA) by employing stress-specific bioluminescent recombinant bacterial cells (RBCs) as whole-cell biosensors. These RBCs carry luxCDABE-operon tightly controlled by promoters that specifically induced to DNA damage (recA), superoxide radicals (sodA), heavy metals (copA) and membrane damage (oprF). The responses of the RBCs following exposure to various concentrations of e-juice/SEA was recorded in real-time that showed dose-dependent stress specific-responses against both the e-juice and vaporized e-juice aerosols produced by the e-cigarette. We also established that high doses of e-juice (4-folds diluted) lead to cell death by repressing the cellular machinery responsible for repairing DNA-damage, superoxide toxicity, ion homeostasis and membrane damage. SEA also caused the cellular damages but the cells showed enhanced bioluminescence expression without significant growth inhibition, indicating that the cells activated their global defense system to repair these damages. DNA fragmentation assay also revealed the disintegration of total cellular DNA at sub-toxic doses of e-juice. Despite their state of matter, the e-juice and its aerosols induce cytotoxicity and alter normal cellular functions, respectively that raises concerns on use of e-cigarettes as alternative to traditional cigarette. The ability of RBCs in detecting both harmful effects and toxicity mechanisms provided a fundamental understanding of biological response to e-juice and aerosols. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Investigating the role of melanin in UVA/UVB- and hydrogen peroxide-induced cellular and mitochondrial ROS production and mitochondrial DNA damage in human melanoma cells.

    Science.gov (United States)

    Swalwell, Helen; Latimer, Jennifer; Haywood, Rachel M; Birch-Machin, Mark A

    2012-02-01

    Skin cancer incidence is dramatically increasing worldwide, with exposure to ultraviolet radiation (UVR) a predominant factor. The UVA component initiates oxidative stress in human skin, although its exact role in the initiation of skin cancer, particularly malignant melanoma, remains unclear and is controversial because there is evidence for a melanin-dependent mechanism in UVA-linked melanoma studies. Nonpigmented (CHL-1, A375), moderately pigmented (FM55, SKmel23), and highly pigmented (FM94, hyperpigmented FM55) human melanoma cell lines have been used to investigate UVA-induced production of reactive oxygen species using FACS analysis, at both the cellular (dihydrorhodamine-123) and the mitochondrial (MitoSOX) level, where most cellular stress is generated. For the first time, downstream mtDNA damage (utilizing a quantitative long-PCR assay) has been investigated. Using UVA, UVB, and H(2)O(2) as cellular stressors, we have explored the dual roles of melanin as a photoprotector and photosensitizer. The presence of melanin has no influence over cellular oxidative stress generation, whereas, in contrast, melanin protects against mitochondrial superoxide generation and mtDNA damage (one-way ANOVA with post hoc Tukey's analysis, Pmelanin binds directly to DNA, it acts as a direct photosensitizer of mtDNA damage during UVA irradiation (Pmelanin. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin.

    Science.gov (United States)

    Nagahama, Masahiro; Takehara, Masaya; Miyamoto, Kazuaki; Ishidoh, Kazumi; Kobayashi, Keiko

    2018-05-20

    Clostridium perfringens iota-toxin is a binary actin-ADP-ribosylating toxin composed of the enzymatic component Ia and receptor binding component Ib. Ib binds to a cell surface receptor, forms Ib oligomer in lipid rafts, and associates with Ia. The Ia-Ib complex then internalizes by endocytosis. Here, we showed that acid sphingomyelinase (ASMase) facilitates the cellular uptake of iota-toxin. Inhibitions of ASMase and lysosomal exocytosis by respective blockers depressed cell rounding induced by iota-toxin. The cytotoxicity of the toxin increased in the presence of Ca 2+ in extracellular fluids. Ib entered target cells in the presence but not the absence of Ca 2+ . Ib induced the extracellular release of ASMase in the presence of Ca 2+ . ASMase siRNA prevented the cell rounding induced by iota-toxin. Furthermore, treatment of the cells with Ib resulted in the production of ceramide in cytoplasmic vesicles. These observations showed that ASMase promotes the internalization of iota-toxin into target cells.

  15. Retinal Pigment Epithelial Cell Culture and Cooperation of L-carnitine in Reducing Stress Induced Cellular Damage

    International Nuclear Information System (INIS)

    Shamsi, Farrukh A.; Al-Rajhi, Ali A.; Athmanathan, S.; Boulton, M.; Chaudhry, Imtiaz A.

    2006-01-01

    Purpose was to show that L-carnitine (LC) is capable of reducing non-oxidative stress in the retinal pigment epithelial cells (RPE) of the human eye. The RPE cells were cultured from donor eyes, obtained immediately after post-mortem. The interaction between bovine serum albumin (BSA) and non-oxidative (sodium hydroxide and methyl methane sulphonate) stress-inducers was observed by recording the change in the absorption profiles of the interacting molecules after incubation in light for 5 hours and after treatment with LC. The isolated and cultured RPE cells from the human eyes were treated with sodium hydroxide or methyl methane sulphonate and/or LC for 5 hours under light, and the qualitative effect on cell morphology after treatment was analyzed by staining cells with Giemsa and visualization by light microscopy. The cell morphology was also qualitatively analyzed by scanning electron microscopy (SEM). L-carnitine and stress-inducers interact with BSA and bring about changes in the spectral profile of the interacted molecules. Light microscopy as well as SEM show that the changes in the cellular morphology, induced by 100 uM concentrations of non-oxidative stress-inducers, are considerably reduced in the presence of 100 uM LC. However, L-carnitine alone does not cause any qualitative damage to the cell morphology during incubation under similar conditions. The results give a preliminary indication that LC has ability to reduce the changes brought about by the non-oxidative stress-inducers in the RPF cells in culture. (author)

  16. Effects of tritiated water ingestion on mice: II. Damage at cellular vis-a-vis subcellular level monitored up to four generations

    International Nuclear Information System (INIS)

    Srivastava, P.N.; Sharan, R.N.; Pozzi, L.

    1983-01-01

    Damage at cellular level is measured using colony forming units in spleen (CFU-S) technique while that at subcellular level by DNA unwinding technique. The damage is monitored up to four generations in Swiss albino mice. The results show drastically reduced colony forming ability in mice bone marrow cells (BMC). On plotting survival fractions (percent of control) for BMC against generations of mice, the plateau is found around 50% survival. The role of DNA in colony forming ability of BMC is tested. The results indicate that, at least, initial impairment of colony ability is not DNA dependent but related to some other factor(s)

  17. LET dependence of linear and quadratic terms in dose-response relationships for cellular damage: correlations with the dimensions and structures of biological targets

    International Nuclear Information System (INIS)

    Barendsen, G.W.; Amsterdam Univ.

    1990-01-01

    To apply information from microdosimetric studies and from cellular responses to the development and testing of hypotheses about mechanisms of radiation action, it is necessary to correlate these data with insights concerning dimensions and structures of cellular constituents and macromolecules. This approach is illustrated by the correlation of cross sections for inactivation with dimensions of the cell nucleus in dependence on the culture conditions and by the comparison of the derived dimensions of critical targets with DNA packing and chromatin structure in cells. A model is suggested in which lethal and potentially lethal damage induced in mammalian cells by single ionising particles involves the induction of two DNA double strand breaks in close proximity in a chromatin fibre, while accumulation of damage causing the contribution, which increases with the square of the dose, might be associated with interaction of single DSBs produced at larger distances. (author)

  18. The Intracellular Destiny of the Protein Corona: A Study on its Cellular Internalization and Evolution.

    Science.gov (United States)

    Bertoli, Filippo; Garry, David; Monopoli, Marco P; Salvati, Anna; Dawson, Kenneth A

    2016-11-22

    It has been well established that the early stages of nanoparticle-cell interactions are governed, at least in part, by the layer of proteins and other biomolecules adsorbed and slowly exchanged with the surrounding biological media (biomolecular corona). Subsequent to membrane interactions, nanoparticles are typically internalized into the cell and trafficked along defined pathways such as, in many cases, the endolysosomal pathway. Indeed, if the original corona is partially retained on the nanoparticle surface, the biomolecules in this layer may play an important role in determining subsequent cellular processing. In this work, using a combination of organelle separation and fluorescence labeling of the initial extracellular corona, we clarify its intracellular evolution as nanoparticles travel within the cell. We show that specific proteins present in the original protein corona are retained on the nanoparticles until they accumulate in lysosomes, and, once there, they are degraded. We also report on how different bare surfaces (amino and carboxyl modified) affect the details of this evolution. One overarching discovery is that the same serum proteins can exhibit different intracellular processing when carried inside cells by nanoparticles, as components of their corona, compared to what is observed when they are transported freely from the extracellular medium.

  19. ATM Is Required for the Prolactin-Induced HSP90-Mediated Increase in Cellular Viability and Clonogenic Growth After DNA Damage.

    Science.gov (United States)

    Karayazi Atici, Ödül; Urbanska, Anna; Gopinathan, Sesha Gopal; Boutillon, Florence; Goffin, Vincent; Shemanko, Carrie S

    2018-02-01

    Prolactin (PRL) acts as a survival factor for breast cancer cells, but the PRL signaling pathway and the mechanism are unknown. Previously, we identified the master chaperone, heat shock protein 90 (HSP90) α, as a prolactin-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) target gene involved in survival, and here we investigated the role of HSP90 in the mechanism of PRL-induced viability in response to DNA damage. The ataxia-telangiectasia mutated kinase (ATM) protein plays a critical role in the cellular response to double-strand DNA damage. We observed that PRL increased viability of breast cancer cells treated with doxorubicin or etoposide. The increase in cellular resistance is specific to the PRL receptor, because the PRL receptor antagonist, Δ1-9-G129R-hPRL, prevented the increase in viability. Two different HSP90 inhibitors, 17-allylamino-17-demethoxygeldanamycin and BIIB021, reduced the PRL-mediated increase in cell viability of doxorubicin-treated cells and led to a decrease in JAK2, ATM, and phosphorylated ATM protein levels. Inhibitors of JAK2 (G6) and ATM (KU55933) abolished the PRL-mediated increase in cell viability of DNA-damaged cells, supporting the involvement of each, as well as the crosstalk of ATM with the PRL pathway in the context of DNA damage. Drug synergism was detected between the ATM inhibitor (KU55933) and doxorubicin and between the HSP90 inhibitor (BIIB021) and doxorubicin. Short interfering RNA directed against ATM prevented the PRL-mediated increase in cell survival in two-dimensional cell culture, three-dimensional collagen gel cultures, and clonogenic cell survival, after doxorubicin treatment. Our results indicate that ATM contributes to the PRL-JAK2-STAT5-HSP90 pathway in mediating cellular resistance to DNA-damaging agents. Copyright © 2018 Endocrine Society.

  20. The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid

    Directory of Open Access Journals (Sweden)

    Hassanin KMA

    2013-05-01

    Full Text Available Kamel MA Hassanin,1 Samraa H Abd El-Kawi,2 Khalid S Hashem1 1Department of Biochemistry, Faculty of Veterinary Medicine, 2Department of Histology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt Background: Nanotechnology has enabled researchers to synthesize nanosize particles that possess increased surface areas. Compared to conventional microparticles, it has resulted in increased interactions with biological targets. Objective: The objective of this study was to determine the protective ability of selenium nanoparticles against hexavalent chromium-induced thyrotoxicity. Design: Twenty male rats were used in the study, and arbitrarily assigned to four groups. Group 1 was the control group, and was given phosphate-buffered saline. Group 2 was the chromium-treated group and was given K2Cr2O7 60 µg/kg body weight intraperitoneally as a single dose on the third day of administration. Group 3 was the nano-selenium-treated group and was given selenium nanoparticles (size 3–20 nm 0.5 mg/kg body weight intraperitoneally daily for 5 consecutive days. Group 4 was the nano-selenium chromium-treated group, which received selenium nanoparticles for 5 days and a single dose of K2Cr2O7 on the third day of administration. Materials and methods: Blood samples were collected from rats for measuring thyroid hormones (free triiodothyronine [T3] and free thyroxine [T4] and oxidative and antioxidant parameters (malondialdehyde [MDA], reduced glutathione [GSH], catalase, and superoxide dismutase [SOD]. Upon dissection, thyroid glands were taken for histopathological examination by using paraffin preparations stained with hematoxylin and eosin (H&E and Masson’s trichrome. Immunohistochemical staining was performed for detecting cellular proliferation using Ki67 antibodies. Results: The present study shows that K2Cr2O7 has a toxic effect on the thyroid gland as a result of inducing a marked oxidative damage and release of reactive oxygen species

  1. [Damage to cranial and peripheral nerves following patency restoration of the internal carotid artery].

    Science.gov (United States)

    Myrcha, P; Ciostek, P; Szopiński, P; Noszczyk, W

    2001-01-01

    The aim of the study was an assessment of the incidence of injury to cranial and peripheral nerves as complication of patency restoration of the internal carotid artery, and analysis of the effect of peripheral nerve injury on the results of carotid patency restoration. From Oct 1987 to Sept 1999 543 procedures were carried out for restoration of patency of the internal carotid artery. After the operation hypoglossus nerve injury was found in 7 cases (1.4%), vagus injury in 9 (1.8%). Signs of exclusively recurrent laryngeal nerve damage were found in 6 cases (1.2%). Glossopharyngeus nerve was damaged in 2 cases (0.4%), transient phrenic nerve palsy as a result of conduction anaesthesia was noted in 2 cases (0.4%). Damage to the transverse cervical nerve was found in 96 cases (60%). In 2 patients (1.2%) lower position of mouth angle was due to section of the mandibular ramus of the facial nerve. In another 2 cases skin sensation disturbances were a consequence of lesion of the auricularis magnus nerve and always they coexisted with signs of transverse cervical nerve damage. damage to the cranial nerves during operation for carotid patency restoration are frequent but mostly they are not connected with any health risks and often they regress spontaneously.

  2. Biomolecular Analysis Capability for Cellular and Omics Research on the International Space Station

    Science.gov (United States)

    Guinart-Ramirez, Y.; Cooley, V. M.; Love, J. E.

    2016-01-01

    International Space Station (ISS) assembly complete ushered a new era focused on utilization of this state-of-the-art orbiting laboratory to advance science and technology research in a wide array of disciplines, with benefits to Earth and space exploration. ISS enabling capability for research in cellular and molecular biology includes equipment for in situ, on-orbit analysis of biomolecules. Applications of this growing capability range from biomedicine and biotechnology to the emerging field of Omics. For example, Biomolecule Sequencer is a space-based miniature DNA sequencer that provides nucleotide sequence data for entire samples, which may be used for purposes such as microorganism identification and astrobiology. It complements the use of WetLab-2 SmartCycler"TradeMark", which extracts RNA and provides real-time quantitative gene expression data analysis from biospecimens sampled or cultured onboard the ISS, for downlink to ground investigators, with applications ranging from clinical tissue evaluation to multigenerational assessment of organismal alterations. And the Genes in Space-1 investigation, aimed at examining epigenetic changes, employs polymerase chain reaction to detect immune system alterations. In addition, an increasing assortment of tools to visualize the subcellular distribution of tagged macromolecules is becoming available onboard the ISS. For instance, the NASA LMM (Light Microscopy Module) is a flexible light microscopy imaging facility that enables imaging of physical and biological microscopic phenomena in microgravity. Another light microscopy system modified for use in space to image life sciences payloads is initially used by the Heart Cells investigation ("Effects of Microgravity on Stem Cell-Derived Cardiomyocytes for Human Cardiovascular Disease Modeling and Drug Discovery"). Also, the JAXA Microscope system can perform remotely controllable light, phase-contrast, and fluorescent observations. And upcoming confocal microscopy

  3. An overview of the international regime governing liability for nuclear damage

    International Nuclear Information System (INIS)

    Sturms, W.; Reye, S.

    1995-01-01

    Since 1986, the IAEA has been seized with considerations of all aspects of international nuclear liability, with a view to establishing a comprehensive international regime that would obtain widest adherence. The practical work is currently being done in the IAEA Standing Committee on Liability for Nuclear Damage. The efforts, which were first concentrated on the improvement of the existing civil liability regime, resulted in adoption, in 1988, of the Joint Protocol to the Vienna Convention and the Paris Convention, combining them into one expanded regime. At present, the work is focused on the following questions: (a) Revision of the Vienna Convention: In this context, specific draft amendments are considered relating to some key issues where need for improvement has been recognized, such as geographical scope, application to military installations, expansion of the definition of damage to cover environmental damage, preventative measures and consequential losses, increase of liability limits, provision of funds by the Installation State, extension of time limits for submission of claims, restriction of exonerations, etc. (b) International State liability and its relationship with the civil liability regime: Emphasis is placed on proposals for Installation State involvement in the provision of public funds in addition to compensation paid by the operator. (c) Elaboration of a supplementary funding system to cover damage exceeding compensation available under the Vienna and Paris Conventions

  4. The Fifth International Ural seminar. Radiation damage physics of metals and alloys. Abstracts

    International Nuclear Information System (INIS)

    2003-01-01

    Presented are the abstracts of The Fifth International Ural seminar Damage physics of metals and alloys. General problems of radiation damage physics, radiation effect on change of microstucture and the properties of metals and alloys, as well as materials for nuclear and thermonuclear energetics are considered. The themes of reports are the following: correlation effects in cascades of atom-atomic collisions; radiation-induced strengthening critical current density in YBa 2 Cu 3 O 7-x superconductors; conditions of forming and hydrides growth in irradiated zirconium alloys [ru

  5. Liability for nuclear damage: an international perspective. Reflections on the revision of the Vienna Convention

    International Nuclear Information System (INIS)

    Lopuski, J.

    1993-01-01

    This book deals with deals of the complex issues of liability and compensation for nuclear damage which have been considered in the course of the work of the IAEA concerning the revision of the Vienna Convention on nuclear liability. It presents, in an orderly way, personal reflections of its author based on his experience gathered in years 1989-1992 when participating in this work. Necessarily it contains in some of its parts references to documents of the IAEA Standing Committee on Nuclear Liability; these documents because of their length could not be reproduced. Consequently these parts may not be fully intelligible for those who have not participated in or closely followed the Committee's work. The IAEA work on liability for nuclear damage was initiated in the wake of the impact made on the world's public opinion by the Chernobyl incident and its transboundary effects; issues of international state liability and full compensation have been raised. But humanitarian ideas have quickly been confronted with cold calculations of the cost of financial protection for victims and an open unwillingness of some nuclear states has been manifested. After three years of discussions no wide consensus could be reached on some basic issues, such as: relationship between international state and civil liability regimes, structure of international legislation, concept of nuclear damage, limits of compensation, role of public funds or jurisdiction. The author presents his approach to these controversial issue, trying to provide at the same time a theoretical outline for the future international legislation on nuclear liability. (author)

  6. Internalization and cellular pools of never growth factor in pheochromocytoma (PC12) cells

    International Nuclear Information System (INIS)

    Neet, K.E.; Kasaian, M.

    1987-01-01

    Nerve Growth Factor (NGF) binds to a cell surface receptor on responsive neuronal cells to initiate cell maintenance and/or differentiation regimes. The purpose of these studies was to define quantitatively the fate of NGF in PC12 cells with respect to various cellular compartments in a single series of biochemical experiments. Different binding methodologies were evaluated in suspension and on plates. 50 pM 125 I-NGF was bound to rat PC12 cells in suspension for 30 min at 37 0 , followed by various methods and combinations of methods to remove subsets of bound ligand. Distinction could be made between NGF bound to fast vs. slow cell surface receptors, NGF bound to slow receptors at the cell surface vs. cell interior, and detergent-soluble vs. cytoskeletally-attached NGF. These treatments defined the relative size of five pools, including the fast receptor (65%), two intracellular compartments (12% and 3%) susceptible to nonionic detergent, and a detergent-stable intracellular pool of ligand (16%). At 37 0 the cold chase stable and the acid stable pools were about the same size because of rapid internalization, but the slow receptor was measurable at 4 0 . Inhibitors were used to define the route of NGF through the cell from the plasma membrane to degradation. Chloroquine caused accumulation of NGF only in pools that were not associated with the cytoskeleton, implicating this compartment in supplying ligand to the lysosome. Results with cytochalasin B and colchicine and suggested both microfilament and microtubule pathways in NGF degradation. A model for the movement of NGF through the cell was developed based on these observations

  7. Adaptive cellular structures and devices with internal features for enhanced structural performance

    Science.gov (United States)

    Pontecorvo, Michael Eugene

    This dissertation aims to develop a family of cellular and repeatable devices that exhibit a variety of force-displacement behaviors. It is envisioned that these cellular structures might be used either as stand-alone elements, or combined and repeated to create multiple types of structures (i.e. buildings, ship hulls, vehicle subfloors, etc.) with the ability to passively or actively perform multiple functions (harmonic energy dissipation, impact mitigation, modulus change) over a range of loading types, amplitudes, and frequencies. To accomplish this goal, this work combines repeatable structural frameworks, such as that provided by a hexagonal cellular structure, with internal structural elements such as springs, viscous dampers, buckling plates, bi-stable von Mises trusses (VMTs), and pneumatic artificial muscles (PAMs). The repeatable framework serves to position damping and load carrying elements throughout the structure, and the configuration of the internal elements allow each cell to be tuned to exhibit a desired force-displacement response. Therefore, gradient structures or structures with variable load paths can be created for an optimal global response to a range of loads. This dissertation focuses on the development of cellular structures for three functions: combined load-carrying capability with harmonic energy dissipation, impact mitigation, and cell modulus variation. One or more conceptual designs are presented for devices that can perform each of these functions, and both experimental measurements and simulations are used to gain a fundamental understanding of each device. Chapter 2 begins with a presentation of a VMT model that is the basis for many of the elements. The equations of motion for the VMT are derived and the static and dynamic behavior of the VMT are discussed in detail. Next, two metrics for the energy dissipation of the VMT - hysteresis loop area and loss factor - are presented. The responses of the VMT to harmonic displacement

  8. A preventive maintenance model for leased equipment subject to internal degradation and external shock damage

    International Nuclear Information System (INIS)

    Zhou, Xiaojun; Wu, Changjie; Li, Yanting; Xi, Lifeng

    2016-01-01

    A periodic preventive maintenance modeling method is proposed for leased equipment with continuous internal degradation and stochastic external shock damage considered simultaneously, which can facilitate the equipment lessor to optimize the maintenance schedule for the same kind of equipment rented by different lessees. A novel interactive mechanism between the continuous internal degradation and the stochastic external shock damage is established on the hazard rate of the equipment with integrating the imperfect effect of maintenance. Two improvement factors are defined for the modeling of imperfect maintenance. The number of failures resulting from internal degradation and from external shocks are both mathematically deduced based on this interactive mechanism. The optimal preventive maintenance scheme is obtained by minimizing the cumulative maintenance cost throughout the lease period. Numerical example shows that the proposed preventive maintenance model not only can reflect the reliability status of the equipment but also can clearly distinguish between the impact from internal degradation and that from external shocks. - Highlights: • We propose an imperfect periodic preventive maintenance model for leased equipment. • It can distinguish between the impact from internal degradation and that from external shocks. • An internal–external interactive mechanism is proposed. • Two improvement factors are introduced into the modeling of imperfect maintenance. • The model is helpful for the PM scheduling of the same equipment rented by different lessees.

  9. Organizing irresponsibility? The (inter)national management of a nuclear accident damages as discursive regime

    International Nuclear Information System (INIS)

    Topcu, Sezin

    2014-01-01

    This article analyzes the historical process related to the international organization of responsibilities and the management of the damages in case of a nuclear disaster. The author shows that the political and legal settings on which the discourse of an 'international regime of civil responsibility' (that emerged in the 1960's) relies, have globally aimed at maintaining a 'historical and spectacular gap' between the damages the nuclear operators are taking responsibility for, and the real and extensive damages engendered by a major accident. She argues that the existence of such a 'gap' is inherent to the nuclear sector, that it is a form of government (both of economic affairs and of the public space) which was historically constructed, and that the existence of such a gap is crucial for the survival of the nuclear industry itself. Thus the notion of 'responsibility' in the nuclear sector appears to serve mainly as a discursive regime, as a means to organize not only responsibilities but also irresponsibilities, whatever the geographic scale (national or international) at which they should be managed

  10. International Co-operation in providing insurance cover for nuclear damage to third parties and for damage to nuclear installations

    International Nuclear Information System (INIS)

    Deprimoz, Jacques

    1983-01-01

    This article in three parts analyses cover for damage to third parties by fixed nuclear installations, cover for damage to third parties during transport of nuclear substances and finally, cover for damage to nuclear installations. Part I reviews the principles of nuclear third party liability and describes nuclear insurance pools, the coverage and contracts provided. Part II describes inter alia the role of pools in transport operations as well as the type of contracts available, while Part III discusses material damage, the pools' capacities and the vast sums involved in indemnifying such damage. (NEA) [fr

  11. REC-2006-A Fractionated Extract of Podophyllum hexandrum Protects Cellular DNA from Radiation-Induced Damage by Reducing the Initial Damage and Enhancing Its Repair In Vivo.

    Science.gov (United States)

    Chaudhary, Pankaj; Shukla, Sandeep Kumar; Sharma, Rakesh Kumar

    2011-01-01

    Podophyllum hexandrum, a perennial herb commonly known as the Himalayan May Apple, is well known in Indian and Chinese traditional systems of medicine. P. hexandrum has been widely used for the treatment of venereal warts, skin infections, bacterial and viral infections, and different cancers of the brain, lung and bladder. This study aimed at elucidating the effect of REC-2006, a bioactive fractionated extract from the rhizome of P. hexandrum, on the kinetics of induction and repair of radiation-induced DNA damage in murine thymocytes in vivo. We evaluated its effect on non-specific radiation-induced DNA damage by the alkaline halo assay in terms of relative nuclear spreading factor (RNSF) and gene-specific radiation-induced DNA damage via semi-quantitative polymerase chain reaction. Whole body exposure of animals with gamma rays (10 Gy) caused a significant amount of DNA damage in thymocytes (RNSF values 17.7 ± 0.47, 12.96 ± 1.64 and 3.3 ± 0.014) and a reduction in the amplification of β-globin gene to 0, 28 and 43% at 0, 15 and 60 min, respectively. Administrating REC-2006 at a radioprotective concentration (15 mg kg(-1) body weight) 1 h before irradiation resulted in time-dependent reduction of DNA damage evident as a decrease in RNSF values 6.156 ± 0.576, 1.647 ± 0.534 and 0.496 ± 0.012, and an increase in β-globin gene amplification 36, 95 and 99%, at 0, 15 and 60 min, respectively. REC-2006 scavenged radiation-induced hydroxyl radicals in a dose-dependent manner stabilized DPPH free radicals and also inhibited superoxide anions. Various polyphenols and flavonoides present in REC-2006 might contribute to scavenging of radiation-induced free radicals, thereby preventing DNA damage and stimulating its repair.

  12. Liability for nuclear damage: an international perspective. Reflections on the revision of the Vienna Convention

    Energy Technology Data Exchange (ETDEWEB)

    Lopuski, J

    1994-12-31

    This book deals with deals of the complex issues of liability and compensation for nuclear damage which have been considered in the course of the work of the IAEA concerning the revision of the Vienna Convention on nuclear liability. It presents, in an orderly way, personal reflections of its author based on his experience gathered in years 1989-1992 when participating in this work. Necessarily it contains in some of its parts references to documents of the IAEA Standing Committee on Nuclear Liability; these documents because of their length could not be reproduced. Consequently these parts may not be fully intelligible for those who have not participated in or closely followed the Committee`s work. The IAEA work on liability for nuclear damage was initiated in the wake of the impact made on the world`s public opinion by the Chernobyl incident and its transboundary effects; issues of international state liability and full compensation have been raised. But humanitarian ideas have quickly been confronted with cold calculations of the cost of financial protection for victims and an open unwillingness of some nuclear states has been manifested. After three years of discussions no wide consensus could be reached on some basic issues, such as: relationship between international state and civil liability regimes, structure of international legislation, concept of nuclear damage, limits of compensation, role of public funds or jurisdiction. The author presents his approach to these controversial issue, trying to provide at the same time a theoretical outline for the future international legislation on nuclear liability. (author).

  13. Liability for nuclear damage: an international perspective. Reflections on the revision of the Vienna Convention

    Energy Technology Data Exchange (ETDEWEB)

    Lopuski, J.

    1993-12-31

    This book deals with deals of the complex issues of liability and compensation for nuclear damage which have been considered in the course of the work of the IAEA concerning the revision of the Vienna Convention on nuclear liability. It presents, in an orderly way, personal reflections of its author based on his experience gathered in years 1989-1992 when participating in this work. Necessarily it contains in some of its parts references to documents of the IAEA Standing Committee on Nuclear Liability; these documents because of their length could not be reproduced. Consequently these parts may not be fully intelligible for those who have not participated in or closely followed the Committee`s work. The IAEA work on liability for nuclear damage was initiated in the wake of the impact made on the world`s public opinion by the Chernobyl incident and its transboundary effects; issues of international state liability and full compensation have been raised. But humanitarian ideas have quickly been confronted with cold calculations of the cost of financial protection for victims and an open unwillingness of some nuclear states has been manifested. After three years of discussions no wide consensus could be reached on some basic issues, such as: relationship between international state and civil liability regimes, structure of international legislation, concept of nuclear damage, limits of compensation, role of public funds or jurisdiction. The author presents his approach to these controversial issue, trying to provide at the same time a theoretical outline for the future international legislation on nuclear liability. (author).

  14. International conventions on civil liability for nuclear damage. Revised 1976 ed.

    International Nuclear Information System (INIS)

    1976-01-01

    This revised edition contains the texts of the following multilateral conventions and instruments concerning civil liability for nuclear damage: The Vienna Convention of 21 May 1963 on Civil Liability for Nuclear Damage; The Paris Convention of 29 July 1960 on Third Party Liability in the Field of Nuclear Energy (incorporating the provisions of the Additional Protocol of 28 January 1964); The Brussels Convention of 31 January 1963; Supplementary to the Paris Convention of 29 July 1960 (and incorporating the provisions of the Additional Protocol signed in Paris on 28 January 1964); and the Brussels Convention of 25 May 1962 on the Liability of Operators of Nuclear Ships. Final Act and Resolutions of the International Conference on Civil Liability for Nuclear Damage, held in Vienna from 29 April to 19 May 1963; Final Act of the International Legal Conference on Maritime Carriage of Nuclear Substances, held in Brussels from 29 November to 2 December 1971; and Convention Relating to Civil Liability in the Field of Maritime Carriage of Nuclear Material, adopted at Brussels on 17 December 1971

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

    International Nuclear Information System (INIS)

    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

  16. Review of the Shoreham Nuclear Power Station Probabilistic Risk Assessment: internal events and core damage frequency

    International Nuclear Information System (INIS)

    Ilberg, D.; Shiu, K.; Hanan, N.; Anavim, E.

    1985-11-01

    A review of the Probabilistic Risk Assessment of the Shoreham Nuclear Power Station was conducted with the broad objective of evaluating its risks in relation to those identified in the Reactor Safety Study (WASH-1400). The scope of the review was limited to the ''front end'' part, i.e., to the evaluation of the frequencies of states in which core damage may occur. Furthermore, the review considered only internally generated accidents, consistent with the scope of the PRA. The review included an assessment of the assumptions and methods used in the Shoreham study. It also encompassed a reevaluation of the main results within the scope and general methodological framework of the Shoreham PRA, including both qualitative and quantitative analyses of accident initiators, data bases, and accident sequences which result in initiation of core damage. Specific comparisons are given between the Shoreham study, the results of the present review, and the WASH-1400 BWR, for the core damage frequency. The effect of modeling uncertainties was considered by a limited sensitivity study so as to show how the results would change if other assumptions were made. This review provides an independently assessed point value estimate of core damage frequency and describes the major contributors, by frontline systems and by accident sequences. 17 figs., 81 tabs

  17. Analysis of core damage frequency, Surry, Unit 1 internal events appendices

    International Nuclear Information System (INIS)

    Bertucio, R.C.; Julius, J.A.; Cramond, W.R.

    1990-04-01

    This document contains the appendices for the accident sequence analyses of internally initiated events for the Surry Nuclear Station, Unit 1. This is one of the five plant analyses conducted as part of the NUREG-1150 effort by the Nuclear Regulatory Commission. NUREG-1150 documents the risk of a selected group of nuclear power plants. The work performed is an extensive reanalysis of that published in November 1986 as NUREG/CR-4450, Volume 3. It addresses comments from numerous reviewers and significant changes to the plant systems and procedures made since the first report. The uncertainty analysis and presentation of results are also much improved. The context and detail of this report are directed toward PRA practitioners who need to know how the work was performed and the details for use in further studies. The mean core damage frequency at Surry was calculated to be 4.0E-5 per year, with a 95% upper bound of 1.3E-4 and 5% lower bound of 6.8E-6 per year. Station blackout type accidents (loss of all AC power) were the largest contributors to the core damage frequency, accounting for approximately 68% of the total. The next type of dominant contributors were Loss of Coolant Accidents (LOCAs). These sequences account for 15% of core damage frequency. No other type of sequence accounts for more than 10% of core damage frequency

  18. Ultrastructural and cellular damage to rat lung with x-rays: a search for target cell in lung tissue

    Energy Technology Data Exchange (ETDEWEB)

    Furuta, I

    1975-03-01

    Radiation effects on the peripheral alveoli of conventional rats were examined by means of electron microscopy. The right hemithorax alone was exposed to various single doses of x rays. The initial cellular lesions selectively involved the cytoplasms of alveolar capillary endothelial (Ed) and type 1 epithelial (Ep 1) cells in a dose-dependent fashion, where the major alterations were multifocal vacuolations and swellings. These lesions became visible as early as 1 hr after 1000 R (the assumed mean lethal dose for Ed cells) and more. However, progenitor Ep 2 cells exhibited no obvious cytoplasmic lesions by the doses below 2000 R, indicating that Ep 2 cells are more resistant to x rays. With time following 1000 R, the capillary Ed blebbing abruptly developed in various forms from the sites presumably other than the Ed junctions. The Ed blebs and interstitial edema progressed until about 2 weeks without recovery, while some signs of cellular recovery were recognized in Ep 1 cells during this period. The observations after a long period of 6 months following 1000 R showed that the typical pulmonary fibrotic changes were initiated in the interstitium perhaps around unrepaired capillaries. Further, inflammatory reaction characterized by massive cellular infiltations was superimposed on developing pulmonary fibrosis. Considering the current knowledge about the cell sensitivity and renewal in stable tissues, the present results imply that capillary Ed cell is the primary target for the radiation lesion leading to the secondary pulmonary alterations.

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

    Energy Technology Data Exchange (ETDEWEB)

    Harris, C.E.

    1994-09-01

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

  20. The law applicable to environmental damage in European private international law

    Directory of Open Access Journals (Sweden)

    Đundić Petar

    2013-01-01

    Full Text Available The paper contains an analysis of choice of law rules in the field of non-contractual liability for damage caused to environment in national legislations of European countries as well as in Private International Law of the European Union. Before the adoption of Regulation of the European Parliament and of the Council on the law applicable to non-contractual obligations (Rome II, special choice of law rules for environmental torts existed in a small number of European national legal orders. This is the fact that gives the rule contained in Article 7 of the Rome II Regulation a particular importance. From the Serbian Private International Law perspective, the significance of that provision is highlighted by the fact that the working draft of the new Serbian Private International Law Act has strictly followed the choice of law rule envisaged by the European legislator for environmental damage. For that reason, a significant part of the paper is dedicated to analysis of said rule, to its interpretation and potential problems which its application could create.

  1. In Vivo Bystander Effect: Cranial X-Irradiation Leads to Elevated DNA Damage, Altered Cellular Proliferation and Apoptosis, and Increased p53 Levels in Shielded Spleen

    International Nuclear Information System (INIS)

    Koturbash, Igor; Loree, Jonathan; Kutanzi, Kristy; Koganow, Clayton; Pogribny, Igor; Kovalchuk, Olga

    2008-01-01

    Purpose: It is well accepted that irradiated cells may 'forward' genome instability to nonirradiated neighboring cells, giving rise to the 'bystander effect' phenomenon. Although bystander effects were well studied by using cell cultures, data for somatic bystander effects in vivo are relatively scarce. Methods and Materials: We set out to analyze the existence and molecular nature of bystander effects in a radiation target-organ spleen by using a mouse model. The animal's head was exposed to X-rays while the remainder of the body was completely protected by a medical-grade shield. Using immunohistochemistry, we addressed levels of DNA damage, cellular proliferation, apoptosis, and p53 protein in the spleen of control animals and completely exposed and head-exposed/body bystander animals. Results: We found that localized head radiation exposure led to the induction of bystander effects in the lead-shielded distant spleen tissue. Namely, cranial irradiation led to increased levels of DNA damage and p53 expression and also altered levels of cellular proliferation and apoptosis in bystander spleen tissue. The observed bystander changes were not caused by radiation scattering and were observed in two different mouse strains; C57BL/6 and BALB/c. Conclusion: Our study proves that bystander effects occur in the distant somatic organs on localized exposures. Additional studies are required to characterize the nature of an enigmatic bystander signal and analyze the long-term persistence of these effects and possible contribution of radiation-induced bystander effects to secondary radiation carcinogenesis

  2. Characterisation of Human Keratinocytes by Measuring Cellular Repair Capacity of UVB-Induced DNA Damage and Monitoring of Cytogenetic Changes in Melanoma Cell Lines

    Energy Technology Data Exchange (ETDEWEB)

    Greinert, R.; Breibart, E.W.; Mitchell, D.; Smida, J.; Volkmer, B

    2000-07-01

    The molecular mechanisms for UV-induced photocarcinogenesis are far from being understood in detail, especially in the case of malignant melanoma of the skin. Nevertheless, it is known that deficiencies in cellular repair processes of UV-induced DNA damage (e.g. in the case of Xeroderma pigmentosum) represent important aetiological factors in the multistep development of skin cancer. The repair kinetics have therefore been studied of an established skin cell line (HaCaT), primary human keratinocytes, melanocytes and melanoma cell lines, using fluorescence microscopy and flow cytometry. Our data show a high degree of interindividual variability in cellular repair capacity for UV-induced DNA lesions, which might be due to individual differences in the degree of tolerable damage and/or the onsets of saturation of the enzymatic repair system. The cytogenetic analysis of melanoma cell lines, using spectral karyotyping (SKY) furthermore proves that malignant melanoma of the skin are characterised by high numbers of chromosomal aberrations. (author)

  3. Damage to cellular DNA from particulate radiations, the efficacy of its processing and the radiosensitivity of mammalian cells. Emphasis on DNA double strand breaks and chromatin breaks

    Science.gov (United States)

    Lett, J. T.

    1992-01-01

    For several years, it has been evident that cellular radiation biology is in a necessary period of consolidation and transition (Lett 1987, 1990; Lett et al. 1986, 1987). Both changes are moving apace, and have been stimulated by studies with heavy charged particles. From the standpoint of radiation chemistry, there is now a consensus of opinion that the DNA hydration shell must be distinguished from bulk water in the cell nucleus and treated as an integral part of DNA (chromatin) (Lett 1987). Concomitantly, sentiment is strengthening for the abandonment of the classical notions of "direct" and "indirect" action (Fielden and O'Neill 1991; O'Neill 1991; O'Neill et al. 1991; Schulte-Frohlinde and Bothe 1991 and references therein). A layer of water molecules outside, or in the outer edge of, the DNA (chromatin) hydration shell influences cellular radiosensitivity in ways not fully understood. Charge and energy transfer processes facilitated by, or involving, DNA hydration must be considered in rigorous theories of radiation action on cells. The induction and processing of double stand breaks (DSBs) in DNA (chromatin) seem to be the predominant determinants of the radiotoxicity of normally radioresistant mammalian cells, the survival curves of which reflect the patterns of damage induced and the damage present after processing ceases, and can be modelled in formal terms by the use of reaction (enzyme) kinetics. Incongruities such as sublethal damage are neither scientifically sound nor relevant to cellular radiation biology (Calkins 1991; Lett 1990; Lett et al. 1987a). Increases in linear energy transfer (LET infinity) up to 100-200 keV micron-1 cause increases in the extents of neighboring chemical and physical damage in DNA denoted by the general term DSB. Those changes are accompanied by decreasing abilities of cells normally radioresistant to sparsely ionizing radiations to process DSBs in DNA and chromatin and to recover from radiation exposure, so they make

  4. Reducing the Risk of Damage to Power Transformers of 110 kV and Above Accompanying Internal Short Circuits

    Energy Technology Data Exchange (ETDEWEB)

    L’vova, M. M. [JSC “R& D Center at Federal Grid Company of the Unified Power System” (Russian Federation); L’vov, S. Yu. [Presselektro LLC (Russian Federation); Komarov, V. B. [IPCE RAS (Russian Federation); Lyut’ko, E. O. [JSC “R& D Center at Federal Grid Company of the Unified Power System” (Russian Federation); Vdoviko, V. P. [EMA Ltd. (Russian Federation); Demchenko, V. V. [JSC “Boguchanskaya HPP” (Russian Federation); Belyaev, S. G. [PKF Konif Ltd. (Russian Federation); Savel’ev, V. A. [Ivanovo State Power University (Russian Federation); L’vov, M. Yu., E-mail: timashova@nte-power.ru; L’vov, Yu. N. [JSC “R& D Center at Federal Grid Company of the Unified Power System” (Russian Federation)

    2015-03-15

    Methods of increasing the operating reliability of power transformers, autotransformers and shunting reactors in order to reduce the risk of damage, which accompany internal short circuits and equipment fires and explosions, are considered.

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

    Science.gov (United States)

    Su-Yuen, Hsu

    2011-01-01

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

  6. Cell type-dependent induction of DNA damage by 1800 MHz radiofrequency electromagnetic fields does not result in significant cellular dysfunctions.

    Directory of Open Access Journals (Sweden)

    Shanshan Xu

    Full Text Available BACKGROUND: Although IARC clarifies radiofrequency electromagnetic fields (RF-EMF as possible human carcinogen, the debate on its health impact continues due to the inconsistent results. Genotoxic effect has been considered as a golden standard to determine if an environmental factor is a carcinogen, but the currently available data for RF-EMF remain controversial. As an environmental stimulus, the effect of RF-EMF on cellular DNA may be subtle. Therefore, more sensitive method and systematic research strategy are warranted to evaluate its genotoxicity. OBJECTIVES: To determine whether RF-EMF does induce DNA damage and if the effect is cell-type dependent by adopting a more sensitive method γH2AX foci formation; and to investigate the biological consequences if RF-EMF does increase γH2AX foci formation. METHODS: Six different types of cells were intermittently exposed to GSM 1800 MHz RF-EMF at a specific absorption rate of 3.0 W/kg for 1 h or 24 h, then subjected to immunostaining with anti-γH2AX antibody. The biological consequences in γH2AX-elevated cell type were further explored with comet and TUNEL assays, flow cytometry, and cell growth assay. RESULTS: Exposure to RF-EMF for 24 h significantly induced γH2AX foci formation in Chinese hamster lung cells and Human skin fibroblasts (HSFs, but not the other cells. However, RF-EMF-elevated γH2AX foci formation in HSF cells did not result in detectable DNA fragmentation, sustainable cell cycle arrest, cell proliferation or viability change. RF-EMF exposure slightly but not significantly increased the cellular ROS level. CONCLUSIONS: RF-EMF induces DNA damage in a cell type-dependent manner, but the elevated γH2AX foci formation in HSF cells does not result in significant cellular dysfunctions.

  7. Quantitative Proteomics Reveals Dynamic Interactions of the Minichromosome Maintenance Complex (MCM) in the Cellular Response to Etoposide Induced DNA Damage.

    Science.gov (United States)

    Drissi, Romain; Dubois, Marie-Line; Douziech, Mélanie; Boisvert, François-Michel

    2015-07-01

    The minichromosome maintenance complex (MCM) proteins are required for processive DNA replication and are a target of S-phase checkpoints. The eukaryotic MCM complex consists of six proteins (MCM2-7) that form a heterohexameric ring with DNA helicase activity, which is loaded on chromatin to form the pre-replication complex. Upon entry in S phase, the helicase is activated and opens the DNA duplex to recruit DNA polymerases at the replication fork. The MCM complex thus plays a crucial role during DNA replication, but recent work suggests that MCM proteins could also be involved in DNA repair. Here, we employed a combination of stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative proteomics with immunoprecipitation of green fluorescent protein-tagged fusion proteins to identify proteins interacting with the MCM complex, and quantify changes in interactions in response to DNA damage. Interestingly, the MCM complex showed very dynamic changes in interaction with proteins such as Importin7, the histone chaperone ASF1, and the Chromodomain helicase DNA binding protein 3 (CHD3) following DNA damage. These changes in interactions were accompanied by an increase in phosphorylation and ubiquitination on specific sites on the MCM proteins and an increase in the co-localization of the MCM complex with γ-H2AX, confirming the recruitment of these proteins to sites of DNA damage. In summary, our data indicate that the MCM proteins is involved in chromatin remodeling in response to DNA damage. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Antioxidant-Rich Fraction of Urtica dioica Mediated Rescue of Striatal Mito-Oxidative Damage in MPTP-Induced Behavioral, Cellular, and Neurochemical Alterations in Rats.

    Science.gov (United States)

    Bisht, Rohit; Joshi, Bhuwan Chandra; Kalia, Ajudhiya Nath; Prakash, Atish

    2017-09-01

    Parkinson's disease (PD) having a complex and multi-factorial neuropathology includes mainly the degeneration of the dopaminergic nigrostriatal pathway, which is a cumulative effect of depleted endogenous antioxidant enzymes, increased oxidative DNA damage, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. The present study was designed to investigate the neuroprotective effect of a potent antioxidant from Urtica dioica in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. MPTP was administered intranigrally for the induction of PD in male Wistar rats. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical, cellular, and neurochemical parameters were measured. Intranigrally repeated administration of MPTP showed significant impairment of motor co-ordination and marked increase of mito-oxidative damage and neuroinflammation in rats. Intranigral MPTP significantly decreases the dopamine and its metabolites with impairment of dopaminergic cell density in rat brain. However, post-treatment with the potent antioxidant fraction of Urtica dioica Linn. (UD) (20, 40, 80 mg/kg) improved the motor function, mito-oxidative defense alteration significantly and dose dependently in MPTP-treated rats. In addition, the potent antioxidant fraction of UD attenuated the pro-inflammatory cytokines (TNF-α and IL-β) and restored the level of dopamine and its metabolites in MPTP-induced PD in rats. Moreover, minocycline (30 mg/kg) with lower dose of UD (20 mg/kg) had significantly potentiated the protective effect of minocycline as compared to its effect with other individual drug-treated groups. In conclusion, Urtica dioica protected the dopaminergic neurons probably by reducing mito-oxidative damage, neuroinflammation, and cellular alteration along with enhanced neurotrophic potential. The above results revealed that the antioxidant rich

  9. Internalization and cellular processing of cholecystokinin in rat pancreatic acinar cells

    International Nuclear Information System (INIS)

    Izzo, R.S.; Pellecchia, C.; Praissman, M.

    1988-01-01

    To evaluate the internalization of cholecystokinin, monoiodinated imidoester of cholecystokinin octapeptide [ 125 I-(IE)-CCK-8] was bound to dispersed pancreatic acinar cells, and surface-bound and internalized radioligand were differentiated by treating with an acidified glycine buffer. The amount of internalized radioligand was four- and sevenfold greater at 24 and 37 degree C than at 4 degree C between 5 and 60 min of association. Specific binding of radioligand to cell surface receptors was not significantly different at these temperatures. Chloroquine, a lysosomotropic agent that blocks intracellular proteolysis, significantly increased the amount of CCK-8 internalized by 18 and 16% at 30 and 60 min of binding, respectively, compared with control. Dithiothreitol (DTT), a sulfhydryl reducing agent, also augmented the amount of CCK-8 radioligand internalized by 25 and 29% at 30 and 60 min, respectively. The effect of chloroquine and DTT on the processing of internalized radioligand was also considered after an initial 60 min of binding of radioligand to acinar cells. After 180 min of processing, the amount of radioligand internalized was significantly greater in the presence of chloroquine compared with controls, whereas the amount of radioligand declined in acinar cells treated with DTT. Internalized and released radioactivity from acinar cells was rebound to pancreatic membrane homogenates to determine the amount of intact radioligand during intracellular processing. Chloroquine significantly increased the amount of intact 125 I-(IE)-CCK-8 radioligand in released and internalized radioactivity while DTT increased the amount of intact radioligand only in internalized samples. This study shows that pancreatic acinar cells rapidly internalize large amounts of CCK-8 and that chloroquine and DTT inhibit intracellular degradation

  10. Cellular and genetic effects and recovery of heat-damaged cells of Saccharomyces cerevisiae by low intensity electromagnetic radiation at 915 MHz

    International Nuclear Information System (INIS)

    Sheikh, I.H.

    1984-01-01

    Studies were conducted on two genetically well known strains of Saccharomyces cerevisiae (Wild Type) and repair deficient mutant (UVS). Results obtained showed clear genetic difference between normal and mutants based on UV sensitivity, percent survival at elevated temperatures and high intensity electromagnetic radiation. At the cellular level, both strains showed a consistent increase in the recovery rate of heat damaged cells when exposed to low intensity FMR as compared to sham (non irradiated cells) at 915 MHz. The percent recovery of wild type was higher than mutant. At the molecular level, the uptake of tritiated uridine into thermally damaged cells which were recovered by low level EMR was significantly higher than sham. Total RNA isolated from irradiated cells and sham showed visible differences in the intensity of RNA bands. Gross quantitative analyses suggest more RNA production in radiation recovered cells as compared to sham. Results presented in this dissertation provide conclusive evidence that low level microwave radiation can be used in the recovery of heat damaged cells

  11. PREFACE: 11th International Conference on Damage Assessment of Structures (DAMAS 2015)

    Science.gov (United States)

    Wahab, M. A.

    2015-07-01

    This volume contains the proceedings of the 11th International Conference on Damage Assessment of Structures (DAMAS) 2015. DAMAS has a long history of almost 20 years. The first DAMAS conference took place in 1995 (Pescara, Italy), followed by a biannual meeting in 1997 (Sheffield, UK), 1999 (Dublin, Ireland), 2001 (Cardiff, UK), 2003 (Southampton, UK), 2005 (Gdansk, Poland), 2007 (Torino, Italy), 2009 (Beijing, China), 2011 (Oxford, UK) and 2013 (Dublin, Ireland). The eleventh edition of DAMAS conference series, DAMAS 2015, is hosted by Ghent University, Belgium, and is held at the congress center Het Pand in Ghent city. Ghent is the capital and the largest city of the East Flanders province of the Flemish region of Belgium. Het Pand is the culture and congress center of Ghent University and is a historical monument. The conference is established as a major international forum for research topics relevant to damage assessment of engineering structures and systems including numerical simulations, signal processing of sensor measurements and theoretical techniques as well as experimental case studies. The presentations of DAMAS 2015 are divided into 6 main sessions, namely 1) Structural Health and Condition Monitoring, 2) Damage in Civil Engineering, 3) Damage in Machineries, 4) Damage in Composite Materials, 5) Sensing and Sensors and 6) Signal Processing. The organising committee is grateful to keynote speakers; Professor Guido De Roeck, Head of Structural Mechanics Division, KULeuven, Belgium, for his keynote lecture entitled 'Structural Health Monitoring: highlights and challenges', Professor Weidong Zhu, Department of Mechanical Engineering, University of Maryland, USA, for his keynote lecture entitled 'Vibration-based Structural Damage Detection: Theory and Applications' and Professor Wieslaw Ostachowicz, Head of the Laboratory of Active Materials and Smart Structures, Polish Academy of Sciences, Poland, for his keynote lecture entitled 'Damage Assessment and

  12. The miRNA Profile of Platelets Stored in a Blood Bank and Its Relation to Cellular Damage from Storage.

    Directory of Open Access Journals (Sweden)

    Thaís Brilhante Pontes

    Full Text Available Millions of blood products are transfused each year, and many lives are directly affected by transfusion. Platelet concentrate (PC is one of the main products derived from blood. Even under good storage conditions, PC is likely to suffer cell damage. The shape of platelets changes after 5 to 7 days of storage at 22°C. Taking into consideration that some platelet proteins undergo changes in their shape and functionality during PC storage. Sixteen PC bags were collected and each PC bag tube was cut into six equal pieces to perform experiments with platelets from six different days of storage. Thus, on the first day of storage, 1/6 of the tube was used for miRNA extraction, and the remaining 5/6 was stored under the same conditions until extraction of miRNAs on each the following five days. Samples were sequenced on an Illumina Platform to demonstrate the most highly expressed miRNAs. Three miRNAs, mir127, mir191 and mir320a were validated by real-time quantitative PCR (RQ-PCR in 100 PC bags tubes. Our method suggests, the use of the miRNAs mir127 and mir320a as biomarkers to assess the "validity period" of PC bags stored in blood banks for long periods. Thus, bags can be tested on the 5th day of storage for the relative expression levels of mir127 and mir320a. Thus, we highlight candidate miRNAs as biomarkers of storage damage that can be used as tools to evaluate the quality of stored PC. The use of miRNAs as biomarkers of damage is unprecedented and will contribute to improved quality of blood products for transfusions.

  13. Protein kinase CK2 localizes to sites of DNA double-strand break regulating the cellular response to DNA damage

    Directory of Open Access Journals (Sweden)

    Olsen Birgitte B

    2012-03-01

    Full Text Available Abstract Background The DNA-dependent protein kinase (DNA-PK is a nuclear complex composed of a large catalytic subunit (DNA-PKcs and a heterodimeric DNA-targeting subunit Ku. DNA-PK is a major component of the non-homologous end-joining (NHEJ repair mechanism, which is activated in the presence of DNA double-strand breaks induced by ionizing radiation, reactive oxygen species and radiomimetic drugs. We have recently reported that down-regulation of protein kinase CK2 by siRNA interference results in enhanced cell death specifically in DNA-PKcs-proficient human glioblastoma cells, and this event is accompanied by decreased autophosphorylation of DNA-PKcs at S2056 and delayed repair of DNA double-strand breaks. Results In the present study, we show that CK2 co-localizes with phosphorylated histone H2AX to sites of DNA damage and while CK2 gene knockdown is associated with delayed DNA damage repair, its overexpression accelerates this process. We report for the first time evidence that lack of CK2 destabilizes the interaction of DNA-PKcs with DNA and with Ku80 at sites of genetic lesions. Furthermore, we show that CK2 regulates the phosphorylation levels of DNA-PKcs only in response to direct induction of DNA double-strand breaks. Conclusions Taken together, these results strongly indicate that CK2 plays a prominent role in NHEJ by facilitating and/or stabilizing the binding of DNA-PKcs and, possibly other repair proteins, to the DNA ends contributing to efficient DNA damage repair in mammalian cells.

  14. Overview of the RPV-2 and INTERN-1 packages: From primary damage to microplasticity

    International Nuclear Information System (INIS)

    Adjanor, G.; Bugat, S.; Domain, C.; Barbu, A.

    2010-01-01

    In the framework of the European project PERFECT, four multiscale simulation packages dedicated to the prediction of evolution of material properties were developed. Among them, the RPV-2 and INTERN-1 are two simulation sequences of similar structure dealing with radiation damage in the reactor pressure vessel and the reactor internal structures, respectively. Both start at the atomic scale, where the neutron spectrum of the specified reactor is used to determine the energy distribution of the primary knocked-on atoms (PKA). A database of molecular dynamics results is then used to integrate the instantaneous production of defect clusters resulting from the displacement cascades initiated by each PKA. Depending on the type of calculation chosen to model long-term diffusion and reactions of defect clusters, precipitates and mixed-clusters, this primary damage enters either in rate equations or in Object Kinetic Monte Carlo simulations. The later correspond to a more accurate (but also more computationally demanding) physical model for diffusion as positions of objects on a lattice are explicitly treated. Finally, the increase of critical resolved shear stress is estimated from these cluster distributions either using an analytical model, taking into account the self and mutual dipole interactions of dislocations pinned on randomly dispersed unshearable obstacles, or by simulating the glide of a single dislocation line in its main slip system. Dislocation dynamics simulations were already used to validate some of the assumptions of the latter models, and will be fully integrated in the next versions of the packages.

  15. Damage on sliding bearings of internal combustion engines. Damage patterns, causes, prevention; Schaeden an Gleitlagern von Verbrennungsmotoren. Erscheinungsbilder, Ursachen, Vermeidung

    Energy Technology Data Exchange (ETDEWEB)

    Ederer, U.G. [Miba Gleitlager GmbH, Laakrichen (Austria)

    2005-07-01

    Bearing failures are consequences of system deficiencies which cause an inadequate function of the hydrodynamic action and, thereby, too high a friction, at least locally. The bearing overheats, what ultimately leads to its destruction and that of adjacent components. These 'consequential damages' are frequently severe. We identify, therefore, early stages of malfunction, already as 'bearing damage'. In this condition, a diagnosis and remedial measures to avoid total destruction are possible. Typical bearing conditions, possible causes and remedies are described herein. (orig.)

  16. The right choice of antihypertensives protects primary human hepatocytes from ethanol- and recombinant human TGF-β1-induced cellular damage

    Directory of Open Access Journals (Sweden)

    Ehnert S

    2013-03-01

    Full Text Available Sabrina Ehnert,1 Teresa Lukoschek,2 Anastasia Bachmann,2 Juan J Martínez Sánchez,1 Georg Damm,3 Natascha C Nussler,4 Stefan Pscherer,5 Ulrich Stöckle,1 Steven Dooley,2 Sebastian Mueller,6 Andreas K Nussler11Eberhard Karls Universität Tübingen, BG Trauma Center, Tübingen, Germany; 2Mol Hepatology - Alcohol Associated Diseases, Department of Medicine II, Medical Faculty, Mannheim, Germany; 3Department of General, Visceral, and Transplantation Surgery, Charité University Medicine, Berlin, Germany; 4Clinic for General, Visceral, Endocrine Surgery and Coloproctology, Clinic Neuperlach, Städtisches Klinikum München GmbH, Munich, Germany; 5Department of Diabetology, Klinikum Traunstein, Kliniken Südostbayern AG, Traunstein, Germany; 6Department of Medicine, Salem Medical Center, Ruprecht-Karls-Universität, Heidelberg, GermanyBackground: Patients with alcoholic liver disease (ALD often suffer from high blood pressure and rely on antihypertensive treatment. Certain antihypertensives may influence progression of chronic liver disease. Therefore, the aim of this study is to investigate the impact of the commonly used antihypertensives amlodipine, captopril, furosemide, metoprolol, propranolol, and spironolactone on alcohol-induced damage toward human hepatocytes (hHeps.Methods: hHeps were isolated by collagenase perfusion. Reactive oxygen species (ROS were measured by fluorescence-based assays. Cellular damage was determined by lactate-dehydrogenase (LDH-leakage. Expression analysis was performed by reverse-transcription polymerase chain reaction and Western blot. Transforming growth factor (TGF-β signaling was investigated by a Smad3/4-responsive luciferase-reporter assay.Results: Ethanol and TGF-β1 rapidly increased ROS in hHeps, causing a release of 40%–60% of total LDH after 72 hours. All antihypertensives dose dependently reduced ethanol-mediated oxidative stress and cellular damage. Similar results were observed for TGF-β1-dependent

  17. Poly(methyl vinyl ether-alt-maleic acid)-functionalized porous silicon nanoparticles for enhanced stability and cellular internalization.

    Science.gov (United States)

    Shahbazi, Mohammad-Ali; Almeida, Patrick V; Mäkilä, Ermei; Correia, Alexandra; Ferreira, Mónica P A; Kaasalainen, Martti; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

    2014-03-01

    Currently, developing a stable nanocarrier with high cellular internalization and low toxicity is a key bottleneck in nanomedicine. Here, we have developed a successful method to covalently conjugate poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of (3-aminopropyl)triethoxysilane-functionalized thermally carbonized porous silicon nanoparticles (APSTCPSi NPs), forming a surface negatively charged nanovehicle with unique properties. This polymer conjugated NPs could modify surface smoothness, charge, and hydrophilicity of the developed NPs, leading to considerable improvement in the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the polymer-conjugated NPs, the cellular internalization was increased in both MDA-MB-231 and MCF-7 breast cancer cells. These results provide a proof-of-concept evidence that such polymer-based PSi nanocomposite can be extensively used as a promising candidate for intracellular drug delivery. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Phyto-mediated nanostructured carriers based on dual vegetable actives involved in the prevention of cellular damage.

    Science.gov (United States)

    Istrati, D; Lacatusu, I; Bordei, N; Badea, G; Oprea, O; Stefan, L M; Stan, R; Badea, N; Meghea, A

    2016-07-01

    The growing scientific interest in exploitation of vegetable bioactives has raised a number of questions regarding their imminent presence in pharmaceutical formulations. This study intends to demonstrate that a dual combination between vegetable oil (e.g. thistle oil, safflower oil, sea buckthorn oil) and a carrot extract represents an optimal approach to formulate safe carrier systems that manifest cell regeneration effect and promising antioxidant and anti-inflammatory activity. Inclusion of both natural actives into lipid carriers imparted a strong negative charge on the nanocarrier surface (up to -45mV) and displayed average sizes of 70nm to 140nm. The entrapment efficiency of carrot extract into nanostructured carriers ranged between 78.3 and 88.3%. The in vitro release study has demonstrated that the entrapment of the extract represents a viable way for an equilibrated release of carotenoids. Besides the excellent antioxidant properties (e.g. scavenging up to 98% of the free oxygen radicals), the results of cellular integrity (e.g. cell viability of 133%) recommend these nanocarriers based on dual carrot extract-bioactive oil as a promising trend for the treatment of certain disorders in which oxidative stress plays a prominent role. In addition, the lipid nanocarriers based on safflower oil and sea buckthorn oil demonstrated an anti-inflammatory effect on LPS induced THP-1 macrophages, by inhibiting the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Patients with HBV-related acute-on-chronic liver failure have increased concentrations of extracellular histones aggravating cellular damage and systemic inflammation.

    Science.gov (United States)

    Li, X; Gou, C; Yao, L; Lei, Z; Gu, T; Ren, F; Wen, T

    2017-01-01

    Acute-on-chronic liver failure (ACLF) is the most common type of liver failure and associated with grave consequences. Systemic inflammation has been linked to its pathogenesis and outcome, but the identifiable triggers are absent. Recently, extracellular histones, especially H4, have been recognized as important mediators of cell damage in various inflammatory conditions. This study aimed to investigate whether extracellular histones have clinical implications in patients with hepatitis B virus (HBV)-related ACLF. One hundred and twelve patients with HBV-related ACLF, 90 patients with chronic hepatitis B, 88 patients with HBV-related liver cirrhosis and 40 healthy volunteers were entered into this study. Plasma histone H4 levels, cytokine profile and clinical data were obtained. Besides, patient's sera were incubated overnight with human L02 hepatocytes or monocytic U937 cells in the presence or absence of antihistone H4 antibody, and cellular damage and cytokine production were evaluated. We found that plasma histone H4 levels were greatly increased in patients with ACLF as compared with chronic hepatitis B, liver cirrhosis and healthy control subjects and were significantly associated with disease severity, systemic inflammation and outcome. Notably, ACLF patients' sera incubation decreased cultured L02 cell integrity and induced profound cytokine production in the supernatant of U937 cells. Antihistone H4 antibody treatment abrogated these adverse effects, thus confirming a cause-effect relationship between extracellular histones and organ injury/dysfunction. The data support the hypothesis that the increased extracellular histone levels in ACLF patients may aggravate disease severity by inducing cellular injury and systemic inflammation. Histone-targeted therapies may have potentially interventional value in clinical practice. © 2016 John Wiley & Sons Ltd.

  20. Cellular internalization of polycation-coated microparticles and its dependence on their zeta potential

    Science.gov (United States)

    Kato, Noritaka; Kondo, Ryosuke

    2018-03-01

    By applying microparticles to HeLa cells, the number of particles adhered on the cell and that of the ones internalized in the cells were evaluated. Three-dimensional tomographic images of the cells with the particles were obtained by multiphoton excitation laser scanning microscopy, and the adhered and internalized particles were counted separately. When the surface charge of the particles was reversed from negative to positive by coating the particles with polycations, both numbers significantly increased owing to the electrostatic attraction between the cells and the polycation-coated particles. Four different positively charged particles were prepared using four different polycations, and the numbers of adhered and internalized particles were compared. Our results suggest that these numbers depended on the zeta potential rather than the molecular structure of the polycation.

  1. Phyto-mediated nanostructured carriers based on dual vegetable actives involved in the prevention of cellular damage

    International Nuclear Information System (INIS)

    Istrati, D.; Lacatusu, I.; Bordei, N.; Badea, G.; Oprea, O.; Stefan, L.M.; Stan, R.; Badea, N.; Meghea, A.

    2016-01-01

    The growing scientific interest in exploitation of vegetable bioactives has raised a number of questions regarding their imminent presence in pharmaceutical formulations. This study intends to demonstrate that a dual combination between vegetable oil (e.g. thistle oil, safflower oil, sea buckthorn oil) and a carrot extract represents an optimal approach to formulate safe carrier systems that manifest cell regeneration effect and promising antioxidant and anti-inflammatory activity. Inclusion of both natural actives into lipid carriers imparted a strong negative charge on the nanocarrier surface (up to − 45 mV) and displayed average sizes of 70 nm to 140 nm. The entrapment efficiency of carrot extract into nanostructured carriers ranged between 78.3 and 88.3%. The in vitro release study has demonstrated that the entrapment of the extract represents a viable way for an equilibrated release of carotenoids. Besides the excellent antioxidant properties (e.g. scavenging up to 98% of the free oxygen radicals), the results of cellular integrity (e.g. cell viability of 133%) recommend these nanocarriers based on dual carrot extract–bioactive oil as a promising trend for the treatment of certain disorders in which oxidative stress plays a prominent role. In addition, the lipid nanocarriers based on safflower oil and sea buckthorn oil demonstrated an anti-inflammatory effect on LPS induced THP-1 macrophages, by inhibiting the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α. - Highlights: • Safety phyto-mediated nanostructured carriers (NLC) based on two kinds of bioactives • Carrot extract incorporation into nanostructured carriers ranged from 78 to 88.3%. • High antioxidant activity of NLC by scavenging up to 98% free oxygen radicals • Extract entrapment represents a viable way for an equilibrated release of carotenoids. • Remarkable regenerative effect of L929 cell, with a proliferation of 133.4%

  2. Phyto-mediated nanostructured carriers based on dual vegetable actives involved in the prevention of cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Istrati, D.; Lacatusu, I.; Bordei, N.; Badea, G.; Oprea, O. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Stefan, L.M. [National Institute of Research and Development for Biological Sciences, Splaiul Independentei Street No. 296, 060031 Bucharest (Romania); Stan, R. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Badea, N., E-mail: nicoleta.badea@gmail.com [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Meghea, A. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania)

    2016-07-01

    The growing scientific interest in exploitation of vegetable bioactives has raised a number of questions regarding their imminent presence in pharmaceutical formulations. This study intends to demonstrate that a dual combination between vegetable oil (e.g. thistle oil, safflower oil, sea buckthorn oil) and a carrot extract represents an optimal approach to formulate safe carrier systems that manifest cell regeneration effect and promising antioxidant and anti-inflammatory activity. Inclusion of both natural actives into lipid carriers imparted a strong negative charge on the nanocarrier surface (up to − 45 mV) and displayed average sizes of 70 nm to 140 nm. The entrapment efficiency of carrot extract into nanostructured carriers ranged between 78.3 and 88.3%. The in vitro release study has demonstrated that the entrapment of the extract represents a viable way for an equilibrated release of carotenoids. Besides the excellent antioxidant properties (e.g. scavenging up to 98% of the free oxygen radicals), the results of cellular integrity (e.g. cell viability of 133%) recommend these nanocarriers based on dual carrot extract–bioactive oil as a promising trend for the treatment of certain disorders in which oxidative stress plays a prominent role. In addition, the lipid nanocarriers based on safflower oil and sea buckthorn oil demonstrated an anti-inflammatory effect on LPS induced THP-1 macrophages, by inhibiting the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α. - Highlights: • Safety phyto-mediated nanostructured carriers (NLC) based on two kinds of bioactives • Carrot extract incorporation into nanostructured carriers ranged from 78 to 88.3%. • High antioxidant activity of NLC by scavenging up to 98% free oxygen radicals • Extract entrapment represents a viable way for an equilibrated release of carotenoids. • Remarkable regenerative effect of L929 cell, with a proliferation of 133.4%.

  3. Biological dosimeter for cellular damage and repair by ionizing radiation. Final technical progress report, May 1, 1993 - April 30, 1996

    International Nuclear Information System (INIS)

    Cress, A.E.

    1998-01-01

    The authors have investigated the alteration of chromatin domains in Human T and B cells after ionizing radiation using three DNA specific dyes, Feulgen, Hoechst and 7-amino actinomycin D. Characterization and differentiation of T and B cells was accomplished using only 4 of a possible 32 image features with the CAS and Quaritex QX7 Digital Image Systems. Human B and T cells were irradiated with 1, 5 and 10 Gy and analyzed during a 1.5 hour recovery period. The chosen features detect a dose dependent change in DNA domains which can be observed as early as 1.5 hours after a 1Gv exposure. The results suggest that the ability of DNA specific dyes to stain chromatin can be used as an early sensitive indicator of DNA damage. The observed alteration of chromatin staining suggests that chromatin structure does observably change in a significant manner during a DNA repair interval. Since these alteration can be detected with DNA specific dyes that stain both AT rich, GC rich or total DNA, these data suggest that a global alteration of the chromatin is occurring after exposure to ionizing radiation

  4. Therapeutic efficacy of inosine against radiation-induced damage at cellular, biochemical and chromosomal levels in swiss albino mice

    International Nuclear Information System (INIS)

    El-Shamy, E.; Sallam, M. H.

    2010-01-01

    Inosine has been used for treatment of various diseases and disorders in medicine. Modulator effect of inosine against γ radiation-induced histological alterations in testis, reduced glutathione (GSH), lipid peroxidation (LPO), acid and alkaline phosphatases activities (AP and ALP) and chromosomal aberrations (CA) in mice was studied at various experimental intervals between 1 and 30 days. Mice exposed to 8 Gy γ-rays showed acute radiation sickness including marked testis histological changes and chromosomal aberrations (CA) in bone marrow cells with 100 % mortality within 22 days. When inosine was given orally at a dose of 80 mg/ kg body wt for 15 consecutive days after exposure to γ-rays, death in radiation + inosine group was reduced to 70 % at 30 days. The radiation - dose reduction factor (DRF) was 1.43. There was significantly lesser degree of damage to testis tissue architecture and various cell populations including spermatogonia, spermatids and leydig cells. Correspondingly, a significant decrease in the LPO and increase in the GSH levels were observed in testis of radiation + inosine group. Similarly, a significant decrease in level of AP and increase in level of ALP were observed. Inosine treatment significantly prevented γ-rays-induced CA frequency in bone marrow cells.

  5. Enhanced cellular delivery of cell-penetrating peptide-peptide nucleic acid conjugates by photochemical internalization

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Nielsen, Peter E

    2011-01-01

    (antisense activity) is still limited by endocytotic entrapment. We have shown that this low bioavailability can be greatly improved by combining CPP-PNA conjugate administration with a photochemical internalization technique using photosensitizers such as aluminum phthalocyanine (AlPcS(2a...

  6. Analysis of core damage frequency: Peach Bottom, Unit 2 internal events appendices

    International Nuclear Information System (INIS)

    Kolaczkowski, A.M.; Cramond, W.R.; Sype, T.T.; Maloney, K.J.; Wheeler, T.A.; Daniel, S.L.

    1989-08-01

    This document contains the appendices for the accident sequence analysis of internally initiated events for the Peach Bottom, Unit 2 Nuclear Power Plant. This is one of the five plant analyses conducted as part of the NUREG-1150 effort for the Nuclear Regulatory Commission. The work performed and described here is an extensive reanalysis of that published in October 1986 as NUREG/CR-4550, Volume 4. It addresses comments from numerous reviewers and significant changes to the plant systems and procedures made since the first report. The uncertainty analysis and presentation of results are also much improved, and considerable effort was expended on an improved analysis of loss of offsite power. The content and detail of this report is directed toward PRA practitioners who need to know how the work was done and the details for use in further studies. The mean core damage frequency is 4.5E-6 with 5% and 95% uncertainty bounds of 3.5E-7 and 1.3E-5, respectively. Station blackout type accidents (loss of all ac power) contributed about 46% of the core damage frequency with Anticipated Transient Without Scram (ATWS) accidents contributing another 42%. The numerical results are driven by loss of offsite power, transients with the power conversion system initially available operator errors, and mechanical failure to scram. 13 refs., 345 figs., 171 tabs

  7. Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities

    Energy Technology Data Exchange (ETDEWEB)

    Edelbrock, Michael A., E-mail: Edelbrock@findlay.edu [The University of Findlay, 1000 North Main Street, Findlay, OH 45840 (United States); Kaliyaperumal, Saravanan, E-mail: Saravanan.Kaliyaperumal@hms.harvard.edu [Division of Comparative Medicine and Pathology, New England Primate Research Center, One Pine Hill Drive, Southborough, MA 01772 (United States); Williams, Kandace J., E-mail: Kandace.williams@utoledo.edu [University of Toledo College of Medicine and Life Sciences, Department of Biochemistry and Cancer Biology, 3000 Transverse Dr., Toledo, OH 43614 (United States)

    2013-03-15

    The field of DNA mismatch repair (MMR) has rapidly expanded after the discovery of the MutHLS repair system in bacteria. By the mid 1990s yeast and human homologues to bacterial MutL and MutS had been identified and their contribution to hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome) was under intense investigation. The human MutS homologue 6 protein (hMSH6), was first reported in 1995 as a G:T binding partner (GTBP) of hMSH2, forming the hMutSα mismatch-binding complex. Signal transduction from each DNA-bound hMutSα complex is accomplished by the hMutLα heterodimer (hMLH1 and hPMS2). Molecular mechanisms and cellular regulation of individual MMR proteins are now areas of intensive research. This review will focus on molecular mechanisms associated with mismatch binding, as well as emerging evidence that MutSα, and in particular, MSH6, is a key protein in MMR-dependent DNA damage response and communication with other DNA repair pathways within the cell. MSH6 is unstable in the absence of MSH2, however it is the DNA lesion-binding partner of this heterodimer. MSH6, but not MSH2, has a conserved Phe-X-Glu motif that recognizes and binds several different DNA structural distortions, initiating different cellular responses. hMSH6 also contains the nuclear localization sequences required to shuttle hMutSα into the nucleus. For example, upon binding to O{sup 6}meG:T, MSH6 triggers a DNA damage response that involves altered phosphorylation within the N-terminal disordered domain of this unique protein. While many investigations have focused on MMR as a post-replication DNA repair mechanism, MMR proteins are expressed and active in all phases of the cell cycle. There is much more to be discovered about regulatory cellular roles that require the presence of MutSα and, in particular, MSH6.

  8. Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities

    International Nuclear Information System (INIS)

    Edelbrock, Michael A.; Kaliyaperumal, Saravanan; Williams, Kandace J.

    2013-01-01

    The field of DNA mismatch repair (MMR) has rapidly expanded after the discovery of the MutHLS repair system in bacteria. By the mid 1990s yeast and human homologues to bacterial MutL and MutS had been identified and their contribution to hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome) was under intense investigation. The human MutS homologue 6 protein (hMSH6), was first reported in 1995 as a G:T binding partner (GTBP) of hMSH2, forming the hMutSα mismatch-binding complex. Signal transduction from each DNA-bound hMutSα complex is accomplished by the hMutLα heterodimer (hMLH1 and hPMS2). Molecular mechanisms and cellular regulation of individual MMR proteins are now areas of intensive research. This review will focus on molecular mechanisms associated with mismatch binding, as well as emerging evidence that MutSα, and in particular, MSH6, is a key protein in MMR-dependent DNA damage response and communication with other DNA repair pathways within the cell. MSH6 is unstable in the absence of MSH2, however it is the DNA lesion-binding partner of this heterodimer. MSH6, but not MSH2, has a conserved Phe-X-Glu motif that recognizes and binds several different DNA structural distortions, initiating different cellular responses. hMSH6 also contains the nuclear localization sequences required to shuttle hMutSα into the nucleus. For example, upon binding to O 6 meG:T, MSH6 triggers a DNA damage response that involves altered phosphorylation within the N-terminal disordered domain of this unique protein. While many investigations have focused on MMR as a post-replication DNA repair mechanism, MMR proteins are expressed and active in all phases of the cell cycle. There is much more to be discovered about regulatory cellular roles that require the presence of MutSα and, in particular, MSH6

  9. Pudendal Nerve and Internal Pudendal Artery Damage May Contribute to Radiation-Induced Erectile Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Nolan, Michael W., E-mail: mwnolan@ncsu.edu [Department of Clinical Sciences, and Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina (United States); Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Marolf, Angela J. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Ehrhart, E.J. [Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado (United States); Rao, Sangeeta [Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado (United States); Kraft, Susan L. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Engel, Stephanie [Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado (United States); Yoshikawa, Hiroto; Golden, Anne E. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Wasserman, Todd H. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); LaRue, Susan M. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States)

    2015-03-15

    Purpose/Objectives: Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation. Methods and Materials: Dogs were treated with 50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes. Results: SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT. Conclusions: This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is

  10. DNA damage in internal organs after cutaneous exposure to sulphur mustard

    International Nuclear Information System (INIS)

    Batal, Mohamed; Boudry, Isabelle; Mouret, Stéphane; Cléry-Barraud, Cécile; Wartelle, Julien; Bérard, Izabel; Douki, Thierry

    2014-01-01

    Sulphur mustard (SM) is a chemical warfare agent that attacks mainly skin, eye and lungs. Due to its lipophilic properties, SM is also able to diffuse through the skin and reach internal organs. DNA represents one of the most critical molecular targets of this powerful alkylating agent which modifies DNA structure by forming monoadducts and biadducts. These DNA lesions are involved in the acute toxicity of SM as well as its long-term carcinogenicity. In the present work we studied the formation and persistence of guanine and adenine monoadducts and guanine biadducts in the DNA of brain, lungs, kidneys, spleen, and liver of SKH-1 mice cutaneously exposed to 2, 6 and 60 mg/kg of SM. SM-DNA adducts were detected in all studied organs, except in liver at the two lowest doses. Brain and lungs were the organs with the highest level of SM-DNA adducts, followed by kidney, spleen and liver. Monitoring the level of adducts for three weeks after cutaneous exposure showed that the lifetime of adducts were not the same in all organs, lungs being the organ with the longest persistence. Diffusion from skin to internal organs was much more efficient at the highest compared to the lowest dose investigated as the result of the loss of the skin barrier function. These data provide novel information on the distribution of SM in tissues following cutaneous exposures and indicate that brain is an important target. - Highlights: • Sulphur mustard reaches internal organs after skin exposure • Adducts are detected in the DNA of internal organs • Brain is the organ with the highest level of DNA damage • The barrier function of skin is lost at high dose of sulphur mustard • DNA adducts persist in organs for 2 or 3 weeks

  11. DNA damage in internal organs after cutaneous exposure to sulphur mustard

    Energy Technology Data Exchange (ETDEWEB)

    Batal, Mohamed [Laboratoire « Lésions des Acides Nucléiques », Université Joseph Fourier – Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble (France); Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche, BP87, F-38702 La Tronche Cedex (France); Boudry, Isabelle; Mouret, Stéphane; Cléry-Barraud, Cécile; Wartelle, Julien [Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche, BP87, F-38702 La Tronche Cedex (France); Bérard, Izabel [Laboratoire « Lésions des Acides Nucléiques », Université Joseph Fourier – Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble (France); Douki, Thierry, E-mail: thierry.douki@cea.fr [Laboratoire « Lésions des Acides Nucléiques », Université Joseph Fourier – Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble (France)

    2014-07-01

    Sulphur mustard (SM) is a chemical warfare agent that attacks mainly skin, eye and lungs. Due to its lipophilic properties, SM is also able to diffuse through the skin and reach internal organs. DNA represents one of the most critical molecular targets of this powerful alkylating agent which modifies DNA structure by forming monoadducts and biadducts. These DNA lesions are involved in the acute toxicity of SM as well as its long-term carcinogenicity. In the present work we studied the formation and persistence of guanine and adenine monoadducts and guanine biadducts in the DNA of brain, lungs, kidneys, spleen, and liver of SKH-1 mice cutaneously exposed to 2, 6 and 60 mg/kg of SM. SM-DNA adducts were detected in all studied organs, except in liver at the two lowest doses. Brain and lungs were the organs with the highest level of SM-DNA adducts, followed by kidney, spleen and liver. Monitoring the level of adducts for three weeks after cutaneous exposure showed that the lifetime of adducts were not the same in all organs, lungs being the organ with the longest persistence. Diffusion from skin to internal organs was much more efficient at the highest compared to the lowest dose investigated as the result of the loss of the skin barrier function. These data provide novel information on the distribution of SM in tissues following cutaneous exposures and indicate that brain is an important target. - Highlights: • Sulphur mustard reaches internal organs after skin exposure • Adducts are detected in the DNA of internal organs • Brain is the organ with the highest level of DNA damage • The barrier function of skin is lost at high dose of sulphur mustard • DNA adducts persist in organs for 2 or 3 weeks.

  12. Charomers-Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery.

    Science.gov (United States)

    Hahn, Ulrich

    2017-12-06

    Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2'-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers-in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

  13. Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery

    Science.gov (United States)

    2017-01-01

    Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld. PMID:29211023

  14. Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ulrich Hahn

    2017-12-01

    Full Text Available Interleukin-6 (IL-6 is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT. Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

  15. Executive order no. 433 of 24th May 1996. Executive order on the international fund for compensation for damages caused by oil pollution, 1992

    International Nuclear Information System (INIS)

    1996-05-01

    The Danish executive order on the international fund for the compensation for damages caused by oil pollution, 1992 is related to the Danish law no. 205 of March 29th 1996, and is based on the International Convention on the Establishment of an International Fund for Compensation for Oil Damage, 1992. The document includes the convention's protocol presented in French, Danish and English. (AB)

  16. National Assembly report on the bill authorizing joining the 2001 International Convention on Civil Liability for Bunker Oil Pollution Damage

    International Nuclear Information System (INIS)

    2010-01-01

    This report first gives an overview of the progressive implementation of measures and international convention to prevent pollution by ships: the Oilpol convention (Convention for the Prevention of Pollution of the Sea by Oil), the Marpol convention (Marine Pollution), and the different international conventions on liability and compensation (International Convention on Civil Liability for Oil Pollution, International Convention on Liability and Compensation for Damage in Connection with the Carriage of Hazardous and Noxious Substances by Sea, convention on other damages). It also describes the French system to struggle against marine pollution. Then, it presents the main arrangements of the 2001 Convention (liability, mandatory insurance and certificate, and so on), expresses some reserves on the chosen arrangement, and comments the impact of this convention

  17. Proceedings of the signature series event of the international society for cellular therapy: "Advancements in cellular therapies and regenerative medicine in digestive diseases," London, United Kingdom, May 3, 2017.

    Science.gov (United States)

    Ciccocioppo, Rachele; Dos Santos, Claudia C; Baumgart, Daniel C; Cangemi, Giuseppina C; Cardinale, Vincenzo; Ciacci, Carolina; De Coppi, Paolo; Haldar, Debashis; Klersy, Catherine; Nostro, M Cristina; Ott, Michael; Piemonti, Lorenzo; Tomei, Alice A; Uygun, Basak; Vetrano, Stefania; Orlando, Giuseppe

    2018-03-01

    A summary of the First Signature Series Event, "Advancements in Cellular Therapies and Regenerative Medicine for Digestive Diseases," held on May 3, 2017, in London, United Kingdom, is presented. Twelve speakers from three continents covered major topics in the areas of cellular therapy and regenerative medicine applied to liver and gastrointestinal medicine as well as to diabetes mellitus. Highlights from their presentations, together with an overview of the global impact of digestive diseases and a proposal for a shared online collection and data-monitoring platform tool, are included in this proceedings. Although growing evidence demonstrate the feasibility and safety of exploiting cell-based technologies for the treatment of digestive diseases, regulatory and methodological obstacles will need to be overcome before the successful implementation in the clinic of these novel attractive therapeutic strategies. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  18. Analysis of core damage frequency from internal events: Methodology guidelines: Volume 1

    International Nuclear Information System (INIS)

    Drouin, M.T.; Harper, F.T.; Camp, A.L.

    1987-09-01

    NUREG-1150 examines the risk to the public from a selected group of nuclear power plants. This report describes the methodology used to estimate the internal event core damage frequencies of four plants in support of NUREG-1150. In principle, this methodology is similar to methods used in past probabilistic risk assessments; however, based on past studies and using analysts that are experienced in these techniques, the analyses can be focused in certain areas. In this approach, only the most important systems and failure modes are modeled in detail. Further, the data and human reliability analyses are simplified, with emphasis on the most important components and human actions. Using these methods, an analysis can be completed in six to nine months using two to three full-time systems analysts and part-time personnel in other areas, such as data analysis and human reliability analysis. This is significantly faster and less costly than previous analyses and provides most of the insights that are obtained by the more costly studies. 82 refs., 35 figs., 27 tabs

  19. Involvement of stress-activated protein kinase in the cellular response to 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents.

    Science.gov (United States)

    Saleem, A; Datta, R; Yuan, Z M; Kharbanda, S; Kufe, D

    1995-12-01

    The cellular response to 1-beta-D-arabinofuranosylcytosine (ara-C) includes activation of Jun/AP-1, induction of c-jun transcription, and programmed cell death. The stress-activated protein (SAP) kinases stimulate the transactivation function of c-jun by amino terminal phosphorylation. The present work demonstrates that ara-C activates p54 SAP kinase. The finding that SAP kinase is also activated by alkylating agents (mitomycin C and cisplatinum) and the topoisomerase I inhibitor 9-amino-camptothecin supports DNA damage as an initial signal in this cascade. The results demonstrate that ara-C also induces binding of SAP kinase to the SH2/SH3-containing adapter protein Grb2. SAP kinase binds to the SH3 domains of Grb2, while interaction of the p85 alpha-subunit of phosphatidylinositol 3-kinase complex. The results also demonstrate that ara-C treatment is associated with inhibition of lipid and serine kinase activities of PI 3-kinase. The potential significance of the ara-C-induced interaction between SAP kinase and PI 3-kinase is further supported by the demonstration that Wortmannin, an inhibitor of PI 3-kinase, stimulates SAP kinase activity. The finding that Wortmannin treatment is also associated with internucleosomal DNA fragmentation may support a potential link between PI 3-kinase and regulation of both SAP kinase and programmed cell death.

  20. Study on the damage effect of 131I-iodinated oil internal radiation in SMMC-7721 hepatoma model in rat

    International Nuclear Information System (INIS)

    Wu Shuyan; Zhang Xuguang; Wang Xiangying; Li Su'an; Mao Dihua

    2004-01-01

    Objective: To investigate the damage effect of 131 I-iodinated oil internal radiation in hepatoma. Methods: SMMC-7721 rat hepatoma model was used to evaluate the damage of 131 I-iodinated oil internal radiation in carcinoma. 131 I-iodinated oil was injected sector-shapely into tumor model of SMMC-7721 hepatoma with arc-needle, matched with routine straight-needle injection. Tumor damage induced by 131 I-iodinated oil intralesion radiation in the carcinoma models are recorded through survival time, weight of rat, local carcinoma, pathology, electron microscopy. Results: Arc-needle injection 131 I-iodinated oil in SMMC-7721 hepatoma at subcutis could increase rat's survival time, the body weight kept less descent, the lumps necrosed wholly. Pathology and ultrastructure detection revealed cell necrosis and collapse, sever nuclear damage was observed in the death cells. The early characteristics of necrosis such as margination of heterochromatin was also found in some tumor cells. Besides, well differentiated tumor cells, degenerative tumor cells and some lymphocytes were seen. Conclusion: Arc-needle injection 131 I-iodinated oil step-by step sector-shapely into tumor is a better method and necrosis is the major effect of 131 I-iodinated oil internal radiation in carcinoma at the level of treated dosage

  1. 3D cellular automata finite element (CAFE) modelling and experimental observation of damage in quasi-brittle nuclear materials: Indentation of a SiC-SiC-fibre ceramic matrix composite

    International Nuclear Information System (INIS)

    Saucedo Mora, Luis; Mostafavi, Mahmoud; Marrow, T. James; Khoshkhou, Danial; Connolly, Brian; Reinhard, Christina; Atwood, Robert; Zhao, Shuang

    2015-01-01

    Cellular automata integrated with finite elements (CAFE) have been used to develop a method to account for the effect of microstructure on quasi-brittle damage development. The microstructure is simulated explicitly by subdividing a finite element into smaller cells. A heterogeneous structure is created from key cells (seeds) using defined characteristics; the influence of the initial finite element mesh is effectively removed during the development of the microstructure. Graded microstructures, textures, particle anisotropy and multiple phases can be readily simulated, such as those in composites and porous materials. A mesh-free framework has been developed to compute the damage development through the microstructure, using cellular automata. With this method, we can study the development of discontinuous cracking and damage coalescence, and its sensitivity to microstructure. Experiments have been carried out to observe the three-dimensional development of damage, using high-resolution synchrotron X-ray computed tomography and digital volume correlation to observe Hertzian indentation of a SiC-SiC fibre composite, quantifying damage by measurement of the displacement fields within the material. The results demonstrate the applicability of the modelling strategy to damage development, and show how model input data may be obtained from small specimen tests, which could be performed at elevated temperatures with irradiated materials. (authors)

  2. Results of international standard problem No. 36 severe fuel damage experiment of a VVER fuel bundle

    Energy Technology Data Exchange (ETDEWEB)

    Firnhaber, M. [Gesellschaft fuer Anlagen-und Reaktorsicherheit, Koeln (Germany); Yegorova, L. [Nuclear Safety Institute of Russian Research Center, Moscow (Russian Federation); Brockmeier, U. [Ruhr-Univ. of Bochum (Germany)] [and others

    1995-09-01

    International Standard Problems (ISP) organized by the OECD are defined as comparative exercises in which predictions with different computer codes for a given physical problem are compared with each other and with a carefully controlled experimental study. The main goal of ISP is to increase confidence in the validity and accuracy of analytical tools used in assessing the safety of nuclear installations. In addition, it enables the code user to gain experience and to improve his competence. This paper presents the results and assessment of ISP No. 36, which deals with the early core degradation phase during an unmitigated severe LWR accident in a Russian type VVER. Representatives of 17 organizations participated in the ISP using the codes ATHLET-CD, ICARE2, KESS-III, MELCOR, SCDAP/RELAP5 and RAPTA. Some participants performed several calculations with different codes. As experimental basis the severe fuel damage experiment CORA-W2 was selected. The main phenomena investigated are thermal behavior of fuel rods, onset of temperature escalation, material behavior and hydrogen generation. In general, the calculations give the right tendency of the experimental results for the thermal behavior, the hydrogen generation and, partly, for the material behavior. However, some calculations deviate in important quantities - e.g. some material behavior data - showing remarkable discrepancies between each other and from the experiments. The temperature history of the bundle up to the beginning of significant oxidation was calculated quite well. Deviations seem to be related to the overall heat balance. Since the material behavior of the bundle is to a great extent influenced by the cladding failure criteria a more realistic cladding failure model should be developed at least for the detailed, mechanistic codes. Regarding the material behavior and flow blockage some models for the material interaction as well as for relocation and refreezing requires further improvement.

  3. The usefulness of the nuclear cardiology in the cellular implant in patients with severe myocardial damage; La utilidad de la cardiologia nuclear en el implante celular en pacientes con dano miocardico severo

    Energy Technology Data Exchange (ETDEWEB)

    Omelas A, M.; Arguero S, R.; Garrido G, M.H.; Rodriguez C, A.; Careaga, G.; Castano G, R.; Nambo, M.J.; Pascual P, J.; Ortega R, A.; Gaxiola A, A.; Magana S, J.A.; Estrada A, H.; Equipo de Tecnicos en Medicina Nuclear [Centro Medico Nacional Siglo XXI IMSS Hospital de Cardiologia-Servicio de Medicina Nuclear Mexico DF (Mexico)

    2005-07-01

    The recent therapeutic advances as the cellular implant as well as those different protocols of image acquisition in the field of the Nuclear Cardiology its have allowed that the patient with severe myocardial damage and without some possibility of revascularization is benefited with these advances. Doubtless the Tl-201 par excellence has an important paper for standardize the more appropriate therapeutic behavior for the heart attack patient; reason by this investigation protocol was developed. The objective of the study was to identify the heart attack regions without viable tissue with SPECT in patient with important myocardial damage without some possibility of traditional revascularization; for the 'Stem cell' cellular implantation therapy. The methodology it was carried out by a study of myocardial perfusion in 10 patients with important myocardial damage previous cellular implants, with PICANUC/ SPECT methodology and using a software (Emory Tool Box) for the image processing validated by the University of Emory Atlanta GA; and using as tracer the Tl - 201 to identify the heart attack regions without presence of viable tissue with an analysis model of 17 segments standardized for the left ventricle; qualifying this way the myocardial perfusion in: 0 (normal), 1 (light), 2 (moderate), 3 (severe), 4 (absent) and x (bad technique). The conclusions were that the SPECT study with PICANUC methodology with Tl-201 is safe and effective for the precise localization for the cellular implantation via direct intra myocardial. (Author)

  4. Smart pH-responsive upconversion nanoparticles for enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

    Science.gov (United States)

    Wang, Sheng; Zhang, Lei; Dong, Chunhong; Su, Lin; Wang, Hanjie; Chang, Jin

    2015-01-01

    A smart pH-responsive photodynamic therapy system based on upconversion nanoparticle loaded PEG coated polymeric lipid vesicles (RB-UPPLVs) was designed and prepared. These RB-UPPLVs which are promising agents for deep cancer photodynamic therapy applications can achieve enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

  5. The effect of tobacco smoke exposure on the generation of reactive oxygen species and cellular membrane damage using co-culture model of blood brain barrier with astrocytes.

    Science.gov (United States)

    Seo, Seung-Beom; Choe, Eun Sang; Kim, Kwang-Sik; Shim, Soon-Mi

    2017-06-01

    Brain tissue is known to be vulnerable to the exposure by tobacco smoke. Tobacco smoke can induce generation of reactive oxygen species (ROS), causing inflammatory activity and blood-brain barrier (BBB) impairment. The aim of the present study was to investigate the effect of tobacco smoke on cell cytotoxicity, generation of ROS, and cellular membrane damage in astrocytes and BBB using a co-culture system. Cell viability of U373MG cells was reduced in a dose-dependent manner, ranging from 96.7% to 40.3% by tobacco smoke condensate (TSC). Cell viability of U373MG co-cultured with human brain microvascular endothelial cells (HBMECs) was 104.9% at the IC 50 value of TSC. Trans-epithelial electric resistance values drastically decreased 80% following 12-h incubation. The value was maintained until 48 h and then increased at 72-h incubation (85%). It then decreased to 75% at 120 h. Generation of ROS increased in a dose-dependent manner, ranging from 102.7% to 107.9%, when various concentrations of TSC (4-16 mg/mL) were administered to the U373MG monoculture. When TSC was added into U373MG co-cultured with HBMECs, production of ROS ranged from 101.7% to 102.6%, slightly increasing over 12 h. Maximum exposure-generated ROS of 104.8% was reached at 24 h. Cell cytotoxicity and oxidative stress levels in the U373MG co-culture model system with HBMECs were lower than U373MG monoculture. HBMECs effectively acted as a barrier to protect the astrocytes (U373MG) from toxicity of TSC.

  6. Compensation for oil pollution damage caused by oil spills from ships and the International Oil Pollution Compensation Fund

    International Nuclear Information System (INIS)

    Jacobsson, M.

    1994-01-01

    Liability and compensation for pollution damage caused by oil spills from laden tankers is governed by two international conventions: the 1969 Civil Liability Convention and the 1971 Fund Convention. The Civil Liability Convention established a system of strict liability for tanker owners and introduced compulsory liability insurance. The Fund Convention created a system of supplementary compensation administered by an intergovernmental organization, the International Oil Pollution Compensation Fund (IOPC Fund), which at present has 56 member states (August 1993). The IOPC Fund pays compensation to victims of oil pollution in member states when the compensation from the ship owner and his insurer is insufficient. (author)

  7. The protection against nuclear risks under the international nuclear liability law: the geographical and technical scope of the international conventions on third party liability for nuclear damage

    International Nuclear Information System (INIS)

    Kissich, S.J.

    2001-10-01

    This Ph.D.-research deals with the International Conventions on Third Party Liability for Nuclear Damage. In 1960, the Paris Convention was established with the aim of providing a special uniform nuclear third party liability regime for Western Europe. This Convention was supplemented in 1963 by the Brussels Supplementary Convention. Also in 1963, the Vienna Convention, which aimed to establish a world-wide system based on the same principles as the Paris Convention, was adopted. A further Convention was adopted in 1971 to ensure that nuclear third party liability law and not maritime law would apply to carriage of nuclear materials by sea. In 1988, the Paris and Vienna Conventions have been linked by the adoption of a Joint Protocol. In 1997, the process of amending the 1963 Vienna Convention was successfully concluded and a Convention on Supplementary Compensation was adopted. This Ph.D.-research consists of seven chapters: following an introduction, the second chapter gives a general view of the existing international legal sources. The third chapter describes the international civil nuclear liability law concept and its leading principles. The main element of this work is the question of the technical and geographical scope of the international nuclear liability conventions (chapter IV and V). The conventions are only applicable to nuclear incidents, which occur in a nuclear installation or incidental to the carriage or storage of nuclear material. The nuclear damage must arise out of the radioactive properties of nuclear substances which are also defined by legal terms. In addition, the scope of the conventions is limited by the nature of the installations. The geographical scope of application is established by the provisions on geographical coverage. Only the 1963 Vienna Convention does not contain any specific provision dealing with the territorial scope of its application. The geographical scope determines where the nuclear incident or the nuclear damage

  8. δ- and γ-tocopherols inhibit phIP/DSS-induced colon carcinogenesis by protection against early cellular and DNA damages.

    Science.gov (United States)

    Chen, Jayson X; Liu, Anna; Lee, Mao-Jung; Wang, Hong; Yu, Siyuan; Chi, Eric; Reuhl, Kenneth; Suh, Nanjoo; Yang, Chung S

    2017-01-01

    Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T), and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T, and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 wk. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Analysis of core damage frequency from internal events: Surry, Unit 1

    International Nuclear Information System (INIS)

    Harper, F.T.

    1986-11-01

    This document contains the accident sequence analyses for Surry, Unit 1; one of the reference plants being examined as part of the NUREG-1150 effort by the Nuclear Regulatory Commission (NRC). 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 Surry, Unit 1, and the accompanying plant damage state frequencies. Sensitivity and uncertainty analyses provide additional insights regarding the dominant contributors to the Surry core damage frequency estimate. The numerical results are driven to some degree by modeling assumptions and data selection for issues such as reactor coolant pump seal LOCAs, common cause failure probabilities, and plant response to station blackout and loss of electrical bust initiators. The sensitivity studies explore the impact of alternate theories and data on these issues

  10. Senate report on the bill authorizing joining the 2001 International Convention on Civil Liability for Bunker Oil Pollution Damage

    International Nuclear Information System (INIS)

    2010-01-01

    This report recalls the different texts concerning the law of the sea: United Nations Convention on the Law of the Sea (UNCLOS) of 1982 which was ratified by France in 1996, the International Convention on Civil Liability for Oil Pollution of 1992, the creation of the International Oil Pollution Compensation Funds, and the International Convention on Liability and Compensation for Damage in Connection with the Carriage of Hazardous and Noxious Substances by sea (HNS) in 1996. While evoking some recent examples of wrecks and pollutions and some already existing French and European initiatives, it describes the implications and consequences of this convention on the French law and for its enforcement, provided that this new treaty is designed to take bunker oil into account as it may induce a significant pollution of the marine environment

  11. Internalization of Sexism, Racism & Classism in Damaged Parenting: A Developmental Dialectical Model.

    Science.gov (United States)

    Pakizegi, B.

    This paper examines the relevance of social structure, in terms of class, race, and gender, in the lives of damaged parents of low power positions who abuse or neglect their children. The predominant view in the understanding and treatment of abusive parents stresses the parent's poor childhood experiences and the "intergenerational…

  12. Compensation for nuclear damage: a comparison among the international regime, Japan and China

    NARCIS (Netherlands)

    Liu, J.; Faure, Michael

    2016-01-01

    Following the Fukushima disaster in Japan in 2011, how the compensation system for nuclear damage should be improved has obtained broad attention. The compensation system, including liability rules, insurance and government involvement, does not only concern to what extent the victims can be

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

    Energy Technology Data Exchange (ETDEWEB)

    Harris, C.E.

    1994-09-01

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

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

    Science.gov (United States)

    Harris, Charles E. (Editor)

    1994-01-01

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

  15. Firmness at Harvest Impacts Postharvest Fruit Softening and Internal Browning Development in Mechanically Damaged and Non-damaged Highbush Blueberries (Vaccinium corymbosum L.).

    Science.gov (United States)

    Moggia, Claudia; Graell, Jordi; Lara, Isabel; González, Guillermina; Lobos, Gustavo A

    2017-01-01

    Fresh blueberries are very susceptible to mechanical damage, which limits postharvest life and firmness. Softening and susceptibility of cultivars "Duke" and "Brigitta" to developing internal browning (IB) after mechanical impact and subsequent storage was evaluated during a 2-year study (2011/2012, 2012/2013). On each season fruit were carefully hand-picked, segregated into soft (<1.60 N), medium (1.61-1.80 N), and firm (1.81-2.00 N) categories, and then either were dropped (32 cm) onto a hard plastic surface or remained non-dropped. All fruit were kept under refrigerated storage (0°C and 85-88% relative humidity) to assess firmness loss and IB after 7, 14, 21, 28, and 35 days. In general, regardless of cultivar or season, high variability in fruit firmness was observed within each commercial harvest, and significant differences in IB and softening rates were found. "Duke" exhibited high softening rates, as well as high and significant r 2 between firmness and IB, but little differences for dropped vs. non-dropped fruit. "Brigitta," having lesser firmness rates, exhibited almost no relationships between firmness and IB (especially for non-dropped fruit), but marked differences between dropping treatments. Firmness loss and IB development were related to firmness at harvest, soft and firm fruit being the most and least damaged, respectively. Soft fruit were characterized by greater IB development during storage along with high soluble solids/acid ratio, which could be used together with firmness to estimate harvest date and storage potential of fruit. Results of this work suggest that the differences in fruit quality traits at harvest could be related to the time that fruit stay on the plant after turning blue, soft fruit being more advanced in maturity. Finally, the observed differences between segregated categories reinforce the importance of analyzing fruit condition for each sorted group separately.

  16. Deoxyribonucleoprotein structure and radiation injury - Cellular radiosensitivity is determined by LET-infinity-dependent DNA damage in hydrated deoxyribonucleoproteins and the extent of its repair

    Science.gov (United States)

    Lett, J. T.; Peters, E. L.

    1992-01-01

    Until recently, OH radicals formed in bulk nuclear water were believed to be the major causes of DNA damage that results in cell death, especially for sparsely ionizing radiations. That hypothesis has now been challenged, if not refuted. Lethal genomic DNA damage is determined mainly by energy deposition in deoxyribonucleoproteins, and their hydration shells, and charge (energy) transfer processes within those structures.

  17. Assessment of beta-emitter radionuclides in biological samples using liquid scintillation counting. Application to the study of internal doses in molecular and cellular biology techniques

    International Nuclear Information System (INIS)

    Sierra, I.; Delgado, A.; Navarro, T.; Macias, M. T.

    2007-01-01

    The radioisotopic techniques used in Molecular and Cellular Biology involve external and internal irradiation risk. It is necessary to control the possible internal contamination associated to the development of these techniques. The internal contamination risk can be due to physical and chemical properties of the labelled compounds, aerosols generated during the performance technique. The aim of this work was to estimate the possible intake of specific beta emitters during the technique development and to propose the required criterions to perform Individual Monitoring. The most representative radioisotopic techniques were selected attending their potential risk of internal contamination. Techniques were analysed applying IAEA methodology according to the used activity in each technique. It was necessary to identify the worker groups that would require individual monitoring on the base of their specific risk. Different measurement procedures were applied to study the possible intake in group risk and more than 160 persons were measured by in vitro bioassay. (Author) 96 refs

  18. Pre-analytical and post-analytical evaluation in the era of molecular diagnosis of sexually transmitted diseases: cellularity control and internal control

    Directory of Open Access Journals (Sweden)

    Loria Bianchi

    2014-06-01

    Full Text Available Background. Increase of molecular tests performed on DNA extracted from various biological materials should not be carried out without an adequate standardization of the pre-analytical and post-analytical phase. Materials and Methods. Aim of this study was to evaluate the role of internal control (IC to standardize pre-analytical phase and the role of cellularity control (CC in the suitability evaluation of biological matrices, and their influence on false negative results. 120 cervical swabs (CS were pre-treated and extracted following 3 different protocols. Extraction performance was evaluated by amplification of: IC, added in each mix extraction; human gene HPRT1 (CC with RT-PCR to quantify sample cellularity; L1 region of HPV with SPF10 primers. 135 urine, 135 urethral swabs, 553 CS and 332 ThinPrep swabs (TP were tested for C. trachomatis (CT and U. parvum (UP with RT-PCR and for HPV by endpoint-PCR. Samples were also tested for cellularity. Results. Extraction protocol with highest average cellularity (Ac/sample showed lowest number of samples with inhibitors; highest HPV positivity was achieved by protocol with greatest Ac/PCR. CS and TP under 300.000 cells/sample showed a significant decrease of UP (P<0.01 and HPV (P<0.005 positivity. Female urine under 40.000 cells/mL were inadequate to detect UP (P<0.05. Conclusions. Our data show that IC and CC allow optimization of pre-analytical phase, with an increase of analytical quality. Cellularity/sample allows better sample adequacy evaluation, crucial to avoid false negative results, while cellularity/PCR allows better optimization of PCR amplification. Further data are required to define the optimal cut-off for result normalization.

  19. Development of integrated damage detection system for international America's Cup class yacht structures using a fiber optic distributed sensor

    Science.gov (United States)

    Akiyoshi, Shimada; Naruse, Hiroshi; Uzawa, Kyoshi; Murayama, Hideaki; Kageyama, Kazuro

    2000-06-01

    We constructed a new health monitoring system to detect damage using a fiber optic distributed sensor, namely a Brillouin optical time domain reflectometer (BOTDR), and installed it in International America's Cup Class (IACC) yachts, the Japanese entry in America's Cup 2000. IACC yachts are designed to be as fast as possible, so it is essential that they are lightweight and encounter minimum water resistance. Advanced composite sandwich structures, made with carbon fiber reinforced plastic (CFRP) skins and a honeycomb core, are used to achieve the lightweight structure. Yacht structure designs push the strength of the materials to their limit and so it is important to detect highly stressed or damaged regions that might cause a catastrophic fracture. The BOTDR measures changes in the Brillouin frequency shift caused by distributed strain along one optical fiber. We undertook two experiments: a pulling test and a four point bending test on a composite beam. The former showed that no slippage occurred between the optical fiber glass and its coating. The latter confirmed that a debonding between the skin and the core of 300 mm length could be found with the BOTDR. Next we examined the effectiveness with which this system can assess the structural integrity of IACC yachts. The results show that our system has the potential for use as a damage detection system for smart structures.

  20. N-Acetyl-L-cysteine protects thyroid cells against DNA damage induced by external and internal irradiation.

    Science.gov (United States)

    Kurashige, Tomomi; Shimamura, Mika; Nagayama, Yuji

    2017-11-01

    We evaluated the effect of the antioxidant N-acetyl-L-cysteine (NAC) on the levels of reactive oxygen species (ROS), DNA double strand breaks (DSB) and micronuclei (MN) induced by internal and external irradiation using a rat thyroid cell line PCCL3. In internal irradiation experiments, ROS and DSB levels increased immediately after 131 I addition and then gradually declined, resulting in very high levels of MN at 24 and 48 h. NAC administration both pre- and also post- 131 I addition suppressed ROS, DSB and MN. In external irradiation experiments with a low dose (0.5 Gy), ROS and DSB increased shortly and could be prevented by NAC administration pre-, but not post-irradiation. In contrast, external irradiation with a high dose (5 Gy) increased ROS and DSB in a bimodal way: ROS and DSB levels increased immediately after irradiation, quickly returned to the basal levels and gradually rose again after >24 h. The second phase was in parallel with an increase in 4-hydroxy-2-nonenal. The number of MN induced by the second wave of ROS/DSB elevations was much higher than that by the first peak. In this situation, NAC administered pre- and post-irradiation comparably suppressed MN induced by a delayed ROS elevation. In conclusion, a prolonged ROS increase during internal irradiation and a delayed ROS increase after external irradiation with a high dose caused serious DNA damage, which were efficiently prevented by NAC. Thus, NAC administration even both after internal or external irradiation prevents ROS increase and eventual DNA damage.

  1. International Court of Justice on Potential Transboundary Damage and its Consequences in Nuclear Law

    International Nuclear Information System (INIS)

    Cletienne, M.

    2010-01-01

    On 4 May 2006, Argentina filed in the International Court of Justice ('ICJ') an application instituting proceedings against Uruguay. Argentina claimed that Uruguay, by authorizing the construction of a pulp mill (the 'CMB mill') and the construction and commissioning of another pulp mill (the 'Orion mill'), breached its obligations under the 1975 Statute of the River Uruguay, a treaty between Argentina and Uruguay, notably the obligation to take all necessary measures for the optimum and rational utilisation of the River Uruguay. On 20 April 2010,1 the court rendered its decision settling this environmental dispute between Argentina and Uruguay. This paper will first summarize the judgement and then consider the main contribution of this decision to international environmental law, e.g. the recognition of an international customary rule to conduct an environmental impact assessment. Finally, the potential consequences of the decision in nuclear law will be addressed in the last part

  2. The Chernobyl case: its repercussions on the International System on Civil Liability for Nuclear Damages

    International Nuclear Information System (INIS)

    Gonzalez Guadarrama, J.L.

    1992-01-01

    With the discovery of the Nuclear Energy the world has been development her life the present investigation is based in the accident of the one of the most important Nuclear Power Plant in the world, situated in the Union of Socialist Sovietic Republics. The Nuclear Power Plant of Chernobyl. Us found in the investigation what not exist one legislation agree with the needs of development of the actual world in matter of the liability civil in case of the nuclear accidents. Found only the Convention of the Vienna. the Convention of the Brussels the which only cover the transportation the Nuclear substances in ships and others transportation medios. The complementary a the convention of the Paris and actually The Communication in case of the nuclear accidents and radiological accidents. In the present work think what the Community International haven the needs of created one legislation with character international what can help a the many countries what have Nuclear Power Plants, on all for protection of the her habitants. The International Atomic Energy Agency together with the International Justice Court and the United Nations Organization (U.N.O.) aplicated the law in matter of the nuclear accidents derivates of the liability responsibility in the use of the Nuclear Plants for elaboration the Electrical Energy or for Investigation in matter the nuclear energy both with identical responsibility civil in case the nuclear accident. (Author)

  3. The Carrier's Liability for Damage Caused by Delay in International Air Transport

    Science.gov (United States)

    Lee, Kang Bin

    2003-01-01

    Delay in the air transport occurs when passengers, baggage or cargo do not arrive at their destination at the time indicated in the contract of carriage. The causes of delay in the carriage of passengers are booking errors or double booking, delayed departure of aircraft, incorrect information regarding the time of departure, failure to land at the scheduled destination and changes in flight schedule or addition of extra landing stops. Delay in the carriage of baggage or cargo may have different causes: no reservation, lack of space, failure to load the baggage or cargo at the right place, or to deliver the covering documents at the right place. The Montreal Convention of 1999 Article 19 provides that 'The carrier is liable for damage occasioned by delay in the carriage by air of passengers, baggage or cargo. Nevertheless, the carder shall not be liable for damage occasioned by delay if it proves that it and its servants and agents took all measures that could reasonably be required to avoid the damage or that it was impossible for it or them to take such measures'. The Montreal Convention Article 22 provides liability limits of the carrier in case of delay for passengers and their baggage and for cargo. In the carriage of persons, the liability of the carrier for each passenger is limited to 4,150 SDR. In the carriage of baggage, the liability of the carrier is limited to 1,000 SDR for each passenger unless a special declaration as to the value of the baggage has been made. In the carriage of cargo, the liability of the carrier is limited to 17 SDR per kilogram unless a special declaration as to the value of the cargo has been made. The Montreal Convention Article 19 has shortcomings: it is silent on the duration of the liability for carriage,andit does not make any distinction between persons and good. It does not give any indication concerning the circumstances to be taken into account in cases of delay, and about the length of delay. In conclusion, it is

  4. Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

    Directory of Open Access Journals (Sweden)

    Borini Paulo

    1999-01-01

    Full Text Available Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehydrogenase, altered in 16% of the cases; alpha-1 globulin, 24%; alpha-2 globulin, 88%; leucocyte counts, 28% was correlated with alterations of bilirubin or liver enzymes. Lactic dehydrogenase was poorly sensitive for detection of hepatocytic or muscular damage. Alterations of alpha-globulins seemed to have been due more to alcohol metabolism-induced increase of lipoproteins than to inflammation. Among indicators of cell damage, serum iron, increased in 40% of the cases, seemed to be related to liver damage while creatine phosphokinase, increased in 84% of the cases, related to muscle damage. Hyperamylasemia was found in 20% of the cases and significantly correlated with levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It was indicated that injuries of liver, pancreas, salivary glands, and muscle occurred in asymptomatic or oligosymptomatic chronic alcoholics.

  5. [Pulse-modulated Electromagnetic Radiation of Extremely High Frequencies Protects Cellular DNA against Damaging Effect of Physico-Chemical Factors in vitro].

    Science.gov (United States)

    Gapeyev, A B; Lukyanova, N A

    2015-01-01

    Using a comet assay technique, we investigated protective effects of. extremely high frequency electromagnetic radiation in combination with the damaging effect of X-ray irradiation, the effect of damaging agents hydrogen peroxide and methyl methanesulfonate on DNA in mouse whole blood leukocytes. It was shown that the preliminary exposure of the cells to low intensity pulse-modulated electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, 20-min exposure, modulation frequencies of 1 and 16 Hz) caused protective effects decreasing the DNA damage by 20-45%. The efficacy of pulse-modulated electromagnetic radiation depended on the type of genotoxic agent and increased in a row methyl methanesulfonate--X-rays--hydrogen peroxide. Continuous electromagnetic radiation was ineffective. The mechanisms of protective effects may be connected with an induction of the adaptive response by nanomolar concentrations of reactive oxygen species formed by pulse-modulated electromagnetic radiation.

  6. Cellular damage of Escherichia coli 0157:H7 and Salmonella spp. in apple juice treated with high hydrostatic pressure and thermal death time disks

    Science.gov (United States)

    Differences in membrane damage including leakage of intracellular UV-materials and loss of viability of Salmonella spp. and Escherichia coli O157:H7 bacteria in apple juice, pH 3.1 following thermal-death-time (TDT) disk and high hydrostatic pressure (HHP) treatments were investigated. Salmonella an...

  7. Difference in cellular damage and cell death in thermal death time disks and high hydrostatic pressure treated Salmonella Enteritidis (ATCC13076) in liquid whole egg

    Science.gov (United States)

    Differences in membrane damage including leakage of intracellular UV-materials and loss of viability of Salmonella Enteritidis (ATCC13076) in liquid whole egg (LWE) following thermal-death-time (TDT) disk and high hydrostatic pressure treatments were examined. Salmonella enteritidis was inoculated ...

  8. Resistance to Internal Damage and Scaling of Concrete Air Entrained By Microspheres

    Science.gov (United States)

    Molendowska, Agnieszka; Wawrzenczyk, Jerzy

    2017-10-01

    This paper report the test results of high strength concrete produced with slag cement and air entrained with polymer microspheres in three diameters. The study focused on determining the effects of the microsphere size and quantity on the air void structure and resistance to internal cracking and scaling of the concrete. The resistance to internal cracking was determined in compliance with the requirements of the modified ASTM C666 A method on beam specimens. The scaling resistance in a 3% NaCl solution was determined using the slab test in accordance with PKN-CEN/TS 12390-9:2007. The air void structure parameters were determined to PN-EN 480-11:1998. The study results indicate that the use of microspheres is an effective air entrainment method providing very good air void structure parameters. The results show high freeze-thaw durability of polymer microsphere-based concrete in exposure class XF3. The scaling resistance test confirms that it is substantially more difficult to protect concrete against scaling in the presence of the 3% NaCl solution (exposure class XF4). Concrete scaling is a complex phenomenon controlled by a number of independent factors.

  9. How much can disaster and climate science contribute to loss and damage mechanisms in international climate policy?

    Science.gov (United States)

    Huggel, Christian; Allen, Simon; Eicken, Hajo; Hansen, Gerrit; Stone, Dáithí

    2015-04-01

    As the 5th Assessment Report of the Intergovernmental Panel on Climate Change (IPCC) recently has shown, there is increasing evidence of observed impacts of climate change on natural and human systems. Some of these impacts are negative and result in damage and loss of lives and assets. In international climate policy negotiations under the UNFCCC the discussions on loss and damage have gained significant traction during the past negotiation rounds. At COP 19 the Warsaw International Mechanism for Loss and Damage (WIM) was created as an institutional arrangement to address this issue. Thereby, loss and damage (L&D) are typically defined as the residual damage and loss that occur beyond mitigation and adaptation efforts. This implies that effective mitigation and adaptation policy can substantially reduce L&D. While there is wide agreement that knowledge and understanding needs to be strengthened on how L&D due to climate change affects countries, in particular highly vulnerable countries and populations, there is still substantial disagreement on several aspects. In fact, after COP20 in Lima a number of options are on the table, including whether L&D should be located under the adaptation framework or form a separate institutional arrangement, or whether a compensation regime should be established to support developing countries. Similarly, the scientific framework for a clear L&D concept, its application in real-world cases, and implications for international climate policy, in particular with respect to questions of responsibility, liability, compensation and financing, is still evolving. Earlier proposals, for instance, have included a threshold concept, with payments released upon crossing of certain thresholds of climate (related) parameters, similar to insurance procedures. The threshold would be defined as a departure of the parameter from baseline conditions, for instance a rainfall event that is more intense than a certain baseline based threshold. Further

  10. Crack and damage assessment in concrete and polymer matrices using liquids released internally from hollow optical fibers

    Science.gov (United States)

    Dry, Carolyn M.; McMillan, William

    1996-05-01

    This was an investigation into the feasibility of using liquid core optical fibers for the detection and self repair of cracking in cement or polymer materials generated by dynamic or static loading. These experiments relied on our current research sponsored by the National Science Foundation. That work on the concept of internal adhesive delivery from hollow fibers for repair was here combined with the nondestructive fiber optic analysis of crack location and volume. The combination of the ability to remotely measure crack occurrence in real time and determine the location and volume of crack damage in the matrix is unique in the field of optic sensors. The combination of this with crack repair, rebonding of any detached or broken fibers, and replenishment of liquid core chemicals, when necessary, make this a potentially powerful sensing and repair tool. Work on this research topic was sponsored by the University of Illinois.

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

    International Nuclear Information System (INIS)

    Kolaczkowski, A.M.; Cramond, W.R.; Sype, T.T.; Maloney, K.J.; Wheeler, T.A.; Daniel, S.L.

    1989-08-01

    This document contains the appendices for the accident sequence analysis of internally initiated events for the Peach Bottom, Unit 2 Nuclear Power Plant. This is one of the five plant analyses conducted as part of the NUREG-1150 effort for the Nuclear Regulatory Commission. The work performed and described here is an extensive reanalysis of that published in October 1986 as NUREG/CR-4550, Volume 4. It addresses comments from numerous reviewers and significant changes to the plant systems and procedures made since the first report. The uncertainty analysis and presentation of results are also much improved, and considerable effort was expended on an improved analysis of loss of offsite power. The content and detail of this report is directed toward PRA practitioners who need to know how the work was done and the details for use in further studies. 58 refs., 58 figs., 52 tabs

  12. Liability and compensation for oil pollution damage: some current threats to the international convention system

    International Nuclear Information System (INIS)

    Chao Wu

    2002-01-01

    The carriage of oil is indispensable to the industrialized nations. In this respect, the carriage of oil is undertaken as a service to society as a whole with its individual members deriving benefits from its carriage to varying degrees. Consequently, after examining the four Conventions in the international system of compensation for oil pollution from ships, it is argued that the general citizenship of those nations pay, in exceptional cases, for a small share of the risk, which is created in part by the citizens, as users of oil. The paper proposes the creation of a fund of last resort that could be conceived either at a regional level or a national level and financed through (indirect) taxation on the population as a whole. This type of fund could have a wider use in the field of marine pollution and protection of marine resources. (author)

  13. Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

    OpenAIRE

    Borini, Paulo; Guimarães, Romeu Cardoso

    1999-01-01

    Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehy...

  14. Application of Deep Learning Architectures for Accurate and Rapid Detection of Internal Mechanical Damage of Blueberry Using Hyperspectral Transmittance Data

    Directory of Open Access Journals (Sweden)

    Zhaodi Wang

    2018-04-01

    Full Text Available Deep learning has become a widely used powerful tool in many research fields, although not much so yet in agriculture technologies. In this work, two deep convolutional neural networks (CNN, viz. Residual Network (ResNet and its improved version named ResNeXt, are used to detect internal mechanical damage of blueberries using hyperspectral transmittance data. The original structure and size of hypercubes are adapted for the deep CNN training. To ensure that the models are applicable to hypercube, we adjust the number of filters in the convolutional layers. Moreover, a total of 5 traditional machine learning algorithms, viz. Sequential Minimal Optimization (SMO, Linear Regression (LR, Random Forest (RF, Bagging and Multilayer Perceptron (MLP, are performed as the comparison experiments. In terms of model assessment, k-fold cross validation is used to indicate that the model performance does not vary with the different combination of dataset. In real-world application, selling damaged berries will lead to greater interest loss than discarding the sound ones. Thus, precision, recall, and F1-score are also used as the evaluation indicators alongside accuracy to quantify the false positive rate. The first three indicators are seldom used by investigators in the agricultural engineering domain. Furthermore, ROC curves and Precision-Recall curves are plotted to visualize the performance of classifiers. The fine-tuned ResNet/ResNeXt achieve average accuracy and F1-score of 0.8844/0.8784 and 0.8952/0.8905, respectively. Classifiers SMO/ LR/RF/Bagging/MLP obtain average accuracy and F1-score of 0.8082/0.7606/0.7314/0.7113/0.7827 and 0.8268/0.7796/0.7529/0.7339/0.7971, respectively. Two deep learning models achieve better classification performance than the traditional machine learning methods. Classification for each testing sample only takes 5.2 ms and 6.5 ms respectively for ResNet and ResNeXt, indicating that the deep learning framework has great

  15. Application of Deep Learning Architectures for Accurate and Rapid Detection of Internal Mechanical Damage of Blueberry Using Hyperspectral Transmittance Data.

    Science.gov (United States)

    Wang, Zhaodi; Hu, Menghan; Zhai, Guangtao

    2018-04-07

    Deep learning has become a widely used powerful tool in many research fields, although not much so yet in agriculture technologies. In this work, two deep convolutional neural networks (CNN), viz. Residual Network (ResNet) and its improved version named ResNeXt, are used to detect internal mechanical damage of blueberries using hyperspectral transmittance data. The original structure and size of hypercubes are adapted for the deep CNN training. To ensure that the models are applicable to hypercube, we adjust the number of filters in the convolutional layers. Moreover, a total of 5 traditional machine learning algorithms, viz. Sequential Minimal Optimization (SMO), Linear Regression (LR), Random Forest (RF), Bagging and Multilayer Perceptron (MLP), are performed as the comparison experiments. In terms of model assessment, k-fold cross validation is used to indicate that the model performance does not vary with the different combination of dataset. In real-world application, selling damaged berries will lead to greater interest loss than discarding the sound ones. Thus, precision, recall, and F1-score are also used as the evaluation indicators alongside accuracy to quantify the false positive rate. The first three indicators are seldom used by investigators in the agricultural engineering domain. Furthermore, ROC curves and Precision-Recall curves are plotted to visualize the performance of classifiers. The fine-tuned ResNet/ResNeXt achieve average accuracy and F1-score of 0.8844/0.8784 and 0.8952/0.8905, respectively. Classifiers SMO/ LR/RF/Bagging/MLP obtain average accuracy and F1-score of 0.8082/0.7606/0.7314/0.7113/0.7827 and 0.8268/0.7796/0.7529/0.7339/0.7971, respectively. Two deep learning models achieve better classification performance than the traditional machine learning methods. Classification for each testing sample only takes 5.2 ms and 6.5 ms respectively for ResNet and ResNeXt, indicating that the deep learning framework has great potential for

  16. Application of Deep Learning Architectures for Accurate and Rapid Detection of Internal Mechanical Damage of Blueberry Using Hyperspectral Transmittance Data

    Science.gov (United States)

    Hu, Menghan; Zhai, Guangtao

    2018-01-01

    Deep learning has become a widely used powerful tool in many research fields, although not much so yet in agriculture technologies. In this work, two deep convolutional neural networks (CNN), viz. Residual Network (ResNet) and its improved version named ResNeXt, are used to detect internal mechanical damage of blueberries using hyperspectral transmittance data. The original structure and size of hypercubes are adapted for the deep CNN training. To ensure that the models are applicable to hypercube, we adjust the number of filters in the convolutional layers. Moreover, a total of 5 traditional machine learning algorithms, viz. Sequential Minimal Optimization (SMO), Linear Regression (LR), Random Forest (RF), Bagging and Multilayer Perceptron (MLP), are performed as the comparison experiments. In terms of model assessment, k-fold cross validation is used to indicate that the model performance does not vary with the different combination of dataset. In real-world application, selling damaged berries will lead to greater interest loss than discarding the sound ones. Thus, precision, recall, and F1-score are also used as the evaluation indicators alongside accuracy to quantify the false positive rate. The first three indicators are seldom used by investigators in the agricultural engineering domain. Furthermore, ROC curves and Precision-Recall curves are plotted to visualize the performance of classifiers. The fine-tuned ResNet/ResNeXt achieve average accuracy and F1-score of 0.8844/0.8784 and 0.8952/0.8905, respectively. Classifiers SMO/ LR/RF/Bagging/MLP obtain average accuracy and F1-score of 0.8082/0.7606/0.7314/0.7113/0.7827 and 0.8268/0.7796/0.7529/0.7339/0.7971, respectively. Two deep learning models achieve better classification performance than the traditional machine learning methods. Classification for each testing sample only takes 5.2 ms and 6.5 ms respectively for ResNet and ResNeXt, indicating that the deep learning framework has great potential for

  17. REC-2006—A Fractionated Extract of Podophyllum hexandrum Protects Cellular DNA from Radiation-Induced Damage by Reducing the Initial Damage and Enhancing Its Repair In Vivo

    Science.gov (United States)

    Chaudhary, Pankaj; Shukla, Sandeep Kumar; Sharma, Rakesh Kumar

    2011-01-01

    Podophyllum hexandrum, a perennial herb commonly known as the Himalayan May Apple, is well known in Indian and Chinese traditional systems of medicine. P. hexandrum has been widely used for the treatment of venereal warts, skin infections, bacterial and viral infections, and different cancers of the brain, lung and bladder. This study aimed at elucidating the effect of REC-2006, a bioactive fractionated extract from the rhizome of P. hexandrum, on the kinetics of induction and repair of radiation-induced DNA damage in murine thymocytes in vivo. We evaluated its effect on non-specific radiation-induced DNA damage by the alkaline halo assay in terms of relative nuclear spreading factor (RNSF) and gene-specific radiation-induced DNA damage via semi-quantitative polymerase chain reaction. Whole body exposure of animals with gamma rays (10 Gy) caused a significant amount of DNA damage in thymocytes (RNSF values 17.7 ± 0.47, 12.96 ± 1.64 and 3.3 ± 0.014) and a reduction in the amplification of β-globin gene to 0, 28 and 43% at 0, 15 and 60 min, respectively. Administrating REC-2006 at a radioprotective concentration (15 mg kg−1 body weight) 1 h before irradiation resulted in time-dependent reduction of DNA damage evident as a decrease in RNSF values 6.156 ± 0.576, 1.647 ± 0.534 and 0.496 ± 0.012, and an increase in β-globin gene amplification 36, 95 and 99%, at 0, 15 and 60 min, respectively. REC-2006 scavenged radiation-induced hydroxyl radicals in a dose-dependent manner stabilized DPPH free radicals and also inhibited superoxide anions. Various polyphenols and flavonoides present in REC-2006 might contribute to scavenging of radiation-induced free radicals, thereby preventing DNA damage and stimulating its repair. PMID:20008078

  18. Radiation and chemical interactions producing cellular and subcellular damage and their repair. Coordinated programme on improvement in radiotherapy of cancer using modifiers of radiosensitivity of cells

    International Nuclear Information System (INIS)

    Kada, T.

    1982-01-01

    As a result of biochemical studies on the DNA repair of damages induced by ionizing radiation as well as on the radiosensitization with chemicals containing halogen atoms, it was suggested that inhibition of the post-irradiation repair by chemical factors may be useful in improving the radiotherapy. It was possbile to prepare an in vitro repair system in combination with transforming DNA of Bacillus subtilis as well as human placenta extracts; it was shown that certain radiosensitizers worked actually as repair inhibitors in this in vitro system

  19. Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins.

    Science.gov (United States)

    Colin, Didier J; Hain, Karolina O; Allan, Lindsey A; Clarke, Paul R

    2015-03-01

    Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

  20. Effects of Lycium barbarum Polysaccharides on Apoptosis, Cellular Adhesion, and Oxidative Damage in Bone Marrow Mononuclear Cells of Mice Exposed to Ionizing Radiation Injury.

    Science.gov (United States)

    Zhou, Jing; Pang, Hua; Li, Wenbo; Liu, Qiong; Xu, Lu; Liu, Qian; Liu, Ying

    2016-01-01

    Lycium barbarum has been used for more than 2500 years as a traditional herb and food in China. We investigated the effects of Lycium barbarum polysaccharides (LBP) on apoptosis, oxidative damage, and expression of adhesion molecules in bone marrow mononuclear cells (BMNC) of mice injured by ionizing radiation. Kunming mice were exposed to X-rays; then mice in the LBP groups were continuously injected with various concentrations of LBP intraperitoneally for 14 days. Mice in the control group were continuously injected with normal saline (NS) by the same route for 14 days. A normal group was set up. After 1, 7, and 14 days of treatment, mice were killed and BMNC were extracted. Cell cycle, apoptosis, and the expression of adhesion molecules CD44 and CD49d were detected by flow cytometry. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were identified by colorimetric analyses. LBP significantly decreased the percentage of G0/G1 phase, apoptosis, MDA level, and expression of CD44 and CD49d and distinctly increased the activity of SOD. LBP showed a protective effect on BMNC against ionizing radiation-induced apoptosis and oxidative damage and altered the expression of adhesion molecule.

  1. Cellular Dynamics of Rad51 and Rad54 in Response to Postreplicative Stress and DNA Damage in HeLa Cells.

    Science.gov (United States)

    Choi, Eui-Hwan; Yoon, Seobin; Hahn, Yoonsoo; Kim, Keun P

    2017-02-01

    Homologous recombination (HR) is necessary for maintenance of genomic integrity and prevention of various mutations in tumor suppressor genes and proto-oncogenes. Rad51 and Rad54 are key HR factors that cope with replication stress and DNA breaks in eukaryotes. Rad51 binds to single-stranded DNA (ssDNA) to form the presynaptic filament that promotes a homology search and DNA strand exchange, and Rad54 stimulates the strand-pairing function of Rad51. Here, we studied the molecular dynamics of Rad51 and Rad54 during the cell cycle of HeLa cells. These cells constitutively express Rad51 and Rad54 throughout the entire cell cycle, and the formation of foci immediately increased in response to various types of DNA damage and replication stress, except for caffeine, which suppressed the Rad51-dependent HR pathway. Depletion of Rad51 caused severe defects in response to postreplicative stress. Accordingly, HeLa cells were arrested at the G2-M transition although a small amount of Rad51 was steadily maintained in HeLa cells. Our results suggest that cell cycle progression and proliferation of HeLa cells can be tightly controlled by the abundance of HR proteins, which are essential for the rapid response to postreplicative stress and DNA damage stress.

  2. International standard problem ISP36. Cora-W2 experiment on severe fuel damage for a Russian type PWR

    International Nuclear Information System (INIS)

    1996-01-01

    An OECD/NEA-CSNI International Standard Problem (ISP) has been performed on the experimental comparison basis of the severe fuel damage experiment CORA-W2. The out-of-pile experiment CORA-W2 was executed in February 1993 at he Forschungszentrum Karlsruhe. The objective of this experiment was the investigation of the behavior of a Russian type PWR fuel element (VVER-1000) during early core degradation. The main difference between a Western type and a Russian type PWR bundle is the B 4 C absorber rod instead of AgInCd. Measured quantities ar boundary conditions, bundle temperature, hydrogen generation and the final bundle configurations after cooldown. The ISP was conducted as a blind exercise. Boundary conditions were estimated using ATHLET-CD. Six different severe accident codes were used. The comparisons between experimental and analytical results were grouped by codes and examined separately. The thermal behavior up to significant oxidation has been predicted quite well. Larger deviations have been observed for the oxidation-induced temperature escalation, both time of onset and maximum temperature as well. The bundle behavior is greatly influenced by chemical interactions involving B 4 C absorber rod material, which failed relatively early at low temperature due to eutectic interaction between B 4 C and SS cladding as well as the SS guide tube. Regarding the complex material interaction larger differences can be recognized between calculated and measured results because of inappropriate models for material relocation and solidification processes and the lack of models describing the interactions of absorber rod materials with the fuel rods. For the total amount of H 2 generated, acceptable agreement could be achieved, if the total of oxidized zirconium was calculated correctly. The oxidation of stainless steel components and B 4 C were not treated. In general the confidence in code predictions decreases with processing core damage. (N.T.)

  3. International standard problem ISP36. Cora-W2 experiment on severe fuel damage for a Russian type PWR

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    An OECD/NEA-CSNI International Standard Problem (ISP) has been performed on the experimental comparison basis of the severe fuel damage experiment CORA-W2. The out-of-pile experiment CORA-W2 was executed in February 1993 at he Forschungszentrum Karlsruhe. The objective of this experiment was the investigation of the behavior of a Russian type PWR fuel element (VVER-1000) during early core degradation. The main difference between a Western type and a Russian type PWR bundle is the B{sub 4}C absorber rod instead of AgInCd. Measured quantities ar boundary conditions, bundle temperature, hydrogen generation and the final bundle configurations after cooldown. The ISP was conducted as a blind exercise. Boundary conditions were estimated using ATHLET-CD. Six different severe accident codes were used. The comparisons between experimental and analytical results were grouped by codes and examined separately. The thermal behavior up to significant oxidation has been predicted quite well. Larger deviations have been observed for the oxidation-induced temperature escalation, both time of onset and maximum temperature as well. The bundle behavior is greatly influenced by chemical interactions involving B{sub 4}C absorber rod material, which failed relatively early at low temperature due to eutectic interaction between B{sub 4}C and SS cladding as well as the SS guide tube. Regarding the complex material interaction larger differences can be recognized between calculated and measured results because of inappropriate models for material relocation and solidification processes and the lack of models describing the interactions of absorber rod materials with the fuel rods. For the total amount of H{sub 2} generated, acceptable agreement could be achieved, if the total of oxidized zirconium was calculated correctly. The oxidation of stainless steel components and B{sub 4}C were not treated. In general the confidence in code predictions decreases with processing core damage. 36 refs.

  4. Existence of a current price as a precondition for abstract method for calculating damages in international and Serbian sales law

    Directory of Open Access Journals (Sweden)

    Fišer-Šobot Sandra

    2014-01-01

    Full Text Available If the contract is avoided and there is a current price for the goods, the party claiming damages may recover the difference between the price fixed by the contract and the current price at specific time and at specific place. Abstract calculation of loss is possible only when the contract goods have current price. Current price is the price generally charged for such goods sold under comparable circumstances in the trade concerned. According to the CISG and Serbian Law of Obligations, for the determination of the current price is relevant time of avoidance. This general rule is not applicable in international sales law when the party claiming damages has avoided the contract after taking over the goods. In that case, the current price at the time of taking over shall be applicable instead of the current price at the time of avoidance. Current price rule contained in the Art. 76(2 of the CISG presupposes that the current price is the price prevailing at the place where the delivery of the goods should have been made, or if there is no current price at the place, the price at such other place as serves as a reasonable substitute, making due allowance for differences in the cost of transporting the goods. Pursuant to Art. 524(2 Of Serbian Law of Obligations, however, relevant is the price in the market of the place of effecting the transaction. Formulation place of effecting the transaction is unclear and vague and can create different problems. Therefore, this rule should be amended and the relevant place should be the place of delivery.

  5. Cellular dosimetry

    International Nuclear Information System (INIS)

    Humm, J.L.; Chin, L.M.

    1989-01-01

    Radiation dose is a useful predictive parameter for describing radiation toxicity in conventional radiotherapy. Traditionally, in vitro radiation biology dose-effect relations are expressed in the form of cell survival curves, a semilog plot of cell survival versus dose. However, the characteristic linear or linear quadratic survival curve shape, for high- and low-LET radiations respectively, is only strictly valid when the radiation dose is uniform across the entire target population. With an external beam of 60 Co gamma rays or x-rays, a uniform field may be readily achievable. When radionuclides are incorporated into a cell milieu, several new problems emerge which can result in a departure from uniformity in energy deposition throughout a cell population. This nonuniformity can have very important consequences for the shape of the survival curve. Cases in which perturbations of source uniformity may arise include: 1. Elemental sources may equilibrate in the cell medium with partition coefficients between the extracellular, cytosol, and nuclear compartments. The effect of preferential cell internalization or binding to cell membrane of some radionuclides can increase or decrease the slope of the survival curve. 2. Radionuclides bound to antibodies, hormones, metabolite precursors, etc., may result in a source localization pattern characteristic of the carrier agent, i.e., the sources may bind to cell surface receptors or antigens, be internalized, bind to secreted antigen concentrated around a fraction of the cell population, or become directly incorporated into the cell DNA. We propose to relate the distribution of energy deposition in cell nuclei to biological correlates of cellular inactivation. The probability of each cell's survival is weighted by its individual radiation burden, and the summation of these probabilities for the cell population can be used to predict the number or fraction of cell survivors

  6. Lipid Replacement Therapy: a Functional Food Approach with New Formulations for Reducing Cellular Oxidative Damage, Cancer-Associated Fatigue and the Adverse Effects of Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Garth L. Nicolson

    2011-04-01

    Full Text Available Backgroud:Cancer-associated fatigue and the chronic adverse effects of cancer therapy can be reduced by Lipid Replacement Therapy (LRT using membrane phospholipid mixtures given as food supplements.Methods:This is a review of the published literature on LRT and its uses.Results: LRT significantly reduced fatigue in cancer patients as well as patients suffering from chronic fatiguing illnesses and other medical conditions. It also reduced the adverse effects of chemotherapy, resulting in improvements in incidence of fatigue, nausea, diarrhea, impaired taste, constipation, insomnia and other quality of life indicators. In other diseases, such as chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses, LRT reduced fatigue by 35.5-43.1% in different clinical trials and increased mitochondrial function.Conclusions: LRT formulations appear to be useful as non-toxic dietary supplements for direct use or placed in functional foods to reduce fatigue and restore mitochondrial and other cellular membrane functions. Formulations of LRT phospholipids are suitable for addition to variousfood products for the treatment of a variety of chronic illnesses as well as their application inanti-aging and other health supplements and products.

  7. Discussing epigenetics in Southern California: a report from the International Symposium on Epigenetic Control and Cellular Plasticity, UCI, December 15-16, 2011.

    Science.gov (United States)

    Rattner, Barbara P

    2012-04-01

    With the goal of discussing how epigenetic control and chromatin remodeling contribute to the various processes that lead to cellular plasticity and disease, this symposium marks the collaboration between the Institut National de la Santé et de la Recherche Médicale (INSERM) in France and the University of California, Irvine (UCI). Organized by Paolo Sassone-Corsi (UCI) and held at the Beckman Center of the National Academy of Sciences at the UCI campus December 15-16, 2011, this was the first of a series of international conferences on epigenetics dedicated to the scientific community in Southern California. The meeting also served as the official kick off for the newly formed Center for Epigenetics and Metabolism at the School of Medicine, UCI (http://cem.igb.uci.edu).

  8. Analysis of oxidative DNA damage, Part II: Synthesis of the internal standard 8-[18O]hydroxy-2'-deoxyguanosine

    NARCIS (Netherlands)

    Hermanns RCA; Zomer G; Stavenuiter JFC; Westra G; Visser T; van de Werken G

    1993-01-01

    In the project 'Oxidative DNA Damage' the first aim is to develop a mass spectrometric method for the quantification of 8-hydroxy-2'- deoxyguanosine (oh8dG). The required precision of the method requires the application of a labeled analogue as an internal standard. This report

  9. ISP-31 OECD/NEA/CSNI International Standard Problem n.31. Cora-13 experiment on severe fuel damage. Comparison report

    International Nuclear Information System (INIS)

    Firnhaber, M.; Trambauer, K.; Hagen, S.; Hofmann, P.; Schanz, G.; Sepold, L.

    1993-07-01

    The severe fuel damage experiment CORA-13 has been offered as CSNI-International Standard Problem (ISP) No. 31. The out-of-pile experiment CORA-13 was executed in November 1990 at Kernforschungszentrum Karlsruhe. The major objectives of this experiment were to investigate the behavior of PWR fuel elements during early core degradation and fast cooldown due to refill. Measured quantities are boundary conditions, bundle temperatures, hydrogen generation and the final bundle configuration. The ISP was conducted as a blind exercise. Boundary conditions which could not be measured, but which are necessary for simplified test simulation (axial power profile, shroud insulation temperature, bundle refill flow) were estimated using ATHLET-CD. Results to the ISP were submitted by 9 participants using different versions of SCDAP/RELAP5, and codes such as FRAS-SFD, ICARE2, KESS-III, MELCOR. The thermal behavior up to significant oxidation has been predicted quite well by most of the codes. In general, the capability of the codes in calculating the main degradation phenomena has been clearly illustrated and weaknesses concerning the modelling of some degradation processes have been identified. Among the degradation phenomena involved in the test, the more severe limitations concern the UO 2 -ZrO 2 dissolution by molten Zr, the solubility limits in the resulting U-Zr-O mixture and the cladding failure by the molten mixture

  10. TiO2, SiO2 and ZrO2 Nanoparticles Synergistically Provoke Cellular Oxidative Damage in Freshwater Microalgae

    Directory of Open Access Journals (Sweden)

    Yinghan Liu

    2018-02-01

    Full Text Available Metal-based nanoparticles (NPs are the most widely used engineered nanomaterials. The individual toxicities of metal-based NPs have been plentifully studied. However, the mixture toxicity of multiple NP systems (n ≥ 3 remains much less understood. Herein, the toxicity of titanium dioxide (TiO2 nanoparticles (NPs, silicon dioxide (SiO2 NPs and zirconium dioxide (ZrO2 NPs to unicellular freshwater algae Scenedesmus obliquus was investigated individually and in binary and ternary combination. Results show that the ternary combination systems of TiO2, SiO2 and ZrO2 NPs at a mixture concentration of 1 mg/L significantly enhanced mitochondrial membrane potential and intracellular reactive oxygen species level in the algae. Moreover, the ternary NP systems remarkably increased the activity of the antioxidant defense enzymes superoxide dismutase and catalase, together with an increase in lipid peroxidation products and small molecule metabolites. Furthermore, the observation of superficial structures of S. obliquus revealed obvious oxidative damage induced by the ternary mixtures. Taken together, the ternary NP systems exerted more severe oxidative stress in the algae than the individual and the binary NP systems. Thus, our findings highlight the importance of the assessment of the synergistic toxicity of multi-nanomaterial systems.

  11. Reduction of oxidative cellular damage by overexpression of the thioredoxin TRX2 gene improves yield and quality of wine yeast dry active biomass

    Directory of Open Access Journals (Sweden)

    Ros Joaquim

    2010-02-01

    Full Text Available Abstract Background Wine Saccharomyces cerevisiae strains, adapted to anaerobic must fermentations, suffer oxidative stress when they are grown under aerobic conditions for biomass propagation in the industrial process of active dry yeast production. Oxidative metabolism of sugars favors high biomass yields but also causes increased oxidation damage of cell components. The overexpression of the TRX2 gene, coding for a thioredoxin, enhances oxidative stress resistance in a wine yeast strain model. The thioredoxin and also the glutathione/glutaredoxin system constitute the most important defense against oxidation. Trx2p is also involved in the regulation of Yap1p-driven transcriptional response against some reactive oxygen species. Results Laboratory scale simulations of the industrial active dry biomass production process demonstrate that TRX2 overexpression increases the wine yeast final biomass yield and also its fermentative capacity both after the batch and fed-batch phases. Microvinifications carried out with the modified strain show a fast start phenotype derived from its enhanced fermentative capacity and also increased content of beneficial aroma compounds. The modified strain displays an increased transcriptional response of Yap1p regulated genes and other oxidative stress related genes. Activities of antioxidant enzymes like Sod1p, Sod2p and catalase are also enhanced. Consequently, diminished oxidation of lipids and proteins is observed in the modified strain, which can explain the improved performance of the thioredoxin overexpressing strain. Conclusions We report several beneficial effects of overexpressing the thioredoxin gene TRX2 in a wine yeast strain. We show that this strain presents an enhanced redox defense. Increased yield of biomass production process in TRX2 overexpressing strain can be of special interest for several industrial applications.

  12. Establishment of a non-radioactive cleavage assay to assess the DNA repair capacity towards oxidatively damaged DNA in subcellular and cellular systems and the impact of copper

    International Nuclear Information System (INIS)

    Hamann, Ingrit; Schwerdtle, Tanja; Hartwig, Andrea

    2009-01-01

    Oxidative stress is involved in many diseases, and the search for appropriate biomarkers is one major focus in molecular epidemiology. 8-Oxoguanine (8-oxoG), a potentially mutagenic DNA lesion, is considered to be a sensitive biomarker for oxidative stress. Another approach consists in assessing the repair capacity towards 8-oxoG, mediated predominantly by the human 8-oxoguanine DNA glycosylase 1 (hOGG1). With respect to the latter, during the last few years so-called cleavage assays have been described, investigating the incision of 32 P-labelled and 8-oxoG damaged oligonucleotides by cell extracts. Within the present study, a sensitive non-radioactive test system based on a Cy5-labelled oligonucleotide has been established. Sources of incision activity are isolated proteins or extracts prepared from cultured cells and peripheral blood mononuclear cells (PBMC). After comparing different oligonucleotide structures, a hairpin-like structure was selected which was not degraded by cell extracts. Applying this test system the impact of copper on the activity of isolated hOGG1 and on hOGG activity in A549 cells was examined, showing a distinct inhibition of the isolated protein at low copper concentration as compared to a modest inhibition of hOGG activity in cells at beginning cytotoxic concentrations. For investigating PBMC, all reaction conditions, including the amounts of oligonucleotide and cell extract as well as the reaction time have been optimized. The incision activities of PBMC protein extracts obtained from different donors have been investigated, and inter-individual differences have been observed. In summary, the established method is as sensitive and even faster than the radioactive technique, and additionally, offers the advantage of reduced costs and low health risk.

  13. Cellular gravity

    NARCIS (Netherlands)

    F.C. Gruau; J.T. Tromp (John)

    1999-01-01

    textabstractWe consider the problem of establishing gravity in cellular automata. In particular, when cellular automata states can be partitioned into empty, particle, and wall types, with the latter enclosing rectangular areas, we desire rules that will make the particles fall down and pile up on

  14. Cellular internalization and morphological analysis after intravenous injection of a highly hydrophilic octahedral rhenium cluster complex - a new promising X-ray contrast agent.

    Science.gov (United States)

    Krasilnikova, Anna A; Solovieva, Anastasiya O; Trifonova, Kristina E; Brylev, Konstantin A; Ivanov, Anton A; Kim, Sung-Jin; Shestopalov, Michael A; Fufaeva, Maria S; Shestopalov, Alexander M; Mironov, Yuri V; Poveshchenko, Alexander F; Shestopalova, Lidia V

    2016-11-01

    The octahedral cluster compound Na 2 H 8 [{Re 6 Se 8 }(P(C 2 H 4 CONH 2 )(C 2 H 4 COO) 2 ) 6 ] has been shown to be highly radio dense, thus becoming a promising X-ray contrast agent. It was also shown that this compound had low cytotoxic effect in vitro, low acute toxicity in vivo and was eliminated rapidly from the body through the urinary tract. The present contribution describes a more detailed cellular internalization assay and morphological analysis after intravenous injection of this hexarhenium cluster compound at different doses. The median lethal dose (LD 50 ) of intravenously administrated compound was calculated (4.67 ± 0.69 g/kg). Results of the study clearly indicated that the cluster complex H n [{Re 6 Se 8 }(P(C 2 H 4 CONH 2 )(C 2 H 4 COO) 2 ) 6 ] n-10 was not internalized into cells in vitro and induced only moderate morphological alterations of kidneys at high doses without any changes in morphology of liver, spleen, duodenum, or heart of mice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Study on evolution of internal damage in CFRP in fatigue process; Hiro katei ni okeru CFRP no naibu sonsho no kento

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, K. [Nagoya Univ. (Japan); Murakami, S. [Nagoya Univ. (Japan). Faculty of Engineering

    1998-05-15

    Development of internal damage evolution in plates and thin tubular speciments of CFRP laminates under static and dynamic loadings are discussed by means of Acoustic Emission measurements and micrographical observations. The mechanical behavior of three kinds of speciments, i.e. undamaged laminate plates [+45deg{sub 4}/-45deg{sub 4}]{sub s}, damaged plates [+45deg{sub 4}/-45deg{sub 4}]{sub s} subjected to drop-weight impact and undamaged tubular speciments [ 45deg]{sub 4}, under quasi-static and fatigue loadings is observed first. Then the mechanism of the resulting inelastic behavior and the change in the mechanical properties are discussed in relation to the evolution of internal damage. Finally the distribution and the evolution of matrix crecks and delamination in the sliced section of the speciments are measured quantitatively in several stages of fatigue process. The dependence of damage distribution on the loading condition is elucidated. Namely, in the case of the stress ratio R=-0.25, the growth of damage zone involving the main crack is localized, and the main crack forms large delamination. On the other hand, for the stress ratio R=0, small cracks are distributed sparsely, but the main crack is not observed until the final stage of the fatifue process. 8 refs., 12 figs.

  16. Vitamins as radioprotectors in vivo II. protection by vitamin A and soybean oil against radiation damage caused by internal radionuclides

    International Nuclear Information System (INIS)

    Harapanhalli, R.S.; Narra, V.R.; Yaghmai, V.; Azure, M.T.; Goddu, M.; Howell, R.W.; Rao, D.V.

    1994-01-01

    Tissue-incorporated radionuclides impart radiation energy over extended periods of time depending on their effective half-lives. The capacity of vitamin A dissolved in soybean oil to protect against the biological effects caused by internal radionuclides is investigated. The radiochemicals examined are DNA-binding 125 IdU, cytoplasmically localized H 125 IPDM and the α-particle emitter 210 Po citrate. As in our previous studies, spermatogenesis in mice is used as the experimental model and spermatogonial cell survival is the biological end point. Surprisingly, soybean oil itself provides substantial and equal protection against the Auger effect of 125 IdU, which is comparable to a high-LET radiation effect, as well as the low-LET effects of H 125 IPDM, the dose modification factors (DMFs) being 3.6 ± 0.9 (SEM) and 3.4 ± 0.9, respectively. The protection afforded by the oil against the effects of 5.3 MeV α particles emitted by 210Po is also significant (DMF = 2.2 ± 0.4). The presence of vitamin A in the oil further enhanced the radioprotection against the effect of 125 IdU (DMF = 4.8 ± 1.3) and H 125 IKPDM (DMF = 5.1 ± 0.6); however, no enhancement is provided against the effects of α particles. These interesting results with soybean oil and vitamin A, together with data on the subcellular distribution of the protectors, provide clues regarding the mechanistic aspects of the protection. In addition, the data for vitamin A reaffirm our earlier conclusion that the mechanism by which DNA-bound Auger emitters impart biological damage is primarily indirect in nature. 29 refs., 7 figs., 2 tabs

  17. Internal state variable plasticity-damage modeling of AISI 4140 steel including microstructure-property relations: temperature and strain rate effects

    Science.gov (United States)

    Nacif el Alaoui, Reda

    Mechanical structure-property relations have been quantified for AISI 4140 steel. under different strain rates and temperatures. The structure-property relations were used. to calibrate a microstructure-based internal state variable plasticity-damage model for. monotonic tension, compression and torsion plasticity, as well as damage evolution. Strong stress state and temperature dependences were observed for the AISI 4140 steel. Tension tests on three different notched Bridgman specimens were undertaken to study. the damage-triaxiality dependence for model validation purposes. Fracture surface. analysis was performed using Scanning Electron Microscopy (SEM) to quantify the void. nucleation and void sizes in the different specimens. The stress-strain behavior exhibited. a fairly large applied stress state (tension, compression dependence, and torsion), a. moderate temperature dependence, and a relatively small strain rate dependence.

  18. Detection, characterization and measure of a new radiation-induced damage in isolated and cellular DNA; Detection, caracterisation et mesure d'un nouveau dommage radio-induit de l'ADN isole et cellulaire

    Energy Technology Data Exchange (ETDEWEB)

    Regulus, P

    2006-10-15

    Deoxyribonucleic acid (DNA) contains the genetic information and chemical injury to this macromolecule may have severe biological consequences. We report here the detection of 4 new radiation-induced DNA lesions by using a high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) approach. For that purpose, the characteristic fragmentation of most 2'-deoxy-ribo nucleosides, the loss of 116 Da corresponding to the loss of the 2-deoxyribose moiety, was used in the so-called neutral loss mode of the HPLC-MS/MS. One of the newly detected lesions, named dCyd341 because it is a 2'-deoxycytidine modification exhibiting a molecular weight of 341 Da, was also detected in cellular DNA. Characterization of this modified nucleoside was performed using NMR and exact mass determination of the product obtained by chemical synthesis. A mechanism of formation was then proposed, in which the first event is the H-abstraction at the C4 position of a 2-deoxyribose moiety. Then, the sugar modification produced exhibits a reactive aldehyde that, through reaction with a vicinal cytosine base, gives rise to dCyd341. dCyd341 could be considered as a complex damage since its formation involves a DNA strand break and a cross-link between a damaged sugar residue and a vicinal cytosine base located most probably on the complementary DNA strand. In addition to its characterization, preliminary biological studies revealed that cells are able to remove the lesion from DNA. Repair studies have revealed the ability of cells to excise the lesion. Identification of the repair systems involved could represent an interesting challenge. (author)

  19. An observation of histological evidence on internal organ damages in mice caused by repeated exposures to motorcycle emissions

    Science.gov (United States)

    Wardoyo, Arinto Y. P.; Juswono, Unggul P.; Noor, Johan A. E.

    2017-05-01

    Motor vehicle emissions have been identified as a source of ultrafine particles, which have significant impacts on human health. Repeated and prolonged exposure to ultrafine particles may have a significant association with organ damage. Here, we evaluated the correlation between repeated exposure to ultrafine particles and organ damage in mice. Motorcycle emissions were injected into an exposure chamber with mice for a period of 20 seconds. This treatment was conducted over 10 days. The mice were sacrificed on the 2nd, 4th, 6th, 8th, and 10th days for organ preparations. Based on the results, motorcycle emission exposure caused organ damage in mice, with different severities depending on the organ. The highest damage was found for the lung, followed by the kidney, erythrocytes, and liver.

  20. Synthesis, characterization and applications of carboxylated and polyethylene-glycolated bifunctionalized InP/ZnS quantum dots in cellular internalization mediated by cell-penetrating peptides.

    Science.gov (United States)

    Liu, Betty R; Winiarz, Jeffrey G; Moon, Jong-Sik; Lo, Shih-Yen; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

    2013-11-01

    Semiconductor nanoparticles, also known as quantum dots (QDs), are widely used in biomedical imaging studies and pharmaceutical research. Cell-penetrating peptides (CPPs) are a group of small peptides that are able to traverse cell membrane and deliver a variety of cargoes into living cells. CPPs deliver QDs into cells with minimal nonspecific absorption and toxic effect. In this study, water-soluble, monodisperse, carboxyl-functionalized indium phosphide (InP)/zinc sulfide (ZnS) QDs coated with polyethylene glycol lipids (designated QInP) were synthesized for the first time. The physicochemical properties (optical absorption, fluorescence and charging state) and cellular internalization of QInP and CPP/QInP complexes were characterized. CPPs noncovalently interact with QInP in vitro to form stable CPP/QInP complexes, which can then efficiently deliver QInP into human A549 cells. The introduction of 500nM of CPP/QInP complexes and QInP at concentrations of less than 1μM did not reduce cell viability. These results indicate that carboxylated and polyethylene-glycolylated (PEGylated) bifunctionalized QInP are biocompatible nanoparticles with potential for use in biomedical imaging studies and drug delivery applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. DNA damage and autophagy

    International Nuclear Information System (INIS)

    Rodriguez-Rocha, Humberto; Garcia-Garcia, Aracely; Panayiotidis, Mihalis I.; Franco, Rodrigo

    2011-01-01

    Both exogenous and endogenous agents are a threat to DNA integrity. Exogenous environmental agents such as ultraviolet (UV) and ionizing radiation, genotoxic chemicals and endogenous byproducts of metabolism including reactive oxygen species can cause alterations in DNA structure (DNA damage). Unrepaired DNA damage has been linked to a variety of human disorders including cancer and neurodegenerative disease. Thus, efficient mechanisms to detect DNA lesions, signal their presence and promote their repair have been evolved in cells. If DNA is effectively repaired, DNA damage response is inactivated and normal cell functioning resumes. In contrast, when DNA lesions cannot be removed, chronic DNA damage triggers specific cell responses such as cell death and senescence. Recently, DNA damage has been shown to induce autophagy, a cellular catabolic process that maintains a balance between synthesis, degradation, and recycling of cellular components. But the exact mechanisms by which DNA damage triggers autophagy are unclear. More importantly, the role of autophagy in the DNA damage response and cellular fate is unknown. In this review we analyze evidence that supports a role for autophagy as an integral part of the DNA damage response.

  2. Identification Of Damages Of Tribological Associations In Crankshaft And Piston Systems Of Two-Stroke Internal Combustion Engines Used As Main Propulsion In Sea-Going Vessels And Proposal Of Probabilistic Description Of Loads As Causes Of These Damages

    Directory of Open Access Journals (Sweden)

    Girtler Jerzy

    2015-04-01

    Full Text Available The article discusses damages of essential tribological associations in crankshaft and piston systems of large power two-stroke engines used as main engines, which take place during transport tasks performed by those ships. Difficulties are named which make preventing those damages impossible, despite the fact that the technical state of engines of this type is identified with the aid of complex diagnostic systems making use of advanced computer technology. It is demonstrated that one of causes of the damages is the lack of research activities oriented on recognising random properties of the loads leading to those damages. A proposal is made for the loads acting at a given time t on tribological associations in crankshaft and piston systems of internal combustion engines used as main engines to be considered as random variables Qt. At the same time the loads examined within a given time interval tr ≤ t ≤ tz would be considered stochastic processes {Q(t: t ≥ 0}. Essential properties of the loads of the abovementioned tribological associations are named and explained by formulating hypotheses which need empirical verification. Interval estimation is proposed for estimating the expected value E(Qt of the load Qt acting at time t. A relation is indicated between the mechanical load and the thermal load acting on tribological associations in the ship main engine crankshaft and piston system. A suggestion is formulated that a stochastic form of the relation between these types of load is to be searched for, rather than statistic relation, and a proposal is made to measure the intensity (strength of the stochastic relation using the Czuprow’s convergence coefficient.

  3. Iron status and its relations with oxidative damage and bone loss during long-duration space flight on the International Space Station.

    Science.gov (United States)

    Zwart, Sara R; Morgan, Jennifer L L; Smith, Scott M

    2013-07-01

    Increases in stored iron and dietary intake of iron during space flight have raised concern about the risk of excess iron and oxidative damage, particularly in bone. The objectives of this study were to perform a comprehensive assessment of iron status in men and women before, during, and after long-duration space flight and to quantify the association of iron status with oxidative damage and bone loss. Fasting blood and 24-h urine samples were collected from 23 crew members before, during, and after missions lasting 50 to 247 d to the International Space Station. Serum ferritin and body iron increased early in flight, and transferrin and transferrin receptors decreased later, which indicated that early increases in body iron stores occurred through the mobilization of iron to storage tissues. Acute phase proteins indicated no evidence of an inflammatory response during flight. Serum ferritin was positively correlated with the oxidative damage markers 8-hydroxy-2'-deoxyguanosine (r = 0.53, P < 0.001) and prostaglandin F2α (r = 0.26, P < 0.001), and the greater the area under the curve for ferritin during flight, the greater the decrease in bone mineral density in the total hip (P = 0.031), trochanter (P = 0.006), hip neck (P = 0.044), and pelvis (P = 0.049) after flight. Increased iron stores may be a risk factor for oxidative damage and bone resorption.

  4. Anisotropy of hardness and laser damage threshold of unidirectional organic NLO crystal in relation to the internal structure

    International Nuclear Information System (INIS)

    Natarajan, V.; Arivanandhan, M.; Sankaranarayanan, K.; Hayakawa, Y.

    2011-01-01

    Highlights: · Growth rate of the unidirectional organic crystals were measured and the variation in the growth rate was explained based on the attachment energy model. · Anisotropic behaviors of hardness and laser damage threshold of the unidirectional materials were analyzed. · The obtained results were explained based on the crystal structure of the material. - Abstract: Unidirectional benzophenone crystals were grown along , and directions by uniaxially solution crystallization method at ambient temperature. The growth rate of the grown crystals was varied with orientation. The optical absorption coefficients of benzophenone were measured as a function of wavelength. The optical absorption study reveals that the benzophenone crystal has very low absorption in the wavelength range of interest. Moreover, the laser damage threshold and micro hardness for , and oriented unidirectional benzophenone crystals were measured using a Q-switched Nd:YAG laser operating at 1064 nm radiation and Vicker's micro hardness tester, respectively. The laser damage threshold is larger for the and oriented crystals compared to oriented crystal at 1064 nm wavelength. The result is consistent with the hardness variation observed for the three different crystallographic directions of benzophenone crystal. The relation between the laser damage profile and mechanical hardness anisotropy is discussed based on the crystal structure of benzophenone.

  5. Cellular internalization and transport of biodegradable polyester dendrimers on a model of the pulmonary epithelium and their formulation in pressurized metered-dose inhalers.

    Science.gov (United States)

    Heyder, Rodrigo S; Zhong, Qian; Bazito, Reinaldo C; da Rocha, Sandro R P

    2017-03-30

    The purpose of this study was to evaluate the effect of generation and surface PEGylation of degradable polyester-based dendrimers nanocarriers on their interactions with an in vitro model of the pulmonary epithelium as well as to assess the ability to formulate such carriers in propellant-based, portable oral-inhalation devices to determine their potential for local and systemic delivery of drugs to and through the lungs. Hydroxyl (-OH) terminated polyester dendrimers of generation 3 and 4 (G3, and G4) were synthesized using a divergent approach. G4 was surface-modified with PEG (1,000Da). All dendrimers and their building blocks were determined to be highly compatible with the model pulmonary epithelium, with toxicity profiles much more favorable than non-degradable polyamidoamine dendrimers (PAMAM). The transport of the species from the apical to basolateral side across polarized Calu-3 monolayers showed to be generation and surface-chemistry (PEGylation) dependent. The extent of the transport is modulated by their interaction with the polarized epithelium and their transient opening of the tight junctions. G3 was the one most efficiently internalized by the epithelium, and had a small impact on the integrity of the monolayer. On the other hand, the PEGylated G4 was the one least internalized by the polarized epithelium, and at the same time had a more pronounced transient impact on the cellular junctions, resulting in more efficient transport across the cell monolayer. PEGylation of the dendrimer surface played other roles as well. PEGylation modulated the degradation profile of the dendrimer, slowing the process in a step-wise fashion - first the PEG layer is shed and then the dendrimer starts degrading. PEGylation also helped increase the solvation of the nanocarriers by the hydrofluoroalkane propellant used in pressurized metered-dose inhalers, resulting in formulations with excellent dispersibility and aerosol quality (deep lung deposition of 88

  6. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

    Science.gov (United States)

    Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Zoica Dinu, Cerasela

    2016-02-01

    Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.

  7. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

    Science.gov (United States)

    Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Dinu, Cerasela Zoica

    2016-01-01

    Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications. PMID:26820775

  8. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

    International Nuclear Information System (INIS)

    Eldawud, Reem; Dinu, Cerasela Zoica; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha

    2016-01-01

    Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications. (paper)

  9. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate.

    Science.gov (United States)

    Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Dinu, Cerasela Zoica

    2016-02-26

    Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.

  10. Cellular metabolism

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  11. Creep-Fatigue Damage Evaluation of a Model Reactor Vessel and Reactor Internals of Sodium Test Facility according to ASME-NH and RCC-MRx Codes

    International Nuclear Information System (INIS)

    Lim, Dong-Won; Lee, Hyeong-Yeon; Eoh, Jae-Hyuk; Son, Seok-Kwon; Kim, Jong-Bum; Jeong, Ji-Young

    2016-01-01

    The objective of the STELLA-2 is to support the specific design approval for PGSFR by synthetic reviews of key safety issues and code validations through the integral effect tests. Due to its high temperature operation in SFRs (and in a testing facility) up to 550 °C, thermally induced creep-fatigue damage is very likely in components including a reactor vessel, reactor internals (interior structures), heat exchangers, pipelines, etc. In this study, structural integrity of the components such as reactor vessel and internals in STELLA-2 has been evaluated against creep-fatigue failures at a concept-design step. As 2D analysis yields far conservative results, a realistic 3D simulation is performed by a commercial software. A design integrity guarding against a creep-fatigue damage failure operating at high temperature was evaluated for the reactor vessel with its internal structure of the STELLA-2. Both the high temperature design codes were used for the evaluation, and results were compared. All the results showed the vessel as a whole is safely designed at the given operating conditions, while the ASME-NH gives a conservative evaluation

  12. Creep-Fatigue Damage Evaluation of a Model Reactor Vessel and Reactor Internals of Sodium Test Facility according to ASME-NH and RCC-MRx Codes

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Dong-Won; Lee, Hyeong-Yeon; Eoh, Jae-Hyuk; Son, Seok-Kwon; Kim, Jong-Bum; Jeong, Ji-Young [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    The objective of the STELLA-2 is to support the specific design approval for PGSFR by synthetic reviews of key safety issues and code validations through the integral effect tests. Due to its high temperature operation in SFRs (and in a testing facility) up to 550 °C, thermally induced creep-fatigue damage is very likely in components including a reactor vessel, reactor internals (interior structures), heat exchangers, pipelines, etc. In this study, structural integrity of the components such as reactor vessel and internals in STELLA-2 has been evaluated against creep-fatigue failures at a concept-design step. As 2D analysis yields far conservative results, a realistic 3D simulation is performed by a commercial software. A design integrity guarding against a creep-fatigue damage failure operating at high temperature was evaluated for the reactor vessel with its internal structure of the STELLA-2. Both the high temperature design codes were used for the evaluation, and results were compared. All the results showed the vessel as a whole is safely designed at the given operating conditions, while the ASME-NH gives a conservative evaluation.

  13. Preharvest internalization of Escherichia coli O157:H7 into lettuce leaves, as affected by insect and physical damage.

    Science.gov (United States)

    Erickson, Marilyn C; Liao, Jean; Payton, Alison S; Riley, David G; Webb, Cathy C; Davey, Lindsey E; Kimbrel, Sophia; Ma, Li; Zhang, Guodong; Flitcroft, Ian; Doyle, Michael P; Beuchat, Larry R

    2010-10-01

    Environmental pests may serve as reservoirs and vectors of zoonotic pathogens to leafy greens; however, it is unknown whether insect pests feeding on plant tissues could redistribute these pathogens present on the surface of leaves to internal sites. This study sought to differentiate the degree of tissue internalization of Escherichia coli O157:H7 when applied at different populations on the surface of lettuce and spinach leaves, and to ascertain whether lettuce-infesting insects or physical injury could influence the fate of either surface or internalized populations of this enteric pathogen. No internalization of E. coli O157:H7 occurred when lettuce leaves were inoculated with 4.4 log CFU per leaf, but it did occur when inoculated with 6.4 log CFU per leaf. Internalization was statistically greater when spinach leaves were inoculated on the abaxial (underside) than when inoculated on the adaxial (topside) side, and when the enteric pathogen was spread after surface inoculation. Brief exposure (∼18 h) of lettuce leaves to insects (5 cabbage loopers, 10 thrips, or 10 aphids) prior to inoculation with E. coli O157:H7 resulted in significantly reduced internalized populations of the pathogen within these leaves after approximately 2 weeks, as compared with leaves not exposed to insects. Surface-contaminated leaves physically injured through file abrasions also had significantly reduced populations of both total and internalized E. coli O157:H7 as compared with nonabraded leaves 2 weeks after pathogen exposure.

  14. Towards a global system of compensation for transboundary nuclear damage: reflexions on the interrelationship of civil and international state liability

    International Nuclear Information System (INIS)

    Handl, G.

    1993-01-01

    International state liability is an essential complementary element of any global and comprehensive nuclear compensation system. Civil liability alone will not be able to fully compensate victims of a nuclear accident and will therefore not fully internalize the costs of nuclear activities. To make it effective and politically acceptable, state liability must be fully integrated procedurally with any civil liability system as a last tier of compensation following a simple process for handling together both civil and state liability claims at the international level, with individuals being able to sue Installation States. 69 refs

  15. Modeling and cellular studies

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    Testing the applicability of mathematical models with carefully designed experiments is a powerful tool in the investigations of the effects of ionizing radiation on cells. The modeling and cellular studies complement each other, for modeling provides guidance for designing critical experiments which must provide definitive results, while the experiments themselves provide new input to the model. Based on previous experimental results the model for the accumulation of damage in Chlamydomonas reinhardi has been extended to include various multiple two-event combinations. Split dose survival experiments have shown that models tested to date predict most but not all the observed behavior. Stationary-phase mammalian cells, required for tests of other aspects of the model, have been shown to be at different points in the cell cycle depending on how they were forced to stop proliferating. These cultures also demonstrate different capacities for repair of sublethal radiation damage

  16. Simulation model and methodology for calculating the damage by internal radiation in a PWR reactor; Modelo de simulacion y metodologia para el calculo del dano por irradiacion en los internos de un reactor PWR

    Energy Technology Data Exchange (ETDEWEB)

    Cadenas Mendicoa, A. M.; Benito Hernandez, M.; Barreira Pereira, P.

    2012-07-01

    This study involves the development of the methodology and three-dimensional models to estimate the damage to the vessel internals of a commercial PWR reactor from irradiation history of operating cycles.

  17. Introducing a true internal standard for the Comet assay to minimize intra- and inter-experiment variability in measures of DNA damage and repair

    Science.gov (United States)

    Zainol, Murizal; Stoute, Julia; Almeida, Gabriela M.; Rapp, Alexander; Bowman, Karen J.; Jones, George D. D.

    2009-01-01

    The Comet assay (CA) is a sensitive/simple measure of genotoxicity. However, many features of CA contribute variability. To minimize these, we have introduced internal standard materials consisting of ‘reference’ cells which have their DNA substituted with BrdU. Using a fluorescent anti-BrdU antibody, plus an additional barrier filter, comets derived from these cells could be readily distinguished from the ‘test’-cell comets, present in the same gel. In experiments to evaluate the reference cell comets as external and internal standards, the reference and test cells were present in separate gels on the same slide or mixed together in the same gel, respectively, before their co-exposure to X-irradiation. Using the reference cell comets as internal standards led to substantial reductions in the coefficient of variation (CoV) for intra- and inter-experimental measures of comet formation and DNA damage repair; only minor reductions in CoV were noted when the reference and test cell comets were in separate gels. These studies indicate that differences between individual gels appreciably contribute to CA variation. Further studies using the reference cells as internal standards allowed greater significance to be obtained between groups of replicate samples. Ultimately, we anticipate that development will deliver robust quality assurance materials for CA. PMID:19828597

  18. Mechanisms of pH-Sensitivity and Cellular Internalization of PEOz-b-PLA Micelles with Varied Hydrophilic/Hydrophobic Ratios and Intracellular Trafficking Routes and Fate of the Copolymer.

    Science.gov (United States)

    Wang, Dishi; Zhou, Yanxia; Li, Xinru; Qu, Xiaoyou; Deng, Yunqiang; Wang, Ziqi; He, Chuyu; Zou, Yang; Jin, Yiguang; Liu, Yan

    2017-03-01

    pH-responsive polymeric micelles have shown promise for the targeted and intracellular delivery of antitumor agents. The present study aimed to elucidate the possible mechanisms of pH-sensitivity and cellular internalization of PEOz-b-PLA micelles in detail, further unravel the effect of hydrophilic/hydrophobic ratio of the micelles on their cellular internalization, and examine the intracellular trafficking routes and fate of PEOz-b-PLA after internalization of the micelles. The results of variations in the size and Zeta potential of PEOz-b-PLA micelles and cross-sectional area of PEOz-b-PLA molecules with pH values suggested that electrostatic repulsion between PEOz chains resulting from ionization of the tertiary amide groups along PEOz chain at pH lower than its pK a was responsible for pH-sensitivity of PEOz-b-PLA micelles. Furthermore, the studies on internalization of PEOz-b-PLA micelles by MCF-7 cells revealed that the uptake of PEOz-b-PLA micelles was strongly influenced by their structural features, and showed that PEOz-b-PLA micelles with hydrophilic/hydrophobic ratio of 1.7-2.0 exhibited optimal cellular uptake. No evident alteration in cellular uptake of PEOz-b-PLA micelles was detected by flow cytometry upon the existence of EIPA and chlorpromazine. However, the intracellular uptake of the micelles in the presence of MβCD and genistein was effectively inhibited. Hence, the internalization of such micelles by MCF-7 cells appeared to proceed mainly through caveolae/lipid raft-mediated endocytosis without being influenced by their hydrophilic/hydrophobic ratio. Confocal micrographs revealed that late endosomes, mitochondria and endoplasmic reticulum were all involved in the intracellular trafficking of PEOz-b-PLA copolymers following their internalization via endocytosis, and then part of them was excreted from tumor cells to extracellular medium. These findings provided valuable information for developing desired PEOz-b-PLA micelles to improve their

  19. Damage Control Resuscitation Supplemented with Vasopressin in a Severe Polytrauma Model with Traumatic Brain Injury and Uncontrolled Internal Hemorrhage.

    Science.gov (United States)

    Dickson, J Michael; Wang, Xu; St John, Alexander E; Lim, Esther B; Stern, Susan A; White, Nathan J

    2018-03-14

    Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of traumatic death worldwide and particularly on the battlefield. They are especially challenging when present simultaneously (polytrauma), and clear blood pressure end points during fluid resuscitation are not well described for this situation. The goal of this study is to evaluate for any benefit of increasing blood pressure using a vasopressor on brain blood flow during initial fluid resuscitation in a swine polytrauma model. We used a swine polytrauma model with simultaneous TBI, femur fracture, and HS with uncontrolled noncompressible internal bleeding from an aortic tear injury. Five animals were assigned to each of three experimental groups (hydroxyethyl starch only [HES], HES + 0.4 U/kg vasopressin, and no fluid resuscitation [No Fluids]). Fluids were given as two 10 mL/kg boluses according to tactical field care guidelines. Primary outcomes were mean arterial blood pressure (MAP) and brain blood flow at 60 min. Secondary outcomes were blood flows in the heart, intestine, and kidney; arterial blood lactate level; and survival at 6 hr. Organ blood flow was measured using injection of colored microspheres. Five animals were tested in each of the three groups. There was a statistically significant increase in MAP with vasopressin compared with other experimental groups, but no significant increase in brain blood flow during the first 60 min of resuscitation. The vasopressin group also exhibited greater total internal hemorrhage volume and rate. There was no difference in survival at 6 hours. In this experimental swine polytrauma model, increasing blood pressure with vasopressin did not improve brain perfusion, likely due to increased internal hemorrhage. Effective hemostasis should remain the top priority for field treatment of the polytrauma casualty with TBI.

  20. Assessing the damage importance rank in acoustic diagnostics of technical conditions of the internal combustion engine with multi-valued logical decision trees

    Directory of Open Access Journals (Sweden)

    Deptuła Adam

    2017-01-01

    Full Text Available This paper presents possible applications of acoustic diagnostics in inspecting the technical condition of an internal combustion engine with autoignition on the example of the Fiat drive unit with the common rail system. As a result of measuring the sound pressure level for specific faults and comparing the noise generated by the motor running smoothly, the detailed maps of changes in the acoustic spectrum may be generated. These results may be helpful in future diagnostics of internal combustion engines. In the paper, we present the results from the scientific works in the area of research, design and operation of internal combustion engines, conducted at the Department of Automotive Engineering, in cooperation with the Laboratory of Hydraulic Drives & Vibroacoustics of Machines at the Wroclaw University of Technology. The broader study has so far allowed us to develop an authoritative method of identifying the type of engine damage using gametree structures. The present works assess the possibility of using multi-valued logic trees.

  1. Health effects of radiation damage

    International Nuclear Information System (INIS)

    Gasimova, K; Azizova, F; Mehdieva, K.

    2012-01-01

    Full text : A summary of the nature of radiactive contamination would be incomplete without some mention of the human health effects relatied to radioactivity and radioactive materials. Several excellent reviews at the variety of levels of detail have been written and should be consulted by the reader. Internal exposures of alpha and beta particles are important for ingested and inhaled radionuclides. Dosimetry models are used to estimate the dose from internally deposited radioactive particles. As mentioned above weighting parameters that take into account the radiation type, the biological half-life and the tissue or organ at risk are used to convert the physically absorbed dose in units of gray (or red) to the biologically significant committed equivalent dose and effective dose, measured in units of Sv (or rem). There is considerable controversy over the shape of the dose-response curve at the chronic low dose levels important for enviromental contamination. Proposed models include linear models, non-linear models and threshold models. Because risks at low dose must be extrapolated from available date at high doses, the shape of the dose-response curve has important implications for the environmental regulations used to protect the general public. The health effect of radiation damage depends on a combination of events of on the cellular, tissue and systemic levels. These lead to mutations and cellular of the irradiated parent cell. The dose level at which significant damage occurs depends on the cell type. Cells that reproduce rapidily, such as those found in bone marrow or the gastrointestinal tract, will be more sensitive to radiation than those that are longer lived, such as striated muscle or nerve cells. The effects of high radiation doses on an organ depends on the various cell types it contains

  2. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal floods during mid-loop operations. Volume 4

    International Nuclear Information System (INIS)

    Kohut, P.

    1994-07-01

    The major objective of the Surry internal flood analysis was to provide an improved understanding of the core damage scenarios arising from internal flood-related events. The mean core damage frequency of the Surry plant due to internal flood events during mid-loop operations is 4.8E-06 per year, and the 5th and 95th percentiles are 2.2E-07 and 1.8E-05 per year, respectively. Some limited sensitivity calculations were performed on three plant improvement options. The most significant result involves modifications of intake-level structure on the canal, which reduced core damage frequency contribution from floods in mid-loop by about 75%

  3. Assessment of radiofrequency exposure from cellular telephone daily use in an epidemiological study: German Validation study of the international case-control study of cancers of the brain--INTERPHONE-Study.

    Science.gov (United States)

    Berg, Gabriele; Schüz, Joachim; Samkange-Zeeb, Florence; Blettner, Maria

    2005-05-01

    The objective of the study is to validate self-reported cellular phone use information by comparing it with the cumulative emitted power and duration of calls measured by software-modified cellular phones (SMP). The information was obtained using a questionnaire developed for the international case-control study on the risk of the use of mobile phones in tumours of the brain or salivary gland (INTERPHONE-study). The study was conducted in Bielefeld, Germany. Volunteers were asked to use SMPs instead of their own cellular phones for a period of 1 month. The SMP recorded the power emitted by the mobile phone handset during each base station contact. Information on cellular phone use for the same time period from traffic records of the network providers and from face-to-face interviews with the participants 3 months after the SMP use was assessed. Pearson's correlation coefficients and linear regression models were used to analyse the association between information from the interview and from the SMP. In total, 1757 personal mobile phone calls were recorded for 45 persons by SMP and traffic records. The correlation between the self-reported information about the number and the duration of calls with the cumulative power of calls was 0.50 (P<0.01) and 0.48 (P<0.01), respectively. Almost 23% of the variance of the cumulative power was explained by either the number or the cumulative duration of calls. After inclusion of possible confounding factors in the regression model, the variance increased to 26%. Minor confounding factors were "network provider", "contract form", and "cellular phone model". The number of calls alone is a sufficient parameter to estimate the cumulative power emitted by the handset of a cellular telephone. The cumulative power emitted by these phones is only associated with number of calls but not with possible confounding factors. Using the mobile phone while driving, mainly in cities, or mainly in rural areas is not associated with the recorded

  4. Stiffness-dependent cellular internalization of matrix-bound BMP-2 and its relation to Smad and non-Smad signaling.

    Science.gov (United States)

    Gilde, Flora; Fourel, Laure; Guillot, Raphael; Pignot-Paintrand, Isabelle; Okada, Takaharu; Fitzpatrick, Vincent; Boudou, Thomas; Albiges-Rizo, Corinne; Picart, Catherine

    2016-12-01

    Surface coatings delivering BMP are a promising approach to render biomaterials osteoinductive. In contrast to soluble BMPs which can interact with their receptors at the dorsal side of the cell, BMPs presented as an insoluble cue physically bound to a biomimetic matrix, called here matrix-bound (bBMP-2), are presented to cells by their ventral side. To date, BMP-2 internalization and signaling studies in cell biology have always been performed by adding soluble (sBMP-2) to cells adhered on cell culture plates or glass slides, which will be considered here as a "reference" condition. However, whether and how matrix-bound BMP-2 can be internalized by cells and its relation to canonical (SMAD) and non-canonical signaling (ALP) remain open questions. In this study, we investigated the uptake and processing of BMP-2 by C2C12 myoblasts. This BMP-2 was presented either embedded in polyelectrolyte multilayer films (matrix-bound presentation) or as soluble form. Using fluorescently labeled BMP-2, we showed that the amount of matrix-bound BMP-2 internalized is dependent on the level of crosslinking of the polyelectrolyte films. Cav-1-mediated internalization is related to both SMAD and ALP signaling, while clathrin-mediated is only related to ALP signaling. BMP-2 internalization was independent of the presentation mode (sBMP-2 versus bBMP-2) for low crosslinked films (soft, EDC10) in striking contrast with high crosslinked (stiff, EDC70) films where internalization was much lower and slower for bBMP-2. As anticipated, internalization of sBMP-2 barely depended on the underlying matrix. Taken together, these results indicate that BMP-2 internalization can be tuned by the underlying matrix and activates downstream BMP-2 signaling, which is key for the effective formation of bone tissue. The presentation of growth factors from material surfaces currently presents significant challenges in academic research, clinics and industry. Being able to deliver efficiently these growth

  5. Analysis of core damage frequency from internal events: Expert judgment elicitation. Part 1: Expert panel results. Part 2: Project staff results

    Energy Technology Data Exchange (ETDEWEB)

    Wheeler, T A; Cramond, W R [Sandia National Laboratories, Albuquerque, NM (United States); Hora, S C [University of Hawii at Hilo (United States); Unwin, S D [Brookhaven National Laboratory (United States)

    1989-04-01

    Quantitative modeling techniques have limitations as to the resolution of important issues in probabilistic risk assessment (PRA). Not all issues can be resolved via the existing set of methods such as fault trees, event trees, statistical analyses, data collection, and computer simulation. Therefore, an expert judgment process was developed to address issues perceived as important to risk in the NUREG-1150 analysis but which could not be resolved with existing techniques. This process was applied to several issues that could significantly affect the internal event core damage frequencies of the PRAs performed on six light water reactors. Detailed descriptions of these issues and the results of the expert judgment elicitation are reported here, as well as an explanation of the methodology used and the procedure followed in performing the overall elicitation task. The process is time-consuming and expensive. However, the results are very useful, and represent an improvement over the draft NUREG-1150 analysis in the areas of expert selection, elicitation training, issue selection and presentation, elicitation of judgment and aggregation of results. The results are presented in two parts. Part documents the expert panel elicitations, where the most important issues were presented to a panel of experts convened from throughout the nuclear power risk assessment community. Part 2 documents the process by which the project staff performed expert judgment on other important issues, using the project staff as panel members. (author)

  6. Redox Role of Lactobacillus casei Shirota Against the Cellular Damage Induced by 2,2′-Azobis (2-Amidinopropane Dihydrochloride-Induced Oxidative and Inflammatory Stress in Enterocytes-Like Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Alberto Finamore

    2018-05-01

    Full Text Available In western societies where most of the day is spent in the postprandial state, the existence of oxidative and inflammatory stress conditions makes postprandial stress an important factor involved in the development of cardiovascular risk factors. A large body of evidence have been accumulated on the anti-inflammatory effects of probiotics, but no information is available on the mechanisms through which intestinal microbiota modulates redox unbalance associated with inflammatory stress. Here, we aimed to investigate the ability of Lactobacillus casei Shirota (LS to induce an antioxidant response to counteract oxidative and inflammatory stress in an in vitro model of enterocytes. Our results show that pretreatment of enterocytes with LS prevents membrane barrier disruption and cellular reactive oxygen species (ROS accumulation inside the cells, modulates the expression of the gastro-intestinal glutathione peroxidase (GPX2 antioxidant enzyme, and reduces p65 phosphorylation, supporting the involvement of the Nfr2 and nuclear factor kappa B pathways in the activation of antioxidant cellular defenses by probiotics. These results suggest, for the first time, a redox mechanism by LS in protecting intestinal cells from AAPH-induced oxidative and inflammatory stress.

  7. Evaluation of potential severe accidents during low power and shutdown operations at Grand Gulf, Unit 1: Analysis of core damage frequency from internally induced flooding events for Plant Operational State 5 during a refueling outage. Volume 4

    International Nuclear Information System (INIS)

    Dandini, V.; Staple, B.; Kirk, H.; Whitehead, D.; Forester, J.

    1994-07-01

    An estimate of the contribution of internal flooding to the mean core damage frequency at the Grand Gulf Nuclear Station was calculated for Plant Operational State 5 during a refueling outage. Pursuant to this objective, flood zones and sources were identified and flood volumes were calculated. Equipment necessary for the maintenance of plant safety was identified and its vulnerability to flooding was determined. Event trees and fault trees were modified or developed as required, and PRA quantification was performed using the IRRAS code. The mean core damage frequency estimate for GGNS during POS 5 was found to be 2.3 E-8 per year

  8. Damaged Skylab

    Science.gov (United States)

    1973-01-01

    The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows a crippled Skylab in orbit. The crew found their home in space to be in serious shape; the heat shield gone, one solar wing gone, and the other jammed. The Marshall Space Flight Center (MSFC) developed, tested, rehearsed, and approved three repair options. These options included a parasol sunshade and a twin-pole sunshade to restore the temperature inside the workshop, and a set of metal cutting tools to free the jammed solar panel.

  9. Relationship between health-related quality of life, disease activity and disease damage in a prospective international multicenter cohort of childhood onset systemic lupus erythematosus patients

    DEFF Research Database (Denmark)

    Moorthy, L N; Baldino, M E; Kurra, V

    2017-01-01

    disease activity and damage. The multinational cohort ( n = 467) had relatively low disease activity and damage. Patient and parent HRQOL scores were significantly correlated. Asian and European patients had the highest HRQOL, while South and North American patients had lower HRQOL scores. Renal, CNS...

  10. Arabidopsis thaliana Yellow Stripe1-Like4 and Yellow Stripe1-Like6 localize to internal cellular membranes and are involved in metal ion homeostasis.

    Directory of Open Access Journals (Sweden)

    Heng-Hsuan eChu

    2013-07-01

    Full Text Available Several members of the Yellow Stripe1-Like (YSL family of transporter proteins are able to transport metal-nicotianamine (NA complexes. Substantial progress has been made in understanding the roles of the Arabidopsis YSLs that are most closely related to the founding member of the family, ZmYS1 (e.g., AtYSL1, AtYSL2 and AtYSL3, but there is little information concerning members of the other two well-conserved YSL clades. Here, we provide evidence that AtYSL4 and AtYSL6, which are the only genes in Arabidopsis belong to YSL Group II, are localized to vacuole membranes and to internal membranes resembling endoplasmic reticulum. Both single and double mutants for YSL4 and YSL6 were rigorously analyzed, and have surprisingly mild phenotypes, in spite of the strong and wide-ranging expression of YSL6. However, in the presence of toxic levels of Mn and Ni, plants with mutations in YSL4 and YSL6 and plants overexpressing GFP-tagged YSL6 showed growth defects, indicating a role for these transporters in heavy metal stress responses.

  11. International

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    This rubric reports on 10 short notes about international economical facts about nuclear power: Electricite de France (EdF) and its assistance and management contracts with Eastern Europe countries (Poland, Hungary, Bulgaria); Transnuclear Inc. company (a 100% Cogema daughter company) acquired the US Vectra Technologies company; the construction of the Khumo nuclear power plant in Northern Korea plays in favour of the reconciliation between Northern and Southern Korea; the delivery of two VVER 1000 Russian reactors to China; the enforcement of the cooperation agreement between Euratom and Argentina; Japan requested for the financing of a Russian fast breeder reactor; Russia has planned to sell a floating barge-type nuclear power plant to Indonesia; the control of the Swedish reactor vessels of Sydkraft AB company committed to Tractebel (Belgium); the renewal of the nuclear cooperation agreement between Swiss and USA; the call for bids from the Turkish TEAS electric power company for the building of the Akkuyu nuclear power plant answered by three candidates: Atomic Energy of Canada Limited (AECL), Westinghouse (US) and the French-German NPI company. (J.S.)

  12. KIN17, XPC, DNA-PKCS and XRCC4 proteins in the cellular response to DNA damages. Relations between nucleotide excision repair and non-homologous end joining in a human syn-genic model

    International Nuclear Information System (INIS)

    Despras, Emmanuelle

    2006-01-01

    The response to genotoxic stress involves many cellular factors in a complex network of mechanisms that aim to preserve the genetic integrity of the organism. These mechanisms enclose the detection and repair of DNA lesions, the regulation of transcription and replication and, eventually, the setting of cell death. Among the nuclear proteins involved in this response, kin17 proteins are zinc-finger proteins conserved through evolution and activated by ultraviolet (UV) or ionizing radiations (IR). We showed that human kin17 protein (HSAkin17) is found in the cell under a soluble form and a form tightly anchored to nuclear structures. A fraction of HSAkin17 protein is directly associated with chromatin. HSAkin17 protein is recruited to nuclear structures 24 hours after treatment with various agents inducing DNA double-strand breaks (DSB) and/or replication forks blockage. Moreover, the reduction of total HSAkin17 protein level sensitizes RKO cells to IR. We also present evidence for the involvement of HSAkin17 protein in DNA replication. This hypothesis was further confirmed by the biochemical demonstration of its belonging to the replication complex. HSAkin17 protein could link DNA replication and DNA repair, a defect in the HSAkin17 pathway leading to an increased radiosensitivity. In a second part, we studied the interactions between two DNA repair mechanisms: nucleotide excision repair (NER) and non-homologous end joining (NHEJ). NER repairs a wide variety of lesions inducing a distortion of the DNA double helix including UV-induced pyrimidine dimers. NHEJ allows the repair of DSB by direct joining of DNA ends. We used a syn-genic model for DNA repair defects based on RNA interference developed in the laboratory. Epstein-Barr virus-derived vectors (pEBV) allow long-term expression of siRNA and specific extinction of the targeted gene. The reduction of the expression of genes involved in NER (XPA and XPC) or NHEJ (DNA-PKcs and XRCC4) leads to the expected

  13. Estimated airborne release of plutonium from Atomics International's Nuclear Materials Development Facility in the Santa Susana site, California, as a result of postulated damage from severe wind and earthquake hazard

    International Nuclear Information System (INIS)

    Mishima, J.; Ayer, J.E.

    1981-09-01

    The potential mass of airborne releases of plutonium (source term) that could result from wind and seismic damage is estimated for the Atomics International Company's Nuclear Materials Development Facility (NMDF) at the Santa Susana site in California. The postulated source terms will be useful as the basis for estimating the potential dose to the maximum exposed individual by inhalation and to the total population living within a prescribed radius of the site. The respirable fraction of airborne particles is thus the principal concern. The estimated source terms are based on the damage ratio, and the potential airborne releases if all enclosures suffer particular levels of damage. In an attempt to provide a realistic range of potential source terms that include most of the normal processing conditions, a best estimate bounded by upper and lower limits is provided. The range of source terms is calculated by combining a high best estimate and a low damage ratio, based on a fraction of enclosures suffering crush or perforation, with the airborne release from enclosures based upon an upper limit, average, and lower limit inventory of dispersible materials at risk. Two throughput levels are considered. The factors used to evaluate the fractional airborne release of materials and the exchange rates between enclosed and exterior atmospheres are discussed. The postulated damage and source terms are discussed for wind and earthquake hazard scenarios in order of their increasing severity

  14. Harmonization of the Romanian legislation in the field of civil liability for nuclear damages with the international legislation in the field

    International Nuclear Information System (INIS)

    Chiripus, Vlad

    2005-01-01

    The paper is an overview of the Romanian legal provisions in the filed of civil liability for nuclear damages in the last three decades introducing the concept and the evolution of its legal regime towards a total harmonization with the European legislation. Its modernity even from (and in spite of) its communist beginnings in 1947 (Law no. 61 regarding the deployment of nuclear activities in the Romanian Socialist Republic) is emphasized. It focuses on the key laws - Law no. 703/2001 on civil liability for nuclear damages, and Government Decision no. 894/2003 for the approval of the Norms for enforcement of Law no. 703/2001- that currently define the Romanian regime for civil liability for nuclear damages. This encompasses the relevant responsibilities of nuclear operators, the Romanian nuclear damage compensation system, statute of limitation for claims, types of insurance and financial guarantees. These refer civil liability for nuclear damages, limits of nuclear operators' liability, specific requirements regarding the insurance, responsibilities of control and supervision bodies, assessment of nuclear damage. This makes Romania - in terms of legislation - one of the most advanced countries in the field. (author)

  15. Acetylation dynamics of human nuclear proteins during the ionizing radiation-induced DNA damage response

    DEFF Research Database (Denmark)

    Bennetzen, Martin; Andersen, J.S.; Lasen, D.H.

    2013-01-01

    Genotoxic insults, such as ionizing radiation (IR), cause DNA damage that evokes a multifaceted cellular DNA damage response (DDR). DNA damage signaling events that control protein activity, subcellular localization, DNA binding, protein-protein interactions, etc. rely heavily on time...

  16. The cellular basis of skin injury after cytotoxic insult

    International Nuclear Information System (INIS)

    Potten, C.S.

    1986-01-01

    It is concluded that although the major target in terms of radiation damage is undoubtedly the epidermis, the skin is a complex tissue made up of many inter-dependent components each of which may constitute an important secondary target. Damage to each component has been considered at the cellular level. The precise inter-relationships and interdependencies remain somewhat obscure. Even within one site, the epidermis, a comprehensive cellular explanation of the various post-irradiation changes is difficult. Substantial bibliography. (UK)

  17. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT).

    Science.gov (United States)

    Bourin, Philippe; Bunnell, Bruce A; Casteilla, Louis; Dominici, Massimo; Katz, Adam J; March, Keith L; Redl, Heinz; Rubin, J Peter; Yoshimura, Kotaro; Gimble, Jeffrey M

    2013-06-01

    Adipose tissue is a rich and very convenient source of cells for regenerative medicine therapeutic approaches. However, a characterization of the population of adipose-derived stromal and stem cells (ASCs) with the greatest therapeutic potential remains unclear. Under the authority of International Federation of Adipose Therapeutics and International Society for Cellular Therapy, this paper sets out to establish minimal definitions of stromal cells both as uncultured stromal vascular fraction (SVF) and as an adherent stromal/stem cells population. Phenotypic and functional criteria for the identification of adipose-derived cells were drawn from the literature. In the SVF, cells are identified phenotypically by the following markers: CD45-CD235a-CD31-CD34+. Added value may be provided by both a viability marker and the following surface antigens: CD13, CD73, CD90 and CD105. The fibroblastoid colony-forming unit assay permits the evaluation of progenitor frequency in the SVF population. In culture, ASCs retain markers in common with other mesenchymal stromal/stem cells (MSCs), including CD90, CD73, CD105, and CD44 and remain negative for CD45 and CD31. They can be distinguished from bone-marrow-derived MSCs by their positivity for CD36 and negativity for CD106. The CFU-F assay is recommended to calculate population doublings capacity of ASCs. The adipocytic, chondroblastic and osteoblastic differentiation assays serve to complete the cell identification and potency assessment in conjunction with a quantitative evaluation of the differentiation either biochemically or by reverse transcription polymerase chain reaction. The goal of this paper is to provide initial guidance for the scientific community working with adipose-derived cells and to facilitate development of international standards based on reproducible parameters. Copyright © 2013 International Society for Cellular Therapy. All rights reserved.

  18. Wireless Cellular Mobile Communications

    OpenAIRE

    Zalud, V.

    2002-01-01

    In this article is briefly reviewed the history of wireless cellular mobile communications, examined the progress in current second generation (2G) cellular standards and discussed their migration to the third generation (3G). The European 2G cellular standard GSM and its evolution phases GPRS and EDGE are described somewhat in detail. The third generation standard UMTS taking up on GSM/GPRS core network and equipped with a new advanced access network on the basis of code division multiple ac...

  19. Biomechanics of cellular solids.

    Science.gov (United States)

    Gibson, Lorna J

    2005-03-01

    Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

  20. New concept of damage evaluation method for core internal materials considering radiation induced stress relaxation (1). Experiments and modeling of radiation effects

    International Nuclear Information System (INIS)

    Miwa, Yukio; Kondo, Keietsu; Okubo, Nariaki; Kaji, Yoshiyuki; Tsukada, Takashi

    2009-01-01

    In order to build the new concept of material damage evaluation method, synergistic effect of radiation and residual stress on material degradation was estimated experimentally, and the effect of radiation induced stress relaxation on retardation of material degradation was observed. (author)

  1. Hydrogen damage in stainless steel

    International Nuclear Information System (INIS)

    Caskey, G.R. Jr.

    1981-01-01

    Hydrogen damage has been studied in a wide variety of stainless steels. Both internal and external hydrogen damage were evaluated by ductility or J-integral under rising tensile loads and by fractography. Analysis of the data has emphasized the potential effects of strain-induced martensite on hydrogen damage. Strain-induced martensite was neither necessary nor sufficient for hydrogen damage in the alloys studied. Neither ductility loss nor fracture-mode change correlated generally with martensite formation. Alloy composition, particularly nickel and nitrogen contents, was the primary factor in resistance to hydrogen damage. Thermomechanical processing, however, could alter the degree of hydrogen damage in an alloy and was critical for optimizing resistance to hydrogen damage. 10 figures, 10 tables

  2. Fractal dimension at the phase transition of inhomogeneous cellular automata

    International Nuclear Information System (INIS)

    da Silva, L.R.

    1988-01-01

    For random binary mixtures of cellular automata in the square lattice, calculations are made of the fractal dimensions associated with the damage spreading and the propagation time of damage at the transition to chaos. Two rules are mixed and universalities of these quantities are sought with respect to change of the rules

  3. Effective photo-enhancement of cellular activity of fluorophore-octaarginine antisense PNA conjugates correlates with singlet oxygen formation, endosomal escape and chromophore lipophilicity

    DEFF Research Database (Denmark)

    Yarani, Reza; Shiraishi, Takehiko; Nielsen, Peter E.

    2018-01-01

    Photochemical internalization (PCI) is a cellular drug delivery method based on the generation of light-induced reactive oxygen species (ROS) causing damage to the endosomal membrane and thereby resulting in drug release to the cytoplasm. In our study a series of antisense fluorophore octaarginin...... indicate that efficient photodynamic endosomal escape is strongly dependent on the quantum yield for photochemical singlet oxygen formation, photostability as well as the lipophilicity of the chromophore....

  4. Evaluation of potential severe accidents during low power and shutdown operations at Grand Gulf, Unit 1: Analysis of core damage frequency from internal fire events for Plant Operational State 5 during a refueling outage. Volume 3

    International Nuclear Information System (INIS)

    Lambright, J.; Yakle, J.

    1994-07-01

    This report, Volume 3, presents the details of the analysis of core damage frequency due to fire during shutdown Plant Operational State 5 at the Grand Gulf Nuclear Station. Insights from previous fire analyses (Peach Bottom, Surry, LaSalle) were used to the greatest extent possible in this analysis. The fire analysis was fully integrated utilizing the same event trees and fault trees that were used in the internal events analysis. In assessing shutdown risk due to fire at Grand Gulf, a detailed screening was performed which included the following elements: (a) Computer-aided vital area analysis; (b) Plant inspections; (c) Credit for automatic fire protection systems; (d) Recovery of random failures; (e) Detailed fire propagation modeling. This screening process revealed that all plant areas had a negligible (<1.0E-8 per year) contribution to fire-induced core damage frequency

  5. Linearizable cellular automata

    International Nuclear Information System (INIS)

    Nobe, Atsushi; Yura, Fumitaka

    2007-01-01

    The initial value problem for a class of reversible elementary cellular automata with periodic boundaries is reduced to an initial-boundary value problem for a class of linear systems on a finite commutative ring Z 2 . Moreover, a family of such linearizable cellular automata is given

  6. Radiation damage

    CERN Document Server

    Heijne, Erik H M; CERN. Geneva

    1998-01-01

    a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

  7. Enumerating bone marrow blasts from nonerythroid cellularity improves outcome prediction in myelodysplastic syndromes and permits a better definition of the intermediate risk category of the Revised International Prognostic Scoring System (IPSS-R).

    Science.gov (United States)

    Calvo, Xavier; Arenillas, Leonor; Luño, Elisa; Senent, Leonor; Arnan, Montserrat; Ramos, Fernando; Pedro, Carme; Tormo, Mar; Montoro, Julia; Díez-Campelo, María; Blanco, María Laura; Arrizabalaga, Beatriz; Xicoy, Blanca; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Meritxell; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes

    2017-07-01

    The Revised International Prognostic Scoring System (IPSS-R) has been recognized as the score with the best outcome prediction capability in MDS, but this brought new concerns about the accurate prognostication of patients classified into the intermediate risk category. The correct enumeration of blasts is essential in prognostication of MDS. Recent data evidenced that considering blasts from nonerythroid cellularity (NECs) improves outcome prediction in the context of IPSS and WHO classification. We assessed the percentage of blasts from total nucleated cells (TNCs) and NECs in 3924 MDS patients from the GESMD, 498 of whom were MDS with erythroid predominance (MDS-E). We assessed if calculating IPSS-R by enumerating blasts from NECs improves prognostication of MDS. Twenty-four percent of patients classified into the intermediate category were reclassified into higher-risk categories and showed shorter overall survival (OS) and time to AML evolution than those who remained into the intermediate one. Likewise, a better distribution of patients was observed, since lower-risk patients showed longer survivals than previously whereas higher-risk ones maintained the outcome expected in this poor prognostic group (median OS < 20 months). Furthermore, our approach was particularly useful for detecting patients at risk of dying with AML. Regarding MDS-E, 51% patients classified into the intermediate category were reclassified into higher-risk ones and showed shorter OS and time to AML. In this subgroup of MDS, IPSS-R was capable of splitting our series in five groups with significant differences in OS only when blasts were assessed from NECs. In conclusion, our easy-applicable approach improves prognostic assessment of MDS patients. © 2017 Wiley Periodicals, Inc.

  8. Measurements of Electromagnetic Fields Emitted from Cellular Base Stations in

    Directory of Open Access Journals (Sweden)

    K. J. Ali

    2013-05-01

    Full Text Available With increasing the usage of mobile communication devices and internet network information, the entry of private telecommunications companies in Iraq has been started since 2003. These companies began to build up cellular towers to accomplish the telecommunication works but they ignore the safety conditions imposed for the health and environment that are considered in random way. These negative health effects which may cause a health risk for life beings and environment pollution. The aim of this work is to determine the safe and unsafe ranges and discuss damage caused by radiation emitted from Asia cell base stations in Shirqat city and discuses the best ways in which can be minimize its exposure level to avoid its negative health effects. Practical measurements of power density around base stations has been accomplished by using a radiation survey meter type (Radio frequency EMF Strength Meter 480846 in two ways. The first way of measurements has been accomplished at a height of 2 meters above ground for different distances from (0-300 meters .The second way is at a distance of 150 meters for different levels from (2-15 meters above ground level. The maximum measured power density is about (3 mW/m2. Results indicate that the levels of power density are far below the RF radiation exposure of USSR safety standards levels. And that means these cellular base station don't cause negative the health effect for life being if the exposure is within the acceptable international standard levels.

  9. Heterogeneous cellular networks

    CERN Document Server

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  10. Cellular decomposition in vikalloys

    International Nuclear Information System (INIS)

    Belyatskaya, I.S.; Vintajkin, E.Z.; Georgieva, I.Ya.; Golikov, V.A.; Udovenko, V.A.

    1981-01-01

    Austenite decomposition in Fe-Co-V and Fe-Co-V-Ni alloys at 475-600 deg C is investigated. The cellular decomposition in ternary alloys results in the formation of bcc (ordered) and fcc structures, and in quaternary alloys - bcc (ordered) and 12R structures. The cellular 12R structure results from the emergence of stacking faults in the fcc lattice with irregular spacing in four layers. The cellular decomposition results in a high-dispersion structure and magnetic properties approaching the level of well-known vikalloys [ru

  11. Cellular Reflectarray Antenna

    Science.gov (United States)

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  12. Cellular radiobiology of heavy-ion beams

    International Nuclear Information System (INIS)

    Tobias, C.A.; Blakely, E.A.; Ngo, F.Q.H.; Roots, R.J.; Yang, T.C.

    1981-01-01

    Progress is reported in the following areas of this research program: relative biological effectiveness and oxygen enhancement ratio of silicon ion beams; heavy ion effects on the cell cycle; the potentiation effect (2 doses of high LET heavy-ion radiations separated by 2 to 3 hours); potentially lethal damage in actively growing cells and plateau growth cells; radiation induced macromolecular lesions and cellular radiation chemistry; lethal effects of dual radiation; and the development of a biophysical repair/misrepair model

  13. Tort Damages

    NARCIS (Netherlands)

    L.T. Visscher (Louis)

    2008-01-01

    textabstractAbstract: In this Chapter, I provide an overview of Law and Economics literature regarding tort damages. Where necessary, attention is also spent to rules of tort liability. Both types of rules provide behavioral incentives to both injurers and victims, with respect to their level of

  14. Radiation damage to DNA: the effect of LET

    Energy Technology Data Exchange (ETDEWEB)

    Ward, J F; Milligan, J R [California Univ., San Diego, La Jolla, CA (United States). School of Medicine

    1997-03-01

    Mechanisms whereby ionizing radiation induced damage are introduced into cellular DNA are discussed. The types of lesions induced are summarized and the rationale is presented which supports the statement that radiation induced singly damaged sites are biologically unimportant. The conclusion that multiply damaged sites are critical is discussed and the mechanisms whereby such lesions are formed are presented. Structures of multiply damaged sites are summarized and problems which they present to cellular repair systems are discussed. Lastly the effects of linear energy transfer on the complexity of multiply damaged sites are surveyed and the consequences of this increased complexity are considered in terms of cell survival and mutation. (author)

  15. VUV spectroscopy of water under cellular conditions

    International Nuclear Information System (INIS)

    Mota, R.; Parafita, R.; Maneira, M. J. P.; Mason, N. J.; Garcia, G.; Ribeiro, P. A.; Raposo, M.; Limao-Vieira, P.

    2006-01-01

    The understanding of radiation damage within cells, and thence mutagenesis, depends upon a detailed knowledge of the spectroscopy and dissociation dynamics of water. Results of a new study of the electronic state spectroscopy of water, using synchrotron radiation are reported. In order to gain some insight into how the spectroscopy and dissociation dynamics of water is influenced by its environment we also report photo-absorption spectra of water within thin films of poly(o-methoxyaniline) which have been suggested as a good mimic for biological membranes in the cellular environment. Comparison of these spectra with those of gaseous water and condensed amorphous water ice suggest that water in such films is similar to gaseous water and does not show the blue shift suggested in some cellular models. The lowest energy of OH production from dissociation of water in the cellular environment may therefore be around 6.7 eV (185 nm). (authors)

  16. Evidence for highly localized damage in internal tin and powder-in-tube Nb{sub 3}Sn strands rolled before reaction obtained from coupled magneto-optical imaging and confocal laser scanning microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Polyanskii, A A; Lee, P J; Jewell, M C; Larbalestier, D C [Applied Superconductivity Center, National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32310 (United States); Barzi, E; Turrioni, D; Zlobin, A V [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States)

    2009-09-15

    Nb{sub 3}Sn strands for high-current, high-field magnets must be cabled before reaction while the conductor is still composed of ductile components. Even though still in the ductile, deformable state, significant damage can occur in this step, which expresses itself by inhomogeneous A15 formation, Sn leakage or even worse effects during later reaction. In this study, we simulate cabling damage by rolling recent high performance powder-in-tube (PIT) and internal tin (IT) strands in controlled increments, applying standard Nb{sub 3}Sn reaction heat treatments, and then examining the local changes using magneto-optical imaging (MOI), scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). These combined characterizations allow any local damage to the filament architecture to be made clear. MOI directly reveals the local variation of superconductivity while CLSM is extremely sensitive in revealing Sn leakage beyond the diffusion barrier into the stabilizing Cu. These techniques reveal a markedly different response to deformation by the PIT and IT strands. The study demonstrates that these tools can provide a local, thorough, and detailed view of how strands degrade and thus complement more complex extracted strand studies.

  17. Magnetohydrodynamics cellular automata

    International Nuclear Information System (INIS)

    Hatori, Tadatsugu.

    1990-02-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

  18. Epigenetics and Cellular Metabolism

    OpenAIRE

    Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

  19. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  20. Magnetohydrodynamic cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Hatori, Tadatsugu [National Inst. for Fusion Science, Nagoya (Japan)

    1990-03-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author).

  1. Magnetohydrodynamic cellular automata

    International Nuclear Information System (INIS)

    Hatori, Tadatsugu

    1990-01-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

  2. Cellular MR Imaging

    Directory of Open Access Journals (Sweden)

    Michel Modo

    2005-07-01

    Full Text Available Cellular MR imaging is a young field that aims to visualize targeted cells in living organisms. In order to provide a different signal intensity of the targeted cell, they are either labeled with MR contrast agents in vivo or prelabeled in vitro. Either (ultrasmall superparamagnetic iron oxide [(USPIO] particles or (polymeric paramagnetic chelates can be used for this purpose. For in vivo cellular labeling, Gd3+- and Mn2+- chelates have mainly been used for targeted hepatobiliary imaging, and (USPIO-based cellular imaging has been focused on imaging of macrophage activity. Several of these magneto-pharmaceuticals have been FDA-approved or are in late-phase clinical trials. As for prelabeling of cells in vitro, a challenge has been to induce a sufficient uptake of contrast agents into nonphagocytic cells, without affecting normal cellular function. It appears that this issue has now largely been resolved, leading to an active research on monitoring the cellular biodistribution in vivo following transplantation or transfusion of these cells, including cell migration and trafficking. New applications of cellular MR imaging will be directed, for instance, towards our understanding of hematopoietic (immune cell trafficking and of novel guided (stem cell-based therapies aimed to be translated to the clinic in the future.

  3. Cellular proliferation and regeneration following tissue damage. Progress report

    International Nuclear Information System (INIS)

    Harding, C.V.

    1977-01-01

    Studies were conducted on the following research projects: effects of x radiation on rabbit lenses; DNA synthesis and mitosis in cultured lenses; serum dependency and actinomycin D sensitivity; changes in ultrastructure; injury-induced growth of vascular endothelium; corneal neovascularization following injury; and human cataractous lenses

  4. Cellular proliferation and regeneration following tissue damage. Progress report. [Eyes

    Energy Technology Data Exchange (ETDEWEB)

    Harding, C.V.

    1976-10-01

    Results are reported from a study of wound healing in tissues of the eye, particularly lens, cornea, and surrounding tissues. The reactions of these tissues to mechanical injuries, as well as injuries induced by chemotoxic agents were studied. It is postulated that a better understanding of the basic reactions of the eye to injurious agents may be of importance in the evaluation of potential environmental hazards.

  5. Microsomal lipid peroxidation as a mechanism of cellular damage. [Dissertation

    Energy Technology Data Exchange (ETDEWEB)

    Kornbrust, D.J.

    1979-01-01

    The NADPH/iron-dependent peroxidation of lipids in rat liver microsomes was found to be dependent on the presence of free ferrous ion and maintains iron in the reduced Fe/sup 2 +/ state. Chelation of iron by EDTA inhibited peroxidation. Addition of iron, after preincubation of microsomes in the absence of iron, did not enhance the rate of peroxidation suggesting that iron acts by initiating peroxidative decomposition of membrane lipids rather than by catalyzing the breakdown of pre-formed hydroperoxides. Liposomes also underwent peroxidation in the presence of ferrous iron at a rate comparable to intact microsomes and was stimulated by ascorbate. Carbon tetrachloride initiated lipid peroxidation in the absence of free metal ions. Rates of in vitro lipid peroxidation of microsomes and homogenates were found to vary widely between different tissues and species. The effects of paraquat on lipid peroxidation was also studied. (DC)

  6. RecQ helicases and cellular responses to DNA damage

    International Nuclear Information System (INIS)

    Wu, Leonard; Hickson, Ian D.

    2002-01-01

    The faithful replication of the genome is essential for the survival of all organisms. It is not surprising therefore that numerous mechanisms have evolved to ensure that duplication of the genome occurs with only minimal risk of mutation induction. One mechanism of genome destabilization is replication fork demise, which can occur when a translocating fork meets a lesion or adduct in the template. Indeed, the collapse of replication forks has been suggested to occur in every replicative cell cycle making this a potentially significant problem for all proliferating cells. The RecQ helicases, which are essential for the maintenance of genome stability, are thought to function during DNA replication. In particular, RecQ helicase mutants display replication defects and have phenotypes consistent with an inability to efficiently reinitiate replication following replication fork demise. Here, we review some current models for how replication fork repair might be effected, and discuss potential roles for RecQ helicases in this process

  7. [Three-month rehabilitation of a patient with the III, IV and VI cranial nerve damage caused by a neurosurgery of the left internal carotid artery aneurysm].

    Science.gov (United States)

    Mosiński, Eliasz; Kikowski, Łukasz; Irzmański, Robert

    Introduction: Oculomotor nerve palsy is an eye condition resulting from damage to the third cranial nerve or a branch thereof. Third nerve damage weakens the muscles innervated by the nerve . Also adversely affect the fourth and sixth nerve , causing impairment of their activity. Rehabilitation third nerve palsy is rarely described in the available literature . The whole process is very difficult , but the effects of physiotherapy is very beneficial for the patient. The aim:The assessment of the influence of the outpatient rehabilitation on the patient's condition after a three-month treatment and the use of physical therapy. Material and methods:Case studies of the 38-yerar-old patient after having operated a big aneurism of the left ICA, which was clipped. After the procedure, the III, IV and VI cranial nerves were deeply impaired and the amnesic aphasia occurred. The patient started the rehabilitation a month after the incident. To assess the process of rehabilitation, the own movement examination of the eyeball was implemented. Active and passive exercises, Tigger Point therapy, kinesiotaping, laser and electrostimulation were inserted. Results: The significant improvement of the eyeball movement has been proved on the basis of the same own examination. A physiotherapy has had a positive influence on the speech disorder, namely amnesic aphasia, and after the month of the rehabilitation it has been completely removed. The positive influence of the rehabilitation, which has been pointed out, is clinically essential. Conclusions: Obtained results have not been described in literature yet, that is why it is essential to widen further research and emphasise the importance of the rehabilitation, which is rarely implemented in an intense way in such medical conditions.

  8. Delayed chromosomal instability induced by DNA damage

    International Nuclear Information System (INIS)

    Morgan, W.F.; Marder, B.A.; Day, J.P.

    1994-01-01

    Cellular exposure to DNA damaging agents rapidly results in a dose dependent increase in chromosomal breakage and gross structural chromosomal rearrangements. Over recent years, evidence has been accumulating indicating genomic instability can manifest multiple generations after cellular exposure to physical and chemical DNA damaging agents. Genomic instability manifests in the progeny of surviving cells, and has been implicated in mutation, gene application, cellular transformation, and cell killing. To investigate chromosome instability following DNA damage, we have used fluorescence in situ hybridization to detect chromosomal rearrangements in a human/hamster somatic hybrid cell line following exposure to ionizing radiation. Delayed chromosomal instability was detected when multiple populations of uniquely arranged metaphases were observed in clonal isolates raised from single cells surviving X-irradiation many generations after exposure. At higher radiation doses, chromosomal instability was observed in a relatively high frequency of surviving clones and, in general, those clones showed delayed chromosome instability also showed reduced survival as measured by colony forming ability

  9. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal events during mid-loop operations. Appendix E (Sections E.9-E.16), Volume 2, Part 3B

    Energy Technology Data Exchange (ETDEWEB)

    Chu, T.L.; Musicki, Z.; Kohut, P.; Yang, J.; Bozoki, G.; Hsu, C.J.; Diamond, D.J.; Wong, S.M. [Brookhaven National Lab., Upton, NY (United States); Bley, D.; Johnson, D. [PLG Inc., Newport Beach, CA (United States)] [and others

    1994-06-01

    Traditionally, probabilistic risk assessments (PRA) of severe accidents in nuclear power plants have considered initiating events potentially occurring only during full power operation. Some previous screening analyses that were performed for other modes of operation suggested that risks during those modes were small relative to full power operation. However, more recent studies and operational experience have implied that accidents during low power and shutdown could be significant contributors to risk. Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The scope of the program includes that of a level-3 PRA. In phase 2, mid-loop operation was selected as the plant configuration to be analyzed based on the results of the phase 1 study. The objective of the phase 2 study is to perform a detailed analysis of the potential accident scenarios that may occur during mid-loop operation, and compare the results with those of NUREG-1150. The scope of the level-1 study includes plant damage state analysis, and uncertainty analysis. Volume 1 summarizes the results of the study. Internal events analysis is documented in Volume 2. It also contains an appendix that documents the part of the phase 1 study that has to do with POSs other than mid-loop operation. Internal fire and internal flood analyses are documented in Volumes 3 and 4. A separate study on seismic analysis, documented in Volume 5, was performed for the NRC by Future Resources Associates, Inc. Volume 6 documents the accident progression, source terms, and consequence analysis.

  10. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit-1: Analysis of core damage frequency from internal events during mid-loop operations. Appendix I, Volume 2, Part 5

    Energy Technology Data Exchange (ETDEWEB)

    Chu, T.L.; Musicki, Z.; Kohut, P.; Yang, J.; Bozoki, G.; Hsu, C.J.; Diamond, D.J. [Brookhaven National Lab., Upton, NY (United States); Bley, D.; Johnson, D. [PLG Inc., Newport Beach, CA (United States); Holmes, B. [AEA Technology, Dorset (United Kingdom)] [and others

    1994-06-01

    Traditionally, probabilistic risk assessments (PRA) of severe accidents in nuclear power plants have considered initiating events potentially occurring only during full power operation. Some previous screening analyses that were performed for other modes of operation suggested that risks during those modes were small relative to full power operation. However, more recent studies and operational experience have implied that accidents during low power and shutdown could be significant contributors to risk. During 1989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the potential risks during low power and shutdown operations. The program includes two parallel projects being performed by Brookhaven National Lab. (BNL) and Sandia National Labs. (SNL). Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The objective of this volume of the report is to document the approach utilized in the level-1 internal events PRA for the Surry plant, and discuss the results obtained. A phased approach was used in the level-1 program. In phase 1, which was completed in Fall 1991, a coarse screening analysis examining accidents initiated by internal events (including internal fire and flood) was performed for all plant operational states (POSs). The objective of the phase 1 study was to identify potential vulnerable plant configurations, to characterize (on a high, medium, or low basis) the potential core damage accident scenarios, and to provide a foundation for a detailed phase 2 analysis.

  11. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit-1: Analysis of core damage frequency from internal events during mid-loop operations. Appendices F-H, Volume 2, Part 4

    International Nuclear Information System (INIS)

    Chu, T.L.; Musicki, Z.; Kohut, P.; Yang, J.; Bozoki, G.; Hsu, C.J.; Diamond, D.J.; Bley, D.; Johnson, D.; Holmes, B.

    1994-06-01

    Traditionally, probabilistic risk assessments (PRA) of severe accidents in nuclear power plants have considered initiating events potentially occurring only during full power operation. Some previous screening analyses that were performed for other modes of operation suggested that risks during those modes were small relative to full power operation. However, more recent studies and operational experience have implied that accidents during low power and shutdown could be significant contributors to risk. Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The scope of the program includes that of a level-3 PRA. In phase 2, mid-loop operation was selected as the plant configuration to be analyzed based on the results of the phase 1 study. The objective of the phase 2 study is to perform a detailed analysis of the potential accident scenarios that may occur during mid-loop operation, and compare the results with those of NUREG-1150. The scope of the level-1 study includes plant damage state analysis, and uncertainty analysis. Volume 1 summarizes the results of the study. Internal events analysis is documented in Volume 2. It also contains an appendix that documents the part of the phase 1 study that has to do with POSs other than mid-loop operation. Internal fire and internal flood analyses are documented in Volumes 3 and 4. A separate study on seismic analysis, documented in Volume 5, was performed for the NRC by Future Resources Associates, Inc. Volume 6 documents the accident progression, source terms, and consequence analysis

  12. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal events during mid-loop operations. Appendix E (Sections E.9-E.16), Volume 2, Part 3B

    International Nuclear Information System (INIS)

    Chu, T.L.; Musicki, Z.; Kohut, P.; Yang, J.; Bozoki, G.; Hsu, C.J.; Diamond, D.J.; Wong, S.M.; Bley, D.; Johnson, D.

    1994-06-01

    Traditionally, probabilistic risk assessments (PRA) of severe accidents in nuclear power plants have considered initiating events potentially occurring only during full power operation. Some previous screening analyses that were performed for other modes of operation suggested that risks during those modes were small relative to full power operation. However, more recent studies and operational experience have implied that accidents during low power and shutdown could be significant contributors to risk. Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The scope of the program includes that of a level-3 PRA. In phase 2, mid-loop operation was selected as the plant configuration to be analyzed based on the results of the phase 1 study. The objective of the phase 2 study is to perform a detailed analysis of the potential accident scenarios that may occur during mid-loop operation, and compare the results with those of NUREG-1150. The scope of the level-1 study includes plant damage state analysis, and uncertainty analysis. Volume 1 summarizes the results of the study. Internal events analysis is documented in Volume 2. It also contains an appendix that documents the part of the phase 1 study that has to do with POSs other than mid-loop operation. Internal fire and internal flood analyses are documented in Volumes 3 and 4. A separate study on seismic analysis, documented in Volume 5, was performed for the NRC by Future Resources Associates, Inc. Volume 6 documents the accident progression, source terms, and consequence analysis

  13. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit-1: Analysis of core damage frequency from internal events during mid-loop operations. Appendix I, Volume 2, Part 5

    International Nuclear Information System (INIS)

    Chu, T.L.; Musicki, Z.; Kohut, P.; Yang, J.; Bozoki, G.; Hsu, C.J.; Diamond, D.J.; Bley, D.; Johnson, D.; Holmes, B.

    1994-06-01

    Traditionally, probabilistic risk assessments (PRA) of severe accidents in nuclear power plants have considered initiating events potentially occurring only during full power operation. Some previous screening analyses that were performed for other modes of operation suggested that risks during those modes were small relative to full power operation. However, more recent studies and operational experience have implied that accidents during low power and shutdown could be significant contributors to risk. During 1989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the potential risks during low power and shutdown operations. The program includes two parallel projects being performed by Brookhaven National Lab. (BNL) and Sandia National Labs. (SNL). Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The objective of this volume of the report is to document the approach utilized in the level-1 internal events PRA for the Surry plant, and discuss the results obtained. A phased approach was used in the level-1 program. In phase 1, which was completed in Fall 1991, a coarse screening analysis examining accidents initiated by internal events (including internal fire and flood) was performed for all plant operational states (POSs). The objective of the phase 1 study was to identify potential vulnerable plant configurations, to characterize (on a high, medium, or low basis) the potential core damage accident scenarios, and to provide a foundation for a detailed phase 2 analysis

  14. Cellularized Cellular Solids via Freeze-Casting.

    Science.gov (United States)

    Christoph, Sarah; Kwiatoszynski, Julien; Coradin, Thibaud; Fernandes, Francisco M

    2016-02-01

    The elaboration of metabolically active cell-containing materials is a decisive step toward the successful application of cell based technologies. The present work unveils a new process allowing to simultaneously encapsulate living cells and shaping cell-containing materials into solid-state macroporous foams with precisely controlled morphology. Our strategy is based on freeze casting, an ice templating materials processing technique that has recently emerged for the structuration of colloids into macroporous materials. Our results indicate that it is possible to combine the precise structuration of the materials with cellular metabolic activity for the model organism Saccharomyces cerevisiae. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Epigenetics and Cellular Metabolism

    Directory of Open Access Journals (Sweden)

    Wenyi Xu

    2016-01-01

    Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  16. Evaluation of potential severe accidents during low power and shutdown operations at Grand Gulf, Unit 1. Analysis of core damage frequency from internal events for plant operational state 5 during a refueling outage. Internal events appendices K to M

    International Nuclear Information System (INIS)

    Forester, J.; Yakle, J.; Walsh, B.; Darby, J.; Whitehead, D.; Staple, B.; Brown, T.

    1994-07-01

    This report provides supporting documentation for various tasks associated with the performance of the probabilistic risk assessment for Plant Operational State 5 (approximately Cold Shutdown as defined by Grand Gulf Technical Specifications) during a refueling outage at Grand Gulf, Unit 1 as documented in Volume 2, Part 1 of NUREG/CR-6143. The report contains the following appendices: K - HEP Locator Files; L - Supporting Information for the Plant Damage State Analysis; M - Summary of Results from the Coarse Screening Analysis - Phase 1A

  17. Assessment of beta-emitter radionuclides in biological samples using liquid scintillation counting. Application to the study of internal doses in molecular and cellular biology techniques; Evaluacion en muestras biologicas de radionucleidos emisores beta mediante espectrometria de centelleo en fase liquida. Aplicaciones al estudio de dosis internas en tecnicas de investigacion de biologia molecular y celular

    Energy Technology Data Exchange (ETDEWEB)

    Sierra, I.; Delgado, A.; Navarro, T.; Macias, M. T.

    2007-07-01

    The radioisotopic techniques used in Molecular and Cellular Biology involve external and internal irradiation risk. It is necessary to control the possible internal contamination associated to the development of these techniques. The internal contamination risk can be due to physical and chemical properties of the labelled compounds, aerosols generated during the performance technique. The aim of this work was to estimate the possible intake of specific beta emitters during the technique development and to propose the required criterions to perform Individual Monitoring. The most representative radioisotopic techniques were selected attending their potential risk of internal contamination. Techniques were analysed applying IAEA methodology according to the used activity in each technique. It was necessary to identify the worker groups that would require individual monitoring on the base of their specific risk. Different measurement procedures were applied to study the possible intake in group risk and more than 160 persons were measured by in vitro bioassay. (Author) 96 refs.

  18. Wireless Cellular Mobile Communications

    Directory of Open Access Journals (Sweden)

    V. Zalud

    2002-12-01

    Full Text Available In this article is briefly reviewed the history of wireless cellularmobile communications, examined the progress in current secondgeneration (2G cellular standards and discussed their migration to thethird generation (3G. The European 2G cellular standard GSM and itsevolution phases GPRS and EDGE are described somewhat in detail. Thethird generation standard UMTS taking up on GSM/GPRS core network andequipped with a new advanced access network on the basis of codedivision multiple access (CDMA is investigated too. A sketch of theperspective of mobile communication beyond 3G concludes this article.

  19. A comparison between the performance degradation of 3T APS due to radiation exposure and the expected internal damage via Monte-Carlo Simulation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Gi Yoon; Kim, Myung Soo; Lim, Kyung Taek; Lee, Eun Jung; Kim, Chan Kyu [Dept. of Nuclear and Quantum Engineering, KAIST, Daejeon (Korea, Republic of); Park, Jong Hwan [Luvantix ADM , Daejeon (Korea, Republic of)

    2015-02-15

    The trend of x-ray image sensor has been evolved from an amorphous silicon sensor to a crystal silicon sensor. A crystal silicon X-ray sensor, meaning a X-ray CIS (CMOS image sensor), is consisted of three transistors (Trs), i.e., a Reset Transistor, a Source Follower and a Select Transistor, and a photodiode. They are highly sensitive to radiation exposure. As the frequency of exposure to radiation increases, the quality of the imaging device dramatically decreases. The most well known effects of a X-ray CIS due to the radiation damage are increments in the reset voltage and dark currents. In this study, a pixel array of a X-ray CIS was made of 20×20 pixels and this pixel array was exposed to a high radiation dose. The radiation source was Co-60 and the total radiation dose was increased from 1 to 9 kGy with a step of 1 kGy. We irradiated the small pixel array to get the increments data of the reset voltage and the dark currents. Also, we simulated the radiation effects of the pixel by MCNP (Monte Carlo N-Particle) simulation. From the comparison of actual data and simulation data, the most affected location could be determined and the cause of the increments of the reset voltage and dark current could be found.

  20. Apportioning liability for transborder damage

    International Nuclear Information System (INIS)

    Krause-Ablass, W.D.

    1988-01-01

    The author analyses the different legal systems applicable to transfrontier nuclear damage. Using examples, he describes the mechanisms enabling a victim of such damage to identify the competent court and the relevant law, according to whether the provisions of the Paris or the Vienna Convention come into play or whether the rules of private international law, incorporated in the various national laws are applicable (NEA) [fr

  1. Radiolabelled cellular blood elements

    International Nuclear Information System (INIS)

    Sinzinger, H.

    1990-01-01

    This book reports on radiolabelled cellular blood elements, covering new advances made during the past several years, in particular the use of Tc-99 as a tracer for blood elements. Coverage extends to several radiolabelled monoclonal antibodies that are specific for blood components and may label blood elements in vivo

  2. Building synthetic cellular organization

    OpenAIRE

    Polka, Jessica K.; Silver, Pamela A.

    2013-01-01

    The elaborate spatial organization of cells enhances, restricts, and regulates protein–protein interactions. However, the biological significance of this organization has been difficult to study without ways of directly perturbing it. We highlight synthetic biology tools for engineering novel cellular organization, describing how they have been, and can be, used to advance cell biology.

  3. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  4. Electromagnetic cellular interactions.

    Science.gov (United States)

    Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

    2011-05-01

    Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Genetic Dominance & Cellular Processes

    Science.gov (United States)

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  6. Irradiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Howe, L.M

    2000-07-01

    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization.

  7. Irradiation damage

    International Nuclear Information System (INIS)

    Howe, L.M.

    2000-01-01

    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization

  8. Sulphonated hypocrellin B sensitized photo damage to ascetic hepatoma cells

    International Nuclear Information System (INIS)

    Yue Jiachang; Wang Tiandun; Pang Suzhen; An Jingyi; Jiang Lijing

    1994-01-01

    The cellular uptake of sulphonated hypocrellin (S-HB), as well as photo damage on cellular viability, lipid peroxidation and intrinsic fluorescence quenching of membrane protein was studied. It was found that S-HB suitable dissolved in aqueous solution, its cellular uptake is slower than HB. The photo damage on cellular viability both photo sensitizers was close to each other, however the photo sensitizers were different in physical and chemical properties. The HB photo damage target of cells was membrane, but the sulphonated HB photo damage target of cells may be part of organelles, besides the membrane. the experiments showed the sulphonated HB would be suggested as a potential advantage for photodynamic therapy of tumor in clinical application

  9. Cellular Senescence in Postmitotic Cells: Beyond Growth Arrest.

    Science.gov (United States)

    Sapieha, Przemyslaw; Mallette, Frédérick A

    2018-04-25

    In mitotic cells, cellular senescence is a permanent state of G1 arrest, that may have evolved in parallel to apoptosis, to limit proliferation of damaged cells and oncogenesis. Recent studies have suggested that postmitotic cells are also capable of entering a state of senescence, although the repercussions of postmitotic cellular senescence (PoMiCS) on tissue health and function are currently ill-defined. In tissues made largely of post-mitotic cells, it is evolutionary advantageous to preserve cellular integrity and cellular senescence of post-mitotic cells may prevent stressor-induced tissue degeneration and promote tissue repair. Paradoxically, PoMiCS may also contribute to disease progression through the generation of inflammatory mediators, termed the senescence-associated secretory phenotype. Here, we discuss the potential roles of PoMiCS and propose to enlarge the current definition of cellular senescence to postmitotic terminally differentiated cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Biochemical Factors Modulating Cellular Neurotoxicity of Methylmercury

    Directory of Open Access Journals (Sweden)

    Parvinder Kaur

    2011-01-01

    Full Text Available Methylmercury (MeHg, an environmental toxicant primarily found in fish and seafood, poses a dilemma to both consumers and regulatory authorities, given the nutritional benefits of fish consumption versus the possible adverse neurological damage. Several studies have shown that MeHg toxicity is influenced by a number of biochemical factors, such as glutathione (GSH, fatty acids, vitamins, and essential elements, but the cellular mechanisms underlying these complex interactions have not yet been fully elucidated. The objective of this paper is to outline the cellular response to dietary nutrients, as well as to describe the neurotoxic exposures to MeHg. In order to determine the cellular mechanism(s of toxicity, the effect of pretreatment with biochemical factors (e.g., N-acetyl cysteine, (NAC; diethyl maleate, (DEM; docosahexaenoic acid, (DHA; selenomethionine, SeM; Trolox and MeHg treatment on intercellular antioxidant status, MeHg content, and other endpoints was evaluated. This paper emphasizes that the protection against oxidative stress offered by these biochemical factors is among one of the major mechanisms responsible for conferring neuroprotection. It is therefore critical to ascertain the cellular mechanisms associated with various dietary nutrients as well as to determine the potential effects of neurotoxic exposures for accurately assessing the risks and benefits associated with fish consumption.

  11. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  12. Nested cellular automata

    International Nuclear Information System (INIS)

    Quasthoff, U.

    1985-07-01

    Cellular automata by definition consist of a finite or infinite number of cells, say of unit length, with each cell having the same transition function. These cells are usually considered as the smallest elements and so the space filled with these cells becomes discrete. Nevertheless, large pictures created by such cellular automata look very fractal. So we try to replace each cell by a couple of smaller cells, which have the same transition functions as the large ones. There are automata where this replacement does not destroy the macroscopic structure. In these cases this nesting process can be iterated. The paper contains large classes of automata with the above properties. In the case of one dimensional automata with two states and next neighbour interaction and a nesting function of the same type a complete classification is given. (author)

  13. Cellular Mechanisms of Somatic Stem Cell Aging

    Science.gov (United States)

    Jung, Yunjoon

    2014-01-01

    Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

  14. Predictability in cellular automata.

    Science.gov (United States)

    Agapie, Alexandru; Andreica, Anca; Chira, Camelia; Giuclea, Marius

    2014-01-01

    Modelled as finite homogeneous Markov chains, probabilistic cellular automata with local transition probabilities in (0, 1) always posses a stationary distribution. This result alone is not very helpful when it comes to predicting the final configuration; one needs also a formula connecting the probabilities in the stationary distribution to some intrinsic feature of the lattice configuration. Previous results on the asynchronous cellular automata have showed that such feature really exists. It is the number of zero-one borders within the automaton's binary configuration. An exponential formula in the number of zero-one borders has been proved for the 1-D, 2-D and 3-D asynchronous automata with neighborhood three, five and seven, respectively. We perform computer experiments on a synchronous cellular automaton to check whether the empirical distribution obeys also that theoretical formula. The numerical results indicate a perfect fit for neighbourhood three and five, which opens the way for a rigorous proof of the formula in this new, synchronous case.

  15. Probabilistic cellular automata.

    Science.gov (United States)

    Agapie, Alexandru; Andreica, Anca; Giuclea, Marius

    2014-09-01

    Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case-connecting the probability of a configuration in the stationary distribution to its number of zero-one borders-the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata.

  16. Wavefront cellular learning automata.

    Science.gov (United States)

    Moradabadi, Behnaz; Meybodi, Mohammad Reza

    2018-02-01

    This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure for the WCLA is necessary in many dynamic areas such as social networks, computer networks, grid computing, and web mining. In this paper, we introduce the WCLA framework as an optimization tool with diffusion capability, study its behavior over time using ordinary differential equation solutions, and present its accuracy using expediency analysis. To show the superiority of the proposed WCLA, we compare the proposed method with some other types of cellular learning automata using two benchmark problems.

  17. Algorithm for cellular reprogramming.

    Science.gov (United States)

    Ronquist, Scott; Patterson, Geoff; Muir, Lindsey A; Lindsly, Stephen; Chen, Haiming; Brown, Markus; Wicha, Max S; Bloch, Anthony; Brockett, Roger; Rajapakse, Indika

    2017-11-07

    The day we understand the time evolution of subcellular events at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology. With data-guided frameworks we can develop better predictions about, and methods for, control over specific biological processes and system-wide cell behavior. Here we describe an approach for optimizing the use of transcription factors (TFs) in cellular reprogramming, based on a device commonly used in optimal control. We construct an approximate model for the natural evolution of a cell-cycle-synchronized population of human fibroblasts, based on data obtained by sampling the expression of 22,083 genes at several time points during the cell cycle. To arrive at a model of moderate complexity, we cluster gene expression based on division of the genome into topologically associating domains (TADs) and then model the dynamics of TAD expression levels. Based on this dynamical model and additional data, such as known TF binding sites and activity, we develop a methodology for identifying the top TF candidates for a specific cellular reprogramming task. Our data-guided methodology identifies a number of TFs previously validated for reprogramming and/or natural differentiation and predicts some potentially useful combinations of TFs. Our findings highlight the immense potential of dynamical models, mathematics, and data-guided methodologies for improving strategies for control over biological processes. Copyright © 2017 the Author(s). Published by PNAS.

  18. Wavefront cellular learning automata

    Science.gov (United States)

    Moradabadi, Behnaz; Meybodi, Mohammad Reza

    2018-02-01

    This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure for the WCLA is necessary in many dynamic areas such as social networks, computer networks, grid computing, and web mining. In this paper, we introduce the WCLA framework as an optimization tool with diffusion capability, study its behavior over time using ordinary differential equation solutions, and present its accuracy using expediency analysis. To show the superiority of the proposed WCLA, we compare the proposed method with some other types of cellular learning automata using two benchmark problems.

  19. Structural damage

    International Nuclear Information System (INIS)

    Gray, R.E.; Bruhn, R.W.

    1992-01-01

    Virtually all structures show some signs of distress due to deterioration of the building components, to changed loads, or to changed support conditions. Changed support conditions result from ground movements. In mining regions many cases of structural distress are attributed to mining without considering alternative causes. This is particularly true of coal mining since it occurs under extensive areas. Coal mining is estimated to have already undermined more than eight million acres and may eventually undermine 40 million acres in the United States. Other nonmetal and metal underground mines impact much smaller areas. Although it is sometimes difficult, even with careful study, to identify the actual cause of damage, persons responsible for underground coal mining should at least be aware of possible causes of building stress other than mine subsidence. This paper presents information on distress to structures and briefly reviews a number of causes of ground movements other than subsidence: Mass movements, dissolution, erosion, frost action, shrinking and swelling, yield into excavations and compressibility

  20. Radiation damage prediction system using damage function

    International Nuclear Information System (INIS)

    Tanaka, Yoshihisa; Mori, Seiji

    1979-01-01

    The irradiation damage analysis system using a damage function was investigated. This irradiation damage analysis system consists of the following three processes, the unfolding of a damage function, the calculation of the neutron flux spectrum of the object of damage analysis and the estimation of irradiation effect of the object of damage analysis. The damage function is calculated by applying the SAND-2 code. The ANISN and DOT3, 5 codes are used to calculate neutron flux. The neutron radiation and the allowable time of reactor operation can be estimated based on these calculations of the damage function and neutron flux. The flow diagram of the process of analyzing irradiation damage by a damage function and the flow diagram of SAND-2 code are presented, and the analytical code for estimating damage, which is determined with a damage function and a neutron spectrum, is explained. The application of the irradiation damage analysis system using a damage function was carried out to the core support structure of a fast breeder reactor for the damage estimation and the uncertainty evaluation. The fundamental analytical conditions and the analytical model for this work are presented, then the irradiation data for SUS304, the initial estimated values of a damage function, the error analysis for a damage function and the analytical results are explained concerning the computation of a damage function for 10% total elongation. Concerning the damage estimation of FBR core support structure, the standard and lower limiting values of damage, the permissible neutron flux and the allowable years of reactor operation are presented and were evaluated. (Nakai, Y.)

  1. Environment Aware Cellular Networks

    KAUST Repository

    Ghazzai, Hakim

    2015-02-01

    The unprecedented rise of mobile user demand over the years have led to an enormous growth of the energy consumption of wireless networks as well as the greenhouse gas emissions which are estimated currently to be around 70 million tons per year. This significant growth of energy consumption impels network companies to pay huge bills which represent around half of their operating expenditures. Therefore, many service providers, including mobile operators, are looking for new and modern green solutions to help reduce their expenses as well as the level of their CO2 emissions. Base stations are the most power greedy element in cellular networks: they drain around 80% of the total network energy consumption even during low traffic periods. Thus, there is a growing need to develop more energy-efficient techniques to enhance the green performance of future 4G/5G cellular networks. Due to the problem of traffic load fluctuations in cellular networks during different periods of the day and between different areas (shopping or business districts and residential areas), the base station sleeping strategy has been one of the main popular research topics in green communications. In this presentation, we present several practical green techniques that provide significant gains for mobile operators. Indeed, combined with the base station sleeping strategy, these techniques achieve not only a minimization of the fossil fuel consumption but also an enhancement of mobile operator profits. We start with an optimized cell planning method that considers varying spatial and temporal user densities. We then use the optimal transport theory in order to define the cell boundaries such that the network total transmit power is reduced. Afterwards, we exploit the features of the modern electrical grid, the smart grid, as a new tool of power management for cellular networks and we optimize the energy procurement from multiple energy retailers characterized by different prices and pollutant

  2. DNA damage, repair and tanning acceleration

    NARCIS (Netherlands)

    Vink, A.A.; Berg, P.T.M. van den; Roza, L.

    1999-01-01

    Exposure of the skin to solar ultraviolet radiation (UV) leads to various adverse effects, such as the induction of cellular damage and mutations, suppression of the skin's immune system, and the induction of skin cancer. These effects are the consequence of various molecular alterations in the skin

  3. Biomolecular condensates: organizers of cellular biochemistry.

    Science.gov (United States)

    Banani, Salman F; Lee, Hyun O; Hyman, Anthony A; Rosen, Michael K

    2017-05-01

    Biomolecular condensates are micron-scale compartments in eukaryotic cells that lack surrounding membranes but function to concentrate proteins and nucleic acids. These condensates are involved in diverse processes, including RNA metabolism, ribosome biogenesis, the DNA damage response and signal transduction. Recent studies have shown that liquid-liquid phase separation driven by multivalent macromolecular interactions is an important organizing principle for biomolecular condensates. With this physical framework, it is now possible to explain how the assembly, composition, physical properties and biochemical and cellular functions of these important structures are regulated.

  4. [Fanconi anemia: cellular and molecular features].

    Science.gov (United States)

    Macé, G; Briot, D; Guervilly, J-H; Rosselli, F

    2007-02-01

    Fanconi anemia (FA) is a recessive human cancer prone syndrome featuring bone marrow failure, developmental abnormalities and hypersensitivity to DNA crosslinking agents exposure. 11 among 12 FA gene have been isolated. The biochemical functions of the FANC proteins remain poorly understood. Anyhow, to cope with DNA crosslinks a cell needs a functional FANC pathway. Moreover, the FANC proteins appear to be involved in cell protection against oxidative damage and in the control of TNF-alpha activity. In this review, we describe the current understanding of the FANC pathway and we present how it may be integrated in the complex networks of proteins involved in maintaining the cellular homeostasis.

  5. Civil Liability for Environmental Damages

    Directory of Open Access Journals (Sweden)

    Daniela Ciochină

    2012-05-01

    Full Text Available We debated in this article the civil liability for environmental damages as stipulated in ourlegislation with reference to Community law. The theory of legal liability in environmental law is basedon the duty of all citizens to respect and protect the environment. Considering the importance ofenvironment in which we live, the liability for environmental damages is treated by the Constitution as aprinciple and a fundamental obligation. Many human activities cause environmental damages and, in linewith the principle of sustainable development, they should be avoided. However, when this is notpossible, they must be regulated (by criminal or administrative law in order to limit their adverse effectsand, according to the polluter pays principle, to internalize in advance their externalities (through taxes,insurances or other forms of financial security products. Communication aims to analyze these issues andlegal regulations dealing with the issue of liability for environmental damage.

  6. Cosserat modeling of cellular solids

    NARCIS (Netherlands)

    Onck, P.R.

    Cellular solids inherit their macroscopic mechanical properties directly from the cellular microstructure. However, the characteristic material length scale is often not small compared to macroscopic dimensions, which limits the applicability of classical continuum-type constitutive models. Cosserat

  7. Evaluation of Structural Cellular Glass

    Science.gov (United States)

    Adams, M. A.; Zwissler, J. G.

    1984-01-01

    Preliminary design information presented. First report discusses state of structural-cellular-glass programs as of June 1979. Second report gives further details of program to develop improved cellular glasses and to characterize properties of glasses and commercially available materials.

  8. Chromatin organization and cellular sensitivity to ionizing radiation

    International Nuclear Information System (INIS)

    Szumiel, I.; Walicka, M.

    1987-01-01

    The paper briefly describes chromatin organization in mammalian cells and reviews experimental work concerning relations between chromatin structure and accesibility of damaged DNA to repair enzymes. The ''contact effect'', the size of super-coiled DNA domains and ADP-ribosylation of chromatin proteins are discussed in relation to cellular radiosensitivity. 88 refs. (author)

  9. Cellular communication through light.

    Directory of Open Access Journals (Sweden)

    Daniel Fels

    Full Text Available Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry.

  10. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  11. Cellular mechanics and motility

    Science.gov (United States)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  12. Thermal expansion behavior in fabricated cellular structures

    International Nuclear Information System (INIS)

    Oruganti, R.K.; Ghosh, A.K.; Mazumder, J.

    2004-01-01

    Thermal expansion behavior of cellular structures is of interest in applications where undesirable deformation and failure are caused by thermal expansion mismatch. This report describes the role of processing-induced effects and metallurgical aspects of melt-processed cellular structures, such as a bi-material structure designed to contract on heating, as well as uni-material structures of regular and stochastic topology. This bi-material structure utilized the principle of internal geometric constraints to alter the expansion behavior of the internal ligaments to create overall contraction of the structure. Homogenization design method was used to design the structure, and fabrication was by direct metal deposition by laser melting of powder in another part of a joint effort. The degree of porosity and grain size in the fabricated structure are characterized and related to the laser deposition parameters. The structure was found to contract upon heating over a short range of temperature subsequent to which normal expansion ensued. Also examined in this report are uni-material cellular structures, in which internal constraints arise from residual stress variations caused by the fabrication process, and thereby alter their expansion characteristics. A simple analysis of thermal strain of this material supports the observed thermal expansion behavior

  13. Cellular vs. organ approaches to dose estimates

    International Nuclear Information System (INIS)

    Adelstein, S.J.; Kassis, A.I.; Sastry, K.S.R.

    1986-01-01

    The cellular distribution of tissue-incorporated radionuclides has generally been neglected in the dosimetry of internal emitters. Traditional dosimetry assumes homogeneous distribution of radionuclides in organs of interest, while presuming that the ranges of particulate radiations are large relative to typical cell diameters. The macroscopic distribution of dose thus calculated has generally served as a sufficient approximation for the energy deposited within radiosensitive sites. However, with the increasing utilization of intracellular agents, such as thallium-201, it has become necessary to examine the microscopic distribution of energy at the cellular level. This is particularly important in the instance of radionuclides that decay by electron capture or by internal conversion with the release of Auger and Coster-Kronig electrons. In many instances, these electrons are released as a dense shower of low-energy particles with ranges of subcellular dimensions. The high electron density in the immediate vicinity of the decaying atom produces a focal deposition of energy that far exceeds the average dose taken over several cell diameters. These studies point out the increasing need to take into account the microscopic distribution of dose on the cellular level as radionuclides distributed in cells become more commonplace, especially if the decay involves electron capture or internal conversion. As radiotracers are developed for the measurement of intracellular functions these factors should be given greater consideration. 16 references, 5 figures, 5 tables

  14. National Assembly report on the bill authorizing joining the 2001 International Convention on Civil Liability for Bunker Oil Pollution Damage; Rapport fait au nom de la Commission des Affaires Etrangeres sur le Projet de Loi n.1792, autorisant l'adhesion a la convention internationale de 2001 sur la responsabilite civile pour les dommages dus a la pollution par les hydrocarbures de soute

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    This report first gives an overview of the progressive implementation of measures and international convention to prevent pollution by ships: the Oilpol convention (Convention for the Prevention of Pollution of the Sea by Oil), the Marpol convention (Marine Pollution), and the different international conventions on liability and compensation (International Convention on Civil Liability for Oil Pollution, International Convention on Liability and Compensation for Damage in Connection with the Carriage of Hazardous and Noxious Substances by Sea, convention on other damages). It also describes the French system to struggle against marine pollution. Then, it presents the main arrangements of the 2001 Convention (liability, mandatory insurance and certificate, and so on), expresses some reserves on the chosen arrangement, and comments the impact of this convention

  15. Targeting Neutrophilic Inflammation Using Polymersome-Mediated Cellular Delivery.

    Science.gov (United States)

    Robertson, James D; Ward, Jon R; Avila-Olias, Milagros; Battaglia, Giuseppe; Renshaw, Stephen A

    2017-05-01

    Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In this study, we deliver therapeutic compounds to neutrophils using biocompatible, nanometer-sized synthetic vesicles, or polymersomes, which are internalized by binding to scavenger receptors and subsequently escape the early endosome through a pH-triggered disassembly mechanism. This allows polymersomes to deliver molecules into the cell cytosol of neutrophils without causing cellular activation. After optimizing polymersome size, we show that polymersomes can deliver the cyclin-dependent kinase inhibitor (R)-roscovitine into human neutrophils to promote apoptosis in vitro. Finally, using a transgenic zebrafish model, we show that encapsulated (R)-roscovitine can speed up inflammation resolution in vivo more efficiently than the free drug. These results show that polymersomes are effective intracellular carriers for drug delivery into neutrophils. This has important consequences for the study of neutrophil biology and the development of neutrophil-targeted therapeutics. Copyright © 2017 The Authors.

  16. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

    OpenAIRE

    Chornokur, Ganna; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Amankwah, Ernest K.; Qu, Xiaotao; Tsai, Ya-Yu; Jim, Heather S. L.; Chen, Zhihua; Chen, Ann Y.; Permuth-Wey, Jennifer; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia

    2015-01-01

    Background\\ud \\ud Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contribu...

  17. Updated Vertical Extent of Collision Damage

    DEFF Research Database (Denmark)

    Tagg, R.; Bartzis, P.; Papanikolaou, P.

    2002-01-01

    The probabilistic distribution of the vertical extent of collision damage is an important and somewhat controversial component of the proposed IMO harmonized damage stability regulations for cargo and passenger ships. The only pre-existing vertical distribution, currently used in the international...

  18. HDACi: cellular effects, opportunities for restorative dentistry.

    LENUS (Irish Health Repository)

    Duncan, H F

    2011-12-01

    Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be \\'tipped\\' by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between \\'normal\\' and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage.

  19. Cellular image classification

    CERN Document Server

    Xu, Xiang; Lin, Feng

    2017-01-01

    This book introduces new techniques for cellular image feature extraction, pattern recognition and classification. The authors use the antinuclear antibodies (ANAs) in patient serum as the subjects and the Indirect Immunofluorescence (IIF) technique as the imaging protocol to illustrate the applications of the described methods. Throughout the book, the authors provide evaluations for the proposed methods on two publicly available human epithelial (HEp-2) cell datasets: ICPR2012 dataset from the ICPR'12 HEp-2 cell classification contest and ICIP2013 training dataset from the ICIP'13 Competition on cells classification by fluorescent image analysis. First, the reading of imaging results is significantly influenced by one’s qualification and reading systems, causing high intra- and inter-laboratory variance. The authors present a low-order LP21 fiber mode for optical single cell manipulation and imaging staining patterns of HEp-2 cells. A focused four-lobed mode distribution is stable and effective in optical...

  20. Validation of self-reported cellular phone use

    DEFF Research Database (Denmark)

    Samkange-Zeeb, Florence; Berg, Gabriele; Blettner, Maria

    2004-01-01

    BACKGROUND: In recent years, concern has been raised over possible adverse health effects of cellular telephone use. In epidemiological studies of cancer risk associated with the use of cellular telephones, the validity of self-reported cellular phone use has been problematic. Up to now there is ......BACKGROUND: In recent years, concern has been raised over possible adverse health effects of cellular telephone use. In epidemiological studies of cancer risk associated with the use of cellular telephones, the validity of self-reported cellular phone use has been problematic. Up to now...... there is very little information published on this subject. METHODS: We conducted a study to validate the questionnaire used in an ongoing international case-control study on cellular phone use, the "Interphone study". Self-reported cellular phone use from 68 of 104 participants who took part in our study...... was compared with information derived from the network providers over a period of 3 months (taken as the gold standard). RESULTS: Using Spearman's rank correlation, the correlation between self-reported phone use and information from the network providers for cellular phone use in terms of the number of calls...

  1. Two-material optimization of plate armour for blast mitigation using hybrid cellular automata

    Science.gov (United States)

    Goetz, J.; Tan, H.; Renaud, J.; Tovar, A.

    2012-08-01

    With the increased use of improvised explosive devices in regions at war, the threat to military and civilian life has risen. Cabin penetration and gross acceleration are the primary threats in an explosive event. Cabin penetration crushes occupants, damaging the lower body. Acceleration causes death at high magnitudes. This investigation develops a process of designing armour that simultaneously mitigates cabin penetration and acceleration. The hybrid cellular automaton (HCA) method of topology optimization has proven efficient and robust in problems involving large, plastic deformations such as crash impact. Here HCA is extended to the design of armour under blast loading. The ability to distribute two metallic phases, as opposed to one material and void, is also added. The blast wave energy transforms on impact into internal energy (IE) inside the solid medium. Maximum attenuation occurs with maximized IE. The resulting structures show HCA's potential for designing blast mitigating armour structures.

  2. RENAL DAMAGE WITH MALIGNANT NEOPLASMS

    Directory of Open Access Journals (Sweden)

    I. B. Kolina

    2015-01-01

    Full Text Available The relationship between renal damage and malignant neoplasms is one of the most actual problems of the medicine of internal diseases. Very often, exactly availability of renal damage determines the forecast of cancer patients. The range of renal pathologies associated with tumors is unusually wide: from the mechanical effect of the tumor or metastases on the kidneys and/or the urinary tract and paraneoplastic manifestations in the form of nephritis or amyloidosis to nephropathies induced with drugs or tumor lysis, etc. Thrombotic complications that develop as a result of exposure to tumor effects, side effects of certain drugs or irradiation also play an important role in the development of the kidney damage. The most frequent variants of renal damage observed in the practice of medical internists (therapists, urologists, surgeons, etc., as well as methods of diagnosis and treatment approaches are described in the article. Timely and successful prevention and treatment of tumor-associated nephropathies give hope for retaining renal functions, therefore, a higher life standard after completion of anti-tumor therapy. Even a shortterm episode of acute renal damage suffered by a cancer patient must be accompanied with relevant examination and treatment. In the caseof transformation of acute renal damage into the chronic kidney disease, such patients need systematic and weighted renoprotective therapy and correct dosing of nephrotoxic drugs.

  3. Efficiency of cellular information processing

    International Nuclear Information System (INIS)

    Barato, Andre C; Hartich, David; Seifert, Udo

    2014-01-01

    We show that a rate of conditional Shannon entropy reduction, characterizing the learning of an internal process about an external process, is bounded by the thermodynamic entropy production. This approach allows for the definition of an informational efficiency that can be used to study cellular information processing. We analyze three models of increasing complexity inspired by the Escherichia coli sensory network, where the external process is an external ligand concentration jumping between two values. We start with a simple model for which ATP must be consumed so that a protein inside the cell can learn about the external concentration. With a second model for a single receptor we show that the rate at which the receptor learns about the external environment can be nonzero even without any dissipation inside the cell since chemical work done by the external process compensates for this learning rate. The third model is more complete, also containing adaptation. For this model we show inter alia that a bacterium in an environment that changes at a very slow time-scale is quite inefficient, dissipating much more than it learns. Using the concept of a coarse-grained learning rate, we show for the model with adaptation that while the activity learns about the external signal the option of changing the methylation level increases the concentration range for which the learning rate is substantial. (paper)

  4. Statistical mechanics of cellular automata

    International Nuclear Information System (INIS)

    Wolfram, S.

    1983-01-01

    Cellular automata are used as simple mathematical models to investigate self-organization in statistical mechanics. A detailed analysis is given of ''elementary'' cellular automata consisting of a sequence of sites with values 0 or 1 on a line, with each site evolving deterministically in discrete time steps according to p definite rules involving the values of its nearest neighbors. With simple initial configurations, the cellular automata either tend to homogeneous states, or generate self-similar patterns with fractal dimensions approx. =1.59 or approx. =1.69. With ''random'' initial configurations, the irreversible character of the cellular automaton evolution leads to several self-organization phenomena. Statistical properties of the structures generated are found to lie in two universality classes, independent of the details of the initial state or the cellular automaton rules. More complicated cellular automata are briefly considered, and connections with dynamical systems theory and the formal theory of computation are discussed

  5. Influence of corona charging in cellular polyethylene film

    International Nuclear Information System (INIS)

    Ortega Brana, Gustavo; Magraner, Francisco; Quijano, Alfredo; Llovera Segovia, Pedro

    2011-01-01

    Cellular polymers have recently attracted attention for their property of exhibiting a piezoelectric constant when they are electrically charged. The electrostatic charge generated in the voids by the internal discharges creates and internal macrodipole which is responsible for the piezoelectric effect. Charging by corona discharge is the most used method for cellular polymers. Many works has been published on polypropylene and polyethylene films mainly focused on the required expansion process or on the results obtained for raw cellular materials electrically activated. Our work is based on commercial polyethylene cellular films which have been physically characterized and electrically activated. The effect of thermal treatment, physical uniaxial or biaxial stretching and corona charging was investigated. The new method of corona charging improved the piezoelectric constant under other activation conditions.

  6. Influence of corona charging in cellular polyethylene film

    Energy Technology Data Exchange (ETDEWEB)

    Ortega Brana, Gustavo; Magraner, Francisco; Quijano, Alfredo [Instituto Tecnologico de la Energia (ITE), Av. Juan de la Cierva 24, Parque Tecnologico de Valencia, 46980 Paterna-Valencia (Spain); Llovera Segovia, Pedro, E-mail: gustavo.ortega@ite.es [Instituto de TecnologIa Electrica - Universitat Politecnica de Valencia, Camino de Vera s/n 46022-Valencia (Spain)

    2011-06-23

    Cellular polymers have recently attracted attention for their property of exhibiting a piezoelectric constant when they are electrically charged. The electrostatic charge generated in the voids by the internal discharges creates and internal macrodipole which is responsible for the piezoelectric effect. Charging by corona discharge is the most used method for cellular polymers. Many works has been published on polypropylene and polyethylene films mainly focused on the required expansion process or on the results obtained for raw cellular materials electrically activated. Our work is based on commercial polyethylene cellular films which have been physically characterized and electrically activated. The effect of thermal treatment, physical uniaxial or biaxial stretching and corona charging was investigated. The new method of corona charging improved the piezoelectric constant under other activation conditions.

  7. Genetic effects from internally deposited radionuclides

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    It was learned in the late 1920's that ionizing radiation could produce genetic effects such as gene mutations and chromosome aberrations. However, at least until 1945, the focus on interest in radiation protection was primarily on somatic effects manifested in the individual exposed. Studies of the genetic effects of radiation using drosophila, however, refocused attention on effects transmitted to the exposed individuals offspring and concern over fallout in the 1950's resulted in efforts to estimate the genetic effects from exposure of human populations to internally deposited radionuclides. No human populations have been identified with burdens of internally deposited radioactive materials which have been shown to produce evidence of transmissible genetic damage. As a result, the research approach has been one in which macromolecular, cellular, and whole animal genetic studies have been combined to estimate genetic effects on humans following the deposition of radioactive materials in the body. The purpose of this report is to update the information available from animal and cellular experiments that relates genetic effects to deposited activity and dose from internally deposited radioactive materials

  8. Modeling cellular effects of coal pollutants

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    The goal of this project is to develop and test models for the dose and dose-rate dependence of biological effects of coal pollutants on mammalian cells in tissue culture. Particular attention is given to the interaction of pollutants with the genetic material (deoxyribonucleic acid, or NDA) in the cell. Unlike radiation, which can interact directly with chromatin, chemical pollutants undergo numerous changes before the ultimate carcinogen becomes covalently bound to the DNA. Synthetic vesicles formed from a phospholipid bilayer are being used to investigate chemical transformations that may occur during the transport of pollutants across cellular membranes. The initial damage to DNA is rapidly modified by enzymatic repair systems in most living organisms. A model has been developed for predicting the effects of excision repair on the survival of human cells exposed to chemical carcinogens. In addition to the excision system, normal human cells also have tolerance mechanisms that permit continued growth and division of cells without removal of the damage. We are investigating the biological effect of damage passed to daughter cells by these tolerance mechanisms

  9. Uncovering the footprints of malicious traffic in cellular data networks

    OpenAIRE

    Raghuramu, A; Zang, H; Chuah, CN

    2015-01-01

    © Springer International Publishing Switzerland 2015. In this paper, we present a comprehensive characterization of malicious traffic generated by mobile devices using Deep Packet Inspection (DPI) records and security event logs from a large US based cellular provider network. Our analysis reveals that 0.17% of mobile devices in the cellular network are affected by security threats. This proportion, while small, is orders of magnitude higher than the last reported (in 2013) infection rate of ...

  10. Harmonising measurements of 8-oxo-7,8-dihydro-2'-deoxyguanosine in cellular DNA and urine

    DEFF Research Database (Denmark)

    Møller, Peter; Cooke, Marcus S; Collins, Andrew

    2012-01-01

    Levels of oxidatively damaged cellular DNA and urinary excretion of damaged 2'-deoxyribonuclosides are widely measured in biomonitoring studies examining the role of oxidative stress induced by environmental exposures, lifestyle factors and development of disease. This has promoted efforts to har...

  11. Chromatin structure and cellular radiosensitivity : A comparison of two human tumour cell lines

    NARCIS (Netherlands)

    Woudstra, EC; Roesink, JM; Rosemann, M; Brunsting, JF; Driessen, C; Orta, T; Konings, AWT; Peacock, JH; Kampinga, HH

    1996-01-01

    The role of variation in susceptibility to DNA damage induction was studied as a determinant for cellular radiosensitivity. Comparison of the radiosensitive HX142 and radioresistant RT112 cell lines previously revealed higher susceptibility to X-ray-induced DNA damage in the sensitive cell line

  12. Damage analysis: damage function development and application

    International Nuclear Information System (INIS)

    Simons, R.L.; Odette, G.R.

    1975-01-01

    The derivation and application of damage functions, including recent developments for the U.S. LMFBR and CTR programs, is reviewed. A primary application of damage functions is in predicting component life expectancies; i.e., the fluence required in a service spectrum to attain a specified design property change. An important part of the analysis is the estimation of the uncertainty in such fluence limit predictions. The status of standardizing the procedures for the derivation and application of damage functions is discussed. Improvements in several areas of damage function development are needed before standardization can be completed. These include increasing the quantity and quality of the data used in the analysis, determining the limitations of the analysis due to the presence of multiple damage mechanisms, and finally, testing of damage function predictions against data obtained from material surveillance programs in operating thermal and fast reactors. 23 references. (auth)

  13. 47 CFR 22.909 - Cellular markets.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets...

  14. Civil liability for nuclear damage

    International Nuclear Information System (INIS)

    1963-01-01

    An international Convention on Civil Liability for Nuclear Damage was adopted in Vienna on 19 May 1963 by a sixty-nation conference convened by the International Atomic Energy Agency. The Convention, which is subject to ratification by the States signing it, will come into force three months after the deposit of the fifth instrument of ratification. The Convention is designee only to establish minimum rules regarding civil liability for nuclear damage; it may thus well be described as a framework convention, the main provisions of which represent the essential common denomination acceptable to as many States as possible. It leaves wide scope for national legislation and regional arrangements with a view to implementing these provisions The Convention does not purport to create a uniform civil law in this field, but it contains the minimal essential for protection of the public and forms the legal basis for uniform world-wide liability rules

  15. The complexity of DNA damage: relevance to biological consequences

    International Nuclear Information System (INIS)

    Ward, J.F.

    1994-01-01

    Ionizing radiation causes both singly and multiply damaged sites in DNA when the range of radical migration is limited by the presence of hydroxyl radical scavengers (e.g. within cells). Multiply damaged sites are considered to be more biologically relevant because of the challenges they present to cellular repair mechanisms. These sites occur in the form of DNA double-strand breaks (dsb) but also as other multiple damages that can be converted to dsb during attempted repair. The presence of a dsb can lead to loss of base sequence information and/or can permit the two ends of a break to separate and rejoin with the wrong partner. (Multiply damaged sites may also be the biologically relevant type of damage caused by other agents, such as UVA, B and/or C light, and some antitumour antibiotics). The quantitative data available from radiation studies of DNA are shown to support the proposed mechanisms for the production of complex damage in cellular DNA, i.e. via scavengable and non-scavengable mechanisms. The yields of complex damages can in turn be used to support the conclusion that cellular mutations are a consequence of the presence of these damages within a gene. (Author)

  16. MSAT and cellular hybrid networking

    Science.gov (United States)

    Baranowsky, Patrick W., II

    Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

  17. Cellular automata analysis and applications

    CERN Document Server

    Hadeler, Karl-Peter

    2017-01-01

    This book focuses on a coherent representation of the main approaches to analyze the dynamics of cellular automata. Cellular automata are an inevitable tool in mathematical modeling. In contrast to classical modeling approaches as partial differential equations, cellular automata are straightforward to simulate but hard to analyze. In this book we present a review of approaches and theories that allow the reader to understand the behavior of cellular automata beyond simulations. The first part consists of an introduction of cellular automata on Cayley graphs, and their characterization via the fundamental Cutis-Hedlund-Lyndon theorems in the context of different topological concepts (Cantor, Besicovitch and Weyl topology). The second part focuses on classification results: What classification follows from topological concepts (Hurley classification), Lyapunov stability (Gilman classification), and the theory of formal languages and grammars (Kůrka classification). These classifications suggest to cluster cel...

  18. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

    As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

  19. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

    Directory of Open Access Journals (Sweden)

    Giovanni Dalmasso

    Full Text Available Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis and the removal of damaged mitochondria by selective autophagy (mitophagy. While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1 mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2 restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3 maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4 our model suggests sources of, and stress conditions

  20. Liability for damage to the global commons

    International Nuclear Information System (INIS)

    Leigh, K.

    1993-01-01

    The 'global commons' discussed in this paper are the areas beyond the limits of national jurisdiction. Responsibility to prevent environmental damage to these areas is clearly recognized in customary international law. On the other hand, although liability for such damage undoubtedly has a useful role to play in protecting these areas, the precise nature of liability for such damage is unclear. Some issues, such as whether liability for such damage is strict or tied to breaching a standard of care and the definition of environmental damage, equally arise in relation to damage to the environment of States. Others, such as who could take action to enforce the liability and the nature of the remedy, raise special problems in the case of damage to the global commons. The work under way in the IAEA Standing Committee on Liability for Nuclear Damage provides an opportunity for clarifying these issues in relation to nuclear damage to the global commons. Treaties dealing with particular types of damage which have recently been adopted or are currently being developed in other fields provide a starting point in dealing with this matter. More work, however, needs to be done

  1. Programmable cellular arrays. Faults testing and correcting in cellular arrays

    International Nuclear Information System (INIS)

    Cercel, L.

    1978-03-01

    A review of some recent researches about programmable cellular arrays in computing and digital processing of information systems is presented, and includes both combinational and sequential arrays, with full arbitrary behaviour, or which can realize better implementations of specialized blocks as: arithmetic units, counters, comparators, control systems, memory blocks, etc. Also, the paper presents applications of cellular arrays in microprogramming, in implementing of a specialized computer for matrix operations, in modeling of universal computing systems. The last section deals with problems of fault testing and correcting in cellular arrays. (author)

  2. Influence of physical and biological factors in cellular radiosensitivity

    International Nuclear Information System (INIS)

    García Lima, Omar

    2016-01-01

    The use of therapeutic radiopharmaceuticals is associated with radiation damage, and this at-nuclear physical properties of radionuclides used and the characteristics of the irradiated cells. The work deals with the damage caused by radiation to DNA, factors that condition and tools that can be used to measure it. It presents current concepts of death and cellular radiosensitivity, based on the pioneering work in this field. Enter the neighborhood effect and adaptive response and evaluates the influence of the same in the paradigms of classical radiobiology. (author)

  3. The DNA damage response in mammalian oocytes

    Directory of Open Access Journals (Sweden)

    John eCarroll

    2013-06-01

    Full Text Available DNA damage is one of the most common insults that challenge all cells. To cope, an elaborate molecular and cellular response has evolved to sense, respond to and correct the damage. This allows the maintenance of DNA fidelity essential for normal cell viability and the prevention of genomic instability that can lead to tumour formation. In the context of oocytes, the impact of DNA damage is not one of tumour formation but of the maintenance of fertility. Mammalian oocytes are particularly vulnerable to DNA damage because physiologically they may lie dormant in the ovary for many years (>40 in humans until they receive the stimulus to grow and acquire the competence to become fertilized. The implication of this is that in some organisms, such as humans, oocytes face the danger of cumulative genetic damage for decades. Thus, the ability to detect and repair DNA damage is essential to maintain the supply of oocytes necessary for reproduction. Therefore, failure to confront DNA damage in oocytes could cause serious anomalies in the embryo that may be propagated in the form of mutations to the next generation allowing the appearance of hereditary disease. Despite the potential impact of DNA damage on reproductive capacity and genetic fidelity of embryos, the mechanisms available to the oocyte for monitoring and repairing such insults have remained largely unexplored until recently. Here, we review the different aspects of the response to DNA damage in mammalian oocytes. Specifically, we address the oocyte DNA damage response from embryonic life to adulthood and throughout oocyte development.

  4. Colonization of bone matrices by cellular components

    Science.gov (United States)

    Shchelkunova, E. I.; Voropaeva, A. A.; Korel, A. V.; Mayer, D. A.; Podorognaya, V. T.; Kirilova, I. A.

    2017-09-01

    Practical surgery, traumatology, orthopedics, and oncology require bioengineered constructs suitable for replacement of large-area bone defects. Only rigid/elastic matrix containing recipient's bone cells capable of mitosis, differentiation, and synthesizing extracellular matrix that supports cell viability can comply with these requirements. Therefore, the development of the techniques to produce structural and functional substitutes, whose three-dimensional structure corresponds to the recipient's damaged tissues, is the main objective of tissue engineering. This is achieved by developing tissue-engineering constructs represented by cells placed on the matrices. Low effectiveness of carrier matrix colonization with cells and their uneven distribution is one of the major problems in cell culture on various matrixes. In vitro studies of the interactions between cells and material, as well as the development of new techniques for scaffold colonization by cellular components are required to solve this problem.

  5. Radiation damage of nonmetallic solids

    International Nuclear Information System (INIS)

    Goland, A.N.

    1975-01-01

    A review of data and information on radiation damage in nonmetallic solids is presented. Discussions are included on defects in nonmetals, radiation damage processes in nonmetals, electronic damage processes, physical damage processes, atomic displacement, photochemical damage processes, and ion implantation

  6. Cellular mechanisms of noise-induced hearing loss.

    Science.gov (United States)

    Kurabi, Arwa; Keithley, Elizabeth M; Housley, Gary D; Ryan, Allen F; Wong, Ann C-Y

    2017-06-01

    Exposure to intense sound or noise can result in purely temporary threshold shift (TTS), or leave a residual permanent threshold shift (PTS) along with alterations in growth functions of auditory nerve output. Recent research has revealed a number of mechanisms that contribute to noise-induced hearing loss (NIHL). The principle cause of NIHL is damage to cochlear hair cells and associated synaptopathy. Contributions to TTS include reversible damage to hair cell (HC) stereocilia or synapses, while moderate TTS reflects protective purinergic hearing adaptation. PTS represents permanent damage to or loss of HCs and synapses. While the substrates of HC damage are complex, they include the accumulation of reactive oxygen species and the active stimulation of intracellular stress pathways, leading to programmed and/or necrotic cell death. Permanent damage to cochlear neurons can also contribute to the effects of NIHL, in addition to HC damage. These mechanisms have translational potential for pharmacological intervention and provide multiple opportunities to prevent HC damage or to rescue HCs and spiral ganglion neurons that have suffered injury. This paper reviews advances in our understanding of cellular mechanisms that contribute to NIHL and their potential for therapeutic manipulation. Published by Elsevier B.V.

  7. Top-down cellular pyramids

    Energy Technology Data Exchange (ETDEWEB)

    Wu, A Y; Rosenfeld, A

    1983-10-01

    A cellular pyramid is an exponentially tapering stack of arrays of processors (cells), where each cell is connected to its neighbors (siblings) on its own level, to a parent on the level above, and to its children on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case. 23 references.

  8. The cellular adaptive response the role in life organisms

    International Nuclear Information System (INIS)

    Smith, H.

    1998-01-01

    Exposure of living cells to ionizing radiation may cause DNA damage that are generally harmful to the organism. This paper discuss the cellular adaptive response which may be seen when cells which have already been exposed to low concentration radiation doses are subsequently exposed to high concentration doses. It also discusses evidence of the adaptive response in laboratory animals and from limited epidemiological studies. (Author)

  9. Radiation induced DNA damage and repair in mutagenesis

    International Nuclear Information System (INIS)

    Strniste, G.F.; Chen, D.J.; Okinaka, R.T.

    1987-01-01

    The central theme in cellular radiobiological research has been the mechanisms of radiation action and the physiological response of cells to this action. Considerable effort has been directed toward the characterization of radiation-induced DNA damage and the correlation of this damage to cellular genetic change that is expressed as mutation or initiating events leading to cellular transformation and ultimately carcinogenesis. In addition, there has been a significant advancement in their understanding of the role of DNA repair in the process of mutation leading to genetic change in cells. There is extensive literature concerning studies that address radiation action in both procaryotic and eucaryotic systems. This brief report will make no attempt to summarize this voluminous data but will focus on recent results from their laboratory of experiments in which they have examined, at both the cellular and molecular levels, the process of ionizing radiation-induced mutagenesis in cultured human cells

  10. Compensation for damage in the case of transfrontier reactor accidents

    International Nuclear Information System (INIS)

    Gornig, G.

    1986-01-01

    The author discusses possibilities to recover in German and Soviet courts claims for the compensation of damage for a German citizen arising from the reactor accident in Chernobyl. Concerning the claims for damage suffered in the Federal Republic of Germany he investigates possible breaches of bilateral or multilateral international agreements and of universal international law by the Soviet Union. (WG) [de

  11. Shock enhancement of cellular materials subjected to intensive pulse loading

    Science.gov (United States)

    Zhang, J.; Fan, J.; Wang, Z.; Zhao, L.; Li, Z.

    2018-03-01

    Cellular materials can dissipate a large amount of energy due to their considerable stress plateau, which contributes to their extensive applications in structural design for crashworthiness. However, in some experiments with specimens subjected to intense impact loads, transmitted stress enhancement has been observed, leading to severe damage to the objects protected. Transmitted stress through two-dimensional Voronoi cellular materials as a protective device is qualitatively studied in this paper. Dimensionless parameters of material properties and loading parameters are defined to give critical conditions for shock enhancement and clarify the correlation between the deformations and stress enhancement. The effect of relative density on this amplifying phenomenon is investigated as well. In addition, local strain fields are calculated by using the optimal local deformation gradient, which gives a clear presentation of deformations and possible local non-uniformity in the crushing process. This research provides valuable insight into the reliability of cellular materials as protective structures.

  12. Femoral nerve damage (image)

    Science.gov (United States)

    The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

  13. Mesoscopic analysis of drying shrinkage damage in a cementitious material

    DEFF Research Database (Denmark)

    Moonen, P.; Pedersen, R.R.; Simone, A.

    2008-01-01

    Concrete and cement-based materials exhibit shrinkage when exposed to drying. Structural effects and inhomogeneity of material properties adverse free shrinkage, hereby inducing stress concentrations and possibly damage. In this contribution, the magnitude of shrinkage- induced damage during...... temperatures are considered: 35 °C and 50 °C. Significantly more micro-damage and higher internal stresses are found for the latter, revealing the importance of drying shrinkage damage, even at laboratory scale....

  14. Cellular senescence and organismal aging.

    Science.gov (United States)

    Jeyapalan, Jessie C; Sedivy, John M

    2008-01-01

    Cellular senescence, first observed and defined using in vitro cell culture studies, is an irreversible cell cycle arrest which can be triggered by a variety of factors. Emerging evidence suggests that cellular senescence acts as an in vivo tumor suppression mechanism by limiting aberrant proliferation. It has also been postulated that cellular senescence can occur independently of cancer and contribute to the physiological processes of normal organismal aging. Recent data have demonstrated the in vivo accumulation of senescent cells with advancing age. Some characteristics of senescent cells, such as the ability to modify their extracellular environment, could play a role in aging and age-related pathology. In this review, we examine current evidence that links cellular senescence and organismal aging.

  15. Origami interleaved tube cellular materials

    International Nuclear Information System (INIS)

    Cheung, Kenneth C; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

    2014-01-01

    A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis. (paper)

  16. Origami interleaved tube cellular materials

    Science.gov (United States)

    Cheung, Kenneth C.; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

    2014-09-01

    A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis.

  17. Cellular Angiofibroma of the Nasopharynx.

    Science.gov (United States)

    Erdur, Zülküf Burak; Yener, Haydar Murat; Yilmaz, Mehmet; Karaaltin, Ayşegül Batioğlu; Inan, Hakki Caner; Alaskarov, Elvin; Gozen, Emine Deniz

    2017-11-01

    Angiofibroma is a common tumor of the nasopharynx region but cellular type is extremely rare in head and neck. A 13-year-old boy presented with frequent epistaxis and nasal obstruction persisting for 6 months. According to the clinical symptoms and imaging studies juvenile angiofibroma was suspected. Following angiographic embolization total excision of the lesion by midfacial degloving approach was performed. Histological examination revealed that the tumor consisted of staghorn blood vessels and irregular fibrous stroma. Stellate fibroblasts with small pyknotic to large vesicular nuclei were seen in a highly cellular stroma. These findings identified cellular angiofibroma mimicking juvenile angiofibroma. This article is about a very rare patient of cellular angiofibroma of nasopharynx.

  18. Antibody-dependent cellular cytotoxicity and skin disease

    International Nuclear Information System (INIS)

    Norris, D.A.; Lee, L.A.

    1985-01-01

    Antibody dependent cellular cytotoxicity (ADCC) is a recently described mechanism of immunologic lysis in which cellular targets sensitized by specific antibodies are efficiently and selectively lysed by Fc receptor (FcR) bearing nonspecific effectors. Immunoglobulins of various classes (IgG, IgM, IgA, IgE) and various cellular effectors (large granular lymphocytes, monocyte/macrophages, T lymphocytes, neutrophils, and eosinophils) can induce ADCC in vitro, and the importance of ADCC in vivo is being tested experimentally in resistance to viral, bacterial, and parasitic infection, in tumor surveillance, in allograft rejection, and in inflammatory diseases. There is much indirect evidence that ADCC may be the mechanism of damage of different cellular targets in skin diseases, but the best direct evidence concerns immunologic keratinocyte damage, especially in cutaneous lupus erythematosus (LE). The authors have shown that keratinocytes of several species are highly susceptible to lymphocyte and monocyte-mediated ADCC, but not to neutrophil or eosinophil ADCC in vitro using two different cytotoxicity assays. In contrast, complement was a relatively ineffective mediator of lysis of metabolically intact keratinocyte targets. Patients with certain cutaneous lupus syndromes have serum antibodies capable of inducing monocyte and lymphocyte ADCC of targets coated with extractable nuclear antigens. The authors have shown that these antigens apparently move to the cell membrane of keratinocytes in vitro following ultraviolet irradiation. In an animal model, they have shown that antibodies to SSA/Ro bind to human keratinocytes in vivo, especially after ultraviolet irradiation

  19. Evaluation of cellular influences caused by calcium carbonate nanoparticles.

    Science.gov (United States)

    Horie, Masanori; Nishio, Keiko; Kato, Haruhisa; Endoh, Shigehisa; Fujita, Katsuhide; Nakamura, Ayako; Kinugasa, Shinichi; Hagihara, Yoshihisa; Yoshida, Yasukazu; Iwahashi, Hitoshi

    2014-03-05

    The cellular effects of calcium carbonate (CaCO₃) nanoparticles were evaluated. Three kinds of CaCO₃ nanoparticles were employed in our examinations. One of the types of CaCO₃ nanoparticles was highly soluble. And solubility of another type of CaCO₃ nanoparticle was lower. A stable CaCO₃ nanoparticle medium dispersion was prepared and applied to human lung carcinoma A549 cells and human keratinocyte HaCaT cells. Then, mitochondrial activity, cell membrane damage, colony formation ability, DNA injury, induction of oxidative stress, and apoptosis were evaluated. Although the influences of CaCO₃ nanoparticles on mitochondrial activity and cell membrane damage were small, "soluble" CaCO₃ nanoparticles exerted some cellular influences. Soluble CaCO₃ nanoparticles also induced a cell morphological change. Colony formation was inhibited by CaCO₃ nanoparticle exposure. In particular, soluble CaCO₃ nanoparticles completely inhibited colony formation. The influence on intracellular the reactive oxygen species (ROS) level was small. Soluble CaCO₃ nanoparticles caused an increase in C/EBP-homologous protein (CHOP) expression and the activation of caspase-3. Moreover, CaCO₃ exposure increased intracellular the Ca²⁺ level and activated calpain. These results suggest that cellular the influences of CaCO₃ nanoparticles are mainly caused by intracellular calcium release and subsequently disrupt the effect of calcium signaling. In conclusion, there is possibility that soluble CaCO₃ nanoparticles induce cellular influences such as a cell morphological change. Cellular influence of CaCO₃ nanoparticles is caused by intracellular calcium release. If inhaled CaCO₃ nanoparticles have the potential to influence cellular events. However, the effect might be not severe because calcium is omnipresent element in cell. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. [Stress-induced cellular adaptive mutagenesis].

    Science.gov (United States)

    Zhu, Linjiang; Li, Qi

    2014-04-01

    The adaptive mutations exist widely in the evolution of cells, such as antibiotic resistance mutations of pathogenic bacteria, adaptive evolution of industrial strains, and cancerization of human somatic cells. However, how these adaptive mutations are generated is still controversial. Based on the mutational analysis models under the nonlethal selection conditions, stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint. The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses, including DNA damages caused by accumulation of intracellular toxic chemicals, limitation of DNA MMR (mismatch repair) activity, upregulation of general stress response and activation of SOS response. These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one. The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity. In addition, gene transcription under stress condition increases the instability of genome in response to DNA damage, resulting in transcription-associated DNA mutagenesis. In this review, we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

  1. Balancing repair and tolerance of DNA damage caused by alkylating agents

    OpenAIRE

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D.

    2012-01-01

    Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial ...

  2. SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

    OpenAIRE

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

    2012-01-01

    Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial fo...

  3. Damage Stability Assessment of an HSC after Grounding

    DEFF Research Database (Denmark)

    Ravn, Erik Sonne; Simonsen, Bo Cerup; Baatrup, Jan

    2000-01-01

    Currently a substantial effort is done within the International Maritime Organisation (IMO) on revision of the High Speed Craft (HSC) Code. A main issue is the extent of bottom damage and raking damage due to grounding on hard rocks and the corresponding requirements to the damage stability...... of the vessel. It has been found that high-speed craft can experience a damage length up to 100% of the ship length. It has, however, also been argued that the damage stability requirements should reflect the size and probability of the damage with a reduction of the demand for the largest damages.......In the present paper a detailed grounding and damage stability analysis is carried out for two specific HSC, a mono-hull (86 m) and a catamaran (69 m). First various grounding scenarios are considered with different values of the forward speed and ground geometry. The results indicate that 100% bottom damage...

  4. Convention on supplementary compensation for nuclear damage

    International Nuclear Information System (INIS)

    Chinese Nuclear Society, Beijing; U.S. Nuclear Energy Institute

    2000-01-01

    The Contracting parties recognize the importance of the measures provided in the Vienna Convention on Civil Liability for Nuclear Damage and the Paris Convention on Third party liability in the Field of Nuclear Energy as well as in national legislation on compensation for nuclear damage consistent with the principles of these conventions. The Contracting parties desire to establish a worldwide liability regime to supplement and enhance these measures with a view to increasing the amount of compensation for nuclear damage and encourage regional and global co-operation to promote a higher level of nuclear safety in accordance with the principle of international partnership and solidarity

  5. Modulation of cellular radiation responses by 2-deoxy-D-glucose and other glycolytic inhibitors: Implications for cancer therapy

    OpenAIRE

    Kalia Vijay; Prabhakara S; Narayanan Vidya

    2009-01-01

    Background: 2-Deoxy-D-glucose (2-DG), a glycolytic inhibitor, was observed earlier to increase DNA, chromosomal, and cellular damage in tumor cells, by inhibiting energy-dependent repair processes. Lonidamine (LND) selectively inhibits glycolysis in cancer cells. It damages the condensed mitochondria in these cells, impairing thereby the activity of hexokinase (predominantly attached to the outer mitochondrial membranes). It inhibits repair of radiation-induced potentially lethal cellular da...

  6. DNA Damage Response and Immune Defence: Links and Mechanisms

    Directory of Open Access Journals (Sweden)

    Björn Schumacher

    2016-08-01

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

  7. Radiation damage in biomolecular systems

    CERN Document Server

    Fuss, Martina Christina

    2012-01-01

    Since the discovery of X-rays and radioactivity, ionizing radiations have been widely applied in medicine both for diagnostic and therapeutic purposes. The risks associated with radiation exposure and handling led to the parallel development of the field of radiation protection. Pioneering experiments done by Sanche and co-workers in 2000 showed that low-energy secondary electrons, which are abundantly generated along radiation tracks, are primarily responsible for radiation damage through successive interactions with the molecular constituents of the medium. Apart from ionizing processes, which are usually related to radiation damage, below the ionization level low-energy electrons can induce molecular fragmentation via dissociative processes such as internal excitation and electron attachment. This prompted collaborative projects between different research groups from European countries together with other specialists from Canada,  the USA and Australia. This book summarizes the advances achieved by these...

  8. Cellular membrane trafficking of mesoporous silica nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Fang, I-Ju [Iowa State Univ., Ames, IA (United States)

    2012-01-01

    This dissertation mainly focuses on the investigation of the cellular membrane trafficking of mesoporous silica nanoparticles. We are interested in the study of endocytosis and exocytosis behaviors of mesoporous silica nanoparticles with desired surface functionality. The relationship between mesoporous silica nanoparticles and membrane trafficking of cells, either cancerous cells or normal cells was examined. Since mesoporous silica nanoparticles were applied in many drug delivery cases, the endocytotic efficiency of mesoporous silica nanoparticles needs to be investigated in more details in order to design the cellular drug delivery system in the controlled way. It is well known that cells can engulf some molecules outside of the cells through a receptor-ligand associated endocytosis. We are interested to determine if those biomolecules binding to cell surface receptors can be utilized on mesoporous silica nanoparticle materials to improve the uptake efficiency or govern the mechanism of endocytosis of mesoporous silica nanoparticles. Arginine-glycine-aspartate (RGD) is a small peptide recognized by cell integrin receptors and it was reported that avidin internalization was highly promoted by tumor lectin. Both RGD and avidin were linked to the surface of mesoporous silica nanoparticle materials to investigate the effect of receptor-associated biomolecule on cellular endocytosis efficiency. The effect of ligand types, ligand conformation and ligand density were discussed in Chapter 2 and 3. Furthermore, the exocytosis of mesoporous silica nanoparticles is very attractive for biological applications. The cellular protein sequestration study of mesoporous silica nanoparticles was examined for further information of the intracellular pathway of endocytosed mesoporous silica nanoparticle materials. The surface functionality of mesoporous silica nanoparticle materials demonstrated selectivity among the materials and cancer and normal cell lines. We aimed to determine

  9. 11th International Conference of Radiation Research

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-07-18

    Topics discussed in the conference included the following: Radiation Physics, Radiation Chemistry and modelling--Radiation physics and dosimetry; Electron transfer in biological media; Radiation chemistry; Biophysical and biochemical modelling; Mechanisms of DNA damage; Assays of DNA damage; Energy deposition in micro volumes; Photo-effects; Special techniques and technologies; Oxidative damage. Molecular and cellular effects-- Photobiology; Cell cycle effects; DNA damage: Strand breaks; DNA damage: Bases; DNA damage Non-targeted; DNA damage: other; Chromosome aberrations: clonal; Chromosomal aberrations: non-clonal; Interactions: Heat/Radiation/Drugs; Biochemical effects; Protein expression; Gene induction; Co-operative effects; ``Bystander'' effects; Oxidative stress effects; Recovery from radiation damage. DNA damage and repair -- DNA repair genes; DNA repair deficient diseases; DNA repair enzymology; Epigenetic effects on repair; and Ataxia and ATM.

  10. The DNA damage response during mitosis

    International Nuclear Information System (INIS)

    Heijink, Anne Margriet; Krajewska, Małgorzata; Vugt, Marcel A.T.M. van

    2013-01-01

    Cells are equipped with a cell-intrinsic signaling network called the DNA damage response (DDR). This signaling network recognizes DNA lesions and initiates various downstream pathways to coordinate a cell cycle arrest with the repair of the damaged DNA. Alternatively, the DDR can mediate clearance of affected cells that are beyond repair through apoptosis or senescence. The DDR can be activated in response to DNA damage throughout the cell cycle, although the extent of DDR signaling is different in each cell cycle phase. Especially in response to DNA double strand breaks, only a very marginal response was observed during mitosis. Early on it was recognized that cells which are irradiated during mitosis continued division without repairing broken chromosomes. Although these initial observations indicated diminished DNA repair and lack of an acute DNA damage-induced cell cycle arrest, insight into the mechanistic re-wiring of DDR signaling during mitosis was only recently provided. Different mechanisms appear to be at play to inactivate specific signaling axes of the DDR network in mitosis. Importantly, mitotic cells not simply inactivate the entire DDR, but appear to mark their DNA damage for repair after mitotic exit. Since the treatment of cancer frequently involves agents that induce DNA damage as well as agents that block mitotic progression, it is clinically relevant to obtain a better understanding of how cancer cells deal with DNA damage during interphase versus mitosis. In this review, the molecular details concerning DDR signaling during mitosis as well as the consequences of encountering DNA damage during mitosis for cellular fate are discussed

  11. The DNA damage response during mitosis

    Energy Technology Data Exchange (ETDEWEB)

    Heijink, Anne Margriet; Krajewska, Małgorzata; Vugt, Marcel A.T.M. van, E-mail: m.vugt@umcg.nl

    2013-10-15

    Cells are equipped with a cell-intrinsic signaling network called the DNA damage response (DDR). This signaling network recognizes DNA lesions and initiates various downstream pathways to coordinate a cell cycle arrest with the repair of the damaged DNA. Alternatively, the DDR can mediate clearance of affected cells that are beyond repair through apoptosis or senescence. The DDR can be activated in response to DNA damage throughout the cell cycle, although the extent of DDR signaling is different in each cell cycle phase. Especially in response to DNA double strand breaks, only a very marginal response was observed during mitosis. Early on it was recognized that cells which are irradiated during mitosis continued division without repairing broken chromosomes. Although these initial observations indicated diminished DNA repair and lack of an acute DNA damage-induced cell cycle arrest, insight into the mechanistic re-wiring of DDR signaling during mitosis was only recently provided. Different mechanisms appear to be at play to inactivate specific signaling axes of the DDR network in mitosis. Importantly, mitotic cells not simply inactivate the entire DDR, but appear to mark their DNA damage for repair after mitotic exit. Since the treatment of cancer frequently involves agents that induce DNA damage as well as agents that block mitotic progression, it is clinically relevant to obtain a better understanding of how cancer cells deal with DNA damage during interphase versus mitosis. In this review, the molecular details concerning DDR signaling during mitosis as well as the consequences of encountering DNA damage during mitosis for cellular fate are discussed.

  12. The DNA damage response during mitosis.

    Science.gov (United States)

    Heijink, Anne Margriet; Krajewska, Małgorzata; van Vugt, Marcel A T M

    2013-10-01

    Cells are equipped with a cell-intrinsic signaling network called the DNA damage response (DDR). This signaling network recognizes DNA lesions and initiates various downstream pathways to coordinate a cell cycle arrest with the repair of the damaged DNA. Alternatively, the DDR can mediate clearance of affected cells that are beyond repair through apoptosis or senescence. The DDR can be activated in response to DNA damage throughout the cell cycle, although the extent of DDR signaling is different in each cell cycle phase. Especially in response to DNA double strand breaks, only a very marginal response was observed during mitosis. Early on it was recognized that cells which are irradiated during mitosis continued division without repairing broken chromosomes. Although these initial observations indicated diminished DNA repair and lack of an acute DNA damage-induced cell cycle arrest, insight into the mechanistic re-wiring of DDR signaling during mitosis was only recently provided. Different mechanisms appear to be at play to inactivate specific signaling axes of the DDR network in mitosis. Importantly, mitotic cells not simply inactivate the entire DDR, but appear to mark their DNA damage for repair after mitotic exit. Since the treatment of cancer frequently involves agents that induce DNA damage as well as agents that block mitotic progression, it is clinically relevant to obtain a better understanding of how cancer cells deal with DNA damage during interphase versus mitosis. In this review, the molecular details concerning DDR signaling during mitosis as well as the consequences of encountering DNA damage during mitosis for cellular fate are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Cellular-based preemption system

    Science.gov (United States)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

    A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

  14. Novel Materials for Cellular Nanosensors

    DEFF Research Database (Denmark)

    Sasso, Luigi

    The monitoring of cellular behavior is useful for the advancement of biomedical diagnostics, drug development and the understanding of a cell as the main unit of the human body. Micro- and nanotechnology allow for the creation of functional devices that enhance the study of cellular dynamics...... modifications for electrochemical nanosensors for the detection of analytes released from cells. Two type of materials were investigated, each pertaining to the two different aspects of such devices: peptide nanostructures were studied for the creation of cellular sensing substrates that mimic in vivo surfaces...... and that offer advantages of functionalization, and conducting polymers were used as electrochemical sensor surface modifications for increasing the sensitivity towards relevant analytes, with focus on the detection of dopamine released from cells via exocytosis. Vertical peptide nanowires were synthesized from...

  15. Global properties of cellular automata

    International Nuclear Information System (INIS)

    Jen, E.

    1986-01-01

    Cellular automata are discrete mathematical systems that generate diverse, often complicated, behavior using simple deterministic rules. Analysis of the local structure of these rules makes possible a description of the global properties of the associated automata. A class of cellular automata that generate infinitely many aperoidic temporal sequences is defined,a s is the set of rules for which inverses exist. Necessary and sufficient conditions are derived characterizing the classes of ''nearest-neighbor'' rules for which arbitrary finite initial conditions (i) evolve to a homogeneous state; (ii) generate at least one constant temporal sequence

  16. Cellular structures with interconnected microchannels

    Science.gov (United States)

    Shaefer, Robert Shahram; Ghoniem, Nasr M.; Williams, Brian

    2018-01-30

    A method for fabricating a cellular tritium breeder component includes obtaining a reticulated carbon foam skeleton comprising a network of interconnected ligaments. The foam skeleton is then melt-infiltrated with a tritium breeder material, for example, lithium zirconate or lithium titanate. The foam skeleton is then removed to define a cellular breeder component having a network of interconnected tritium purge channels. In an embodiment the ligaments of the foam skeleton are enlarged by adding carbon using chemical vapor infiltration (CVI) prior to melt-infiltration. In an embodiment the foam skeleton is coated with a refractory material, for example, tungsten, prior to melt infiltration.

  17. Force control for mechanoinduction of impedance variation in cellular organisms

    International Nuclear Information System (INIS)

    Nam, Joo Hoo; Chen, Peter C Y; Lu, Zhe; Luo, Hong; Lin, Wei; Ge, Ruowen

    2010-01-01

    Constantly exposed to various forms of mechanical forces inherent in their physical environment (such as gravity, stress induced by fluid flow or cell–cell interactions, etc), cellular organisms sense such forces and convert them into biochemical signals through the processes of mechanosensing and mechanotransduction that eventually lead to biological changes. The effect of external forces on the internal structures and activities in a cellular organism may manifest in changes its physical properties, such as impedance. Studying variation in the impedance of a cellular organism induced by the application of an external mechanical force represents a meaningful endeavor (from a biosystems perspective) in exploring the complex mechanosensing and mechanotransduction mechanisms that govern the behavior of a cellular organism under the influence of external mechanical stimuli. In this paper we describe the development of an explicit force-feedback control system for exerting an indentation force on a cellular organism while simultaneously measuring its impedance. To demonstrate the effectiveness of this force-control system, we have conducted experiments using zebrafish embryos as a test model of a cellular organism. We report experimental results demonstrating that the application of a properly controlled external force leads to a significant change in the impedance of a zebrafish embryo. These results offer support for a plausible explanation that activities of pore canals in the chorion are responsible for the observed change in impedance.

  18. Cell damage by bilirubin and light

    International Nuclear Information System (INIS)

    Granli, T.

    1993-01-01

    Large doses of light are given to newborns during phototherapy for hyperbilirubinemia. Tissues containing concentrations of bilirubin almost in the mM range may be subjected to irradiation. Therefore it is of interest to study cellular effects of light and bilirubin on cells. In order to select the optimal wavelength, possible detrimental effects of light on cells must be taken into consideration among a number of other factors. In this study cellular effects of selected wavelengths of blue-green light are compared. It is not clear whether cullular damage occurs in vivo during phototherapy of newborns. Since a possibility exists that some adverse effects are caused by light, one should choose wavelengths where these effects are minimal without loosing therapeutic efficiency. Todays knowledge of the photochemical mechanisms of phototherapy, indicates that short waved light with wavelengths below 450 nm has a low therapeutic effect. The data in this paper indicate that the cellular damage is most severe at short wavelengths, and these should be reduced to a minimum in the spectra of phototherapy lamps. Further studies of possible side effects of phototherapy should be made. 64 refs., 34 figs., 1 tab

  19. Molecular and cellular mechanisms of cadmium carcinogenesis

    International Nuclear Information System (INIS)

    Waisberg, Michael; Joseph, Pius; Hale, Beverley; Beyersmann, Detmar

    2003-01-01

    Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd 2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate

  20. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN...

  1. Repaglinide at a cellular level

    DEFF Research Database (Denmark)

    Krogsgaard Thomsen, M; Bokvist, K; Høy, M

    2002-01-01

    To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in ra...

  2. Cellular automaton for surface reactions

    Energy Technology Data Exchange (ETDEWEB)

    Pechatnikov, E L [AN SSSR, Chernogolovka (Russian Federation). Otdelenie Inst. Khimicheskoj Fiziki; Frankowicz, A; Danielak, R [Uniwersytet Jagiellonski, Cracow (Poland)

    1994-06-01

    A new algorithm which overcomes some specific difficulties arising in modeling of heterogeneous catalytic processes by cellular automata (CA) technique is proposed. The algorithm was tested with scheme introduced by Ziff, Gulari and Barshad and showed a good agreement with their results. The problem of the physical adequacy and interpretation of the algorithm was discussed. (author). 10 refs, 4 figs.

  3. Cellular Automata and the Humanities.

    Science.gov (United States)

    Gallo, Ernest

    1994-01-01

    The use of cellular automata to analyze several pre-Socratic hypotheses about the evolution of the physical world is discussed. These hypotheses combine characteristics of both rigorous and metaphoric language. Since the computer demands explicit instructions for each step in the evolution of the automaton, such models can reveal conceptual…

  4. Cellular buckling in long structures

    NARCIS (Netherlands)

    Hunt, G.W.; Peletier, M.A.; Champneys, A.R.; Woods, P.D.; Wadee, M.A.; Budd, C.J.; Lord, G.J.

    2000-01-01

    A long structural system with an unstable (subcritical)post-buckling response that subsequently restabilizes typically deformsin a cellular manner, with localized buckles first forming and thenlocking up in sequence. As buckling continues over a growing number ofcells, the response can be described

  5. Information theory based approaches to cellular signaling.

    Science.gov (United States)

    Waltermann, Christian; Klipp, Edda

    2011-10-01

    Cells interact with their environment and they have to react adequately to internal and external changes such changes in nutrient composition, physical properties like temperature or osmolarity and other stresses. More specifically, they must be able to evaluate whether the external change is significant or just in the range of noise. Based on multiple external parameters they have to compute an optimal response. Cellular signaling pathways are considered as the major means of information perception and transmission in cells. Here, we review different attempts to quantify information processing on the level of individual cells. We refer to Shannon entropy, mutual information, and informal measures of signaling pathway cross-talk and specificity. Information theory in systems biology has been successfully applied to identification of optimal pathway structures, mutual information and entropy as system response in sensitivity analysis, and quantification of input and output information. While the study of information transmission within the framework of information theory in technical systems is an advanced field with high impact in engineering and telecommunication, its application to biological objects and processes is still restricted to specific fields such as neuroscience, structural and molecular biology. However, in systems biology dealing with a holistic understanding of biochemical systems and cellular signaling only recently a number of examples for the application of information theory have emerged. This article is part of a Special Issue entitled Systems Biology of Microorganisms. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. The DNA-damage response in human biology and disease

    DEFF Research Database (Denmark)

    Jackson, Stephen P; Bartek, Jiri

    2009-01-01

    , signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management....

  7. Damage-induced tensile instability

    International Nuclear Information System (INIS)

    Hult, J.

    1975-01-01

    The paper presents a unified description of ductile and brittle rupture phenomena in structural components under tensile loading with particular emphasis on creep rupture. Two structural elements are analyzed in detail: 1) the uniform tensile bar subject to a Heaviside history of tensile force and superimposed such loadings, i.e. staircase histories, and 2) the thinwalled spherical pressure vessel subject to a Heaviside history of internal pressure. For both these structures the conditions for instantaneous as well as delayed rupture are analysed. It is shown that a state of mechanical instability will be reached at a certain load or after a certain time. The cases of purely ductile rupture and purely brittle fracture are identified as two limiting cases of this general instability phenomenon. The Kachanov-Rabotnov damage law implies that a structural component will fail in tension only when it has reached a state of complete damage, i.e. zero load carrying capacity. The extended law predicts failure at an earlier stage of the deterioration process and is therefore more compatible with experimental observation. Further experimental support is offered by predictions for staircase loading histories, both step-up and step-down type. The presented damage theory here predicts strain histories which are in closer agreement with test data than predictions based on other phenomenological theories

  8. Radiation damage to mushrooms

    International Nuclear Information System (INIS)

    Sattler, P.W.

    1986-01-01

    This document contains newspaper cuttings and correspondence with various ministries in Hessen on the subject of radiation damage to mushrooms from the Odenwald area. The reader is given, amongst other things, detailed information on radiation damage to different types of mushroom in 1986. (MG) [de

  9. Animal damage to birch

    Science.gov (United States)

    James S. Jordan; Francis M. Rushmore

    1969-01-01

    A relatively few animal species are responsible for most of the reported damage to the birches. White-tailed deer, yellow-bellied sapsuckers, porcupines, moose, and hares are the major animals involved. We will review reports of damage, discuss the underlying causes, and describe possible methods of control. For example, heavy deer browsing that eliminates birch...

  10. Animal damage management handbook.

    Science.gov (United States)

    Hugh C. Black

    1994-01-01

    This handbook treats animal damage management (ADM) in the West in relation to forest, range, and recreation resources; predator management is not addressed. It provides a comprehensive reference of safe, effective, and practical methods for managing animal damage on National Forest System lands. Supporting information is included in references after each chapter and...

  11. Nuclear damage - civil liability

    International Nuclear Information System (INIS)

    Simoes, A.C.

    1980-01-01

    An analysis is made of the civil liability for nuclear damage since there is a need to adjust the existing rules to the new situations created. The conventions that set up the new disciplining rules not considered in the common law for the liability of nuclear damage are also mentioned. (A.L.) [pt

  12. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan

    2005-01-01

    Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva...... to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is inhibited...

  13. Cellular Chaperones As Therapeutic Targets in ALS to Restore Protein Homeostasis and Improve Cellular Function

    Directory of Open Access Journals (Sweden)

    Bernadett Kalmar

    2017-09-01

    Full Text Available Heat shock proteins (Hsps are ubiquitously expressed chaperone proteins that enable cells to cope with environmental stresses that cause misfolding and denaturation of proteins. With aging this protein quality control machinery becomes less effective, reducing the ability of cells to cope with damaging environmental stresses and disease-causing mutations. In neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS, such mutations are known to result in protein misfolding, which in turn results in the formation of intracellular aggregates cellular dysfunction and eventual neuronal death. The exact cellular pathology of ALS and other neurodegenerative diseases has been elusive and thus, hindering the development of effective therapies. However, a common scheme has emerged across these “protein misfolding” disorders, in that the mechanism of disease involves one or more aspects of proteostasis; from DNA transcription, RNA translation, to protein folding, transport and degradation via proteosomal and autophagic pathways. Interestingly, members of the Hsp family are involved in each of these steps facilitating normal protein folding, regulating the rate of protein synthesis and degradation. In this short review we summarize the evidence that suggests that ALS is a disease of protein dyshomeostasis in which Hsps may play a key role. Overwhelming evidence now indicates that enabling protein homeostasis to cope with disease-causing mutations might be a successful therapeutic strategy in ALS, as well as other neurodegenerative diseases. Novel small molecule co-inducers of Hsps appear to be able to achieve this aim. Arimoclomol, a hydroxylamine derivative, has shown promising results in cellular and animal models of ALS, as well as other protein misfolding diseases such as Inclusion Body Myositis (IBM. Initial clinical investigations of Arimoclomol have shown promising results. Therefore, it is possible that the long series of

  14. Recent trends in fracture and damage mechanics

    CERN Document Server

    Zybell, Lutz

    2016-01-01

    This book covers a wide range of topics in fracture and damage mechanics. It presents historical perspectives as well as recent innovative developments, presented by peer reviewed contributions from internationally acknowledged authors.  The volume deals with the modeling of fracture and damage in smart materials, current industrial applications of fracture mechanics, and it explores advances in fracture testing methods. In addition, readers will discover trends in the field of local approach to fracture and approaches using analytical mechanics. Scholars in the fields of materials science, engineering and computational science will value this volume which is dedicated to Meinhard Kuna on the occasion of his 65th birthday in 2015. This book incorporates the proceedings of an international symposium that was organized to honor Meinhard Kuna’s contributions to the field of theoretical and applied fracture and damage mechanics.

  15. 6th International Microbeam Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Dr Kevin M. Prise

    2004-01-01

    The extended abstracts which are submitted here present a summary of the proceedings of the 6th International Workshop/12th LH Gray Workshop: Microbeam Probes of Cellular Radiation Response, held at St. Catherine's College, University of Oxford, UK on March, 29th-31st, 2003. In 1993 the 4th LH Gray Workshop entitled ''Microbeam Probes of Cellular Radiation Response'' was held at the Gray Cancer Institute in Northwood. This was organized by Prof BD Michael, Dr M. Folkard and Dr KM Prise and brought together 40 participants interested in developing and applying new microbeam technology to problems in radiation biology (1). The workshop was an undoubted success and has spawned a series of subsequent workshops every two years. In the past, these workshops have been highly successful in bringing together groups interested in developing and applying micro-irradiation techniques to the study of cell and tissue damage by ionizing radiations. Following the first microbeam workshop, there has been a rapid growth in the number of centres developing radiobiology microbeams, or planning to do so and there are currently 15-20 worldwide. Much of the recent research using microbeams has used them to study low-dose effects and ''non-targeted'' responses such bystander effects, genomic instability and adaptive responses. The goal of the 6th workshop was to build on our knowledge of the development of microbeam approaches and the application to radiation biology in the future with the meeting stretching over a 3 day period. Over 80 participants reviewed the current state of radiobiology microbeam research worldwide and reported on new technological developments both in the fields of physics and biology.

  16. Potential cellular receptors involved in hepatitis C virus entry into cells

    Directory of Open Access Journals (Sweden)

    Muellhaupt Beat

    2005-04-01

    Full Text Available Abstract Hepatitis C virus (HCV infects hepatocytes and leads to permanent, severe liver damage. Since the genomic sequence of HCV was determined, progress has been made towards understanding the functions of the HCV-encoded proteins and identifying the cellular receptor(s responsible for adsorption and penetration of the virus particle into the target cells. Several cellular receptors for HCV have been proposed, all of which are associated with lipid and lipoprotein metabolism. This article reviews the cellular receptors for HCV and suggests a general model for HCV entry into cells, in which lipoproteins play a crucial role.

  17. Frost damage of concrete subject to confinement

    DEFF Research Database (Denmark)

    Hasholt, Marianne Tange

    2016-01-01

    When internal frost damage is observed in real concrete structures, the usual pattern is cracks with a preferred orientation parallel to the exposed surface. When exposing concrete with poor frost resistance to a standardised freeze/thaw test in the laboratory, the orientations of the resulting...

  18. Climate policy: Transparency for Loss and Damage

    Science.gov (United States)

    Mechler, Reinhard

    2017-10-01

    Loss and Damage (L&D) has been gaining traction since the Paris Agreement took the issue on as a separate article, arguably creating a third pillar of international climate policy. Debate so far has led to vague definitions of the remit of the L&D mechanism; research on actor perspectives may help to propel this discourse forward.

  19. 7 CFR 51.1560 - Damage.

    Science.gov (United States)

    2010-01-01

    ... of defects, which materially detracts from the edible or marketing quality, or the internal or... 7 Agriculture 2 2010-01-01 2010-01-01 false Damage. 51.1560 Section 51.1560 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing...

  20. Project of law authorizing the approval of the protocol at the convention of November 27, 1992 dealing with the creation of an international indemnification fund for the damages due to the pollution by hydrocarbons; Projet de loi autorisant l'approbation du protocole a la convention du 27 novembre 1992 portant creation d'un fonds international d'indemnisation pour les dommages dus a la pollution par les hydrocarbures

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-04-01

    A series of recent tanker-ship wrecks has shown the insufficiency of the international indemnification fund (FIPOL 71) created in December 18, 1971 by the international maritime organization for victims of oil spill damages. The total available amount of the fund was raised to about 160 million euros by the protocols adopted in 1992, but despite this improvement, the fund remained far below the real damage costs of the recent maritime catastrophes. For this reason, a new protocol has been created which implements a complementary fund which can mobilize an additional amount of about 662 million euros. This new protocol has also redefined the rules of the financial participation of the contracting states. The present document is a project of law authorizing the approval of this protocol by France. It recalls the historical events that led to its creation, the changes added with respect to the previous protocol and its juridical framework inside the European Community. The text of the new protocol is attached. (J.S.)

  1. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

    Science.gov (United States)

    Sada, Kiminori; Nishikawa, Takeshi; Kukidome, Daisuke; Yoshinaga, Tomoaki; Kajihara, Nobuhiro; Sonoda, Kazuhiro; Senokuchi, Takafumi; Motoshima, Hiroyuki; Matsumura, Takeshi; Araki, Eiichi

    2016-01-01

    We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

  2. Chromatin modifications and the DNA damage response to ionizing radiation

    International Nuclear Information System (INIS)

    Kumar, Rakesh; Horikoshi, Nobuo; Singh, Mayank; Gupta, Arun; Misra, Hari S.; Albuquerque, Kevin; Hunt, Clayton R.; Pandita, Tej K.

    2013-01-01

    In order to survive, cells have evolved highly effective repair mechanisms to deal with the potentially lethal DNA damage produced by exposure to endogenous as well as exogenous agents. Ionizing radiation exposure induces highly lethal DNA damage, especially DNA double-strand breaks (DSBs), that is sensed by the cellular machinery and then subsequently repaired by either of two different DSB repair mechanisms: (1) non-homologous end joining, which re-ligates the broken ends of the DNA and (2) homologous recombination, that employs an undamaged identical DNA sequence as a template, to maintain the fidelity of DNA repair. Repair of DSBs must occur within the natural context of the cellular DNA which, along with specific proteins, is organized to form chromatin, the overall structure of which can impede DNA damage site access by repair proteins. The chromatin complex is a dynamic structure and is known to change as required for ongoing cellular processes such as gene transcription or DNA replication. Similarly, during the process of DNA damage sensing and repair, chromatin needs to undergo several changes in order to facilitate accessibility of the repair machinery. Cells utilize several factors to modify the chromatin in order to locally open up the structure to reveal the underlying DNA sequence but post-translational modification of the histone components is one of the primary mechanisms. In this review, we will summarize chromatin modifications by the respective chromatin modifying factors that occur during the DNA damage response.

  3. Metabolite Damage and Metabolite Damage Control in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  4. Dynamic cellular uptake of mixed-monolayer protected nanoparticles.

    Science.gov (United States)

    Carney, Randy P; Carney, Tamara M; Mueller, Marie; Stellacci, Francesco

    2012-12-01

    Nanoparticles (NPs) are gaining increasing attention for potential application in medicine; consequently, studying their interaction with cells is of central importance. We found that both ligand arrangement and composition on gold nanoparticles play a crucial role in their cellular internalization. In our previous investigation, we showed that 66-34OT nanoparticles coated with stripe-like domains of hydrophobic (octanethiol, OT, 34%) and hydrophilic (11-mercaptoundecane sulfonate, MUS, 66%) ligands permeated through the cellular lipid bilayer via passive diffusion, in addition to endo-/pino-cytosis. Here, we show an analysis of NP internalization by DC2.4, 3T3, and HeLa cells at two temperatures and multiple time points. We study four NPs that differ in their surface structures and ligand compositions and report on their cellular internalization by intracellular fluorescence quantification. Using confocal laser scanning microscopy we have found that all three cell types internalize the 66-34OT NPs more than particles coated only with MUS, or particles coated with a very similar coating but lacking any detectable ligand shell structure, or 'striped' particles but with a different composition (34-66OT) at multiple data points.

  5. DNA damage and polyploidization.

    Science.gov (United States)

    Chow, Jeremy; Poon, Randy Y C

    2010-01-01

    A growing body of evidence indicates that polyploidization triggers chromosomal instability and contributes to tumorigenesis. DNA damage is increasingly being recognized for its roles in promoting polyploidization. Although elegant mechanisms known as the DNA damage checkpoints are responsible for halting the cell cycle after DNA damage, agents that uncouple the checkpoints can induce unscheduled entry into mitosis. Likewise, defects of the checkpoints in several disorders permit mitotic entry even in the presence of DNA damage. Forcing cells with damaged DNA into mitosis causes severe chromosome segregation defects, including lagging chromosomes, chromosomal fragments and chromosomal bridges. The presence of these lesions in the cleavage plane is believed to abort cytokinesis. It is postulated that if cytokinesis failure is coupled with defects of the p53-dependent postmitotic checkpoint pathway, cells can enter S phase and become polyploids. Progress in the past several years has unraveled some of the underlying principles of these pathways and underscored the important role of DNA damage in polyploidization. Furthermore, polyploidization per se may also be an important determinant of sensitivity to DNA damage, thereby may offer an opportunity for novel therapies.

  6. Universal map for cellular automata

    International Nuclear Information System (INIS)

    García-Morales, V.

    2012-01-01

    A universal map is derived for all deterministic 1D cellular automata (CAs) containing no freely adjustable parameters and valid for any alphabet size and any neighborhood range (including non-symmetrical neighborhoods). The map can be extended to an arbitrary number of dimensions and topologies and to arbitrary order in time. Specific CA maps for the famous Conway's Game of Life and Wolfram's 256 elementary CAs are given. An induction method for CAs, based in the universal map, allows mathematical expressions for the orbits of a wide variety of elementary CAs to be systematically derived. -- Highlights: ► A universal map is derived for all deterministic 1D cellular automata (CA). ► The map is generalized to 2D for Von Neumann, Moore and hexagonal neighborhoods. ► A map for all Wolfram's 256 elementary CAs is derived. ► A map for Conway's “Game of Life” is obtained.

  7. Simulating physics with cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Vichniac, G Y

    1984-01-01

    Cellular automata are dynamical systems where space, time, and variables are discrete. They are shown on two-dimensional examples to be capable of non-numerical simulations of physics. They are useful for faithful parallel processing of lattice models. At another level, they exhibit behaviours and illustrate concepts that are unmistakably physical, such as non-ergodicity and order parameters, frustration, relaxation to chaos through period doublings, a conspicuous arrow of time in reversible microscopic dynamics, causality and light-cone, and non-separability. In general, they constitute exactly computable models for complex phenomena and large-scale correlations that result from very simple short-range interactions. The author studies their space, time, and intrinsic symmetries and the corresponding conservation laws, with an emphasis on the conservation of information obeyed by reversible cellular automata. 60 references.

  8. CELLULAR RESPONSES TO EGG-OIL (CHARISMON©

    Directory of Open Access Journals (Sweden)

    Jürgen Bereiter-Hahn

    2014-01-01

    Full Text Available Egg-oil (Charismon© is known for its beneficial action in wound healing and other skin irritancies and its antibacterial activity. The physiological basis for these actions has been investigated using cells in culture: HaCaT-cells (immortalized human keratinocytes, human endothelial cells in culture (HUVEC, peripheral blood mononuclear lymphocytes (PBML and a full thickness human skin model (FTSM. Emphasis was on the influence of egg-oil on cell migration and IL-8 production in HaCaT cells, respiration, mitochondrial membrane potential, reactive oxygen (ROS production and proliferation in HUVEC and HaCaT cells, cytokine and interleukin production in PBML and UV-light induced damage of FTSM. IL-8 production by HaCaT cells is stimulated by egg-oil whilst in phythemagglutinin-activated PBMLs production of the interleukins IL-2, IL-6, IL-10 and IFN-γ and TFN-α is reduced. ROS-production after H2O2 stimulation first is enhanced but later on reduced. Respiration becomes activated due to partial uncoupling of the mitochondrial respiratory chain and proliferation of HaCaT and HUVEC is reduced. Recovery of human epidermis cells in FTSM after UV-irradiation is strongly supported by egg-oil. These results support the view that egg-oil acts through reduction of inflammatory processes and ROS production. Both these processes are equally important in cellular aging as in healing of chronic wounds.

  9. Cellular Adhesion and Adhesion Molecules

    OpenAIRE

    SELLER, Zerrin

    2014-01-01

    In recent years, cell adhesion and cell adhesion molecules have been shown to be important for many normal biological processes, including embryonic cell migration, immune system functions and wound healing. It has also been shown that they contribute to the pathogenesis of a large number of common human disorders, such as rheumatoid arthritis and tumor cell metastasis in cancer. In this review, the basic mechanisms of cellular adhesion and the structural and functional features of adhes...

  10. Cellular automata with voting rule

    International Nuclear Information System (INIS)

    Makowiec, D.

    1996-01-01

    The chosen local interaction - the voting (majority) rule applied to the square lattice is known to cause the non ergodic cellular automata behaviour. Presented computer simulation results verify two cases of non ergodicity. The first one is implicated by the noise introduced to the local interactions and the second one follows properties of the initial lattice configuration selected at random. For the simplified voting rule - non symmetric voting, the critical behaviour has been explained rigorously. (author)

  11. Research on garlic capsule and selenium-vitamin A, vitamin B, vitamin C applied in therapy of acute hepatocellular damage in a rat model

    Directory of Open Access Journals (Sweden)

    Jacob Kehinde Akintunde

    2015-10-01

    Conclusions: Collectively, the results suggest that therapeutic dose of lisinopril elicits toxicity in male rats through induction of oxidative damage and depletion of cellular adenosine triphosphate. The reversal effects of GAR and SACE during lisinopril treatment suggest that these antioxidants may find clinical application in cellular damage involving ROS and adenosine triphosphate.

  12. Parvovirus infection-induced DNA damage response

    Science.gov (United States)

    Luo, Yong; Qiu, Jianming

    2014-01-01

    Parvoviruses are a group of small DNA viruses with ssDNA genomes flanked by two inverted terminal structures. Due to a limited genetic resource they require host cellular factors and sometimes a helper virus for efficient viral replication. Recent studies have shown that parvoviruses interact with the DNA damage machinery, which has a significant impact on the life cycle of the virus as well as the fate of infected cells. In addition, due to special DNA structures of the viral genomes, parvoviruses are useful tools for the study of the molecular mechanisms underlying viral infection-induced DNA damage response (DDR). This review aims to summarize recent advances in parvovirus-induced DDR, with a focus on the diverse DDR pathways triggered by different parvoviruses and the consequences of DDR on the viral life cycle as well as the fate of infected cells. PMID:25429305

  13. Sublethal damages: their nature and repair

    Energy Technology Data Exchange (ETDEWEB)

    Saenko, A.S.; Synzynys, B.I.; Trofimova, S.F. (Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii, Obninsk (USSR)); Gotlib, V.Ya.; Pelevina, I.I. (AN SSSR, Moscow. Inst. Khimicheskoj Fiziki)

    1983-05-12

    The molecular nature of sublethal damage (SLD) arising after ionizing irradiation of cultured mammalian cells was considered on the basis of data on DNA repair and cell recovery after SLD observed in lymphosarcoma cells as well as of literature data. The rate of SLD recovery and that of restoration of the cell's ability to initiate DNA synthesis were shown to be similar in new replicons. These data along with knowledge about the role of exchange type chromosomal aberrations in reproductive death permitted us to propose the hypothesis that conformational changes of chromatine - most probably, relaxation of condensed chromosomal material - are damage registered as SLD at the cellular level. Double-strand breaks and a slowly repaired part of DNA single-strand breaks are candidates for SLD.

  14. Cellular communications a comprehensive and practical guide

    CERN Document Server

    Tripathi, Nishith

    2014-01-01

    Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

  15. Dynamic maps of UV damage formation and repair for the human genome.

    Science.gov (United States)

    Hu, Jinchuan; Adebali, Ogun; Adar, Sheera; Sancar, Aziz

    2017-06-27

    Formation and repair of UV-induced DNA damage in human cells are affected by cellular context. To study factors influencing damage formation and repair genome-wide, we developed a highly sensitive single-nucleotide resolution damage mapping method [high-sensitivity damage sequencing (HS-Damage-seq)]. Damage maps of both cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] from UV-irradiated cellular and naked DNA revealed that the effect of transcription factor binding on bulky adducts formation varies, depending on the specific transcription factor, damage type, and strand. We also generated time-resolved UV damage maps of both CPDs and (6-4)PPs by HS-Damage-seq and compared them to the complementary repair maps of the human genome obtained by excision repair sequencing to gain insight into factors that affect UV-induced DNA damage and repair and ultimately UV carcinogenesis. The combination of the two methods revealed that, whereas UV-induced damage is virtually uniform throughout the genome, repair is affected by chromatin states, transcription, and transcription factor binding, in a manner that depends on the type of DNA damage.

  16. LSD and Genetic Damage

    Science.gov (United States)

    Dishotsky, Norman I.; And Others

    1971-01-01

    Reviews studies of the effects of lysergic acid diethylamide (LSD) on man and other organisms. Concludes that pure LSD injected in moderate doses does not cause chromosome or detectable genetic damage and is not a teratogen or carcinogen. (JM)

  17. Diabetes and nerve damage

    Science.gov (United States)

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  18. A rigorous treatment of uncertainty quantification for Silicon damage metrics

    International Nuclear Information System (INIS)

    Griffin, P.

    2016-01-01

    These report summaries the contributions made by Sandia National Laboratories in support of the International Atomic Energy Agency (IAEA) Nuclear Data Section (NDS) Technical Meeting (TM) on Nuclear Reaction Data and Uncertainties for Radiation Damage. This work focused on a rigorous treatment of the uncertainties affecting the characterization of the displacement damage seen in silicon semiconductors. (author)

  19. Calculating externalities from damages in occupational health and safety

    Energy Technology Data Exchange (ETDEWEB)

    Burtraw, D; Shefftz, J

    1994-07-01

    This paper surveys the theoretical basis for the possibility that coal miner occupational health and safety damages are not adequately internalized into the production cost of mining coal and thereby impose an external cost on society.

  20. Calculating externalities from damages in occupational health and safety

    International Nuclear Information System (INIS)

    Burtraw, D.; Shefftz, J.

    1994-01-01

    This paper surveys the theoretical basis for the possibility that coal miner occupational health and safety damages are not adequately internalized into the production cost of mining coal and thereby impose an external cost on society

  1. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal events during mid-loop operations, Appendices A--D. Volume 2, Part 2

    International Nuclear Information System (INIS)

    Chu, T.L.; Musicki, Z.; Kohut, P.

    1994-06-01

    During 1989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the Potential risks during low Power and shutdown operations. The program includes two parallel projects being performed by Brookhaven National Laboratory (BNL) and Sandia National Laboratories (SNL). Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the Plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The objective of this report is to document the approach utilized in the Surry plant and discuss the results obtained. A parallel report for the Grand Gulf plant is prepared by SNL. This study shows that the core-damage frequency during mid-loop operation at the Surry plant is comparable to that of power operation. We recognize that there is very large uncertainty in the human error probabilities in this study. This study identified that only a few procedures are available for mitigating accidents that may occur during shutdown. Procedures written specifically for shutdown accidents would be useful. This document, Volume 2, Pt. 2 provides appendices A through D of this report

  2. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal events during mid-loop operations, Main report (Chapters 7--12). Volume 2, Part 1B

    International Nuclear Information System (INIS)

    Chu, T.L.; Musicki, Z.; Kohut, P.

    1994-06-01

    During 1989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the potential risks during low power and shutdown operations. The program includes two parallel projects being performed by Brookhaven National Laboratory (BNL) and Sandia National Laboratories (SNL). Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The objective of this report is to document the approach utilized in the Surry plant and discuss the results obtained. A parallel report for the Grand Gulf plant is prepared by SNL. This study shows that the core-damage frequency during mid-loop operation at the Surry plant is comparable to that of power operation. We recognize that there is very large uncertainty in the human error probabilities in this study. This study identified that only a few procedures are available for mitigating accidents that may occur during shutdown. Procedures written specific shutdown accidents would be useful

  3. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal fires during mid-loop operations. Volume 3, Part 1, Main report

    International Nuclear Information System (INIS)

    Musicki, Z.; Chu, T.L.; Yang, J.; Ho, V.; Hou, Y.M.; Lin, J.; Siu, N.

    1994-07-01

    During l989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the potential risks during low power and shutdown operations. The program includes two parallel projects being performed by Brookhaven National Laboratory (BNL) and Sandia National Laboratories (SNL). Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than fun power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The objective of this report is to document the approach utilized in ' the Surry plant and discuss the results obtained. A parallel report for the Grand Gulf plant is prepared by SNL. This study shows that the core-damage frequency during mid-loop operation at the Surry plant is comparable to that of power operation. We recognize that there is very large uncertainty in the human error probabilities in this study. This study identified that only a few. procedures are available for mitigating accidents that may occur during shutdown. Procedures written specifically for shutdown accidents would be useful

  4. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal events during mid-loop operations, Appendices E (Sections E.1--E.8). Volume 2, Part 3A

    International Nuclear Information System (INIS)

    Chu, T.L.; Musicki, Z.; Kohut, P.

    1994-06-01

    During 1989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the potential risks during low power and shutdown operations. The program includes two parallel projects being performed by Brookhaven National Laboratory (BNL) and Sandia National Laboratories (SNL). Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The objective of this report is to document the approach utilized in the Surry plant and discuss the results obtained. A parallel report for the Grand Gulf plant is prepared by SNL. This study shows that the core-damage frequency during mid-loop operation at the Surry plant is comparable to that of power operation. The authors recognize that there is very large uncertainty in the human error probabilities in this study. This study identified that only a few procedures are available for mitigating accidents that may occur during shutdown. Procedures written specifically for shutdown accidents would be useful

  5. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal events during mid-loop operations, Main report (Chapters 1--6). Volume 2, Part 1A

    International Nuclear Information System (INIS)

    Chu, T.L.; Musicki, Z.; Kohut, P.

    1992-06-01

    During 1989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the potential risks during low power and shutdown operations. The program includes two parallel projects being performed by Brookhaven National Laboratory (BNL) and Sandia National Laboratories (SNL). Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The objective of this report is to document the approach utilized in the Surry plant and discuss the results obtained. A parallel report for the Grand Gulf plant is prepared by SNL. This study shows that the core-damage frequency during mid-loop operation at the Surry plant is comparable to that of power operation. We recognize that there is very large uncertainty in the human error probabilities in this study. This study identified that only a few procedures are available for mitigating accidents that may occur during shutdown written specifically for shutdown accidents would be useful. This document presents Chapters 1--6 of the report

  6. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal events during mid-loop operations, Appendices A--D. Volume 2, Part 2

    Energy Technology Data Exchange (ETDEWEB)

    Chu, T.L.; Musicki, Z.; Kohut, P. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1994-06-01

    During 1989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the Potential risks during low Power and shutdown operations. The program includes two parallel projects being performed by Brookhaven National Laboratory (BNL) and Sandia National Laboratories (SNL). Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the Plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The objective of this report is to document the approach utilized in the Surry plant and discuss the results obtained. A parallel report for the Grand Gulf plant is prepared by SNL. This study shows that the core-damage frequency during mid-loop operation at the Surry plant is comparable to that of power operation. We recognize that there is very large uncertainty in the human error probabilities in this study. This study identified that only a few procedures are available for mitigating accidents that may occur during shutdown. Procedures written specifically for shutdown accidents would be useful. This document, Volume 2, Pt. 2 provides appendices A through D of this report.

  7. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    International Nuclear Information System (INIS)

    Feinendegen, L.E.; Sondhaus, C.A.; Altman, K.I.

    1998-01-01

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts

  8. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Feinendegen, L.E. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.; Bond, V.P. [Washington State Univ., Richland, WA (United States); Sondhaus, C.A. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Radiology and Radiation Control Office; Altman, K.I. [Univ. of Rochester Medical Center, NY (United States). Dept. of Biochemistry and Biophysics

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

  9. DNA alkylation damage as a sensor of nitrosative stress in Mycobacterium tuberculosis

    OpenAIRE

    Durbach, S I; Springer, B; Machowski, E E; North, R J; Papavinasasundaram, K G; Colston, M J; Böttger, E C; Mizrahi, V

    2003-01-01

    One of the cellular consequences of nitrosative stress is alkylation damage to DNA. To assess whether nitrosative stress is registered on the genome of Mycobacterium tuberculosis, mutants lacking an alkylation damage repair and reversal operon were constructed. Although hypersensitive to the genotoxic effects of N-methyl-N′-nitro-N-nitrosoguanidine in vitro, the mutants displayed no phenotype in vivo, suggesting that permeation of nitrosative stress to the level of cytotoxic DNA damage is res...

  10. Urinary excretion of biomarkers of oxidatively damaged DNA and RNA in hereditary hemochromatosis

    DEFF Research Database (Denmark)

    Broedbaek, Kasper; Poulsen, Henrik E; Weimann, Allan

    2009-01-01

    Oxidatively generated damage to nucleic acids is considered to play a significant role in carcinogenesis, and it has been shown that people with hereditary hemochromatosis are at increased risk of cancer. In this study we used a new refined liquid chromatography-tandem mass spectrometry method...... of the iron overload seen in this disease. By this mechanism cellular damage resulting in end organ damage, typically seen in the liver of such patients, may be mediated....

  11. Functional analysis of molecular mechanisms of radiation induced apoptosis, that are not mediated by DNA damages

    International Nuclear Information System (INIS)

    Angermeier, Marita; Moertl, Simone

    2012-01-01

    The effects of low-dose irradiation pose new challenges on the radiation protection efforts. Enhanced cellular radiation sensitivity is displayed by disturbed cellular reactions and resulting damage like cell cycle arrest, DNA repair and apoptosis. Apoptosis serves as genetically determinate parameter for the individual radiation sensitivity. In the frame of the project the radiation-induced apoptosis was mechanistically investigated. Since ionizing radiation induced direct DNA damage and generates a reactive oxygen species, the main focus of the research was the differentiation and weighting of DNA damage mediated apoptosis and apoptosis caused by the reactive oxygen species (ROS).

  12. The cellular approach to band structure calculations

    International Nuclear Information System (INIS)

    Verwoerd, W.S.

    1982-01-01

    A short introduction to the cellular approach in band structure calculations is given. The linear cellular approach and its potantial applicability in surface structure calculations is given some consideration in particular

  13. Dermal damage from ultraviolet radiation

    International Nuclear Information System (INIS)

    Kligman, L.H.

    1988-01-01

    Ultraviolet (UV) radiation is increasingly recognized as the cause of a vast number of changes in the skin of humans and animals. These include alterations at the molecular, cellular, tissue and systematic levels. In the recent past, much has been learned about the immediate effects in skin of acute UV exposure (i.e. sunburn) with its epidermal cell death, inflammation and vasolidation. With chronic exposure, many of the clinical and histologic effects can be seen only after decades. Visually, these are hyper- and hypopigmented macules, dry scaly, wrinkled skin with a variety of benign, pre-malignant and malignant neoplasms. All epidermal in origin, they lead, inexorably in humans, to the appearance the authors described as photo-aged. Underlying many of these visible manifestations are drastic changes in the dermis. These relate chiefly to destruction of mature collagen, with a compensatory overproduction of reticulin fibers, hyperplasia of elastic fibers eventuating in elastosis, increased levels of the glycosaminoglycans (GAGs) comprising the ground substance and changes in the microvasculature. First described in actinically damaged humans, systematic investigation required an animal model

  14. Studies of cellular radiosensitivity in hereditary disorders of nervous system and muscle

    Energy Technology Data Exchange (ETDEWEB)

    Brennan, S.; Lewis, P.D. (Royal Postgraduate Medical School, London (UK))

    1983-12-01

    Skin fibroblasts from patients with familial dysautonomia, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease show normal sensitivity to ionising radiation, as measured by post-irradiation clonal growth. Previous reports of cellular hypersensitivity to ionising radiation and other DNA-damaging agents in familial dysautonomia and Duchenne muscular dystrophy have not been confirmed.

  15. Studies of cellular radiosensitivity in hereditary disorders of nervous system and muscle

    International Nuclear Information System (INIS)

    Brennan, S.; Lewis, P.D.

    1983-01-01

    Skin fibroblasts from patients with familial dysautonomia, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease show normal sensitivity to ionising radiation, as measured by post-irradiation clonal growth. Previous reports of cellular hypersensitivity to ionising radiation and other DNA-damaging agents in familial dysautonomia and Duchenne muscular dystrophy have not been confirmed. (author)

  16. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

    NARCIS (Netherlands)

    Chornokur, G.; Lin, H.Y.; Tyrer, J.P.; Lawrenson, K.; Dennis, J.; Amankwah, E.K.; Qu, X.; Tsai, Y.Y.; Jim, H.S.; Chen, Z.; Chen, A.Y.; Permuth-Wey, J.; Aben, K.; Anton-Culver, H.; Antonenkova, N.; Bruinsma, F.; Bandera, E.V.; Bean, Y.T.; Beckmann, M.W.; Bisogna, M.; Bjorge, L.; Bogdanova, N.; Brinton, L.A.; Brooks-Wilson, A.; Bunker, C.H.; Butzow, R.; Campbell, I.G.; Carty, K.; Chang-Claude, J.; Cook, L.S.; Cramer, D.W; Cunningham, J.M.; Cybulski, C.; Dansonka-Mieszkowska, A.; Bois, A. du; Despierre, E.; Dicks, E.; Doherty, J.A.; Dork, T.; Durst, M.; Easton, D.F.; Eccles, D.M.; Edwards, R.P.; Ekici, A.B.; Fasching, P.A.; Fridley, B.L.; Gao, Y.T.; Gentry-Maharaj, A.; Giles, G.G.; Glasspool, R.; Goodman, M.T.; Gronwald, J.; Harrington, P.; Harter, P.; Hein, A.; Heitz, F.; Hildebrandt, M.A.T.; Hillemanns, P.; Hogdall, C.K.; Hogdall, E.; Hosono, S.; Jakubowska, A.; Jensen, A.; Ji, B.T.; Karlan, B.Y.; Kelemen, L.E.; Kellar, M.; Kiemeney, L.A.L.M.; Krakstad, C.; Kjaer, S.K.; Kupryjanczyk, J.; Lambrechts, D.; Lambrechts, S.; Le, N.D.; Lee, A.W.; Lele, S.; Leminen, A.; Lester, J.; Levine, D.A.; Liang, D.; Lim, B.K.; Lissowska, J.; Lu, K.; Lubinski, J.; Lundvall, L.; Massuger, L.F.A.G.; Matsuo, K.; McGuire, V.; McLaughlin, J.R.; McNeish, I.; Menon, U.; Milne, R.L.; Modugno, F.; Moysich, K.B.; Ness, R.B.; Nevanlinna, H.; Eilber, U.; Odunsi, K.; Olson, S.H.; Orlow, I., et al.

    2015-01-01

    BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As

  17. Legal protection against nuclear damage

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1959-04-15

    The IAEA Director General appointed an international Panel of Experts to go into the question of Civil Liability and State Responsibility for Nuclear Hazards. The Panel had before it certain basic postulates formulated after a preliminary and tentative consideration of the subject. From the viewpoint of the public, the first postulate is, of course, that the use of nuclear energy be regulated by adequate licensing and control mechanisms so as to prevent any accidents. To the extent, however, that nuclear damage cannot be prevented, there must be liability on the part of the enterprise which caused the damage and, where damage exceeds its liability or its financial resources there should be some assurance of compensation by the State. This should be so not only within the borders of one State, but especially also on an international basis. Security should be required for the possible liability of the enterprises connected with a nuclear incident. Litigation with respect to liability should be concentrated in the most convenient tribunal and be governed by a single clearly defined law. The methods of distribution should meet general standards of equity and be as expeditious as possible. Emergency measures, especially evacuation, first aid and decontamination, should be organized and financed without delay. At the same time, the liability of an enterprise should not exceed its reasonable financial capabilities. This means that a ceiling should be imposed upon the amount of third party liability to which an enterprise could be held. And the liability should generally be such as can be covered by adequate financial security. Uniformity in the treatment of victims of nuclear incidents in all these fields is a desirable goal. Yet, if a rule adopted on an international level or suggested by uniform legislation were to be viable, it should adapt itself to the social, economic and legal order already existing in individual States. This may mean that in certain fields it

  18. Legal protection against nuclear damage

    International Nuclear Information System (INIS)

    1959-01-01

    The IAEA Director General appointed an international Panel of Experts to go into the question of Civil Liability and State Responsibility for Nuclear Hazards. The Panel had before it certain basic postulates formulated after a preliminary and tentative consideration of the subject. From the viewpoint of the public, the first postulate is, of course, that the use of nuclear energy be regulated by adequate licensing and control mechanisms so as to prevent any accidents. To the extent, however, that nuclear damage cannot be prevented, there must be liability on the part of the enterprise which caused the damage and, where damage exceeds its liability or its financial resources there should be some assurance of compensation by the State. This should be so not only within the borders of one State, but especially also on an international basis. Security should be required for the possible liability of the enterprises connected with a nuclear incident. Litigation with respect to liability should be concentrated in the most convenient tribunal and be governed by a single clearly defined law. The methods of distribution should meet general standards of equity and be as expeditious as possible. Emergency measures, especially evacuation, first aid and decontamination, should be organized and financed without delay. At the same time, the liability of an enterprise should not exceed its reasonable financial capabilities. This means that a ceiling should be imposed upon the amount of third party liability to which an enterprise could be held. And the liability should generally be such as can be covered by adequate financial security. Uniformity in the treatment of victims of nuclear incidents in all these fields is a desirable goal. Yet, if a rule adopted on an international level or suggested by uniform legislation were to be viable, it should adapt itself to the social, economic and legal order already existing in individual States. This may mean that in certain fields it

  19. Extended abstracts: Microbeam Probes of Cellular Radiatio