WorldWideScience

Sample records for repair enhancer decoys

  1. Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

    Science.gov (United States)

    Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

    2014-01-01

    Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy. PMID:25460932

  2. Antineoplastic effect of decoy oligonucleotide derived from MGMT enhancer.

    Directory of Open Access Journals (Sweden)

    Tamar Canello

    Full Text Available Silencing of O(6-methylguanine-DNA-methyltransferase (MGMT in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1 within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN. Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy.

  3. Aptamer-Mediated Codelivery of Doxorubicin and NF-κB Decoy Enhances Chemosensitivity of Pancreatic Tumor Cells

    Directory of Open Access Journals (Sweden)

    David Porciani

    2015-01-01

    Full Text Available Aptamers able to bind efficiently cell-surface receptors differentially expressed in tumor and in healthy cells are emerging as powerful tools to perform targeted anticancer therapy. Here, we present a novel oligonucleotide chimera, composed by an RNA aptamer and a DNA decoy. Our assembly is able to (i target tumor cells via an antitransferrin receptor RNA aptamer and (ii perform selective codelivery of a chemotherapeutic drug (Doxorubicin and of an inhibitor of a cell-survival factor, the nuclear factor κB decoy oligonucleotide. Both payloads are released under conditions found in endolysosomal compartments (low pH and reductive environment. Targeting and cytotoxicity of the oligonucleotidic chimera were assessed by confocal microscopy, cell viability, and Western blot analysis. These data indicated that the nuclear factor κB decoy does inhibit nuclear factor κB activity and ultimately leads to an increased therapeutic efficacy of Doxorubicin selectively in tumor cells.

  4. ET-09DECOY OLIGONUCLEOTIDE DERIVED FROM MGMT ENHANCER HAS AN ANTINEOPLASTIC ACTIVITY IN-VITRO AND IN-VIVO

    Science.gov (United States)

    Canello, Tamar; Ovadia, Haim; Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

    2014-01-01

    INTRODUCTION: Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, correlates with a better therapeutic response and with increased survival. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through binding of p65/NF-kappaB homodimers to the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer. METHODS AND RESULTS: In an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to MGMT enhancer, the potential of the MGMT-kB1-LODN to enhance cell killing was studied in vitro in two glioma cell lines (T98G and U87) and a melanoma cell line (A375P). All three cell lines manifested a significant enhanced cell killing effect following exposure to temozolomide (TMZ) when first transfected with MGMT-kb1-LODN, and also induced a significant cell killing when administered as monotherapy. These results were confirmed also in-vivo on A375P Melanoma xenografts. Intratumoral (Intralesional - IL) injection of MGMT-kB1-LODN with or without IP injection of TMZ induced significant tumor growth inhibition either as a monotherapy or in combination with TMZ. The long-term effect of MGMT-kB1-LODN monotherapy was evaluated using a repetitive IL injection every 4 to 5 days for 55 days with either MGMT-κB1 LODN or control ODN or vehicle. A significant difference (p < 0.01) in tumor volume was obtained by MGMT-κB1-LODN compared to both control groups. Moreover, two out of the seven mice treated with MGMT-κB1-LODN demonstrated tumor regression by day 55 and no tumor recurrence was observed five months later. CONCLUSION: The results of these experiments show that the MGMT-kB1-LODN has a substantial antineoplastic effect when used either in combination with

  5. Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Park, Serk In, E-mail: serkin@korea.edu [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); The BK21 Plus Program for Biomedical Sciences, Korea University College of Medicine, Seoul (Korea, Republic of); Department of Medicine and Center for Bone Biology, Vanderbilt University School of Medicine, Nashville, TN (United States); Park, Sung-Jun [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); Laboratory of Obesity and Aging Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Lee, Junghan; Kim, Hye Eun; Park, Su Jin; Sohn, Jeong-Won [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); Park, Yun Gyu, E-mail: parkyg@korea.ac.kr [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

    2016-01-15

    The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to γ-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time- and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to γ-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to γ-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from γ-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach. - Highlights: • γ-Irradiation induced CREB phosphorylation and CRE-directed transcription in tumor. • γ-Irradiation-induced transcriptional activation of CREB was via p38 MAPK pathway. • CRE blockade increased radiosensitivity of tumor cells but not of normal cells. • CRE decoy oligonucleotides or p38 MAPK inhibitors can be used as radiosensitizers.

  6. Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity

    International Nuclear Information System (INIS)

    Park, Serk In; Park, Sung-Jun; Lee, Junghan; Kim, Hye Eun; Park, Su Jin; Sohn, Jeong-Won; Park, Yun Gyu

    2016-01-01

    The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to γ-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time- and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to γ-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to γ-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from γ-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach. - Highlights: • γ-Irradiation induced CREB phosphorylation and CRE-directed transcription in tumor. • γ-Irradiation-induced transcriptional activation of CREB was via p38 MAPK pathway. • CRE blockade increased radiosensitivity of tumor cells but not of normal cells. • CRE decoy oligonucleotides or p38 MAPK inhibitors can be used as radiosensitizers.

  7. Mini Review: Biomaterials for Enhancing Neuronal Repair

    Science.gov (United States)

    Cangellaris, Olivia V.; Gillette, Martha U.

    2018-04-01

    As they differentiate from neuroblasts, nascent neurons become highly polarized and elongate. Neurons extend and elaborate fine and fragile cellular extensions that form circuits enabling long-distance communication and signal integration within the body. While other organ systems are developing, projections of differentiating neurons find paths to distant targets. Subsequent post-developmental neuronal damage is catastrophic because the cues for reinnervation are no longer active. Advances in biomaterials are enabling fabrication of micro-environments that encourage neuronal regrowth and restoration of function by recreating these developmental cues. This mini-review considers new materials that employ topographical, chemical, electrical, and/or mechanical cues for use in neuronal repair. Manipulating and integrating these elements in different combinations will generate new technologies to enhance neural repair.

  8. Camouflage, Concealment, and Decoys

    Science.gov (United States)

    2010-11-26

    otherwise dull Note. Use canned milk or powdered eggs to increase the binding properties of field-expedient paints. RADAR-ABSORBING MATERIAL 3-72. RAM... falsification of evidence, inducing him to react in a manner prejudicial to his interests. decoy An imitation in any sense of a person, an object

  9. Decoy State Quantum Key Distribution

    Science.gov (United States)

    Lo, Hoi-Kwong

    2005-10-01

    Quantum key distribution (QKD) allows two parties to communicate in absolute security based on the fundamental laws of physics. Up till now, it is widely believed that unconditionally secure QKD based on standard Bennett-Brassard (BB84) protocol is limited in both key generation rate and distance because of imperfect devices. Here, we solve these two problems directly by presenting new protocols that are feasible with only current technology. Surprisingly, our new protocols can make fiber-based QKD unconditionally secure at distances over 100km (for some experiments, such as GYS) and increase the key generation rate from O(η2) in prior art to O(η) where η is the overall transmittance. Our method is to develop the decoy state idea (first proposed by W.-Y. Hwang in "Quantum Key Distribution with High Loss: Toward Global Secure Communication", Phys. Rev. Lett. 91, 057901 (2003)) and consider simple extensions of the BB84 protocol. This part of work is published in "Decoy State Quantum Key Distribution", . We present a general theory of the decoy state protocol and propose a decoy method based on only one signal state and two decoy states. We perform optimization on the choice of intensities of the signal state and the two decoy states. Our result shows that a decoy state protocol with only two types of decoy states--a vacuum and a weak decoy state--asymptotically approaches the theoretical limit of the most general type of decoy state protocols (with an infinite number of decoy states). We also present a one-decoy-state protocol as a special case of Vacuum+Weak decoy method. Moreover, we provide estimations on the effects of statistical fluctuations and suggest that, even for long distance (larger than 100km) QKD, our two-decoy-state protocol can be implemented with only a few hours of experimental data. In conclusion, decoy state quantum key distribution is highly practical. This part of work is published in "Practical Decoy State for Quantum Key Distribution

  10. Detector decoy quantum key distribution

    International Nuclear Information System (INIS)

    Moroder, Tobias; Luetkenhaus, Norbert; Curty, Marcos

    2009-01-01

    Photon number resolving detectors can enhance the performance of many practical quantum cryptographic setups. In this paper, we employ a simple method to estimate the statistics provided by such a photon number resolving detector using only a threshold detector together with a variable attenuator. This idea is similar in spirit to that of the decoy state technique, and is especially suited to those scenarios where only a few parameters of the photon number statistics of the incoming signals have to be estimated. As an illustration of the potential applicability of the method in quantum communication protocols, we use it to prove security of an entanglement-based quantum key distribution scheme with an untrusted source without the need for a squash model and by solely using this extra idea. In this sense, this detector decoy method can be seen as a different conceptual approach to adapt a single-photon security proof to its physical, full optical implementation. We show that in this scenario, the legitimate users can now even discard the double click events from the raw key data without compromising the security of the scheme, and we present simulations on the performance of the BB84 and the 6-state quantum key distribution protocols.

  11. Tracking the decoy: Maximizing the decoy effect through sequential experimentation

    NARCIS (Netherlands)

    Kaptein, M.C.; Emden, R. van; Iannuzzi, D.

    2016-01-01

    The decoy effect is one of the best known human biases violating rational choice theory. According to a large body of literature, people may be persuaded to switch from one offer to another by the presence of a third option (the decoy) that, rationally, should have no influence on the

  12. Tracking the decoy : Maximizing the decoy effect through sequential experimentation

    NARCIS (Netherlands)

    Kaptein, M.C; Van Emden, Robin; Iannuzzi, Davide

    2016-01-01

    The decoy effect is one of the best known human biases violating rational choice theory. According to a large body of literature, people may be persuaded to switch from one offer to another by the presence of a third option (the decoy) that, rationally, should have no influence on the

  13. Tracking the decoy: maximizing the decoy effect through sequential experimentation

    NARCIS (Netherlands)

    Kaptein, M.C.; van Emden, R.; Iannuzzi, D.

    2016-01-01

    The decoy effect is one of the best known human biases violating rational choice theory. According to a large body of literature, people may be persuaded to switch from one offer to another by the presence of a third option (the decoy) that, rationally, should have no influence on the

  14. Apparatus for enhancing tissue repair in mammals

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor); Parker, Clayton R. (Inventor)

    2007-01-01

    An apparatus is disclosed for enhancing tissue repair in mammals, with the apparatus comprising: a sleeve for encircling a portion of a mammalian body part, said sleeve comprising an electrically conductive coil capable of generating an electromagnetic field when an electrical current is applied thereto, means for supporting the sleeve on the mammalian body part; and means for supplying the electrically conductive coil with a square wave time varying electrical current sufficient to create a time varying electromagnetic force of from approximately 0.05 gauss to 0.05 gauss within the interior of the coil in order that when the sleeve is placed on a mammalian body part and the time varying electromagnetic force of from approximately 0.05 gauss to 0.05 gauss is generated on the mammalian body part for an extended period of time, tissue regeneration within the mammalian body part is increased to a rate in excess of the normal tissue regeneration rate that would occur without application of the time varying electromagnetic force.

  15. Advanced repair methods for enhanced reactor safety

    International Nuclear Information System (INIS)

    Kornfeldt, H.

    1993-01-01

    A few innovative concepts are described of the ABB Atom Service Division for repair and mitigation techniques for primary systems in nuclear power plants. The concepts are based on Shape Memory Alloy (SMA) technology. A basic feature of all methods is that welding and component replacement is being avoided and the radiation dose imposed on maintenance personnel reduced. The SMA-based repair methods give plant operators new ways to meet increased safety standards and rising maintenance costs. (Z.S.) 4 figs

  16. Contextual effects and psychological features influencing decoy options: A review and research agenda

    Directory of Open Access Journals (Sweden)

    David Gonzalez-Prieto

    2013-01-01

    Full Text Available Purpose: The purpose of this paper is to develop future research proposals aiming to contribute the extant theory which explains decoy effects.Design/methodology/approach: Firstly, a review of the existing literature about decoy options and its interactions with contextual effects that could affect their performance is presented. Next, two research proposals are presented: the introduction of a double decoy choice set and the evaluation of decoy effect under different levels of cognitive effort in a purchasing process.Findings and Originality/value: For the research proposal concerning double decoy choice sets, different hypothesis are introduced based on the different theories aiming to explain the effect of simple decoy choice sets. This hypothesis predict different outcomes for the same experimental design, fact that could provide further support for at least one of the current explanations for decoy effects. Regarding the effect of decoy options under different levels of cognitive effort, implications for experimental design for sequential purchasing process are expected. Especially for those designed with complex options, with many steps or high number of options.Originality/value: Two new research proposal approaches are presented in order enhance the current theory. Moreover, both have managerial implications concerning the real usage of decoy options in reduced choice sets as well as in sequential purchasing processes.

  17. Resident enhanced repair: novel repair process action on plasmid DNA transformed into Escherichia coli K-12

    International Nuclear Information System (INIS)

    Strike, P.; Roberts, R.J.

    1982-01-01

    The survival of UV-irradiated DNA of plasmid NTP16 was monitored after its transformation into recipient cells containing an essentially homologous undamaged plasmid, pLV9. The presence of pLV9 resulted in a substantial increase in the fraction of damaged NTP16 molecules which survived in the recipient cells. This enhanced survival requires the host uvrA + and uvrB + gene products, but not the host recA + gene product. The requirement for both homologous DNA and the uvrA + gene products suggests that a novel repair process may act on plasmid DNA. Possible mechanisms for this process are considered

  18. Preoperative methylprednisolone enhances recovery after endovascular aortic repair

    DEFF Research Database (Denmark)

    de la Motte, Louise; Kehlet, Henrik; Vogt, Katja

    2014-01-01

    OBJECTIVE: To evaluate effects of preoperative high-dose glucocorticoid on the inflammatory response and recovery after endovascular aortic aneurysm repair (EVAR). BACKGROUND: The postimplantation syndrome after EVAR may delay recovery due to the release of proinflammatory mediators....... Glucocorticoids may reduce postoperative inflammatory responses and enhance recovery, but with limited information on EVAR. METHODS: A single-center, randomized, double-blind, placebo-controlled trial of 153 patients undergoing elective EVAR between November 2009 and January 2013. Patients received 30 mg.......001) and fulfillment of discharge criteria was shorter [2 days (IQR = 2-4 days) vs 3 days (IQR = 3-4 days)] (P factor receptor were also reduced (P

  19. Improving decoy databases for protein folding algorithms

    KAUST Repository

    Lindsey, Aaron; Yeh, Hsin-Yi (Cindy); Wu, Chih-Peng; Thomas, Shawna; Amato, Nancy M.

    2014-01-01

    energetically stable) from non-native structures. Decoy databases are collections of non-native structures used to test and verify these functions. We present a method to evaluate and improve the quality of decoy databases by adding novel structures and removing

  20. Enhancement of postreplication repair in Chinese hamster cells

    International Nuclear Information System (INIS)

    D'Ambrosio, S.M.; Setlow, R.B.

    1976-01-01

    Alkaline sedimentation profiles of pulse-labeled DNA from Chinese hamster cells showed that DNA from cells treated with N-acetoxy-acetylaminofluorene or ultraviolet radiation was made in segments smaller than those from untreated cells. Cells treated with a small dose (2.5 μM) of N-acetoxy-acetylaminofluorene or(2.5 J . m -2 ) 254-nm radiation, several hours before a larger dose (7 to 10 μM) of N-acetoxy-acetylaminofluorene or 5.0 J . m -2 of 254-nm radiation, also synthesized small DNA after the second dose. However, the rate at which this small DNA was joined together into parental size was appreciably greater than in absence of the small dose. This enhancement of postreplication repair (as a result of the initial small dose) was not observed when cells were incubated with cycloheximide between the two treatments. The results suggest that N-acetoxy-acetylaminofluorene and ultraviolet-damaged DNA from Chinese hamster cells are repaired by similar postreplicative mechanisms that require de novo protein synthesis for enhancement

  1. Apparatus and method for enhancing tissue repair in mammals

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor); Parker, Clayton R. (Inventor)

    2009-01-01

    An apparatus is introduced for the use of enhancing tissue repair in mammals. The apparatus includes a sleeve; an electrically conductive coil; a sleeve support; an electrical circuit configured to supply the coil with a square wave time varying electrical current sufficient to create approximately 0.05 gauss to 0.5 gauss. When in use, the sleeve of the apparatus is placed on a mammalian body part and the time varying electromagnetic force of from approximately 0.05 gauss to 0.5 gauss is generated on the mammalian body for an extended period of time so that the tissue is encouraged to be regenerated in the mammalian body part at a rate in excess of the normal tissue regeneration rate relative to regeneration without application of the time varying electromagnetic force.

  2. Improving decoy databases for protein folding algorithms

    KAUST Repository

    Lindsey, Aaron

    2014-01-01

    Copyright © 2014 ACM. Predicting protein structures and simulating protein folding are two of the most important problems in computational biology today. Simulation methods rely on a scoring function to distinguish the native structure (the most energetically stable) from non-native structures. Decoy databases are collections of non-native structures used to test and verify these functions. We present a method to evaluate and improve the quality of decoy databases by adding novel structures and removing redundant structures. We test our approach on 17 different decoy databases of varying size and type and show significant improvement across a variety of metrics. We also test our improved databases on a popular modern scoring function and show that they contain a greater number of native-like structures than the original databases, thereby producing a more rigorous database for testing scoring functions.

  3. A new dimension in improved radiation protection by enhanced DNA repair

    International Nuclear Information System (INIS)

    Riklis, E.

    1997-01-01

    Radioprotection and photo protection were dependent until now on measures to reduce the amount of damage formed by ionizing and ultraviolet radiations. In both cases the measures are not completely satisfactory: the classical radioprotectors are toxic arid exert serious side effects, and afford a protection factor not higher than around 2. The sunscreens filters are effective for certain wavelength ranges only, and not enough is known about the possible effects of the filters when they absorb light and turn into other chemical entities. Both approaches do not give an answer to damages which are formed in spite of the partial reduction of damage. A new approach offered here is dealing with the damage on a cellular / molecular level, by enhancing the activity of the natural repair enzymes whose task is to remove radiation and photoproducts, rejoin DNA strand breaks and repair the DNA. A combination of vitamins and antioxidants is fulfilling these tasks and provides protection from both ionizing and ultraviolet radiations by enhancing several folds the repair of DNA in living cells. Such a combination which contains the repair enhancers niacinamide and nordihydroguaiaretic acid is employed in preparations named EDNAR ( Enhanced DNA Repair, Patent pending) which demonstrate excellent results of enhancing DNA repair as measured by repair synthesis, and protecting the skin from sunburns as well as skin burns following radiotherapy. These lotions and creams, when not containing any chemical filters yet demonstrating a protective effect, may be called 'the sunscreens without sunscreens'. (author)

  4. Enhanced DNA repair of cyclobutane pyrimidine dimers changes the biological response to UV-B radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yarosh, Daniel B

    2002-11-30

    The goal of DNA repair enzyme therapy is the same as that for gene therapy: to rescue a defective proteome/genome by introducing a substitute protein/DNA. The danger of inadequate DNA repair is highlighted in the genetic disease xeroderma pigmentosum. These patients are hypersensitive to sunlight and develop multiple cutaneous neoplasms very early in life. The bacterial DNA repair enzyme T4 endonuclease V was shown over 25 years ago to be capable of reversing the defective repair in xeroderma pigmentosum cells. This enzyme, packaged in an engineered delivery vehicle, has been shown to traverse the stratum corneum, reach the nuclei of living cells of the skin, and enhance the repair of UV-induced cyclobutane pyrimidine dimers (CPD). In such a system, changes in DNA repair, mutagenesis, and cell signaling can be studied without manipulation of the genome.

  5. DecoyFinder: an easy-to-use python GUI application for building target-specific decoy sets.

    Science.gov (United States)

    Cereto-Massagué, Adrià; Guasch, Laura; Valls, Cristina; Mulero, Miquel; Pujadas, Gerard; Garcia-Vallvé, Santiago

    2012-06-15

    Decoys are molecules that are presumed to be inactive against a target (i.e. will not likely bind to the target) and are used to validate the performance of molecular docking or a virtual screening workflow. The Directory of Useful Decoys database (http://dud.docking.org/) provides a free directory of decoys for use in virtual screening, though it only contains a limited set of decoys for 40 targets.To overcome this limitation, we have developed an application called DecoyFinder that selects, for a given collection of active ligands of a target, a set of decoys from a database of compounds. Decoys are selected if they are similar to active ligands according to five physical descriptors (molecular weight, number of rotational bonds, total hydrogen bond donors, total hydrogen bond acceptors and the octanol-water partition coefficient) without being chemically similar to any of the active ligands used as an input (according to the Tanimoto coefficient between MACCS fingerprints). To the best of our knowledge, DecoyFinder is the first application designed to build target-specific decoy sets. A complete description of the software is included on the application home page. A validation of DecoyFinder on 10 DUD targets is provided as Supplementary Table S1. DecoyFinder is freely available at http://URVnutrigenomica-CTNS.github.com/DecoyFinder.

  6. Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target.

    Science.gov (United States)

    Hiu, Takeshi; Farzampour, Zoya; Paz, Jeanne T; Wang, Eric Hou Jen; Badgely, Corrine; Olson, Andrew; Micheva, Kristina D; Wang, Gordon; Lemmens, Robin; Tran, Kevin V; Nishiyama, Yasuhiro; Liang, Xibin; Hamilton, Scott A; O'Rourke, Nancy; Smith, Stephen J; Huguenard, John R; Bliss, Tonya M; Steinberg, Gary K

    2016-02-01

    Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem's potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

  7. Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization

    Directory of Open Access Journals (Sweden)

    Jianfeng Zhang

    2015-06-01

    Full Text Available Background/Aims: Transplantation of mesenchymal stem cells (MSCs improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells. Methods: We isolated macrophages (BM-MΦ from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs co-cultured with PLGF-treated macrophages. Results: PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay. Conclusion: Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.

  8. Enhanced radiosensitivity and defective DNA repair in cultured fibroblasts derived from Rothmund Thomson syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Smith, P J; Paterson, M C [Atomic Energy of Canada Ltd., Chalk River, Ontario. Radiation Biology Branch

    1982-01-01

    Rothmund Thomson syndrome (RTS) is an oculocutaneous and cancer-prone disorder in which enhanced carcinogen sensitivity, mediated through abnormal DNA metabolism, may be an associated factor. Cultured fibroblasts from 4 RTS patients have been examined for their colony-forming abilities and DNA repair capacities following ..gamma..-irradiation. 2 of the 4 RTS strains showed enhanced sensitivity following hypoxic ..gamma..-irradiation, and 1 of these 2 strains also showed enhanced sensitivity under oxic conditions. Defective DNA repair was implicated in the above abnormal responses to ..gamma..-radiation since both strains displayed reduced levels of repair synthesis and slow removal of radiogenic DNA lesions (assayed by their sensitivity to strand-incising activities present in protein extracts of Micrococcus luteus cells). A hypothesis is presented to rationalize the origin and heterogeneity of these laboratory phenotypes of RTS.

  9. Repair in schizosaccharomyces pombe as measured by recovery from caffeine enhancement of radiation-induced lethality

    International Nuclear Information System (INIS)

    Gentner, N.E.; Werner, M.M.

    1975-01-01

    Inhibition of DNA repair by caffeine is manifested in Schizosaccharomyces pombe wild-type cells as an enhancement of UV- or γ-irradiation-induced lethality. The progress of DNA repair processes involving one or more caffeine-sensitive steps may be conveniently followed by measuring the concomitant decrease of this lethal enhancement effect. By measuring, during post-irradiation incubation, the ability of cells to overcome susceptibility to repair inhibition by caffeine, we have determined the time course and requirements for repair in S. pombe. Recovery began immediately and took 150-200 min after γ-irradiation and more than 500 min after UV-irradiation, for exposures which gave about 10% survival in the absence of caffeine. An incubation medium capable of supporting growth was required for caffeine-sensitive repair; no recovery occurred under liquid holding conditions. Survival curves after various recovery times indicated that a logarithmic phase cell population was homogeneous with respect to caffeine-sensitive repair of both UV- and γ-ray-induced damage. Recovery from caffeine inhibition was compared for cells of different physiological states (logarithmic and stationary phase); although the importance of the physiological state was not the same for the two types of radiation, recovery was found to occur more rapidly in the more radiation-resistant state, in each case. (orig.) [de

  10. Enhancement of ultraviolet-DNA repair in denV gene transfectants and T4 endonuclease V-liposome recipients

    International Nuclear Information System (INIS)

    Kibitel, J.T.; Yee, V.; Yarosh, D.B.

    1991-01-01

    The phage T4 denV gene, coding for the pyrimidine-dimer specific T4 endonuclease V, was transfected into human repair-proficient fibroblasts, repair-deficient xeroderma pigmentosum fibroblasts, and wild type CHO hamster cells. Transfectants maintained denV DNA and expressed denV mRNA. Purified T4 endonuclease V encapsulated in liposomes was also used to treat repair-proficient and -deficient human cells. The denV transfected clones and liposome-treated cells showed increased unscheduled DNA synthesis and enhanced removal of pyrimidine dimers compared to controls. Both denV gene transfection and endonuclease V liposome treatment enhanced post-UV survival in xeroderma pigmentosum cells but had no effect on survival in repair-proficient human or hamster cells. The results demonstrate that an exogenous DNA repair enzyme can correct the DNA repair defect in xeroderma pigmentosum cells and enhance DNA repair in normal cells. (author)

  11. APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair.

    Science.gov (United States)

    Nowarski, Roni; Wilner, Ofer I; Cheshin, Ori; Shahar, Or D; Kenig, Edan; Baraz, Leah; Britan-Rosich, Elena; Nagler, Arnon; Harris, Reuben S; Goldberg, Michal; Willner, Itamar; Kotler, Moshe

    2012-07-12

    APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy.

  12. Enhanced capacity of DNA repair in human cytomegalovirus-infected cells

    International Nuclear Information System (INIS)

    Nishiyama, Y.; Rapp, F.

    1981-01-01

    Plaque formation in Vero cells by UV-irradiated herpes simplex virus was enhanced by infection with human cytomegalovirus (HCMV), UV irradiation, or treatment with methylmethanesulfonate. Preinfection of Vero cells with HCMV enhanced reactivation of UV-irradiated herpes simplex virus more significantly than did treatment with UV or methylmethanesulfonate alone. A similar enhancement by HCMV was observed in human embryonic fibroblasts, but not in xeroderma pigmentosum (XP12BE) cells. It was also found that HCMV infection enhanced hydroxyurea-resistant DNA synthesis induced by UV light or methylmethanesulfonate. Alkaline sucrose gradient sedimentation analysis revealed an enhanced rate of synthesis of all size classes of DNA in UV-irradiated HCMV-infected Vero cells. However, HCMV infection did not induce repairable lesions in cellular DNA and did not significantly inhibit host cell DNA synthesis, unlike UV or methylmethanesulfonate. These results indicate that HCMV enhanced DNA repair capacity in the host cells without producing detectable lesions in cellular DNA and without inhibiting DNA synthesis. This repair appeared to be error proof for UV-damaged herpes simplex virus DNA when tested with herpes simplex virus thymidine kinase-negative mutants

  13. Heparin octasaccharide decoy liposomes inhibit replication of multiple viruses

    Science.gov (United States)

    Hendricks, Gabriel L.; Velazquez, Lourdes; Pham, Serena; Qaisar, Natasha; Delaney, James C.; Viswanathan, Karthik; Albers, Leila; Comolli, James C.; Shriver, Zachary; Knipe, David M.; Kurt-Jones, Evelyn A.; Fygenson, Deborah K.; Trevejo, Jose M.

    2016-01-01

    Heparan sulfate (HS) is a ubiquitous glycosaminoglycan that serves as a cellular attachment site for a number of significant human pathogens, including respiratory syncytial virus (RSV), human parainfluenza virus 3 (hPIV3), and herpes simplex virus (HSV). Decoy receptors can target pathogens by binding to the receptor pocket on viral attachment proteins, acting as ‘molecular sinks’ and preventing the pathogen from binding to susceptible host cells. Decoy receptors functionalized with HS could bind to pathogens and prevent infection, so we generated decoy liposomes displaying HS-octasaccharide (HS-octa). These decoy liposomes significantly inhibited RSV, hPIV3, and HSV infectivity in vitro to a greater degree than the original HS-octa building block. The degree of inhibition correlated with the density of HS-octa displayed on the liposome surface. Decoy liposomes with HS-octa inhibited infection of viruses to a greater extent than either full-length heparin or HS-octa alone. Decoy liposomes were effective when added prior to infection or following the initial infection of cells in vitro. By targeting the well-conserved receptor-binding sites of HS-binding viruses, decoy liposomes functionalized with HS-octa are a promising therapeutic antiviral agent and illustrate the utility of the liposome delivery platform. PMID:25637710

  14. Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair

    Directory of Open Access Journals (Sweden)

    Sibel Naska

    2016-01-01

    Full Text Available Here, we asked whether we could identify pharmacological agents that enhance endogenous stem cell function to promote skin repair, focusing on skin-derived precursors (SKPs, a dermal precursor cell population. Libraries of compounds already used in humans were screened for their ability to enhance the self-renewal of human and rodent SKPs. We identified and validated five such compounds, and showed that two of them, alprostadil and trimebutine maleate, enhanced the repair of full thickness skin wounds in middle-aged mice. Moreover, SKPs isolated from drug-treated skin displayed long-term increases in self-renewal when cultured in basal growth medium without drugs. Both alprostadil and trimebutine maleate likely mediated increases in SKP self-renewal by moderate hyperactivation of the MEK-ERK pathway. These findings identify candidates for potential clinical use in human skin repair, and provide support for the idea that pharmacological activation of endogenous tissue precursors represents a viable therapeutic strategy.

  15. Electrical stimulation enhances cell migration and integrative repair in the meniscus

    Science.gov (United States)

    Yuan, Xiaoning; Arkonac, Derya E.; Chao, Pen-hsiu Grace; Vunjak-Novakovic, Gordana

    2014-01-01

    Electrical signals have been applied towards the repair of articular tissues in the laboratory and clinical settings for over seventy years. We focus on healing of the meniscus, a tissue essential to knee function with limited innate repair potential, which has been largely unexplored in the context of electrical stimulation. Here we demonstrate for the first time that electrical stimulation enhances meniscus cell migration and integrative tissue repair. We optimize pulsatile direct current electrical stimulation parameters on cells at the micro-scale, and apply these to healing of full-thickness defects in explants at the macro-scale. We report increased expression of the adenosine A2b receptor in meniscus cells after stimulation at the micro- and macro-scale, and propose a role for A2bR in meniscus electrotransduction. Taken together, these findings advance our understanding of the effects of electrical signals and their mechanisms of action, and contribute to developing electrotherapeutic strategies for meniscus repair. PMID:24419206

  16. Enhancing repair of radiation-induced strand breaks in cellular DNA as a radiotherapeutic potential

    International Nuclear Information System (INIS)

    Nair, C.K.K.

    2014-01-01

    Protection of mammalian organisms including man from deleterious effects of ionizing radiation is of paramount importance and development of effective approaches to combat radiation damages using non-toxic radioprotectors is of considerable interest for defence, nuclear industries, radiation accidents, space travels, etc., besides the protection of normal tissues during radiotherapy of tumours. Many synthetic as well as natural compounds have been investigated in the recent past for their efficacy to protect the biological systems from radiation induced damages. They include sulfhydryl compounds, antioxidants, plant extracts, immune-modulators, and other agents. However, the inherent toxicity of many of the synthetic agents at the effective radio-protective concentration warranted further search for safer and more effective radio-protectors. In this context, therapeutic radioprotectors which are effective on post irradiation administration are of special relevance. One of the property that can be applied while screening for such radiation protective therapeutics is their ability to enhance repair of radiation-induced lesions in cellular DNA in terms of cellular repair index based on the parameters of the DNA following comet assay. Post irradiation administration of some natural and synthetic agents have shown their potential to enhance repair of radiation-induced strand breaks in cellular DNA in mice. These include phytoceuticals such as gallic acid, sesamol etc., extracts of medicinal plants such as Andrographis panniculata, and a few synthetic compounds such as tocopherol-mono-glucoside. The talk will give an overview of the work on DNA repair enhancement by a few natural and synthetic agents. (author)

  17. Mesenchymal stem cells and their conditioned medium can enhance the repair of uterine defects in a rat model

    Directory of Open Access Journals (Sweden)

    Chi-Hong Ho

    2018-03-01

    Conclusion: This study demonstrated that transplantation of MSCs could enhance uterine defect repair by paracrine effects involving IL-6, which are findings that may be applied to facilitate uterine wound healing in the removal of huge intramural masses.

  18. Double-stranded RNA transcribed from vector-based oligodeoxynucleotide acts as transcription factor decoy

    International Nuclear Information System (INIS)

    Xiao, Xiao; Gang, Yi; Wang, Honghong; Wang, Jiayin; Zhao, Lina; Xu, Li; Liu, Zhiguo

    2015-01-01

    Highlights: • A shRNA vector based transcription factor decoy, VB-ODN, was designed. • VB-ODN for NF-κB inhibited cell viability in HEK293 cells. • VB-ODN inhibited expression of downstream genes of target transcription factors. • VB-ODN may enhance nuclear entry ratio for its feasibility of virus production. - Abstract: In this study, we designed a short hairpin RNA vector-based oligodeoxynucleotide (VB-ODN) carrying transcription factor (TF) consensus sequence which could function as a decoy to block TF activity. Specifically, VB-ODN for Nuclear factor-κB (NF-κB) could inhibit cell viability and decrease downstream gene expression in HEK293 cells without affecting expression of NF-κB itself. The specific binding between VB-ODN produced double-stranded RNA and NF-κB was evidenced by electrophoretic mobility shift assay. Moreover, similar VB-ODNs designed for three other TFs also inhibit their downstream gene expression but not that of themselves. Our study provides a new design of decoy for blocking TF activity

  19. Double-stranded RNA transcribed from vector-based oligodeoxynucleotide acts as transcription factor decoy

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Xiao [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Gang, Yi [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi Province (China); Wang, Honghong [No. 518 Hospital of Chinese People’s Liberation Army, Xi’an 710043, Shaanxi Province (China); Wang, Jiayin [The Genome Institute, Washington University in St. Louis, St. Louis, MO 63108 (United States); Zhao, Lina [Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Xu, Li, E-mail: lxuhelen@163.com [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Liu, Zhiguo, E-mail: liuzhiguo@fmmu.edu.cn [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China)

    2015-02-06

    Highlights: • A shRNA vector based transcription factor decoy, VB-ODN, was designed. • VB-ODN for NF-κB inhibited cell viability in HEK293 cells. • VB-ODN inhibited expression of downstream genes of target transcription factors. • VB-ODN may enhance nuclear entry ratio for its feasibility of virus production. - Abstract: In this study, we designed a short hairpin RNA vector-based oligodeoxynucleotide (VB-ODN) carrying transcription factor (TF) consensus sequence which could function as a decoy to block TF activity. Specifically, VB-ODN for Nuclear factor-κB (NF-κB) could inhibit cell viability and decrease downstream gene expression in HEK293 cells without affecting expression of NF-κB itself. The specific binding between VB-ODN produced double-stranded RNA and NF-κB was evidenced by electrophoretic mobility shift assay. Moreover, similar VB-ODNs designed for three other TFs also inhibit their downstream gene expression but not that of themselves. Our study provides a new design of decoy for blocking TF activity.

  20. Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen receptor-β.

    Science.gov (United States)

    Lu, Jun-Yu; Jin, Peng; Gao, Wei; Wang, De-Zhi; Sheng, Jian-Qiu

    2017-06-13

    Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway. Human CRC cell lines were used to examine the regulation of MLH1 expression by over-expression and depletion of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), under the treatment with 17β-estradiol or β-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation assays were used to identify the estrogen response elements in the proximal promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined in vitro and in vivo. We found that mismatch repair ability and microsatellite stability of cells were enhanced by estrogen via induction of MLH1 expression, which was mediated by ERβ, through a transcriptional activation process. Furthermore, we identified that ERβ exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 expression mediated by ERβ.

  1. Regret salience and accountability in the decoy effect

    Directory of Open Access Journals (Sweden)

    Terry Connolly

    2013-03-01

    Full Text Available Two experiments examined the impact on the decoy effect of making salient the possibility of post-decision regret, a manipulation that has been shown in several earlier studies to stimulate critical examination and improvement of decision process. Experiment 1 (N = 62 showed that making regret salient eliminated the decoy effect in a personal preference task. Experiment 2 (N = 242 replicated this finding for a different personal preference task and for a prediction task. It also replicated previous findings that external accountability demands do not reduce, and may exacerbate, the decoy effect. We interpret both effects in terms of decision justification, with different justification standards operating for different audiences. The decoy effect, in this account, turns on accepting a weak justification, which may be seen as adequate for an external audience or one's own inattentive self but inadequate under the more critical review triggered by making regret possibilities salient. Seeking justification to others (responding to accountability demands thus maintains or exacerbates the decoy effect; seeking justification to oneself (responding to regret salience reduces or eliminates it. The proposed mechanism provides a theoretical account both of the decoy effect itself and of how regret priming provides an effective debiasing procedure for it.

  2. Biochemical evidence for deficient DNA repair leading to enhanced G2 chromatid radiosensitivity and susceptibility to cancer

    International Nuclear Information System (INIS)

    Gantt, R.; Parshad, R.; Price, F.M.; Sanford, K.K.

    1986-01-01

    Human tumor cells and cells from cancer-prone individuals, compared with those from normal individuals, show a significantly higher incidence of chromatid breaks and gaps seen in metaphase cells immediately after G2 X irradiation. Previous studies with DNA repair-deficient mutants and DNA repair inhibitors strongly indicate that the enhancement results from a G2 deficiency(ies) in DNA repair. We report here biochemical evidence for a DNA repair deficiency that correlates with the cytogenetic studies. In the alkaline elution technique, after a pulse label with radioactive thymidine in the presence of 3-acetylaminobenzamide (a G2-phase blocker) and X irradiation, DNA from tumor or cancer-prone cells elutes more rapidly during the postirradiation period than that from normal cells. These results indicate that the DNA of tumor and cancer-prone cells either repairs more slowly or acquires more breaks than that of normal cells; breaks can accumulate during incomplete or deficient repair processes. The kinetic difference between normal and tumor or cancer-prone cells in DNA strand-break repair reaches a maximum within 2 h, and this maximum corresponds to the kinetic difference in chromatid aberration incidence following X irradiation reported previously. These findings support the concept that cells showing enhanced G2 chromatid radiosensitivity are deficient in DNA repair. The findings could also lead to a biochemical assay for cancer susceptibility

  3. Post radiation protection and enhancement of DNA repair of beta glucan isolated from Ganoderma lucidum

    International Nuclear Information System (INIS)

    Pillai, Thulasi G.; Nair, C.K.K.; Uma Devi, P.

    2013-01-01

    Ganoderma lucidum (Fr) P. Karst, commonly known as Reishi in Japan and Ling Zhi in China, is well known for its medicinal properties. G. lucidum contains a number of components among which the polysaccharides, particularly beta-glucan, and triterpenoids are the major active components. Radioprotective effect of a beta glucan (BG) isolated from the mushroom G. lucidum against radiation induced damage was investigated taking mouse survival and chromosomal aberrations as end points. DNA repair enhancing property of BG was determined by comet assay in human peripheral blood leucocytes. Young Swiss albino mice were exposed to whole body γ-irradiation. For mouse survival study, BG was administered orally 5 min after 8 Gy radiation exposures and at 4 Gy exposure for chromosomal aberrations. BG at 500 ug/kg body wt produced 66% mouse survival at 30 days given post irradiation. In chromosomal aberrations significant reduction in number of aberrant cells and different types of aberrations was observed in BG administered group compared to RT along treated group. For DNA repair, the comet parameters were studied at 2 Gy γ-irradiation with 15 min intervals. The comet parameters were reduced to normal levels after 120 min of exposure. The DNA repairing ability of BG contributes to the post radio protective effect of BG. (author)

  4. Tumor endothelium marker-8 based decoys exhibit superiority over capillary morphogenesis protein-2 based decoys as anthrax toxin inhibitors.

    Directory of Open Access Journals (Sweden)

    Chenguang Cai

    Full Text Available Anthrax toxin is the major virulence factor produced by Bacillus anthracis. The toxin consists of three protein subunits: protective antigen (PA, lethal factor, and edema factor. Inhibition of PA binding to its receptors, tumor endothelium marker-8 (TEM8 and capillary morphogenesis protein-2 (CMG2 can effectively block anthrax intoxication, which is particularly valuable when the toxin has already been overproduced at the late stage of anthrax infection, thus rendering antibiotics ineffectual. Receptor-like agonists, such as the mammalian cell-expressed von Willebrand factor type A (vWA domain of CMG2 (sCMG2, have demonstrated potency against the anthrax toxin. However, the soluble vWA domain of TEM8 (sTEM8 was ruled out as an anthrax toxin inhibitor candidate due to its inferior affinity to PA. In the present study, we report that L56A, a PA-binding-affinity-elevated mutant of sTEM8, could inhibit anthrax intoxication as effectively as sCMG2 in Fisher 344 rats. Additionally, pharmacokinetics showed that L56A and sTEM8 exhibit advantages over sCMG2 with better lung-targeting and longer plasma retention time, which may contribute to their enhanced protective ability in vivo. Our results suggest that receptor decoys based on TEM8 are promising anthrax toxin inhibitors and, together with the pharmacokinetic studies in this report, may contribute to the development of novel anthrax drugs.

  5. Twin Screw Extruder Production of MTTP Decoy Flares SERDP WP-1240

    National Research Council Canada - National Science Library

    Campbell, Carol

    2005-01-01

    The objective of this effort is to develop an environmentally acceptable decoy flare formulation and process to produce aircraft decoy flares without the use of HAP or Volatile Organic Compounds (VOC...

  6. Metformin enhances radiosensitivity via inhibition of DNA repair pathway in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Youn Kyoung; Kim, Mi Sook; Lee, Ji Young; Song, Kyung Hee; Choi, Kyul; Kim, Eun Ho; Ha, Hun Joo [Ewha Womans University, Seoul (Korea, Republic of)

    2014-04-15

    In this study, we provide a scientific rationale for the clinical application of metformin as a radiosensitizer in colorectal cancer. Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women worldwide. Currently, it is one of the commonest chemoradiotherapy worked better than the radiotherapy or chemotherapy in colorectal cancer. To enhance radiosensitivity of tumor cells for chemoradiotherapy, it is to use potential anticancer agents that act as radiosensitizers. Metformin, one of the most widely used antidiabetic drugs, has recently been associated with potential antitumorigenic effects. Our data shows that metformin combined with radiation enhances the efficacy of radiotherapy and down-regulates DNA repair proteins. Therefore, we provides a scientific rationale for the clinical application of metformin as a radiosensitizer in colorectal cancer.

  7. Metformin enhances radiosensitivity via inhibition of DNA repair pathway in colorectal cancer

    International Nuclear Information System (INIS)

    Jeong, Youn Kyoung; Kim, Mi Sook; Lee, Ji Young; Song, Kyung Hee; Choi, Kyul; Kim, Eun Ho; Ha, Hun Joo

    2014-01-01

    In this study, we provide a scientific rationale for the clinical application of metformin as a radiosensitizer in colorectal cancer. Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women worldwide. Currently, it is one of the commonest chemoradiotherapy worked better than the radiotherapy or chemotherapy in colorectal cancer. To enhance radiosensitivity of tumor cells for chemoradiotherapy, it is to use potential anticancer agents that act as radiosensitizers. Metformin, one of the most widely used antidiabetic drugs, has recently been associated with potential antitumorigenic effects. Our data shows that metformin combined with radiation enhances the efficacy of radiotherapy and down-regulates DNA repair proteins. Therefore, we provides a scientific rationale for the clinical application of metformin as a radiosensitizer in colorectal cancer

  8. Caffeine-enhanced survival of radiation-sensitive, repair-deficient Chinese hamster cells

    International Nuclear Information System (INIS)

    Utsumi, H.; Elkind, M.M.

    1983-01-01

    A clone of V79 Chinese hamster cells (V79-AL162/S-10) with unique properties has been isolated after a challenge of parental cells (V79-AL162) with 1 mM ouabain. Compared with parental cells, or with other clones isolated after the ouabain challenge, these cells form smaller colonies, are more sensitive to both x rays and fission-spectrum neutrons, and respond atypically to a postirradiation treatment with caffeine. Their enhanced response to x rays results mainly from a large reduction in the shoulder of their survival curve, probably because in late S phase, the most resistant phase in the cell cycle, the survival curve of these cells has a reduced shoulder width. Caffeine, and to a lesser extent theophylline, added to the colony-forming medium immediately after exposure appreciably increases the width of the shoulder of these sensitive cells, whereas caffeine has the opposite effect on the response of normal V79 cells. Thus the unique response of the V79-AL162/S-10 cells to a radiation posttreatment with caffeine (increased survival) results from a net increase in their ability to repair damage that is otherwise lethal; caffeine treatment ordinarly prevents normal V79 cells from repairing damage that is only potentially lethal

  9. E. coli mismatch repair enhances AT-to-GC mutagenesis caused by alkylating agents.

    Science.gov (United States)

    Nakano, Kota; Yamada, Yoko; Takahashi, Eizo; Arimoto, Sakae; Okamoto, Keinosuke; Negishi, Kazuo; Negishi, Tomoe

    2017-03-01

    Alkylating agents are known to induce the formation of O 6 -alkylguanine (O 6 -alkG) and O 4 -alkylthymine (O 4 -alkT) in DNA. These lesions have been widely investigated as major sources of mutations. We previously showed that mismatch repair (MMR) facilitates the suppression of GC-to-AT mutations caused by O 6 -methylguanine more efficiently than the suppression of GC-to-AT mutations caused by O 6 -ethylguanine. However, the manner by which O 4 -alkyT lesions are repaired remains unclear. In the present study, we investigated the repair pathway involved in the repair of O 4 -alkT. The E. coli CC106 strain, which harbors Δprolac in its genomic DNA and carries the F'CC106 episome, can be used to detect AT-to-GC reverse-mutation of the gene encoding β-galactosidase. Such AT-to-GC mutations should be induced through the formation of O 4 -alkT at AT base pairs. As expected, an O 6 -alkylguanine-DNA alkyltransferase (AGT) -deficient CC106 strain, which is defective in both ada and agt genes, exhibited elevated mutant frequencies in the presence of methylating agents and ethylating agents. However, in the UvrA-deficient strain, the methylating agents were less mutagenic than in wild-type, while ethylating agents were more mutagenic than in wild-type, as observed with agents that induce O 6 -alkylguanine modifications. Unexpectedly, the mutant frequencies decreased in a MutS-deficient strain, and a similar tendency was observed in MutL- or MutH-deficient strains. Thus, MMR appears to promote mutation at AT base pairs. Similar results were obtained in experiments employing double-mutant strains harboring defects in both MMR and AGT, or MMR and NER. E. coli MMR enhances AT-to-GC mutagenesis, such as that caused by O 4 -alkylthymine. We hypothesize that the MutS protein recognizes the O 4 -alkT:A base pair more efficiently than O 4 -alkT:G. Such a distinction would result in misincorporation of G at the O 4 -alkT site, followed by higher mutation frequencies in wild

  10. Transformation of ultraviolet-irradiated human fibroblasts by simian virus 40 is enhanced by cellular DNA repair functions

    International Nuclear Information System (INIS)

    Hall, J.D.

    1981-01-01

    Human fibroblasts irradiated with ultraviolet light were either tested for survival (colony formation) or infected with simian virus 40 and examined for transformation (foci formation). For normal cell cultures, the fractions of surviving colonies which were also transformed increased with increasing irradiation dose. In contrast, little increase in the transformation of ultraviolet-irradiated repair-deficient (xeroderma pigmentosum and xeroderma pigmentosum variant) cells was observed. Similar experiments with xeroderma pigmentosum variant cells treated with caffeine following irradiation indicated that, under these conditions, the deficient cells produced more transformants among the survivors of ultraviolet irradiation than did unirradiated cells. These results suggest (1) that DNA repair functions, not DNA damage per se, are required for enhanced viral transformation in normal cells; (2) that functions involved in excision repair and functions needed for replication of ultraviolet-damaged DNA appear necessary for this stimulation; and (3) that blocking DNA replication in ultraviolet-irradiated xeroderma pigmentosum variant cells by caffeine enhances viral transformation. (Auth.)

  11. Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles

    DEFF Research Database (Denmark)

    Cogoi, S; Jakobsen, U; Pedersen, E B

    2016-01-01

    KRAS is mutated in >90% of pancreatic ductal adenocarcinomas. As its inactivation leads to tumour regression, mutant KRAS is considered an attractive target for anticancer drugs. In this study we report a new delivery strategy for a G4-decoy oligonucleotide that sequesters MAZ, a transcription fa...

  12. Decoys Selection in Benchmarking Datasets: Overview and Perspectives

    Science.gov (United States)

    Réau, Manon; Langenfeld, Florent; Zagury, Jean-François; Lagarde, Nathalie; Montes, Matthieu

    2018-01-01

    Virtual Screening (VS) is designed to prospectively help identifying potential hits, i.e., compounds capable of interacting with a given target and potentially modulate its activity, out of large compound collections. Among the variety of methodologies, it is crucial to select the protocol that is the most adapted to the query/target system under study and that yields the most reliable output. To this aim, the performance of VS methods is commonly evaluated and compared by computing their ability to retrieve active compounds in benchmarking datasets. The benchmarking datasets contain a subset of known active compounds together with a subset of decoys, i.e., assumed non-active molecules. The composition of both the active and the decoy compounds subsets is critical to limit the biases in the evaluation of the VS methods. In this review, we focus on the selection of decoy compounds that has considerably changed over the years, from randomly selected compounds to highly customized or experimentally validated negative compounds. We first outline the evolution of decoys selection in benchmarking databases as well as current benchmarking databases that tend to minimize the introduction of biases, and secondly, we propose recommendations for the selection and the design of benchmarking datasets. PMID:29416509

  13. Towards creating believable decoy project folders for detecting data theft

    NARCIS (Netherlands)

    Thaler, S.; den Hartog, J.; Petkovic, M.

    2016-01-01

    Digital data theft is difficult to detect and typically it also takes a long time to discover that data has been stolen. This paper introduces a data-driven approach based on Markov chains to create believable decoy project folders which can assist in detecting potentially ongoing attacks. This can

  14. Adaptive response to ionizing radiation in normal human skin fibroblasts. Enhancement of DNA repair rate and modulation of gene expression

    International Nuclear Information System (INIS)

    Toledo, S.M. de; Mitchel, R.E.J.; Azzam, E.; Ottawa Univ., ON; Raaphorst, G.P.

    1994-01-01

    Low doses and dose rates of ionizing radiation enhance the rate of DNA repair in human fibroblasts and protect the cells against radiation-induced micronucleus formation. Chronic exposures reduce the mRNA levels of the genes topoisomerase II and FACC-1 (Fanconi's anemia, group C). (authors). 11 refs., 1 tab., 2 figs

  15. Genetic defects in DNA repair system and enhancement of intergenote transformation efficiency in Bacillus subtilis Marburg

    International Nuclear Information System (INIS)

    Matsumoto, K.; Takahashi, H.; Saito, H.; Ikeda, Y.

    1978-01-01

    Mechanisms of inefficiency in heterospecies transformation were studied with a transformation system consisting of Bacillus subtilis 168TI (trpC2thy) as recipient and of DNA prepared from partially hybrid strains of B. subtilis which had incorporated trp + DNA of B. amyloliquefaciens 203 (formerly, B. megaterium 203) in the chromosome (termed intergenote). The intergenote transformation was not so efficient as the corresponding homospecies transformation and the efficiency appeared to relate inversely with the length of heterologous portion in the intergenote. When a variety of ultraviolet light (UV) sensitive mutants, deficient in host-cell reactivation capacity, were used as recipients for the intergenote transformation, 2 out of 16 mutants exhibited significantly enhanced transformation efficiency of the trpC marker. Genetic studies by transformation showed that the trait relating to the enhancement of intergenote-transformation efficiency was always associated with the UV sensitivity, suggesting that these two traits are determined by a single gene. The efficiency of intergenote transformation was highly affected also by DNA concentration; the lower the concentration, the less the efficiency. When, however, the UV sensitive mutant was used as recipient, the effect of DNA concentration was largely diminished, suggesting the reduction of DNA-inactivating activity in the UV sensitive recipient. These results were discussed in relation to a possible excision-repair system selectively correcting the mismatched DNA in the course of intergenote transformation. (orig.) [de

  16. Exploring decoy effects on computerized task preferences in rhesus monkeys (Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Audrey E. Parrish

    2018-05-01

    Full Text Available The asymmetric dominance effect or decoy effect emerges when a third inferior option is introduced to a choice set. The decoy option, although typically not chosen, impacts relative preference for the original two options. This decisional bias stands in contrast with rational choice theory, which dictates that choice behavior should remain consistent for the original options with the addition of different alternatives to a choice set such as the decoy. In the current study, we assessed the decoy effect in rhesus monkeys using a computerized task battery that introduced two different computerized tasks, including a matching-to-sample task and a psychomotor task called PURSUIT. Decoy tasks were designed such that they were inferior versions of these original task options, requiring longer time to completion (via slowed cursor speeds and subsequently reduced reinforcement rates. Monkeys learned to associate unique icons for each task (including for decoy tasks, and used these icons to select their preferred task from a choice set of two to three task options. Monkeys learned to perform all tasks, but did not show evidence of the decoy effect using this task preference paradigm. We discuss the role of initial task preference (and task biases, task type (symbolic vs. perceptual, and decoy effect sizes in light of these findings. We contrast the current results to previous findings of the decoy effect in rhesus monkeys using a perceptual paradigm as well as to other evidence of the decoy effect in non-primate animal species.

  17. Development of biodegradable polycaprolactone film as an internal fixation material to enhance tendon repair: an in vitro study.

    Science.gov (United States)

    Hu, Jian-Zhong; Zhou, Yong-Chun; Huang, Li-Hua; Lu, Hong-Bin

    2013-08-19

    Current tendon repair techniques do not provide sufficient tensile strength at the repair site, and thus early active motion rehabilitation after tendon repair is discouraged. To enhance the post-operative tensile strength, we proposed and tested an internal fixation technique using a polycaprolactone (PCL) biofilm. PCL was chosen for its good biocompatibility, excellent mechanical strength, and an appropriate degradation time scale. PCL biofilms were prepared by a modified melt-molding/leaching technique, and the physical and mechanical properties and in vitro degradation rate were assessed. The pore size distribution of the biofilm and the paratenon of native tendons were observed using scanning electron microscopy. Next, we determined whether this biofilm could enhance the tensile strength of repaired tendons. We performed tensile tests on rabbit Achilles tendons that were first lacerated and then repaired: 1) using modified Kessler suture combined with running peripheral suture ('control' group), or 2) using biofilm to wrap the tendon and then fixation with sutures ('biofilm' group). The influence of different repair techniques on tendon tensile strength was evaluated by mechanical testing. The novel biofilm had supple texture and a smooth surface. The mean thickness of the biofilm was 0.25 mm. The mean porosity of the biofilm was 45.3%. The paratenon of the rabbit Achilles tendon had pores with diameters ranging from 1 to 9 μm, which were similar to the 4-12 μm diameter pores in the biofilm cross-section. The weight loss of the biofilms at 4 weeks was only 0.07%. The molecular weight of PCL biofilms did not change after immersion in phosphate buffered saline for 4 weeks. The failure loads of the biofilm were similar before (48 ± 9 N) and after immersion (47 ± 7 N, P > 0.1). The biofilm group had ~70% higher mean failure loads and 93% higher stiffness compared with the control group. We proposed and tested an internal fixation technique

  18. Inhibition of oncostatin M in osteoarthritic synovial fluid enhances GAG production in osteoarthritic cartilage repair

    Directory of Open Access Journals (Sweden)

    M Beekhuizen

    2013-09-01

    Full Text Available Mediators in the synovial fluid are thought to play a major role in osteoarthritic cartilage turnover. The purpose of the current study was to investigate the role of oncostatin M (OSM in osteoarthritis (OA by evaluating the presence of the cytokine and its receptors in the OA joint and interfering with its activity in synovial fluid co-cultured with cartilage explants. OSM levels were increased in the synovial fluid of osteoarthritic patients compared to healthy donors. Immunohistochemistry confirmed the presence of both the leukaemia inhibitory factor (LIF and OSM receptors for OSM throughout the whole depth of osteoarthritic cartilage and synovial tissue, whereas in healthy cartilage their presence seemed more restricted to the superficial zone. Blocking OSM activity, using an activity inhibiting antibody, in 25 % osteoarthritic synovial fluid added to OA cartilage explant cultures increased glycosaminoglycan (GAG content from 18.6 mg/g to 24.3 mg/g (P < 0.03 and total production from 7.0 mg/g to 11.9 mg/g (P < 0.003. However, OSM exogenously added to cartilage explant cultures reflecting low and high concentrations in the synovial fluid (5 and 50 pg/mL did not affect cartilage matrix turnover, suggesting that factors present in the synovial fluid act in concert with OSM to inhibit GAG production. The current study indicates the potential to enhance cartilage repair in osteoarthritis by modulating the joint environment by interfering with OSM activity.

  19. 2006-2008 annual review on aerial infrared decoy flares

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Ernst-Christian [NATO Munitions Safety Information Analysis Center, Brussels (Belgium)

    2009-02-15

    The most recent progress in the field of advanced aerial infrared decoy flare technology is documented. 71 references from the public domain are given. Recently, two reviews on progress in the field of aerial infrared decoy flares have been prepared by the author. The fast development in the field already delayed the preparation of the second report by nearly a year.Hence, the objective of the present paper is to report about recent advances in the field of aerial infrared countermeasures and related topics. The paper treats information published between January, 2005 and September, 30, 2008. Depending on the progress, it is intended to report occasionally in the future about new developments and scientific findings in this field. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

  20. An Effectiveness Analysis of the Tactical Employment of Decoys

    Science.gov (United States)

    1994-06-03

    desert made it impossible to hide the dense concentration of vehicles in the three assembly areas: 1st Armoured Division in Assembly Area (AA) Murrayfield...North, 24th Armoured Brigade in AA Murrayfield South, and 10th Armoured Division in AA Melting Pot. However, an ingenious combination of decoys and...hood, configured to resemble an ammo carrier, was often draped over tanks to disguise thenm12 To reinforce the story that the British main attack would

  1. Effects of towed-decoys against an anti-air missile with a monopulse seeker

    OpenAIRE

    Yeh, Jia-Hsin

    1995-01-01

    This thesis evaluates the protection provided by towed decoys deployed by an aircraft during an engagement against an anti-air missile equipped with a monopulse seeker. The research emphasizes the use of passive decoys. Many of the operational parameters required before the deployment of towed-decoy are investigated, including the strength of reflection, the tether length, the direction of release, under different missile incoming directions. This thesis evaluated two reflection cases. One is...

  2. Design and Implementation of Decoy Enhanced Dynamic Virtualization Networks

    Science.gov (United States)

    2016-12-12

    attacks against the critical server infrastructures within both government organizations and businesses, and the number of data breaches increases...luring techniques and engagement servers to entice an attacker away from the valuable servers. As the average time to identify and resolve a data breach for

  3. Plasmid (pKM101)-mediated enhancement of repair and mutagenesis: dependence on chromosomal genes in 'Escherichia coli' K-12

    International Nuclear Information System (INIS)

    Walker, G.C.

    1977-01-01

    The drug resistance plasmid pKM101 plays a major role in the Ames Salmonella/microsome carcinogen detecting system by enhancing chemical mutagenesis. It is shown that in Escherichia coli K-12 the plasmid pKM101 enhances both spontaneous and methyl methanesulfonate-caused reversion of an ochre mutation, bacterial survival after ultaviolet irradiation, and reactivation of ultraviolet-irradiated lambda in unirradiated cells. All these effects are shown to be dependent on the recA + lexA + genotype but not on the recB + recC + or recF + genotypes. The recA lexA-dependence of the plasmid-mediated repair and mutagenesis suggests an interaction with the cell's inducible error-prone repair system. The presence of pKM101 is shown to cause an additional increase in methyl methanesulfonate mutagenesis in a tif mutant beyond that caused by growth at 42 0 . The presence of the plasmid raises the level of the Weigle-reactivation curve for the reactivation of ultraviolet-irradiated lambda in E. coli and causes a shift of the maximum to a higher UV fluence. These observations suggest that pKM101 does not exert its effects by altering the regulation of the cell's error-prone repair system but rather by supplying a mechanistic component or components. (orig.) [de

  4. TLR9 agonists oppositely modulate DNA repair genes in tumor versus immune cells and enhance chemotherapy effects.

    Science.gov (United States)

    Sommariva, Michele; De Cecco, Loris; De Cesare, Michelandrea; Sfondrini, Lucia; Ménard, Sylvie; Melani, Cecilia; Delia, Domenico; Zaffaroni, Nadia; Pratesi, Graziella; Uva, Valentina; Tagliabue, Elda; Balsari, Andrea

    2011-10-15

    Synthetic oligodeoxynucleotides expressing CpG motifs (CpG-ODN) are a Toll-like receptor 9 (TLR9) agonist that can enhance the antitumor activity of DNA-damaging chemotherapy and radiation therapy in preclinical mouse models. We hypothesized that the success of these combinations is related to the ability of CpG-ODN to modulate genes involved in DNA repair. We conducted an in silico analysis of genes implicated in DNA repair in data sets obtained from murine colon carcinoma cells in mice injected intratumorally with CpG-ODN and from splenocytes in mice treated intraperitoneally with CpG-ODN. CpG-ODN treatment caused downregulation of DNA repair genes in tumors. Microarray analyses of human IGROV-1 ovarian carcinoma xenografts in mice treated intraperitoneally with CpG-ODN confirmed in silico findings. When combined with the DNA-damaging drug cisplatin, CpG-ODN significantly increased the life span of mice compared with individual treatments. In contrast, CpG-ODN led to an upregulation of genes involved in DNA repair in immune cells. Cisplatin-treated patients with ovarian carcinoma as well as anthracycline-treated patients with breast cancer who are classified as "CpG-like" for the level of expression of CpG-ODN modulated DNA repair genes have a better outcome than patients classified as "CpG-untreated-like," indicating the relevance of these genes in the tumor cell response to DNA-damaging drugs. Taken together, the findings provide evidence that the tumor microenvironment can sensitize cancer cells to DNA-damaging chemotherapy, thereby expanding the benefits of CpG-ODN therapy beyond induction of a strong immune response.

  5. Cell factory-derived bioactive molecules with polymeric cryogel scaffold enhance the repair of subchondral cartilage defect in rabbits.

    Science.gov (United States)

    Gupta, Ankur; Bhat, Sumrita; Chaudhari, Bhushan P; Gupta, Kailash C; Tägil, Magnus; Zheng, Ming Hao; Kumar, Ashok; Lidgren, Lars

    2017-06-01

    We have explored the potential of cell factory-derived bioactive molecules, isolated from conditioned media of primary goat chondrocytes, for the repair of subchondral cartilage defects. Enzyme-linked immunosorbent assay (ELISA) confirms the presence of transforming growth factor-β1 in an isolated protein fraction (12.56 ± 1.15 ng/mg protein fraction). These bioactive molecules were used alone or with chitosan-agarose-gelatin cryogel scaffolds, with and without chondrocytes, to check whether combined approaches further enhance cartilage repair. To evaluate this, an in vivo study was conducted on New Zealand rabbits in which a subchondral defect (4.5 mm wide × 4.5 mm deep) was surgically created. Starting after the operation, bioactive molecules were injected at the defect site at regular intervals of 14 days. Histopathological analysis showed that rabbits treated with bioactive molecules alone had cartilage regeneration after 4 weeks. However, rabbits treated with bioactive molecules along with scaffolds, with or without cells, showed cartilage formation after 3 weeks; 6 weeks after surgery, the cartilage regenerated in rabbits treated with either bioactive molecules alone or in combinations showed morphological similarities to native cartilage. No systemic cytotoxicity or inflammatory response was induced by any of the treatments. Further, ELISA was done to determine systemic toxicity, which showed no difference in concentration of tumour necrosis factor-α in blood serum, before or after surgery. In conclusion, intra-articular injection with bioactive molecules alone may be used for the repair of subchondral cartilage defects, and bioactive molecules along with chondrocyte-seeded scaffolds further enhance the repair. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Enhancement of osteogenesis and biodegradation control by brushite coating on Mg-Nd-Zn-Zr alloy for mandibular bone repair.

    Science.gov (United States)

    Guan, Xingmin; Xiong, Meiping; Zeng, Feiyue; Xu, Bin; Yang, Lingdi; Guo, Han; Niu, Jialin; Zhang, Jian; Chen, Chenxin; Pei, Jia; Huang, Hua; Yuan, Guangyin

    2014-12-10

    To diminish incongruity between bone regeneration and biodegradation of implant magnesium alloy applied for mandibular bone repair, a brushite coating was deposited on a matrix of a Mg-Nd-Zn-Zr (hereafter, denoted as JDBM) alloy to control the degradation rate of the implant and enhance osteogenesis of the mandible bone. Both in vitro and in vivo evaluations were carried out in the present work. Viability and adhesion assays of rabbit bone marrow mesenchyal stem cells (rBM-MSCs) were applied to determine the biocompatibility of a brushite-coated JDBM alloy. Osteogenic gene expression was characterized by quantitative real-time polymerase chain reaction (RT-PCR). Brushite-coated JDBM screws were implanted into mandible bones of rabbits for 1, 4, and 7 months, respectively, using 316L stainless steel screws as a control group. In vivo biodegradation rate was determined by synchrotron radiation X-ray microtomography, and osteogenesis was observed and evaluated using Van Gieson's picric acid-fuchsin. Both the naked JDBM and brushite-coated JDBM samples revealed adequate biosafety and biocompatibility as bone repair substitutes. In vitro results showed that brushite-coated JDBM considerably induced osteogenic differentiation of rBM-MSCs. And in vivo experiments indicated that brushite-coated JDBM screws presented advantages in osteoconductivity and osteogenesis of mandible bone of rabbits. Degradation rate was suppressed at a lower level at the initial stage of implantation when new bone tissue formed. Brushite, which can enhance oeteogenesis and partly control the degradation rate of an implant, is an appropriate coating for JDBM alloys used for mandibular repair. The Mg-Nd-Zn-Zr alloy with brushite coating possesses great potential for clinical applications for mandibular repair.

  7. Targeting DNA double strand break repair with hyperthermia and DNA-PKcs inhibition to enhance the effect of radiation treatment.

    Science.gov (United States)

    van Oorschot, Bregje; Granata, Giovanna; Di Franco, Simone; Ten Cate, Rosemarie; Rodermond, Hans M; Todaro, Matilde; Medema, Jan Paul; Franken, Nicolaas A P

    2016-10-04

    Radiotherapy is based on the induction of lethal DNA damage, primarily DNA double-strand breaks (DSB). Efficient DSB repair via Non-Homologous End Joining or Homologous Recombination can therefore undermine the efficacy of radiotherapy. By suppressing DNA-DSB repair with hyperthermia (HT) and DNA-PKcs inhibitor NU7441 (DNA-PKcsi), we aim to enhance the effect of radiation.The sensitizing effect of HT for 1 hour at 42°C and DNA-PKcsi [1 μM] to radiation treatment was investigated in cervical and breast cancer cells, primary breast cancer sphere cells (BCSCs) enriched for cancer stem cells, and in an in vivo human tumor model. A significant radio-enhancement effect was observed for all cell types when DNA-PKcsi and HT were applied separately, and when both were combined, HT and DNA-PKcsi enhanced radio-sensitivity to an even greater extent. Strikingly, combined treatment resulted in significantly lower survival rates, 2 to 2.5 fold increase in apoptosis, more residual DNA-DSB 6 h post treatment and a G2-phase arrest. In addition, tumor growth analysis in vivo showed significant reduction in tumor growth and elevated caspase-3 activity when radiation was combined with HT and DNA-PKcsi compared to radiation alone. Importantly, no toxic side effects of HT or DNA-PKcsi were found.In conclusion, inhibiting DNA-DSB repair using HT and DNA-PKcsi before radiotherapy leads to enhanced cytotoxicity in cancer cells. This effect was even noticed in the more radio-resistant BCSCs, which are clearly sensitized by combined treatment. Therefore, the addition of HT and DNA-PKcsi to conventional radiotherapy is promising and might contribute to more efficient tumor control and patient outcome.

  8. The Decoy Effect as a Nudge: Boosting Hand Hygiene With a Worse Option.

    Science.gov (United States)

    Li, Meng; Sun, Yan; Chen, Hui

    2018-05-01

    This article provides the first test of the decoy effect as a nudge to influence real-world behavior. The decoy effect is the phenomenon that an additional but worse option can boost the appeal of an existing option. It has been widely demonstrated in hypothetical choices, but its usefulness in real-world settings has been subject to debate. In three longitudinal experiments in food-processing factories, we tested two decoy sanitation options that were worse than the existing sanitizer spray bottle. Results showed that the presence of a decoy, but not an additional copy of the original sanitizer bottle in a different color, drastically increased food workers' hand sanitizer use from the original sanitizer bottle and, consequently, improved workers' passing rate in hand sanitary tests from 60% to 70% to above 90% for 20 days. These findings indicate that the decoy effect can be a powerful nudge technique to influence real-world behavior.

  9. Decoy-state quantum key distribution with two-way classical postprocessing

    International Nuclear Information System (INIS)

    Ma Xiongfeng; Fung, C.-H.F.; Chen Kai; Lo, H.-K.; Dupuis, Frederic; Tamaki, Kiyoshi

    2006-01-01

    Decoy states have recently been proposed as a useful method for substantially improving the performance of quantum key distribution (QKD) protocols when a coherent-state source is used. Previously, data postprocessing schemes based on one-way classical communications were considered for use with decoy states. In this paper, we develop two data postprocessing schemes for the decoy-state method using two-way classical communications. Our numerical simulation (using parameters from a specific QKD experiment as an example) results show that our scheme is able to extend the maximal secure distance from 142 km (using only one-way classical communications with decoy states) to 181 km. The second scheme is able to achieve a 10% greater key generation rate in the whole regime of distances. We conclude that decoy-state QKD with two-way classical postprocessing is of practical interest

  10. Sensitization to radiation and alkylating agents by inhibitors of poly(ADP-ribose) polymerase is enhanced in cells deficient in DNA double-strand break repair.

    Science.gov (United States)

    Löser, Dana A; Shibata, Atsushi; Shibata, Akiko K; Woodbine, Lisa J; Jeggo, Penny A; Chalmers, Anthony J

    2010-06-01

    As single agents, chemical inhibitors of poly(ADP-ribose) polymerase (PARP) are nontoxic and have clinical efficacy against BRCA1- and BRCA2-deficient tumors. PARP inhibitors also enhance the cytotoxicity of ionizing radiation and alkylating agents but will only improve clinical outcomes if tumor sensitization exceeds effects on normal tissues. It is unclear how tumor DNA repair proficiency affects the degree of sensitization. We have previously shown that the radiosensitizing effect of PARP inhibition requires DNA replication and will therefore affect rapidly proliferating tumors more than normal tissues. Because many tumors exhibit defective DNA repair, we investigated the impact of double-strand break (DSB) repair integrity on the sensitizing effects of the PARP inhibitor olaparib. Sensitization to ionizing radiation and the alkylating agent methylmethane sulfonate was enhanced in DSB repair-deficient cells. In Artemis(-/-) and ATM(-/-) mouse embryo fibroblasts, sensitization was replication dependent and associated with defective repair of replication-associated damage. Radiosensitization of Ligase IV(-/-) mouse embryo fibroblasts was independent of DNA replication and is explained by inhibition of "alternative" end joining. After methylmethane sulfonate treatment, PARP inhibition promoted replication-independent accumulation of DSB, repair of which required Ligase IV. Our findings predict that the sensitizing effects of PARP inhibitors will be more pronounced in rapidly dividing and/or DNA repair defective tumors than normal tissues and show their potential to enhance the therapeutic ratio achieved by conventional DNA-damaging agents.

  11. The application of viral vectors to enhance regeneration after peripheral nerve repair

    NARCIS (Netherlands)

    Tannemaat, Martijn R; Verhaagen, J.; Malessy, Martijn J A

    2008-01-01

    OBJECTIVE: Despite great advancements in surgical repair techniques, a considerable degree of functional impairment remains in the majority of patients after peripheral nerve reconstruction. New concepts to promote regeneration of the peripheral nerve are needed since it is generally held that

  12. Enhanced base excision repair capacity in carotid atherosclerosis may protect nuclear DNA but not mitochondrial DNA

    DEFF Research Database (Denmark)

    Skarpengland, Tonje; B. Dahl, Tuva; Skjelland, Mona

    2016-01-01

    Lesional and systemic oxidative stress has been implicated in the pathogenesis of atherosclerosis, potentially leading to accumulation of DNA base lesions within atherosclerotic plaques. Although base excision repair (BER) is a major pathway counteracting oxidative DNA damage, our knowledge on BER...

  13. Mismatch repair deficiency does not enhance ENU mutagenesis in the zebrafish germ line.

    NARCIS (Netherlands)

    Feitsma, H.; de Bruijn, E.; van de Belt, J.; Nijman, I.J.; Cuppen, E.

    2008-01-01

    S(N)1-type alkylating agents such as N-ethyl-N-nitrosourea (ENU) are very potent mutagens. They act by transferring their alkyl group to DNA bases, which, upon mispairing during replication, can cause single base pair mutations in the next replication cycle. As DNA mismatch repair (MMR) proteins are

  14. Human embryonic stem cells have enhanced repair of multiple forms of DNA damage

    DEFF Research Database (Denmark)

    Maynard, Scott; Swistowska, Anna Maria; Lee, Jae Wan

    2008-01-01

    cells compared with various differentiated murine cells. Using single-cell gel electrophoresis (comet assay) we found that human embryonic stem cells (BG01, I6) have more efficient repair of different types of DNA damage (generated from H2O2, UV-C, ionizing radiation, or psoralen) than human primary...

  15. Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype.

    Science.gov (United States)

    Yuldasheva, Nadira Y; Rashid, Sheikh Tawqeer; Haywood, Natalie J; Cordell, Paul; Mughal, Romana; Viswambharan, Hema; Imrie, Helen; Sukumar, Piruthivi; Cubbon, Richard M; Aziz, Amir; Gage, Matthew; Mbonye, Kamatamu Amanda; Smith, Jessica; Galloway, Stacey; Skromna, Anna; Scott, D Julian A; Kearney, Mark T; Wheatcroft, Stephen B

    2014-09-01

    Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R(+/-)). Endothelial regeneration after arterial injury was accelerated in IGF1R(+/-) mice. Although the yield of angiogenic progenitor cells was lower in IGF1R(+/-) mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R(+/-) bone marrow-derived CD117(+) cells into wild-type mice. IGF1R(+/-) cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117(+) cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury. © 2014 American Heart Association, Inc.

  16. Molecular mechanism of radioadaptive response: A cross-adaptive response for enhanced repair of DNA damage in adapted cells

    International Nuclear Information System (INIS)

    Takaji Ikushima

    1997-01-01

    The radioadaptive response (RAR) has been attributed to the induction of a repair mechanism by low doses of ionizing radiation, but the molecular nature of the mechanism is not yet elucidated. We have characterized RAR in a series of experiments in cultured Chinese hamster V79 cells. A 4-h interval is required for the full expression of RAR, which decays with the progression of cell proliferation. Treatments with inhibitors of poly(ADP-ribose) polymerase, protein- or RNA synthesis, and protein kinase C suppress the RAR expression. The RAR cross-reacts on clastogenic lesions induced by other physical and chemical DNA-damaging agents. The presence of newly synthesised proteins has been detected during the expression period. Experiments performed using single-cell gel electrophoresis provided more direct evidence for a faster and enhaced DNA repair rate in adapted cells. Here, using single-cell gel electrophoresis, a cross-adaptive response has been demonstrated for enhanced repair of DNA damage induced by neocarzinostatin in radio-adapted cells. (author)

  17. Loss of CHD1 causes DNA repair defects and enhances prostate cancer therapeutic responsiveness

    DEFF Research Database (Denmark)

    Kari, Vijayalakshmi; Mansour, Wael Yassin; Raul, Sanjay Kumar

    2016-01-01

    The CHD1 gene, encoding the chromo-domain helicase DNA-binding protein-1, is one of the most frequently deleted genes in prostate cancer. Here, we examined the role of CHD1 in DNA double-strand break (DSB) repair in prostate cancer cells. We show that CHD1 is required for the recruitment of Ct......-homologous end joining. Together, we provide evidence for a previously unknown role of CHD1 in DNA DSB repair via HR and show that CHD1 depletion sensitizes cells to PARP inhibitors, which has potential therapeutic relevance. Our findings suggest that CHD1 deletion, like BRCA1/2 mutation in ovarian cancer, may...... serve as a marker for prostate cancer patient stratification and the utilization of targeted therapies such as PARP inhibitors, which specifically target tumors with HR defects....

  18. An Enhanced Vacuum Cure Technique for On-Aircraft Repair of Carbon-Bismaleimide Composites

    Science.gov (United States)

    Rider, Andrew N.; Baker, Alan A.; Wang, Chun H.; Smith, Graeme

    2011-06-01

    Carbon/bismaleimide (BMI) composite is increasingly employed in critical load carrying aircraft structures designed to operate at temperatures approaching 180°C. The high post-cure temperature (above 220°C) required to fully react the BMI resin, however, renders existing on-aircraft prepreg or wet layup repair methods invalid. This paper presents a new on-aircraft repair technique for carbon/BMI composites. The composite prepregs are first warm-staged to improve the ability to evacuate entrapped air. Then the patch is cured in the scarf cavity using the vacuum bag technique, followed by off-aircraft post-cure. The fully cured patch then can be bonded using a structural adhesive.

  19. Endogenous repair mechanisms enhanced in Parkinson's disease following stem cell therapy

    Directory of Open Access Journals (Sweden)

    Eleonora Napoli

    2017-01-01

    Full Text Available This mini-review highlights the innovative observation that transplanted human neural stem cells can bring about endogenous brain repair through the stimulation of multiple regenerative processes in the neurogenic area (i.e., subventricular zone [SVZ] in an animal model of Parkinson's disease (PD. In addition, we convey that identifying anti-inflammatory cytokines, therapeutic proteomes, and neurotrophic factors within the SVZ may be essential to induce brain repair and behavioral recovery. This work opens up a new area of research for further understanding the pathology and treatment of PD. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

  20. Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair

    Science.gov (United States)

    Agarwal, Rachit; García, Andrés J.

    2015-01-01

    Bone tissue has a remarkable ability to regenerate and heal itself. However, large bone defects and complex fractures still present a significant challenge to the medical community. Current treatments center on metal implants for structural and mechanical support and auto- or allo-grafts to substitute long bone defects. Metal implants are associated with several complications such as implant loosening and infections. Bone grafts suffer from donor site morbidity, reduced bioactivity, and risk of pathogen transmission. Surgical implants can be modified to provide vital biological cues, growth factors and cells in order to improve osseointegration and repair of bone defects. Here we review strategies and technologies to engineer metal surfaces to promote osseointegration with the host tissue. We also discuss strategies for modifying implants for cell adhesion and bone growth via integrin signaling and growth factor and cytokine delivery for bone defect repair. PMID:25861724

  1. Adult Stem Cell Based Enhancement of Nerve Conduit for Peripheral Nerve Repair

    Science.gov (United States)

    2016-10-01

    accompanied by injuries to peripheral nerves; if not repaired, the trauma can lead to significant dysfunction and disability . While nerves have the ability to...recovery, minimized disability , and increased quality of life for our wounded warriors. 2. KEYWORDS: Stem Cell, Nerve Conduit, Peripheral Nerve...would be a paradigm shift away from ordering X-rays at 10-12 weeks and only ordering a CT scan. It has the potential to change the standard of care

  2. Chronic Prosopis Glandulosa Treatment Blunts Neutrophil Infiltration and Enhances Muscle Repair after Contusion Injury

    Directory of Open Access Journals (Sweden)

    Cindy George

    2015-01-01

    Full Text Available The current treatment options for soft tissue injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscle. The current study aimed to evaluate the effects of oral Prosopis glandulosa treatment on inflammation and regeneration in skeletal muscle after contusion injury, in comparison to a conventional treatment. The gastrocnemius muscle of rats was subjected to mass-drop injury and muscle samples collected after 1-, 3 h, 1- and 7 days post-injury. Rats were treated with P. glandulosa (100 mg/kg/day either for 8 weeks prior to injury (up until day 7 post-injury, only post-injury, or with topically applied diclofenac post-injury (0.57 mg/kg. Neutrophil (His48-positive and macrophage (F4/80-positive infiltration was assessed by means of immunohistochemistry. Indicators of muscle satellite cell proliferation (ADAM12 and regeneration (desmin were used to evaluate muscle repair. Chronic P. glandulosa and diclofenac treatment (p < 0.0001 was associated with suppression of the neutrophil response to contusion injury, however only chronic P. glandulosa treatment facilitated more effective muscle recovery (increased ADAM12 (p < 0.05 and desmin (p < 0.001 expression, while diclofenac treatment had inhibitory effects on repair, despite effective inhibition of neutrophil response. Data indicates that P. glandulosa treatment results in more effective muscle repair after contusion.

  3. Investigation of sequential growth factor delivery during cuprizone challenge in mice aimed to enhance oligodendrogliogenesis and myelin repair.

    Directory of Open Access Journals (Sweden)

    Jennifer K Sabo

    Full Text Available Repair in multiple sclerosis involves remyelination, a process in which axons are provided with a new myelin sheath by new oligodendrocytes. Bone morphogenic proteins (BMPs are a family of growth factors that have been shown to influence the response of oligodendrocyte progenitor cells (OPCs in vivo during demyelination and remyelination in the adult brain. We have previously shown that BMP4 infusion increases numbers of OPCs during cuprizone-induced demyelination, while infusion of Noggin, an endogenous antagonist of BMP4 increases numbers of mature oligodendrocytes and remyelinated axons following recovery. Additional studies have shown that insulin-like growth factor-1 (IGF-1 promotes the survival of OPCs during cuprizone-induced demyelination. Based on these data, we investigated whether myelin repair could be further enhanced by sequential infusion of these agents firstly, BMP4 to increase OPC numbers, followed by either Noggin or IGF-1 to increase the differentiation and survival of the newly generated OPCs. We identified that sequential delivery of BMP4 and IGF-1 during cuprizone challenge increased the number of mature oligodendrocytes and decreased astrocyte numbers following recovery compared with vehicle infused mice, but did not alter remyelination. However, sequential delivery of BMP4 and Noggin during cuprizone challenge did not alter numbers of oligodendrocytes or astrocytes in the corpus callosum compared with vehicle infused mice. Furthermore, electron microscopy analysis revealed no change in average myelin thickness in the corpus callosum between vehicle infused and BMP4-Noggin infused mice. Our results suggest that while single delivery of Noggin or IGF-1 increased the production of mature oligodendrocytes in vivo in the context of demyelination, only Noggin infusion promoted remyelination. Thus, sequential delivery of BMP4 and Noggin or IGF-1 does not further enhance myelin repair above what occurs with delivery of Noggin

  4. Deterministic Encapsulation of Human Cardiac Stem Cells in Variable Composition Nanoporous Gel Cocoons To Enhance Therapeutic Repair of Injured Myocardium.

    Science.gov (United States)

    Kanda, Pushpinder; Alarcon, Emilio I; Yeuchyk, Tanya; Parent, Sandrine; de Kemp, Robert A; Variola, Fabio; Courtman, David; Stewart, Duncan J; Davis, Darryl R

    2018-04-20

    Although cocooning explant-derived cardiac stem cells (EDCs) in protective nanoporous gels (NPGs) prior to intramyocardial injection boosts long-term cell retention, the number of EDCs that finally engraft is trivial and unlikely to account for salutary effects on myocardial function and scar size. As such, we investigated the effect of varying the NPG content within capsules to alter the physical properties of cocoons without influencing cocoon dimensions. Increasing NPG concentration enhanced cell migration and viability while improving cell-mediated repair of injured myocardium. Given that the latter occurred with NPG content having no detectable effect on the long-term engraftment of transplanted cells, we found that changing the physical properties of cocoons prompted explant-derived cardiac stem cells to produce greater amounts of cytokines, nanovesicles, and microRNAs that boosted the generation of new blood vessels and new cardiomyocytes. Thus, by altering the physical properties of cocoons by varying NPG content, the paracrine signature of encapsulated cells can be enhanced to promote greater endogenous repair of injured myocardium.

  5. Fine-scale features on bioreplicated decoys of the emerald ash borer provide necessary visual verisimilitude

    Science.gov (United States)

    Domingue, Michael J.; Pulsifer, Drew P.; Narkhede, Mahesh S.; Engel, Leland G.; Martín-Palma, Raúl J.; Kumar, Jayant; Baker, Thomas C.; Lakhtakia, Akhlesh

    2014-03-01

    The emerald ash borer (EAB), Agrilus planipennis, is an invasive tree-killing pest in North America. Like other buprestid beetles, it has an iridescent coloring, produced by a periodically layered cuticle whose reflectance peaks at 540 nm wavelength. The males perform a visually mediated ritualistic mating flight directly onto females poised on sunlit leaves. We attempted to evoke this behavior using artificial visual decoys of three types. To fabricate decoys of the first type, a polymer sheet coated with a Bragg-stack reflector was loosely stamped by a bioreplicating die. For decoys of the second type, a polymer sheet coated with a Bragg-stack reflector was heavily stamped by the same die and then painted green. Every decoy of these two types had an underlying black absorber layer. Decoys of the third type were produced by a rapid prototyping machine and painted green. Fine-scale features were absent on the third type. Experiments were performed in an American ash forest infested with EAB, and a European oak forest home to a similar pest, the two-spotted oak borer (TSOB), Agrilus biguttatus. When pinned to leaves, dead EAB females, dead TSOB females, and bioreplicated decoys of both types often evoked the complete ritualized flight behavior. Males also initiated approaches to the rapidly prototyped decoy, but would divert elsewhere without making contact. The attraction of the bioreplicated decoys was also demonstrated by providing a high dc voltage across the decoys that stunned and killed approaching beetles. Thus, true bioreplication with fine-scale features is necessary to fully evoke ritualized visual responses in insects, and provides an opportunity for developing insecttrapping technologies.

  6. DNA double strand break repair is enhanced by P53 following induction by DNA damage and is dependent on the C-terminal domain of P53

    International Nuclear Information System (INIS)

    Wei Tang; Powell, Simon N.

    1996-01-01

    Purpose: The tumor suppressor gene p53 can mediate cell cycle arrest or apoptosis in response to DNA damage. Accumulating evidence suggests that it may also directly or indirectly influence the DNA repair machinery. In the present study, we investigated whether p53, induced by DNA damage, could enhance the rejoining of double-strand DNA breaks. Materials and Methods: DNA double-strand breaks (dsb) were made by restriction enzyme digestion of a plasmid, between a promoter and a 'reporter' gene: luciferase (LUC) or chloramphenicol acetyl-transferase (CAT). Linear or circular plasmid DNA (LUC or CAT) was co-transfected with circular β-Gal plasmid (to normalize for uptake) into mouse embryonic fibroblasts genetically matched to be (+/+) or (-/-) for p53. Their ability to rejoin linearized plasmid was measured by the luciferase or CAT activity detected in rescued plasmids. The activity detected in cells transfected with linear plasmid was scored relative to the activity detected in cells transfected with circular plasmid. Results: Ionizing radiation (IR, 2 Gy) enhanced the dsb repair activity in wild type p53 cells; however, p53 null cells lose this effect, indicating that the enhancement of dsb repair was p53-dependent. REF cells with dominant-negative mutant p53 showed a similar induction compared with the parental REF cells with wild-type p53. This ala-143 mutant p53 prevents cell cycle arrest and transactivation of p21 WAF1/cip1) following IR, indicating that the p53-dependent enhancement of DNA repair is distinct from transactivation. Immortalized murine embryonic fibroblasts, 10(1)VasK1 cells, which express p53 cDNA encoding a temperature-sensitive mutant in the DNA sequence specific binding domain (ala135 to val135) with an alternatively spliced C-terminal domain (ASp53: amino-acids 360-381) and, 10(1)Val5 cells, which express the normal spliced p53 (NSp53) with the same temperature-sensitive mutant were compared. It was found that 10(1)VasK1 cells showed no DNA

  7. General Theory of Decoy-State Quantum Cryptography with Dark Count Rate Fluctuation

    International Nuclear Information System (INIS)

    Xiang, Gao; Shi-Hai, Sun; Lin-Mei, Liang

    2009-01-01

    The existing theory of decoy-state quantum cryptography assumes that the dark count rate is a constant, but in practice there exists fluctuation. We develop a new scheme of the decoy state, achieve a more practical key generation rate in the presence of fluctuation of the dark count rate, and compare the result with the result of the decoy-state without fluctuation. It is found that the key generation rate and maximal secure distance will be decreased under the influence of the fluctuation of the dark count rate

  8. Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair

    Science.gov (United States)

    2015-01-01

    There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays. PMID:26016986

  9. Enhancement of postreplication repair in ultraviolet-light-irradiated Chinese hamster cells by irradiation in G2 or s-phase

    International Nuclear Information System (INIS)

    D'Ambrosio, S.M.; Aebersold, P.M.; Setlow, R.B.

    1978-01-01

    Postreplication repair in synchronous Chinese hamster cells was determined after split doses of ultraviolet (uv) radiation. Repair was enhanced by irradiation of cells in G 2 or S-phase with a small dose of uv radiation at least 1.5 h before a three-fold larger dose of uv. There was significantly greater enhancement when the first dose was given in G 2 than when it was given in the S-phase 0.5 to 1.5 h before the test dose. These data indicate that enhancement of postreplication repair does not require active DNA replication and qualitatively is independent of when in the cell cycle the cells are irradiated

  10. Analysing the bioactive makeup of demineralised dentine matrix on bone marrow mesenchymal stem cells for enhanced bone repair.

    Science.gov (United States)

    Avery, S J; Sadaghiani, L; Sloan, A J; Waddington, R J

    2017-07-10

    Dentine matrix has proposed roles for directing mineralised tissue repair in dentine and bone; however, the range of bioactive components in dentine and specific biological effects on bone-derived mesenchymal stem cells (MSCs) in humans are less well understood. The aims of this study were to further elucidate the biological response of MSCs to demineralised dentine matrix (DDM) in enhancing wound repair responses and ascertain key contributing components. Dentine was obtained from human teeth and DDM proteins solubilised with ethylenediaminetetraacetic acid (EDTA). Bone marrow derived MSCs were commercially obtained. Cells with a more immature phenotype were then selected by preferential fibronectin adhesion (FN-BMMSCs) for use in subsequent in vitro assays. DDM at 10 µg/mL reduced cell expansion, attenuated apoptosis and was the minimal concentration capable of inducing osteoblastic differentiation. Enzyme-linked immunosorbent assay (ELISA) quantification of growth factors indicated physiological levels produced the above responses; transforming growth factor β (TGF-β1) was predominant (15.6 ng/mg DDM), with relatively lower concentrations of BMP-2, FGF, VEGF and PDGF (6.2-4.7 ng/mg DDM). Fractionation of growth factors from other DDM components by heparin affinity chromatography diminished osteogenic responses. Depletion of biglycan from DDM also attenuated osteogenic potency, which was partially rescued by the isolated biglycan. Decorin depletion from DDM had no influence on osteogenic potency. Collectively, these results demonstrate the potential of DDM for the delivery of physiological levels of growth factors for bone repair processes, and substantiate a role for biglycan as an additional adjuvant for driving osteogenic pathways.

  11. Enhanced Critical Size Defect Repair in Rabbit Mandible by Electrospun Gelatin/β-TCP Composite Nanofibrous Membranes

    Directory of Open Access Journals (Sweden)

    Mingming Xu

    2015-01-01

    Full Text Available The design and fabrication of biodegradable barrier membranes with satisfactory structure and composition remain a considerable challenge for periodontal tissue regeneration. We have developed a biomimetic nanofibrous membrane made from a composite of gelatin and β-tricalcium phosphate (β-TCP. We previously confirmed the in vitro biological performance of the membrane material, but the efficacy of the membranes in promoting bone repair in situ has not yet been examined. Gelatin/β-TCP composite nanofibers were fabricated by incorporation of 20 wt.% β-TCP nanoparticles into electrospun gelatin nanofibers. Electron microscopy showed that the composite membranes presented a nonwoven structure with an interconnected porous network and had a rough surface due to the β-TCP nanoparticles, which were distributed widely and uniformly throughout the gelatin-fiber matrix. The repair efficacy of rabbit mandible defects implanted with bone substitute (Bio-Oss and covered with the gelatin/β-TCP composite nanofibrous membrane was evaluated in comparison with pure gelatin nanofibrous membrane. Gross observation, histological examination, and immunohistochemical analysis showed that new bone formation and defect closure were significantly enhanced by the composite membranes compared to the pure gelatin ones. From these results, we conclude that nanofibrous gelatin/β-TCP composite membranes could serve as effective barrier membranes for guided tissue regeneration.

  12. Inhibition of androgen receptor by decoy molecules delays progression to castration-recurrent prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jae-Kyung Myung

    Full Text Available Androgen receptor (AR is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD. Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD.

  13. Comparison of four species of snails as potential decoys to intercept schistosome miracidia.

    Science.gov (United States)

    Laracuente, A; Brown, R A; Jobin, W

    1979-01-01

    Preliminary studies have shown that various species of aquatic snails may be used as decoys or "sponges" to intercept schistosome miracidia, thereby preventing the miracidia from reaching the snails which normally serve as their intermediate host. In this study, four species of snails were evaluated as candidate decoys for field trials: Marisa cornuarietis, Pomacea australis, Helisoma caribaeum, and Tarebia granifera. In the laboratory all four species caused considerable reductions in the proportion of Biomphalaria glabrata infected by miracidia of Schistosoma mansoni. The most effective decoys were M. cornuarietis and H. caribaeum, both of which caused experimental infection levels of 90% to decrease to 25% when five decoy snails were present for each target snail. When ten decoy snails were present for each target snail, the proportion infected decreased to 1%. M. cornuarietis was chosen as the candidate for field trials because it was found more frequently in Puerto Rico than was H. caribaeum. Initial field trials in two ponds showed that M. cornuarietis blocked infections at a ratio of 6 decoys to 1 target snail, confirming the laboratory results. Further studies in flowing water are needed before the technique can be generally evaluated in an endemic area.

  14. Mismatch repair deficiency does not enhance ENU mutagenesis in the zebrafish germ line.

    Science.gov (United States)

    Feitsma, Harma; de Bruijn, Ewart; van de Belt, Jose; Nijman, Isaac J; Cuppen, Edwin

    2008-07-01

    S(N)1-type alkylating agents such as N-ethyl-N-nitrosourea (ENU) are very potent mutagens. They act by transferring their alkyl group to DNA bases, which, upon mispairing during replication, can cause single base pair mutations in the next replication cycle. As DNA mismatch repair (MMR) proteins are involved in the recognition of alkylation damage, we hypothesized that ENU-induced mutation rates could be increased in a MMR-deficient background, which would be beneficial for mutagenesis approaches. We applied a standard ENU mutagenesis protocol to adult zebrafish deficient in the MMR gene msh6 and heterozygous controls to study the effect of MMR on ENU-induced DNA damage. Dose-dependent lethality was found to be similar for homozygous and heterozygous mutants, indicating that there is no difference in ENU resistance. Mutation discovery by high-throughput dideoxy resequencing of genomic targets in outcrossed progeny of the mutagenized fish did also not reveal any differences in germ line mutation frequency. These results may indicate that the maximum mutation load for zebrafish has been reached with the currently used, highly optimized ENU mutagenesis protocol. Alternatively, the MMR system in the zebrafish germ line may be saturated very rapidly, thereby having a limited effect on high-dose ENU mutagenesis.

  15. A compromised yeast RNA polymerase II enhances UV sensitivity in the absence of global genome nucleotide excision repair.

    Science.gov (United States)

    Wong, J M; Ingles, C J

    2001-02-01

    Nucleotide excision repair is the major pathway responsible for removing UV-induced DNA damage, and is therefore essential for cell survival following exposure to UV radiation. In this report, we have assessed the contributions of some components of the RNA polymerase II (Pol II) transcription machinery to UV resistance in Saccharomyces cerevisiae. Deletion of the gene encoding the Pol II elongation factor TFIIS (SII) resulted in enhanced UV sensitivity, but only in the absence of global genome repair dependent on the RAD7 and RAD16 genes, a result seen previously with deletions of RAD26 and RAD28, yeast homologs of the human Cockayne syndrome genes CSB and CSA, respectively. A RAD7/16-dependent reduction in survival after UV irradiation was also seen in the presence of mutations in RNA Pol II that confer a defect in its response to SII, as well as with other mutations which reside in regions of the largest subunit of Pol II not involved in SII interactions. Indeed, an increase in UV sensitivity was achieved by simply decreasing the steadystate level of RNA Pol II. Truncation of the C-terminal domain and other RNA Pol II mutations conferred sensitivity to the ribonucleotide reductase inhibitor hydroxyurea and induction of RNR1 and RNR2 mRNAs after UV irradiation was attenuated in these mutant cells. That UV sensitivity can be a consequence of mutations in the RNA Pol II machinery in yeast cells suggests that alterations in transcriptional programs could underlie some of the pathophysiological defects seen in the human disease Cockayne syndrome.

  16. Non‐diluted seawater enhances nasal ciliary beat frequency and wound repair speed compared to diluted seawater and normal saline

    Science.gov (United States)

    Bonnomet, Arnaud; Luczka, Emilie; Coraux, Christelle

    2016-01-01

    Background The regulation of mucociliary clearance is a key part of the defense mechanisms developed by the airway epithelium. If a high aggregate quality of evidence shows the clinical effectiveness of nasal irrigation, there is a lack of studies showing the intrinsic role of the different irrigation solutions allowing such results. This study investigated the impact of solutions with different pH and ionic compositions, eg, normal saline, non‐diluted seawater and diluted seawater, on nasal mucosa functional parameters. Methods For this randomized, controlled, blinded, in vitro study, we used airway epithelial cells obtained from 13 nasal polyps explants to measure ciliary beat frequency (CBF) and epithelial wound repair speed (WRS) in response to 3 isotonic nasal irrigation solutions: (1) normal saline 0.9%; (2) non‐diluted seawater (Physiomer®); and (3) 30% diluted seawater (Stérimar). The results were compared to control (cell culture medium). Results Non‐diluted seawater enhanced the CBF and the WRS when compared to diluted seawater and to normal saline. When compared to the control, it significantly enhanced CBF and slightly, though nonsignificantly, improved the WRS. Interestingly, normal saline markedly reduced the number of epithelial cells and ciliated cells when compared to the control condition. Conclusion Our results suggest that the physicochemical features of the nasal wash solution is important because it determines the optimal conditions to enhance CBF and epithelial WRS thus preserving the respiratory mucosa in pathological conditions. Non‐diluted seawater obtains the best results on CBF and WRS vs normal saline showing a deleterious effect on epithelial cell function. PMID:27101776

  17. Non-diluted seawater enhances nasal ciliary beat frequency and wound repair speed compared to diluted seawater and normal saline.

    Science.gov (United States)

    Bonnomet, Arnaud; Luczka, Emilie; Coraux, Christelle; de Gabory, Ludovic

    2016-10-01

    The regulation of mucociliary clearance is a key part of the defense mechanisms developed by the airway epithelium. If a high aggregate quality of evidence shows the clinical effectiveness of nasal irrigation, there is a lack of studies showing the intrinsic role of the different irrigation solutions allowing such results. This study investigated the impact of solutions with different pH and ionic compositions, eg, normal saline, non-diluted seawater and diluted seawater, on nasal mucosa functional parameters. For this randomized, controlled, blinded, in vitro study, we used airway epithelial cells obtained from 13 nasal polyps explants to measure ciliary beat frequency (CBF) and epithelial wound repair speed (WRS) in response to 3 isotonic nasal irrigation solutions: (1) normal saline 0.9%; (2) non-diluted seawater (Physiomer®); and (3) 30% diluted seawater (Stérimar). The results were compared to control (cell culture medium). Non-diluted seawater enhanced the CBF and the WRS when compared to diluted seawater and to normal saline. When compared to the control, it significantly enhanced CBF and slightly, though nonsignificantly, improved the WRS. Interestingly, normal saline markedly reduced the number of epithelial cells and ciliated cells when compared to the control condition. Our results suggest that the physicochemical features of the nasal wash solution is important because it determines the optimal conditions to enhance CBF and epithelial WRS thus preserving the respiratory mucosa in pathological conditions. Non-diluted seawater obtains the best results on CBF and WRS vs normal saline showing a deleterious effect on epithelial cell function. © 2016 The Authors International Forum of Allergy & Rhinology, published by ARSAAOA, LLC.

  18. Thromboxane A{sub 2} receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment

    Energy Technology Data Exchange (ETDEWEB)

    Minamino, Tsutomu [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ito, Yoshiya [Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ohkubo, Hirotoki [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Hosono, Kanako; Suzuki, Tatsunori [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sato, Takehito [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ae, Takako; Shibuya, Akitaka [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sakagami, Hiroyuki [Departments of Anatomy, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Narumiya, Shuh [Department of Pharmacology, Kyoto University School of Medicine, Kyoto, 606-8315 (Japan); Koizumi, Wasaburo [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Majima, Masataka, E-mail: mmajima@med.kitasato-u.ac.jp [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan)

    2012-02-15

    It is thought that thromboxane A{sub 2} (TxA{sub 2}) contributes to the progression of inflammation during acute hepatic injury; however, it is still unknown whether TxA{sub 2} is involved in liver repair. The objective of the present study was to examine the role of TxA{sub 2} receptor (TP) signaling in liver injury and repair in response to toxic injury. Carbon tetrachloride (CCl{sub 4}) was used to induce liver injury in TP knockout (TP{sup −/−}) mice and wild-type (WT) mice. In WT mice, serum levels of alanine aminotransferase (ALT) and the size of the necrotic area peaked at 24 and 48 h, respectively, and then declined. In TP{sup −/−} mice, the changes in ALT levels were similar to WT mice, but liver regeneration was impaired as evidenced by remained elevated levels of hepatic necrosis and by delayed hepatocyte proliferation, which was associated with the reduced expression of growth factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and hepatocyte growth factor (HGF). In TP{sup −/−} mice, the accumulation of hepatic CD11b{sup +}/F4/80{sup +} macrophages in injured livers was attenuated, and the hepatic expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, the C―C chemokine receptor (CCR2), was reduced compared to WT. Additionally, the application of the TP receptor agonist, U-46619, enhanced the expression of MCP-1/CCL2 and CCR2 in peritoneal macrophages, which was associated with increased levels of IL-6, TNFα and HGF. These results suggested that TP receptor signaling facilitates liver recovery following CCl{sub 4}-induced hepatotoxicity by affecting the expression of hepatotrophic growth factors, and through the recruitment of macrophages mediated by MCP-1/CCL2-CCR2 expression. -- Highlights: ► TP enhances liver regeneration by CCl{sub 4}. ► TP accumulates macrophages. ► TP up-regulates MCP-1.

  19. Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA interaction.

    Science.gov (United States)

    Klaus, Miriam; Prokoph, Nina; Girbig, Mathias; Wang, Xuecong; Huang, Yong-Heng; Srivastava, Yogesh; Hou, Linlin; Narasimhan, Kamesh; Kolatkar, Prasanna R; Francois, Mathias; Jauch, Ralf

    2016-05-05

    The transcription factor (TF) SOX18 drives lymphatic vessel development in both embryogenesis and tumour-induced neo-lymphangiogenesis. Genetic disruption of Sox18 in a mouse model protects from tumour metastasis and established the SOX18 protein as a molecular target. Here, we report the crystal structure of the SOX18 DNA binding high-mobility group (HMG) box bound to a DNA element regulating Prox1 transcription. The crystals diffracted to 1.75Å presenting the highest resolution structure of a SOX/DNA complex presently available revealing water structure, structural adjustments at the DNA contact interface and non-canonical conformations of the DNA backbone. To explore alternatives to challenging small molecule approaches for targeting the DNA-binding activity of SOX18, we designed a set of five decoys based on modified Prox1-DNA. Four decoys potently inhibited DNA binding of SOX18 in vitro and did not interact with non-SOX TFs. Serum stability, nuclease resistance and thermal denaturation assays demonstrated that a decoy circularized with a hexaethylene glycol linker and terminal phosphorothioate modifications is most stable. This SOX decoy also interfered with the expression of a luciferase reporter under control of a SOX18-dependent VCAM1 promoter in COS7 cells. Collectively, we propose SOX decoys as potential strategy for inhibiting SOX18 activity to disrupt tumour-induced neo-lymphangiogenesis. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin.

    Directory of Open Access Journals (Sweden)

    Benjamin C Thompson

    Full Text Available Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV radiation and affects DNA damage and repair. Nicotinamide (vitamin B3 reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2 solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.

  1. Photoluminescence Enhancement and Structure Repairing of Monolayer MoSe 2 by Hydrohalic Acid Treatment

    KAUST Repository

    Han, Hau-Vei

    2015-12-30

    Atomically thin two-dimensional transition-metal dichalcogenides (TMDCs) have attracted much attention recently due to their unique electronic and optical properties for future optoelectronic devices. The chemical vapor deposition (CVD) method is able to generate TMDCs layers with a scalable size and a controllable thickness. However, the TMDC monolayers grown by CVD may incorporate structural defects, and it is fundamentally important to understand the relation between photoluminescence and structural defects. In this report, point defects (Se vacancies) and oxidized Se defects in CVD-grown MoSe2 monolayers are identified by transmission electron microscopy and X-ray photoelectron spectroscopy. These defects can significantly trap free charge carriers and localize excitons, leading to the smearing of free band-to-band exciton emission. Here, we report that the simple hydrohalic acid treatment (such as HBr) is able to efficiently suppress the trap-state emission and promote the neutral exciton and trion emission in defective MoSe2 monolayers through the p-doping process, where the overall photoluminescence intensity at room temperature can be enhanced by a factor of 30. We show that HBr treatment is able to activate distinctive trion and free exciton emissions even from highly defective MoSe2 layers. Our results suggest that the HBr treatment not only reduces the n-doping in MoSe2 but also reduces the structural defects. The results provide further insights of the control and tailoring the exciton emission from CVD-grown monolayer TMDCs.

  2. Extracorporeal shockwave enhanced regeneration of fibrocartilage in a delayed tendon-bone insertion repair model.

    Science.gov (United States)

    Chow, Dick Ho Kiu; Suen, Pui Kit; Huang, Le; Cheung, Wing-Hoi; Leung, Kwok-Sui; Ng, Chun; Shi, San Qiang; Wong, Margaret Wan Nar; Qin, Ling

    2014-04-01

    Fibrous tissue is often formed in delayed healing of tendon bone insertion (TBI) instead of fibrocartilage. Extracorporeal shockwave (ESW) provides mechanical cues and upregulates expression of fibrocartilage-related makers and cytokines. We hypothesized that ESW would accelerate fibrocartilage regeneration at the healing interface in a delayed TBI healing model. Partial patellectomy with shielding at the TBI interface was performed on 32 female New Zealand White Rabbits for establishing this delayed TBI healing model. The rabbits were separated into the control and ESW group for evaluations at postoperative week 8 and 12. Shielding was removed at week 4 and a single ESW treatment was applied at week 6. Fibrocartilage regeneration was evaluated histomorphologically and immunohistochemically. Vickers hardness of the TBI matrix was measured by micro-indentation. ESW group showed higher fibrocartilage area, thickness, and proteoglycan deposition than the control in week 8 and 12. ESW increased expression of SOX9 and collagen II significantly in week 8 and 12, respectively. ESW group showed a gradual transition of hardness from bone to fibrocartilage to tendon, and had a higher Vickers hardness than the control group at week 12. In conclusion, ESW enhanced fibrocartilage regeneration at the healing interface in a delayed TBI healing model. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  3. Parameter optimization in biased decoy-state quantum key distribution with both source errors and statistical fluctuations

    Science.gov (United States)

    Zhu, Jian-Rong; Li, Jian; Zhang, Chun-Mei; Wang, Qin

    2017-10-01

    The decoy-state method has been widely used in commercial quantum key distribution (QKD) systems. In view of the practical decoy-state QKD with both source errors and statistical fluctuations, we propose a universal model of full parameter optimization in biased decoy-state QKD with phase-randomized sources. Besides, we adopt this model to carry out simulations of two widely used sources: weak coherent source (WCS) and heralded single-photon source (HSPS). Results show that full parameter optimization can significantly improve not only the secure transmission distance but also the final key generation rate. And when taking source errors and statistical fluctuations into account, the performance of decoy-state QKD using HSPS suffered less than that of decoy-state QKD using WCS.

  4. MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression.

    Science.gov (United States)

    Xu, Meixiang; Cross, Courtney E; Speidel, Jordan T; Abdel-Rahman, Sherif Z

    2016-10-01

    The O 6 -methylguanine-DNA methyltransferase (MGMT) protein removes O 6 -alkyl-guanine adducts from DNA. MGMT expression can thus alter the sensitivity of cells and tissues to environmental and chemotherapeutic alkylating agents. Previously, we defined the haplotype structure encompassing single nucleotide polymorphisms (SNPs) in the MGMT promoter/enhancer (P/E) region and found that haplotypes, rather than individual SNPs, alter MGMT promoter activity. The exact mechanism(s) by which these haplotypes exert their effect on MGMT promoter activity is currently unknown, but we noted that many of the SNPs comprising the MGMT P/E haplotypes are located within or in close proximity to putative transcription factor binding sites. Thus, these haplotypes could potentially affect transcription factor binding and, subsequently, alter MGMT promoter activity. In this study, we test the hypothesis that MGMT P/E haplotypes affect MGMT promoter activity by altering transcription factor (TF) binding to the P/E region. We used a promoter binding TF profiling array and a reporter assay to evaluate the effect of different P/E haplotypes on TF binding and MGMT expression, respectively. Our data revealed a significant difference in TF binding profiles between the different haplotypes evaluated. We identified TFs that consistently showed significant haplotype-dependent binding alterations (p ≤ 0.01) and revealed their role in regulating MGMT expression using siRNAs and a dual-luciferase reporter assay system. The data generated support our hypothesis that promoter haplotypes alter the binding of TFs to the MGMT P/E and, subsequently, affect their regulatory function on MGMT promoter activity and expression level.

  5. Role of oxygen in enhancement in repair of radiation injuries in Tribolium

    International Nuclear Information System (INIS)

    Ng, M.C.

    1977-01-01

    The oxygen enhancement ratio (OER) was determined for various biological responses in Tribolium confusum McGill Black. The biological responses included acute lethality of the adults and larvae; sexual sterilization of the male and female adults; fecundity of the females and hatchability of their eggs as well as the competitiveness of the males. The OER for acute lethality for the male and female adults was found to be 2.25-2.38, regardless of the type of inert gas used to achieve anaerobiosis. Acute lethality for the larvae showed an OER of 2.79. The OER for male and female sexual sterilization was 2.35 and 3.37 respectively. With irradiation carried out in oxygen, the results suggested that at the tissue level of the adults and the male reproductive organ, there is a certain degree of hypoxia. Sexual sterilization of the males by radiation is attributed to the induction of dominant lethal mutation in the sperms, and that of the females involves a combination of dominant lethals and decreased egg production. The OER for egg hatchability at a hatchability level of 50% of the control for irradiated females was 4.0, a surprisingly higher value than that of any other biological responses studied. The OER for fecundity of irradiated females and for male competitiveness were roughly estimated to be 2.8 and 2.3-2.7 respectively. Since the OER for male sexual sterilization is basically the same as that for acute lethality for adults, it is expected that the competitiveness, which depends on the amount of somatic damage by radiation, will not be protected to a much greater extent by anaerobic irradiation than sterilization. It is clearly demonstrated that OER values are specific for the particular end point scored. Even within the same organism, different OER can be obtained with different biological responses

  6. Human induced pluripotent cells resemble embryonic stem cells demonstrating enhanced levels of DNA repair and efficacy of nonhomologous end-joining

    Energy Technology Data Exchange (ETDEWEB)

    Fan Jinshui; Robert, Carine [Department of Radiation Oncology, University of Maryland School of Medicine, 655 West Baltimore Street, BRB 7-023A, Baltimore, MD 21201 (United States); Jang, Yoon-Young; Liu Hua; Sharkis, Saul; Baylin, Stephen Bruce [Johns Hopkins University School of Medicine, Department of Oncology, Baltimore, MD 21231-1000 (United States); Rassool, Feyruz Virgilia, E-mail: frassool@som.umaryland.edu [Department of Radiation Oncology, University of Maryland School of Medicine, 655 West Baltimore Street, BRB 7-023A, Baltimore, MD 21201 (United States)

    2011-08-01

    Highlights: {yields} iPSC and hESC demonstrate a similar cell cycle profile, with increased S phase cells and decreased G0/G1. {yields} iPSC and hESC increased ROS and decreased DSBs, compared with differentiated parental cells. {yields} iPSC and hESC demonstrate elevated DSB repair activity, including nonhomologous end-joining, compared with differentiated parental cells. {yields} iPSC however show a partial apoptotic response to DNA damage, compared to hESC. {yields} DNA damage responses may constitute important markers for the efficacy of iPSC reprogramming. - Abstract: To maintain the integrity of the organism, embryonic stem cells (ESC) need to maintain their genomic integrity in response to DNA damage. DNA double strand breaks (DSBs) are one of the most lethal forms of DNA damage and can have disastrous consequences if not repaired correctly, leading to cell death, genomic instability and cancer. How human ESC (hESC) maintain genomic integrity in response to agents that cause DSBs is relatively unclear. Adult somatic cells can be induced to 'dedifferentiate' into induced pluripotent stem cells (iPSC) and reprogram into cells of all three germ layers. Whether iPSC have reprogrammed the DNA damage response is a critical question in regenerative medicine. Here, we show that hESC demonstrate high levels of endogenous reactive oxygen species (ROS) which can contribute to DNA damage and may arise from high levels of metabolic activity. To potentially counter genomic instability caused by DNA damage, we find that hESC employ two strategies: First, these cells have enhanced levels of DNA repair proteins, including those involved in repair of DSBs, and they demonstrate elevated nonhomologous end-joining (NHEJ) activity and repair efficacy, one of the main pathways for repairing DSBs. Second, they are hypersensitive to DNA damaging agents, as evidenced by a high level of apoptosis upon irradiation. Importantly, iPSC, unlike the parent cells they are derived

  7. Human induced pluripotent cells resemble embryonic stem cells demonstrating enhanced levels of DNA repair and efficacy of nonhomologous end-joining

    International Nuclear Information System (INIS)

    Fan Jinshui; Robert, Carine; Jang, Yoon-Young; Liu Hua; Sharkis, Saul; Baylin, Stephen Bruce; Rassool, Feyruz Virgilia

    2011-01-01

    Highlights: → iPSC and hESC demonstrate a similar cell cycle profile, with increased S phase cells and decreased G0/G1. → iPSC and hESC increased ROS and decreased DSBs, compared with differentiated parental cells. → iPSC and hESC demonstrate elevated DSB repair activity, including nonhomologous end-joining, compared with differentiated parental cells. → iPSC however show a partial apoptotic response to DNA damage, compared to hESC. → DNA damage responses may constitute important markers for the efficacy of iPSC reprogramming. - Abstract: To maintain the integrity of the organism, embryonic stem cells (ESC) need to maintain their genomic integrity in response to DNA damage. DNA double strand breaks (DSBs) are one of the most lethal forms of DNA damage and can have disastrous consequences if not repaired correctly, leading to cell death, genomic instability and cancer. How human ESC (hESC) maintain genomic integrity in response to agents that cause DSBs is relatively unclear. Adult somatic cells can be induced to 'dedifferentiate' into induced pluripotent stem cells (iPSC) and reprogram into cells of all three germ layers. Whether iPSC have reprogrammed the DNA damage response is a critical question in regenerative medicine. Here, we show that hESC demonstrate high levels of endogenous reactive oxygen species (ROS) which can contribute to DNA damage and may arise from high levels of metabolic activity. To potentially counter genomic instability caused by DNA damage, we find that hESC employ two strategies: First, these cells have enhanced levels of DNA repair proteins, including those involved in repair of DSBs, and they demonstrate elevated nonhomologous end-joining (NHEJ) activity and repair efficacy, one of the main pathways for repairing DSBs. Second, they are hypersensitive to DNA damaging agents, as evidenced by a high level of apoptosis upon irradiation. Importantly, iPSC, unlike the parent cells they are derived from, mimic hESC in their ROS levels

  8. Testing the effect of time pressure on asymmetric dominance and compromise decoys in choice

    Directory of Open Access Journals (Sweden)

    Jonathan Pettibone

    2012-07-01

    Full Text Available Dynamic, connectionist models of decision making, such as decision field theory (Roe, Busemeyer, and Townsend, 2001, propose that the effect of context on choice arises from a series of pairwise comparisons between attributes of alternatives across time. As such, they predict that limiting the amount of time to make a decision should decrease rather than increase the size of contextual effects. This prediction was tested across four levels of time pressure on both the asymmetric dominance (Huber, Payne, and Puto, 1982 and compromise (Simonson, 1989 decoy effects in choice. Overall, results supported this prediction, with both types of decoy effects found to be larger as time pressure decreased.

  9. Down-regulation of DNA mismatch repair enhances initiation and growth of neuroblastoma and brain tumour multicellular spheroids.

    Directory of Open Access Journals (Sweden)

    Samuel L Collins

    Full Text Available Multicellular tumour spheroid (MCTS cultures are excellent model systems for simulating the development and microenvironmental conditions of in vivo tumour growth. Many documented cell lines can generate differentiated MCTS when cultured in suspension or in a non-adhesive environment. While physiological and biochemical properties of MCTS have been extensively characterized, insight into the events and conditions responsible for initiation of these structures is lacking. MCTS are formed by only a small subpopulation of cells during surface-associated growth but the processes responsible for this differentiation are poorly understood and have not been previously studied experimentally. Analysis of gene expression within spheroids has provided clues but to date it is not known if the observed differences are a cause or consequence of MCTS growth. One mechanism linked to tumourigenesis in a number of cancers is genetic instability arising from impaired DNA mismatch repair (MMR. This study aimed to determine the role of MMR in MCTS initiation and development. Using surface-associated N2a and CHLA-02-ATRT culture systems we have investigated the impact of impaired MMR on MCTS growth. Analysis of the DNA MMR genes MLH1 and PMS2 revealed both to be significantly down-regulated at the mRNA level compared with non-spheroid-forming cells. By using small interfering RNA (siRNA against these genes we show that silencing of MLH1 and PMS2 enhances both MCTS initiation and subsequent expansion. This effect was prolonged over several passages following siRNA transfection. Down-regulation of DNA MMR can contribute to tumour initiation and progression in N2a and CHLA-02-ATRT MCTS models. Studies of surface-associated MCTS differentiation may have broader applications in studying events in the initiation of cancer foci.

  10. 1,4 Naphthoquinone protects radiation induced cell death and DNA damage in lymphocytes by activation Nrf2/are pathway and enhancing DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Nazir M; Sandur, Santosh K; Checker, Rahul; Sharma, Deepak; Poduval, T.B., E-mail: nazirbiotech@rediffmail.com [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai (India)

    2012-07-01

    enhanced DNA repair in NQ treated lymphocytes. Furthermore, microarray analysis indicated that treatment of lymphocytes with NQ induces upregulation of several DNA repair genes including mismatch repair (Msh6, Pms2, and Rfc1), nucleotide and base excision repair pathways like pole4, parp1, parp4. Induction of these genes in NQ treated lymphocytes were confirmed by quantitative real time PCR. Further, treatment of lymphocytes with NQ resulted in increased expression of proteins as revealed by 2D protein blot analysis. Proteomic analysis of these spots corresponds to RIKEN protein which is known to exhibits as radio-resistance in the cells. Thus in addition to anti-cancer and anti-parasitic activity, NQ offered protection against a-radiation-induced cell death in lymphocytes via activation of Nrf-2/ARE and DNA repair pathways. (author)

  11. In Vivo Evaluation of a Novel Oriented Scaffold-BMSC Construct for Enhancing Full-Thickness Articular Cartilage Repair in a Rabbit Model.

    Directory of Open Access Journals (Sweden)

    Shuaijun Jia

    Full Text Available Tissue engineering (TE has been proven usefulness in cartilage defect repair. For effective cartilage repair, the structural orientation of the cartilage scaffold should mimic that of native articular cartilage, as this orientation is closely linked to cartilage mechanical functions. Using thermal-induced phase separation (TIPS technology, we have fabricated an oriented cartilage extracellular matrix (ECM-derived scaffold with a Young's modulus value 3 times higher than that of a random scaffold. In this study, we test the effectiveness of bone mesenchymal stem cell (BMSC-scaffold constructs (cell-oriented and random in repairing full-thickness articular cartilage defects in rabbits. While histological and immunohistochemical analyses revealed efficient cartilage regeneration and cartilaginous matrix secretion at 6 and 12 weeks after transplantation in both groups, the biochemical properties (levels of DNA, GAG, and collagen and biomechanical values in the oriented scaffold group were higher than that in random group at early time points after implantation. While these differences were not evident at 24 weeks, the biochemical and biomechanical properties of the regenerated cartilage in the oriented scaffold-BMSC construct group were similar to that of native cartilage. These results demonstrate that an oriented scaffold, in combination with differentiated BMSCs can successfully repair full-thickness articular cartilage defects in rabbits, and produce cartilage enhanced biomechanical properties.

  12. From Extraction of Local Structures of Protein Energy Landscapes to Improved Decoy Selection in Template-Free Protein Structure Prediction.

    Science.gov (United States)

    Akhter, Nasrin; Shehu, Amarda

    2018-01-19

    Due to the essential role that the three-dimensional conformation of a protein plays in regulating interactions with molecular partners, wet and dry laboratories seek biologically-active conformations of a protein to decode its function. Computational approaches are gaining prominence due to the labor and cost demands of wet laboratory investigations. Template-free methods can now compute thousands of conformations known as decoys, but selecting native conformations from the generated decoys remains challenging. Repeatedly, research has shown that the protein energy functions whose minima are sought in the generation of decoys are unreliable indicators of nativeness. The prevalent approach ignores energy altogether and clusters decoys by conformational similarity. Complementary recent efforts design protein-specific scoring functions or train machine learning models on labeled decoys. In this paper, we show that an informative consideration of energy can be carried out under the energy landscape view. Specifically, we leverage local structures known as basins in the energy landscape probed by a template-free method. We propose and compare various strategies of basin-based decoy selection that we demonstrate are superior to clustering-based strategies. The presented results point to further directions of research for improving decoy selection, including the ability to properly consider the multiplicity of native conformations of proteins.

  13. From Extraction of Local Structures of Protein Energy Landscapes to Improved Decoy Selection in Template-Free Protein Structure Prediction

    Directory of Open Access Journals (Sweden)

    Nasrin Akhter

    2018-01-01

    Full Text Available Due to the essential role that the three-dimensional conformation of a protein plays in regulating interactions with molecular partners, wet and dry laboratories seek biologically-active conformations of a protein to decode its function. Computational approaches are gaining prominence due to the labor and cost demands of wet laboratory investigations. Template-free methods can now compute thousands of conformations known as decoys, but selecting native conformations from the generated decoys remains challenging. Repeatedly, research has shown that the protein energy functions whose minima are sought in the generation of decoys are unreliable indicators of nativeness. The prevalent approach ignores energy altogether and clusters decoys by conformational similarity. Complementary recent efforts design protein-specific scoring functions or train machine learning models on labeled decoys. In this paper, we show that an informative consideration of energy can be carried out under the energy landscape view. Specifically, we leverage local structures known as basins in the energy landscape probed by a template-free method. We propose and compare various strategies of basin-based decoy selection that we demonstrate are superior to clustering-based strategies. The presented results point to further directions of research for improving decoy selection, including the ability to properly consider the multiplicity of native conformations of proteins.

  14. Virus encoded MHC-like decoys diversify the inhibitory KIR repertoire.

    Directory of Open Access Journals (Sweden)

    Paola Carrillo-Bustamante

    Full Text Available Natural killer (NK cells are circulating lymphocytes that play an important role in the control of viral infections and tumors. Their functions are regulated by several activating and inhibitory receptors. A subset of these receptors in human NK cells are the killer immunoglobulin-like receptors (KIRs, which interact with the highly polymorphic MHC class I molecules. One important function of NK cells is to detect cells that have down-regulated MHC expression (missing-self. Because MHC molecules have non polymorphic regions, their expression could have been monitored with a limited set of monomorphic receptors. Surprisingly, the KIR family has a remarkable genetic diversity, the function of which remains poorly understood. The mouse cytomegalovirus (MCMV is able to evade NK cell responses by coding "decoy" molecules that mimic MHC class I. This interaction was suggested to have driven the evolution of novel NK cell receptors. Inspired by the MCMV system, we develop an agent-based model of a host population infected with viruses that are able to evolve MHC down-regulation and decoy molecules. Our simulations show that specific recognition of MHC class I molecules by inhibitory KIRs provides excellent protection against viruses evolving decoys, and that the diversity of inhibitory KIRs will subsequently evolve as a result of the required discrimination between host MHC molecules and decoy molecules.

  15. Modeling, Simulation, and Analysis of a Decoy State Enabled Quantum Key Distribution System

    Science.gov (United States)

    2015-03-26

    ltsnet.net Colin V. McLaughlin Research Physicist, Advanced Photonics Naval Research Laboratory, Washington, DC 20375 Colin.Mclaughlin@nrl.navy.mil...and dirty version. In this figure, the green and red decoy Y1 yields appear to vary more than the black and blue signal Y1 yields. As illustrated

  16. Delayed Toxicity Associated with Soluble Anthrax Toxin Receptor Decoy-Ig Fusion Protein Treatment

    Science.gov (United States)

    Cote, Christopher; Welkos, Susan; Manchester, Marianne; Young, John A. T.

    2012-01-01

    Soluble receptor decoy inhibitors, including receptor-immunogloubulin (Ig) fusion proteins, have shown promise as candidate anthrax toxin therapeutics. These agents act by binding to the receptor-interaction site on the protective antigen (PA) toxin subunit, thereby blocking toxin binding to cell surface receptors. Here we have made the surprising observation that co-administration of receptor decoy-Ig fusion proteins significantly delayed, but did not protect, rats challenged with anthrax lethal toxin. The delayed toxicity was associated with the in vivo assembly of a long-lived complex comprised of anthrax lethal toxin and the receptor decoy-Ig inhibitor. Intoxication in this system presumably results from the slow dissociation of the toxin complex from the inhibitor following their prolonged circulation. We conclude that while receptor decoy-Ig proteins represent promising candidates for the early treatment of B. anthracis infection, they may not be suitable for therapeutic use at later stages when fatal levels of toxin have already accumulated in the bloodstream. PMID:22511955

  17. Genetic diversity and antimicrobial resistance of Campylobacter and Salmonella strains isolated from decoys and raptors.

    Science.gov (United States)

    Jurado-Tarifa, E; Torralbo, A; Borge, C; Cerdà-Cuéllar, M; Ayats, T; Carbonero, A; García-Bocanegra, I

    2016-10-01

    Infections caused by thermotolerant Campylobacter spp. and Salmonella spp. are the leading causes of human gastroenteritis worldwide. Wild birds can act as reservoirs of both pathogens. A survey was carried out to determine the prevalence, genetic diversity and antimicrobial resistance of thermotolerant Campylobacter and Salmonella in waterfowl used as decoys and wild raptors in Andalusia (Southern Spain). The overall prevalence detected for Campylobacter was 5.9% (18/306; CI95%: 3.25-8.52) in decoys and 2.3% (9/387; CI95%: 0.82-3.83) in wild raptors. Isolates were identified as C. jejuni, C. coli and C. lari in both bird groups. Salmonella was isolated in 3.3% (10/306; CI95%: 2.3-4.3) and 4.6% (18/394; CI95%: 3.5-5.6) of the decoys and raptors, respectively. Salmonella Enteritidis and Typhimurium were the most frequently identified serovars, although Salmonella serovars Anatum, Bredeney, London and Mikawasima were also isolated. Pulsed-field gel electrophoresis analysis of isolates showed higher genetic diversity within Campylobacter species compared to Salmonella serovars. Campylobacter isolates showed resistance to gentamicin, ciprofloxacin and tetracycline, while resistance to erythromycin and tetracycline was found in Salmonella isolates. The results indicate that both decoys and raptors can act as natural carriers of Campylobacter and Salmonella in Spain, which may have important implications for public and animal health. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Decoy-state quantum key distribution with both source errors and statistical fluctuations

    International Nuclear Information System (INIS)

    Wang Xiangbin; Yang Lin; Peng Chengzhi; Pan Jianwei

    2009-01-01

    We show how to calculate the fraction of single-photon counts of the 3-intensity decoy-state quantum cryptography faithfully with both statistical fluctuations and source errors. Our results rely only on the bound values of a few parameters of the states of pulses.

  19. Enhancement of the repair of dog alveolar cleft by an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture.

    Science.gov (United States)

    Yuanzheng, Chen; Yan, Gao; Ting, Li; Yanjie, Fu; Peng, Wu; Nan, Bai

    2015-05-01

    -rich fibrin are capable of improving the repair of dog alveolar cleft, and the mixture of them is more potent than each one of them used singly for enhancing new bone regeneration.

  20. Enhancement of excision-repair efficiency by conditioned medium from density-inhibited cultures in V79 Chinese hamster cells

    International Nuclear Information System (INIS)

    Nakano, S.

    1979-01-01

    Conditioned medium from density-inhibited V79 Chinese hamster cell cultures, given as a post-treatment to UV-irradiated homologous cells, was demonstrated to reduce the lethal action of ultraviolet light by temporarily blocking DNA replication. Since the increased survival was not affected by various nontoxic concentrations of caffeine, such protective effect would be attributable to the prolonged intervention of excision repair before DNA replication during the post-treatment period. The influence of conditioned medium on the UV-induced mutation at the ouabain-resistance locus was also examined and a significant decrease in mutation frequecy was noted. The observed reduction in killing and mutation as a result of post-incubation in conditioned medium, which delays DNA replication, would be interpreted as evidence that conditioned medium provides a longer period of time for an error-free excision-repair process, leaving lesion in DNA available for error-prone post-replication repair. (Auth.)

  1. DNA repair

    International Nuclear Information System (INIS)

    Setlow, R.

    1978-01-01

    Some topics discussed are as follows: difficulty in extrapolating data from E. coli to mammalian systems; mutations caused by UV-induced changes in DNA; mutants deficient in excision repair; other postreplication mechanisms; kinds of excision repair systems; detection of repair by biochemical or biophysical means; human mutants deficient in repair; mutagenic effects of UV on XP cells; and detection of UV-repair defects among XP individuals

  2. NRU vessel repair and return to service: enhancing a Canadian R and D asset for the future

    Energy Technology Data Exchange (ETDEWEB)

    Cox, D.S.; Arnold, J.B.; Lee, J.K., E-mail: coxd@aecl.ca [Atomic Energy of Canada Limited, Chalk River, Ontario (Canada)

    2013-07-01

    The National Research Universal (NRU) reactor was successfully returned to high power operation in 2010 August, after completing extensive inspections and repairs of the calandria vessel, in response to a small leak of heavy water that was discovered in 2009 May. The aluminum alloy vessel material had corroded from the outside surface over many years, and required application of weld build-up and plated weld repair at ten locations, executed by remote tooling deployed from inside the reactor vessel. Many specialized remotely operated tools were developed for inspection, sampling and repair operations. In parallel with the repair efforts, important maintenance activities were performed, enabled by the de-fuelled state with the heavy water drained from the vessel. Two annual inspection cycles have now been completed since the reactor was returned to high power operation, confirming the fitness of the vessel for continued operation. The NRU reactor is now entering its 56th year of operation and the current operating licence extends to 2016. Based on the outcome of a comprehensive Integrated Safety Review, AECL is continuing to implement major equipment upgrades and process improvements to support safe and reliable operation through 2021, for the benefit of Canadians and the world. (author)

  3. Myc Decoy Oligodeoxynucleotide Inhibits Growth and Modulates Differentiation of Mouse Embryonic Stem Cells as a Model of Cancer Stem Cells.

    Science.gov (United States)

    Johari, Behrooz; Ebrahimi-Rad, Mina; Maghsood, Faezeh; Lotfinia, Majid; Saltanatpouri, Zohreh; Teimoori-Toolabi, Ladan; Sharifzadeh, Zahra; Karimipoor, Morteza; Kadivar, Mehdi

    2017-01-01

    Myc (c-Myc) alone activates the embryonic stem cell-like transcriptional module in both normal and transformed cells. Its dysregulation might lead to increased cancer stem cells (CSCs) population in some tumor cells. In order to investigate the potential of Myc decoy oligodeoxynucleotides for differentiation therapy, mouse embryonic stem cells (mESCs) were used in this study as a model of CSCs. To our best of knowledge this is the first report outlining the application of Myc decoy in transcription factor decoy "TFD" strategy for inducing differentiation in mESCs. A 20-mer double-stranded Myc transcription factor decoy and scrambled oligodeoxynucleotides (ODNs) were designed, analyzed by electrophoretic mobility shift (EMSA) assay and transfected into the mESCs under 2 inhibitors (2i) condition. Further investigations were carried out using fluorescence and confocal microscopy, cell proliferation and apoptosis analysis, alkaline phosphatase and embryoid body formation assay, real-time PCR and western blotting. EMSA data showed that Myc decoy ODNs bound specifically to c-Myc protein. They were found to be localized in both cytoplasm and nucleus of mESCs. Our results revealed the potential capability of Myc decoy ODNs to decrease cell viability by (16.1±2%), to increase the number of cells arrested in G0/G1 phases and apoptosis by (14.2±3.1%) and (12.1±3.2%), respectively regarding the controls. Myc decoy could also modulate differentiation in mESCs despite the presence of 2i/LIF in our medium the presence of 2i/LIF in our medium. The optimized Myc decoy ODNs approach might be considered as a promising alternative strategy for differentiation therapy investigations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Cell cycle inhibitor, p19INK4d, promotes cell survival and decreases chromosomal aberrations after genotoxic insult due to enhanced DNA repair.

    Science.gov (United States)

    Scassa, María E; Marazita, Mariela C; Ceruti, Julieta M; Carcagno, Abel L; Sirkin, Pablo F; González-Cid, Marcela; Pignataro, Omar P; Cánepa, Eduardo T

    2007-05-01

    Genome integrity and cell proliferation and survival are regulated by an intricate network of pathways that includes cell cycle checkpoints, DNA repair and recombination, and programmed cell death. It makes sense that there should be a coordinated regulation of these different processes, but the components of such mechanisms remain unknown. In this report, we demonstrate that p19INK4d expression enhances cell survival under genotoxic conditions. By using p19INK4d-overexpressing clones, we demonstrated that p19INK4d expression correlates with the cellular resistance to UV treatment with increased DNA repair activity against UV-induced lesions. On the contrary, cells transfected with p19INK4d antisense cDNA show reduced ability to repair DNA damage and increased sensitivity to genotoxic insult when compared with their p19INK4d-overexpressing counterparts. Consistent with these findings, our studies also show that p19INK4d-overexpressing cells present not only a minor accumulation of UV-induced chromosomal aberrations but a lower frequency of spontaneous chromosome abnormalities than p19INK4d-antisense cells. Lastly, we suggest that p19INK4d effects are dissociated from its role as CDK4/6 inhibitor. The results presented herein support a crucial role for p19INK4d in regulating genomic stability and overall cell viability under conditions of genotoxic stress. We propose that p19INK4d would belong to a protein network that would integrate DNA repair, apoptotic and checkpoint mechanisms in order to maintain the genomic integrity.

  5. Biomechanical comparison of four double-row speed-bridging rotator cuff repair techniques with or without medial or lateral row enhancement.

    Science.gov (United States)

    Pauly, Stephan; Fiebig, David; Kieser, Bettina; Albrecht, Bjoern; Schill, Alexander; Scheibel, Markus

    2011-12-01

    Biomechanical comparison of four different Speed-Bridge configurations with or without medial or lateral row reinforcement. Reinforcement of the knotless Speed-Bridge double-row repair technique with additional medial mattress- or lateral single-stitches was hypothesized to improve biomechanical repair stability at time zero. Controlled laboratory study: In 36 porcine fresh-frozen shoulders, the infraspinatus tendons were dissected and shoulders were randomized to four groups: (1) Speed-Bridge technique with single tendon perforation per anchor (STP); (2) Speed-Bridge technique with double tendon perforation per anchor (DTP); (3) Speed-Bridge technique with medial mattress-stitch reinforcement (MMS); (4) Speed-Bridge technique with lateral single-stitch reinforcement (LSS). All repairs were cyclically loaded from 10-60 N up to 10-200 N (20 N stepwise increase) using a material testing device. Forces at 3 and 5 mm gap formation, mode of failure and maximum load to failure were recorded. The MMS-technique with double tendon perforation showed significantly higher ultimate tensile strength (338.9 ± 90.0 N) than DTP (228.3 ± 99.9 N), LSS (188.9 ± 62.5 N) and STP-technique (122.2 ± 33.8 N). Furthermore, the MMS-technique provided increased maximal force resistance until 3 and 5 mm gap formation (3 mm: 77.8 ± 18.6 N; 5 mm: 113.3 ± 36.1 N) compared with LSS, DTP and STP (P row defect by tendon sawing first, then laterally. No anchor pullout occurred. Double tendon perforation per anchor and additional medial mattress stitches significantly enhance biomechanical construct stability at time zero in this ex vivo model when compared with the all-knotless Speed-Bridge rotator cuff repair.

  6. Differential expression of SOS genes in an E. coli mutant producing unstable lexA protein enhances excision repair but inhibits mutagenesis

    International Nuclear Information System (INIS)

    Peterson, K.R.; Ganesan, A.K.; Mount, D.W.; Stanford Univ., CA)

    1986-01-01

    The SOS response is displayed following treatments which damage DNA or inhibit DNA replication. Two associated activities include enhanced capacity for DNA repair resulting from derepression of the recA, uvrA, uvrB and uvrD genes and increased mutagenesis due to derepression of recA, umuC and umuD. These changes are the consequence of the derepression of at least seventeen unlinked operons negatively regulated by LexA repressor. Following treatments that induce the SOS response, a signal molecule interacts with RecA protein, converting it to an activated form. Activated RecA protein facilitates the proteolytic cleavage of LexA repressor, which results in derepression of the regulon. The cell then enters a new physiological state during which time DNA repair processes are augmented. The lexA41 mutant of E. coli is a uv-resistant derivative of another mutant, lexA3, which produces a repressor that is not cleaved following inducing treatments. The resultant protein is unstable. Lac operon fusions to most of the genes in the SOS regulon were used to show that the various damage-inducible genes were derepressed to different extents. uvrA, B, and D were almost fully derepressed. Consistent with this finding, the rate of removal of T4 endonuclease V-sensitive sites was more rapid in the uv-irradiated lexA41 mutant than in normal cells, suggesting a more active excision repair system. We propose that the instability of the LexA41 protein reduces the intracellular concentration of repressor to a level that allows a high level of excision repair. The additional observation that SOS mutagenesis was only weakly induced in a lexA41 uvrA - mutant implies that the mutant protein partially represses one or more genes whose products promote SOS mutagenesis. 17 refs., 4 figs., 1 tab

  7. Quantum secure direct communication network with superdense coding and decoy photons

    International Nuclear Information System (INIS)

    Deng Fuguo; Li Xihan; Li Chunyan; Zhou Ping; Zhou Hongyu

    2007-01-01

    A quantum secure direct communication network scheme is proposed with quantum superdense coding and decoy photons. The servers on a passive optical network prepare and measure the quantum signal, i.e. a sequence of the d-dimensional Bell states. After confirming the security of the photons received from the receiver, the sender codes his secret message on them directly. For preventing a dishonest server from eavesdropping, some decoy photons prepared by measuring one photon in the Bell states are used to replace some original photons. One of the users on the network can communicate to any other one. This scheme has the advantage of high capacity, and it is more convenient than others as only a sequence of photons is transmitted in quantum line

  8. DECOY: Documenting Experiences with Cigarettes and Other Tobacco in Young Adults

    Science.gov (United States)

    Berg, Carla J.; Haardörfer, Regine; Lewis, Michael; Getachew, Betelihem; Lloyd, Steven A.; Thomas, Sarah Fretti; Lanier, Angela; Trepanier, Kelleigh; Johnston, Teresa; Grimsley, Linda; Foster, Bruce; Benson, Stephanie; Smith, Alicia; Barr, Dana Boyd; Windle, Michael

    2016-01-01

    Objectives We examined psychographic characteristics associated with tobacco use among Project DECOY participants. Methods Project DECOY is a 2-year longitudinal mixed-methods study examining risk for tobacco use among 3418 young adults across 7 Georgia colleges/universities. Baseline measures included sociodemographics, tobacco use, and psychographics using the Values, Attitudes, and Lifestyle Scale. Bivariate and multivariable analyses were conducted to identify correlates of tobacco use. Results Past 30-day use prevalence was: 13.3% cigarettes; 11.3% little cigars/cigarillos (LCCs); 3.6% smokeless tobacco; 10.9% e-cigarettes; and 12.2% hookah. Controlling for sociodemographics, correlates of cigarette use included greater novelty seeking (p fashion orientation (p = .007). Correlates of smokeless tobacco use included greater novelty seeking (p = .006) and less intellectual curiosity (p fashion orientation (p = .044), and self-focused thinking (p = .002), and less social conservatism (p products. PMID:27103410

  9. Surveillance of Influenza Viruses in Waterfowl Used As Decoys in Andalusia, Spain

    Science.gov (United States)

    Jurado-Tarifa, Estefanía; Napp, Sebastian; Gómez-Pacheco, Juan Manuel; Fernández-Morente, Manuel; Jaén-Téllez, Juan Antonio; Arenas, Antonio; García-Bocanegra, Ignacio

    2014-01-01

    A longitudinal study was carried out to determine the seroprevalence of avian influenza viruses (AIVs) in waterfowl used as decoys in Andalusia, southern Spain. A total of 2319 aquatic birds from 193 flocks were analyzed before and after the hunting season 2011–2012. In the first sampling, 403 out of 2319 (18.0%, CI95%: 15.8–19.0) decoys showed antibodies against AIVs by ELISA. The AI seroprevalence was significantly higher in geese (21.0%) than in ducks (11.7%) (P<0.001). Besides, the spatial distribution of AIVs was not homogeneous as significant differences among regions were observed. The prevalence of antibodies against AIVs subtypes H5 and H7 were 1.1% and 0.3%, respectively, using hemagglutination inhibition test (HI). The overall and H5 seroprevalences slightly increased after the hunting period (to 19.2% and 1.4%, respectively), while the H7 seroprevalence remained at the same level (0.3%). The proportion of flocks infected by AIVs was 65.3%, while 11.2% and 4.9% of flocks were positive for H5 and H7, respectively. Viral shedding was not detected in any of the 47 samples positive by both ELISA and HI, tested by RRT-PCR. The individual incidence after the hunting season was 3.4%. The fact that 57 animals seroconverted, 15 of which were confirmed by HI (12 H5 and 3 H7), was indication of contact with AIVs during the hunting period. The results indicate that waterfowl used as decoys are frequently exposed to AIVs and may be potentially useful as sentinels for AIVs monitoring. The seroprevalence detected and the seropositivity against AIVs H5 and H7, suggest that decoys can act as reservoirs of AIVs, which may be of animal and public health concern. PMID:24901946

  10. Radiosensitization of tumour cell lines by the polyphenol Gossypol results from depressed double-strand break repair and not from enhanced apoptosis.

    Science.gov (United States)

    Kasten-Pisula, Ulla; Windhorst, Sabine; Dahm-Daphi, Jochen; Mayr, Georg; Dikomey, Ekkehard

    2007-06-01

    New drugs are needed to increase the efficiency of radiotherapy in order to improve the therapeutic outcome of tumour patients. In this respect, the polyphenol Gossypol might be of interest, because of its effect on apoptosis and DNA repair, which is either mediated directly or indirectly via the inositol phosphate metabolism. It was investigated, whether these effects result in enhanced radiosensitivity of tumour cells. Tumour cell lines investigated: A549, FaDu, H1299, MCF7 and Du145. Cell cycle distribution was determined by FACS analysis, apoptosis was measured by DAPI staining and caspase3/7 activity. Double-strand breaks (DSB) were investigated via gammaH2AX-foci and cell survival by colony formation assay. The level of inositol phosphates was determined by HPLC, protein expression by Western blot. In A549 cells, Gossypol at concentrations 1microM strongly affects proliferation with only a modest arrest in the G1-phase, but with no increase in the fraction of apoptotic cells or the number of additional DSB. Additional DSB were only seen in FaDu cells, where Gossypol (2microM) was extremely toxic with a plating efficiency even found to be enhanced by Gossypol. For some tumour cell lines treatment with low concentrations of Gossypol can be used to inhibit DSB repair capacity and with that to increase the cellular radiosensitivity.

  11. Targeting the MET oncogene by concomitant inhibition of receptor and ligand via an antibody-"decoy" strategy.

    Science.gov (United States)

    Basilico, Cristina; Modica, Chiara; Maione, Federica; Vigna, Elisa; Comoglio, Paolo M

    2018-04-25

    MET, a master gene sustaining "invasive growth," is a relevant target for cancer precision therapy. In the vast majority of tumors, wild-type MET behaves as a "stress-response" gene and relies on the ligand (HGF) to sustain cell "scattering," invasive growth and apoptosis protection (oncogene "expedience"). In this context, concomitant targeting of MET and HGF could be crucial to reach effective inhibition. To test this hypothesis, we combined an anti-MET antibody (MvDN30) inducing "shedding" (i.e., removal of MET from the cell surface), with a "decoy" (i.e., the soluble extracellular domain of the MET receptor) endowed with HGF-sequestering ability. To avoid antibody/decoy interaction-and subsequent neutralization-we identified a single aminoacid in the extracellular domain of MET-lysine 842-that is critical for MvDN30 binding and engineered the corresponding recombinant decoyMET (K842E). DecoyMET K842E retains the ability to bind HGF with high affinity and inhibits HGF-induced MET phosphorylation. In HGF-dependent cellular models, MvDN30 antibody and decoyMET K842E used in combination cooperate in restraining invasive growth, and synergize in blocking cancer cell "scattering." The antibody and the decoy unbridle apoptosis of colon cancer stem cells grown in vitro as spheroids. In a preclinical model, built by orthotopic transplantation of a human pancreatic carcinoma in SCID mice engineered to express human HGF, concomitant treatment with antibody and decoy significantly reduces metastatic spread. The data reported indicate that vertical targeting of the MET/HGF axis results in powerful inhibition of ligand-dependent MET activation, providing proof of concept in favor of combined target therapy of MET "expedience." © 2018 UICC.

  12. Environmental enrichment and brain repair: harnessing the therapeutic effects of cognitive stimulation and physical activity to enhance experience-dependent plasticity.

    Science.gov (United States)

    Hannan, A J

    2014-02-01

    Environmental enrichment (EE) increases levels of novelty and complexity, inducing enhanced sensory, cognitive and motor stimulation. In wild-type rodents, EE has been found to have a range of effects, such as enhancing experience-dependent cellular plasticity and cognitive performance, relative to standard-housed controls. Whilst environmental enrichment is of course a relative term, dependent on the nature of control environmental conditions, epidemiological studies suggest that EE has direct clinical relevance to a range of neurological and psychiatric disorders. EE has been demonstrated to induce beneficial effects in animal models of a wide variety of brain disorders. The first evidence of beneficial effects of EE in a genetically targeted animal model was generated using Huntington's disease transgenic mice. Subsequent studies found that EE was also therapeutic in mouse models of Alzheimer's disease, consistent with epidemiological studies of relevant environmental modifiers. EE has also been found to ameliorate behavioural, cellular and molecular deficits in animal models of various neurological and psychiatric disorders, including Parkinson's disease, stroke, traumatic brain injury, epilepsy, multiple sclerosis, depression, schizophrenia and autism spectrum disorders. This review will focus on the effects of EE observed in animal models of neurodegenerative brain diseases, at molecular, cellular and behavioural levels. The proposal that EE may act synergistically with other approaches, such as drug and cell therapies, to facilitate brain repair will be discussed. I will also discuss the therapeutic potential of 'enviromimetics', drugs which mimic or enhance the therapeutic effects of cognitive activity and physical exercise, for both neuroprotection and brain repair. © 2013 British Neuropathological Society.

  13. Enhancement of abdominal wall defect repair using allogenic platelet-rich plasma with commercial polyester/cotton fabric (Damour) in a canine model

    Science.gov (United States)

    ABOUELNASR, Khaled; HAMED, Mohamed; LASHEN, Samah; EL-ADL, Mohamed; ELTAYSH, Rasha; TAGAWA, Michihito

    2017-01-01

    Platelet-rich plasma (PRP) has an important role in musculoskeletal surgery; however, it has been underutilized for accelerating the healing of abdominal wall defects in veterinary practice. Therefore, the aim of this study was to evaluate the use of commercial polyester/cotton fabric (Damour) as a new composite mesh for the repair of experimentally induced abdominal wall defects in canine models, and to investigate the possible role of PRP for improving such repair and reducing allied complications. For this purpose, abdominal wall defects were created in 24 healthy mongrel dogs and then repaired with mesh alone (control group) or mesh and allogenic PRP (PRP group). Dogs were euthanized after 2 or 4 months for gross examination of implantation site, detection of adhesion score and hernia recurrence. Moreover, tissue samples were collected for histological and gene expression analyses for neovascularization, collagen formation and tissue incorporation. Hernia recurrence was not recorded in PRP-treated dogs that also displayed significantly more neovascularization and less severe adhesion to the underlings (1.08 ± 0.51) in comparison to control group (2.08 ± 0.99). Histological and molecular evaluation confirmed the gross findings that collagen deposition, new vessel formation, and overexpression of angiogenic and myofibroplastic genes (COL1α1, COL3α1, VEGF and TGFβ1) were observed more frequently in the PRP group, at both time points. In conclusion, we found that addition of allogenic PRP to Damour mesh enhanced neovessel formation, and increased tissue deposition and incorporation, with subsequent reduction of peritoneal adhesion and recurrence rate. PMID:28603214

  14. Importance of the pharmacological profile of the bound ligand in enrichment on nuclear receptors: toward the use of experimentally validated decoy ligands.

    Science.gov (United States)

    Lagarde, Nathalie; Zagury, Jean-François; Montes, Matthieu

    2014-10-27

    The evaluation of virtual ligand screening methods is of major importance to ensure their reliability. Taking into account the agonist/antagonist pharmacological profile should improve the quality of the benchmarking data sets since ligand binding can induce conformational changes in the nuclear receptor structure and such changes may vary according to the agonist/antagonist ligand profile. We indeed found that splitting the agonist and antagonist ligands into two separate data sets for a given nuclear receptor target significantly enhances the quality of the evaluation. The pharmacological profile of the ligand bound in the binding site of the target structure was also found to be an additional critical parameter. We also illustrate that active compound data sets for a given pharmacological activity can be used as a set of experimentally validated decoy ligands for another pharmacological activity to ensure a reliable and challenging evaluation of virtual screening methods.

  15. Molecular biological mechanisms I. DNA repair

    International Nuclear Information System (INIS)

    Friedl, A.A.

    2000-01-01

    Cells of all living systems possess a variety of mechanisms that allow to repair spontaneous and exogeneously induced DNA damage. DNA repair deficiencies may invoke enhanced sensitivity towards DNA-damaging agents such as ionizing radiation. They may also enhance the risk of cancer development, both spontaneously or after induction. This article reviews several DNA repair mechanisms, especially those dealing with DNA double-strand breaks, and describes hereditary diseases associated with DNA repair defects. (orig.) [de

  16. Adenovirus-Mediated Delivery of Decoy Hyper Binding Sites Targeting Oncogenic HMGA1 Reduces Pancreatic and Liver Cancer Cell Viability.

    Science.gov (United States)

    Hassan, Faizule; Ni, Shuisong; Arnett, Tyler C; McKell, Melanie C; Kennedy, Michael A

    2018-03-30

    High mobility group AT-hook 1 (HMGA1) protein is an oncogenic architectural transcription factor that plays an essential role in early development, but it is also implicated in many human cancers. Elevated levels of HMGA1 in cancer cells cause misregulation of gene expression and are associated with increased cancer cell proliferation and increased chemotherapy resistance. We have devised a strategy of using engineered viruses to deliver decoy hyper binding sites for HMGA1 to the nucleus of cancer cells with the goal of sequestering excess HMGA1 at the decoy hyper binding sites due to binding competition. Sequestration of excess HMGA1 at the decoy binding sites is intended to reduce HMGA1 binding at the naturally occurring genomic HMGA1 binding sites, which should result in normalized gene expression and restored sensitivity to chemotherapy. As proof of principle, we engineered the replication defective adenovirus serotype 5 genome to contain hyper binding sites for HMGA1 composed of six copies of an individual HMGA1 binding site, referred to as HMGA-6. A 70%-80% reduction in cell viability and increased sensitivity to gemcitabine was observed in five different pancreatic and liver cancer cell lines 72 hr after infection with replication defective engineered adenovirus serotype 5 virus containing the HMGA-6 decoy hyper binding sites. The decoy hyper binding site strategy should be general for targeting overexpression of any double-stranded DNA-binding oncogenic transcription factor responsible for cancer cell proliferation.

  17. [Ru(bipy)3]2+ nanoparticle-incorporate dental light cure resin to promote photobiomodulation therapy for enhanced vital pulp tissue repair

    Science.gov (United States)

    Mosca, Rodrigo C.; Young, Nicholas; Zeituni, Carlos A.; Arany, Praveen R.

    2018-02-01

    The use of nanoparticle on dental light cure resin is not new, currently several compounds (nanoadditives) are used to promote better communication between the restorative material and biological tissues. The interest for this application is growing up to enhance mechanical proprieties to dental tissue cells regeneration. Bioactive nanoparticles and complex compounds with multiple functions are the major target for optimizing the restorative materials. In this work, we incorporate [Ru(bipy)3]2+ nanoparticles, that absorbs energy at 450 nm (blue-light) and emits strongly at 620 nm (red-light), in PLGA Microspheres and insert it in Dental Light Cure Resin to promote the Photobiomodulation Therapy (PBM) effects to accelerate dental pulp repair by in vitro using cytotoxicity and proliferation assay.

  18. Transplantation of Allogeneic PW1pos/Pax7neg Interstitial Cells Enhance Endogenous Repair of Injured Porcine Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Fiona C. Lewis, BSc, PhD

    2017-12-01

    Full Text Available Skeletal muscle-derived PW1pos/Pax7neg interstitial cells (PICs express and secrete a multitude of proregenerative growth factors and cytokines. Utilizing a porcine preclinical skeletal muscle injury model, delivery of allogeneic porcine PICs (pPICs significantly improved and accelerated myofiber regeneration and neocapillarization, compared with saline vehicle control-treated muscles. Allogeneic pPICs did not contribute to new myofibers or capillaries and were eliminated by the host immune system. In conclusion, allogeneic pPIC transplantation stimulated the endogenous stem cell pool to bring about enhanced autologous skeletal muscle repair and regeneration. This allogeneic cell approach is considered a cost-effective, easy to apply, and readily available regenerative therapeutic strategy.

  19. Benchmark of four popular virtual screening programs: construction of the active/decoy dataset remains a major determinant of measured performance.

    Science.gov (United States)

    Chaput, Ludovic; Martinez-Sanz, Juan; Saettel, Nicolas; Mouawad, Liliane

    2016-01-01

    In a structure-based virtual screening, the choice of the docking program is essential for the success of a hit identification. Benchmarks are meant to help in guiding this choice, especially when undertaken on a large variety of protein targets. Here, the performance of four popular virtual screening programs, Gold, Glide, Surflex and FlexX, is compared using the Directory of Useful Decoys-Enhanced database (DUD-E), which includes 102 targets with an average of 224 ligands per target and 50 decoys per ligand, generated to avoid biases in the benchmarking. Then, a relationship between these program performances and the properties of the targets or the small molecules was investigated. The comparison was based on two metrics, with three different parameters each. The BEDROC scores with α = 80.5, indicated that, on the overall database, Glide succeeded (score > 0.5) for 30 targets, Gold for 27, FlexX for 14 and Surflex for 11. The performance did not depend on the hydrophobicity nor the openness of the protein cavities, neither on the families to which the proteins belong. However, despite the care in the construction of the DUD-E database, the small differences that remain between the actives and the decoys likely explain the successes of Gold, Surflex and FlexX. Moreover, the similarity between the actives of a target and its crystal structure ligand seems to be at the basis of the good performance of Glide. When all targets with significant biases are removed from the benchmarking, a subset of 47 targets remains, for which Glide succeeded for only 5 targets, Gold for 4 and FlexX and Surflex for 2. The performance dramatic drop of all four programs when the biases are removed shows that we should beware of virtual screening benchmarks, because good performances may be due to wrong reasons. Therefore, benchmarking would hardly provide guidelines for virtual screening experiments, despite the tendency that is maintained, i.e., Glide and Gold display better

  20. Field test of a practical secure communication network with decoy-state quantum cryptography.

    Science.gov (United States)

    Chen, Teng-Yun; Liang, Hao; Liu, Yang; Cai, Wen-Qi; Ju, Lei; Liu, Wei-Yue; Wang, Jian; Yin, Hao; Chen, Kai; Chen, Zeng-Bing; Peng, Cheng-Zhi; Pan, Jian-Wei

    2009-04-13

    We present a secure network communication system that operated with decoy-state quantum cryptography in a real-world application scenario. The full key exchange and application protocols were performed in real time among three nodes, in which two adjacent nodes were connected by approximate 20 km of commercial telecom optical fiber. The generated quantum keys were immediately employed and demonstrated for communication applications, including unbreakable real-time voice telephone between any two of the three communication nodes, or a broadcast from one node to the other two nodes by using one-time pad encryption.

  1. Overcoming preexisting humoral immunity to AAV using capsid decoys.

    Science.gov (United States)

    Mingozzi, Federico; Anguela, Xavier M; Pavani, Giulia; Chen, Yifeng; Davidson, Robert J; Hui, Daniel J; Yazicioglu, Mustafa; Elkouby, Liron; Hinderer, Christian J; Faella, Armida; Howard, Carolann; Tai, Alex; Podsakoff, Gregory M; Zhou, Shangzhen; Basner-Tschakarjan, Etiena; Wright, John Fraser; High, Katherine A

    2013-07-17

    Adeno-associated virus (AAV) vectors delivered through the systemic circulation successfully transduce various target tissues in animal models. However, similar attempts in humans have been hampered by the high prevalence of neutralizing antibodies to AAV, which completely block vector transduction. We show in both mouse and nonhuman primate models that addition of empty capsid to the final vector formulation can, in a dose-dependent manner, adsorb these antibodies, even at high titers, thus overcoming their inhibitory effect. To further enhance the safety of the approach, we mutated the receptor binding site of AAV2 to generate an empty capsid mutant that can adsorb antibodies but cannot enter a target cell. Our work suggests that optimizing the ratio of full/empty capsids in the final formulation of vector, based on a patient's anti-AAV titers, will maximize the efficacy of gene transfer after systemic vector delivery.

  2. Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair.

    Science.gov (United States)

    Shafiq, Muhammad; Jung, Youngmee; Kim, Soo Hyun

    2016-06-01

    Stem cells are a promising solution for the treatment of a variety of diseases. However, the limited survival and engraftment of transplanted cells due to a hostile ischemic environment is a bottleneck for effective utilization and commercialization. Within this environment, the majority of transplanted cells undergo apoptosis prior to participating in lineage differentiation and cellular integration. Therefore, in order to maximize the clinical utility of stem/progenitor cells, strategies must be employed to increase their adhesion, retention, and engraftment in vivo. Here, we reviewed key strategies that are being adopted to enhance the survival, retention, and engraftment of transplanted stem cells through the manipulation of both the stem cells and the surrounding environment. We describe how preconditioning of cells or cell manipulations strategies can enhance stem cell survival and engraftment after transplantation. We also discuss how biomaterials can enhance the function of stem cells for effective tissue regeneration. Biomaterials can incorporate or mimic extracellular function (ECM) function and enhance survival or differentiation of transplanted cells in vivo. Biomaterials can also promote angiogenesis, enhance engraftment and differentiation, and accelerate electromechanical integration of transplanted stem cells. Insight gained from this review may direct the development of future investigations and clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. NF-κB decoy oligodeoxynucleotide mitigates wear particle-associated bone loss in the murine continuous infusion model.

    Science.gov (United States)

    Lin, Tzu-Hua; Pajarinen, Jukka; Sato, Taishi; Loi, Florence; Fan, Changchun; Córdova, Luis A; Nabeshima, Akira; Gibon, Emmanuel; Zhang, Ruth; Yao, Zhenyu; Goodman, Stuart B

    2016-09-01

    Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Wear particle-induced chronic inflammation is associated with the development of periprosthetic osteolysis. Modulation of NF-κB signaling in macrophages, osteoclasts, and mesenchymal stem cells could potentially mitigate this disease. In the current study, we examined the effects of local delivery of decoy NF-κB oligo-deoxynucleotide (ODN) on wear particle-induced bone loss in a murine continuous femoral particle infusion model. Ultra-high molecular weight polyethylene particles (UHMWPE) with or without lipopolysaccharide (LPS) were infused via osmotic pumps into hollow titanium rods placed in the distal femur of mice for 4weeks. Particle-induced bone loss was evaluated by μCT, and immunohistochemical analysis of sections from the femur. Particle infusion alone resulted in reduced bone mineral density and trabecular bone volume fraction in the distal femur. The decoy ODN reversed the particle-associated bone volume fraction loss around the implant, irrespective of the presence of LPS. Particle-infusion with LPS increased bone mineral density in the distal femur compared with particle-infusion alone. NF-κB decoy ODN reversed or further increased the bone mineral density in the femur (3-6mm from the distal end) exposed to particles alone or particles plus LPS. NF-κB decoy ODN also inhibited macrophage infiltration and osteoclast number, but had no significant effects on osteoblast numbers in femurs exposed to wear particles and LPS. Our study suggests that targeting NF-κB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced osteolysis. Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Chronic inflammation is crucial for the development of wear particle-associated bone loss. Modulation of NF-κB signaling in macrophages (pro-inflammatory cells), osteoclasts (bone

  4. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 with improved proof-reading enhances homology-directed repair.

    Science.gov (United States)

    Kato-Inui, Tomoko; Takahashi, Gou; Hsu, Szuyin; Miyaoka, Yuichiro

    2018-05-18

    Genome editing using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) predominantly induces non-homologous end joining (NHEJ), which generates random insertions or deletions, whereas homology-directed repair (HDR), which generates precise recombination products, is useful for wider applications. However, the factors that determine the ratio of HDR to NHEJ products after CRISPR/Cas9 editing remain unclear, and methods by which the proportion of HDR products can be increased have not yet been fully established. We systematically analyzed the HDR and NHEJ products after genome editing using various modified guide RNAs (gRNAs) and Cas9 variants with an enhanced conformational checkpoint to improve the fidelity at endogenous gene loci in HEK293T cells and HeLa cells. We found that these modified gRNAs and Cas9 variants were able to enhance HDR in both single-nucleotide substitutions and a multi-kb DNA fragment insertion. Our results suggest that the original CRISPR/Cas9 system from the bacterial immune system is not necessarily the best option for the induction of HDR in genome editing and indicate that the modulation of the kinetics of conformational checkpoints of Cas9 can optimize the HDR/NHEJ ratio.

  5. TOB1 Deficiency Enhances the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Tendon-Bone Healing in a Rat Rotator Cuff Repair Model

    Directory of Open Access Journals (Sweden)

    Yulei Gao

    2016-01-01

    Full Text Available Background/Aims: This study investigated the effect of silencing TOB1 (Transducer of ERBB2, 1 expression in bone marrow-derived mesenchymal stem cells (MSCs on MSC-facilitated tendon-bone healing in a rat supraspinatus repair model. Methods: Rat MSCs were transduced with a recombinant lentivirus encoding short hairpin RNA (shRNA against TOB1. MSC cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assays. The effect of MSCs with TOB1 deficiency on tendon-bone healing in a rat rotator cuff repair model was evaluated by biomechanical testing, histological analysis and collagen type I and II gene expression. An upstream regulator (miR-218 of TOB1 was determined in MSCs. Results: We found that knockdown of TOB1 significantly increased the proliferative activity of rat MSCs in vitro. When MSCs with TOB1 deficiency were injected into injured rat supraspinatus tendon-bone junctions, the effect on tendon-bone healing was enhanced compared to treatment with control MSCs with normal TOB1 expression, as evidenced by elevated levels of ultimate load to failure and stiffness, increased amount of fibrocartilage and augmented expression of collagen type I and type II genes. In addition, we found that the TOB1 3′ untranslated region is a direct target of miR-218. Similar to the effect of TOB1 deficiency, overexpression of miR-218 effectively promoted tendon-bone healing in rat. Conclusion: These results suggest that TOB1 may play a negative role in the effect of MSCs on tendon-bone healing, and imply that expression of TOB1 may be regulated by miR-218.

  6. Can a pairwise contact potential stabilize native protein folds against decoys obtained by threading?

    Science.gov (United States)

    Vendruscolo, M; Najmanovich, R; Domany, E

    2000-02-01

    We present a method to derive contact energy parameters from large sets of proteins. The basic requirement on which our method is based is that for each protein in the database the native contact map has lower energy than all its decoy conformations that are obtained by threading. Only when this condition is satisfied one can use the proposed energy function for fold identification. Such a set of parameters can be found (by perceptron learning) if Mp, the number of proteins in the database, is not too large. Other aspects that influence the existence of such a solution are the exact definition of contact and the value of the critical distance Rc, below which two residues are considered to be in contact. Another important novel feature of our approach is its ability to determine whether an energy function of some suitable proposed form can or cannot be parameterized in a way that satisfies our basic requirement. As a demonstration of this, we determine the region in the (Rc, Mp) plane in which the problem is solvable, i.e., we can find a set of contact parameters that stabilize simultaneously all the native conformations. We show that for large enough databases the contact approximation to the energy cannot stabilize all the native folds even against the decoys obtained by gapless threading.

  7. Meningocele repair

    Science.gov (United States)

    ... is surgery to repair birth defects of the spine and spinal membranes. Meningocele and myelomeningocele ... is covered by a sterile dressing. Your child may then be transferred to a neonatal intensive ...

  8. New treatment of periodontal diseases by using NF-kappaB decoy oligodeoxynucleotides via prevention of bone resorption and promotion of wound healing.

    Science.gov (United States)

    Shimizu, Hideo; Nakagami, Hironori; Morita, Shosuke; Tsukamoto, Ikuyo; Osako, Mariana Kiomy; Nakagami, Futoshi; Shimosato, Takashi; Minobe, Noriko; Morishita, Ryuichi

    2009-09-01

    Nuclear factor-kappa B (NF-kappaB) is involved in osteoclast differentiation and activation. Thus, the blockade of the NF-kappaB pathway might be a novel therapeutic strategy for treating bone metabolic diseases. Periodontitis is subgingival inflammation caused by bacterial infection; this disease also is thought to be a chronic focal point responsible for systemic diseases. In this study, NF-kappaB decoy oligodeoxynucleotides (ODNs) were topically applied for experimental periodontitis in a debris-accumulation model and wound healing in a bone-defect model of beagle dogs to investigate the effect of decoy ODN on bone metabolism. Application of NF-kappaB decoy ODN significantly reduced interleukin-6 activity in crevicular fluid and improved alveolar bone loss in the analysis of dental radiographs and DEXA. Direct measurement of exposed root that lost alveolar bone support revealed that NF-kappaB decoy treatment dramatically protected bone from loss. In a bone-defect model, NF-kappaB decoy ODN promoted the healing process as compared with control scrambled decoy in micro-CT analysis. Overall, inhibition of NF-kappaB by decoy strategy prevented the progression of bone loss in periodontitis and promoted the wound healing in bone defects through the inhibition of osteoclastic bone resorption. Targeting of NF-kappaB might be a potential therapy in various bone metabolic diseases.

  9. Poly(lactic-co-glycolide) polymer constructs cross-linked with human BMP-6 and VEGF protein significantly enhance rat mandible defect repair.

    Science.gov (United States)

    Das, Anusuya; Fishero, Brian A; Christophel, J Jared; Li, Ching-Ju; Kohli, Nikita; Lin, Yong; Dighe, Abhijit S; Cui, Quanjun

    2016-04-01

    We have previously shown that the combined delivery of mesenchymal stem cells (MSCs), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 6 (BMP-6) induces significantly more bone formation than that induced by the delivery of any single factor or a combination of any two factors. We now determine whether the exogenous addition of VEGF and BMP-6 is sufficient for bone healing when MSCs are not provided. Poly(lactic-co-glycolic acid) (PLAGA) microsphere-based three-dimensional scaffolds (P) were fabricated by thermal sintering of PLAGA microspheres. The scaffolds were chemically cross-linked with 200 ng recombinant human VEGF (P(VEGF)) or BMP-6 (P(BMP-6)) or both (P(VEGF+BMP-6)) by the EDC-NHS-MES method. Release of the proteins from the scaffolds was detected for 21 days in vitro which confirmed their comparable potential to supply the proteins in vivo. The scaffolds were delivered to a critical-sized mandibular defect created in 32 Sprague Dawley rats. Significant bone regeneration was observed only in rats with P(VEGF+BMP-6) scaffolds at weeks 2, 8 and 12 as revealed by micro-computer tomography. Vascular ingrowth was higher in the P(VEGF+BMP-6) group as seen by microfil imaging than in other groups. Trichrome staining revealed that a soft callus formed in P(VEGF), P(BMP-6) and P(VEGF+BMP-6) but not in P. MSCs isolated from rat femurs displayed expression of the bone-specific marker osteocalcin when cultured with P(VEGF), P(BMP-6), or P(VEGF+BMP-6) but not with P. Robust mineralization and increased alkaline phosphatase gene expression were seen in rat MSCs when cultured on P(VEGF+BMP-6) but not on P, P(VEGF), or P(BMP-6). Thus, unlike the delivery of VEGF or BMP-6 alone, the combined delivery of VEGF and BMP-6 to the bone defect significantly enhanced bone repair through the enhancement of angiogenesis and the differentiation of endogenously recruited MSCs into the bone repair site.

  10. Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

    Science.gov (United States)

    Das, Anusuya; Barker, Daniel A; Wang, Tiffany; Lau, Cheryl M; Lin, Yong; Botchwey, Edward A

    2014-01-01

    In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid) (PLAGA) microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2) improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P) receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3) via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1) mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

  11. Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

    Directory of Open Access Journals (Sweden)

    Anusuya Das

    Full Text Available In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid (PLAGA microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2 improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3 via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1 mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

  12. DNA repair

    International Nuclear Information System (INIS)

    Van Zeeland, A.A.

    1984-01-01

    In this chapter a series of DNA repair pathways are discussed which are available to the cell to cope with the problem of DNA damaged by chemical or physical agents. In the case of microorganisms our knowledge about the precise mechanism of each DNA repair pathway and the regulation of it has been improved considerably when mutants deficient in these repair mechanisms became available. In the case of mammalian cells in culture, until recently there were very little repair deficient mutants available, because in almost all mammalian cells in culture at least the diploid number of chromosomes is present. Therefore the frequency of repair deficient mutants in such populations is very low. Nevertheless because replica plating techniques are improving some mutants from Chinese hamsters ovary cells and L5178Y mouse lymphoma cells are now available. In the case of human cells, cultures obtained from patients with certain genetic diseases are available. A number of cells appear to be sensitive to some chemical or physical mutagens. These include cells from patients suffering from xeroderma pigmentosum, Ataxia telangiectasia, Fanconi's anemia, Cockayne's syndrome. However, only in the case of xeroderma pigmentosum cells, has the sensitivity to ultraviolet light been clearly correlated with a deficiency in excision repair of pyrimidine dimers. Furthermore the work with strains obtained from biopsies from man is difficult because these cells generally have low cloning efficiencies and also have a limited lifespan in vitro. It is therefore very important that more repair deficient mutants will become available from established cell lines from human or animal origin

  13. Purified Human Skeletal Muscle-Derived Stem Cells Enhance the Repair and Regeneration in the Damaged Urethra.

    Science.gov (United States)

    Nakajima, Nobuyuki; Tamaki, Tetsuro; Hirata, Maki; Soeda, Shuichi; Nitta, Masahiro; Hoshi, Akio; Terachi, Toshiro

    2017-10-01

    Postoperative damage of the urethral rhabdosphincter and nerve-vascular networks is a major complication of radical prostatectomy and generally causes incontinence and/or erectile dysfunction. The human skeletal muscle-derived stem cells, which have a synchronized reconstitution capacity of muscle-nerve-blood vessel units, were applied to this damage. Cells were enzymatically extracted from the human skeletal muscle, sorted using flow cytometry as CD34/45 (Sk-34) and CD29/34/45 (Sk-DN/29) fractions, and separately cultured/expanded in appropriate conditions within 2 weeks. Urethral damage was induced by manually removing one third of the wall of the muscle layer in nude rats. A mixture of expanded Sk-34 and Sk-DN/29 cells was applied on the damaged portion for the cell transplantation (CT) group. The same amount of media was used for the non-CT (NT) group. Urethral pressure profile was evaluated via electrical stimulation to assess functional recovery. Cell engraftments and differentiations were detected using immunohistochemistry and immunoelectron microscopy. Expression of angiogenic cytokines was also analyzed using reverse transcriptase-polymerase chain reaction and protein array. At 6 weeks after transplantation, the CT group showed a significantly higher functional recovery than the NT group (70.2% and 39.1%, respectively; P cells differentiated into skeletal muscle fibers, nerve-related Schwann cells, perineuriums, and vascular pericytes. Active paracrine angiogenic cytokines in the mixed cells were also detected with enhanced vascular formation in vivo. The transplantation of Sk-34 and Sk-DN/29 cells is potentially useful for the reconstitution of postoperative damage of the urethral rhabdosphincter and nerve-vascular networks.

  14. Hacking on decoy-state quantum key distribution system with partial phase randomization

    Science.gov (United States)

    Sun, Shi-Hai; Jiang, Mu-Sheng; Ma, Xiang-Chun; Li, Chun-Yan; Liang, Lin-Mei

    2014-04-01

    Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states.

  15. Hacking on decoy-state quantum key distribution system with partial phase randomization.

    Science.gov (United States)

    Sun, Shi-Hai; Jiang, Mu-Sheng; Ma, Xiang-Chun; Li, Chun-Yan; Liang, Lin-Mei

    2014-04-23

    Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states.

  16. Decoy-state BB84 protocol using space division multiplexing in silicon photonics

    DEFF Research Database (Denmark)

    Bacco, Davide; Ding, Yunhong; Dalgaard, Kjeld

    2017-01-01

    Quantum key distribution (QKD), a technique based on quantum physics, provides unconditional secure quantum keys to be shared between two or more clients (Alice and Bob) [1]. Most QKD systems are implemented in a point-to-point link using bulky and expensive devices. Consequently a large scale...... experiments have already demonstrated conventional binary QKD systems, using polarization and phase reference degrees of freedom [2, 3]. In this paper, we show the first silicon chip-to-chip decoy-state BB84 protocol based on spatial degrees of freedom (the cores of a multi-core fiber-MCF-). By tuning...... the superposition of the quantum state between cores, combined with a positive/negative phase relation. A train of weak coherent pulses (5 kHz repetition and 10 ns wide) are injected into the transmitter chip (Alice), where multiple variable optical attenuators (VOAs) are used to decrease the number of photons per...

  17. Practical long-distance quantum key distribution system using decoy levels

    International Nuclear Information System (INIS)

    Rosenberg, D; Peterson, C G; Harrington, J W; Rice, P R; Dallmann, N; Tyagi, K T; McCabe, K P; Hughes, R J; Nordholt, J E; Nam, S; Baek, B; Hadfield, R H

    2009-01-01

    Quantum key distribution (QKD) has the potential for widespread real-world applications, but no secure long-distance experiment has demonstrated the truly practical operation needed to move QKD from the laboratory to the real world due largely to limitations in synchronization and poor detector performance. Here, we report results obtained using a fully automated, robust QKD system based on the Bennett Brassard 1984 (BB84) protocol with low-noise superconducting nanowire single-photon detectors (SNSPDs) and decoy levels to produce a secret key with unconditional security over a record 140.6 km of optical fibre, an increase of more than a factor of five compared with the previous record for unconditionally secure key generation in a practical QKD system.

  18. Comparative Biochemical and Functional Analysis of Viral and Human Secreted Tumor Necrosis Factor (TNF) Decoy Receptors*

    Science.gov (United States)

    Pontejo, Sergio M.; Alejo, Ali; Alcami, Antonio

    2015-01-01

    The blockade of tumor necrosis factor (TNF) by etanercept, a soluble version of the human TNF receptor 2 (hTNFR2), is a well established strategy to inhibit adverse TNF-mediated inflammatory responses in the clinic. A similar strategy is employed by poxviruses, encoding four viral TNF decoy receptor homologues (vTNFRs) named cytokine response modifier B (CrmB), CrmC, CrmD, and CrmE. These vTNFRs are differentially expressed by poxviral species, suggesting distinct immunomodulatory properties. Whereas the human variola virus and mouse ectromelia virus encode one vTNFR, the broad host range cowpox virus encodes all vTNFRs. We report the first comprehensive study of the functional and binding properties of these four vTNFRs, providing an explanation for their expression profile among different poxviruses. In addition, the vTNFRs activities were compared with the hTNFR2 used in the clinic. Interestingly, CrmB from variola virus, the causative agent of smallpox, is the most potent TNFR of those tested here including hTNFR2. Furthermore, we demonstrate a new immunomodulatory activity of vTNFRs, showing that CrmB and CrmD also inhibit the activity of lymphotoxin β. Similarly, we report for the first time that the hTNFR2 blocks the biological activity of lymphotoxin β. The characterization of vTNFRs optimized during virus-host evolution to modulate the host immune response provides relevant information about their potential role in pathogenesis and may be used to improve anti-inflammatory therapies based on soluble decoy TNFRs. PMID:25940088

  19. Comparative Biochemical and Functional Analysis of Viral and Human Secreted Tumor Necrosis Factor (TNF) Decoy Receptors.

    Science.gov (United States)

    Pontejo, Sergio M; Alejo, Ali; Alcami, Antonio

    2015-06-26

    The blockade of tumor necrosis factor (TNF) by etanercept, a soluble version of the human TNF receptor 2 (hTNFR2), is a well established strategy to inhibit adverse TNF-mediated inflammatory responses in the clinic. A similar strategy is employed by poxviruses, encoding four viral TNF decoy receptor homologues (vTNFRs) named cytokine response modifier B (CrmB), CrmC, CrmD, and CrmE. These vTNFRs are differentially expressed by poxviral species, suggesting distinct immunomodulatory properties. Whereas the human variola virus and mouse ectromelia virus encode one vTNFR, the broad host range cowpox virus encodes all vTNFRs. We report the first comprehensive study of the functional and binding properties of these four vTNFRs, providing an explanation for their expression profile among different poxviruses. In addition, the vTNFRs activities were compared with the hTNFR2 used in the clinic. Interestingly, CrmB from variola virus, the causative agent of smallpox, is the most potent TNFR of those tested here including hTNFR2. Furthermore, we demonstrate a new immunomodulatory activity of vTNFRs, showing that CrmB and CrmD also inhibit the activity of lymphotoxin β. Similarly, we report for the first time that the hTNFR2 blocks the biological activity of lymphotoxin β. The characterization of vTNFRs optimized during virus-host evolution to modulate the host immune response provides relevant information about their potential role in pathogenesis and may be used to improve anti-inflammatory therapies based on soluble decoy TNFRs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Improvement of adhesion performance of mortar-repair interface with inducing crack path into repair

    Directory of Open Access Journals (Sweden)

    A. Satoh

    2015-10-01

    Full Text Available The most important performance for repair materials is adhesion to the substrate. The authors experimentally find out that high modulus fine aggregates in repair material enhance strength of it as well as the strength of the interface repaired with it, compared to the ordinary repair without fine aggregates. This paper elaborates the mechanisms for that with fractographic observation and FEM analysis based on the results of experiment. Also the authors discuss the ways for enhancing the strength and ductility of the repaired mortar

  1. Repair process and a repaired component

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, III, Herbert Chidsey; Simpson, Stanley F.

    2018-02-20

    Matrix composite component repair processes are disclosed. The matrix composite repair process includes applying a repair material to a matrix composite component, securing the repair material to the matrix composite component with an external securing mechanism and curing the repair material to bond the repair material to the matrix composite component during the securing by the external securing mechanism. The matrix composite component is selected from the group consisting of a ceramic matrix composite, a polymer matrix composite, and a metal matrix composite. In another embodiment, the repair process includes applying a partially-cured repair material to a matrix composite component, and curing the repair material to bond the repair material to the matrix composite component, an external securing mechanism securing the repair material throughout a curing period, In another embodiment, the external securing mechanism is consumed or decomposed during the repair process.

  2. Motorcycle Repair.

    Science.gov (United States)

    Hein, Jim; Bundy, Mike

    This motorcycle repair curriculum guide contains the following ten areas of study: brake systems, clutches, constant mesh transmissions, final drives, suspension, mechanical starting mechanisms, electrical systems, fuel systems, lubrication systems, and overhead camshafts. Each area consists of one or more units of instruction. Each instructional…

  3. The cis decoy against the estrogen response element suppresses breast cancer cells via target disrupting c-fos not mitogen-activated protein kinase activity.

    Science.gov (United States)

    Wang, Li Hua; Yang, Xiao Yi; Zhang, Xiaohu; Mihalic, Kelly; Xiao, Weihua; Farrar, William L

    2003-05-01

    Breast cancer, the most common malignancy in women, has been demonstrated to be associated with the steroid hormone estrogen and its receptor (ER), a ligand-activated transcription factor. Therefore, we developed a phosphorothiolate cis-element decoy against the estrogen response element (ERE decoy) to target disruption of ER DNA binding and transcriptional activity. Here, we showed that the ERE decoy potently ablated the 17beta-estrogen-inducible cell proliferation and induced apoptosis of human breast carcinoma cells by functionally affecting expression of c-fos gene and AP-1 luciferase gene reporter activity. Specificity of the decoy was demonstrated by its ability to directly block ER binding to a cis-element probe and transactivation. Moreover, the decoy failed to inhibit ER-mediated mitogen-activated protein kinase signaling pathways and cell growth of ER-negative breast cancer cells. Taken together, these data suggest that estrogen-mediated cell growth of breast cancer cells can be preferentially restricted via targeted disruption of ER at the level of DNA binding by a novel and specific decoy strategy applied to steroid nuclear receptors.

  4. Turbine repair process, repaired coating, and repaired turbine component

    Science.gov (United States)

    Das, Rupak; Delvaux, John McConnell; Garcia-Crespo, Andres Jose

    2015-11-03

    A turbine repair process, a repaired coating, and a repaired turbine component are disclosed. The turbine repair process includes providing a turbine component having a higher-pressure region and a lower-pressure region, introducing particles into the higher-pressure region, and at least partially repairing an opening between the higher-pressure region and the lower-pressure region with at least one of the particles to form a repaired turbine component. The repaired coating includes a silicon material, a ceramic matrix composite material, and a repaired region having the silicon material deposited on and surrounded by the ceramic matrix composite material. The repaired turbine component a ceramic matrix composite layer and a repaired region having silicon material deposited on and surrounded by the ceramic matrix composite material.

  5. Quercetin suppresses DNA double-strand break repair and enhances the radiosensitivity of human ovarian cancer cells via p53-dependent endoplasmic reticulum stress pathway

    Directory of Open Access Journals (Sweden)

    Gong C

    2017-12-01

    Full Text Available Cheng Gong,1 Zongyuan Yang,1 Lingyun Zhang,2 Yuehua Wang,2 Wei Gong,2 Yi Liu3 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of Oncology, XiangYang Central Hospital, Hubei University of Arts and Science, XiangYang, 3Department of Medicinal Chemistry, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China Abstract: Quercetin is proven to have anticancer effects for many cancers. However, the role of tumor suppressor p53 on quercetin’s radiosensitization and regulation of endoplasmic reticulum (ER stress response in this process remains obscure. Here, quercetin exposure resulted in ER stress, prolonged DNA repair, and the expression of p53 protein; phosphorylation on serine 15 and 20 increased in combination with X-irradiation. Quercetin pretreatment could potentiate radiation-induced cell death. The combination of irradiation and quercetin treatment aggravated DNA damages and caused typical apoptotic cell death; as well the expression of Bax and p21 elevated and the expression of Bcl-2 decreased. Knocking down of p53 could reverse all the above effects under quercetin in combination with radiation. In addition, quercetin-induced radiosensitization was through stimulation of ATM phosphorylation. In human ovarian cancer xenograft model, combined treatment of quercetin and radiation significantly restrained the growth of tumors, accompanied with the activation of p53, CCAAT/enhancer-binding protein homologous protein, and γ-H2AX. Overall, these results indicated that quercetin acted as a promising radiosensitizer through p53-dependent ER stress signals. Keywords: quercetin, p53, endoplasmic reticulum stress, DNA double-strand breaks, eIF-2α (eukaryotic initiation factor 2α, ATM kinase

  6. Spontaneous mutation by mutagenic repair of spontaneous lesions in DNA

    International Nuclear Information System (INIS)

    Hastings, P.J.; Quah, S.-K.; Borstel, R.C. von

    1976-01-01

    It is stated that strains of yeast carrying mutations in many of the steps in pathways repairing radiation-induced damage to DNA have enhanced spontaneous mutation rates. Most strains isolated because they have enhanced spontaneous mutation carry mutations in DNA repair systems. This suggests that much spontaneous mutation arises by mutagenic repair of spontaneous lesions. (author)

  7. Induced repair and mutagenesis in animal cells

    International Nuclear Information System (INIS)

    Takimoto, Koichi

    1981-01-01

    Induced repair and mutagenesis of animal cells against UV were studied in contrast with SOS repair of E. coli primarily by the use of viruses. Since UV-enhanced reactivation is a phenomenon similar to UV-reactivation (mutagenesis) and the presence of lesion bypass synthsis has been suggested, UV-enhanced reactivation has several common aspects with SOS reactivation of E. coli. However, correlation is not necessarily noted between increase in the viral survival rate and mutagenesis, nor do protease blockers exert any effect. Therefore, SOS repair of E. coli may have different mechansms from induced repair and mutagenesis in animal cells. (Ueda, J.)

  8. A decoy set for the thermostable subdomain from chicken villin headpiece, comparison of different free energy estimators

    Directory of Open Access Journals (Sweden)

    Tosatto Silvio CE

    2005-12-01

    Full Text Available Abstract Background Estimators of free energies are routinely used to judge the quality of protein structural models. As these estimators still present inaccuracies, they are frequently evaluated by discriminating native or native-like conformations from large ensembles of so-called decoy structures. Results A decoy set is obtained from snapshots taken from 5 long (100 ns molecular dynamics (MD simulations of the thermostable subdomain from chicken villin headpiece. An evaluation of the energy of the decoys is given using: i a residue based contact potential supplemented by a term for the quality of dihedral angles; ii a recently introduced combination of four statistical scoring functions for model quality estimation (FRST; iii molecular mechanics with solvation energy estimated either according to the generalized Born surface area (GBSA or iv the Poisson-Boltzmann surface area (PBSA method. Conclusion The decoy set presented here has the following features which make it attractive for testing energy scoring functions: 1 it covers a broad range of RMSD values (from less than 2.0 Å to more than 12 Å; 2 it has been obtained from molecular dynamics trajectories, starting from different non-native-like conformations which have diverse behaviour, with secondary structure elements correctly or incorrectly formed, and in one case folding to a native-like structure. This allows not only for scoring of static structures, but also for studying, using free energy estimators, the kinetics of folding; 3 all structures have been obtained from accurate MD simulations in explicit solvent and after molecular mechanics (MM energy minimization using an implicit solvent method. The quality of the covalent structure therefore does not suffer from steric or covalent problems. The statistical and physical effective energy functions tested on the set behave differently when native simulation snapshots are included or not in the set and when averaging over the

  9. Security analysis of the decoy method with the Bennett–Brassard 1984 protocol for finite key lengths

    International Nuclear Information System (INIS)

    Hayashi, Masahito; Nakayama, Ryota

    2014-01-01

    This paper provides a formula for the sacrifice bit-length for privacy amplification with the Bennett–Brassard 1984 protocol for finite key lengths, when we employ the decoy method. Using the formula, we can guarantee the security parameter for a realizable quantum key distribution system. The key generation rates with finite key lengths are numerically evaluated. The proposed method improves the existing key generation rate even in the asymptotic setting. (paper)

  10. Decoy receptor 3 suppresses FasL-induced apoptosis via ERK1/2 activation in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yi; Li, Dechun; Zhao, Xin; Song, Shiduo; Zhang, Lifeng; Zhu, Dongming [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China); Wang, Zhenxin [Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China); Chen, Xiaochen [Department of Pathology, The Obstetrics & Gynecology Hospital of Fudan University, Shanghai 200090 (China); Zhou, Jian, E-mail: zhoujian20150602@126.com [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China)

    2015-08-07

    Resistance to Fas Ligand (FasL) mediated apoptosis plays an important role in tumorigenesis. Decoy receptor 3 (DcR3) is reported to interact with FasL and is overexpressed in some malignant tumors. We sought to investigate the role of DcR3 in resistance to FasL in pancreatic cancer. We compared expression of apoptosis related genes between FasL-resistant SW1990 and FasL-sensitive Patu8988 pancreatic cell lines by microarray analysis. We explored the impact of siRNA knockdown of, or exogenous supplementation with, DcR3 on FasL-induced cell growth inhibition in pancreatic cancer cell lines and expression of proteins involved in apoptotic signaling. We assessed the level of DcR3 protein and ERK1/2 phosphorylation in tumor and non-tumor tissue samples of 66 patients with pancreatic carcinoma. RNAi knockdown of DcR3 expression in SW1990 cells reduced resistance to FasL-induced apoptosis, and supplementation of Patu8988 with rDcR3 had the opposite effect. RNAi knockdown of DcR3 in SW1990 cells elevated expression of caspase 3, 8 and 9, and reduced ERK1/2 phosphorylation (P < 0.05), but did not alter phosphorylated-Akt expression. 47 tumor tissue specimens, but only 15 matched non-tumor specimens stained for DcR3 (χ{sup 2} = 31.1447, P < 0.001). The proliferation index of DcR3 positive specimens (14.26  ±  2.67%) was significantly higher than that of DcR3 negative specimens (43.58  ±  7.88%, P < 0.01). DcR3 expression positively correlated with p-ERK1/2 expression in pancreatic cancer tissues (r = 0.607, P < 0.001). DcR3 enhances ERK1/2 phosphorylation and opposes FasL signaling in pancreatic cancer cells. - Highlights: • We investigated the role of DcR3 in FasL resistance in pancreatic cancer. • Knockdown of DcR3 in SW1990 cells reduced resistance to FasL-induced apoptosis. • DcR3 knockdown also elevated caspase expression, and reduced ERK1/2 phosphorylation. • Tumor and non-tumor tissues were collected from 66 pancreatic carcinoma patients

  11. G4-DNA formation in the HRAS promoter and rational design of decoy oligonucleotides for cancer therapy.

    Directory of Open Access Journals (Sweden)

    Alexandro Membrino

    Full Text Available HRAS is a proto-oncogene involved in the tumorigenesis of urinary bladder cancer. In the HRAS promoter we identified two G-rich elements, hras-1 and hras-2, that fold, respectively, into an antiparallel and a parallel quadruplex (qhras-1, qhras-2. When we introduced in sequence hras-1 or hras-2 two point mutations that block quadruplex formation, transcription increased 5-fold, but when we stabilized the G-quadruplexes by guanidinium phthalocyanines, transcription decreased to 20% of control. By ChIP we found that sequence hras-1 is bound only by MAZ, while hras-2 is bound by MAZ and Sp1: two transcription factors recognizing guanine boxes. We also discovered by EMSA that recombinant MAZ-GST binds to both HRAS quadruplexes, while Sp1-GST only binds to qhras-1. The over-expression of MAZ and Sp1 synergistically activates HRAS transcription, while silencing each gene by RNAi results in a strong down-regulation of transcription. All these data indicate that the HRAS G-quadruplexes behave as transcription repressors. Finally, we designed decoy oligonucleotides mimicking the HRAS quadruplexes, bearing (R-1-O-[4-(1-Pyrenylethynyl phenylmethyl] glycerol and LNA modifications to increase their stability and nuclease resistance (G4-decoys. The G4-decoys repressed HRAS transcription and caused a strong antiproliferative effect, mediated by apoptosis, in T24 bladder cancer cells where HRAS is mutated.

  12. Metabolic modulation of mammalian DNA excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Schrader, T.J.

    1988-01-01

    First, ultraviolet light (UVL)- and dimethylsulfate (DMS)-induced excision repair was examined in quiescent and lectin-stimulated bovine lymphocytes. Upon mitogenic stimulation, UVL-induced repair increased by a factor of 2 to 3, and reached this maximum 2 days before the onset of DNA replication. However, DMS-induced repair increased sevenfold in parallel with DNA replication. Repair patch sizes were smaller for DMS-induced damage reflecting patches of 7 nucleotides in quiescent lymphocytes compared to 20 nucleotides induced by UVL. The patch size increased during lymphocyte stimulation until one day prior to the peak of DNA replication when patch sizes of 45 and 35 nucleotides were produced in response to UVL- and DMS-induced damage, respectively. At the peak of DNA replication, the patch sizes were equal for both damaging agents at 34 nucleotides. In the second study, a small amount of repair replication was observed in undamaged quiescent and concanavalin A-stimulated bovine lymphocytes as well as in human T98G glioblastoma cells. Repair incorporation doubled in the presence of hydroxyurea. Thirdly, the enhanced repair replication induced by the poly (ADP-ribose) polymerase inhibitor, 3-aminobenzamide, (3-AB), could not be correlated either with an increased rate of repair in the presence of 3-AB or with the use of hydroxyurea in the repair protocol. Finally, treatment of unstimulated lymphocytes with hyperthermia was accompanied by decreased repair replication while the repair patches remained constant at 20 nucleotides.

  13. A 7-mer knowledge-based potential for detecting native protein structures from decoys

    DEFF Research Database (Denmark)

    Røgen, Peter

    for faster sampling methods. Background: The C-alpha atoms define a polygonal curve in 3-space which is smoothened by the method presented in [1] and is illustrated below. The geometry of a 7-mer is described by two numbers that describe how stretched and curved the smoothening of the 7-mer is. These two...... numbers are called length and distance excess, c.f. [2], and give one point in the length - distance excess - plane, LDE-plane. Method: Given a sequence of amino acids, we break it down to all its 7-mers and search a database of known 3d-structures for similar 7-mer sequences. For the query 7-mer we...... define an energy function in the LDE-plane. This energy is given by the 7-mer found and depends linearly on some design parameters. The energy function of the full query sequence, F, is then a sum over all 7-mers. For a protein P and a decoy D we ideally want F(D)-F(P)=constant.RMSD( D , P ), where 0...

  14. A paralogous decoy protects Phytophthora sojae apoplastic effector PsXEG1 from a host inhibitor.

    Science.gov (United States)

    Ma, Zhenchuan; Zhu, Lin; Song, Tianqiao; Wang, Yang; Zhang, Qi; Xia, Yeqiang; Qiu, Min; Lin, Yachun; Li, Haiyang; Kong, Liang; Fang, Yufeng; Ye, Wenwu; Wang, Yan; Dong, Suomeng; Zheng, Xiaobo; Tyler, Brett M; Wang, Yuanchao

    2017-02-17

    The extracellular space (apoplast) of plant tissue represents a critical battleground between plants and attacking microbes. Here we show that a pathogen-secreted apoplastic xyloglucan-specific endoglucanase, PsXEG1, is a focus of this struggle in the Phytophthora sojae -soybean interaction. We show that soybean produces an apoplastic glucanase inhibitor protein, GmGIP1, that binds to PsXEG1 to block its contribution to virulence. P. sojae , however, secretes a paralogous PsXEG1-like protein, PsXLP1, that has lost enzyme activity but binds to GmGIP1 more tightly than does PsXEG1, thus freeing PsXEG1 to support P. sojae infection. The gene pair encoding PsXEG1 and PsXLP1 is conserved in many Phytophthora species, and the P. parasitica orthologs PpXEG1 and PpXLP1 have similar functions. Thus, this apoplastic decoy strategy may be widely used in Phytophthora pathosystems. Copyright © 2017, American Association for the Advancement of Science.

  15. Poxvirus-encoded TNF decoy receptors inhibit the biological activity of transmembrane TNF.

    Science.gov (United States)

    Pontejo, Sergio M; Alejo, Ali; Alcami, Antonio

    2015-10-01

    Poxviruses encode up to four different soluble TNF receptors, named cytokine response modifier B (CrmB), CrmC, CrmD and CrmE. These proteins mimic the extracellular domain of the cellular TNF receptors to bind and inhibit the activity of TNF and, in some cases, other TNF superfamily ligands. Most of these ligands are released after the enzymic cleavage of a membrane precursor. However, transmembrane TNF (tmTNF) is not only a precursor of soluble TNF but also exerts specific pro-inflammatory and immunological activities. Here, we report that viral TNF receptors bound and inhibited tmTNF and describe some interesting differences in their activity against the soluble cytokine. Thus, CrmE, which does not inhibit mouse soluble TNF, could block murine tmTNF-induced cytotoxicity. We propose that this anti-tmTNF effect should be taken into consideration when assessing the role of viral TNF decoy receptors in the pathogenesis of poxvirus.

  16. Assessment of semiempirical enthalpy of formation in solution as an effective energy function to discriminate native-like structures in protein decoy sets.

    Science.gov (United States)

    Urquiza-Carvalho, Gabriel Aires; Fragoso, Wallace Duarte; Rocha, Gerd Bruno

    2016-08-05

    In this work, we tested the PM6, PM6-DH+, PM6-D3, and PM7 enthalpies of formation in aqueous solution as scoring functions across 33 decoy sets to discriminate native structures or good models in a decoy set. In each set these semiempirical quantum chemistry methods were compared according to enthalpic and geometric criteria. Enthalpically, we compared the methods according to how much lower was the enthalpy of each native, when compared with the mean enthalpy of its set. Geometrically, we compared the methods according to the fraction of native contacts (Q), which is a measure of geometric closeness between an arbitrary structure and the native. For each set and method, the Q of the best decoy was compared with the Q0 , which is the Q of the decoy closest to the native in the set. It was shown that the PM7 method is able to assign larger energy differences between the native structure and the decoys in a set, arguably because of a better description of dispersion interactions, however PM6-DH+ was slightly better than the rest at selecting geometrically good models in the absence of a native structure in the set. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Angular (Gothic) aortic arch leads to enhanced systolic wave reflection, central aortic stiffness, and increased left ventricular mass late after aortic coarctation repair: evaluation with magnetic resonance flow mapping.

    Science.gov (United States)

    Ou, Phalla; Celermajer, David S; Raisky, Olivier; Jolivet, Odile; Buyens, Fanny; Herment, Alain; Sidi, Daniel; Bonnet, Damien; Mousseaux, Elie

    2008-01-01

    We sought to investigate the mechanism whereby a particular deformity of the aortic arch, an angulated Gothic shape, might lead to hypertension late after anatomically successful repair of aortic coarctation. Fifty-five normotensive patients with anatomically successful repair of aortic coarctation and either a Gothic (angulated) or a Romanesque (smooth and rounded) arch were studied with magnetic resonance angiography and flow mapping in both the ascending and descending aortas. Systolic waveforms, central aortic stiffness, and pulse velocity were measured. We hypothesized that arch angulation would result in enhanced systolic wave reflection with loss of energy across the aortic arch, as well as increased central aortic stiffness. Twenty patients were found to have a Gothic, and 35 a Romanesque, arch. Patients with a Gothic arch showed markedly augmented systolic wave reflection (12 +/- 6 vs 5 +/- 0.3 mL, P Gothic arch (5.6 +/- 1.1 vs 4.1 +/- 1 m/s, P Gothic aortic arch is associated with increased systolic wave reflection, as well as increased central aortic stiffness and left ventricular mass index. These findings explain (at least in part) the association between this pattern of arch geometry and late hypertension at rest and on exercise in subjects after coarctation repair.

  18. Brain aneurysm repair

    Science.gov (United States)

    ... aneurysm repair; Dissecting aneurysm repair; Endovascular aneurysm repair - brain; Subarachnoid hemorrhage - aneurysm ... Your scalp, skull, and the coverings of the brain are opened. A metal clip is placed at ...

  19. DNA repair , cell repair and radiosensitivity

    International Nuclear Information System (INIS)

    Zhestyanikov, V.D.

    1983-01-01

    Data obtained in laboratory of radiation cytology and literature data testifying to a considerable role of DNA repair in cell sensitivity to radiation and chemical DNA-tropic agents have been considered. Data pointing to the probability of contribution of inducible repair of DNA into plant cells sensitivity to X-rays are obtained. Certain violations of DNA repair do not result in the increase of radiosensitivity. It is assumed that in the cases unknown mechanisms of DNA repair operate

  20. Human Milk Contains Novel Glycans That Are Potential Decoy Receptors for Neonatal Rotaviruses*

    Science.gov (United States)

    Yu, Ying; Lasanajak, Yi; Song, Xuezheng; Hu, Liya; Ramani, Sasirekha; Mickum, Megan L.; Ashline, David J.; Prasad, B. V. Venkataram; Estes, Mary K.; Reinhold, Vernon N.; Cummings, Richard D.; Smith, David F.

    2014-01-01

    Human milk contains a rich set of soluble, reducing glycans whose functions and bioactivities are not well understood. Because human milk glycans (HMGs) have been implicated as receptors for various pathogens, we explored the functional glycome of human milk using shotgun glycomics. The free glycans from pooled milk samples of donors with mixed Lewis and Secretor phenotypes were labeled with a fluorescent tag and separated via multidimensional HPLC to generate a tagged glycan library containing 247 HMG targets that were printed to generate the HMG shotgun glycan microarray (SGM). To investigate the potential role of HMGs as decoy receptors for rotavirus (RV), a leading cause of severe gastroenteritis in children, we interrogated the HMG SGM with recombinant forms of VP8* domains of the RV outer capsid spike protein VP4 from human neonatal strains N155(G10P[11]) and RV3(G3P[6]) and a bovine strain, B223(G10P[11]). Glycans that were bound by RV attachment proteins were selected for detailed structural analyses using metadata-assisted glycan sequencing, which compiles data on each glycan based on its binding by antibodies and lectins before and after exo- and endo-glycosidase digestion of the SGM, coupled with independent MSn analyses. These complementary structural approaches resulted in the identification of 32 glycans based on RV VP8* binding, many of which are novel HMGs, whose detailed structural assignments by MSn are described in a companion report. Although sialic acid has been thought to be important as a surface receptor for RVs, our studies indicated that sialic acid is not required for binding of glycans to individual VP8* domains. Remarkably, each VP8* recognized specific glycan determinants within a unique subset of related glycan structures where specificity differences arise from subtle differences in glycan structures. PMID:25048705

  1. An ImageJ-based algorithm for a semi-automated method for microscopic image enhancement and DNA repair foci counting

    International Nuclear Information System (INIS)

    Klokov, D.; Suppiah, R.

    2015-01-01

    Proper evaluation of the health risks of low-dose ionizing radiation exposure heavily relies on the ability to accurately measure very low levels of DNA damage in cells. One of the most sensitive methods for measuring DNA damage levels is the quantification of DNA repair foci that consist of macromolecular aggregates of DNA repair proteins, such as γH2AX and 53BP1, forming around individual DNA double-strand breaks. They can be quantified using immunofluorescence microscopy and are widely used as markers of DNA double-strand breaks. However this quantification, if performed manually, may be very tedious and prone to inter-individual bias. Low-dose radiation studies are especially sensitive to this potential bias due to a very low magnitude of the effects anticipated. Therefore, we designed and validated an algorithm for the semi-automated processing of microscopic images and quantification of DNA repair foci. The algorithm uses ImageJ, a freely available image analysis software that is customizable to individual cellular properties or experimental conditions. We validated the algorithm using immunolabeled 53BP1 and γH2AX in normal human fibroblast AG01522 cells under both normal and irradiated conditions. This method is easy to learn, can be used by nontrained personnel, and can help avoiding discrepancies in inter-laboratory comparison studies examining the effects of low-dose radiation. (author)

  2. Enrichment of G2/M cell cycle phase in human pluripotent stem cells enhances HDR-mediated gene repair with customizable endonucleases.

    Science.gov (United States)

    Yang, Diane; Scavuzzo, Marissa A; Chmielowiec, Jolanta; Sharp, Robert; Bajic, Aleksandar; Borowiak, Malgorzata

    2016-02-18

    Efficient gene editing is essential to fully utilize human pluripotent stem cells (hPSCs) in regenerative medicine. Custom endonuclease-based gene targeting involves two mechanisms of DNA repair: homology directed repair (HDR) and non-homologous end joining (NHEJ). HDR is the preferred mechanism for common applications such knock-in, knock-out or precise mutagenesis, but remains inefficient in hPSCs. Here, we demonstrate that synchronizing synchronizing hPSCs in G2/M with ABT phase increases on-target gene editing, defined as correct targeting cassette integration, 3 to 6 fold. We observed improved efficiency using ZFNs, TALENs, two CRISPR/Cas9, and CRISPR/Cas9 nickase to target five genes in three hPSC lines: three human embryonic stem cell lines, neural progenitors and diabetic iPSCs. neural progenitors and diabetic iPSCs. Reversible synchronization has no effect on pluripotency or differentiation. The increase in on-target gene editing is locus-independent and specific to the cell cycle phase as G2/M phase enriched cells show a 6-fold increase in targeting efficiency compared to cells in G1 phase. Concurrently inhibiting NHEJ with SCR7 does not increase HDR or improve gene targeting efficiency further, indicating that HR is the major DNA repair mechanism after G2/M phase arrest. The approach outlined here makes gene editing in hPSCs a more viable tool for disease modeling, regenerative medicine and cell-based therapies.

  3. An ImageJ-based algorithm for a semi-automated method for microscopic image enhancement and DNA repair foci counting

    Energy Technology Data Exchange (ETDEWEB)

    Klokov, D., E-mail: dmitry.klokov@cnl.ca [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada); Suppiah, R. [Queen' s Univ., Dept. of Biomedical and Molecular Sciences, Kingston, Ontario (Canada)

    2015-06-15

    Proper evaluation of the health risks of low-dose ionizing radiation exposure heavily relies on the ability to accurately measure very low levels of DNA damage in cells. One of the most sensitive methods for measuring DNA damage levels is the quantification of DNA repair foci that consist of macromolecular aggregates of DNA repair proteins, such as γH2AX and 53BP1, forming around individual DNA double-strand breaks. They can be quantified using immunofluorescence microscopy and are widely used as markers of DNA double-strand breaks. However this quantification, if performed manually, may be very tedious and prone to inter-individual bias. Low-dose radiation studies are especially sensitive to this potential bias due to a very low magnitude of the effects anticipated. Therefore, we designed and validated an algorithm for the semi-automated processing of microscopic images and quantification of DNA repair foci. The algorithm uses ImageJ, a freely available image analysis software that is customizable to individual cellular properties or experimental conditions. We validated the algorithm using immunolabeled 53BP1 and γH2AX in normal human fibroblast AG01522 cells under both normal and irradiated conditions. This method is easy to learn, can be used by nontrained personnel, and can help avoiding discrepancies in inter-laboratory comparison studies examining the effects of low-dose radiation. (author)

  4. Monitoring of West Nile virus, Usutu virus and Meaban virus in waterfowl used as decoys and wild raptors in southern Spain.

    Science.gov (United States)

    Jurado-Tarifa, E; Napp, S; Lecollinet, S; Arenas, A; Beck, C; Cerdà-Cuéllar, M; Fernández-Morente, M; García-Bocanegra, I

    2016-12-01

    In the last decade, the number of emerging flaviviruses described worldwide has increased considerably, with wild birds acting as the main reservoir hosts of these viruses. We carried out an epidemiological survey to determine the seroprevalence of antigenically related flaviviruses, particularly West Nile virus (WNV), Usutu virus (USUV) and Meaban virus (MBV), in waterfowl used as decoys and wild raptors in Andalusia (southern Spain), the region considered to have the highest risk of flaviviruses circulation in Spain. The overall flaviviruses seroprevalence according to bELISA was 13.0% in both in decoys (n=1052) and wild raptors (n=123). Specific antibodies against WNV, USUV and MBV were confirmed by micro virus neutralization tests in 12, 38 and 4 of the seropositive decoys, respectively. This is the first study on WNV and USUV infections in decoys and the first report of MBV infections in waterfowl and raptors. Moreover we report the first description of WNV infections in short-toed snake eagle (Circaetus gallicus) and Montagu's harrier (Circus pygargus). The seropositivity obtained indicates widespread but not homogeneous distribution of WNV and USUV in Andalusia. The results also confirm endemic circulation of WNV, USUV and MBV in both decoys and wild raptors in southern Spain. Our results highlight the need to implement surveillance and control programs not only for WNV but also for other related flaviviruses. Further research is needed to determine the eco-epidemiological role that waterfowl and wild raptors play in the transmission of emerging flaviviruses, especially in decoys, given their close interactions with humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Promoting peripheral myelin repair.

    Science.gov (United States)

    Zhou, Ye; Notterpek, Lucia

    2016-09-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Differentiating normal hyaline cartilage from post-surgical repair tissue using fast gradient echo imaging in delayed gadolinium-enhanced MRI (dGEMRIC) at 3 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Trattnig, Siegfried; Pinker, Katja; Welsch, Goetz H. [Medical University of Vienna, MR Center-High field MR, Department of Radiology, Vienna (Austria); Mamisch, Tallal C. [Inselspital Bern, Orthopedic Surgery Department, Bern (Switzerland); Domayer, Stephan [Medical University of Vienna, MR Center-High field MR, Department of Radiology, Vienna (Austria); Medical University of Vienna, Department of Orthopaedics, Vienna (Austria); Szomolanyi, Pavol [Medical University of Vienna, MR Center-High field MR, Department of Radiology, Vienna (Austria); Slovak Academy of Sciences, Department of Imaging Methods, Institute of Measurement Science, Bratislava (Slovakia); Marlovits, Stefan; Kutscha-Lissberg, Florian [Medical University of Vienna, Department of Traumatology, Center for Joints and Cartilage, Vienna (Austria)

    2008-06-15

    The purpose was to evaluate the relative glycosaminoglycan (GAG) content of repair tissue in patients after microfracturing (MFX) and matrix-associated autologous chondrocyte transplantation (MACT) of the knee joint with a dGEMRIC technique based on a newly developed short 3D-GRE sequence with two flip angle excitation pulses. Twenty patients treated with MFX or MACT (ten in each group) were enrolled. For comparability, patients from each group were matched by age (MFX: 37.1 {+-} 16.3 years; MACT: 37.4 {+-} 8.2 years) and postoperative interval (MFX: 33.0 {+-} 17.3 months; MACT: 32.0 {+-} 17.2 months). The {delta} relaxation rate ({delta}R1) for repair tissue and normal hyaline cartilage and the relative {delta}R1 were calculated, and mean values were compared between both groups using an analysis of variance. The mean {delta}R1 for MFX was 1.07 {+-} 0.34 versus 0.32 {+-} 0.20 at the intact control site, and for MACT, 1.90 {+-} 0.49 compared to 0.87 {+-} 0.44, which resulted in a relative {delta}R1 of 3.39 for MFX and 2.18 for MACT. The difference between the cartilage repair groups was statistically significant. The new dGEMRIC technique based on dual flip angle excitation pulses showed higher GAG content in patients after MACT compared to MFX at the same postoperative interval and allowed reducing the data acquisition time to 4 min. (orig.)

  7. The relationship of plasma decoy receptor 3 and coronary collateral circulation in patients with coronary artery disease.

    Science.gov (United States)

    Yan, Youyou; Song, Dandan; Liu, Lulu; Meng, Xiuping; Qi, Chao; Wang, Junnan

    2017-11-15

    Previously, decoy receptor 3 (DcR3) was found to be a potential angiogenetic factor, while the relationship of DcR3 with coronary collateral circulation formation has not been investigated. In this study, we aimed to investigate whether plasma decoy receptor 3 levels was associated with CCC formation and evaluate its predictive power for CCC status in patients with coronary artery disease. Among patients who underwent coronary angiography with coronary artery disease and had a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrope Cohen classification. Patients with grade 2 or 3 collateral degree were enrolled in good CCC group and patients with grade 0 or 1 collateral degree were enrolled in poor CCC group. Plasma DcR3 level was significantly higher in good CCC group (328.00±230.82 vs 194.84±130.63ng/l, p<0.01) and positively correlated with Rentrope grade (p<0.01). In addition, plasma DcR3 was also positively correlated with VEGF-A. Both ROC (receiver operating characteristic curve) and multinomial logistical regression analysis showed that plasma DcR3 displayed potent predictive power for CCC status. Higher plasma DcR3 level was related to better CCC formation and displayed potent predictive power for CCC status. Copyright © 2017. Published by Elsevier Inc.

  8. TRAM-Derived Decoy Peptides inhibits the inflammatory response in mouse mammary epithelial cells and a mastitis model in mice.

    Science.gov (United States)

    Hu, Xiaoyu; Tian, Yuan; Wang, Tiancheng; Zhang, Wenlong; Wang, Wei; Gao, Xuejiao; Qu, Shihui; Cao, Yongguo; Zhang, Naisheng

    2015-10-05

    It has been proved that TRAM-Derived Decoy peptides have anti-inflammatory properties. In this study, we synthesized a TRAM-Derived decoy peptide (TM6), belongs to TRAM TIR domain, of which sequence is "N"-RQIKIWFQNRRMKWK, KENFLRDTWCNFQFY-"C" and evaluated the effects of TM6 on lipopolysaccharide-induced mastitis in mice. In vivo, LPS-induced mice mastitis model was established by injection of LPS through the duct of mammary gland. TM6 was injected 1h before or after LPS treatment. In vitro, primary mouse mammary epithelial cells were used to investigate the effects of TM6 on LPS-induced inflammatory responses. The results showed that TM6 inhibited LPS-induced mammary gland histopathologic changes, MPO activity, and TNF-α, IL-1β and IL-6 production in mice. In vitro, TM6 significantly inhibited LPS-induced TNF-α and IL-6 production, as well as NF-κB and MAPKs activation. In conclusion, this study demonstrated that TM6 had protective effects on LPS-mastitis and may be a promising therapeutic reagent for mastitis treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. A PCR-Based Method to Construct Lentiviral Vector Expressing Double Tough Decoy for miRNA Inhibition.

    Directory of Open Access Journals (Sweden)

    Huiling Qiu

    Full Text Available DNA vector-encoded Tough Decoy (TuD miRNA inhibitor is attracting increased attention due to its high efficiency in miRNA suppression. The current methods used to construct TuD vectors are based on synthesizing long oligonucleotides (~90 mer, which have been costly and problematic because of mutations during synthesis. In this study, we report a PCR-based method for the generation of double Tough Decoy (dTuD vector in which only two sets of shorter oligonucleotides (< 60 mer were used. Different approaches were employed to test the inhibitory potency of dTuDs. We demonstrated that dTuD is the most efficient method in miRNA inhibition in vitro and in vivo. Using this method, a mini dTuD library against 88 human miRNAs was constructed and used for a high-throughput screening (HTS of AP-1 pathway-related miRNAs. Seven miRNAs (miR-18b-5p, -101-3p, -148b-3p, -130b-3p, -186-3p, -187-3p and -1324 were identified as candidates involved in AP-1 pathway regulation. This novel method allows for an accurate and cost-effective generation of dTuD miRNA inhibitor, providing a powerful tool for efficient miRNA suppression in vitro and in vivo.

  10. Free-space measurement-device-independent quantum-key-distribution protocol using decoy states with orbital angular momentum

    International Nuclear Information System (INIS)

    Wang Le; Zhao Sheng-Mei; Cheng Wei-Wen; Gong Long-Yan

    2015-01-01

    In this paper, we propose a measurement-device-independent quantum-key-distribution (MDI-QKD) protocol using orbital angular momentum (OAM) in free space links, named the OAM-MDI-QKD protocol. In the proposed protocol, the OAM states of photons, instead of polarization states, are used as the information carriers to avoid the reference frame alignment, the decoy-state is adopted to overcome the security loophole caused by the weak coherent pulse source, and the high efficient OAM-sorter is adopted as the measurement tool for Charlie to obtain the output OAM state. Here, Charlie may be an untrusted third party. The results show that the authorized users, Alice and Bob, could distill a secret key with Charlie’s successful measurements, and the key generation performance is slightly better than that of the polarization-based MDI-QKD protocol in the two-dimensional OAM cases. Simultaneously, Alice and Bob can reduce the number of flipping the bits in the secure key distillation. It is indicated that a higher key generation rate performance could be obtained by a high dimensional OAM-MDI-QKD protocol because of the unlimited degree of freedom on OAM states. Moreover, the results show that the key generation rate and the transmission distance will decrease as the growth of the strength of atmospheric turbulence (AT) and the link attenuation. In addition, the decoy states used in the proposed protocol can get a considerable good performance without the need for an ideal source. (paper)

  11. Enhanced radiosensitivity of cultured fibroblasts from ataxia telangiectasia heterozygotes manifested by defective colony-forming ability and reduced DNA repair replication after hypoxic γ-irradiation

    International Nuclear Information System (INIS)

    Paterson, M.C.; Anderson, A.K.; Smith, B.P.; Smith, P.J.

    1979-01-01

    We have measured the sensitivity to γ-ray inactivation of diploid skin fibroblasts cultured from 10 persons in four families with ataxia telangiectasia (AT). Persons heterozygous for AT, including parents of afflicted patients, are not as yet detectable by any specific clinical or laboratory marker but are believed to constitute a substantial portion of the middle-aged cancer population. In one AT family, fibroblast strains from both parents exhibited a colony-forming ability after hypoxic irradiation which was intermediate between that displayed by five control strains from normal children and that from the affected child. In the remaining three families, cultures from only one parent were available; one parental strain displayed an intermediate survival capacity as above, whereas the other two responded normally. The homozygous recessive strains from the five afflicted children in the four families were all equally hypersensitive to hypoxic γ-ray inactivation. The three presumed AT heterozygous strains that displayed intermediate rayiosensitivity also carried out γ-rad-induced DNA repair replication to an extent intermediate between those in normals and AT homozygotes. These findings suggest that a numerically significant, cancer-prone subpopulation of humans carrying one normal and one abnormal AT gene may also be moderately sensitive to lethal effects of hypoxic γ-rays due to a defect in the enzymatic repair of DNA

  12. Rapid road repair vehicle

    Science.gov (United States)

    Mara, Leo M.

    1998-01-01

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find an the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was was heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past.

  13. A STAT3-decoy oligonucleotide induces cell death in a human colorectal carcinoma cell line by blocking nuclear transfer of STAT3 and STAT3-bound NF-κB

    Directory of Open Access Journals (Sweden)

    Le Coquil Stéphanie

    2011-04-01

    Full Text Available Abstract Background The transcription factor STAT3 (signal transducer and activator of transcription 3 is frequently activated in tumor cells. Activated STAT3 forms homodimers, or heterodimers with other TFs such as NF-κB, which becomes activated. Cytoplasmic STAT3 dimers are activated by tyrosine phosphorylation; they interact with importins via a nuclear localization signal (NLS one of which is located within the DNA-binding domain formed by the dimer. In the nucleus, STAT3 regulates target gene expression by binding a consensus sequence within the promoter. STAT3-specific decoy oligonucleotides (STAT3-decoy ODN that contain this consensus sequence inhibit the transcriptional activity of STAT3, leading to cell death; however, their mechanism of action is unclear. Results The mechanism of action of a STAT3-decoy ODN was analyzed in the colon carcinoma cell line SW 480. These cells' dependence on activated STAT3 was verified by showing that cell death is induced by STAT3-specific siRNAs or Stattic. STAT3-decoy ODN was shown to bind activated STAT3 within the cytoplasm, and to prevent its translocation to the nucleus, as well as that of STAT3-associated NF-κB, but it did not prevent the nuclear transfer of STAT3 with mutations in its DNA-binding domain. The complex formed by STAT3 and the STAT3-decoy ODN did not associate with importin, while STAT3 alone was found to co-immunoprecipitate with importin. Leptomycin B and vanadate both trap STAT3 in the nucleus. They were found here to oppose the cytoplasmic trapping of STAT3 by the STAT3-decoy ODN. Control decoys consisting of either a mutated STAT3-decoy ODN or a NF-κB-specific decoy ODN had no effect on STAT3 nuclear translocation. Finally, blockage of STAT3 nuclear transfer correlated with the induction of SW 480 cell death. Conclusions The inhibition of STAT3 by a STAT3-decoy ODN, leading to cell death, involves the entrapment of activated STAT3 dimers in the cytoplasm. A mechanism is

  14. Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells

    International Nuclear Information System (INIS)

    Sanlioglu, Ahter D; Dirice, Ercument; Aydin, Cigdem; Erin, Nuray; Koksoy, Sadi; Sanlioglu, Salih

    2005-01-01

    Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells. Despite this promising feature, TRAIL resistance observed in cancer cells seriously challenged the use of TRAIL as a death ligand in gene therapy. The current dispute concerns whether or not TRAIL receptor expression pattern is the primary determinant of TRAIL sensitivity in cancer cells. This study investigates TRAIL receptor expression pattern and its connection to TRAIL resistance in breast cancer cells. In addition, a DcR2 siRNA approach and a complementary gene therapy modality involving IKK inhibition (AdIKKβKA) were also tested to verify if these approaches could sensitize MCF7 breast cancer cells to adenovirus delivery of TRAIL (Ad5hTRAIL). TRAIL sensitivity assays were conducted using Molecular Probe's Live/Dead Cellular Viability/Cytotoxicity Kit following the infection of breast cancer cells with Ad5hTRAIL. The molecular mechanism of TRAIL induced cell death under the setting of IKK inhibition was revealed by Annexin V binding. Novel quantitative Real Time RT-PCR and flow cytometry analysis were performed to disclose TRAIL receptor composition in breast cancer cells. MCF7 but not MDA-MB-231 breast cancer cells displayed strong resistance to adenovirus delivery of TRAIL. Only the combinatorial use of Ad5hTRAIL and AdIKKβKA infection sensitized MCF7 breast cancer cells to TRAIL induced cell death. Moreover, novel quantitative Real Time RT-PCR assays suggested that while the level of TRAIL Decoy Receptor-4 (TRAIL-R4) expression was the highest in MCF7 cells, it was the lowest TRAIL receptor expressed in MDA-MB-231 cells. In addition, conventional flow cytometry analysis demonstrated that TRAIL resistant MCF7 cells exhibited substantial levels of TRAIL-R4 expression but not TRAIL decoy receptor-3 (TRAIL-R3) on surface. On the contrary, TRAIL sensitive MDA-MB-231 cells displayed very low levels of surface TRAIL-R4

  15. Collision Repair Campaign

    Science.gov (United States)

    The Collision Repair Campaign targets meaningful risk reduction in the Collision Repair source category to reduce air toxic emissions in their communities. The Campaign also helps shops to work towards early compliance with the Auto Body Rule.

  16. Retinal detachment repair

    Science.gov (United States)

    ... medicines Problems breathing You may not recover full vision. ... detachments can be repaired. Failure to repair the retina always results in loss of vision to some degree. After surgery, the quality of ...

  17. Equipment for construction and repair of pipework

    International Nuclear Information System (INIS)

    Roehrich, H.

    1987-01-01

    More stringent requirements on the integrity of safety-related components in power plants with a view to ensuring the availability of these installations and to rationalizing in-service inspections and repairs have resulted in rapid enhancement of the inspection and repair methods used. Piping systems are increasingly being visually inspected, tested and possibly subjected to remote-control repair from the interior using remotely controlled inspection vehicles. This calls for machines with high levels of reliability which may be operated by means of remote control. Technical developments make it possible nowadays to perform operations that were largely out of the question a decade ago. (orig.) [de

  18. 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.

  19. CLUB-MARTINI: Selecting Favourable Interactions amongst Available Candidates, a Coarse-Grained Simulation Approach to Scoring Docking Decoys.

    Directory of Open Access Journals (Sweden)

    Qingzhen Hou

    Full Text Available Large-scale identification of native binding orientations is crucial for understanding the role of protein-protein interactions in their biological context. Measuring binding free energy is the method of choice to estimate binding strength and reveal the relevance of particular conformations in which proteins interact. In a recent study, we successfully applied coarse-grained molecular dynamics simulations to measure binding free energy for two protein complexes with similar accuracy to full-atomistic simulation, but 500-fold less time consuming. Here, we investigate the efficacy of this approach as a scoring method to identify stable binding conformations from thousands of docking decoys produced by protein docking programs. To test our method, we first applied it to calculate binding free energies of all protein conformations in a CAPRI (Critical Assessment of PRedicted Interactions benchmark dataset, which included over 19000 protein docking solutions for 15 benchmark targets. Based on the binding free energies, we ranked all docking solutions to select the near-native binding modes under the assumption that the native-solutions have lowest binding free energies. In our top 100 ranked structures, for the 'easy' targets that have many near-native conformations, we obtain a strong enrichment of acceptable or better quality structures; for the 'hard' targets without near-native decoys, our method is still able to retain structures which have native binding contacts. Moreover, in our top 10 selections, CLUB-MARTINI shows a comparable performance when compared with other state-of-the-art docking scoring functions. As a proof of concept, CLUB-MARTINI performs remarkably well for many targets and is able to pinpoint near-native binding modes in the top selections. To the best of our knowledge, this is the first time interaction free energy calculated from MD simulations have been used to rank docking solutions at a large scale.

  20. Enhancement of mechanical strength of TiO2/high-density polyethylene composites for bone repair with silane-coupling treatment

    International Nuclear Information System (INIS)

    Hashimoto, Masami; Takadama, Hiroaki; Mizuno, Mineo; Kokubo, Tadashi

    2006-01-01

    Mechanical properties of composites made up of high-density polyethylene (HDPE) and silanated TiO 2 particles for use as a bone-repairing material were investigated in comparison with those of the composites of HDPE with unsilanized TiO 2 particles. The interfacial morphology and interaction between silanated TiO 2 and HDPE were analyzed by means of Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). The absorption in spectral bands related to the carboxyl bond in the silane-coupling agent, the vinyl group in the HDPE, and the formation of the ether bond was studied in order to assess the influence of the silane-coupling agent. The SEM micrograph showed that the 'bridging effect' between HDPE and TiO 2 was brought about by the silane-coupling agent. The use of the silane-coupling agent and the increase of the hot-pressing pressure for shaping the composites facilitated the penetration of polymer into cavities between individual TiO 2 particles, which increased the density of the composite. Therefore, mechanical properties such as bending yield strength and Young's modulus increased from 49 MPa and 7.5 GPa to 65 MPa and 10 GPa, respectively, after the silane-coupling treatment and increase in the hot-pressing pressure

  1. Adaptive response to ionizing radiation in normal human skin fibroblasts. Enhancement of DNA repair rate and modulation of gene expression. Reponse adaptative au rayonnement ionisant des fibroblastes de peau humaine. Augmentation de la vitesse de reparation de l'ADN et variation de l'expression des genes

    Energy Technology Data Exchange (ETDEWEB)

    Toledo, S.M. de; Mitchel, R.E.J. (Atomic Energy of Canada Ltd., Chalk River, ON (Canada). Chalk River Nuclear Labs.); Azzam, E. (Atomic Energy of Canada Ltd., Chalk River, ON (Canada). Chalk River Nuclear Labs. Ottawa Univ., ON (Canada). Dept. of Biology); Raaphorst, G.P. (Ottawa Univ., ON (Canada). Dept. of Biology)

    Low doses and dose rates of ionizing radiation enhance the rate of DNA repair in human fibroblasts and protect the cells against radiation-induced micronucleus formation. Chronic exposures reduce the mRNA levels of the genes topoisomerase II and FACC-1 (Fanconi's anemia, group C). (authors). 11 refs., 1 tab., 2 figs.

  2. Systems Maintenance Automated Repair Tasks (SMART)

    Science.gov (United States)

    Schuh, Joseph; Mitchell, Brent; Locklear, Louis; Belson, Martin A.; Al-Shihabi, Mary Jo Y.; King, Nadean; Norena, Elkin; Hardin, Derek

    2010-01-01

    SMART is a uniform automated discrepancy analysis and repair-authoring platform that improves technical accuracy and timely delivery of repair procedures for a given discrepancy (see figure a). SMART will minimize data errors, create uniform repair processes, and enhance the existing knowledge base of engineering repair processes. This innovation is the first tool developed that links the hardware specification requirements with the actual repair methods, sequences, and required equipment. SMART is flexibly designed to be useable by multiple engineering groups requiring decision analysis, and by any work authorization and disposition platform (see figure b). The organizational logic creates the link between specification requirements of the hardware, and specific procedures required to repair discrepancies. The first segment in the SMART process uses a decision analysis tree to define all the permutations between component/ subcomponent/discrepancy/repair on the hardware. The second segment uses a repair matrix to define what the steps and sequences are for any repair defined in the decision tree. This segment also allows for the selection of specific steps from multivariable steps. SMART will also be able to interface with outside databases and to store information from them to be inserted into the repair-procedure document. Some of the steps will be identified as optional, and would only be used based on the location and the current configuration of the hardware. The output from this analysis would be sent to a work authoring system in the form of a predefined sequence of steps containing required actions, tools, parts, materials, certifications, and specific requirements controlling quality, functional requirements, and limitations.

  3. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  4. 'Regular' and 'emergency' repair

    International Nuclear Information System (INIS)

    Luchnik, N.V.

    1975-01-01

    Experiments on the combined action of radiation and a DNA inhibitor using Crepis roots and on split-dose irradiation of human lymphocytes lead to the conclusion that there are two types of repair. The 'regular' repair takes place twice in each mitotic cycle and ensures the maintenance of genetic stability. The 'emergency' repair is induced at all stages of the mitotic cycle by high levels of injury. (author)

  5. Repair kinetics in tissues

    International Nuclear Information System (INIS)

    Thames, H.D.

    1989-01-01

    Monoexponential repair kinetics is based on the assumption of a single, dose-independent rate of repair of sublethal injury in the target cells for tissue injury after exposure to ionizing radiation. Descriptions of the available data based on this assumption have proved fairly successful for both acutely responding (skin, lip mucosa, gut) and late-responding (lung, spinal cord) normal tissues. There are indications of biphasic exponential repair in both categories, however. Unfortunately, the data usually lack sufficient resolution to permit unambiguous determination of the repair rates. There are also indications that repair kinetics may depend on the size of the dose. The data are conflicting on this account, however, with suggestions of both faster and slower repair after larger doses. Indeed, experiments that have been explicitly designed to test this hypothesis show either no effect (gut, spinal cord), faster repair after higher doses (lung, kidney), or slower repair after higher doses (skin). Monoexponential repair appears to be a fairly accurate description that provides an approximation to a more complicated picture, the elucidation of whose details will, however, require very careful and extensive experimental study. (author). 30 refs.; 1 fig

  6. Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects

    Directory of Open Access Journals (Sweden)

    Fu YC

    2015-12-01

    Full Text Available Yin-Chih Fu,1–4 Yan-Hsiung Wang,1,5 Chung-Hwan Chen,1,3,4 Chih-Kuang Wang,1,6 Gwo-Jaw Wang,1,3,4 Mei-Ling Ho1,3,7,8 1Orthopaedic Research Center, 2Graduate Institute of Medicine, 3Department of Orthopaedics, 4Department of Orthopaedics, College of Medicine, 5School of Dentistry, College of Dental Medicine, 6Department of Medicinal and Applied Chemistry, 7Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, TaiwanAbstract: Most allogenic bone graft substitutes have only osteoconductive properties. Developing new strategies to improve the osteoinductive activity of bone graft substitutes is both critical and practical for clinical application. Previously, we developed novel simvastatin-encapsulating poly(lactic-co-glycolic acid microspheres (SIM/PLGA that slowly release simvastatin and enhance fracture healing. In this study, we combined SIM/PLGA with a rapidly absorbable calcium sulfate (CS bone substitute and studied the effect on bone healing in critical-sized calvarial bone defects in a rat model. The cytotoxicity and cytocompatibility of this combination was tested in vitro using lactate dehydrogenase leakage and a cell attachment assay, respectively. Combination treatment with SIM/PLGA and the CS bone substitute had no cytotoxic effect on bone marrow stem cells. Compared with the control, cell adhesion was substantially enhanced following combination treatment with SIM/PLGA and the CS bone substitute. In vivo, implantation of the combination bone substitute promoted healing of critical-sized calvarial bone defects in rats; furthermore, production of bone morphogenetic protein-2 and neovascularization were enhanced in the area of the defect. In summary, the combination of SIM/PLGA and a CS bone substitute has osteoconductive and osteoinductive properties, indicating that it could be used for regeneration

  7. Free-space measurement-device-independent quantum-key-distribution protocol using decoy states with orbital angular momentum

    Science.gov (United States)

    Wang, Le; Zhao, Sheng-Mei; Gong, Long-Yan; Cheng, Wei-Wen

    2015-12-01

    In this paper, we propose a measurement-device-independent quantum-key-distribution (MDI-QKD) protocol using orbital angular momentum (OAM) in free space links, named the OAM-MDI-QKD protocol. In the proposed protocol, the OAM states of photons, instead of polarization states, are used as the information carriers to avoid the reference frame alignment, the decoy-state is adopted to overcome the security loophole caused by the weak coherent pulse source, and the high efficient OAM-sorter is adopted as the measurement tool for Charlie to obtain the output OAM state. Here, Charlie may be an untrusted third party. The results show that the authorized users, Alice and Bob, could distill a secret key with Charlie’s successful measurements, and the key generation performance is slightly better than that of the polarization-based MDI-QKD protocol in the two-dimensional OAM cases. Simultaneously, Alice and Bob can reduce the number of flipping the bits in the secure key distillation. It is indicated that a higher key generation rate performance could be obtained by a high dimensional OAM-MDI-QKD protocol because of the unlimited degree of freedom on OAM states. Moreover, the results show that the key generation rate and the transmission distance will decrease as the growth of the strength of atmospheric turbulence (AT) and the link attenuation. In addition, the decoy states used in the proposed protocol can get a considerable good performance without the need for an ideal source. Project supported by the National Natural Science Foundation of China (Grant Nos. 61271238 and 61475075), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20123223110003), the Natural Science Research Foundation for Universities of Jiangsu Province of China (Grant No. 11KJA510002), the Open Research Fund of Key Laboratory of Broadband Wireless Communication and Sensor Network Technology, Ministry of Education, China (Grant No. NYKL2015011), and the

  8. Nano-biphasic calcium phosphate/polyvinyl alcohol composites with enhanced bioactivity for bone repair via low-temperature three-dimensional printing and loading with platelet-rich fibrin.

    Science.gov (United States)

    Song, Yue; Lin, Kaifeng; He, Shu; Wang, Chunmei; Zhang, Shuaishuai; Li, Donglin; Wang, Jimeng; Cao, Tianqing; Bi, Long; Pei, Guoxian

    2018-01-01

    As a newly emerging three-dimensional (3D) printing technology, low-temperature robocasting can be used to fabricate geometrically complex ceramic scaffolds at low temperatures. Here, we aimed to fabricate 3D printed ceramic scaffolds composed of nano-biphasic calcium phosphate (BCP), polyvinyl alcohol (PVA), and platelet-rich fibrin (PRF) at a low temperature without the addition of toxic chemicals. Corresponding nonprinted scaffolds were prepared using a freeze-drying method. Compared with the nonprinted scaffolds, the printed scaffolds had specific shapes and well-connected internal structures. The incorporation of PRF enabled both the sustained release of bioactive factors from the scaffolds and improved biocompatibility and biological activity toward bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. Additionally, the printed BCP/PVA/PRF scaffolds promoted significantly better BMSC adhesion, proliferation, and osteogenic differentiation in vitro than the printed BCP/PVA scaffolds. In vivo, the printed BCP/PVA/PRF scaffolds induced a greater extent of appropriate bone formation than the printed BCP/PVA scaffolds and nonprinted scaffolds in a critical-size segmental bone defect model in rabbits. These experiments indicate that low-temperature robocasting could potentially be used to fabricate 3D printed BCP/PVA/PRF scaffolds with desired shapes and internal structures and incorporated bioactive factors to enhance the repair of segmental bone defects.

  9. Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells.

    Science.gov (United States)

    Choi, Young Eun; Battelli, Chiara; Watson, Jacqueline; Liu, Joyce; Curtis, Jennifer; Morse, Alexander N; Matulonis, Ursula A; Chowdhury, Dipanjan; Konstantinopoulos, Panagiotis A

    2014-05-15

    The promise of PARP-inhibitors(PARPis) in the management of epithelial ovarian cancer(EOC) is tempered by the fact that approximately 50% of patients with homologous recombination (HR)-proficient tumors do not respond well to these agents. Combination of PARPis with agents that inhibit HR may represent an effective strategy to enhance their activity in HR-proficient tumors. Using a bioinformatics approach, we identified that heat shock protein 90 inhibitors(HSP90i) may suppress HR and thus revert HR-proficient to HR-deficient tumors. Analysis of publicly available gene expression data showed that exposure of HR-proficient breast cancer cell lines to HSP90i 17-AAG(17-allylamino-17-demethoxygeldanamycin) downregulated HR, ATM and Fanconi Anemia pathways. In HR-proficient EOC cells, 17-AAG suppressed HR as assessed using the RAD51 foci formation assay and this was further confirmed using the Direct Repeat-GFP reporter assay. Furthermore, 17-AAG downregulated BRCA1 and/or RAD51 protein levels, and induced significantly more γH2AX activation in combination with olaparib compared to olaparib alone. Finally, sublethal concentrations of 17-AAG sensitized HR-proficient EOC lines to olaparib and carboplatin but did not affect sensitivity of the HR-deficient OVCAR8 line arguing that the 17-AAG mediated sensitization is dependent on suppression of HR. These results provide a preclinical rationale for using a combination of olaparib/17-AAG in HR-proficient EOC.

  10. Enhanced granulocyte growth on peritoneal cell-coated membranes following irradiation: a dual effect of humoral stimulation and repair of x ray-induced damage to the microenvironment

    International Nuclear Information System (INIS)

    Turner, A.R.; Pfrimmer, W.J.; Boggs, D.R.; Carpe, A.I.

    1978-01-01

    An experimental model of the hematopoietic microenvironment was created by allowing a peritoneal cell coating to form on a disk of cellulose acetate placed in the peritoneal cavity of mice. An effective microenvironment capable of supporting colony growth, primarily granulocytic, was established if the cellulose acetate disk was in the peritoneum for 3 to 5 days. Its effectiveness was hampered by transferring it to another mouse or by exposure to toxic agents such as a propylene glycol-ethanol mixture or irradiation. An exponential dose-related decrease in colony formation was seen with increasing doses or irradiation of the microenvironment before colonization. After a low dose of irradiation, recovery of colony support capacity occurred over a 6-day period. Enhancement of colony growth was seen when cell injection was delayed for 2 to 3 days after irradiation. The effects of irradiation on the cellular stroma were separated from the systemic changes in the host by transferring an established hematopoietic microenvironment to a secondary host. It was shown that there are two distinct effects of irradiation on granulocytic colony growth; one was a short-lived period, 2 to 3 days of stimulation, presumably humoral, and the other was dose-dependent reversible microenvironment damage

  11. Snowmobile Repair. Teacher Edition.

    Science.gov (United States)

    Hennessy, Stephen S.; Conrad, Rex

    This teacher's guide contains 14 units on snowmobile repair: (1) introduction to snowmobile repair; (2) skis, front suspension, and steering; (3) drive clutch; (4) drive belts; (5) driven clutch; (6) chain drives; (7) jackshafts and axles; (8) rear suspension; (9) tracks; (10) shock absorbers; (11) brakes; (12) engines; (13) ignition and…

  12. DNA repair genes

    International Nuclear Information System (INIS)

    Morimyo, Mitsuoki

    1995-01-01

    Fission yeast S. pombe is assumed to be a good model for cloning of human DNA repair genes, because human gene is normally expressed in S. pombe and has a very similar protein sequence to yeast protein. We have tried to elucidate the DNA repair mechanisms of S. pombe as a model system for those of mammals. (J.P.N.)

  13. Cell sensitivity to irradiation and DNA repair processes

    International Nuclear Information System (INIS)

    Kozubek, S.; Krasavin, E.A.

    1984-01-01

    A new model of oxygen effect realisation is proposed for E.coli cells. The model explains differencies in oxygen enhancement ratio (OER) between wild type cells and repair deficient mutants. These differencies are logically linked to corresponding defects in repair systems. A quantitative analysis has been performed. The dependence of OER and cell sensitivity on the properties of cultivation medium is considered, too. Decreasing OER and increasing sensitivity in poor conditions are explained as the consequence of the shift of repair capacity from slow to fast repair system

  14. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  15. How to implement decoy-state quantum key distribution for a satellite uplink with 50-dB channel loss

    International Nuclear Information System (INIS)

    Meyer-Scott, Evan; Yan, Zhizhong; MacDonald, Allison; Bourgoin, Jean-Philippe; Huebel, Hannes; Jennewein, Thomas

    2011-01-01

    Quantum key distribution (QKD) takes advantage of fundamental properties of quantum physics to allow two distant parties to share a secret key; however, QKD is hampered by a distance limitation of a few hundred kilometers on Earth. The most immediate solution for global coverage is to use a satellite, which can receive separate QKD transmissions from two or more ground stations and act as a trusted node to link these ground stations. In this article we report on a system capable of performing QKD in the high loss regime expected in an uplink to a satellite using weak coherent pulses and decoy states. Such a scenario profits from the simplicity of its receiver payload, but has so far been considered to be infeasible due to very high transmission losses (40-50 dB). The high loss is overcome by implementing an innovative photon source and advanced timing analysis. Our system handles up to 57 dB photon loss in the infinite key limit, confirming the viability of the satellite uplink scenario. We emphasize that while this system was designed with a satellite uplink in mind, it could just as easily overcome high losses on any free space QKD link.

  16. How to implement decoy-state quantum key distribution for a satellite uplink with 50-dB channel loss

    Science.gov (United States)

    Meyer-Scott, Evan; Yan, Zhizhong; MacDonald, Allison; Bourgoin, Jean-Philippe; Hübel, Hannes; Jennewein, Thomas

    2011-12-01

    Quantum key distribution (QKD) takes advantage of fundamental properties of quantum physics to allow two distant parties to share a secret key; however, QKD is hampered by a distance limitation of a few hundred kilometers on Earth. The most immediate solution for global coverage is to use a satellite, which can receive separate QKD transmissions from two or more ground stations and act as a trusted node to link these ground stations. In this article we report on a system capable of performing QKD in the high loss regime expected in an uplink to a satellite using weak coherent pulses and decoy states. Such a scenario profits from the simplicity of its receiver payload, but has so far been considered to be infeasible due to very high transmission losses (40-50 dB). The high loss is overcome by implementing an innovative photon source and advanced timing analysis. Our system handles up to 57 dB photon loss in the infinite key limit, confirming the viability of the satellite uplink scenario. We emphasize that while this system was designed with a satellite uplink in mind, it could just as easily overcome high losses on any free space QKD link.

  17. Novel VEGF decoy receptor fusion protein conbercept targeting multiple VEGF isoforms provide remarkable anti-angiogenesis effect in vivo.

    Directory of Open Access Journals (Sweden)

    Qin Wang

    Full Text Available VEGF family factors are known to be the principal stimulators of abnormal angiogenesis, which play a fundamental role in tumor and various ocular diseases. Inhibition of VEGF is widely applied in antiangiogenic therapy. Conbercept is a novel decoy receptor protein constructed by fusing VEGF receptor 1 and VEGF receptor 2 extracellular domains with the Fc region of human immunoglobulin. In this study, we systematically evaluated the binding affinity of conbercept with VEGF isoforms and PlGF by using anti-VEGF antibody (Avastin as reference. BIACORE and ELISA assay results indicated that conbercept could bind different VEGF-A isoforms with higher affinity than reference. Furthermore, conbercept could also bind VEGF-B and PlGF, whereas Avastin showed no binding. Oxygen-induced retinopathy model showed that conbercept could inhibit the formation of neovasularizations. In tumor-bearing nude mice, conbercept could also suppress tumor growth very effectively in vivo. Overall, our study have demonstrated that conbercept could bind with high affinity to multiple VEGF isoforms and consequently provide remarkable anti-angiogenic effect, suggesting the possibility to treat angiogenesis-related diseases such as cancer and wet AMD etc.

  18. Conserved Fever Pathways across Vertebrates: A Herpesvirus Expressed Decoy TNF-α Receptor Delays Behavioral Fever in Fish.

    Science.gov (United States)

    Rakus, Krzysztof; Ronsmans, Maygane; Forlenza, Maria; Boutier, Maxime; Piazzon, M Carla; Jazowiecka-Rakus, Joanna; Gatherer, Derek; Athanasiadis, Alekos; Farnir, Frédéric; Davison, Andrew J; Boudinot, Pierre; Michiels, Thomas; Wiegertjes, Geert F; Vanderplasschen, Alain

    2017-02-08

    Both endotherms and ectotherms (e.g., fish) increase their body temperature to limit pathogen infection. Ectotherms do so by moving to warmer places, hence the term "behavioral fever." We studied the manifestation of behavioral fever in the common carp infected by cyprinid herpesvirus 3, a native carp pathogen. Carp maintained at 24°C died from the infection, whereas those housed in multi-chamber tanks encompassing a 24°C-32°C gradient migrated transiently to the warmest compartment and survived as a consequence. Behavioral fever manifested only at advanced stages of infection. Consistent with this, expression of CyHV-3 ORF12, encoding a soluble decoy receptor for TNF-α, delayed the manifestation of behavioral fever and promoted CyHV-3 replication in the context of a temperature gradient. Injection of anti-TNF-α neutralizing antibodies suppressed behavioral fever, and decreased fish survival in response to infection. This study provides a unique example of how viruses have evolved to alter host behavior to increase fitness. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Optimizing pressurized contact area in rotator cuff repair: the diamondback repair.

    Science.gov (United States)

    Burkhart, Stephen S; Denard, Patrick J; Obopilwe, Elifho; Mazzocca, Augustus D

    2012-02-01

    The purpose of this study was to compare tendon-bone footprint contact area over time under physiologic loads for 4 different rotator cuff repair techniques: single row (SR), triangle double row (DR), chain-link double row (CL), and diamondback double row (DBK). A supraspinatus tear was created in 28 human cadavers. Tears were fixed with 1 of 4 constructs: SR, DR, CL, or DBK. Immediate post-repair measurements of pressurized contact area were taken in neutral rotation and 0° of abduction. After a static tensile load, pressurized contact area was observed over a 160-minute period after repair. Cyclic loading was then performed. The DBK repair had the highest pressurized contact area initially, as well as the highest pressurized contact area and lowest percentage decrease in pressurized contact area after 160 minutes of testing. The DBK repair had significantly larger initial pressurized contact than CL (P = .003) and SR (P = .004) but not DR (P = .06). The DBK technique was the only technique that produced a pressurized contact area that exceeded the native footprint both at initial repair (P = .01) and after 160 minutes of testing (P = .01). DBK had a significantly larger mean pressurized contact area than all the repairs after 160 minutes of testing (P = .01). DBK had a significantly larger post-cyclic loading pressurized contact area than CL (P = .01) and SR (P = .004) but not DR (P = .07). This study showed that a diamondback repair (a modification of the transosseous repair) can significantly increase the rotator cuff pressurized contact area in comparison with other standard rotator cuff repair constructs when there is sufficient tendon mobility to perform a double-row repair without excessive tension on the repair site. The persistent pressurized contact area of a DBK repair may be desirable to enhance healing potential when there is sufficient tendon mobility to perform a double-row repair, particularly for large or massive rotator cuff tears where it is

  20. SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response

    DEFF Research Database (Denmark)

    Mund, Andreas; Schubert, Tobias; Staege, Hannah

    2012-01-01

    -dependent manner. Moreover, SPOC1 localizes at endogenous repair foci, including OPT domains and accumulates at large DSB repair foci characteristic for delayed repair at heterochromatic sites. SPOC1 depletion enhances the kinetics of ionizing radiation-induced foci (IRIF) formation after γ-irradiation (γ-IR), non...

  1. Repairing fuel for reinsertion

    International Nuclear Information System (INIS)

    Krukshenk, A.

    1986-01-01

    Eqiupment for nuclear reactor fuel assembly repairing produced by Westinghouse and Brawn Bovery companies is described. Repair of failed fuel assemblies replacement of defect fuel elements gives a noticeable economical effect. Thus if the cost of a new fuel assembly is 450-500 thousand dollars, the replacement of one fuel element in it costs approximately 40-60 thousand dollars. In simple cases repairing includes either removal of failed fuel elements from a fuel assembly and its reinsertion with the rest of fuel elements into the reactor core (reactor refueling), or replacement of unfailed fuel elements from one fuel assembly to a new one (fuel assembly overhaul and reconditioning)

  2. Gadolinium-enhanced cardiac MR exams of human subjects are associated with significant increases in the DNA repair marker 53BP1, but not the damage marker γH2AX.

    Directory of Open Access Journals (Sweden)

    Jennifer S McDonald

    Full Text Available Magnetic resonance imaging is considered low risk, yet recent studies have raised a concern of potential damage to DNA in peripheral blood leukocytes. This prospective Institutional Review Board-approved study examined potential double-strand DNA damage by analyzing changes in the DNA damage and repair markers γH2AX and 53BP1 in patients who underwent a 1.5 T gadolinium-enhanced cardiac magnetic resonance (MR exam. Sixty patients were enrolled (median age 55 years, 39 males. Patients with history of malignancy or who were receiving chemotherapy, radiation therapy, or steroids were excluded. MR sequence data were recorded and blood samples obtained immediately before and after MR exposure. An automated immunofluorescence assay quantified γH2AX or 53BP1 foci number in isolated peripheral blood mononuclear cells. Changes in foci number were analyzed using the Wilcoxon signed-rank test. Clinical and MR procedural characteristics were compared between patients who had a >10% increase in γH2AX or 53BP1 foci numbers and patients who did not. The number of γH2AX foci did not significantly change following cardiac MR (median foci per cell pre-MR = 0.11, post-MR = 0.11, p = .90, but the number of 53BP1 foci significantly increased following MR (median foci per cell pre-MR = 0.46, post-MR = 0.54, p = .0140. Clinical and MR characteristics did not differ significantly between patients who had at least a 10% increase in foci per cell and those who did not. We conclude that MR exposure leads to a small (median 25% increase in 53BP1 foci, however the clinical relevance of this increase is unknown and may be attributable to normal variation instead of MR exposure.

  3. DNA Repair Systems

    Indian Academy of Sciences (India)

    DNA molecule which makes it ideal for storage and propagation of genetic information. ... of these errors are broadly referred to as DNA repair. DNA can ... changes occur in the human genome per day. ..... nails, frequent physical and mental.

  4. Brain aneurysm repair - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000123.htm Brain aneurysm repair - discharge To use the sharing features ... this page, please enable JavaScript. You had a brain aneurysm . An aneurysm is a weak area in ...

  5. Ventral hernia repair

    Science.gov (United States)

    ... incarcerated) in the hernia and become impossible to push back in. This is usually painful. The blood supply ... you are lying down or that you cannot push back in. Risks The risks of ventral hernia repair ...

  6. Omphalocele repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100033.htm Omphalocele repair - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Omphalocele is an abdominal wall defect at the base ...

  7. Celebrating DNA's Repair Crew.

    Science.gov (United States)

    Kunkel, Thomas A

    2015-12-03

    This year, the Nobel Prize in Chemistry has been awarded to Tomas Lindahl, Aziz Sancar, and Paul Modrich for their seminal studies of the mechanisms by which cells from bacteria to man repair DNA damage that is generated by normal cellular metabolism and stress from the environment. These studies beautifully illustrate the remarkable power of DNA repair to influence life from evolution through disease susceptibility. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Are Toll-Like Receptors and Decoy Receptors Involved in the Immunopathogenesis of Systemic Lupus Erythematosus and Lupus-Like Syndromes?

    Directory of Open Access Journals (Sweden)

    Giuliana Guggino

    2012-01-01

    Full Text Available In this paper we focus our attention on the role of two families of receptors, Toll-like receptors (TLR and decoy receptors (DcR involved in the generation of systemic lupus erythematosus (SLE and lupus-like syndromes in human and mouse models. To date, these molecules were described in several autoimmune disorders such as rheumatoid arthritis, antiphospholipids syndrome, bowel inflammation, and SLE. Here, we summarize the findings of recent investigations on TLR and DcR and their role in the immunopathogenesis of the SLE.

  9. MAZ-binding G4-decoy with locked nucleic acid and twisted intercalating nucleic acid modifications suppresses KRAS in pancreatic cancer cells and delays tumor growth in mice

    DEFF Research Database (Denmark)

    Cogoi, Susanna; Zorzet, Sonia; Rapozzi, Valentina

    2013-01-01

    and stability, two polycyclic aromatic hydrocarbon units (TINA or AMANY) were inserted internally, to cap the quadruplex. The most active G4-decoy (2998), which had two para-TINAs, strongly suppressed KRAS expression in Panc-1 cells. It also repressed their metabolic activity (IC50 = 520 nM), and it inhibited...... cell growth and colony formation by activating apoptosis. We finally injected 2998 and control oligonucleotides 5153, 5154 (2 nmol/mouse) intratumorally in SCID mice bearing a Panc-1 xenograft. After three treatments, 2998 reduced tumor xenograft growth by 64% compared with control and increased...

  10. Predictable repair of provisional restorations.

    Science.gov (United States)

    Hammond, Barry D; Cooper, Jeril R; Lazarchik, David A

    2009-01-01

    The importance of provisional restorations is often downplayed, as they are thought of by some as only "temporaries." As a result, a less-than-ideal provisional is sometimes fabricated, in part because of the additional chair time required to make provisional modifications when using traditional techniques. Additionally, in many dental practices, these provisional restorations are often fabricated by auxillary personnel who may not be as well trained in the fabrication process. Because provisionals play an important role in achieving the desired final functional and esthetic result, a high-quality provisional restoration is essential to fabricating a successful definitive restoration. This article describes a method for efficiently and predictably repairing both methacrylate and bis-acryl provisional restorations using flowable composite resin. By use of this relatively simple technique, provisional restorations can now be modified or repaired in a timely and productive manner to yield an exceptional result. Successful execution of esthetic and restorative dentistry requires attention to detail in every aspect of the case. Fabrication of high-quality provisional restorations can, at times, be challenging and time consuming. The techniques for optimizing resin provisional restorations as described in this paper are pragmatic and will enhance the delivery of dental treatment.

  11. Radiobiological significance of DNA repair

    International Nuclear Information System (INIS)

    Kuzin, A.M.

    1978-01-01

    A short outline is given on the history of the problem relating to the repair of radiation injuries, specifically its molecular mechanisms. The most urgent problems which currently confront the researchers are noted. This is a further study on the role of DNA repair in post-radiation recovery, search for ways to activate and suppress DNA repair, investigations into the activity balance of various repair enzymes as well as the problem of errors in the structure of repairing DNA. An important role is attached to the investigations of DNA repair in solving a number of practical problems

  12. Recombinational repair: workshop summary

    International Nuclear Information System (INIS)

    Howard-Flanders, P.

    1983-01-01

    Recombinational repair may or may not be synonymous with postreplication repair. Considerable progress has been made in the study of the relevant enzymes, particularly those from bacteria. In this workshop we focus on the recombination enzyme RecA protein. What structural changes take place in the protein and in DNA during repair. How does homologous pairing take place. How is ATP hydrolysis coupled to the stand exchange reaction and the formation of heteroduplx DNA. Turning to another enzyme needed for certain kinds of bacterial recombination, we will ask whether the purified recB protein and recC protein complement each other and are sufficient for exonuclease V activity. In higher cells, we would like to know whether sister exchanges, which occur in bacteria after uv irradiation, are also seen in animal cells

  13. A novel nonsteroidal antifibrotic oligo decoy containing the TGF-beta element found in the COL1A1 gene which regulates murine schistosomiasis liver fibrosis.

    Science.gov (United States)

    Boros, D L; Singh, K P; Gerard, H C; Hudson, A P; White, S L; Cutroneo, K R

    2005-08-01

    Schistosomiasis mansoni disseminated worm eggs in mice and humans induce granulomatous inflammations and cumulative fibrosis causing morbidity and possibly mortality. In this study, intrahepatic and I.V. injections of a double-stranded oligodeoxynucleotide decoy containing the TGF-beta regulatory element found in the distal promoter of the COL1A1 gene into worm-infected mice suppressed TGF-beta1, COL1A1, tissue inhibitor of metalloproteinase-1, and decreased COL3A1 mRNAs to a lesser extent. Sequence comparisons within the mouse genome found homologous sequences within the COL3A1, TGF-beta1, and TIMP-1 5' flanking regions. Cold competition gel mobility shift assays using these homologous sequences with 5' and 3' flanking regions found in the natural COL1A1 gene showed competition. Competitive gel mobility assays in a separate experiment showed no competition using a 5-base mutated or scrambled sequence. Explanted liver granulomas from saline-injected mice incorporated 10.45 +/- 1.7% (3)H-proline into newly synthesized collagen, whereas decoy-treated mice showed no collagen synthesis. Compared with the saline control schistosomiasis mice phosphorothioate double-stranded oligodeoxynucleotide treatment decreased total liver collagen content (i.e. hydroxy-4-proline) by 34%. This novel molecular approach has the potential to be employed as a novel antifibrotic treatment modality. (c) 2005 Wiley-Liss, Inc.

  14. Meniscal repair devices.

    Science.gov (United States)

    Barber, F A; Herbert, M A

    2000-09-01

    Meniscal repair devices not requiring accessory incisions are attractive. Many factors contribute to their clinical effectiveness including their biomechanical characteristics. This study compared several new meniscal repair devices with standard meniscal suture techniques. Using a porcine model, axis-of-insertion loads were applied to various meniscal sutures and repair devices. A single device or stitch was placed in a created meniscal tear and a load applied. Both loads and modes of failure were recorded. The load-to-failure data show stratification into 4 distinct statistical groups. Group A, 113 N for a double vertical stitch; group B, 80 N for a single vertical stitch; group C, 57 N for the BioStinger, 56 N for a horizontal mattress stitch, and 50 N for the T-Fix stitch; and group D, 33 N for the Meniscus Arrow (inserted by hand or gun), 32 N for the Clearfix screw, 31 N for the SDsorb staple, 30 N for the Mitek meniscal repair system, and 27 N for the Biomet staple. The failure mechanism varied. Sutures broke away from the knot. The Meniscus Arrow and BioStinger pulled through the inner rim with the crossbar intact. The Clearfix screw failed by multiple mechanisms, whereas 1 leg of the SDsorb staple always pulled out of the outer rim. The Mitek device usually failed by pullout from the inner rim. The Biomet staple always broke at the crosshead or just below it. Although the surgeon should be aware of the material properties of the repair technique chosen for a meniscal repair, this information is only an indication of device performance and may not correlate with clinical healing results.

  15. DNA repair and cancer

    International Nuclear Information System (INIS)

    Rathore, Shakuntla; Joshi, Pankaj Kumar; Gaur, Sudha

    2012-01-01

    DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecule that encode it's genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many one million individual molecular lesions per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions include potentially harmful mutation in cell's genome which affect the survival of it's daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. Inherited mutation that affect DNA repair genes are strongly associated with high cancer risks in humans. Hereditary non polyposis colorectal cancer (HNPCC) is strongly associated with specific mutation in the DNA mismatch repair pathway. BRCA1, BRCA2 two famous mutation conferring a hugely increased risk of breast cancer on carrier, are both associated with a large number of DNA repair pathway, especially NHEJ and homologous recombination. Cancer therapy procedures such as chemotherapy and radiotherapy work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death. Cells that are most rapidly dividing most typically cancer cells are preferentially affected. The side effect is that other non-cancerous but rapidly dividing cells such as stem cells in the bone marrow are also affected. Modern cancer treatment attempt to localize the DNA damage to cells and tissue only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body). (author)

  16. Biological radiolesions and repair

    International Nuclear Information System (INIS)

    Laskowski, W.

    1981-01-01

    In 7 chapters, the book answers the following questions: 1) What reactions are induced in biological matter by absorption of radiation energy. 2) In what parts of the cell do the radiation-induced reactions with detectable biological effects occur. 3) In which way are these cell components changed by different qualities of radiation. 4) What are the cell mechanisms by which radiation-induced changes can be repaired. 5) What is the importance of these repair processes for man, his life and evolution. At the end of each chapter, there is a bibliography of relevant publications in this field. (orig./MG) [de

  17. Repair of DNA damage in the human metallothionein gene family

    International Nuclear Information System (INIS)

    Leadon, S.A.; Snowden, M.M.

    1987-01-01

    In order to distinguish enhanced repair of a sequence due to its transcriptional activity from enhanced repair due to chromatin alterations brought about by integration of a sequence into the genome, we have investigated the repair of damage both in endogenous genes and in cell lines that contain an integrated gene with an inducible promoter. The endogenous genes we are studying are the metallothioneins (MTs), a multigene family in man consisting of about 10-12 members. Cultured cells were exposed to 10-J/m 2 uv light and allowed to repair in the presence of bromodeoxyuridine. The DNA was then isolated, digested with Eco RI, and fully hybrid density DNA made by semiconservative synthesis was separated from unreplicated DNA by centrifugation in CsCl density gradients. Unreplicated, parental-density DNA was then reacted with a monoclonal antibody against bromouracil. 1 ref., 1 fig., 1 tab

  18. Use of duraseal in repair of cerebrospinal fluid leaks.

    Science.gov (United States)

    Chin, Christopher J; Kus, Lukas; Rotenberg, Brian W

    2010-10-01

    The purpose of our article is to review the use of the DuraSeal Sealant System (Confluent Surgical Inc., Waltham, MA) in the repair of complex cerebrospinal fluid (CSF) leaks in endoscopic skull-base surgery. Retrospective chart review. London Health Sciences Centre. A database of endoscopic skull-base cases between 2007 and 2009 that involved CSF leakage repaired with DuraSeal was created. Demographic data and operative reports were collected and analyzed qualitatively. Recurrence of CSF leak after repair. Five cases were identified that met study criteria. In four of the five cases, the repair was successful. There were no complications related to DuraSeal use. Comparison to a subset of patients using Tisseel Fibrin Sealant (Baxter, Toronto, ON) for repair did not show a significant difference in failure rate (χ2 = 0.029, p = .858). There are a variety of techniques described to repair CSF rhinorrhea, with various studies demonstrating the advantages of using tissue glues in CSF leak repairs. We used DuraSeal in five patients to enhance graft strength and form a watertight seal. The system was effective in the majority of patients. Our study is the first to report on endoscopic endonasal repair of CSF leaks using DuraSeal.

  19. Composite Repair System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — GTL has developed an innovative composite repair methodology known as the Composite Repair System (CRS). In this phase I effort, CRS is being developed for the...

  20. About the Collision Repair Campaign

    Science.gov (United States)

    EPA developed the Collision Repair Campaign to focus on meaningful risk reduction in the Collision Repair source sector to complement ongoing community air toxics work and attain reductions at a faster rate.

  1. Vesicovaginal Fistula Repair During Pregnancy

    African Journals Online (AJOL)

    Vesicovaginal Fistula Repair During Pregnancy: A Case Report ... Abstract. We report a repair of Vesicovaginal fistula during pregnancy that was aimed at preventing another spontaneous ... practices that encourage teenage marriage and girl.

  2. Ship Repair Workflow Cost Model

    National Research Council Canada - National Science Library

    McDevitt, Mike

    2003-01-01

    The effects of intermittent work patterns and funding on the costs of ship repair and maintenance were modeled for the San Diego region in 2002 for Supervisor of Shipbuilding and Repair (SUPSHIP) San Diego...

  3. Scaffolds for Tendon and Ligament Repair and Regeneration

    Science.gov (United States)

    Ratcliffe, Anthony; Butler, David L; Dyment, Nathaniel A; Cagle, Paul J; Proctor, Christopher S; Ratcliffe, Seena S; Flatow, Evan L

    2015-01-01

    Enhanced tendon and ligament repair would have a major impact on orthopaedic surgery outcomes, resulting in reduced repair failures and repeat surgeries, more rapid return to function, and reduced health care costs. Scaffolds have been used for mechanical and biologic reinforcement of repair and regeneration with mixed results. This review summarizes efforts made using biologic and synthetic scaffolds using rotator cuff and ACL as examples of clinical applications, discusses recent advances that have shown promising clinical outcomes, and provides insight into future therapy. PMID:25650098

  4. Social repair of relationships

    DEFF Research Database (Denmark)

    Fahnøe, Kristian Relsted

    2017-01-01

    organisations, friends and family, and communities. These social relations are viewed as the foundation of citizenship as experienced and practised. Focusing on how two dimensions of lived citizenship, namely rights-responsibilities and belonging, are affected by the social repairs, the chapter shows how...

  5. Comprehensive Small Engine Repair.

    Science.gov (United States)

    Hires, Bill; And Others

    This curriculum guide contains the basic information needed to repair all two- and four-stroke cycle engines. The curriculum covers four areas, each consisting of one or more units of instruction that include performance objectives, suggested activities for teacher and students, information sheets, assignment sheets, job sheets, visual aids,…

  6. Patent urachus repair - slideshow

    Science.gov (United States)

    ... Drugs & Supplements Videos & Tools About MedlinePlus Show Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Patent urachus repair - series—Normal anatomy URL of this ...

  7. Patent urachus repair

    Science.gov (United States)

    ... Drugs & Supplements Videos & Tools About MedlinePlus Show Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Patent urachus repair URL of this page: //medlineplus.gov/ ...

  8. DNA Repair Systems

    Indian Academy of Sciences (India)

    Thanks to the pioneering research work of Lindahl, Sancar, Modrich and their colleagues, we now have an holistic awareness of how DNA damage occurs and how the damage is rectified in bacteria as well as in higher organisms including human beings. A comprehensive understanding of DNA repair has proven crucial ...

  9. Aircraft Propeller Hub Repair

    Energy Technology Data Exchange (ETDEWEB)

    Muth, Thomas R [ORNL; Peter, William H [ORNL

    2015-02-13

    The team performed a literature review, conducted residual stress measurements, performed failure analysis, and demonstrated a solid state additive manufacturing repair technique on samples removed from a scrapped propeller hub. The team evaluated multiple options for hub repair that included existing metal buildup technologies that the Federal Aviation Administration (FAA) has already embraced, such as cold spray, high velocity oxy-fuel deposition (HVOF), and plasma spray. In addition the team helped Piedmont Propulsion Systems, LLC (PPS) evaluate three potential solutions that could be deployed at different stages in the life cycle of aluminum alloy hubs, in addition to the conventional spray coating method for repair. For new hubs, a machining practice to prevent fretting with the steel drive shaft was recommended. For hubs that were refurbished with some material remaining above the minimal material condition (MMC), a silver interface applied by an electromagnetic pulse additive manufacturing method was recommended. For hubs that were at or below the MMC, a solid state additive manufacturing technique using ultrasonic welding (UW) of thin layers of 7075 aluminum to the hub interface was recommended. A cladding demonstration using the UW technique achieved mechanical bonding of the layers showing promise as a viable repair method.

  10. Role of DNA repair in repair of cytogenetic damages. Slowly repaired DNA injuries involved in cytogenetic damages repair

    International Nuclear Information System (INIS)

    Zaichkina, S.I.; Rozanova, O.M.; Aptikaev, G.F.; Ganassi, E.Eh.

    1989-01-01

    Caffeine was used to study the kinetics of cytogenetic damages repair in Chinese hamster fibroblasts. Its half-time (90 min) was shown to correlate with that of repair of slowly repaired DNA damages. The caffeine-induced increase in the number of irreparable DNA damages, attributed to inhibition of double-strand break repair, is in a quantitative correlation with the effect of the cytogenetic damage modification

  11. Cleft lip and palate repair

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002979.htm Cleft lip and palate repair To use the sharing features on this ... Cheiloplasty; Cleft rhinoplasty; Palatoplasty; Tip rhinoplasty Patient Instructions Cleft lip and palate repair - discharge Images Cleft lip repair - series References ...

  12. DNA repair in human cells

    International Nuclear Information System (INIS)

    Regan, J.D.; Carrier, W.L.; Kusano, I.; Furuno-Fukushi, I.; Dunn, W.C. Jr.; Francis, A.A.; Lee, W.H.

    1982-01-01

    Our primary objective is to elucidate the molecular events in human cells when cellular macromolecules such as DNA are damaged by radiation or chemical agents. We study and characterize (i) the sequence of DNA repair events, (ii) the various modalities of repair, (iii) the genetic inhibition of repair due to mutation, (iv) the physiological inhibition of repair due to mutation, (v) the physiological inhibition of repair due to biochemical inhibitors, and (vi) the genetic basis of repair. Our ultimate goals are to (i) isolate and analyze the repair component of the mutagenic and/or carcinogenic event in human cells, and (ii) elucidate the magnitude and significance of this repair component as it impinges on the practical problems of human irradiation or exposure to actual or potential chemical mutagens and carcinogens. The significance of these studies lies in (i) the ubiquitousness of repair (most organisms, including man, have several complex repair systems), (ii) the belief that mutagenic and carcinogenic events may arise only from residual (nonrepaired) lesions or that error-prone repair systems may be the major induction mechanisms of the mutagenic or carcinogenic event, and (iii) the clear association of repair defects and highly carcinogenic disease states in man [xeroderma pigmentosum (XP)

  13. The journey of DNA repair.

    Science.gov (United States)

    Saini, Natalie

    2015-12-01

    21 years ago, the DNA Repair Enzyme was declared "Molecule of the Year". Today, we are celebrating another "year of repair", with the 2015 Nobel Prize in Chemistry being awarded to Aziz Sancar, Tomas Lindahl and Paul Modrich for their collective work on the different DNA repair pathways.

  14. Repair of traumatized mammalian hair cells via sea anemone repair proteins.

    Science.gov (United States)

    Tang, Pei-Ciao; Smith, Karen Müller; Watson, Glen M

    2016-08-01

    Mammalian hair cells possess only a limited ability to repair damage after trauma. In contrast, sea anemones show a marked capability to repair damaged hair bundles by means of secreted repair proteins (RPs). Previously, it was found that recovery of traumatized hair cells in blind cavefish was enhanced by anemone-derived RPs; therefore, the ability of anemone RPs to assist recovery of damaged hair cells in mammals was tested here. After a 1 h incubation in RP-enriched culture media, uptake of FM1-43 by experimentally traumatized murine cochlear hair cells was restored to levels comparable to those exhibited by healthy controls. In addition, RP-treated explants had significantly more normally structured hair bundles than time-matched traumatized control explants. Collectively, these results indicate that anemone-derived RPs assist in restoring normal function and structure of experimentally traumatized hair cells of the mouse cochlea. © 2016. Published by The Company of Biologists Ltd.

  15. EFL LEARNERS REPAIR SEQUENCE TYPES ANALYSIS AS PEER- ASSESSMENT IN ORAL PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Novia Trisanti

    2017-04-01

    Full Text Available There are certain concerns that EFL teacher needs to observe in assessing students oral performance, such as the amount of words which the learners utter, the grammatical errors that they make, the hesitation and certain expression that they produce. This paper attempts to give overview of research results using qualitative method which show the impacts of repair sequence types analysis on those elements needed to be observed as students peer and self-assessment to enhance their speaking ability. The subject was tertiary level learners of English Department, State University of Semarang, Indonesia in 2012. Concerning the repair types, there are four repair sequences as reviewed by Buckwalter (2001, they are Self-Initiated Self Repair (SISR, Self-Initiated Other Repair (SIOR, Other-Initiated Self Repair (OISR, and Other-Initiated Other Repair (OIOR. Having the repair sequences types anaysis, the students investigated the repair sequence of their peers while they performed in class conversation. The modified peer- assessment guideline as proposed by Brown (2004 was used in identifying, categorizing and classifying the types of repair sequences in their peers oral performance. While, the peer-assessment can be a valuable additional means to improve students speaking since it is one of the motives that drive peer- evaluation, along with peer- verification, also peer and self- enhancement. The analysis results were then interpreted to see whether there was significant finding related to the students’ oral performance enhancement.

  16. Repair mechanisms and exposure standards

    International Nuclear Information System (INIS)

    Mills, W.A.

    1978-01-01

    The following topics are discussed; public policy for setting radiation standards; use of linear, nonthreshold theory in setting radiation standards; dose-rate dependence; occupational exposure to radiation; radon inhalation from radium in the soil in the vicinity of the phosphate industry; relation of repair mechanisms for cell survival to cancer induction; application of information on genetic repair to humans and to cancer induction; importance of repair processes in radiation protection standards; corrective factors for repair processes; relation of repair processes to age, sex, and other factors; and population distribution in radiosensitivity

  17. Anterior cruciate ligament repair - past, present and future.

    Science.gov (United States)

    Mahapatra, Piyush; Horriat, Saman; Anand, Bobby S

    2018-06-15

    This article provides a detailed narrative review on the history and current concepts surrounding ligamentous repair techniques in athletic patients. In particular, we will focus on the anterior cruciate ligament (ACL) as a case study in ligament injury and ligamentous repair techniques. PubMed (MEDLINE), EMBASE and Cochrane Library databases for papers relating to primary anterior cruciate ligament reconstruction were searched by all participating authors. All relevant historical papers were included for analysis. Additional searches of the same databases were made for papers relating to biological enhancement of ligament healing. The poor capacity of the ACL to heal is one of the main reasons why the current gold standard surgical treatment for an ACL injury in an athletic patient is ACL reconstruction with autograft from either the hamstrings or patella tendon. It is hypothesised that by preserving and repairing native tissues and negating the need for autograft that primary ACL repair may represent a key step change in the treatment of ACL injuries. The history of primary ACL repair will be discussed and the circumstances that led to the near-abandonment of primary ACL repair techniques will be reviewed. There has been a recent resurgence in interest with regards to primary ACL repair. Improvements in imaging now allow for identification of tear location, with femoral-sided injuries, being more suitable for repair. We will discuss in details strategies for improving the mechanical and biological environment in order to allow primary healing to occur. In particular, we will explain mechanical supplementation such as Internal Brace Ligament Augmentation and Dynamic Intraligamentary Stabilisation techniques. These are novel techniques that aim to protect the primary repair by providing a stabilising construct that connects the femur and the tibia, thus bridging the repair. In addition, biological supplementation is being investigated as an adjunct and we will

  18. Repair promoted by plasmid pKM101 is different from SOS repair

    International Nuclear Information System (INIS)

    Goze, A.; Devoret, R.

    1979-01-01

    In E. coli K12 bacteria carrying plasmid pKM101, prophage lambda was induced at UV doses higher than in plasmid-less parental bacteria. UV-induced reactivation per se was less effective. Bacteria with pKM101 showed no alteration in their division cycle. Plasmid PKM101 coded for a constitutive error-prone repair different from the inducible error-prone repair called SOS repair. Plasmid pKM101 protected E. coli bacteria from UV damage but slightly sensitized them to X-ray lesions. Protection against UV damage was effective in mutant bacteria deficient in DNA excision-repair provided that the recA, lexA and uvrE genes were functional. Survival of phages lambda and S13 after UV irradiation was enhanced in bacteria carrying plasmid pKM101; phage lambda mutagenesis was also increased. Plasmid pKM101 repaired potentially lethal DNA lesions, although Wild-type DNA sequences may not necessarily be restored; hence the mutations observed are the traces of the original DNA lesions. (Auth.)

  19. Identify High-Quality Protein Structural Models by Enhanced K-Means.

    Science.gov (United States)

    Wu, Hongjie; Li, Haiou; Jiang, Min; Chen, Cheng; Lv, Qiang; Wu, Chuang

    2017-01-01

    Background. One critical issue in protein three-dimensional structure prediction using either ab initio or comparative modeling involves identification of high-quality protein structural models from generated decoys. Currently, clustering algorithms are widely used to identify near-native models; however, their performance is dependent upon different conformational decoys, and, for some algorithms, the accuracy declines when the decoy population increases. Results. Here, we proposed two enhanced K -means clustering algorithms capable of robustly identifying high-quality protein structural models. The first one employs the clustering algorithm SPICKER to determine the initial centroids for basic K -means clustering ( SK -means), whereas the other employs squared distance to optimize the initial centroids ( K -means++). Our results showed that SK -means and K -means++ were more robust as compared with SPICKER alone, detecting 33 (59%) and 42 (75%) of 56 targets, respectively, with template modeling scores better than or equal to those of SPICKER. Conclusions. We observed that the classic K -means algorithm showed a similar performance to that of SPICKER, which is a widely used algorithm for protein-structure identification. Both SK -means and K -means++ demonstrated substantial improvements relative to results from SPICKER and classical K -means.

  20. DNA repair deficiency in neurodegeneration

    DEFF Research Database (Denmark)

    Jeppesen, Dennis Kjølhede; Bohr, Vilhelm A; Stevnsner, Tinna V.

    2011-01-01

    Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive...... neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative...... base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby...

  1. Handbook of Equipment Repair.

    Science.gov (United States)

    1981-05-14

    state of leapin- fn’rw.rd. Tn recent years, many mechanical repair workers often write and ask us to reprint the book. In our consideration, however...ast 4iron 1. .-eat _--OSIS-RTS 5.5 . . 4-5 t4- cast -3.01 -6 ~.0 ’ ɘ.᝱ 5,,:e j?24 2 * 10- 5 aron C l 50 S lcon : Ielt rSSIS-RQTS-s;.4 u a 2.47 5at- .0

  2. MR imaging of cartilage and its repair in the knee - a review

    International Nuclear Information System (INIS)

    Trattnig, S.; Welsch, G.W.; Domayer, S.; Mosher, T.; Eckstein, F.

    2009-01-01

    Chondral injuries are common lesions of the knee joint, and many patients could benefit from cartilage repair. Widespread cartilage repair techniques require sophisticated noninvasive follow-up using MRI. In addition to the precise morphological assessment of this area of cartilage repair, the cartilage's biochemical constitution can be determined using biochemical MRI techniques. The combination of the clinical outcome after cartilage repair together with the morphological and biochemical description of the cartilage repair tissue as well as the surrounding cartilage can lead to an optimal follow-up evaluation. The present article on MR imaging techniques of cartilage repair focuses on morphological description and scoring using techniques from conventional 2D through advanced isotropic 3D MRI sequences. Furthermore the ultrastructure of the repair tissue and the surrounding cartilage is evaluated in-vivo by biochemical T1-delayed gadolinium enhanced MRI of cartilage (dGEMRIC), T2 relaxation, and diffusion-weighted imaging techniques. (orig.)

  3. Scoring protein interaction decoys using exposed residues (SPIDER): a novel multibody interaction scoring function based on frequent geometric patterns of interfacial residues.

    Science.gov (United States)

    Khashan, Raed; Zheng, Weifan; Tropsha, Alexander

    2012-08-01

    Accurate prediction of the structure of protein-protein complexes in computational docking experiments remains a formidable challenge. It has been recognized that identifying native or native-like poses among multiple decoys is the major bottleneck of the current scoring functions used in docking. We have developed a novel multibody pose-scoring function that has no theoretical limit on the number of residues contributing to the individual interaction terms. We use a coarse-grain representation of a protein-protein complex where each residue is represented by its side chain centroid. We apply a computational geometry approach called Almost-Delaunay tessellation that transforms protein-protein complexes into a residue contact network, or an undirectional graph where vertex-residues are nodes connected by edges. This treatment forms a family of interfacial graphs representing a dataset of protein-protein complexes. We then employ frequent subgraph mining approach to identify common interfacial residue patterns that appear in at least a subset of native protein-protein interfaces. The geometrical parameters and frequency of occurrence of each "native" pattern in the training set are used to develop the new SPIDER scoring function. SPIDER was validated using standard "ZDOCK" benchmark dataset that was not used in the development of SPIDER. We demonstrate that SPIDER scoring function ranks native and native-like poses above geometrical decoys and that it exceeds in performance a popular ZRANK scoring function. SPIDER was ranked among the top scoring functions in a recent round of CAPRI (Critical Assessment of PRedicted Interactions) blind test of protein-protein docking methods. Copyright © 2012 Wiley Periodicals, Inc.

  4. Causes and Implications of Readmission after Abdominal Aortic Aneurysm Repair

    Science.gov (United States)

    Greenblatt, David Yu; Greenberg, Caprice C.; Kind, Amy J.H.; Havlena, Jeffrey A.; Mell, Matthew W.; Nelson, Matthew T.; Smith, Maureen A.; Kent, K. Craig

    2012-01-01

    Objective To determine the frequency, causes, predictors, and consequences of 30-day readmission after abdominal aortic aneurysm (AAA) repair. Summary Background Data CMS will soon reduce total Medicare reimbursements for hospitals with higher-than-predicted 30-day readmission rates after vascular surgical procedures including AAA repair. However, causes and factors leading to readmission in this population have never before been systematically analyzed. Methods We analyzed elective AAA repairs over a two-year period from the CMS Chronic Conditions Warehouse, a 5% national sample of Medicare beneficiaries. Results 2481 patients underwent AAA repair – 1502 endovascular (EVAR) and 979 open. 30-day readmission rates were equivalent for EVAR (13.3%) and open repair (12.8%). While wound complication was the most common reason for readmission after both procedures, the relative frequency of other causes differed – e.g., bowel obstruction was common following open repair and graft complication after EVAR. In multivariate analyses, preoperative comorbidities had a modest effect on readmission; however, postoperative factors including serious complications leading to prolonged length of stay and discharge destination other than home had a profound influence on the probability of readmission. The one-year mortality in readmitted patients was 23.4% versus 4.5% in those not readmitted (preadmission is common after AAA repair. Adjusting for comorbidities, postoperative events predict readmission, suggesting that proactively preventing, detecting, and managing postoperative complications may provide an approach to decreasing readmissions, with the potential to reduce cost and possibly enhance long-term survival. PMID:22964736

  5. Parametric study on patch repaired CFRP laminates using FEA

    Energy Technology Data Exchange (ETDEWEB)

    Kashfuddoja, M.; Ramji, M. [Indian Institute of Technology. Engineering Optics Lab. Dept. of Mechanical Engineering, Hyderabad (India)

    2012-07-01

    Carbon fibre reinforced plastic (CFRP) composite laminates have become popular for structural applications as they are lighter, stronger and tougher. Composite structures are also susceptible to damage while in service. For improved service life, the damage needs to be repaired so that repair structure integrity is enhanced. Various parameters like patch size and shape, it's layup sequence and adhesive thickness would influence the performance of the repaired structure. In present work, a parametric study is carried out using finite element analysis (FEA) to investigate the influence of various parameters involved in composite repair. The panel is made of carbon / epoxy composite laminate with stacking sequence of (0/{+-}45/900)s and is subjected to tensile load. Damaged CFRP laminates is repaired by symmetrical patch adhesively bonded over the damaged area. Circular patch of different stacking sequence and size is considered. Influence of adhesive material and it's thickness on repair efficiency is also investigated. The influence of various repair parameters on peel stress is also analysed. (Author)

  6. Improving Aviation Depot Level Repairable (AVDLR) Inventory and Repair Management

    National Research Council Canada - National Science Library

    Baird, Dennis

    1997-01-01

    .... Additionally, research was conducted to document the management process for determining repair requirements at the Naval Inventory Control Point Philadelphia and how those requirements are accepted...

  7. DNA repair processes and their impairment in some human diseases

    International Nuclear Information System (INIS)

    Cleaver, J.E.

    1977-01-01

    Some human diseases show enhanced sensitivity to the action of environmental mutagens, and among these several are known which are defective in the repair of damaged DNA. Xeroderma pigmentosum (XP) is mainly defective in excision repair of a large variety of damaged DNA bases caused by ultraviolet light and chemical mutagens. XP involves at least 6 distinct groups, some of which may lack cofactors required for excising damage from chromatin. As a result of these defects the sensitivity of XP cells to many mutagens is increased 5- to 10-fold. Ataxia telangiectasia and Fanconi's anemia may similarly involve defects in repair of certain DNA base damage or cross-links, respectively. But most of these and other mutagen-sensitive diseases only show increases of about 2-fold in sensitivity to mutagens, and the biochemical defects in the diseases may be more complex and less directly involved in DNA repair than in XP. (Auth.)

  8. When is cartilage repair successful?

    International Nuclear Information System (INIS)

    Raudner, M.; Roehrich, S.; Zalaudek, M.; Trattnig, S.; Schreiner, M.M.

    2017-01-01

    Focal cartilage lesions are a cause of long-term disability and morbidity. After cartilage repair, it is crucial to evaluate long-term progression or failure in a reproducible, standardized manner. This article provides an overview of the different cartilage repair procedures and important characteristics to look for in cartilage repair imaging. Specifics and pitfalls are pointed out alongside general aspects. After successful cartilage repair, a complete, but not hypertrophic filling of the defect is the primary criterion of treatment success. The repair tissue should also be completely integrated to the surrounding native cartilage. After some months, the transplants signal should be isointense compared to native cartilage. Complications like osteophytes, subchondral defects, cysts, adhesion and chronic bone marrow edema or joint effusion are common and have to be observed via follow-up. Radiological evaluation and interpretation of postoperative changes should always take the repair method into account. (orig.) [de

  9. Inhibition of DNA repair by Pentoxifylline and related methylxanthine derivatives

    International Nuclear Information System (INIS)

    Boehm, Lothar; Roos, Wynand Paul; Serafin, Antonio Mendes

    2003-01-01

    The methylxanthine drug Pentoxifylline is reviewed for new properties which have emerged only relatively recently and for which clinical applications can be expected. After a summary on the established systemic effects of Pentoxifylline on the microcirculation and reduction of tumour anoxia, the role of the drug in the treatment of vasoocclusive disorders, cerebral ischemia, infectious diseases, septic shock and acute respiratory distress, the review focuses on another level of drug action which is based on in vitro observations in a variety of cell lines. Pentoxifylline and the related drug Caffeine are known radiosensitizers especially in p53 mutant cells. The explanation that the drug abrogates the G2 block and shortens repair in G2 by promoting early entry into mitosis is not anymore tenable because enhancement of radiotoxicity requires presence of the drug during irradiation and fails when the drug is added after irradiation at the G2 maximum. Repair assays by measurement of recovery ratios and by delayed plating experiments indeed strongly suggested a role in repair which is now confirmed for Pentoxifylline by constant field gel electrophoresis (CFGE) measurements and for Pentoxifylline and for Caffeine by use of a variety of repair mutants. The picture now emerging shows that Caffeine and Pentoxifylline inhibit homologous recombination by targeting members of the PIK kinase family (ATM and ATR) which facilitate repair in G2. Pentoxifylline induced repair inhibition between irradiation dose fractions to counter interfraction repair has been successfully applied in a model for stereotactic surgery. Another realistic avenue of application of Pentoxifylline in tumour therapy comes from experiments which show that repair events in G2 can be targeted directly by addition of cytotoxic drugs and Pentoxifylline at the G2 maximum. Under these conditions massive dose enhancement factors of up to 80 have been observed suggesting that it may be possible to realise

  10. Galectin-7 is important for normal uterine repair following menstruation.

    Science.gov (United States)

    Evans, Jemma; Yap, Joanne; Gamage, Thillini; Salamonsen, Lois; Dimitriadis, Evdokia; Menkhorst, Ellen

    2014-08-01

    Menstruation involves the shedding of the functional layer of the endometrium in the absence of pregnancy. At sites where tissue shedding is complete, re-epithelialization of the tissue is essential for repair and termination of bleeding. The complement of growth factors that mediate post-menstrual endometrial repair are yet to be completely elucidated. Galectins regulate many cell functions important for post-menstrual repair, such as cell adhesion and migration. Galectin-7 has a well characterized role in re-epithelialization and wound healing. We hypothesized that galectin-7 would be important in re-epithelialization during post-menstrual repair. We aimed to identify endometrial expression of galectin-7 in women undergoing normal endometrial repair and in women with amenorrhoea who do not experience endometrial breakdown and repair, and to determine whether galectin-7 enhances endometrial re-epithelialization in vitro. Galectin-7 immunolocalized to the endometrial luminal and glandular epithelium during the late secretory and menstrual phases, and to decidualized stroma in regions exhibiting tissue breakdown. Immunostaining intensity was significantly reduced in the endometrium of women with amenorrhoea compared with normally cycling woman. ELISA identified galectin-7 in menstrual fluid at significantly elevated levels compared with matched peripheral plasma. Exogenous galectin-7 (2.5 µg/ml) significantly enhanced endometrial epithelial wound repair in vitro; this was abrogated by inhibition of integrin binding. Galectin-7 elevated epithelial expression of extracellular matrix-related molecules likely involved in repair including β-catenin, contactin and TGF-β1. In conclusion, galectin-7 is produced by the premenstrual and menstrual endometrium, where it accumulates in menstrual fluid and likely acts as a paracrine factor to facilitate post-menstrual endometrial re-epithelialization. © The Author 2014. Published by Oxford University Press on behalf of the

  11. Engineered Heart Repair.

    Science.gov (United States)

    Fujita, B; Zimmermann, W-H

    2017-08-01

    There is a pressing need for the development of advanced heart failure therapeutics. Current state-of-the-art is protection from neurohumoral overstimulation, which fails to address the underlying cause of heart failure, namely loss of cardiomyocytes. Implantation of stem cell-derived cardiomyocytes via tissue-engineered myocardium is being advanced to realize the remuscularization of the failing heart. Here, we discuss pharmacological challenges pertaining to the clinical translation of tissue-engineered heart repair with a focus on engineered heart muscle (EHM). © 2017 American Society for Clinical Pharmacology and Therapeutics.

  12. Mapping of repair genes

    International Nuclear Information System (INIS)

    Hori, Tadaaki

    1985-01-01

    Chromosome mapping of repair genes involved in U.V. sensitivity is reported. Twenty-three of 25 hybrid cells were resistant to U.V. light. Survival curves of 2 U.V.-resistant cell strains, which possessed mouse chromosomes and human chromosome No.7 - 16, were similar to those of wild strain (L5178Y). On the other hand, survival curves of U.V.-sensitive hybrid cells was analogous to those of Q31. There was a definitive difference in the frequency of inducible chromosome aberrations between U.V. resistant and sensitive mouse-human hybrid cells. U.V.-resistant cell strains possessed the ability of excision repair. Analysis of karyotype in hybrid cells showed that the difference in U.V. sensitivity is dependent upon whether or not human chromosome No.13 is present. Synteny test on esterase D-determining locus confirmed that there is an agreement between the presence of chromosome No.13 and the presence of human esterase D activity. These results led to a conclusion that human genes which compensate recessive character of U.V.-sensitive mutant strain, Q31, with mouse-human hybrid cells are located on the locus of chromosome No.13. (Namekawa, K.)

  13. Repairs in 104 Gy/h?

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    In 1989 it was found that in each unit of the MAPS Candu nuclear power station in India the centre portion of the heavy water inlet manifold opposite the 300 mm inlet pipe had torn away. Equipment for remote inspection, repair and removal of debris in an area with constricted and difficult access and radiation fields of about 10 4 Gy/h was developed by Ricardo Hitec of the United Kingdom. This consists of a work performing manipulator, TV viewing systems and a posting tube manipulator for insertion of tools and debris containers into the calandria. A variety of special end effector and tools were also developed jointly with AEA Technology. A first repair campaign was carried out on Unit 1 in 1991. Following a detailed TV survey of the damage a reappraisal of the situation was undertaken and a programme of equipment enhancement carried out. In July 1992 a second repair campaign took place on Unit 2. The difficulties encountered and the degree of success achieved are described. Work proceeded at an intensive level for 14 days when the campaign was ended in view of the exhaustion both of personnel and the equipment. Although more work could have been done a major improvement had been achieved. (UK)

  14. Handbook of adhesive bonded structural repair

    CERN Document Server

    Wegman, Raymond F

    1992-01-01

    Provides repair methods for adhesive bonded and composite structures; identifies suitable materials and equipment for repairs; describes damage evaluation criteria and techniques, and methods of inspection before and after repair.

  15. [Constitutional mismatch repair deficiency syndrome

    NARCIS (Netherlands)

    Jongmans, M.C.J.; Gidding, C.E.M.; Loeffen, J.; Wesseling, P.; Mensenkamp, A.; Hoogerbrugge, N.

    2015-01-01

    BACKGROUND: Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. CASE DESCRIPTION: An 8-year-old

  16. Clamp wins pipe repair prize

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2001-04-01

    This paper describes the permanent pipeline repair system, developed by Tekmar, which is powered by seawater hydraulics and is easily installed and tested by any workclass remotely operated vehicle (rov). Details are given of the two main components of the system, namely, the diverless high pressure split repair clamp and the rov-operated tool to install it.

  17. Nucleotide excision repair in yeast

    NARCIS (Netherlands)

    Eijk, Patrick van

    2012-01-01

    Nucleotide Excision Repair (NER) is a conserved DNA repair pathway capable of removing a broad spectrum of DNA damage. In human cells a defect in NER leads to the disorder Xeroderma pigmentosum (XP). The yeast Saccharomyces cerevisiae is an excellent model organism to study the mechanism of NER. The

  18. My journey to DNA repair.

    Science.gov (United States)

    Lindahl, Tomas

    2013-02-01

    I completed my medical studies at the Karolinska Institute in Stockholm but have always been devoted to basic research. My longstanding interest is to understand fundamental DNA repair mechanisms in the fields of cancer therapy, inherited human genetic disorders and ancient DNA. I initially measured DNA decay, including rates of base loss and cytosine deamination. I have discovered several important DNA repair proteins and determined their mechanisms of action. The discovery of uracil-DNA glycosylase defined a new category of repair enzymes with each specialized for different types of DNA damage. The base excision repair pathway was first reconstituted with human proteins in my group. Cell-free analysis for mammalian nucleotide excision repair of DNA was also developed in my laboratory. I found multiple distinct DNA ligases in mammalian cells, and led the first genetic and biochemical work on DNA ligases I, III and IV. I discovered the mammalian exonucleases DNase III (TREX1) and IV (FEN1). Interestingly, expression of TREX1 was altered in some human autoimmune diseases. I also showed that the mutagenic DNA adduct O(6)-methylguanine (O(6)mG) is repaired without removing the guanine from DNA, identifying a surprising mechanism by which the methyl group is transferred to a residue in the repair protein itself. A further novel process of DNA repair discovered by my research group is the action of AlkB as an iron-dependent enzyme carrying out oxidative demethylation. Copyright © 2013. Production and hosting by Elsevier Ltd.

  19. The journey of DNA repair

    OpenAIRE

    Saini, Natalie

    2015-01-01

    21 years ago, the DNA Repair Enzyme was declared “Molecule of the Year”. Today, we are celebrating another “year of repair”, with the 2015 Nobel Prize in Chemistry being awarded to Aziz Sancar, Tomas Lindahl and Paul Modrich for their collective work on the different DNA repair pathways.

  20. Procedures for maintenance and repairs

    International Nuclear Information System (INIS)

    Pickel, E.

    1981-01-01

    After a general review of the operation experience in the history of more than 12 operating years, the organization in the plant will be shown with special aspect to quality assurance, capacity of the workshops and connected groups as radiation protection, chemical laboratories etc. The number, time intervals and manpower effort for the repeating tests will be discussed. Reasons and examples for back-fitting activities in the plant are given. Besides special repair and maintenance procedures as repair of the steam generators, in-service inspection of the reactor pressure vessel, repair of a feed-water pipe and repair of the core structure in the pressure vessel, the general system to handle maintenance and repair-work in the KWO-plant will be shown. This includes also the detailed planning of the annual refueling and revision of the plant. (orig./RW)

  1. Advances in biologic augmentation for rotator cuff repair

    Science.gov (United States)

    Patel, Sahishnu; Gualtieri, Anthony P.; Lu, Helen H.; Levine, William N.

    2016-01-01

    Rotator cuff tear is a very common shoulder injury that often necessitates surgical intervention for repair. Despite advances in surgical techniques for rotator cuff repair, there is a high incidence of failure after surgery because of poor healing capacity attributed to many factors. The complexity of tendon-to-bone integration inherently presents a challenge for repair because of a large biomechanical mismatch between the tendon and bone and insufficient regeneration of native tissue, leading to the formation of fibrovascular scar tissue. Therefore, various biological augmentation approaches have been investigated to improve rotator cuff repair healing. This review highlights recent advances in three fundamental approaches for biological augmentation for functional and integrative tendon–bone repair. First, the exploration, application, and delivery of growth factors to improve regeneration of native tissue is discussed. Second, applications of stem cell and other cell-based therapies to replenish damaged tissue for better healing is covered. Finally, this review will highlight the development and applications of compatible biomaterials to both better recapitulate the tendon–bone interface and improve delivery of biological factors for enhanced integrative repair. PMID:27750374

  2. Insights on accelerated skeletal repair in Cushing's disease

    Directory of Open Access Journals (Sweden)

    So-Young Kim

    2015-06-01

    In this patient, spontaneous recovery of trabecular bone architecture was reflected by the early correction in TBS. Subsequent TPTD treatment was associated with marked improvement in BMD, presumably due to enhanced mineralization. Complete skeletal repair was achieved by this two-step mechanism in a very short time following successful surgical treatment for Cushing's disease.

  3. Biomarkers of oxidative damage to DNA and repair

    DEFF Research Database (Denmark)

    Loft, Steffen; Høgh Danielsen, Pernille; Mikkelsen, Lone

    2008-01-01

    environmental factors, including particulate air pollution, cause oxidative damage to DNA, whereas diets rich in fruit and vegetables or antioxidant supplements may reduce the levels and enhance repair. Urinary excretion of 8-oxodG, genotype and expression of OGG1 have been associated with risk of cancer...

  4. Robotic repair of retrocaval ureter: A case series | Nayak | African ...

    African Journals Online (AJOL)

    Subjects and methods: This is a prospective case series of five consecutive patients who underwent robotic retrocaval ureter repair at our institute from August 2006 to September 2009. Pre-operative imaging included intravenous urogram, contrast enhanced CT scan and diuretic renography. All cases were done through a ...

  5. Wound repair in Pocillopora

    Science.gov (United States)

    Rodríguez-Villalobos, Jenny Carolina; Work, Thierry M.; Calderon-Aguileraa, Luis Eduardo

    2016-01-01

    Corals routinely lose tissue due to causes ranging from predation to disease. Tissue healing and regeneration are fundamental to the normal functioning of corals, yet we know little about this process. We described the microscopic morphology of wound repair in Pocillopora damicornis. Tissue was removed by airbrushing fragments from three healthy colonies, and these were monitored daily at the gross and microscopic level for 40 days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40 d). On histology, from Day 8 onwards, tissues at the lesion site were microscopically indistinguishable from adjacent normal tissues with evidence of zooxanthellae in gastrodermis. Inflammation was not evident. P. damicornis manifested a unique mode of regeneration involving projections of cell-covered mesoglea from the surface body wall that anastomosed to form gastrovascular canals.

  6. Repairing Nanoparticle Surface Defects.

    Science.gov (United States)

    Marino, Emanuele; Kodger, Thomas E; Crisp, Ryan W; Timmerman, Dolf; MacArthur, Katherine E; Heggen, Marc; Schall, Peter

    2017-10-23

    Solar devices based on semiconductor nanoparticles require the use of conductive ligands; however, replacing the native, insulating ligands with conductive metal chalcogenide complexes introduces structural defects within the crystalline nanostructure that act as traps for charge carriers. We utilized atomically thin semiconductor nanoplatelets as a convenient platform for studying, both microscopically and spectroscopically, the development of defects during ligand exchange with the conductive ligands Na 4 SnS 4 and (NH 4 ) 4 Sn 2 S 6 . These defects can be repaired via mild chemical or thermal routes, through the addition of L-type ligands or wet annealing, respectively. This results in a higher-quality, conductive, colloidally stable nanomaterial that may be used as the active film in optoelectronic devices. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  7. Reward optimization of a repairable system

    Energy Technology Data Exchange (ETDEWEB)

    Castro, I.T. [Departamento de Matematicas, Facultad de Veterinaria, Universidad de Extremadura, Avenida de la Universidad, s/n. 10071 Caceres (Spain)]. E-mail: inmatorres@unex.es; Perez-Ocon, R. [Departamento de Estadistica e Investigacion Operativa, Facultad de Ciencias, Universidad de Granada, Avenida de Severo Ochoa, s/n. 18071 Granada (Spain)]. E-mail: rperezo@ugr.es

    2006-03-15

    This paper analyzes a system subject to repairable and non-repairable failures. Non-repairable failures lead to replacement of the system. Repairable failures, first lead to repair but they lead to replacement after a fixed number of repairs. Operating and repair times follow phase type distributions (PH-distributions) and the pattern of the operating times is modelled by a geometric process. In this context, the problem is to find the optimal number of repairs, which maximizes the long-run average reward per unit time. To this end, the optimal number is determined and it is obtained by efficient numerical procedures.

  8. Reward optimization of a repairable system

    International Nuclear Information System (INIS)

    Castro, I.T.; Perez-Ocon, R.

    2006-01-01

    This paper analyzes a system subject to repairable and non-repairable failures. Non-repairable failures lead to replacement of the system. Repairable failures, first lead to repair but they lead to replacement after a fixed number of repairs. Operating and repair times follow phase type distributions (PH-distributions) and the pattern of the operating times is modelled by a geometric process. In this context, the problem is to find the optimal number of repairs, which maximizes the long-run average reward per unit time. To this end, the optimal number is determined and it is obtained by efficient numerical procedures

  9. Plasmid mediated enhancement of uv resistance in Streptococcus faecalis

    International Nuclear Information System (INIS)

    Miehl, R.; Miller, M.; Yasbin, R.E.

    1980-01-01

    A 38.5-Mdal plasmid of Streptococcus faecalis subdp. zymogenes has been shown to enhance survival following uv irradiation. In addition, the presence of this plasmid increases the mutation frequencies following uv irradiation and enhanced W-reactivation. The data presented indicate that S. faecalis has an inducible error-prone repair system and that the plasmid enhances these repair functions

  10. Tissue repair capacity and repair kinetics deduced from multifractionated or continuous irradiation regimens with incomplete repair

    International Nuclear Information System (INIS)

    Thames, H.D. Jr.; Peters, L.J.

    1984-01-01

    A model is proposed for cell survival after multiple doses, when the interfraction interval is insufficient for complete Elkind repair. In the limit of ever-increasing number of ever-smaller fractional doses, the model transforms into the accumulation model of survival after continuous irradiation. When adapted to describe tissue responses to isoeffective multifractionated regimens, wherein repair is incomplete, a generalization of the usually linear plot of reciprocal total dose versus dose per fraction is obtained, in which downward curvature is evident. There is an advantage in studying tissue responses to multifractionated regimens with incomplete repair in the interfraction intervals, or continuous exposures at various dose rates since, in addition to determination of repair capacity, there is an estimate of repair kinetics. Results of analyses of previously published data are presented as illustration. Estimated from the response of three acutely responding normal tissues in the mouse (jejunum, colon and bone marrow), repair halftimes ranged from 0.3-0.9 h and values of β/delta were approximately 0.1 Gy -1 . From the response of mouse lung (LD50 for pneumonitis) to multifractionated regimens with incomplete repair, the repair halftime was estimated at 1.5 h and β/delta was 0.27 Gy -1 . In the rat spinal cord β/delta was 0.7 Gy -1 and Tsub(1/2) was 1.5 h. (U.K.)

  11. Predicting fatigue service life extension of RC bridges with externally bonded CFRP repairs : [project brief].

    Science.gov (United States)

    2015-12-01

    Externally bonded carbon fiber reinforced polymer composites (CFRPs) are increasingly used to : repair concrete bridges. CFRP design techniques are a proven approach for enhancing the strength : of existing structures. This project investigated the d...

  12. The Design of Intelligent Repair Welding Mechanism and Relative Control System of Big Gear

    Directory of Open Access Journals (Sweden)

    Hong-Yu LIU

    2014-10-01

    Full Text Available Effective repair of worn big gear has large influence on ensuring safety production and enhancing economic benefits. A kind of intelligent repair welding method was put forward mainly aimed at the big gear restriction conditions of high production cost, long production cycle and high- intensity artificial repair welding work. Big gear repair welding mechanism was designed in this paper. The work principle and part selection of big gear repair welding mechanism was introduced. The three dimensional mode of big gear repair welding mechanism was constructed by Pro/E three dimensional design software. Three dimensional motions can be realized by motor controlling ball screw. According to involute gear feature, the complicated curve motion on curved gear surface can be transformed to linear motion by orientation. By this way, the repair welding on worn gear area can be realized. In the design of big gear repair welding mechanism control system, Siemens S7-200 series hardware was chosen. Siemens STEP7 programming software was chosen as system design tool. The entire repair welding process was simulated by experiment simulation. It provides a kind of practical and feasible method for the intelligent repair welding of big worn gear.

  13. A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year.

    Science.gov (United States)

    Siclari, Alberto; Mascaro, Gennaro; Gentili, Chiara; Cancedda, Ranieri; Boux, Eugenio

    2012-03-01

    Bone marrow stimulation techniques in cartilage repair such as drilling are limited by the formation of fibrous to hyaline-like repair tissue. It has been suggested such techniques can be enhanced by covering the defect with scaffolds. We present an innovative approach using a polyglycolic acid (PGA)-hyaluronan scaffold with platelet-rich-plasma (PRP) in drilling. We asked whether (1) PRP immersed in a cell-free PGA-hyaluronan scaffold improves patient-reported 1-year outcomes for the Knee injury and Osteoarthritis Score (KOOS), and (2) implantation of the scaffold in combination with bone marrow stimulation leads to the formation of hyaline-like cartilage repair tissue. We reviewed 52 patients who had arthroscopic implantation of the PGA-hyaluronan scaffold immersed with PRP in articular cartilage defects of the knee pretreated with Pridie drilling. Patients were assessed by KOOS. At 9 months followup, histologic staining was performed in specimens obtained from five patients to assess the repair tissue quality. The KOOS subscores improved for pain (55 to 91), symptoms (57 to 88), activities of daily living (69 to 86), sports and recreation (36 to 70), and quality of life (38 to 73). The histologic evaluation showed a homogeneous hyaline-like cartilage repair tissue. The cell-free PGA-hyaluronan scaffold combined with PRP leads to cartilage repair and improved patient-reported outcomes (KOOS) during 12 months of followup. Histologic sections showed morphologic features of hyaline-like repair tissue. Long-term followup is needed to determine if the cartilage repair tissue is durable. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

  14. Residual stress by repair welds

    International Nuclear Information System (INIS)

    Mochizuki, Masahito; Toyoda, Masao

    2003-01-01

    Residual stress by repair welds is computed using the thermal elastic-plastic analysis with phase-transformation effect. Coupling phenomena of temperature, microstructure, and stress-strain fields are simulated in the finite-element analysis. Weld bond of a plate butt-welded joint is gouged and then deposited by weld metal in repair process. Heat source is synchronously moved with the deposition of the finite-element as the weld deposition. Microstructure is considered by using CCT diagram and the transformation behavior in the repair weld is also simulated. The effects of initial stress, heat input, and weld length on residual stress distribution are studied from the organic results of numerical analysis. Initial residual stress before repair weld has no influence on the residual stress after repair treatment near weld metal, because the initial stress near weld metal releases due to high temperature of repair weld and then stress by repair weld regenerates. Heat input has an effect for residual stress distribution, for not its magnitude but distribution zone. Weld length should be considered reducing the magnitude of residual stress in the edge of weld bead; short bead induces high tensile residual stress. (author)

  15. Monogenic diseases of DNA repair

    DEFF Research Database (Denmark)

    Keijzers, Guido; Bakula, Daniela; Scheibye-Knudsen, Morten

    2017-01-01

    Maintaining the stability of the genome is essential for all organisms, and it is not surprising that damage to DNA has been proposed as an explanation for multiple chronic diseases.1-5 Conserving a pristine genome is therefore of central importance to our health. To overcome the genotoxic stress...... of a growing number of human diseases. Notably, many of these monogenic DNA-repair disorders display features of accelerated aging, supporting the notion that genome maintenance is a key factor for organismal longevity. This review focuses on the physiological consequences of loss of DNA repair, particularly...... in the context of monogenic DNA-repair diseases....

  16. Repairing and Upgrading Your PC

    CERN Document Server

    Thompson, Robert

    2009-01-01

    Repairing and Upgrading Your PC delivers start-to-finish instructions, simple enough for even the most inexperienced PC owner, for troubleshooting, repairing, and upgrading your computer. Written by hardware experts Robert Bruce Thompson and Barbara Fritchman Thompson, this book covers it all: how to troubleshoot a troublesome PC, how to identify which components make sense for an upgrade, and how to tear it all down and put it back together. This book shows how to repair and upgrade all of your PC's essential components.

  17. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Science.gov (United States)

    2010-07-01

    ... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.” (a... killing or growth inhibition of repair deficient bacteria in a set of repair proficient and deficient...

  18. 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

  19. Advanced Inspection and Repair Welding Techniques for SCC Countermeasures

    International Nuclear Information System (INIS)

    Takagi, T.; Nishimoto, K.; Uchimoto, T.

    2012-01-01

    Feasibility studies of advanced inspection and repair welding techniques were conducted in the framework of the Nuclear and Industry Safety Agency of Japan (NISA) project on the enhancement of ageing management and maintenance of NPPs. In this paper, features of NDE methods investigated in the projects, main results of research activities and prospect of nickel based alloy weld inspection are discussed. We also make a review for the integrity and reliability evaluation techniques for repair welding of ageing plants which were intensively investigated in view of regulatory criteria, in NISA project. (author)

  20. Innovative repair of subsidence damage

    International Nuclear Information System (INIS)

    Marino, G.G.

    1992-01-01

    In order to improve handling of subsidence damages the Illinois Mine Subsidence Insurance Fund supported the development of novel cost-effective methods of repair. The research in developing the repairs was directed towards the most common and costly damages that had been observed. As a result repair techniques were designed for structurally cracked foundations in the tension zone; structurally cracked foundations in the compression zone; and damaged or undamaged tilted foundations. When appropriate the postulated methods would result in: 1. significant cost savings (over conventional procedures); 2. a structural capacity greater than when the foundation was uncracked; and 3. an aesthetic appeal. All the postulated repair methodologies were laboratory and/or field tested. This paper will summarize the essentials of each technique developed and the test results

  1. Umbilical hernia repair - series (image)

    Science.gov (United States)

    ... treatment. The indications for umbilical hernia repair include: incarcerated (strangulated) umbilical hernia defects not spontaneously closed by 4 to 5 years of age children under 2 with very large defects unacceptable to ...

  2. Mammalian DNA Repair. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Wood, Richard D.

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  3. Canadian company innovates dam repair

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    Successful repair without any downtime, of the Sabana Yegua power and irrigation structure in the western Dominican Republic by Aquatic Sciences Ltd., a St. Catherine, Ontario-based underwater specialist company, is discussed. The structure was damaged by Hurricane George last when when rising water levels damaged a major valve in the control gate chamber. The repair strategy designed by Aquatic Sciences used a remotely operated vehicle with a mechanical arm for minor tasks which placed a specially-made plug into the inlet pipe. The work was completed in one week, saving the utility company a great deal of money by making it possible to make the repairs remotely in the gate chamber without having to drain the tunnel, as would have been necessary had the repair been completed manually. The remotely operated vehicles use a scanning sonar as well as light to find their way. They are particularly well adapted to work underwater under low-visibility conditions

  4. Betonreparationers holdbarhed (Durability of Concrete Repairs)

    DEFF Research Database (Denmark)

    Brimnes, Eydbjørn; Dali, Bogi í; Larsen, Erik Stoklund

    1999-01-01

    Concrete repairs on 11 pillars on bridges built in the sixties and repaired 8 to 9 years ago have been examined. Especially the chloride penetration in the repair concrete have been measured. Chloride penetration in the repair concrete is much lower than in the original concrete....

  5. 40 CFR 63.1005 - Leak repair.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Leak repair. 63.1005 Section 63.1005... Standards for Equipment Leaks-Control Level 1 § 63.1005 Leak repair. (a) Leak repair schedule. The owner or operator shall repair each leak detected no later than 15 calendar days after it is detected, except as...

  6. 40 CFR 63.1024 - Leak repair.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Leak repair. 63.1024 Section 63.1024... Standards for Equipment Leaks-Control Level 2 Standards § 63.1024 Leak repair. (a) Leak repair schedule. The owner or operator shall repair each leak detected as soon as practical, but not later than 15 calendar...

  7. 40 CFR 65.105 - Leak repair.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Leak repair. 65.105 Section 65.105... FEDERAL AIR RULE Equipment Leaks § 65.105 Leak repair. (a) Leak repair schedule. The owner or operator shall repair each leak detected as soon as practical but not later than 15 calendar days after it is...

  8. Laparoscopic Repair of Inguinal Hernias

    OpenAIRE

    Carter, Jonathan; Duh, Quan-Yang

    2011-01-01

    For patients with recurrent inguinal hernia, or bilateral inguinal hernia, or for women, laparoscopic repair offers significant advantages over open techniques with regard to recurrence risk, pain, and recovery. For unilateral first-time hernias, either laparoscopic or open repair with mesh can offer excellent results. The major drawback of laparoscopy is that the technique requires a significant number of cases to master. For surgeons in group practice, it makes sense to have one surgeon in ...

  9. Repair Types, Procedures - Part 1

    Science.gov (United States)

    2010-05-01

    Affordable Combat Aircraft, AGARD - CP -600, 1997. [17] Helbling J, Grover R and Ratwani M. M “Analysis and Structural Test of Composite Reinforcement to...considered suitable for the composite patch repair of aluminum structure. Ductile adhesives such as FM- 73 are preferred over brittle adhesives Repair Types...zone. A proper cure cycle is followed as prescribed by the adhesive manufacturer. For FM- 73 adhesive cure at 2500F (1210C) for 120 minutes is

  10. Gamma-ray induced inhibition of DNA synthesis in ataxia telangiectasia fibroblasts is a function of excision repair capacity

    International Nuclear Information System (INIS)

    Smith, P.J.; Paterson, M.C.

    1980-01-01

    The extent of the deficiency in γ-ray induced DNA repair synthesis in an ataxia telangiectasia (AT) human fibroblast strain was found to show no oxygen enhancement, consistent with a defect in the repair of base damage. Repair deficiency, but not repair proficiency, in AT cells was accompanied by a lack of inhibition of DNA synthesis by either γ-rays or the radiomimetic drug bleomycin. Experiments with 4-nitroquinoline 1-oxide indicated that lack of inhibition was specific for radiogenic-type damage. Thus excision repair, perhaps by DNA strand incision or chromatin modification, appears to halt replicon initiation in irradiated repair proficient cells whereas in repair defective AT strains this putatively important biological function is inoperative

  11. Laparoscopic repair of postoperative perineal hernia.

    LENUS (Irish Health Repository)

    Ryan, Stephen

    2010-01-01

    Perineal hernias are infrequent complications following abdominoperineal operations. Various approaches have been described for repair of perineal hernias including open transabdominal, transperineal or combined abdominoperineal repairs. The use of laparoscopic transabdominal repair of perineal hernias is not well-described. We present a case report demonstrating the benefits of laparoscopic repair of perineal hernia following previous laparoscopic abdominoperineal resection (APR) using a nonabsorbable mesh to repair the defect. We have demonstrated that the use of laparoscopy with repair of the pelvic floor defect using a non absorbable synthetic mesh offers an excellent alternative with many potential advantages over open transabdominal and transperineal repairs.

  12. Overlapping sphincteroplasty and posterior repair.

    Science.gov (United States)

    Crane, Andrea K; Myers, Erinn M; Lippmann, Quinn K; Matthews, Catherine A

    2014-12-01

    Knowledge of how to anatomically reconstruct extensive posterior-compartment defects is variable among gynecologists. The objective of this video is to demonstrate an effective technique of overlapping sphincteroplasty and posterior repair. In this video, a scripted storyboard was constructed that outlines the key surgical steps of a comprehensive posterior compartment repair: (1) surgical incision that permits access to posterior compartment and perineal body, (2) dissection of the rectovaginal space up to the level of the cervix, (3) plication of the rectovaginal muscularis, (4) repair of internal and external anal sphincters, and (5) reconstruction of the perineal body. Using a combination of graphic illustrations and live video footage, tips on repair are highlighted. The goals at the end of repair are to: (1) have improved vaginal caliber, (2) increase rectal tone along the entire posterior vaginal wall, (3) have the posterior vaginal wall at a perpendicular plane to the perineal body, (4) reform the hymenal ring, and (5) not have an overly elongated perineal body. This video provides a step-by-step guide on how to perform an overlapping sphincteroplasty and posterior repair.

  13. Scarf Repair of Composite Laminates

    Directory of Open Access Journals (Sweden)

    Xie Zonghong

    2016-01-01

    Full Text Available The use of composite materials, such as carbon-fiber reinforced plastic (CFRP composites, aero-structures has led to an increased need of advanced assembly joining and repair technologies. Adhesive bonded repairs as an alternative to recover full or part of initial strength were investigated. Tests were conducted with the objective of evaluating the effectiveness of techniques used for repairing damage fiber reinforced laminated composites. Failure loads and failure modes were generated and compared with the following parameters: scarf angles, roughness of grind tool and number of external plies. Results showed that scarf angle was the critical parameter and the largest tensile strength was observed with the smallest scarf angle. Besides, the use of external plies at the outer surface could not increase the repairs efficiency for large scarf angle. Preparing the repair surfaces by sanding them with a sander ranging from 60 to 100 grit number had significant effect on the failure load. These results allowed the proposal of design principles for repairing CFRP structures.

  14. Aging and DNA repair capability. [Review

    Energy Technology Data Exchange (ETDEWEB)

    Tice, R R

    1977-01-01

    A review of the literature on DNA repair processes in relation to aging is presented under the following headings: DNA repair processes; age-related occurrence of unrepaired DNA lesions; DNA repair capability as a function of age; tissue-specific DNA repair capability; acceleration of the aging process by exposure to DNA damaging agents; human genetic syndromes; and longevity and DNA repair processes. (HLW)

  15. Repair of potentially lethal and sublethal radiation damage in x-irradiated ascites tumor cells

    International Nuclear Information System (INIS)

    Tsuboi, Atsushi; Okamoto, Mieko; Tsuchiya, Takehiko.

    1985-01-01

    The ability of cells to repair cellular radiation damage during the growth of TMT-3 ascites tumor and the effect of host reaction on the repair ability were examined by using an in vitro assay of cell clonogenicity after in situ irradiation of tumor cells. In single-dose experiments, the repair of potentially lethal radiation damage (PLD) was observed in stationary phase cells (12-day tumor) of the unirradiated host, but not in exponential phase cells (3-day tumor) of the unirradiated host animals. However, if previously irradiated host animals were used, even the exponentially growing tumor cells showed repair of PLD. In two-dose experiments, the ability to repair sublethal radiation damage (SLD) in exponential phase tumor cells was less than that of stationary phase cells in the unirradiated host. In the pre-irradiated host, the extent of the repair in exponential phase cells was somewhat enhanced. These results suggest that irradiation of host animals might suppress a factor that inhibits repair, resulting in enhancement of the repair capability of tumor cells. (author)

  16. The bases for optimisation of scheduled repairs and tests of safety systems to improve the NPP productive efficiency

    International Nuclear Information System (INIS)

    Bilej, D.V.; Vasil'chenko, S.V.; Vlasenko, N.I.; Vasil'chenko, V.N.; Skalozubov, V.I.

    2004-01-01

    In the frames of risk-informed approaches the paper proposed the theoretical bases for methods of optimisation of scheduled repairs and tests of safety systems at nuclear power plants. The optimisation criterion is the objective risk function minimising. This function depends on the scheduled repairs/tests periodicity and the allowed time to bring the system channel to a state of non-operability. The main optimisation direct is to reduce the repair time with the purpose of enhancement of productive efficiency

  17. Polymer nanocomposites for high-temperature composite repair

    Energy Technology Data Exchange (ETDEWEB)

    Sheng, Xia [Iowa State Univ., Ames, IA (United States)

    2008-01-01

    A novel repair agent for resin-injection repair of advanced high temperature composites was developed and characterized. The repair agent was based on bisphenol E cyanate ester (BECy) and reinforced with alumina nanoparticles. To ensure good dispersion and compatibility with the BECy matrix in nanocomposites, the alumina nanoparticles were functionalized with silanes. The BECy nanocomposites, containing bare and functionalized alumina nanoparticles, were prepared and evaluated for their thermal, mechanical, rheological, and viscoelastic properties. The monomer of BECy has an extremely low viscosity at ambient temperature, which is good for processability. The cured BECy polymer is a highly cross-linked network with excellent thermal mechanical properties, with a high glass transition temperature (Tg) of 270 C and decomposition temperature above 350 C. The incorporation of alumina nanoparticles enhances the mechanical and rheological properties of the BECy nanocomposites. Additionally, the alumina nanoparticles are shown to catalyze the cure of BECy. Characterization of the nanocomposites included dynamic mechanical analysis, differential scanning calorimetry, thermogravimetric analysis, rheological and rheokinetic evaluation, and transmission electron microscopy. The experimental results show that the BECy nanocomposite is a good candidate as repair agent for resin-injection repair applications.

  18. Protracted radiation-induced alterations in hematopoietic repair and recovery

    International Nuclear Information System (INIS)

    Seed, T.M.; Fritz, T.E.

    1997-01-01

    Pathologic predisposition of beagle dogs under chronic, low daily dose (7.5 cGy day -1 ) whole-body gamma irradiation has been studied relative to molecular repair and hematopoietic competency. Molecular repair, assessed by a microscopy-based unscheduled DNA synthesis (UDS) response, was measured within proliferative and nonproliferative marrow myeloid elements of dogs with markedly different hematopoietic capacities (low capacity, aplasia-prone [AA + ] versus high capacity, myeloproliferative disease-prone [MPD + ]) under protracted radiation stress. Results indicated that protracted exposure elicited a net increase in UDS-repair capacity that was largely independent of exposure duration. This enhanced capacity resulted from the increased strength of the UDS signal together with an expanded number of positively responding cells. The combined response was strong in primitive blasts and weak in more differentiated myelocytic cells. The UDS repair response of the MPD + dogs was significantly greater than that of the AA + animals and was clearly modified relative to the controls. These results suggest that both resiliency and pathologic potential of the hematopoietic system under protracted radiation stress is, in part, associated with an augmentable DNA repair within the more primitive myeloid marrow elements. (author)

  19. 49 CFR 1242.42 - Administration, repair and maintenance, machinery repair, equipment damaged, dismantling retired...

    Science.gov (United States)

    2010-10-01

    ... repair, equipment damaged, dismantling retired property, fringe benefits, other casualties and insurance, lease rentals, joint facility rents, other rents, depreciation, joint facility, repairs billed to others... maintenance, machinery repair, equipment damaged, dismantling retired property, fringe benefits, other...

  20. The biomechanical effects of polytetrafluoroethylene suture augmentations in lateral-row rotator cuff repairs in an ovine model.

    Science.gov (United States)

    Beimers, Lijkele; Lam, Patrick H; Murrell, George A C

    2014-10-01

    This study investigated the biomechanical effects of expanded polytetrafluoroethylene (ePTFE) suture augmentation patches in rotator cuff repair constructs. The infraspinatus tendon in 24 cadaveric ovine shoulders was repaired using an inverted horizontal mattress suture with 2 knotless bone anchors (ArthroCare, Austin, TX, USA) in a lateral-row configuration. Four different repair groups (6 per group) were created: (1) standard repair using inverted horizontal mattress sutures, (2) repair with ePTFE suture augmentations on the bursal side of the tendon, (3) repair with ePTFE suture augmentations on the articular side, and, (4) repair with ePTFE suture augmentations on both sides of the tendon. Footprint contact pressure, stiffness, and the load to failure of the repair constructs were measured. Repairs with ePTFE suture augmentations on the bursal side exerted significantly more footprint contact pressure (0.40 ± 0.01 MPa) than those on the articular side (0.34 ± 0.02 MPa, P = .04) and those on both sides (0.33 ± 0.02 MPa, P = .01). At 15 degrees of abduction, ePTFE-augmented repairs on the bursal side had higher footprint contact pressure (0.26 ± 0.03 MPa) compared with standard repairs (0.15 ± 0.02 MPa, P = .01) and with ePTFE-augmented repairs on the articular side (0.18 ± 0.02 MPa, P = .03). The ePTFE-augmented repairs on the bursal side demonstrated significantly higher failure loads (178 ± 18 N) than standard repairs (120 ± 17 N, P = .04). Inverted horizontal mattress sutures augmented with ePTFE patches on the bursal side of the tendon enhanced footprint contact pressures and the ultimate load to failure of lateral-row rotator cuff repairs in an ovine model. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  1. Imaging of cartilage repair procedures

    International Nuclear Information System (INIS)

    Sanghvi, Darshana; Munshi, Mihir; Pardiwala, Dinshaw

    2014-01-01

    The rationale for cartilage repair is to prevent precocious osteoarthritis in untreated focal cartilage injuries in the young and middle-aged population. The gamut of surgical techniques, normal postoperative radiological appearances, and possible complications have been described. An objective method of recording the quality of repair tissue is with the magnetic resonance observation of cartilage repair tissue (MOCART) score. This scoring system evaluates nine parameters that include the extent of defect filling, border zone integration, signal intensity, quality of structure and surface, subchondral bone, subchondral lamina, and records presence or absence of synovitis and adhesions. The five common techniques of cartilage repair currently offered include bone marrow stimulation (microfracture or drilling), mosaicplasty, synthetic resorbable scaffold grafts, osteochondral allograft transplants, and autologous chondrocyte implantation (ACI). Complications of cartilage repair procedures that may be demonstrated on magnetic resonance imaging (MRI) include plug loosening, graft protuberance, graft depression, and collapse in mosaicplasty, graft hypertrophy in ACI, and immune response leading to graft rejection, which is more common with synthetic grafts and cadaveric allografts

  2. Reprogramming Cells for Brain Repair

    Directory of Open Access Journals (Sweden)

    Randall D. McKinnon

    2013-08-01

    Full Text Available At present there are no clinical therapies that can repair traumatic brain injury, spinal cord injury or degenerative brain disease. While redundancy and rewiring of surviving circuits can recover some lost function, the brain and spinal column lack sufficient endogenous stem cells to replace lost neurons or their supporting glia. In contrast, pre-clinical studies have demonstrated that exogenous transplants can have remarkable efficacy for brain repair in animal models. Mesenchymal stromal cells (MSCs can provide paracrine factors that repair damage caused by ischemic injury, and oligodendrocyte progenitor cell (OPC grafts give dramatic functional recovery from spinal cord injury. These studies have progressed to clinical trials, including human embryonic stem cell (hESC-derived OPCs for spinal cord repair. However, ESC-derived allografts are less than optimal, and we need to identify a more appropriate donor graft population. The cell reprogramming field has developed the ability to trans-differentiate somatic cells into distinct cell types, a technology that has the potential to generate autologous neurons and glia which address the histocompatibility concerns of allografts and the tumorigenicity concerns of ESC-derived grafts. Further clarifying how cell reprogramming works may lead to more efficient direct reprogram approaches, and possibly in vivo reprogramming, in order to promote brain and spinal cord repair.

  3. Systemic levels of the anti-inflammatory decoy receptor soluble RAGE (receptor for advanced glycation end products) are decreased in dogs with inflammatory bowel disease.

    Science.gov (United States)

    Heilmann, Romy M; Otoni, Cristiane C; Jergens, Albert E; Grützner, Niels; Suchodolski, Jan S; Steiner, Jörg M

    2014-10-15

    Inflammatory bowel disease (IBD) is a common condition in dogs, and a dysregulated innate immunity is believed to play a major role in its pathogenesis. S100A12 is an endogenous damage-associated molecular pattern molecule, which is involved in phagocyte activation and is increased in serum/fecal samples from dogs with IBD. S100A12 binds to the receptor of advanced glycation end products (RAGE), a pattern-recognition receptor, and results of studies in human patients with IBD and other conditions suggest a role of RAGE in chronic inflammation. Soluble RAGE (sRAGE), a decoy receptor for inflammatory proteins (e.g., S100A12) that appears to function as an anti-inflammatory molecule, was shown to be decreased in human IBD patients. This study aimed to evaluate serum sRAGE and serum/fecal S100A12 concentrations in dogs with IBD. Serum and fecal samples were collected from 20 dogs with IBD before and after initiation of medical treatment and from 15 healthy control dogs. Serum sRAGE and serum and fecal S100A12 concentrations were measured by ELISA, and were compared between dogs with IBD and healthy controls, and between dogs with a positive outcome (i.e., clinical remission, n=13) and those that were euthanized (n=6). The relationship of serum sRAGE concentrations with clinical disease activity (using the CIBDAI scoring system), serum and fecal S100A12 concentrations, and histologic disease severity (using a 4-point semi-quantitative grading system) was tested. Serum sRAGE concentrations were significantly lower in dogs with IBD than in healthy controls (p=0.0003), but were not correlated with the severity of histologic lesions (p=0.4241), the CIBDAI score before (p=0.0967) or after treatment (p=0.1067), the serum S100A12 concentration before (p=0.9214) and after treatment (p=0.4411), or with the individual outcome (p=0.4066). Clinical remission and the change in serum sRAGE concentration after treatment were not significantly associated (p=0.5727); however, serum s

  4. Cartilage repair: Generations of autologous chondrocyte transplantation

    International Nuclear Information System (INIS)

    Marlovits, Stefan; Zeller, Philip; Singer, Philipp; Resinger, Christoph; Vecsei, Vilmos

    2006-01-01

    Articular cartilage in adults has a limited capacity for self-repair after a substantial injury. Surgical therapeutic efforts to treat cartilage defects have focused on delivering new cells capable of chondrogenesis into the lesions. Autologous chondrocyte transplantation (ACT) is an advanced cell-based orthobiologic technology used for the treatment of chondral defects of the knee that has been in clinical use since 1987 and has been performed on 12,000 patients internationally. With ACT, good to excellent clinical results are seen in isolated post-traumatic lesions of the knee joint in the younger patient, with the formation of hyaline or hyaline-like repair tissue. In the classic ACT technique, chondrocytes are isolated from small slices of cartilage harvested arthroscopically from a minor weight-bearing area of the injured knee. The extracellular matrix is removed by enzymatic digestion, and the cells are then expanded in monolayer culture. Once a sufficient number of cells has been obtained, the chondrocytes are implanted into the cartilage defect, using a periosteal patch over the defect as a method of cell containment. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. Further improvements in tissue engineering have contributed to the next generation of ACT techniques, where cells are combined with resorbable biomaterials, as in matrix-associated autologous chondrocyte transplantation (MACT). These biomaterials secure the cells in the defect area and enhance their proliferation and differentiation

  5. Cartilage repair: Generations of autologous chondrocyte transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Marlovits, Stefan [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)]. E-mail: stefan.marlovits@meduniwien.ac.at; Zeller, Philip [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Singer, Philipp [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Resinger, Christoph [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Vecsei, Vilmos [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2006-01-15

    Articular cartilage in adults has a limited capacity for self-repair after a substantial injury. Surgical therapeutic efforts to treat cartilage defects have focused on delivering new cells capable of chondrogenesis into the lesions. Autologous chondrocyte transplantation (ACT) is an advanced cell-based orthobiologic technology used for the treatment of chondral defects of the knee that has been in clinical use since 1987 and has been performed on 12,000 patients internationally. With ACT, good to excellent clinical results are seen in isolated post-traumatic lesions of the knee joint in the younger patient, with the formation of hyaline or hyaline-like repair tissue. In the classic ACT technique, chondrocytes are isolated from small slices of cartilage harvested arthroscopically from a minor weight-bearing area of the injured knee. The extracellular matrix is removed by enzymatic digestion, and the cells are then expanded in monolayer culture. Once a sufficient number of cells has been obtained, the chondrocytes are implanted into the cartilage defect, using a periosteal patch over the defect as a method of cell containment. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. Further improvements in tissue engineering have contributed to the next generation of ACT techniques, where cells are combined with resorbable biomaterials, as in matrix-associated autologous chondrocyte transplantation (MACT). These biomaterials secure the cells in the defect area and enhance their proliferation and differentiation.

  6. Advanced Strategies for Articular Cartilage Defect Repair

    Directory of Open Access Journals (Sweden)

    Fergal J. O'Brien

    2013-02-01

    Full Text Available Articular cartilage is a unique tissue owing to its ability to withstand repetitive compressive stress throughout an individual’s lifetime. However, its major limitation is the inability to heal even the most minor injuries. There still remains an inherent lack of strategies that stimulate hyaline-like articular cartilage growth with appropriate functional properties. Recent scientific advances in tissue engineering have made significant steps towards development of constructs for articular cartilage repair. In particular, research has shown the potential of biomaterial physico-chemical properties significantly influencing the proliferation, differentiation and matrix deposition by progenitor cells. Accordingly, this highlights the potential of using such properties to direct the lineage towards which such cells follow. Moreover, the use of soluble growth factors to enhance the bioactivity and regenerative capacity of biomaterials has recently been adopted by researchers in the field of tissue engineering. In addition, gene therapy is a growing area that has found noteworthy use in tissue engineering partly due to the potential to overcome some drawbacks associated with current growth factor delivery systems. In this context, such advanced strategies in biomaterial science, cell-based and growth factor-based therapies that have been employed in the restoration and repair of damaged articular cartilage will be the focus of this review article.

  7. Analytical and numerical study concerning the behaviour of single-sided bonded patch repairs

    Directory of Open Access Journals (Sweden)

    Gheorghi OPATCHI

    2011-06-01

    Full Text Available Adhesive bonded joints are used in the assembling of structural parts, especially of those which are made from dissimilar materials. Lightweight fibre reinforced polymer composites and other adhesive bonded components represent a major proportion of a modern aircraft. Bonded patch repair technology has been widely used to repair cracked thin-walled structures to extend their service life, because a correctly executed repair significantly enhances the structural performance.In practice, the single-sided bonded patch repair is the most used because a good solution like the double-sided repair may not be an option if the access to the structure is only available from one side.This paper presents a relatively simple and effective design procedure for the single strapped bonded joints. Also, the influence of various geometrical parameters of the joint is evaluated. The analytical development is validated based on nonlinear finite element analyses.

  8. DNA repair in PHA stimulated human lymphocytes

    International Nuclear Information System (INIS)

    Catena, C.; Mattoni, A.

    1984-01-01

    Damage an repair of radiation induced DNA strand breaks were measured by alkaline lysis and hydroxyapatite chromatography. PHA stimulated human lymphocytes show that the rejoining process is complete within the first 50 min., afterwords secondary DNA damage and chromatid aberration. DNA repair, in synchronized culture, allows to evaluate individual repair capacity and this in turn can contribute to the discovery of individual who, although they do not demonstrate apparent clinical signs, are carriers of DNA repair deficiency. Being evident that a correlation exists between DNA repair capacity and carcinogenesis, the possibility of evaluating the existent relationship between DNA repair and survival in tumor cells comes therefore into discussion

  9. Role of DNA repair in repair of cytogenetic damages. Contribution of repair of single-strand DNA breaks to cytogenetic damages repair

    International Nuclear Information System (INIS)

    Rozanova, O.M.; Zaichkina, S.I.; Aptikaev, G.F.; Ganassi, E.Eh.

    1989-01-01

    The comparison was made between the results of the effect of poly(ADP-ribosylation) ingibitors (e.g. nicotinamide and 3-aminobenzamide) and a chromatin proteinase ingibitor, phenylmethylsulfonylfluoride, on the cytogenetic damages repair, by a micronuclear test, and DNA repair in Chinese hamster fibroblasts. The values of the repair half-periods (5-7 min for the cytogenetic damages and 5 min for the rapidly repaired DNA damages) and a similar modyfying effect with regard to radiation cytogenetic damages and kynetics of DNA damages repair were found to be close. This confirms the contribution of repair of DNA single-strand breaks in the initiation of structural damages to chromosomes

  10. Incore inspection and repairing device

    International Nuclear Information System (INIS)

    Ito, Arata; Kimura, Motohiko

    1998-01-01

    The present invention provides a device for inspecting and repairing the inside of a reactor container even if it is narrow, with no trouble by using a swimming-type operation robot. Namely, the device of the present invention conducts inspection and repairing operations for the inside of the reactor by introducing a swimming type operation robot into the reactor container. The swimming-type operation robot comprises a robot main body having a propeller, a balancer operably disposed to the robot main body and an inspection and repairing unit attached detachable to the balancer. In the device of the present invention, since the inspection and preparing unit is attached detachably to the swimming robot, a robot which transports tools is formed as a standard product. As a result, the production cost can be reduced, and the reliability of products can be improved. Appropriate operations can be conducted by using best tools. (I.S.)

  11. Mitochondrial DNA repair and aging

    International Nuclear Information System (INIS)

    Mandavilli, Bhaskar S.; Santos, Janine H.; Van Houten, Bennett

    2002-01-01

    The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis

  12. Mitochondrial DNA repair and aging

    Energy Technology Data Exchange (ETDEWEB)

    Mandavilli, Bhaskar S.; Santos, Janine H.; Van Houten, Bennett

    2002-11-30

    The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis.

  13. Primary unilateral cleft lip repair

    OpenAIRE

    Adenwalla, H. S.; Narayanan, P. V.

    2009-01-01

    The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform clos...

  14. Studies on DNA repair in Bacillus subtilis

    International Nuclear Information System (INIS)

    Inoue, Tadashi; Kada, Tsuneo

    1977-01-01

    An enzyme which enhances the priming activity of γ-irradiated DNA for type I DNA polymerase (EC 2.7.7.7) was identified and partially purified from extracts of Bacillus subtilis cells. The enzyme preferentially degraded γ-irradiated DNA into acid-soluble materials. DNA preparations treated with heat, ultraviolet light, pancreatic DNAase (EC 3.1.4.5) or micrococcal DNAase (EC 3.1.4.7) were not susceptible to the enzyme. However, sonication rendered DNA susceptible to the enzyme to some extent. From these results, it is supposed that this enzyme may function by 'cleaning' damaged terminals produced by γ-irradiation to serve as effective primer of sites for repair synthesis by the type I DNA polymerase

  15. Genetics of x-ray induced double strand break repair in saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Budd, M.E.

    1982-07-01

    The possible fates of x-ray-induced double-strand breaks in Saccharomyces cerevisiae were examined. One possible pathway which breaks can follow, the repair pathway, was studied by assaying strains with mutations in the RAD51, RAD54, and RAD57 loci for double-strand break repair. In order of increasing radiation sensitivity one finds: rad57-1(23 0 )> rad51-1(30 0 )> rad54-3(36 0 ). At 36 0 , rad54-3 cells cannot repair double-strand breaks, while 23 0 , they can. Strains with the rad57-1 mutation can rejoin broken chromosomes at both temperatures. However, the low survival at 36 0 shows that the assay is not distinguishing large DNA fragments which allow cell survival from those which cause cell death. A rad51-1 strain could also rejoin broken chromosomes, and was thus capable of incomplete repair. The data can be explained with the hypothesis that rad54-3 cells are blocked in an early step of repair, while rad51-1 and rad57-1 strains are blocked in a later step of repair. The fate of double-strand breaks when they are left unrepaired was investigated with the rad54-3 mutation. If breaks are prevented from entering the RAD54 repair pathway they become uncommitted lesions. These lesions are repaired slower than the original breaks. One possible fate for an uncommitted lesion is conversion into a fixed lesion, which is likely to be an unrepairable or misrepaired double-strand break. The presence of protein synthesis after irradiation increases the probability that a break will enter the repair pathway. Evidence shows that increased probability of repair results from enhanced synthesis of repair proteins shortly after radiation

  16. Validation of newly developed physical laparoscopy simulator in transabdominal preperitoneal (TAPP) inguinal hernia repair.

    Science.gov (United States)

    Nishihara, Yuichi; Isobe, Yoh; Kitagawa, Yuko

    2017-12-01

    A realistic simulator for transabdominal preperitoneal (TAPP) inguinal hernia repair would enhance surgeons' training experience before they enter the operating theater. The purpose of this study was to create a novel physical simulator for TAPP inguinal hernia repair and obtain surgeons' opinions regarding its efficacy. Our novel TAPP inguinal hernia repair simulator consists of a physical laparoscopy simulator and a handmade organ replica model. The physical laparoscopy simulator was created by three-dimensional (3D) printing technology, and it represents the trunk of the human body and the bendability of the abdominal wall under pneumoperitoneal pressure. The organ replica model was manually created by assembling materials. The TAPP inguinal hernia repair simulator allows for the performance of all procedures required in TAPP inguinal hernia repair. Fifteen general surgeons performed TAPP inguinal hernia repair using our simulator. Their opinions were scored on a 5-point Likert scale. All participants strongly agreed that the 3D-printed physical simulator and organ replica model were highly useful for TAPP inguinal hernia repair training (median, 5 points) and TAPP inguinal hernia repair education (median, 5 points). They felt that the simulator would be effective for TAPP inguinal hernia repair training before entering the operating theater. All surgeons considered that this simulator should be introduced in the residency curriculum. We successfully created a physical simulator for TAPP inguinal hernia repair training using 3D printing technology and a handmade organ replica model created with inexpensive, readily accessible materials. Preoperative TAPP inguinal hernia repair training using this simulator and organ replica model may be of benefit in the training of all surgeons. All general surgeons involved in the present study felt that this simulator and organ replica model should be used in their residency curriculum.

  17. DNA damage and repair in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Szaflik, Jacek P. [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Zaras, Magdalena [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Wozniak, Katarzyna [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Szaflik, Jerzy [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Blasiak, Janusz, E-mail: januszb@biol.uni.lodz.pl [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland)

    2009-10-02

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  18. DNA damage and repair in age-related macular degeneration

    International Nuclear Information System (INIS)

    Szaflik, Jacek P.; Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika; Zaras, Magdalena; Wozniak, Katarzyna; Szaflik, Jerzy; Blasiak, Janusz

    2009-01-01

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  19. Niobium, catalyst repair kit

    International Nuclear Information System (INIS)

    Tanabe, K.

    1991-01-01

    This paper reports that niobium oxides, when small amounts are added to known catalysts, enhance catalytic activity and selectivity and prolong catalyst life. Moreover, niobium oxides exhibit a pronounced effect as supports of metal or metal oxide catalysts. Recently we found that the surface acidity of hydrated niobium pentoxide, niobic acid (Nb 2 O 5 · nH 2 O), corresponds to the acidity of 70% sulfuric acid and exhibits high catalytic activity, selectivity, and stability for acid-catalyzed reactions in which water molecules participate. Although there are few differences in electronegativity and ionic radius between niobium and its neighbors in the periodic table, it is interesting that the promoter effect, support effect, and acidic nature of niobium compounds are quite different from those of compounds of the surrounding elements. Here we review what's known of niobium compounds from the viewpoint of their pronounced catalytic behavior

  20. Some important advances in DNA repair study on the mammalian cells

    International Nuclear Information System (INIS)

    Xia Shouxuan.

    1991-01-01

    In the recent years the study of DNA damage and repair in the mammalian cells has gone deeply at gene level and got the following advances: (1) For a long time DNA has been considered to be an uniform unit in case of damage and repair. Now this concept should be replaced by the non-random distribution of damage and heterogenous repair in the genome. These would allow us to study cellular mutagenesis, carcinogenesis, aging and dying processes in great detail, and would be beneficial to the elucidation of mechanisms of radiation sickness and chemical toxicology. (2) The advent of new techniques in molecular biology has made it possible to isolate and clone the human DNA repair genes. Up to now more than ten human DNA repair genes have been cloned and these works would have an important impact on the theoretical and practical study in this field. Because DNA repair system is very complicate, voluminous work should be done in the future. (3) The technique of gene transfer has been efficiently used in the study of DNA repair in mammalian cells and has made great contribution in the cellular engineering. It could modify the genetic behavior of the gene-accepting cells, and enhance the DNA repair ability to physical and chemical damages. Human gene therapy for DNA deficient diseases is now on the day

  1. The Heterochromatic Barrier to DNA Double Strand Break Repair: How to Get the Entry Visa

    Directory of Open Access Journals (Sweden)

    Aaron A. Goodarzi

    2012-09-01

    Full Text Available Over recent decades, a deep understanding of pathways that repair DNA double strand breaks (DSB has been gained from biochemical, structural, biophysical and cellular studies. DNA non-homologous end-joining (NHEJ and homologous recombination (HR represent the two major DSB repair pathways, and both processes are now well understood. Recent work has demonstrated that the chromatin environment at a DSB significantly impacts upon DSB repair and that, moreover, dramatic modifications arise in the chromatin surrounding a DSB. Chromatin is broadly divided into open, transcriptionally active, euchromatin (EC and highly compacted, transcriptionally inert, heterochromatin (HC, although these represent extremes of a spectrum. The HC superstructure restricts both DSB repair and damage response signaling. Moreover, DSBs within HC (HC-DSBs are rapidly relocalized to the EC-HC interface. The damage response protein kinase, ataxia telangiectasia mutated (ATM, is required for HC-DSB repair but is dispensable for the relocalization of HC-DSBs. It has been proposed that ATM signaling enhances HC relaxation in the DSB vicinity and that this is a prerequisite for HC-DSB repair. Hence, ATM is essential for repair of HC-DSBs. Here, we discuss how HC impacts upon the response to DSBs and how ATM overcomes the barrier that HC poses to repair.

  2. Early postoperative repair status after rotator cuff repair cannot be accurately classified using questionnaires of patient function and isokinetic strength evaluation.

    Science.gov (United States)

    Colliver, Jessica; Wang, Allan; Joss, Brendan; Ebert, Jay; Koh, Eamon; Breidahl, William; Ackland, Timothy

    2016-04-01

    This study investigated if patients with an intact tendon repair or partial-thickness retear early after rotator cuff repair display differences in clinical evaluations and whether early tendon healing can be predicted using these assessments. We prospectively evaluated 60 patients at 16 weeks after arthroscopic supraspinatus repair. Evaluation included the Oxford Shoulder Score, 11-item version of the Disabilities of the Arm, Shoulder and Hand, visual analog scale for pain, 12-item Short Form Health Survey, isokinetic strength, and magnetic resonance imaging (MRI). Independent t tests investigated clinical differences in patients based on the Sugaya MRI rotator cuff classification system (grades 1, 2, or 3). Discriminant analysis determined whether intact repairs (Sugaya grade 1) and partial-thickness retears (Sugaya grades 2 and 3) could be predicted. No differences (P repair was intact. The ability to discriminate between groups was enhanced with up to 5 variables entered; however, only 87% of the partial-retear group and 36% of the intact-repair group were correctly classified. No differences in clinical scores existed between patients stratified by the Sugaya MRI classification system at 16 weeks. An intact repair or partial-thickness retear could not be accurately predicted. Our results suggest that correct classification of healing in the early postoperative stages should involve imaging. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  3. Outreach Materials for the Collision Repair Campaign

    Science.gov (United States)

    The Collision Repair Campaign offers outreach materials to help collision repair shops reduce toxic air exposure. Materials include a DVD, poster, training video, and materials in Spanish (materiales del outreach en español).

  4. Intern's Experiences with Episiotomy and its Repair

    African Journals Online (AJOL)

    repair is inadequately done, it may leave the woman suffering from perineal pain and other long term conditions with serious impact on the .... The maternity section had an average of ... with the job of performing episiotomy repair necessitating.

  5. Nucleotide excision repair in the test tube.

    NARCIS (Netherlands)

    N.G.J. Jaspers (Nicolaas); J.H.J. Hoeijmakers (Jan)

    1995-01-01

    textabstractThe eukaryotic nucleotide excision-repair pathway has been reconstituted in vitro, an achievement that should hasten the full enzymological characterization of this highly complex DNA-repair pathway.

  6. DNA excision repair as a component of adaptation to low doses of ionizing radiation Escherichia coli

    International Nuclear Information System (INIS)

    Huang, H.; Claycamp, H.G.

    1993-01-01

    In this study the authors examined whether or not DNA excision repair is a component of adaptation induced by very low-dose ionizing radiation in Escherichia coli, a well-characterized prokaryote, and investigated the relationship between enhanced excision repair and the SOS response. Their data suggest that there seems to be narrow 'windows' of dose-effect for the induction of SOS-independent DNA excision repair. Being similar to mammalian cell studies, the dose range for this effect was about 200-fold less than D 37 for radiation survival. (author)

  7. Role of nuclear hexokinase II in DNA repair

    International Nuclear Information System (INIS)

    Khanna, S.; Bhatt, A.N.; Dwarakanath, B.S.; Kalaiarasan, P.; Brahmachari, V.

    2012-01-01

    A common signature of many cancer cells is a high glucose catabolic rate primarily due to the over expression of Type II hexokinase (HKII; responsible for the phosphorylation of glucose), generally known as cytosolic and mitochondrial bound enzyme that also suppresses cell death. Although, nuclear localization and transcriptional regulation of HKII has been reported in yeast; we and few others have recently demonstrated its nuclear localization in malignant cell lines. Interestingly, modification of a human glioma cell line (BMG-1) for enhancing glycolysis through mitochondrial respiration (OPMBMG cells) resulted in a higher nuclear localization of HKII as compared to the parental cells with concomitant increase in DNA repair and radio-resistance. Further, the glucose phosphorylation activity of the nuclear HKII was nearly 2 folds higher in the relatively more radioresistant HeLa cells (human cervical cancer cell line) as compared to MRC-5 cells (human normal lung fibroblast cell line). Therefore, we hypothesize that nuclear HKII facilitates DNA repair, in a hither to unknown mechanism, that may partly contribute to the enhanced resistance of highly glycolytic cells to radiation. Sequence alignment studies suggest that the isoenzymes, HKI and HKII share strong homology in the kinase active site, which is also found in few protein kinases. Interestingly HKI has been shown to phosphorylate H2A in-vitro. Further, in-silico protein-protein interaction data suggest that HKII can interact with several DNA repair proteins including ATM. Taken together; available experimental evidences as well as in-silico predictions strongly suggest that HKII may play a role in DNA repair by phosphorylation of certain DNA repair proteins. (author)

  8. Regression Models for Repairable Systems

    Czech Academy of Sciences Publication Activity Database

    Novák, Petr

    2015-01-01

    Roč. 17, č. 4 (2015), s. 963-972 ISSN 1387-5841 Institutional support: RVO:67985556 Keywords : Reliability analysis * Repair models * Regression Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.782, year: 2015 http://library.utia.cas.cz/separaty/2015/SI/novak-0450902.pdf

  9. Microwave Oven Repair. Teacher Edition.

    Science.gov (United States)

    Smreker, Eugene

    This competency-based curriculum guide for teachers addresses the skills a technician will need to service microwave ovens and to provide customer relations to help retain the customer's confidence in the product and trust in the service company that performs the repair. The guide begins with a task analysis, listing 20 cognitive tasks and 5…

  10. Cloning human DNA repair genes

    International Nuclear Information System (INIS)

    Jeggo, P.A.; Carr, A.M.; Lehmann, A.R.

    1994-01-01

    Many human genes involved in the repair of UV damage have been cloned using different procedures and they have been of great value in assisting the understanding of the mechanism of nucleotide excision-repair. Genes involved in repair of ionizing radiation damage have proved more difficult to isolate. Positional cloning has localized the XRCC5 gene to a small region of chromosome 2q33-35, and a series of yeast artificial chromosomes covering this region have been isolated. Very recent work has shown that the XRCC5 gene encodes the 80 kDa subunit of the Ku DNA-binding protein. The Ku80 gene also maps to this region. Studies with fission yeast have shown that radiation sensitivity can result not only from defective DNA repair but also from abnormal cell cycle control following DNA damage. Several genes involved in this 'check-point' control in fission yeast have been isolated and characterized in detail. It is likely that a similar checkpoint control mechanism exists in human cells. (author)

  11. Pure robotic retrocaval ureter repair

    Directory of Open Access Journals (Sweden)

    Ashok k. Hemal

    2008-12-01

    Full Text Available PURPOSE: To demonstrate the feasibility of pure robotic retrocaval ureter repair. MATERIALS AND METHODS: A 33 year old female presented with right loin pain and obstruction on intravenous urography with the classical "fish-hook" appearance. She was counseled on the various methods of repair and elected to have a robot assisted repair. The following steps are performed during a pure robotic retrocaval ureter repair. The patient is placed in a modified flank position, pneumoperitoneum created and ports inserted. The colon is mobilized to expose the retroperitoneal structures: inferior vena cava, right gonadal vein, right ureter, and duodenum. The renal pelvis and ureter are mobilized and the renal pelvis transected. The ureter is transposed anterior to the inferior vena cava and a pyelopyelostomy is performed over a JJ stent. RESULTS: This patient was discharged on postoperative day 3. The catheter and drain tube were removed on day 1. Her JJ stent was removed at 6 weeks postoperatively. The postoperative intravenous urography at 3 months confirmed normal drainage of contrast medium. CONCLUSION: Pure robotic retrocaval ureter is a feasible procedure; however, there does not appear to be any great advantage over pure laparoscopy, apart from the ergonomic ease for the surgeon as well the simpler intracorporeal suturing.

  12. Discrete time analysis of a repairable machine

    OpenAIRE

    Alfa, Attahiru Sule; Castro, I. T.

    2002-01-01

    We consider, in discrete time, a single machine system that operates for a period of time represented by a general distribution. This machine is subject to failures during operations and the occurrence of these failures depends on how many times the machine has previously failed. Some failures are repairable and the repair times may or may not depend on the number of times the machine was previously repaired. Repair times also have a general distribution. The operating times...

  13. Repair of steam turbines by welding

    International Nuclear Information System (INIS)

    Bohnstedt, H.J.; Loebert, P.

    1987-01-01

    In some cases, turbine parts can be repaired by welding, even rotating parts such as the shaft or the blades. Practical examples of successful repair work are explained, as for instance: welding of the last web of the turbine wheel of two MD-rotors, repair of erosion damage on turbine blades, of solid-matter erosion on a medium-pressure blading, or welding repair of a high-pressure turbine casing. (DG) [de

  14. Recent advances in DNA repair and recombination.

    Science.gov (United States)

    Iwanejko, L A; Jones, N J

    1998-09-11

    The subjects of the talks at this 1-day DNA Repair Network meeting, held at City University, London on December 15, 1997, encompassed a range of topics and reflected some of the current areas of research in the United Kingdom. Topics included DNA double-strand break repair, V(D)J recombination, DNA ligases, the RecQ family of helicases and Bloom's syndrome, UVB and immunosuppression, the repair of oxidative damage and mismatch repair mechanisms.

  15. Use of Drosophila to study DNA repair

    International Nuclear Information System (INIS)

    Boyd, J.B.; Harris, P.V.; Sakaguchi, K.

    1988-01-01

    This paper discusses Drosophila, the premier metazoan organism for analyzing many fundamental features of eukaryotic gene regulation. The authors present adaptations of several approaches for studying DNA repair to an analysis of repair-defective mutants in Drosophila. A current understanding of Drosophila DNA repair is described

  16. 30 CFR 56.6801 - Vehicle repair.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Vehicle repair. 56.6801 Section 56.6801 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Vehicle repair. Vehicles containing explosive material and oxidizers shall not be taken into a repair...

  17. The two faces of plan repair

    NARCIS (Netherlands)

    Van der Krogt, R.P.J.; De Weerdt, M.M.

    2004-01-01

    Plan repair has two faces. Alternately, a plan repair method looks like a planning method, or looks like a method that does exactly the opposite, i.e., removing actions from a plan. We propose a general framework for plan repair that shows the relation between these two alternating steps. Any plan

  18. 30 CFR 57.14104 - Tire repairs.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Tire repairs. 57.14104 Section 57.14104 Mineral... Devices and Maintenance Requirements § 57.14104 Tire repairs. (a) Before a tire is removed from a vehicle for tire repair, the valve core shall be partially removed to allow for gradual deflation and then...

  19. 30 CFR 56.14104 - Tire repairs.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Tire repairs. 56.14104 Section 56.14104 Mineral... Devices and Maintenance Requirements § 56.14104 Tire repairs. (a) Before a tire is removed from a vehicle for tire repair, the valve core shall be partially removed to allow for gradual deflation and then...

  20. Cetuximab Induces Eme1-Mediated DNA Repair: a Novel Mechanism for Cetuximab Resistance

    Directory of Open Access Journals (Sweden)

    Agnieszka Weinandy

    2014-03-01

    Full Text Available Overexpression of the epidermal growth factor receptor (EGFR is observed in a large number of neoplasms. The monoclonal antibody cetuximab/Erbitux is frequently applied to treat EGFR-expressing tumors. However, the application of cetuximab alone or in combination with radio- and/or chemotherapy often yields only little benefit for patients. In the present study, we describe a mechanism that explains resistance of both tumor cell lines and cultured primary human glioma cells to cetuximab. Treatment of these cells with cetuximab promoted DNA synthesis in the absence of increased proliferation, suggesting that DNA repair pathways were activated. Indeed, we observed that cetuximab promoted the activation of the DNA damage response pathway and prevented the degradation of essential meiotic endonuclease 1 homolog 1 (Eme1, a heterodimeric endonuclease involved in DNA repair. The increased levels of Eme1 were necessary for enhanced DNA repair, and the knockdown of Eme1 was sufficient to prevent efficient DNA repair in response to ultraviolet-C light or megavoltage irradiation. These treatments reduced the survival of tumor cells, an effect that was reversed by cetuximab application. Again, this protection was dependent on Eme1. Taken together, these results suggest that cetuximab initiates pathways that result in the stabilization of Eme1, thereby resulting in enhanced DNA repair. Accordingly, cetuximab enhances DNA repair, reducing the effectiveness of DNA-damaging therapies. This aspect should be considered when using cetuximab as an antitumor agent and suggests that Eme1 is a negative predictive marker.

  1. Mediator MED23 Links Pigmentation and DNA Repair through the Transcription Factor MITF.

    Science.gov (United States)

    Xia, Min; Chen, Kun; Yao, Xiao; Xu, Yichi; Yao, Jiaying; Yan, Jun; Shao, Zhen; Wang, Gang

    2017-08-22

    DNA repair is related to many physiological and pathological processes, including pigmentation. Little is known about the role of the transcriptional cofactor Mediator complex in DNA repair and pigmentation. Here, we demonstrate that Mediator MED23 plays an important role in coupling UV-induced DNA repair to pigmentation. The loss of Med23 specifically impairs the pigmentation process in melanocyte-lineage cells and in zebrafish. Med23 deficiency leads to enhanced nucleotide excision repair (NER) and less DNA damage following UV radiation because of the enhanced expression and recruitment of NER factors to chromatin for genomic stability. Integrative analyses of melanoma cells reveal that MED23 controls the expression of a melanocyte master regulator, Mitf, by modulating its distal enhancer activity, leading to opposing effects on pigmentation and DNA repair. Collectively, the Mediator MED23/MITF axis connects DNA repair to pigmentation, thus providing molecular insights into the DNA damage response and skin-related diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Chemotherapeutic Drugs: DNA Damage and Repair in Glioblastoma.

    Science.gov (United States)

    Annovazzi, Laura; Mellai, Marta; Schiffer, Davide

    2017-05-26

    Despite improvements in therapeutic strategies, glioblastoma (GB) remains one of the most lethal cancers. The presence of the blood-brain barrier, the infiltrative nature of the tumor and several resistance mechanisms account for the failure of current treatments. Distinct DNA repair pathways can neutralize the cytotoxicity of chemo- and radio-therapeutic agents, driving resistance and tumor relapse. It seems that a subpopulation of stem-like cells, indicated as glioma stem cells (GSCs), is responsible for tumor initiation, maintenance and recurrence and they appear to be more resistant owing to their enhanced DNA repair capacity. Recently, attention has been focused on the pivotal role of the DNA damage response (DDR) in tumorigenesis and in the modulation of therapeutic treatment effects. In this review, we try to summarize the knowledge concerning the main molecular mechanisms involved in the removal of genotoxic lesions caused by alkylating agents, emphasizing the role of GSCs. Beside their increased DNA repair capacity in comparison with non-stem tumor cells, GSCs show a constitutive checkpoint expression that enables them to survive to treatments in a quiescent, non-proliferative state. The targeted inhibition of checkpoint/repair factors of DDR can contribute to eradicate the GSC population and can have a great potential therapeutic impact aiming at sensitizing malignant gliomas to treatments, improving the overall survival of patients.

  3. Science and animal models of marrow stimulation for cartilage repair.

    Science.gov (United States)

    Fortier, Lisa A; Cole, Brian J; McIlwraith, C Wayne

    2012-03-01

    Microfracture of subchondral bone to enhance cartilage repair is a popular surgical technique used in human and animal patients. Clinical results with resolution or improvement in pain are promising and last on average for 2 to 3 years. Animal studies aimed at understanding microfracture indicate that the repair tissue continues to remodel toward chondrogenesis for at least a year, but longer term results are not available to gain insight into the mechanism of microfracture function or failure over time. Subchondral bone sclerosis and central lesional osteophyte formation following subchondral bone microfracture have been observed in animal models of microfracture, but studies do not provide any insight into the etiology of these pathologies. The continued maturation of microfracture repair tissue over time supports further investigation of microfracture or microfracture-augmented cartilage repair procedures with caution for the investigator and clinician to be observant for conditions that lead to subchondral bone sclerosis or central osteophyte formation, and what affect these boney reactions have on clinical outcome.

  4. DNA repair in mutagen-injured higher plants

    International Nuclear Information System (INIS)

    Veleminsky, J.; Gichner, T.

    1978-01-01

    Data are summarized proving the occurrence of photoreactivation of UV-induced pyrimidine dimers in cells of Nicotiana tabucum, Gingko and carrot, the excision of dimers in cells of Nicotiana tabacum, Gingko and carrot, the excision of dimers in protoplasts of carrot and in embryos of Lathyrus sativus, and the repair of DNA single-strand breaks induced in carrot protoplasts and barley embryonic cells by ionizing radiation. In irradiated barley embryos the unscheduled DNA synthesis and higher accessibility of induced primers to DNA polymerase I of E. coli were observed preferentially in G 1 cells with diffused chromatin. These reactions were inhibited by caffeine and EDTA. Unscheduled DNA synthesis was also observed in synchronized irradiated root cuttings of Vicia faba and in barley embryos treated with 4-nitroquinoline oxide, the latter being inhibited by caffeine and hydroxyurea. Repair synthesis was also established in barley embryos treated with mutagenic N-methyl-N-nitrosourea under conditions that postponed the onset of germination after the treatment. The same conditions enhanced the repair of DNA single-strand breaks induced by this mutagen and several other monofunctional alkylating compounds. From tissues of barley and of Phaseolus multiflorus, endonucleases for apurinic sites were isolated and characterized. Some of them are located in chromatin, others in chloroplasts. The relation between DNA repair and genetic effects of mutagens in higher plants is also discussed. (Auth.)

  5. A vision on the future of articular cartilage repair

    Directory of Open Access Journals (Sweden)

    M Cucchiarini

    2014-05-01

    Full Text Available An AO Foundation (Davos, Switzerland sponsored workshop "Cell Therapy in Cartilage Repair" from the Symposium "Where Science meets Clinics" (September 5-7, 2013, Davos gathered leaders from medicine, science, industry, and regulatory organisations to debate the vision of cell therapy in articular cartilage repair and the measures that could be taken to narrow the gap between vision and current practice. Cell-based therapy is already in clinical use to enhance the repair of cartilage lesions, with procedures such as microfracture and articular chondrocyte implantation. However, even though long term follow up is good from a clinical perspective and some of the most rigorous randomised controlled trials in the regenerative medicine/orthopaedics field show beneficial effect, none of these options have proved successful in restoring the original articular cartilage structure and functionality in patients so far. With the remarkable recent advances in experimental research in cell biology (new sources for chondrocytes, stem cells, molecular biology (growth factors, genes, biomaterials, biomechanics, and translational science, a combined effort between scientists and clinicians with broad expertise may allow development of an improved cell therapy for cartilage repair. This position paper describes the current state of the art in the field to help define a procedure adapted to the clinical situation for upcoming translation in the patient.

  6. Thermosetting Polymer-Matrix Composites for Strucutral Repair Applications

    Energy Technology Data Exchange (ETDEWEB)

    Goertzen, William Kirby [Iowa State Univ., Ames, IA (United States)

    2007-12-01

    Several classes of thermosetting polymer matrix composites were evaluated for use in structural repair applications. Initial work involved the characterization and evaluation of woven carbon fiber/epoxy matrix composites for structural pipeline repair. Cyanate ester resins were evaluated as a replacement for epoxy in composites for high-temperature pipe repair applications, and as the basis for adhesives for resin infusion repair of high-temperature composite materials. Carbon fiber/cyanate ester matrix composites and fumed silica/cyanate ester nanocomposites were evaluated for their thermal, mechanical, viscoelastic, and rheological properties as they relate to their structure, chemistry, and processing characteristics. The bisphenol E cyanate ester under investigation possesses a high glass transition temperature, excellent mechanical properties, and unique ambient temperature processability. The incorporate of fumed silica served to enhance the mechanical and rheological properties of the polymer and reduce thermal expansion without sacrificing glass transition or drastically altering curing kinetics. Characterization of the composites included dynamic mechanical analysis, thermomechanical analysis, differential scanning calorimetry, thermogravimetric analysis, rheological and rheokinetic evaluation, and transmission electron microscopy.

  7. DNA repair and induction of plasminogen activator in human fetal cells treated with ultraviolet light

    International Nuclear Information System (INIS)

    Ben-Ishai, R.; Sharon, R.; Rothman, M.; Miskin, R.

    1984-01-01

    We have tested human fetal fibroblasts for development associated changes in DNA repair by utilizing nucleoid sedimentation as an assay for excision repair. Among skin fibroblasts the rate of excision repair was significantly higher in non-fetal cells than in fibroblasts derived from an 8 week fetus; this was evident by a delay in both the relaxation and the restoration of DNA supercoiling in nucleoids after irradiation. Skin fibroblasts derived at 12 week gestation were more repair proficient than those derived at 8 week gestation. However, they exhibited a somewhat lower rate of repair than non-fetal cells. The same fetal and non-fetal cells were also tested for induction of the protease plasminogen activator (PA) after u.v. irradiation. Enhancement of PA was higher in skin fibroblasts derived at 8 week than in those derived at 12 week gestation and was absent in non-fetal skin fibroblasts. These results are consistent with our previous findings that in human cells u.v. light-induced PA synthesis is correlated with reduced DNA repair capacity. Excision repair and PA inducibility were found to depend on tissue of origin in addition to gestational stage, as shown for skin and lung fibroblasts from the same 12 week fetus. Lung compared to skin fibroblasts exhibited lower repair rates and produced higher levels of PA after irradiation. The sedimentation velocity of nucleoids, prepared from unirradiated fibroblasts, in neutral sucrose gradients with or without ethidium bromide, indicated the presence of DNA strand breaks in fetal cells. It is proposed that reduced DNA repair in fetal cells may result from alterations in DNA supercoiling, and that persistent DNA strand breaks enhance transcription of PA gene(s)

  8. Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Karen L.; Dashner, Erica J. [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Tsosie, Ranalda [Department of Chemistry and Biochemistry, University of Montana, Missoula, MT 59812 (United States); Cho, Young Mi [Department of Food and Nutrition, College of Human Ecology, Hanyang University, Seoul 133-791 (Korea, Republic of); Lewis, Johnnye [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Community Environmental Health Program, University of New Mexico Health Sciences Center College of Pharmacy, Albuquerque, NM 87131 (United States); Hudson, Laurie G., E-mail: lhudson@salud.unm.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

    2016-01-15

    Uranium has radiological and non-radiological effects within biological systems and there is increasing evidence for genotoxic and carcinogenic properties attributable to uranium through its heavy metal properties. In this study, we report that low concentrations of uranium (as uranyl acetate; < 10 μM) is not cytotoxic to human embryonic kidney cells or normal human keratinocytes; however, uranium exacerbates DNA damage and cytotoxicity induced by hydrogen peroxide, suggesting that uranium may inhibit DNA repair processes. Concentrations of uranyl acetate in the low micromolar range inhibited the zinc finger DNA repair protein poly(ADP-ribose) polymerase (PARP)-1 and caused zinc loss from PARP-1 protein. Uranyl acetate exposure also led to zinc loss from the zinc finger DNA repair proteins Xeroderma Pigmentosum, Complementation Group A (XPA) and aprataxin (APTX). In keeping with the observed inhibition of zinc finger function of DNA repair proteins, exposure to uranyl acetate enhanced retention of induced DNA damage. Co-incubation of uranyl acetate with zinc largely overcame the impact of uranium on PARP-1 activity and DNA damage. These findings present evidence that low concentrations of uranium can inhibit DNA repair through disruption of zinc finger domains of specific target DNA repair proteins. This may provide a mechanistic basis to account for the published observations that uranium exposure is associated with DNA repair deficiency in exposed human populations. - Highlights: • Low micromolar concentration of uranium inhibits polymerase-1 (PARP-1) activity. • Uranium causes zinc loss from multiple DNA repair proteins. • Uranium enhances retention of DNA damage caused by ultraviolet radiation. • Zinc reverses the effects of uranium on PARP activity and DNA damage repair.

  9. Is laparoscopic inguinal hernia repair more effective than open repair

    International Nuclear Information System (INIS)

    Aly, O.; Green, A.; Joy, M.; Wong, C.H.; Malik, M

    2011-01-01

    To systematically review randomized controlled trials, (RCT) evidence comparing Lichtenstein to total extraperitoneal (TEP) hernia repair in terms of clinical and cost effectiveness. Study Design: Case series. Place and Duration of Study: The study was conducted at University of Abderdeen, U.K. Methodology: A comprehensive online literature search was undertaken using databases such as MEDLINE, PubMed, EMBASE and Springerlink. Studies were then short listed according to the selection criteria (RCT with over 100 subject and English language publications from 1995 onwards) and appraised using the SIGN Methodology Checklist. A meta analysis of the data was also performed using RevMan software. Results: Analysis of reported data shows that TEP has less postoperative pain and return to work than Lichtenstein method. Operation time is shown to be longer in the TEP but this difference is shortened with increasing surgeon experience. The meta-analysis of the data on complications shows that there are no significant differences between the two types of procedures. TEP causes more short-term recurrences which are attributed to the learning curve effect. Long term recurrence rates on the other hand show no significant differences. At present TEP is slightly more expensive than Lichtenstein repair. Conclusion: Both TEP and Lichtenstein repair are clinically effective procedures. The choice between them should be made on a case-by-case basis; which depends on the patient's preference and characteristics such as age, work and health status. (author)

  10. Complex networks under dynamic repair model

    Science.gov (United States)

    Chaoqi, Fu; Ying, Wang; Kun, Zhao; Yangjun, Gao

    2018-01-01

    Invulnerability is not the only factor of importance when considering complex networks' security. It is also critical to have an effective and reasonable repair strategy. Existing research on network repair is confined to the static model. The dynamic model makes better use of the redundant capacity of repaired nodes and repairs the damaged network more efficiently than the static model; however, the dynamic repair model is complex and polytropic. In this paper, we construct a dynamic repair model and systematically describe the energy-transfer relationships between nodes in the repair process of the failure network. Nodes are divided into three types, corresponding to three structures. We find that the strong coupling structure is responsible for secondary failure of the repaired nodes and propose an algorithm that can select the most suitable targets (nodes or links) to repair the failure network with minimal cost. Two types of repair strategies are identified, with different effects under the two energy-transfer rules. The research results enable a more flexible approach to network repair.

  11. Current Biomechanical Concepts for Rotator Cuff Repair

    Science.gov (United States)

    2013-01-01

    For the past few decades, the repair of rotator cuff tears has evolved significantly with advances in arthroscopy techniques, suture anchors and instrumentation. From the biomechanical perspective, the focus in arthroscopic repair has been on increasing fixation strength and restoration of the footprint contact characteristics to provide early rehabilitation and improve healing. To accomplish these objectives, various repair strategies and construct configurations have been developed for rotator cuff repair with the understanding that many factors contribute to the structural integrity of the repaired construct. These include repaired rotator cuff tendon-footprint motion, increased tendon-footprint contact area and pressure, and tissue quality of tendon and bone. In addition, the healing response may be compromised by intrinsic factors such as decreased vascularity, hypoxia, and fibrocartilaginous changes or aforementioned extrinsic compression factors. Furthermore, it is well documented that torn rotator cuff muscles have a tendency to atrophy and become subject to fatty infiltration which may affect the longevity of the repair. Despite all the aforementioned factors, initial fixation strength is an essential consideration in optimizing rotator cuff repair. Therefore, numerous biomechanical studies have focused on elucidating the strongest devices, knots, and repair configurations to improve contact characteristics for rotator cuff repair. In this review, the biomechanical concepts behind current rotator cuff repair techniques will be reviewed and discussed. PMID:23730471

  12. DNA single-strand breaks during repair of uv damage in human fibroblasts and abnormalities of repair in xeroderma pigmentosum

    International Nuclear Information System (INIS)

    Fornace, A.J. Jr.; Kohn, K.W.; Kann, H.E. Jr.

    1976-01-01

    The method of DNA alkaline elution was applied to a study of the formation and resealing of DNA single-strand breaks after irradiation of human fibroblasts with ultraviolet light (UV). The general features of the results were consistent with current concepts of DNA excision repair, in that breaks appeared rapidly after uv, and resealed slowly in normal fibroblasts, whereas breaks did not appear in those cells of patients with xeroderma pigmentosum (XP) that are known to have defects in DNA repair synthesis. The appearance of breaks required a short post-uv incubation, consistent with the expected action of an endonuclease. Cells of the variant form of XP characterized by normal DNA repair synthesis exhibited normal production of breaks after uv, but were slower than normal cells in resealing these breaks. This difference was enhanced by caffeine. A model is proposed to relate this finding with a previously described defect in post-replication repair in these XP variant cells. DNA crosslinking appears to cause an underestimate in the measurement of DNA breakage after uv

  13. Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells.

    Science.gov (United States)

    Browning, Cynthia L; Qin, Qin; Kelly, Deborah F; Prakash, Rohit; Vanoli, Fabio; Jasin, Maria; Wise, John Pierce

    2016-09-01

    Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels and Rad51 mislocalization to the cytoplasm. The response of proteins involved in Rad51 nuclear import and nucleofilament formation displayed varying responses to prolonged Cr(VI) exposure. BRCA2 formed nuclear foci after prolonged Cr(VI) exposure, while Rad51C foci formation was suppressed. These results suggest that particulate Cr(VI), a major chemical carcinogen, inhibits HR repair by targeting Rad51, causing DNA double strand breaks to be repaired by a low fidelity, Rad51-independent repair pathway. These results further enhance our understanding of the underlying mechanism of Cr(VI)-induced chromosome instability and thus, carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. [Constitutional mismatch repair deficiency syndrome].

    Science.gov (United States)

    Jongmans, Marjolijn C; Gidding, Corrie E; Loeffen, Jan; Wesseling, Pieter; Mensenkamp, Arjen; Hoogerbrugge, Nicoline

    2015-01-01

    Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. An 8-year-old girl was diagnosed with CMMR-D syndrome after she developed a brain tumour at the age of 4 and a T-cell non-Hodgkin lymphoma at the age of 6. She had multiple hyperpigmented skin lesions and died of myelodysplastic syndrome at the age of 11. In children with cancer CMMR-D syndrome can be recognized particularly if there are multiple primary malignancies and skin hyperpigmentations and hypopigmentations. The parents of these children are at high risk for colorectal and endometrial cancer (Lynch syndrome), amongst others.

  15. Mitochondrial base excision repair assays

    DEFF Research Database (Denmark)

    Maynard, Scott; de Souza-Pinto, Nadja C; Scheibye-Knudsen, Morten

    2010-01-01

    The main source of mitochondrial DNA (mtDNA) damage is reactive oxygen species (ROS) generated during normal cellular metabolism. The main mtDNA lesions generated by ROS are base modifications, such as the ubiquitous 8-oxoguanine (8-oxoG) lesion; however, base loss and strand breaks may also occur....... Many human diseases are associated with mtDNA mutations and thus maintaining mtDNA integrity is critical. All of these lesions are repaired primarily by the base excision repair (BER) pathway. It is now known that mammalian mitochondria have BER, which, similarly to nuclear BER, is catalyzed by DNA...... glycosylases, AP endonuclease, DNA polymerase (POLgamma in mitochondria) and DNA ligase. This article outlines procedures for measuring oxidative damage formation and BER in mitochondria, including isolation of mitochondria from tissues and cells, protocols for measuring BER enzyme activities, gene...

  16. Repair welding and online radiography

    International Nuclear Information System (INIS)

    Nuding, W.; Grimm, R.; Link, R.; Schroeder, P.; Schroeder, G.

    1990-01-01

    The status of a joint project is reported, which is to develop a computerized testing and welding system for repair work in turbine blades. An X-ray radiographic testing device consisting of microfocus tube, manipulator and image processing system, is modified for this purpose so as to offer a greater number of image points scanned for image processing, and to thus achieve a better resolution for reliable detection of even very small defects. The consistency of the X-ray tube performance, which is a pre-requisite for automation, is to be achieved by a wa tercooled, high-duty tube head. The recording of defect coordinates in the repair zone is done for input into a welding robot to be developed by other partners in the project, so as to allow automated welding work. (orig.) [de

  17. Primary unilateral cleft lip repair.

    Science.gov (United States)

    Adenwalla, H S; Narayanan, P V

    2009-10-01

    The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform closed alar dissection and extensive primary septoplasty in all these patients. This has improved the overall result and has no long-term deleterious effect on the growth of the nose or of the maxilla. Other refinements have been used for prevention of a high-riding nostril, and correction of the vestibular web.

  18. Primary unilateral cleft lip repair

    Directory of Open Access Journals (Sweden)

    Adenwalla H

    2009-10-01

    Full Text Available The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform closed alar dissection and extensive primary septoplasty in all these patients. This has improved the overall result and has no long-term deleterious effect on the growth of the nose or of the maxilla. Other refinements have been used for prevention of a high-riding nostril, and correction of the vestibular web.

  19. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    These antimicrobial peptides are implicated in the resistance of epithelial surfaces to microbial colonisation and have been shown to be upregulated...be equivalent to standard autograft repair in rodent models. Outcomes have now been validated in a large animal (swine) model with 5 cm ulnar nerve...Goals of the Project Task 1– Determine mechanical properties, seal strength and resistance to biodegradation of candidate photochemical nerve wrap

  20. Repair of EL4 leaks

    International Nuclear Information System (INIS)

    1985-03-01

    The reactor shutdown was decided on the 15th of November 1984, because the evolution of the carbon dioxide quantity in the helium blanket of the heavy water. Leaks have been localized on three different channels. Repairs have been made in hard conditions taking into account the reactor state (materials strongly irradiated). The restart has been authorized on the 24th of January 1985 [fr

  1. Silk film biomaterials for ocular surface repair

    Science.gov (United States)

    Lawrence, Brian David

    Current biomaterial approaches for repairing the cornea's ocular surface upon injury are partially effective due to inherent material limitations. As a result there is a need to expand the biomaterial options available for use in the eye, which in turn will help to expand new clinical innovations and technology development. The studies illustrated here are a collection of work to further characterize silk film biomaterials for use on the ocular surface. Silk films were produced from regenerated fibroin protein solution derived from the Bombyx mori silkworm cocoon. Methods of silk film processing and production were developed to produce consistent biomaterials for in vitro and in vivo evaluation. A wide range of experiments was undertaken that spanned from in vitro silk film material characterization to in vivo evaluation. It was found that a variety of silk film properties could be controlled through a water-annealing process. Silk films were then generated that could be use in vitro to produce stratified corneal epithelial cell sheets comparable to tissue grown on the clinical standard substrate of amniotic membrane. This understanding was translated to produce a silk film design that enhanced corneal healing in vivo on a rabbit injury model. Further work produced silk films with varying surface topographies that were used as a simplified analog to the corneal basement membrane surface in vitro. These studies demonstrated that silk film surface topography is capable of directing corneal epithelial cell attachment, growth, and migration response. Most notably epithelial tissue development was controllably directed by the presence of the silk surface topography through increasing cell sheet migration efficiency at the individual cellular level. Taken together, the presented findings represent a comprehensive characterization of silk film biomaterials for use in ocular surface reconstruction, and indicate their utility as a potential material choice in the

  2. Mutagenic DNA repair in enterobacteria

    International Nuclear Information System (INIS)

    Sedgwick, S.G.; Chao Ho; Woodgate, R.

    1991-01-01

    Sixteen species of enterobacteria have been screened for mutagenic DNA repair activity. In Escherichia coli, mutagenic DNA repair is encoded by the umuDC operon. Synthesis of UmuD and UmuC proteins is induced as part of the SOS response to DNA damage, and after induction, the UmuD protein undergoes an autocatalytic cleavage to produce the carboxy-terminal UmuD' fragment needed for induced mutagenesis. The presence of a similar system in other species was examined by using a combined approach of inducible-mutagenesis assays, cross-reactivity to E. coli UmuD and UmuD' antibodies to test for induction and cleavage of UmuD-like proteins, and hybridization with E. coli and Salmonella typhimurium u mu DNA probes to map umu-like genes. The results indicate a more widespread distribution of mutagenic DNA repair in other species than was previously thought. They also show that umu loci can be more complex in other species than in E. coli. Differences in UV-induced mutability of more than 200-fold were seen between different species of enteric bacteria and even between multiple natural isolates of E. coli, and yet some of the species which display a poorly mutable phenotype still have umu-like genes and proteins. It is suggested that umuDC genes can be curtailed in their mutagenic activities but that they may still participate in some other, unknown process which provides the continued stimulus for their retention

  3. Comparing Biomechanical Properties, Repair Times, and Value of Common Core Flexor Tendon Repairs.

    Science.gov (United States)

    Chauhan, Aakash; Schimoler, Patrick; Miller, Mark C; Kharlamov, Alexander; Merrell, Gregory A; Palmer, Bradley A

    2018-05-01

    The aim of the study was to compare biomechanical strength, repair times, and repair values for zone II core flexor tendon repairs. A total of 75 fresh-frozen human cadaveric flexor tendons were harvested from the index through small finger and randomized into one of 5 repair groups: 4-stranded cross-stitch cruciate (4-0 polyester and 4-0 braided suture), 4-stranded double Pennington (2-0 knotless barbed suture), 4-stranded Pennington (4-0 double-stranded braided suture), and 6-stranded modified Lim-Tsai (4-0 looped braided suture). Repairs were measured in situ and their repair times were measured. Tendons were linearly loaded to failure and multiple biomechanical values were measured. The repair value was calculated based on operating room costs, repair times, and suture costs. Analysis of variance (ANOVA) and Tukey post hoc statistical analysis were used to compare repair data. The braided cruciate was the strongest repair ( P > .05) but the slowest ( P > .05), and the 4-stranded Pennington using double-stranded suture was the fastest ( P > .05) to perform. The total repair value was the highest for braided cruciate ( P > .05) compared with all other repairs. Barbed suture did not outperform any repairs in any categories. The braided cruciate was the strongest of the tested flexor tendon repairs. The 2-mm gapping and maximum load to failure for this repair approached similar historical strength of other 6- and 8-stranded repairs. In this study, suture cost was negligible in the overall repair cost and should be not a determining factor in choosing a repair.

  4. Hsp90: A New Player in DNA Repair?

    Directory of Open Access Journals (Sweden)

    Rosa Pennisi

    2015-10-01

    Full Text Available Heat shock protein 90 (Hsp90 is an evolutionary conserved molecular chaperone that, together with Hsp70 and co-chaperones makes up the Hsp90 chaperone machinery, stabilizing and activating more than 200 proteins, involved in protein homeostasis (i.e., proteostasis, transcriptional regulation, chromatin remodeling, and DNA repair. Cells respond to DNA damage by activating complex DNA damage response (DDR pathways that include: (i cell cycle arrest; (ii transcriptional and post-translational activation of a subset of genes, including those associated with DNA repair; and (iii triggering of programmed cell death. The efficacy of the DDR pathways is influenced by the nuclear levels of DNA repair proteins, which are regulated by balancing between protein synthesis and degradation as well as by nuclear import and export. The inability to respond properly to either DNA damage or to DNA repair leads to genetic instability, which in turn may enhance the rate of cancer development. Multiple components of the DNA double strand breaks repair machinery, including BRCA1, BRCA2, CHK1, DNA-PKcs, FANCA, and the MRE11/RAD50/NBN complex, have been described to be client proteins of Hsp90, which acts as a regulator of the diverse DDR pathways. Inhibition of Hsp90 actions leads to the altered localization and stabilization of DDR proteins after DNA damage and may represent a cell-specific and tumor-selective radiosensibilizer. Here, the role of Hsp90-dependent molecular mechanisms involved in cancer onset and in the maintenance of the genome integrity is discussed and highlighted.

  5. Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium.

    Science.gov (United States)

    Cooper, Karen L; Dashner, Erica J; Tsosie, Ranalda; Cho, Young Mi; Lewis, Johnnye; Hudson, Laurie G

    2016-01-15

    Uranium has radiological and non-radiological effects within biological systems and there is increasing evidence for genotoxic and carcinogenic properties attributable to uranium through its heavy metal properties. In this study, we report that low concentrations of uranium (as uranyl acetate; uranium exacerbates DNA damage and cytotoxicity induced by hydrogen peroxide, suggesting that uranium may inhibit DNA repair processes. Concentrations of uranyl acetate in the low micromolar range inhibited the zinc finger DNA repair protein poly(ADP-ribose) polymerase (PARP)-1 and caused zinc loss from PARP-1 protein. Uranyl acetate exposure also led to zinc loss from the zinc finger DNA repair proteins Xeroderma Pigmentosum, Complementation Group A (XPA) and aprataxin (APTX). In keeping with the observed inhibition of zinc finger function of DNA repair proteins, exposure to uranyl acetate enhanced retention of induced DNA damage. Co-incubation of uranyl acetate with zinc largely overcame the impact of uranium on PARP-1 activity and DNA damage. These findings present evidence that low concentrations of uranium can inhibit DNA repair through disruption of zinc finger domains of specific target DNA repair proteins. This may provide a mechanistic basis to account for the published observations that uranium exposure is associated with DNA repair deficiency in exposed human populations. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Analysis and Modeling of Friction Stir Processing-Based Crack Repairing in 2024 Aluminum Alloy

    Institute of Scientific and Technical Information of China (English)

    Jun-Gang Ren; Lei Wang; Dao-Kui Xu; Li-Yang Xie; Zhan-Chang Zhang

    2017-01-01

    A friction stir processing-based method was used to repair cracks in the 2024 aluminum alloy plates.The temperature field and plastic material flow pattern were analyzed on the basis of experimental and finite element simulation results.Microstructure and tensile properties of the repaired specimens were studied.The results showed that the entire crack repairing was a solid-phase process and plastic materials tended to flow toward the shoulder center and then resulted in the repairing of cracks.Meanwhile,the coarse grain structures were refined in repaired zone (RZ),while the grains in thermal-mechanically affected zone and heat-affected zone were elongated and driven to grow up.Meanwhile,large phases are crushed into small particles and dispersed inside the RZ.Finally,the strength of the repaired specimens can be restored dramatically and their ductility can be partially restored.After heat treatment,the tensile properties of the repaired specimens can be further enhanced.

  7. The transcription fidelity factor GreA impedes DNA break repair.

    Science.gov (United States)

    Sivaramakrishnan, Priya; Sepúlveda, Leonardo A; Halliday, Jennifer A; Liu, Jingjing; Núñez, María Angélica Bravo; Golding, Ido; Rosenberg, Susan M; Herman, Christophe

    2017-10-12

    Homologous recombination repairs DNA double-strand breaks and must function even on actively transcribed DNA. Because break repair prevents chromosome loss, the completion of repair is expected to outweigh the transcription of broken templates. However, the interplay between DNA break repair and transcription processivity is unclear. Here we show that the transcription factor GreA inhibits break repair in Escherichia coli. GreA restarts backtracked RNA polymerase and hence promotes transcription fidelity. We report that removal of GreA results in markedly enhanced break repair via the classic RecBCD-RecA pathway. Using a deep-sequencing method to measure chromosomal exonucleolytic degradation, we demonstrate that the absence of GreA limits RecBCD-mediated resection. Our findings suggest that increased RNA polymerase backtracking promotes break repair by instigating RecA loading by RecBCD, without the influence of canonical Chi signals. The idea that backtracked RNA polymerase can stimulate recombination presents a DNA transaction conundrum: a transcription fidelity factor that compromises genomic integrity.

  8. DNA repair in Mycobacterium tuberculosis revisited.

    Science.gov (United States)

    Dos Vultos, Tiago; Mestre, Olga; Tonjum, Tone; Gicquel, Brigitte

    2009-05-01

    Our understanding of Mycobacterium tuberculosis DNA repair mechanisms is still poor compared with that of other bacterial organisms. However, the publication of the first complete M. tuberculosis genome sequence 10 years ago boosted the study of DNA repair systems in this organism. A first step in the elucidation of M. tuberculosis DNA repair mechanisms was taken by Mizrahi and Andersen, who identified homologs of genes involved in the reversal or repair of DNA damage in Escherichia coli and related organisms. Genes required for nucleotide excision repair, base excision repair, recombination, and SOS repair and mutagenesis were identified. Notably, no homologs of genes involved in mismatch repair were identified. Novel characteristics of the M. tuberculosis DNA repair machinery have been found over the last decade, such as nonhomologous end joining, the presence of Mpg, ERCC3 and Hlr - proteins previously presumed to be produced exclusively in mammalian cells - and the recently discovered bifunctional dCTP deaminase:dUTPase. The study of these systems is important to develop therapeutic agents that can counteract M. tuberculosis evolutionary changes and to prevent adaptive events resulting in antibiotic resistance. This review summarizes our current understanding of the M. tuberculosis DNA repair system.

  9. Treatment and Controversies in Paraesophageal Hernia Repair

    Directory of Open Access Journals (Sweden)

    P. Marco eFisichella

    2015-04-01

    Full Text Available Background: Historically all paraesophageal hernias were repaired surgically, today intervention is reserved for symptomatic paraesophageal hernias. In this review, we describe the indications for repair and explore the controversies in paraesophageal hernia repair, which include a comparison of open to laparoscopic paraesophageal hernia repair, the necessity of complete sac excision, the routine performance of fundoplication, and the use of mesh for hernia repair.Methods: We searched Pubmed for papers published between 1980 and 2015 using the following keywords: hiatal hernias, paraesophageal hernias, regurgitation, dysphagia, gastroesophageal reflux disease, aspiration, GERD, endoscopy, manometry, pH monitoring, proton pump inhibitors, anemia, iron deficiency anemia, Nissen fundoplication, sac excision, mesh, mesh repair. Results: Indications for paraesophageal hernia repair have changed, and currently symptomatic paraesophageal hernias are recommended for repair. In addition, it is important not to overlook iron-deficiency anemia and pulmonary complaints, which tend to improve with repair. Current practice favors a laparoscopic approach, complete sac excision, primary crural repair with or without use of mesh, and a routine fundoplication.

  10. Ultrasound determination of rotator cuff tear repairability

    Science.gov (United States)

    Tse, Andrew K; Lam, Patrick H; Walton, Judie R; Hackett, Lisa

    2015-01-01

    Background Rotator cuff repair aims to reattach the torn tendon to the greater tuberosity footprint with suture anchors. The present study aimed to assess the diagnostic accuracy of ultrasound in predicting rotator cuff tear repairability and to assess which sonographic and pre-operative features are strongest in predicting repairability. Methods The study was a retrospective analysis of measurements made prospectively in a cohort of 373 patients who had ultrasounds of their shoulder and underwent rotator cuff repair. Measurements of rotator cuff tear size and muscle atrophy were made pre-operatively by ultrasound to enable prediction of rotator cuff repairability. Tears were classified following ultrasound as repairable or irreparable, and were correlated with intra-operative repairability. Results Ultrasound assessment of rotator cuff tear repairability has a sensitivity of 86% (p tear size (p tear size ≥4 cm2 or anteroposterior tear length ≥25 mm indicated an irreparable rotator cuff tear. Conclusions Ultrasound assessment is accurate in predicting rotator cuff tear repairability. Tear size or anteroposterior tear length and age were the best predictors of repairability. PMID:27582996

  11. Additivity versus repair inhibition in fractionated treatments combining drugs and X rays: a theoretical analysis

    International Nuclear Information System (INIS)

    Begg, A.C.

    1987-01-01

    Drugs which inhibit the repair of radiation damage could potentially be useful for enhancing the effects of radiotherapy. In pre-clinical combined modality studies, however, it is often difficult to state with certainty whether or not a drug has inhibited radiation damage repair. This paper shows that several commonly used parameters for assessing repair can give the wrong answer regarding the presence of drug-induced repair inhibition. These parameters are; the difference in radiation dose between 1 and n fractions to give the same effect, the fractional recovered dose per fraction interval, FR, and the related parameter FREC. A further parameter used for treatment comparisons is the enhancement ratio for the drug (D.E.R.; ratio of radiation doses, with and without drug, to cause a given effect). An increasing D.E.R. with increasing number of radiation fractions has been taken as an indication that the drug inhibited repair. The present report demonstrates that this, too, can be misleading. From an analysis based on a linear-quadratic survival curve for X rays, it is suggested that deriving and comparing alpha/beta ratios (ratio of the linea to quadratic coefficients) gives the best indication of drug-induced changes in survival curve shape which may reflect underlying changes in repair capacity

  12. Self-repair in a Bidirectionally Coupled Astrocyte-Neuron (AN System based on Retrograde Signaling

    Directory of Open Access Journals (Sweden)

    John eWade

    2012-09-01

    Full Text Available In this paper we demonstrate that retrograde signaling via astrocytes may underpin self-repair in the brain. Faults manifest themselves in silent or near silent neurons caused by low transmission probability synapses; the enhancement of the transmission probability of a healthy neighbouring synapse by retrograde signaling can enhance the transmission probability of the faulty synapse (repair. Our model of self-repair is based on recent research showing that retrograde signaling via astrocytes can increase the probability of neurotransmitter release at damaged or low transmission probability synapses. The model demonstrates that astrocytes are capable of bidirectional communication with neurons which leads to modulation of synaptic activity, and that indirect signaling through retrograde messengers such as endocannabinoids leads to modulation of synaptic transmission probability. Although our model operates at the level of cells, it provides a new research direction on brain-like self-repair which can be extended to networks of astrocytes and neurons. It also provides a biologically inspired basis for developing highly adaptive, distributed computing systems that can, at fine levels of granularity, fault detect, diagnose and self-repair autonomously, without the traditional constraint of a central fault detect/repair unit.

  13. Intrinsic radiosensitivity and PLD repair in osteosarcoma cell lines

    International Nuclear Information System (INIS)

    Sugimoto, M.; Toguchida, J.; Kotoura, Y.; Yamamuro, T.; Utsumi, H.

    1992-01-01

    The response to radiation of seven osteosarcoma cell lines was analysed by in vitro colony-forming assay and compared with that of eight human fibroblast strains. The values of D 0 , the surviving fraction after 2 Gy (S2Gy), and the mean inactivation dose (D-bar) of osteosarcoma cells in log-phase culture were significantly higher than those of fibroblast strains (p<0.01). PLD (potentially lethal damage) repair of osteosarcoma cells evaluated in the plateau phase of growth showed great variation for enhancement of survival, although all of the values were maximised within 12 h after irradiation. In the osteosarcoma, intrinsic radiosensitivity in vitro reflected the clinical response to radiation. However, the capacity for PLD repair might not be a good indicator for predicting the results of radiation therapy. (author)

  14. A study of everyday repair: informing interaction design

    OpenAIRE

    Maestri, Leah Adriana

    2012-01-01

    Repair is typically seen in design as the restoration of broken objects to their original state. Repair by non-experts, or everyday repair, can often lead to novel forms of repair resulting in the creative repurposing of objects that are often unforeseen by designers. Using a grounded theory approach, this study describes key aspects of repair including: the techniques non-experts employ for repairing their objects; the motivations that prompt acts of repair; and the outcomes that result fr...

  15. Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription*

    Science.gov (United States)

    Nadkarni, Aditi; Burns, John A.; Gandolfi, Alberto; Chowdhury, Moinuddin A.; Cartularo, Laura; Berens, Christian; Geacintov, Nicholas E.; Scicchitano, David A.

    2016-01-01

    DNA adducts derived from carcinogenic polycyclic aromatic hydrocarbons like benzo[a]pyrene (B[a]P) and benzo[c]phenanthrene (B[c]Ph) impede replication and transcription, resulting in aberrant cell division and gene expression. Global nucleotide excision repair (NER) and transcription-coupled DNA repair (TCR) are among the DNA repair pathways that evolved to maintain genome integrity by removing DNA damage. The interplay between global NER and TCR in repairing the polycyclic aromatic hydrocarbon-derived DNA adducts (+)-trans-anti-B[a]P-N6-dA, which is subject to NER and blocks transcription in vitro, and (+)-trans-anti-B[c]Ph-N6-dA, which is a poor substrate for NER but also blocks transcription in vitro, was tested. The results show that both adducts inhibit transcription in human cells that lack both NER and TCR. The (+)-trans-anti-B[a]P-N6-dA lesion exhibited no detectable effect on transcription in cells proficient in NER but lacking TCR, indicating that NER can remove the lesion in the absence of TCR, which is consistent with in vitro data. In primary human cells lacking NER, (+)-trans-anti-B[a]P-N6-dA exhibited a deleterious effect on transcription that was less severe than in cells lacking both pathways, suggesting that TCR can repair the adduct but not as effectively as global NER. In contrast, (+)-trans-anti-B[c]Ph-N6-dA dramatically reduces transcript production in cells proficient in global NER but lacking TCR, indicating that TCR is necessary for the removal of this adduct, which is consistent with in vitro data showing that it is a poor substrate for NER. Hence, both global NER and TCR enhance the recovery of gene expression following DNA damage, and TCR plays an important role in removing DNA damage that is refractory to NER. PMID:26559971

  16. N-Butyrate alters chromatin accessibility to DNA repair enzymes

    International Nuclear Information System (INIS)

    Smith, P.J.

    1986-01-01

    Current evidence suggests that the complex nature of mammalian chromatin can result in the concealment of DNA damage from repair enzymes and their co-factors. Recently it has been proposed that the acetylation of histone proteins in chromatin may provide a surveillance system whereby damaged regions of DNA become exposed due to changes in chromatin accessibility. This hypothesis has been tested by: (i) using n-butyrate to induce hyperacetylation in human adenocarcinoma (HT29) cells; (ii) monitoring the enzymatic accessibility of chromatin in permeabilised cells; (iii) measuring u.v. repair-associated nicking of DNA in intact cells and (iv) determining the effects of n-butyrate on cellular sensitivity to DNA damaging agents. The results indicate that the accessibility of chromatin to Micrococcus luteus u.v. endonuclease is enhanced by greater than 2-fold in n-butyrate-treated cells and that there is a corresponding increase in u.v. repair incision rates in intact cells exposed to the drug. Non-toxic levels of n-butyrate induce a block to G1 phase transit and there is a significant growth delay on removal of the drug. Resistance of HT29 cells to u.v.-radiation and adriamycin is enhanced in n-butyrate-treated cells whereas X-ray sensitivity is increased. Although changes in the responses of cells to DNA damaging agents must be considered in relation to the effects of n-butyrate on growth rate and cell-cycle distribution, the results are not inconsistent with the proposal that increased enzymatic-accessibility/repair is biologically favourable for the resistance of cells to u.v.-radiation damage. Overall the results support the suggested operation of a histone acetylation-based chromatin surveillance system in human cells

  17. Influence of repair length on residual stress in the repair weld of a clad plate

    International Nuclear Information System (INIS)

    Jiang Wenchun; Xu, X.P.; Gong, J.M.; Tu, S.T.

    2012-01-01

    Highlights: ► Residual stress in the repair weld of a stainless steel clad plate is investigated. ► The effect of repair length on residual stress has been studied. ► Large tensile residual stress is generated in the repair weld and heat affected zone. ► With the increase of repair length, transverse stress is decreased. ► Repair length has little effect on longitudinal stress. - Abstract: A 3-D sequential coupling finite element simulation is performed to investigate the temperature field and residual stress in the repair weld of a stainless steel clad plate. The effect of repair length on residual stress has been studied, aiming to provide a reference for repairing the cracked clad plate. The results show that large tensile residual stresses are generated in the repair weld and heat affected zone (HAZ), and then decrease gradually away from the weld and HAZ. The residual stresses through thickness in the clad layer are relative uniform, while they are non-uniform in the base metal. A discontinuous stress distribution is generated across the interface between weld metal and base metal. The repair length has a great effect on transverse stress. With the increase of repair length, the transverse stress is decreased. When the repair length is increased to 14 cm, the peak of transverse stress has been decreased below yield strength, and the transverse stress in the weld and HAZ has also been greatly decreased. But the repair length has little effect on longitudinal stress.

  18. Laparoscopic repair for vesicouterine fistulae

    Directory of Open Access Journals (Sweden)

    Rafael A. Maioli

    2015-10-01

    Full Text Available ABSTRACT Objective: The purpose of this video is to present the laparoscopic repair of a VUF in a 42-year-old woman, with gross hematuria, in the immediate postoperative phase following a cesarean delivery. The obstetric team implemented conservative management, including Foley catheter insertion, for 2 weeks. She subsequently developed intermittent hematuria and cystitis. The urology team was consulted 15 days after cesarean delivery. Cystoscopy indicated an ulcerated lesion in the bladder dome of approximately 1.0cm in size. Hysterosalpingography and a pelvic computed tomography scan indicated a fistula. Materials and Methods: Laparoscopic repair was performed 30 days after the cesarean delivery. The patient was placed in the lithotomy position while also in an extreme Trendelenburg position. Pneumoperitoneum was established using a Veress needle in the midline infra-umbilical region, and a primary 11-mm port was inserted. Another 11-mm port was inserted exactly between the left superior iliac spine and the umbilicus. Two other 5-mm ports were established under laparoscopic guidance in the iliac fossa on both sides. The omental adhesions in the pelvis were carefully released and the peritoneum between the bladder and uterus was incised via cautery. Limited cystotomy was performed, and the specific sites of the fistula and the ureteral meatus were identified; thereafter, the posterior bladder wall was adequately mobilized away from the uterus. The uterine rent was then closed using single 3/0Vicryl sutures and two-layer watertight closure of the urinary bladder was achieved by using 3/0Vicryl sutures. An omental flap was mobilized and inserted between the uterus and the urinary bladder, and was fixed using two 3/0Vicryl sutures, followed by tube drain insertion. Results: The operative time was 140 min, whereas the blood loss was 100ml. The patient was discharged 3 days after surgery, and the catheter was removed 12 days after surgery

  19. Underwater coating repair cuts nuclear maintenance costs

    International Nuclear Information System (INIS)

    Stuart, C.O.

    1993-01-01

    This article discusses the cleaning and recoating/repair of condensate tanks or other vessels in a nuclear power plant. The topics of the article include the safety and regulatory need for this system of repair, a description of the work done on the Brown's Ferry MK-1 suppression chamber, coating failure mechanisms, qualitative inspection, quantitative inspection, quantitative inspection results, spot repairs, and economic considerations

  20. PTMC in post-MV repair status

    Directory of Open Access Journals (Sweden)

    Lachikarathman Devegowda

    2016-09-01

    Full Text Available MV repair in the rheumatic population is feasible with acceptable long-term results.1 Incidence of mitral stenosis (MS following mitral valve (MV repair for severe rheumatic mitral regurgitation (MR and usefulness of percutaneous transluminal mitral valvuloplasty (PTMC in these patients is not described in literature. We report a case of successful PTMC in severe MS following MV repair for severe rheumatic MR.

  1. Early discharge after external anal sphincter repair

    DEFF Research Database (Denmark)

    Rosenberg, J; Kehlet, H

    1999-01-01

    PURPOSE: The aim of this study was to describe an accelerated-stay program for repair of the external anal sphincter. METHODS: Twenty consecutive patients undergoing overlapping repair of the external anal sphincter were included in the study. Effect parameters were length of hospitalization....... CONCLUSION: We have described a safe accelerated-stay program (24 to 48 hours) for overlapping repair of external anal sphincter....

  2. Endogenous DNA Damage and Repair Enzymes

    Directory of Open Access Journals (Sweden)

    Arne Klungland

    2016-06-01

    Full Text Available Tomas Lindahl completed his medical studies at Karolinska Institute in 1970. Yet, his work has always been dedicated to unraveling fundamental mechanisms of DNA decay and DNA repair. His research is characterized with groundbreaking discoveries on the instability of our genome, the identification of novel DNA repair activities, the characterization of DNA repair pathways, and the association to diseases, throughout his 40 years of scientific career.

  3. Hepatopancreaticobiliary Values after Thoracoabdominal Aneurysm Repair

    OpenAIRE

    Wu, Darrell; Coselli, Joseph S.; Johnson, Michael L.; LeMaire, Scott A.

    2014-01-01

    Background: After thoracoabdominal aortic aneurysm (TAAA) repair, blood tests assessing hepatopancreaticobiliary (HPB) organs commonly have abnormal results. The clinical significance of such abnormalities is difficult to determine because the expected postoperative levels have not been characterized. Therefore, we sought to establish expected trends in HPB laboratory values after TAAA repair. Methods: This 5-year study comprised 155 patients undergoing elective Crawford extent II TAAA repair...

  4. * Hypoxia Biomimicry to Enhance Monetite Bone Defect Repair.

    Science.gov (United States)

    Drager, Justin; Ramirez-GarciaLuna, Jose Luis; Kumar, Abhishek; Gbureck, Uwe; Harvey, Edward J; Barralet, Jake E

    2017-12-01

    Tissue hypoxia is a critical driving force for angiogenic and osteogenic responses in bone regeneration and is, at least partly, under the control of the Hypoxia Inducible Factor-1α (HIF-1α) pathway. Recently, the widely used iron chelator deferoxamine (DFO) has been found to elevate HIF-1α levels independent of oxygen concentrations, thereby, creating an otherwise normal environment that mimics the hypoxic state. This has the potential to augment the biological properties of inorganic scaffolds without the need of recombinant growth factors. This pilot study investigates the effect of local delivery of DFO on bone formation and osseointegration of an anatomically matched bone graft substitute, in the treatment of segmental bone defects. Three-dimensional printing was used to create monetite grafts, which were implanted into 10 mm midshaft ulnar defects in eight rabbits. Starting postoperative day 4, one graft site in each animal was injected with 600 μL (200 μM) of DFO every 48 h for six doses. Saline was injected in the contralateral limb as a control. At 8 weeks, micro-CT and histology were used to determine new bone growth, vascularity, and assess osseointegration. Six animals completed the protocol. Bone metric analysis using micro-CT showed a significantly greater amount of new bone formed (19.5% vs. 13.65% p = 0.042) and an increase in bone-implant contact area (63.1 mm 2 vs. 33.2 mm 2 p = 0.03) in the DFO group compared with control. Vascular channel volume was significantly greater in the DFO group (20.9% vs. 16.2% p = 0.004). Histology showed increased bone formation within the osteotomy gap, more bone integrated with the graft surface as well as more matured soft tissue callus in the DFO group. This study demonstrates a significant increase in new bone formation after delivery of DFO in a rabbit long bone defect bridged by a 3D-printed bioresorbable bone graft substitute. Given the safety, ease of handling, and low expense of this medication, the results of this study support further investigation into the use of iron chelators in creating a biomimetic environment for bone healing in segmental bone loss.

  5. Biological methods to enhance bone healing and fracture repair.

    Science.gov (United States)

    Verdonk, René; Goubau, Yannick; Almqvist, Fredrik K; Verdonk, Peter

    2015-04-01

    This article looks into normal physiological fracture healing with special emphasis on the diamond concept. A precise definition of nonunion of long bones is described. Most often inadequate fixation (too rigid or too loose) is the reason for nonunion in long bone fractures. Because a critical bone defect cannot be bridged, it may lead directly or indirectly (lack of fixation) to nonunion. Individual inadequate local biological characteristics are also often found to be the cause; poor soft tissue coverage as well as a lack of periosteum and muscle or fascia or skin defects can lead to compromised vascularity in situ. Systemic factors are now much more recognized, e.g., smoking, diabetes, and cachexia, as well as the limited impact of some medications, e.g., nonsteroidal anti-inflammatory drugs and steroids. Today's mode of treatment for nonunion is approached in this article, and suggestions for appropriate treatment of long bone nonunion is presented. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  6. Chromatin dynamics during DSB repair

    Czech Academy of Sciences Publication Activity Database

    Falk, Martin; Lukášová, Emilie; Gabrielová, Barbora; Ondřej, Vladan; Kozubek, Stanislav

    2007-01-01

    Roč. 1773, č. 10 (2007), s. 1534-1545 ISSN 0167-4889 R&D Projects: GA ČR(CZ) GP204/06/P349; GA ČR(CZ) 1QS500040508; GA AV ČR(CZ) IAA1065203; GA MŠk(CZ) 1P05OC084 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : chromatin structure * double- strand breaks (DSB) * DNA repair Subject RIV: BO - Biophysics Impact factor: 4.374, year: 2007

  7. Root justifications for ontology repair

    CSIR Research Space (South Africa)

    Moodley, K

    2011-08-01

    Full Text Available stream_source_info Moodley_2011.pdf.txt stream_content_type text/plain stream_size 32328 Content-Encoding ISO-8859-1 stream_name Moodley_2011.pdf.txt Content-Type text/plain; charset=ISO-8859-1 Root Justi cations... the ontology, based on the no- tion of root justi cations [8, 9]. In Section 5, we discuss the implementation of a Prot eg e3 plugin which demonstrates our approach to ontology repair. In this section we also discuss some experimental results comparing...

  8. Concrete structures protection, repair and rehabilitation

    CERN Document Server

    Woodson, R Dodge

    2009-01-01

    The success of a repair or rehabilitation project depends on the specific plans designed for it. Concrete Structures: Protection, Repair and Rehabilitation provides guidance on evaluating the condition of the concrete in a structure, relating the condition of the concrete to the underlying cause or causes of that condition, selecting an appropriate repair material and method for any deficiency found, and using the selected materials and methods to repair or rehabilitate the structure. Guidance is also provided for engineers focused on maintaining concrete and preparing concrete investigation r

  9. DNA damage and repair in plants

    International Nuclear Information System (INIS)

    Britt, A.B.

    1996-01-01

    The biological impact of any DNA damaging agent is a combined function of the chemical nature of the induced lesions and the efficiency and accuracy of their repair. Although much has been learned frommicrobes and mammals about both the repair of DNA damage and the biological effects of the persistence of these lesions, much remains to be learned about the mechanism and tissue-specificity of repair in plants. This review focuses on recent work on the induction and repair of DNA damage in higher plants, with special emphasis on UV-induced DNA damage products. (author)

  10. DNA repair in non-mammalian animals

    International Nuclear Information System (INIS)

    Mitani, Hiroshi

    1984-01-01

    Studies on DNA repair have been performed using microorganisms such as Escherichia coli and cultured human and mammalian cells. However, it is well known that cultured organic cells differ from each other in many respects, although DNA repair is an extremely fundamental function of organisms to protect genetic information from environmental mutagens such as radiation and 0 radicals developing in the living body. To answer the question of how DNA repair is different between the animal species, current studies on DNA repair of cultured vertebrate cells using the methods similar to those in mammalian experiments are reviewed. (Namekawa, K.)

  11. Efficacy of a Cell-Cycle Decoying Killer Adenovirus on 3-D Gelfoam®-Histoculture and Tumor-Sphere Models of Chemo-Resistant Stomach Carcinomatosis Visualized by FUCCI Imaging.

    Directory of Open Access Journals (Sweden)

    Shuya Yano

    Full Text Available Stomach cancer carcinomatosis peritonitis (SCCP is a recalcitrant disease. The goal of the present study was to establish an in vitro-in vivo-like imageable model of SCCP to develop cell-cycle-based therapeutics of SCCP. We established 3-D Gelfoam® histoculture and tumor-sphere models of SCCP. FUCCI-expressing MKN-45 stomach cancer cells were transferred to express the fluorescence ubiquinized cell-cycle indicator (FUCCI. FUCCI-expressing MKN-45 cells formed spheres on agarose or on Gelfoam® grew into tumor-like structures with G0/G1 cancer cells in the center and S/G2 cancer cells located in the surface as indicated by FUCCI imaging when the cells fluoresced red or green, respectively. We treated FUCCI-expressing cancer cells forming SCCP tumors in Gelfoam® histoculture with OBP-301, cisplatinum (CDDP, or paclitaxel. CDDP or paclitaxel killed only cycling cancer cells and were ineffective against G1/G2 MKN-45 cells in tumors growing on Gelfoam®. In contrast, the telomerase-dependent adenovirus OBP-301 decoyed the MKN-45 cells in tumors on Gelfoam® to cycle from G0/G1 phase to S/G2 phase and reduced their viability. CDDP- or paclitaxel-treated MKN-45 tumors remained quiescent and did not change in size. In contrast, OB-301 reduced the size of the MKN-45 tumors on Gelfoam®. We examined the cell cycle-related proteins using Western blotting. CDDP increased the expression of p53 and p21 indicating cell cycle arrest. In contrast, OBP-301 decreased the expression of p53 and p21 Furthermore, OBP-301 increased the expression of E2F and pAkt as further indication of cell cycle decoy. This 3-D Gelfoam® histoculture and FUCCI imaging are powerful tools to discover effective therapy of SCCP such as OBP-301.

  12. Efficacy of a Cell-Cycle Decoying Killer Adenovirus on 3-D Gelfoam®-Histoculture and Tumor-Sphere Models of Chemo-Resistant Stomach Carcinomatosis Visualized by FUCCI Imaging

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M.

    2016-01-01

    Stomach cancer carcinomatosis peritonitis (SCCP) is a recalcitrant disease. The goal of the present study was to establish an in vitro-in vivo-like imageable model of SCCP to develop cell-cycle-based therapeutics of SCCP. We established 3-D Gelfoam® histoculture and tumor-sphere models of SCCP. FUCCI-expressing MKN-45 stomach cancer cells were transferred to express the fluorescence ubiquinized cell-cycle indicator (FUCCI). FUCCI-expressing MKN-45 cells formed spheres on agarose or on Gelfoam® grew into tumor-like structures with G0/G1 cancer cells in the center and S/G2 cancer cells located in the surface as indicated by FUCCI imaging when the cells fluoresced red or green, respectively. We treated FUCCI-expressing cancer cells forming SCCP tumors in Gelfoam® histoculture with OBP-301, cisplatinum (CDDP), or paclitaxel. CDDP or paclitaxel killed only cycling cancer cells and were ineffective against G1/G2 MKN-45 cells in tumors growing on Gelfoam®. In contrast, the telomerase-dependent adenovirus OBP-301 decoyed the MKN-45 cells in tumors on Gelfoam® to cycle from G0/G1 phase to S/G2 phase and reduced their viability. CDDP- or paclitaxel-treated MKN-45 tumors remained quiescent and did not change in size. In contrast, OB-301 reduced the size of the MKN-45 tumors on Gelfoam®. We examined the cell cycle-related proteins using Western blotting. CDDP increased the expression of p53 and p21 indicating cell cycle arrest. In contrast, OBP-301 decreased the expression of p53 and p21 Furthermore, OBP-301 increased the expression of E2F and pAkt as further indication of cell cycle decoy. This 3-D Gelfoam® histoculture and FUCCI imaging are powerful tools to discover effective therapy of SCCP such as OBP-301. PMID:27673332

  13. X-ray repair cross complementing protein 1 in base excision repair

    DEFF Research Database (Denmark)

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Akbari, Mansour

    2012-01-01

    X-ray Repair Cross Complementing protein 1 (XRCC1) acts as a scaffolding protein in the converging base excision repair (BER) and single strand break repair (SSBR) pathways. XRCC1 also interacts with itself and rapidly accumulates at sites of DNA damage. XRCC1 can thus mediate the assembly of large...

  14. CrowdAidRepair: A Crowd-Aided Interactive Data Repairing Method

    KAUST Repository

    Zhou, Jian

    2016-03-25

    Data repairing aims at discovering and correcting erroneous data in databases. Traditional methods relying on predefined quality rules to detect the conflict between data may fail to choose the right way to fix the detected conflict. Recent efforts turn to use the power of crowd in data repairing, but the crowd power has its own drawbacks such as high human intervention cost and inevitable low efficiency. In this paper, we propose a crowd-aided interactive data repairing method which takes the advantages of both rule-based method and crowd-based method. Particularly, we investigate the interaction between crowd-based repairing and rule-based repairing, and show that by doing crowd-based repairing to a small portion of values, we can greatly improve the repairing quality of the rule-based repairing method. Although we prove that the optimal interaction scheme using the least number of values for crowd-based repairing to maximize the imputation recall is not feasible to be achieved, still, our proposed solution identifies an efficient scheme through investigating the inconsistencies and the dependencies between values in the repairing process. Our empirical study on three data collections demonstrates the high repairing quality of CrowdAidRepair, as well as the efficiency of the generated interaction scheme over baselines.

  15. Beyond xeroderma pigmentosum: DNA damage and repair in an ecological context. A tribute to James E. Cleaver.

    Science.gov (United States)

    Karentz, Deneb

    2015-01-01

    The ability to repair DNA is a ubiquitous characteristic of life on Earth and all organisms possess similar mechanisms for dealing with DNA damage, an indication of a very early evolutionary origin for repair processes. James E. Cleaver's career (initiated in the early 1960s) has been devoted to the study of mammalian ultraviolet radiation (UVR) photobiology, specifically the molecular genetics of xeroderma pigmentosum and other human diseases caused by defects in DNA damage recognition and repair. This work by Jim and others has influenced the study of DNA damage and repair in a variety of taxa. Today, the field of DNA repair is enhancing our understanding of not only how to treat and prevent human disease, but is providing insights on the evolutionary history of life on Earth and how natural populations are coping with UVR-induced DNA damage from anthropogenic changes in the environment such as ozone depletion. © 2014 The American Society of Photobiology.

  16. DNA damage repair and radiosensitivity

    International Nuclear Information System (INIS)

    Suzuki, Norio

    2003-01-01

    Tailored treatment is not new in radiotherapy; it has been the major subject for the last 20-30 years. Radiation responses and RBE (relative biological effectiveness) depend on assay systems, endpoints, type of tissues and tumors, radiation quality, dose rate, dose fractionation, physiological and environmental factors etc, Latent times to develop damages also differ among tissues and endpoints depending on doses and radiation quality. Recent progress in clarification of radiation induced cell death, especially of apoptotic cell death, is quite important for understanding radiosensitivity of tumor cure process as well as of tumorigenesis. Apoptotic cell death as well as dormant cells had been unaccounted and missed into a part of reproductive cell death. Another area of major progress has been made in clarifying repair mechanisms of radiation damage, i.e., non-homologous end joining (NHEJ) and homologous recombinational repair (HRR). New approaches and developments such as cDNA or protein micro arrays and so called informatics in addition to basic molecular biological analysis are expected to aid identifying molecules and their roles in signal transduction pathways, which are multi-factorial and interactive each other being involved in radiation responses. (authors)

  17. Repairing liner of the reactor

    International Nuclear Information System (INIS)

    Aguilar H, F.

    2001-07-01

    Due to the corrosion problems of the aluminum coating of the reactor pool, a periodic inspections program by ultrasound to evaluate the advance grade and the corrosion speed was settled down. This inspections have shown the necessity to repair some areas, in those that the slimming is significant, of not making it can arrive to the water escape of the reactor pool. The objective of the repair is to place patches of plates of 1/4 inch aluminum thickness in the areas of the reactor 'liner', in those that it has been detected by ultrasound a smaller thickness or similar to 3 mm. To carry out this the fuels are move (of the core and those that are decaying) to a temporary storage, the structure of the core is confined in a tank that this placed inside the pool of the reactor, a shield is placed in the thermal column and it is completely extracted the water for to leave uncover the 'liner' of the reactor. (Author)

  18. KNEE PROPRIOCEPTION FOLLOWING MENISCAL REPAIR

    Directory of Open Access Journals (Sweden)

    Brytsko A. A.

    2018-02-01

    Full Text Available Background. It is well known that meniscectomy leads to osteoarthritis of the knee and proprioception impairment. Objective. The aim of this study was to assess retrospectively the joint position sense after meniscal suture and partial medial meniscal resection and to estimate the patients’ satisfaction with knee function. Material and Methods. We evaluated the outcomes of 27 patients after meniscal repair and compared them to those of 24 patients after partial meniscal resection. We estimated the joint position sense at 30°, 45° and 60° of flexion using the Biodex system 4 Pro. All patients were assessed with the IKDC 2000 subjective knee score. Results. A statistically significant worsening in reproducing the injured joint position in comparison to the healthy limb in both groups was observed. These impairments were mostly expressed at 45° and 60° of knee flexion, and were worsening over time in the group of patients who had undergone medial meniscal resection. An average value by the IKDC 2000 scale after 24 months in the meniscorrhaphy group was 76.73 ± 11.17% and 68.93 ± 14.76% after partial medial meniscal resection. Сonclusion. The control over position of the knee is not impaired after meniscal repair. An overall satisfaction with joint function is higher in patients who undergo meniscal suture in comparison to the partial medial meniscal resection group.

  19. Dynamic modeling method for infrared smoke based on enhanced discrete phase model

    Science.gov (United States)

    Zhang, Zhendong; Yang, Chunling; Zhang, Yan; Zhu, Hongbo

    2018-03-01

    The dynamic modeling of infrared (IR) smoke plays an important role in IR scene simulation systems and its accuracy directly influences the system veracity. However, current IR smoke models cannot provide high veracity, because certain physical characteristics are frequently ignored in fluid simulation; simplifying the discrete phase as a continuous phase and ignoring the IR decoy missile-body spinning. To address this defect, this paper proposes a dynamic modeling method for IR smoke, based on an enhanced discrete phase model (DPM). A mathematical simulation model based on an enhanced DPM is built and a dynamic computing fluid mesh is generated. The dynamic model of IR smoke is then established using an extended equivalent-blackbody-molecule model. Experiments demonstrate that this model realizes a dynamic method for modeling IR smoke with higher veracity.

  20. A geometric process repair model for a repairable cold standby system with priority in use and repair

    International Nuclear Information System (INIS)

    Zhang Yuanlin; Wang Guanjun

    2009-01-01

    In this paper, a deteriorating cold standby repairable system consisting of two dissimilar components and one repairman is studied. For each component, assume that the successive working times form a decreasing geometric process while the consecutive repair times constitute an increasing geometric process, and component 1 has priority in use and repair. Under these assumptions, we consider a replacement policy N based on the number of repairs of component 1 under which the system is replaced when the number of repairs of component 1 reaches N. Our problem is to determine an optimal policy N* such that the average cost rate (i.e. the long-run average cost per unit time) of the system is minimized. The explicit equation of the average cost rate of the system is derived and the corresponding optimal replacement policy N* can be determined analytically or numerically. Finally, a numerical example with Weibull distribution is given to illustrate some theoretical results in this paper.

  1. Phytochemicals radiosensitize cancer cells by inhibiting DNA repair

    International Nuclear Information System (INIS)

    Singh, Rana P.

    2017-01-01

    Solid tumors are mostly treated with radiotherapy. Radiotherapy is toxic to normal tissues and also promote the invasiveness and radioresistance in cancer cells. The resistance against radiotherapy and adverse effects to normal cells reduce the overall therapeutic effects of the treatment. Radiosensitizing agents usually show limited success during clinical trials. Therefore, the search and development of new radiosensitizers showing selective response to only cancer cells is desirable. We analyzed the radiosensitizing effects including cell death effect of silibinin, a phytochemical on prostate cancer cells. Silibinin enhanced gamma radiation (2.5-10 Gy) induced inhibition in colony formation selectively in prostate cancer cells. In cell cycle progression, G2/M phase is the most sensitive phase for radiation-induced damage which was delayed by the compound treatment in radiation exposed cells. The lower concentrations of silibinin substantially enhanced radiation-induced apoptosis. A prolonged reactive oxygen species production was also observed in these treatments EGFR signaling pathway can contribute to radiation-induced pro-survival mechanisms and to the therapeutic resistance. Agent treatment reduced the IR-induced EGFR phosphorylation and consequently reversed the resistance mediating mechanisms within the cancer cell. Thus, inhibiting DNA repair in cancer cells would enhance therapeutic response of radiation in cancer cells. Silibinin affected the localization of EGFR and DNA-dependent protein kinase, the DNA-PK is known to be an important mediator of DSB repair in human cells, and showed increased number of pH2AX (ser139) foci, and thus indicating lower DNA repair in these cancer cells. This was also confirmed in the tumor xenograft study. Our findings suggest that a combination of silibinin with radiation could be an effective treatment of radioresistant human prostate cancer and warrants further investigation. (author)

  2. Repairing method and repairing device of incore structure

    International Nuclear Information System (INIS)

    Uraki, Keiichi; Okamura, Hisanobu; Matsumoto, Toshimi

    1998-01-01

    In structures or equipment made of stainless steel, Ni-based alloy or a low alloy steel and undergoing neutron irradiation and causing a crack-like defect in a reactor pressure vessel, a plate is applied to a region where the crack-like detect is caused, and pressure is applied locally to bond the plate by generated resistance. Namely, electric current is supplied to the portion to be bonded while pressurizing to bond it by generated resistance heat. Then the propagation of cracks can be prevented and occurrence of cracks upon repairing can be prevented relative to a structural member undergoing neutron irradiation in the reactor pressure vessel and causing a crack-like defect thereby enabling to provide effects of preventing occurrence of an accident due to stress corrosion cracking of a nuclear power plant and prolonging the integrity of the plant. (N.H.)

  3. Base Sequence Context Effects on Nucleotide Excision Repair

    Directory of Open Access Journals (Sweden)

    Yuqin Cai

    2010-01-01

    Full Text Available Nucleotide excision repair (NER plays a critical role in maintaining the integrity of the genome when damaged by bulky DNA lesions, since inefficient repair can cause mutations and human diseases notably cancer. The structural properties of DNA lesions that determine their relative susceptibilities to NER are therefore of great interest. As a model system, we have investigated the major mutagenic lesion derived from the environmental carcinogen benzo[a]pyrene (B[a]P, 10S (+-trans-anti-B[a]P-2-dG in six different sequence contexts that differ in how the lesion is positioned in relation to nearby guanine amino groups. We have obtained molecular structural data by NMR and MD simulations, bending properties from gel electrophoresis studies, and NER data obtained from human HeLa cell extracts for our six investigated sequence contexts. This model system suggests that disturbed Watson-Crick base pairing is a better recognition signal than a flexible bend, and that these can act in concert to provide an enhanced signal. Steric hinderance between the minor groove-aligned lesion and nearby guanine amino groups determines the exact nature of the disturbances. Both nearest neighbor and more distant neighbor sequence contexts have an impact. Regardless of the exact distortions, we hypothesize that they provide a local thermodynamic destabilization signal for repair.

  4. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    Science.gov (United States)

    Im, Gun-Il

    2016-04-01

    Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair.

  5. International congress on DNA damage and repair: Book of abstracts

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    This document contains the abstracts of 105 papers presented at the Congress. Topics covered include the Escherichia coli nucleotide excision repair system, DNA repair in malignant transformations, defective DNA repair, and gene regulation. (TEM)

  6. International congress on DNA damage and repair: Book of abstracts

    International Nuclear Information System (INIS)

    1987-01-01

    This document contains the abstracts of 105 papers presented at the Congress. Topics covered include the Escherichia coli nucleotide excision repair system, DNA repair in malignant transformations, defective DNA repair, and gene regulation

  7. Laparoscopic Inguinal Hernia Repair in a Developing Nation: Short ...

    African Journals Online (AJOL)

    bilateral hernias, and recurrent hernias), there are data demonstrating an ... no reports of laparoscopic inguinal hernia repair from the. Anglophone ... MATERIALS AND METHODS .... inguinal hernia repair has advantages over open repair for.

  8. DNA Repair and Ethnic Differences in Prostate Cancer Risk

    National Research Council Canada - National Science Library

    Goldman, Radoslav

    2008-01-01

    .... To evaluate this hypothesis we quantify DNA repair capacity in blood cells using comet assay and evaluate how this repair capacity is related to genetic variants in OGG1 and XRCC1 DNA repair genes...

  9. DNA Repair and Ethnic Differences in Prostate Cancer Risk

    National Research Council Canada - National Science Library

    Goldman, Radoslav

    2007-01-01

    .... To evaluate this hypothesis we quantify DNA repair capacity in blood cells using comet assay and evaluate how this repair capacity is related to genetic variants in OGG1 and XRCC1 DNA repair genes...

  10. DNA Repair and Ethnic Differences in Prostate Cancer Risk

    National Research Council Canada - National Science Library

    Goldman, Radoslav

    2006-01-01

    .... To evaluate this hypothesis, we quantify DNA repair capacity in blood cells using comet assay and evaluate how this repair capacity is related to genetic variants in OGG1 and XRCC1 DNA repair genes...

  11. DNA repair related to radiation therapy

    International Nuclear Information System (INIS)

    Klein, W.

    1979-01-01

    The DNA excision repair capacity of peripheral human lymphocytes after radiation therapy has been analyzed. Different forms of application of the radiation during the therapy have been taken into account. No inhibition of repair was found if cells were allowed a certain amount of accomodation to radiation, either by using lower doses or longer application times. (G.G.)

  12. Maintenance and Repair of Concrete Structures

    NARCIS (Netherlands)

    Bijen, J.M.J.M.

    1989-01-01

    In 1987 and 1988 a series of articles was published in the Dutchjournal "Cement" about maintenance and repair of concrete structures. The series was written to promote the transfer of know-how concerning maintenance and repair of concrete structures. Use has been made of know-how developed in the

  13. VEHICLE REPAIR AND MAINTENANCE COSTS IN NIGERIA ...

    African Journals Online (AJOL)

    A standard model was established for the prediction of repair and maintenance costs of vehicles in a non-profit making government parastatal. The model was derived based on data collected over a ten year period from a non-profit making government parastatal, and it predicts repair and maintenance costs as a linear ...

  14. 30 CFR 57.6801 - Vehicle repair.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Vehicle repair. 57.6801 Section 57.6801 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... and Underground § 57.6801 Vehicle repair. Vehicles containing explosive material and oxidizers shall...

  15. Dysphagia in children with repaired oesophageal atresia

    NARCIS (Netherlands)

    Coppens, C.H.; Engel-Hoek, L. van den; Scharbatke, H.E.; Groot, S.A. de; Draaisma, J.M.T.

    2016-01-01

    Dysphagia is a common problem in children with repaired oesophageal atresia (OA). Abnormalities in the oropharyngeal and oesophageal phase have hardly been studied. The aims of this study were to assess the prevalence of dysphagia in children with repaired OA and to identify and differentiate oral

  16. Human DNA repair and recombination genes

    International Nuclear Information System (INIS)

    Thompson, L.H.; Weber, C.A.; Jones, N.J.

    1988-09-01

    Several genes involved in mammalian DNA repair pathways were identified by complementation analysis and chromosomal mapping based on hybrid cells. Eight complementation groups of rodent mutants defective in the repair of uv radiation damage are now identified. At least seven of these genes are probably essential for repair and at least six of them control the incision step. The many genes required for repair of DNA cross-linking damage show overlap with those involved in the repair of uv damage, but some of these genes appear to be unique for cross-link repair. Two genes residing on human chromosome 19 were cloned from genomic transformants using a cosmid vector, and near full-length cDNA clones of each gene were isolated and sequenced. Gene ERCC2 efficiently corrects the defect in CHO UV5, a nucleotide excision repair mutant. Gene XRCC1 normalizes repair of strand breaks and the excessive sister chromatid exchange in CHO mutant EM9. ERCC2 shows a remarkable /approximately/52% overall homology at both the amino acid and nucleotide levels with the yeast RAD3 gene. Evidence based on mutation induction frequencies suggests that ERCC2, like RAD3, might also be an essential gene for viability. 100 refs., 4 tabs

  17. Tumor relapse present in oncologic nasal repair

    International Nuclear Information System (INIS)

    Galvez Chavez, Julio Cesar; Sanchez Wals, Lenia; Monzon Fernandez, Abel Nicolas; Morales Tirado, Roxana

    2009-01-01

    Tumor relapse is one of the more fearsome complications of the oncologic course and also to obscure the life prognosis, causing the loss of many reconstructions and of exhausting the repairing surgical possibilities. The aim of this study was to determine the relapse frequency, the repercussion on the repair and the subsequent medical course of patients operated on malign nasal tumors

  18. The Weekend Effect in AAA Repair.

    Science.gov (United States)

    O'Donnell, Thomas F X; Li, Chun; Swerdlow, Nicholas J; Liang, Patric; Pothof, Alexander B; Patel, Virendra I; Giles, Kristina A; Malas, Mahmoud B; Schermerhorn, Marc L

    2018-04-18

    Conflicting reports exist regarding whether patients undergoing surgery on the weekend or later in the week experience worse outcomes. We identified patients undergoing abdominal aortic aneurysm (AAA) repair in the Vascular Quality Initiative between 2009 and 2017 [n = 38,498; 30,537 endovascular aneurysm repair (EVAR) and 7961 open repair]. We utilized mixed effects logistic regression to compare adjusted rates of perioperative mortality based on the day of repair. Tuesday was the most common day for elective repair (22%), Friday for symptomatic repairs (20%), and ruptured aneurysms were evenly distributed. Patients with ruptured aneurysms experienced similar adjusted mortality whether they underwent repair during the week or on weekends. Transfers of ruptured AAA were more common over the weekend. However, patients transferred on the weekend experienced higher adjusted mortality than those transferred during the week (28% vs 21%, P = 0.02), despite the fact that during the week, transferred patients actually experienced lower adjusted mortality than patients treated at the index hospital (21% vs 31%, P AAA repair. However, patients with ruptured AAA transferred on the weekend experienced higher mortality than those transferred during the week, suggesting a need for improvement in weekend transfer processes.

  19. Self repairing composites for drone air vehicles

    Science.gov (United States)

    Dry, Carolyn

    2015-04-01

    The objective of this effort was to demonstrate the feasibility of impact-initiated delivery of repair chemicals through hollow fiber architectures embedded within graphite fiber reinforced polymer matrix composites, representative of advanced drone aircraft component material systems. Self-repairing structures through coupon and elements were demonstrated, and evaluated.

  20. 26 CFR 1.162-4 - Repairs.

    Science.gov (United States)

    2010-04-01

    ... the cost of acquisition or production or the gain or loss basis of the taxpayer's plant, equipment, or other property, as the case may be, is not increased by the amount of such expenditures. Repairs in the... incidental repairs which neither materially add to the value of the property nor appreciably prolong its life...

  1. DNA Damage, Repair, and Cancer Metabolism

    Science.gov (United States)

    Turgeon, Marc-Olivier; Perry, Nicholas J. S.; Poulogiannis, George

    2018-01-01

    Although there has been a renewed interest in the field of cancer metabolism in the last decade, the link between metabolism and DNA damage/DNA repair in cancer has yet to be appreciably explored. In this review, we examine the evidence connecting DNA damage and repair mechanisms with cell metabolism through three principal links. (1) Regulation of methyl- and acetyl-group donors through different metabolic pathways can impact DNA folding and remodeling, an essential part of accurate double strand break repair. (2) Glutamine, aspartate, and other nutrients are essential for de novo nucleotide synthesis, which dictates the availability of the nucleotide pool, and thereby influences DNA repair and replication. (3) Reactive oxygen species, which can increase oxidative DNA damage and hence the load of the DNA-repair machinery, are regulated through different metabolic pathways. Interestingly, while metabolism affects DNA repair, DNA damage can also induce metabolic rewiring. Activation of the DNA damage response (DDR) triggers an increase in nucleotide synthesis and anabolic glucose metabolism, while also reducing glutamine anaplerosis. Furthermore, mutations in genes involved in the DDR and DNA repair also lead to metabolic rewiring. Links between cancer metabolism and DNA damage/DNA repair are increasingly apparent, yielding opportunities to investigate the mechanistic basis behind potential metabolic vulnerabilities of a substantial fraction of tumors. PMID:29459886

  2. FLEXOR TENDON REPAIR IN THE HAND

    African Journals Online (AJOL)

    Method of Repair. Cases. AGE, SEX ... method is at fault and not the dexterity of the operator or his technique. .... Physio- therapy seldom makes stiff fingers work, but it prevents .... or repaired later by direct suture, graft or transplant. No. of.

  3. Plan Repair as an Extension of Planning

    NARCIS (Netherlands)

    Van der Krogt, R.P.J.; De Weerdt, M.M.

    2005-01-01

    In dynamic environments, agents have to deal with changing situations. In these cases, repairing a plan is often more efficient than planning from scratch, but existing planning techniques are more advanced than existing plan repair techniques. Therefore, we propose a straightforward method to

  4. Using repair priorities in systems with redundacies

    NARCIS (Netherlands)

    Sleptchenko, A.V.; Adan, I.J.B.F.; Van Houtum, G.-J.

    2014-01-01

    In this paper, we present and analyze a mathematical model for the computation of the system availability for a system of parallel machines with redundancies and repair priorities. Using the presented models, we show that the repair priorities have a strong effect on the performance of the system.

  5. Repair of Temporal Bone Encephalocele following Canal Wall Down Mastoidectomy

    Directory of Open Access Journals (Sweden)

    Sarantis Blioskas

    2014-01-01

    Full Text Available We report a rare case of a temporal bone encephalocele after a canal wall down mastoidectomy performed to treat chronic otitis media with cholesteatoma. The patient was treated successfully via an intracranial approach. An enhanced layer-by-layer repair of the encephalocele and skull base deficit was achieved from intradurally to extradurally, using temporalis fascia, nasal septum cartilage, and artificial dural graft. After a 22-month follow-up period the patient remains symptom free and no recurrence is noted.

  6. Pulmonary Embolism after Arthroscopic Rotator Cuff Repair: A Case Report

    Directory of Open Access Journals (Sweden)

    Tadashi Yamamoto

    2013-01-01

    Full Text Available Total hip/knee arthroplasty may cause venous thromboembolism (VTE as a postoperative complication. However, there are few reports on VTE after arthroscopic shoulder surgery. We report a patient who developed pulmonary embolism (PE 6 days after arthroscopic rotator cuff repair but recovered without sequelae. In this case, the possibility of DVT of the lower limbs was denied by contrast-enhanced CT. Most possibly, the source of PE was deep vein thrombosis (DVT of the upper limb under Desault fixation which showed arthroscopic surgery-related swelling postoperatively.

  7. Pollen DNA repair after treatment with the mutagens 4-nitroquinoline-1-oxide, ultraviolet and near-ultraviolet irradiation, and boron dependence of repair

    International Nuclear Information System (INIS)

    Jackson, J.F.; Linskens, H.F.; Katholieke Universiteit Nijmegen

    1979-01-01

    Irradiation of dry, mature pollen from Petuna hybrida with near-ultraviolet light from an erythemal-sunlamp gave rise to a repair-like, unscheduled DNA synthesis during the early stages of in vitro germination. Like that brought about by far-ultraviolet light from a germicidal lamp, this DNA synthesis is enhanced by hydroxyurea added to the germination medium, and reduced by photoreactivating light given after ultraviolet irradiation and before germination begins. It is concluded that pollen, often receiving considerable exposure to sunlight, has, in addition to the protection afforded by the ultraviolet filtering effects of yellow pigments, also the capacity to repair ultraviolet produced changes in DNA, by both photoreactivation and dark repair processes. (orig./AJ) [de

  8. Mutagenesis and repair of DNA

    International Nuclear Information System (INIS)

    Janion, C.; Grzesiuk, E.; Fabisiewicz, A.; Tudek, B.; Ciesla, J.; Graziewicz, M.; Wojcik, A.; Speina, E.

    1998-01-01

    Full text. The discovery that the mfd gene codes for a transcription-coupling repair factor (TRCF) prompted us to re-investigate the MFD (mutation frequency decline) phenomenon in E.coli K-12 strain when mutations were induced by ultraviolet light, halogen light or MMS-treatment. These studies revealed that: (i) the process of MFD involves the proofreading activity of DNA pol III and the mismatch repair system, as well as, TRCF and the UvrABC-excinuclease (ii) a semi-rich plate test may be replaced by a rich liquid medium, (iii) the T-T pyrimidine dimers are the lesions excised with the highest activity, and (iv) overproduction of UmuD(D'C) proteins leads to a great increase in mutant frequency in irradiated and MMS-treated cells. The role of mismatch repair (MR) in MMS-induced mutagenesis is obscured by the fact that the spectra of mutational specificity are different in bacteria proficient and deficient in MR. It has been found that transposons Tn10 (and Tn5) when inserted into chromosomal DNA of E. coli influence the phenotype lowering the survival and frequency of mutations induced by UV or halogen light irradiation. This is connected with a deficiency of UmuD(D') and UmuC proteins. Transformation of bacteria with plasmids bearing the umuD(D')C genes, suppresses the effects of the transposon insertion, a phenomenon which has not been described before. Single-stranded DNA of M13mp18 phage was oxidized in vitro by a hydroxyl radical generating system including hypoxanthine/xanthine oxidase/Fe3+/EDTA, and it was found that Fapy-Ade, Fapy-Gua, 8-oxyAde and thymine glycol were the main products formed. Replication of the oxidized template by T7 phage DNA polymerase, Klenow fragment of polymerase I, or polymerase beta from bovine thymus has revealed that oxidized pyrimidines are stronger blockers than oxidized purines for T7 phage and Klenow fragment polymerases and the blocking potency depends on the neighboring bases and on the type of polymerase. Studies of

  9. Saturation of DNA repair in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, F E; Setlow, R B

    1979-01-01

    Excision repair seems to reach a plateau in normal human cells at a 254 nm dose near 20 J/m/sup 2/. We measured excision repair in normal human fibroblasts up to 80 J/m/sup 2/. The four techniques used (unscheduled DNA synthesis, photolysis of BrdUrd incorporated during repair, loss of sites sensitive to a UV endonuclease from Micrococcus luteus, and loss of pyrimidine dimers from DNA) showed little difference between the two doses. Moreover, the loss of endonuclease sites in 24h following two 20 J/m/sup 2/ doses separated by 24h was similar to the loss observed following one dose. Hence, we concluded that the observed plateau in excision repair is real and does not represent some inhibitory process at high doses but a true saturation of one of the rate limiting steps in repair.

  10. On the optimal degree of imperfect repair

    International Nuclear Information System (INIS)

    Finkelstein, Maxim

    2015-01-01

    A simple cost-wise comparison between the minimal and perfect repair of a system is discussed first using a relevant example. The main focus of this note, however, is on imperfect (general) repair. The best repair for our system in this case is defined as the one that corresponds to the optimal level (extent) of repair actions that minimize the long-run expected cost per unit of time. This complex optimization problem is considered for a specific imperfect repair model (Kijima II), using the developed earlier asymptotic approach to the corresponding virtual age modelling. It is shown that the optimal solution exists when the failure rate of a system tends to infinity as t tends to infinity and the corresponding cost function decreases sufficiently fast. An example illustrating the optimization procedure is considered

  11. Contact Dermatitis In Automobile Repair workers

    Directory of Open Access Journals (Sweden)

    Joshi M P

    1997-01-01

    Full Text Available Automobile repair workers are at risk of developing skin morbidity including occupational dermatoses because of their exposure to mineral oils, petroleum products and its derivatives and lubricating oil. This cross- sectional study was carried out at Maharashtra State Road Transport Corporation workshops in Nagpur city to investigate prevalence of skin morbidity including contact dermatitis in automobile repair workers. The study included 288 (49.9% automobile repair workers 180 (31.3% workshop office staff and 109 (18.8% divisional office employees. Dermatitis was the commonest skin morbidity in all the study subjects and it was significantly more prevalent in automobile repair workers. Folliculitis was detected in 13.2% of auto â€" repair workers and was not seen in the other two groups. Increasing trend of skin morbidity was correlated with the length of service of employees. Proper protective measures along with suitable washing facilities should be provided

  12. Imperfect repair and lifesaving in heterogeneous populations

    Energy Technology Data Exchange (ETDEWEB)

    Finkelstein, Maxim [Department of Mathematical Statistics, University of the Free State, PO Box 339, 9300 Bloemfontein (South Africa) and Max Planck Institute for Demographic Research, Rostock (Germany)]. E-mail: FinkelM.SCl@mail.uovs.ac.za

    2007-12-15

    In this theoretical paper we generalize the notion of minimal repair to the heterogeneous case, when the lifetime distribution function can be modeled by continuous or a discrete mixture of distributions. The statistical (black box) minimal repair and the minimal repair based on information just before the failure of an object are considered. The corresponding failure (intensity) rate processes are defined and analyzed. Demographic lifesaving model is also considered: each life is saved (cured) with some probability (or equivalently a proportion of individuals who would have died are now resuscitated and given another chance). Those who are saved experience the statistical minimal repair. Both of these models are based on the Poisson or non-homogeneous Poisson processes of underlying events, which allow for considering heterogeneity. We also consider the new model of imperfect repair in the homogeneous case and present generalizations to the heterogeneous setting.

  13. Stochastic Modelling Of The Repairable System

    Directory of Open Access Journals (Sweden)

    Andrzejczak Karol

    2015-11-01

    Full Text Available All reliability models consisting of random time factors form stochastic processes. In this paper we recall the definitions of the most common point processes which are used for modelling of repairable systems. Particularly this paper presents stochastic processes as examples of reliability systems for the support of the maintenance related decisions. We consider the simplest one-unit system with a negligible repair or replacement time, i.e., the unit is operating and is repaired or replaced at failure, where the time required for repair and replacement is negligible. When the repair or replacement is completed, the unit becomes as good as new and resumes operation. The stochastic modelling of recoverable systems constitutes an excellent method of supporting maintenance related decision-making processes and enables their more rational use.

  14. Male Fertility After Inguinal Hernia Mesh Repair

    DEFF Research Database (Denmark)

    Kohl, Andreas Pagh; Andresen, Kristoffer; Rosenberg, Jacob

    2017-01-01

    OBJECTIVE:: To determine whether patients who receive an inguinal hernia repair father the same number of children as the background population. BACKGROUND:: Although the effect of inguinal hernia repair on male fertility has previously been investigated through indirect measures, no previous...... studies have evaluated the final measure of male fertility, which is the number of children fathered by patients. METHODS:: Prospectively collected data on 32,621 male patients between the ages of 18 and 55 years who received 1 or more inguinal hernia repairs during the years 1998 to 2012 were found in 5...... hernia repair using Lichtenstein technique or laparoscopic approach did not father fewer children than expected. Thus, inguinal hernia repair using Lichtenstein or laparoscopic approach did not impair male fertility....

  15. Oxidative DNA damage & repair: An introduction.

    Science.gov (United States)

    Cadet, Jean; Davies, Kelvin J A

    2017-06-01

    This introductory article should be viewed as a prologue to the Free Radical Biology & Medicine Special Issue devoted to the important topic of Oxidatively Damaged DNA and its Repair. This special issue is dedicated to Professor Tomas Lindahl, co-winner of the 2015 Nobel Prize in Chemistry for his seminal discoveries in the area repair of oxidatively damaged DNA. In the past several years it has become abundantly clear that DNA oxidation is a major consequence of life in an oxygen-rich environment. Concomitantly, survival in the presence of oxygen, with the constant threat of deleterious DNA mutations and deletions, has largely been made possible through the evolution of a vast array of DNA repair enzymes. The articles in this Oxidatively Damaged DNA & Repair special issue detail the reactions by which intracellular DNA is oxidatively damaged, and the enzymatic reactions and pathways by which living organisms survive such assaults by repair processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Repair of DNA in xeroderma pigmentosum conjunctiva

    International Nuclear Information System (INIS)

    Newsome, D.A.; Kraemer, K.H.; Robbins, J.H.

    1975-01-01

    Xeroderma pigmentosum (XP) is an autosomal recessive disease with tumor formation on sun-exposed areas of the skin and eyes. Cells from most XP patients are deficient in repairing DNA damaged by ultraviolet (uv) light as shown by a reduced rate of tritiated thymidine (3HTdR) incorporation during their DNA repair synthesis. We have studied such repair synthesis in conjunctival cells from an XP patient with a conjunctival epithelioma and from normal cadaver conjunctiva. Cultured conjunctival cells were irradiated with uv light and then incubated with 3HTdR. Autoradiograms were prepared and showed that uv radiation induced a considerably slower rate of DNA repair synthesis in the XP cells than in normal cells. Many of the ocular abnormalities of XP, including tumor formation, may be the result of this defective DNA repair process

  17. Fibre autoradiography of repair and replication in DNA from single cells: the effect of DNA synthesis inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Ockey, C.H.

    1982-04-01

    DNA fibre autoradiography, after incorporation of high specific activity /sup 3/H-thymidine and /sup 3/H-deoxycytidine, has been used to investigate repair in DNA fibres from single cells following UV, or methyl-methane sulphonate (MMS) treatment. Asynchronously growing human fibroblasts, leucocytes, and HeLa cells at different phases of the cell cycle have been investigated. Isotope incorporation in repair could be differentiated from that involved in replication by the distribution and density of silver grains along the DNA fibres. Grain distribution due to repair was continuous over long stretches of the fibres and was at a low density, occasionally interspersed with short slightly denser segments. Replication labelling on the other hand, was dense and usually in short tandem segments. Repair labelling was of a similar overall density in fibres from a single cell, but differed in intensity from cell to cell. In mutagen treated Go (leucocytes) of G/sub 1/ (HeLa cells), repair labelling was not increased by the presence of the DNA inhibitors, hydroxyurea (HU) or 5-fluorodeoxyuridine (FUdR). Repair was not detectable in S cells however without the use of these inhibitors to reduce endogenous nucleoside production. FUdR enhanced the repair labelling in S cells only slightly, while HU increased it beyond that observed in UV irradiated, HU treated, G/sub 1/ cells. The intensity of repair labelling in fibres from mutagen treated S cells appears to be proportional to the degree of reduction of DNA chain elongation in replicons.

  18. 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.

  19. Factors modifying 3-aminobenzamide cytotoxicity in normal and repair-deficient human fibroblasts

    International Nuclear Information System (INIS)

    Boorstein, R.J.; Pardee, A.B.

    1984-01-01

    3-Aminobenzamide (3-AB), an inhibitor of poly(ADP-ribosylation), is lethal to human fibroblasts with damaged DNA. Its cytotoxicity was determined relative to a number of factors including the types of lesions, the kinetics of repair, and the availability of alternative repair systems. A variety of alkylating agent, UV or gamma irradiation, or antimetabolites were used to create DNA lesions. 3-AB enhanced lethality with monofunctional alkylating agents only. Within this class of compounds, methylmethanesulfonate (MMS) treatments made cells more sensitive to 3-AB than did treatment with methylnitrosourea (MNU) or methylnitronitrosoguanidine (MNNG). 3-AB interfered with a dynamic repair process lasting several days, since human fibroblasts remained sensitive to 3-AB for 36-48 hours following MMS treatment. During this same interval 3-AB caused these cells to arrest in G 2 phase. Alkaline elution analysis also revealed that this slow repair was delayed further by 3-AB. Human mutant cell defective in DNA repair differed in their responses to 3-AB. Greater lethality with 3-AB could be dependent on inability of the mutant cells to repair damage by other processes

  20. Differential recruitment of DNA Ligase I and III to DNA repair sites

    Science.gov (United States)

    Mortusewicz, Oliver; Rothbauer, Ulrich; Cardoso, M. Cristina; Leonhardt, Heinrich

    2006-01-01

    DNA ligation is an essential step in DNA replication, repair and recombination. Mammalian cells contain three DNA Ligases that are not interchangeable although they use the same catalytic reaction mechanism. To compare the recruitment of the three eukaryotic DNA Ligases to repair sites in vivo we introduced DNA lesions in human cells by laser microirradiation. Time lapse microscopy of fluorescently tagged proteins showed that DNA Ligase III accumulated at microirradiated sites before DNA Ligase I, whereas we could detect only a faint accumulation of DNA Ligase IV. Recruitment of DNA Ligase I and III to repair sites was cell cycle independent. Mutational analysis and binding studies revealed that DNA Ligase I was recruited to DNA repair sites by interaction with PCNA while DNA Ligase III was recruited via its BRCT domain mediated interaction with XRCC1. Selective recruitment of specialized DNA Ligases may have evolved to accommodate the particular requirements of different repair pathways and may thus enhance efficiency of DNA repair. PMID:16855289

  1. The effect of higher order chromatin structure on DNA damage and repair

    International Nuclear Information System (INIS)

    Yasui, L.S.; Warters, R.L.; Higashikubo, R.

    1985-01-01

    Alterations in chromatin structure are thought to play an important role in various radiobiological end points, i.e., DNA damage, DNA damage repair and cell survival. The authors use here the isoleucine deprivation technique to decondense higher order chromatin structure and asses X-ray induced DNA damage, DNA damage repair and cell survival on cells with decondensed chromatin as compared to controls. This chromatin decondensation manifests itself as a 30 fold decrease in nuclear area occupied by heterochromatin, an increased rate of Micrococcal nuclease digestion, 15% increased ethidium bromide intercalation and an altered binding capacity of Hl histone. These chromatin/nuclear changes do not affect X-ray induced DNA damage as measured by the alkaline elution technique or cell survival but slows DNA damage repair by 2 fold. Therefore, even though the chromatin appears more accessible to DNA damage and repair processes, these particular nuclear changes do not affect the DNA damaging effects of X-rays and in addition, repair is not enhanced by the ''relaxed'' state of chromatin. It is proposed that the altered metabolic state of isoleucine deprived cells provides a less efficient system for the repair of X-ray induced DNA damage

  2. Cartilage Repair Surgery: Outcome Evaluation by Using Noninvasive Cartilage Biomarkers Based on Quantitative MRI Techniques?

    Science.gov (United States)

    Jungmann, Pia M.; Baum, Thomas; Bauer, Jan S.; Karampinos, Dimitrios C.; Link, Thomas M.; Li, Xiaojuan; Trattnig, Siegfried; Rummeny, Ernst J.; Woertler, Klaus; Welsch, Goetz H.

    2014-01-01

    Background. New quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair. PMID:24877139

  3. Cartilage Repair Surgery: Outcome Evaluation by Using Noninvasive Cartilage Biomarkers Based on Quantitative MRI Techniques?

    Directory of Open Access Journals (Sweden)

    Pia M. Jungmann

    2014-01-01

    Full Text Available Background. New quantitative magnetic resonance imaging (MRI techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC, and diffusion weighted imaging (DWI are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair.

  4. Injecting a liquid bacteria-based repair system to make porous network conrete healed

    NARCIS (Netherlands)

    Sangadji, S.; Wiktor, V.A.C.; Jonkers, H.M.; Schlangen, H.E.J.G.

    2013-01-01

    Bacteria induced calcite precipitation has been proven to be effective in making concrete structure self-healing. In Microlab TU Delft, the concept has been enhanced by developing a liquid bacteria-based concrete repair system. The solution contains calcite precipitating bacteria, nutrients and

  5. Dynamic CE-MRA for endoleak classification after endovascular aneurysm repair.

    NARCIS (Netherlands)

    Laan, M.J. van der; Bakker, C.J.; Blankensteijn, J.D.; Bartels, L.W.

    2006-01-01

    AIM: To evaluate the value of dynamic contrast enhanced magnetic resonance angiography (CE-MRA) for classification of endoleaks after endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: Twenty-eight patients, between 2 days and 54 months after EVAR, were evaluated with CTA, MRI and dynamic

  6. Dynamic CE=MRA for endoleak classification after endovascular aneurysm repair

    NARCIS (Netherlands)

    van der Laan, MJ; Bakker, CJG; Blankensteijn, JD; Bartels, LW

    Aim. To evaluate the value of dynamic contrast enhanced magnetic resonance angiography (CE-MRA)for classification of endoleaks after endovascular aneurysm repair (EVAR). Materials and methods. Twenty-eight patients, between 2 days and 54 months after EVAR, were evaluated with CTA, MRI and dynamic

  7. Development of cost effective fenceline monitoring approaches to support advanced leak detection and repair strategies

    Science.gov (United States)

    Cost-effective fence line and process monitoring systems to support advanced leak detection and repair (LDAR) strategies can enhance protection of public health, facilitate worker safety, and help companies realize cost savings by reducing lost product. The U.S. EPA Office of Re...

  8. New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins.

    Science.gov (United States)

    Dutta, Arijit; Yang, Chunying; Sengupta, Shiladitya; Mitra, Sankar; Hegde, Muralidhar L

    2015-05-01

    Oxidized bases in the mammalian genome, which are invariably mutagenic due to their mispairing property, are continuously induced by endogenous reactive oxygen species and more abundantly after oxidative stress. Unlike bulky base adducts induced by UV and other environmental mutagens in the genome that block replicative DNA polymerases, oxidatively damaged bases such as 5-hydroxyuracil, produced by oxidative deamination of cytosine in the template strand, do not block replicative polymerases and thus need to be repaired prior to replication to prevent mutation. Following up our earlier studies, which showed that the Nei endonuclease VIII like 1 (NEIL1) DNA glycosylase, one of the five base excision repair (BER)-initiating enzymes in mammalian cells, has enhanced expression during the S-phase and higher affinity for replication fork-mimicking single-stranded (ss) DNA substrates, we recently provided direct experimental evidence for NEIL1's role in replicating template strand repair. The key requirement for this event, which we named as the 'cow-catcher' mechanism of pre-replicative BER, is NEIL1's non-productive binding (substrate binding without product formation) to the lesion base in ss DNA template to stall DNA synthesis, causing fork regression. Repair of the lesion in reannealed duplex is then carried out by NEIL1 in association with the DNA replication proteins. NEIL1 (and other BER-initiating enzymes) also interact with several accessory and non-canonical proteins including the heterogeneous nuclear ribonucleoprotein U and Y-box-binding protein 1 as well as high mobility group box 1 protein, whose precise roles in BER are still obscure. In this review, we have discussed the recent advances in our understanding of oxidative genome damage repair pathways with particular focus on the pre-replicative template strand repair and the role of scaffold factors like X-ray repairs cross-complementing protein 1 and poly (ADP-ribose) polymerase 1 and other accessory

  9. Laparoscopic repair of large suprapubic hernias.

    Science.gov (United States)

    Sikar, Hasan Ediz; Çetin, Kenan; Eyvaz, Kemal; Kaptanoglu, Levent; Küçük, Hasan Fehmi

    2017-09-01

    Suprapubic hernia is the term to describe ventral hernias located less than 4 cm above the pubic arch in the midline. Hernias with an upper margin above the arcuate line encounter technical difficulties, and the differences in repair methods forced us to define them as large suprapubic hernias. To present our experience with laparoscopic repair of large suprapubic hernias that allows adequate mesh overlap. Nineteen patients with suprapubic incisional hernias who underwent laparoscopic repair between May 2013 and January 2015 were included in the study. Patients with laparoscopic extraperitoneal repair who had a suprapubic hernia with an upper margin below the arcuate line were excluded. Two men and 17 women, with a mean age of 58.2, underwent laparoscopic repair. Most of the incisions were midline vertical (13/68.4%). Twelve (63.1%) of the patients had previous incisional hernia repair (PIHR group); the mean number of previous incisional hernia repair was 1.4. Mean defect size of the PIHR group was higher than in patients without previous repair - 107.3 cm 2 vs. 50.9 cm 2 (p < 0.05). Mean operating time of the PIHR group was higher than in patients without repair - 126 min vs. 77.9 min (p < 0.05). Although all complications occurred in the PIHR group, there was no statistically significant difference. Laparoscopic repair of large suprapubic hernias can be considered as the first option in treatment. The low recurrence rates reported in the literature and the lack of recurrence, as observed in our study, support this view.

  10. [SOS-repair--60 years].

    Science.gov (United States)

    Zavil'gel'skiĭ, G B

    2013-01-01

    This review integrates 60 years of research on SOS-repair and SOS-mutagenesis in procaryotes and eucaryotes, from Jean Weigle experiment in 1953 year (mutagenesis of lambda bacteriophage in UV-irradiated bacteria) to the latest achievements in studying SOS-mutagenesis on all living organisms--Eukarya, Archaea and Bacteria. A key role in establishing of a biochemical basis for SOS-mutagenesis belonges to the finding in 1998-1999 years that specific error-prone DNA polymerases (PolV and others) catalysed translesion synthesis on damaged DNA. This review focuses on recent studies addressing the new models for SOS-induced mutagenesis in Escherichia coli and Home sapiens cells.

  11. Laparoscopic repair of vesicovaginal fistula

    Directory of Open Access Journals (Sweden)

    Miłosz Wilczyński

    2011-06-01

    Full Text Available A vesicovaginal fistula is one of the complications that a gynaecologist is bound to face after oncological operations, especially in postmenopausal women. Over the years there have been introduced many techniques of surgical treatment of this entity, including transabdominal and transvaginal approaches.We present a case of a 46-year-old patient who suffered from urinary leakage via the vagina due to the presence of a vesicovaginal fistula that developed after radical abdominal hysterectomy and subsequent radiotherapy. The decision was made to repair it laparoscopically due to retracted, fibrous and scarred tissue in the vaginal apex that precluded a transvaginal approach. A small cystotomy followed by an excision of fistula borders was performed. After six-month follow-up no recurrence of the disease has been noted.We conclude that laparoscopy is an interesting alternative to traditional approaches that provides comparable results.

  12. Vibration in car repair work.

    Science.gov (United States)

    Hansson, J E; Eklund, L; Kihlberg, S; Ostergren, C E

    1987-03-01

    The main objective of the study was to find efficient hand tools which caused only minor vibration loading. Vibration measurements were carried out under standardised working conditions. The time during which car body repairers in seven companies were exposed to vibration was determined. Chisel hammers, impact wrenches, sanders and saws were the types of tools which generated the highest vibration accelerations. The average daily exposure at the different garages ranged from 22 to 70 min. The risk of vibration injury is currently rated as high. The difference between the highest and lowest levels of vibration was considerable in most tool categories. Therefore the choice of tool has a major impact on the magnitude of vibration exposure. The importance of choosing the right tools and working methods is discussed and a counselling service on vibration is proposed.

  13. Difference in vascular patterns between transosseous-equivalent and transosseous rotator cuff repair.

    Science.gov (United States)

    Urita, Atsushi; Funakoshi, Tadanao; Horie, Tatsunori; Nishida, Mutsumi; Iwasaki, Norimasa

    2017-01-01

    Vascularity is the important factor of biologic healing of the repaired tissue. The purpose of this study was to clarify sequential vascular patterns of repaired rotator cuff by suture techniques. We randomized 21 shoulders in 20 patients undergoing arthroscopic rotator cuff repair into 2 groups: transosseous-equivalent repair (TOE group, n = 10) and transosseous repair (TO group, n = 11). Blood flow in 4 regions inside the cuff (lateral articular, lateral bursal, medial articular, and medial bursal), in the knotless suture anchor in the TOE group, and in the bone tunnel in the TO group was measured using contrast-enhanced ultrasound at 1 month, 2 months, 3 months, and 6 months postoperatively. The sequential vascular pattern inside the repaired rotator cuff was different between groups. The blood flow in the lateral articular area at 1 month, 2 months, and 3 months (P = .002, .005, and .025) and that in the lateral bursal area at 2 months (P = .031) in the TO group were significantly greater than those in the TOE group postoperatively. Blood flow was significantly greater for the bone tunnels in the TO group than for the knotless suture anchor in the TOE group at 1 month and 2 months postoperatively (P = .041 and .009). This study clarified that the sequential vascular pattern inside the repaired rotator cuff depends on the suture technique used. Bone tunnels through the footprint may contribute to biologic healing by increasing blood flow in the repaired rotator cuff. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  14. Attenuated DNA damage repair by trichostatin A through BRCA1 suppression.

    Science.gov (United States)

    Zhang, Yin; Carr, Theresa; Dimtchev, Alexandre; Zaer, Naghmeh; Dritschilo, Anatoly; Jung, Mira

    2007-07-01

    Recent studies have demonstrated that some histone deacetylase (HDAC) inhibitors enhance cellular radiation sensitivity. However, the underlying mechanism for such a radiosensitizing effect remains unexplored. Here we show evidence that treatment with the HDAC inhibitor trichostatin A (TSA) impairs radiation-induced repair of DNA damage. The effect of TSA on the kinetics of DNA damage repair was measured by performing the comet assay and gamma-H2AX focus analysis in radioresistant human squamous carcinoma cells (SQ-20B). TSA exposure increased the amount of radiation-induced DNA damage and slowed the repair kinetics. Gene expression profiling also revealed that a majority of the genes that control cell cycle, DNA replication and damage repair processes were down-regulated after TSA exposure, including BRCA1. The involvement of BRCA1 was further demonstrated by expressing ectopic wild-type BRCA1 in a BRCA1 null cell line (HCC-1937). TSA treatment enhanced radiation sensitivity of HCC-1937/wtBRCA1 clonal cells, which restored cellular radiosensitivity (D(0) = 1.63 Gy), to the control level (D(0) = 1.03 Gy). However, TSA had no effect on the level of radiosensitivity of BRCA1 null cells. Our data demonstrate for the first time that TSA treatment modulates the radiation-induced DNA damage repair process, in part by suppressing BRCA1 gene expression, suggesting that BRCA1 is one of molecular targets of TSA.

  15. The DNA translocase RAD5A acts independently of the other main DNA repair pathways, and requires both its ATPase and RING domain for activity in Arabidopsis thaliana.

    Science.gov (United States)

    Klemm, Tobias; Mannuß, Anja; Kobbe, Daniela; Knoll, Alexander; Trapp, Oliver; Dorn, Annika; Puchta, Holger

    2017-08-01

    Multiple pathways exist to repair DNA damage induced by methylating and crosslinking agents in Arabidopsis thaliana. The SWI2/SNF2 translocase RAD5A, the functional homolog of budding yeast Rad5 that is required for the error-free branch of post-replicative repair, plays a surprisingly prominent role in the repair of both kinds of lesions in Arabidopsis. Here we show that both the ATPase domain and the ubiquitination function of the RING domain of the Arabidopsis protein are essential for the cellular response to different forms of DNA damage. To define the exact role of RAD5A within the complex network of DNA repair pathways, we crossed the rad5a mutant line with mutants of different known repair factors of Arabidopsis. We had previously shown that RAD5A acts independently of two main pathways of replication-associated DNA repair defined by the helicase RECQ4A and the endonuclease MUS81. The enhanced sensitivity of all double mutants tested in this study indicates that the repair of damaged DNA by RAD5A also occurs independently of nucleotide excision repair (AtRAD1), single-strand break repair (AtPARP1), as well as microhomology-mediated double-strand break repair (AtTEB). Moreover, RAD5A can partially complement for a deficient AtATM-mediated DNA damage response in plants, as the double mutant shows phenotypic growth defects. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  16. Shuttle Repair Tools Automate Vehicle Maintenance

    Science.gov (United States)

    2013-01-01

    Successfully building, flying, and maintaining the space shuttles was an immensely complex job that required a high level of detailed, precise engineering. After each shuttle landed, it entered a maintenance, repair, and overhaul (MRO) phase. Each system was thoroughly checked and tested, and worn or damaged parts replaced, before the shuttle was rolled out for its next mission. During the MRO period, workers needed to record exactly what needed replacing and why, as well as follow precise guidelines and procedures in making their repairs. That meant traceability, and with it lots of paperwork. In 2007, the number of reports generated during electrical system repairs was getting out of hand-placing among the top three systems in terms of paperwork volume. Repair specialists at Kennedy Space Center were unhappy spending so much time at a desk and so little time actually working on the shuttle. "Engineers weren't spending their time doing technical work," says Joseph Schuh, an electrical engineer at Kennedy. "Instead, they were busy with repetitive, time-consuming processes that, while important in their own right, provided a low return on time invested." The strain of such inefficiency was bad enough that slow electrical repairs jeopardized rollout on several occasions. Knowing there had to be a way to streamline operations, Kennedy asked Martin Belson, a project manager with 30 years experience as an aerospace contractor, to co-lead a team in developing software that would reduce the effort required to document shuttle repairs. The result was System Maintenance Automated Repair Tasks (SMART) software. SMART is a tool for aggregating and applying information on every aspect of repairs, from procedures and instructions to a vehicle s troubleshooting history. Drawing on that data, SMART largely automates the processes of generating repair instructions and post-repair paperwork. In the case of the space shuttle, this meant that SMART had 30 years worth of operations

  17. Analysis for a two-dissimilar-component cold standby repairable system with repair priority

    International Nuclear Information System (INIS)

    Leung, Kit Nam Francis; Zhang Yuanlin; Lai, Kin Keung

    2011-01-01

    In this paper, a cold standby repairable system consisting of two dissimilar components and one repairman is studied. Assume that working time distributions and repair time distributions of the two components are both exponential, and Component 1 has repair priority when both components are broken down. After repair, Component 1 follows a geometric process repair while Component 2 obeys a perfect repair. Under these assumptions, using the perfect repair model, the geometric process repair model and the supplementary variable technique, we not only study some important reliability indices, but also consider a replacement policy T, under which the system is replaced when the working age of Component 1 reaches T. Our problem is to determine an optimal policy T* such that the long-run average loss per unit time (i.e. average loss rate) of the system is minimized. The explicit expression for the average loss rate of the system is derived, and the corresponding optimal replacement policy T* can be found numerically. Finally, a numerical example for replacement policy T is given to illustrate some theoretical results and the model's applicability. - Highlights: → A two-dissimilar-component cold standby system with repair priority is formulated. → The successive up/repair times of Component 1 form a decreasing/increasing geometric process. → Not only some reliability indices but also a replacement policy are studied.

  18. Phenomenology of an inducible mutagenic DNA repair pathway in Escherichia coli: SOS repair hypothesis

    International Nuclear Information System (INIS)

    Radman, M.

    1974-01-01

    A hypothesis is proposed according to which E. coli possesses an inducible DNA repair system. This hypothetical repair, which we call SOS repair, is manifested only following damage to DNA, and requires de novo protein synthesis. SOS repair in E. coli requires some known genetic elements: recA + , lex + and probably zab + . Mutagenesis by ultraviolet light is observed only under conditions of functional SOS repair: we therefore suspect that this is a mutation-prone repair. A number of phenomena and experiments is reviewed which at this point can best be interpreted in terms of an inducible mutagenic DNA repair system. Two recently discovered phenomena support the proposed hypothesis: existence of a mutant (tif) which, after a shift to elevated temperature, mimicks the effect of uv irradiation in regard to repair of phage lambda and uv mutagenesis, apparent activation of SOS repair by introduction into the recipient cell of damaged plasmid or Hfr DNA. Several specific predictions based on SOS repair hypothesis are presented in order to stimulate further experimental tests. (U.S.)

  19. Initial experience of laparoscopic incisional hernia repair.

    Science.gov (United States)

    Razman, J; Shaharin, S; Lukman, M R; Sukumar, N; Jasmi, A Y

    2006-06-01

    Laparoscopic repair of ventral and incisional hernia has become increasingly popular as compared to open repair. The procedure has the advantages of minimal access surgery, reduction of post operative pain and the recurrence rate. A prospective study of laparoscopic incisional hernia repair was performed in our center from August 2002 to April 2004. Eighteen cases (n: 18) were performed during the study period. Fifteen cases (n: 15) had open hernia repair previously. Sixteen patients (n: 16) had successful repair of the hernia with the laparoscopic approach and two cases were converted to open repair. The mean hernia defect size was 156cm2. There was no intraoperative or immediate postoperative complication. The mean operating time was 100 +/- 34 minutes (75 - 180 minutes). The postoperative pain was graded as mild to moderate according to visual analogue score. The mean day of discharge after surgery was two days (1 - 3 days). During follow up, three patients (16.7%) developed seroma at the hernia sac which was resolved with conservative management after three weeks. One (5.6%) patient developed recurrence six months after surgery. In conclusion, laparoscopic repair of incisional hernia particularly recurrent hernia has been shown to be safe and effective in our centre. However, careful patient selection and acquiring the necessary advanced laparoscopic surgical skills coupled with the proper use of equipment are mandatory before embarking on this procedure.

  20. Repair of DNA damage in Deinococcus radiodurans

    International Nuclear Information System (INIS)

    Evans, D.M.

    1984-01-01

    The repair of DNA lesions in Deinococcus radiodurans was examined with particular reference to DNA excision repair of ultraviolet light (UV) induced pyrimidine dimers. The characteristics of excision repair via UV endonucleases α and β in vivo varied with respect to (a) the substrate range of the enzymes, (b) the rate of repair of DNA damage (c) the requirement for a protein synthesised in response to DNA damage to attenuate exonuclease action at repairing regions. UV endonuclease α is postulated to incise DNA in a different manner from UV endonuclease β thus defining the method of subsequent repair. Several DNA damage specific endonuclease activities independent of α and β are described. Mutations of the uvsA, uvsF and uvsG genes resulted in an increase in single-strand breaks in response to DNA damage producing uncontrolled DNA degradation. Evidence is presented that these genes have a role in limiting the access of UV endonuclease β to DNA lesions. uvsF and uvsG are also shown to be linked to the mtoA gene. Mutation of uvsH and reo-1 produces further distinct phenotypes which are discussed. An overall model of excision repair of DNA damage in Deinococcus radiodurans is presented. (author)

  1. Magnetic Resonance Imaging of Cartilage Repair

    Science.gov (United States)

    Trattnig, Siegfried; Winalski, Carl S.; Marlovits, Stephan; Jurvelin, Jukka S.; Welsch, Goetz H.; Potter, Hollis G.

    2011-01-01

    Articular cartilage lesions are a common pathology of the knee joint, and many patients may benefit from cartilage repair surgeries that offer the chance to avoid the development of osteoarthritis or delay its progression. Cartilage repair surgery, no matter the technique, requires a noninvasive, standardized, and high-quality longitudinal method to assess the structure of the repair tissue. This goal is best fulfilled by magnetic resonance imaging (MRI). The present article provides an overview of the current state of the art of MRI of cartilage repair. In the first 2 sections, preclinical and clinical MRI of cartilage repair tissue are described with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure of cartilage repair. In the third section, a short overview is provided on the regulatory issues of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) regarding MR follow-up studies of patients after cartilage repair surgeries. PMID:26069565

  2. High performance repairing of reinforced concrete structures

    International Nuclear Information System (INIS)

    Iskhakov, I.; Ribakov, Y.; Holschemacher, K.; Mueller, T.

    2013-01-01

    Highlights: ► Steel fibered high strength concrete is effective for repairing concrete elements. ► Changing fibers’ content, required ductility of the repaired element is achieved. ► Experiments prove previously developed design concepts for two layer beams. -- Abstract: Steel fibered high strength concrete (SFHSC) is an effective material that can be used for repairing concrete elements. Design of normal strength concrete (NSC) elements that should be repaired using SFHSC can be based on general concepts for design of two-layer beams, consisting of SFHSC in the compressed zone and NSC without fibers in the tensile zone. It was previously reported that such elements are effective when their section carries rather large bending moments. Steel fibers, added to high strength concrete, increase its ultimate deformations due to the additional energy dissipation potential contributed by fibers. When changing the fibers’ content, a required ductility level of the repaired element can be achieved. Providing proper ductility is important for design of structures to dynamic loadings. The current study discusses experimental results that form a basis for finding optimal fiber content, yielding the highest Poisson coefficient and ductility of the repaired elements’ sections. Some technological issues as well as distribution of fibers in the cross section of two-layer bending elements are investigated. The experimental results, obtained in the frame of this study, form a basis for general technological provisions, related to repairing of NSC beams and slabs, using SFHSC.

  3. Hepatopancreaticobiliary Values after Thoracoabdominal Aneurysm Repair

    Science.gov (United States)

    Wu, Darrell; Coselli, Joseph S.; Johnson, Michael L.; LeMaire, Scott A.

    2014-01-01

    Background: After thoracoabdominal aortic aneurysm (TAAA) repair, blood tests assessing hepatopancreaticobiliary (HPB) organs commonly have abnormal results. The clinical significance of such abnormalities is difficult to determine because the expected postoperative levels have not been characterized. Therefore, we sought to establish expected trends in HPB laboratory values after TAAA repair. Methods: This 5-year study comprised 155 patients undergoing elective Crawford extent II TAAA repair. In accordance with a prospective study protocol, all repairs involved left-sided heart bypass, selective visceral perfusion, and cold renal perfusion. Blood levels of aspartate transaminase (AST), alanine transaminase (ALT), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), total bilirubin, amylase, and lipase were measured before TAAA repair and for 7 days afterward. Ratios between postoperative and baseline levels were compared for each time point with 95% confidence intervals. Results: Temporal patterns for the laboratory values varied greatly. Amylase, lipase, and AST underwent significant early increases before decreasing to preoperative levels. LDH increased immediately and remained significantly elevated, whereas ALT increased more gradually. GGT remained near baseline through postoperative day 4, and then increased to more than twice baseline. Total bilirubin never differed significantly from baseline. After adjusted analysis, the ischemic time predicted the maximum AST, lipase, GGT, and LDH values. Conclusions: Although most HPB laboratory values increase significantly after elective TAAA repair, the temporal trends for different values vary substantially. The ischemic time predicts the maximum AST, lipase, GGT, and LDH levels. These trends should be considered when laboratory values are assessed after TAAA repair. PMID:26798731

  4. Radiation damage and its repair in non-sporulating bacteria

    International Nuclear Information System (INIS)

    Moseley, B.E.B.

    1984-01-01

    A review is given of radiation damage and its repair in non-sporulating bacteria. The identification and measurement of radiation damage in the DNA of the bacteria after exposure to ultraviolet radiation and ionizing radiation is described. Measuring the extent of DNA repair and ways of isolating repair mutants are also described. The DNA repair mechanisms for UV-induced damage are discussed including photoreactivation repair, excision repair, post-replication recombination repair and induced error-prone repair. The DNA repair mechanisms for ionizing radiation damage are also discussed including the repair of both single and double-strand breaks. Other aspects discussed include the effects of growth, irradiation medium and recovery medium on survival, DNA repair in humans, the commercial use of UV and ionizing radiations and the future of ionizing irradiation as a food treatment process. (U.K.)

  5. Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere for cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jianhua; Yang, Qiu; Cheng, Niangmei [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Tao, Xiaojun [Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, Hunan (China); Zhang, Zhihua; Sun, Xiaomin [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Zhang, Qiqing, E-mail: zhangqiq@126.com [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Key Laboratory of Biomedical Materials of Tianjin, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192 (China)

    2016-04-01

    For cartilage repair, ideal scaffolds should mimic natural extracellular matrix (ECM) exhibiting excellent characteristics, such as biocompatibility, suitable porosity, and good cell affinity. This study aimed to prepare a collagen/silk fibroin composite scaffold incorporated with poly-lactic-co-glycolic acid (PLGA) microsphere that can be applied in repairing cartilage. To obtain optimum conditions for manufacturing a composite scaffold, a scaffold composed of different collagen-to-silk fibroin ratios was evaluated by determining porosity, water absorption, loss rate in hot water, and cell proliferation. Results suggested that the optimal ratio of collagen and silk fibroin composite scaffold was 7:3. The microstructure and morphological characteristics of the obtained scaffold were also examined through scanning electron microscopy and Fourier transform infrared spectroscopy. The results of in vitro fluorescence staining of bone marrow stromal cells revealed that collagen/silk fibroin composite scaffold enhanced cell proliferation without eliciting side effects. The prepared composite scaffold incorporated with PLGA microsphere was implanted in fully thick articular cartilage defects in rabbits. Collagen/silk fibroin composite scaffold with PLGA microspheres could enhance articular cartilage regeneration and integration between the repaired cartilage and the surrounding cartilage. Therefore, this composite will be a promising material for cartilage repair and regeneration. - Highlights: • Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere proposed for cartilage repair was created. • In vivo, scaffold could enhance cartilage regeneration and integration between the repaired and surrounding cartilage. • In vitro, scaffold exhibits excellent characteristics, such as, improved porosity water absorption and good cell affinity.

  6. Diverless pipeline repair system for deep water

    Energy Technology Data Exchange (ETDEWEB)

    Spinelli, Carlo M. [Eni Gas and Power, Milan (Italy); Fabbri, Sergio; Bachetta, Giuseppe [Saipem/SES, Venice (Italy)

    2009-07-01

    SiRCoS (Sistema Riparazione Condotte Sottomarine) is a diverless pipeline repair system composed of a suite of tools to perform a reliable subsea pipeline repair intervention in deep and ultra deep water which has been on the ground of the long lasting experience of Eni and Saipem in designing, laying and operating deep water pipelines. The key element of SiRCoS is a Connection System comprising two end connectors and a repair spool piece to replace a damaged pipeline section. A Repair Clamp with elastomeric seals is also available for pipe local damages. The Connection System is based on pipe cold forging process, consisting in swaging the pipe inside connectors with suitable profile, by using high pressure seawater. Three swaging operations have to be performed to replace the damaged pipe length. This technology has been developed through extensive theoretical work and laboratory testing, ending in a Type Approval by DNV over pipe sizes ranging from 20 inches to 48 inches OD. A complete SiRCoS system has been realised for the Green Stream pipeline, thoroughly tested in workshop as well as in shallow water and is now ready, in the event of an emergency situation.The key functional requirements for the system are: diverless repair intervention and fully piggability after repair. Eni owns this technology and is now available to other operators under Repair Club arrangement providing stand-by repair services carried out by Saipem Energy Services. The paper gives a description of the main features of the Repair System as well as an insight into the technological developments on pipe cold forging reliability and long term duration evaluation. (author)

  7. Repair-modification of radiodamaged genes

    International Nuclear Information System (INIS)

    Volpe, P.; Institute of Experimental Medicine, Rome; Eremenko, T.

    1995-01-01

    It is proposed that through repair-modification, the modified base 5mC may have facilitated the divergent evolution of coding (hypomethylated exon) and uncoding (hypermethylated promoter and intron) sequences in eukaryotic genes. The radioinduced repair patches appearing in regions lacking 5mC are fully reconstructed by excision-repair, whereas those appearing in regions containing 5mC are incompletely reconstructed by this conventional mechanism. Such a second class of repair patches may, however, become fully reconstructed, in the S phase, by repair-modification. In fact, while DNA polymerase β - which is a key enzyme of excision-repair - is active through the whole interphase. DNA methylase - which is responsible for post-synthetic DNA modification - is essentially active in S. Uncoupling of these two enzyme systems, outside S, might explain why in unsynchronised cells repair patches of non-replicating strands are hypomethylated when compared with specific methylation of replicating strands. In other words, excision-repair would always be able to re-establish the primary ATGC language of both damaged unmethylated and methylated regions, while repair-modification would be able to re-establish the modified ATGC(5mC) language of the damaged methylated regions, only in S, but not in G 1 or G 2 . In these two phases, when DNA methylation is inversely correlated with pre-mRNA transcription (as in the case of many tissue-specific genes), such demethylation might induce a silent transcriptional unit to become active. (Author)

  8. DNA excision repair in permeable human fibroblasts

    International Nuclear Information System (INIS)

    Kaufmann, W.K.; Bodell, W.J.; Cleaver, J.E.

    1983-01-01

    U.v. irradiation of confluent human fibroblasts activated DNA repair, aspects of which were characterized in the cells after they were permeabilized. Incubation of intact cells for 20 min between irradiation and harvesting was necessary to obtain a maximum rate of reparative DNA synthesis. Cells harvested immediately after irradiation before repair was initiated displayed only a small stimulation of DNA synthesis, indicating that permeable cells have a reduced capacity to recognize pyrimidine dimers and activate repair. The distribution of sizes of DNA strands labeled during 10 min of reparative DNA synthesis resembled that of parental DNA. However, during a 60-min incubation of permeable cells at 37 degrees C, parental DNA and DNA labeled by reparative DNA synthesis were both cleaved to smaller sizes. Cleavage also occurred in unirradiated cells, indicating that endogenous nuclease was active during incubation. Repair patches synthesized in permeable cells displayed increased sensitivity to digestion by micrococcal nuclease. However, the change in sensitivity during a chase with unlabeled DNA precursors was small, suggesting that reassembly of nucleosome structure at sites of repair was impaired. To examine whether this deficiency was due to a preponderance of incomplete or unligated repair patches, 3H-labeled (repaired) DNA was purified, then digested with exonuclease III and nuclease S1 to probe for free 3' ends and single-stranded regions. About 85% of the [3H]DNA synthesized during a 10-min pulse resisted digestion, suggesting that a major fraction of the repair patches that were filled were also ligated. U.v. light-activated DNA synthesis in permeable cells, therefore, appears to represent the continuation of reparative gap-filling at sites of excision repair activated within intact cells. Gap-filling and ligation were comparatively efficient processes in permeable cells

  9. [Compressive anterior thoracoplasty (modified Abramson's repair) for pectus carinatum repair].

    Science.gov (United States)

    Álvarez Muñoz, V; Prado Valle, M A; López López, A J; Martínez Suárez, M A; Oviedo Gutiérrez, M; Montalvo Ávalos, C; Fernández García, L

    2014-04-15

    For anterior protruding chest wall deformities treatment, mainly pectus carinatum, pediatric surgeons have been managing either orthotic methods or open surgical repairs. Anterior compressive thoracoplasty (Abramson's technique) has widened the therapeutic options. We describe herein a modification of this technique in the first reported Europen series. From 2010 to 2012, a total of five patients (four male and one female) underwent a modified Abramson's technique to correct pectus carinatum or combined protrusion of the chest at our center. We report the operative technique used for these reconstructions. In all five cases, the operation was completed uneventfully and with excellent results either for the surgical team or the patients. Mean operative time was 190 minutes and hospitalization lasted for three to six days, at the time of analgesic drugs withdrawal. We consider the anterior compresive thorocoplasty (modified Abramson's technique) a safe and feasible method to correct protruding chest deformities, particularly in those patients with stiff chest or lack of compliance, in order to avoid the agressive open procedures.

  10. Weld Repair of Thin Aluminum Sheet

    Science.gov (United States)

    Beuyukian, C. S.; Mitchell, M. J.

    1986-01-01

    Weld repairing of thin aluminum sheets now possible, using niobium shield and copper heat sinks. Refractory niobium shield protects aluminum adjacent to hole, while copper heat sinks help conduct heat away from repair site. Technique limits tungsten/inert-gas (TIG) welding bombardment zone to melt area, leaving surrounding areas around weld unaffected. Used successfully to repair aluminum cold plates on Space Shuttle, Commercial applications, especially in sealing fractures, dents, and holes in thin aluminum face sheets or clad brazing sheet in cold plates, heat exchangers, coolers, and Solar panels. While particularly suited to thin aluminum sheet, this process also used in thicker aluminum material to prevent surface damage near weld area.

  11. Initial Development of Composite Repair Resins With Low Hazardous Air Pollutant Contents

    National Research Council Canada - National Science Library

    LaScala, John J; Bingham, Scott; Andrews, Kevin S; Sands, James M; Palmese, Guiseppe R

    2008-01-01

    Unsaturated polyester-based repair resins, such a Bondo, are widely used for automotive repair, marine repair, sporting equipment repair, and household repair of metal, composites, plastics, and wood...

  12. Mesenchymal stem cells overexpressing Ihh promote bone repair.

    Science.gov (United States)

    Zou, Shasha; Chen, Tingting; Wang, Yanan; Tian, Ruhui; Zhang, Lingling; Song, Pingping; Yang, Shi; Zhu, Yong; Guo, Xizhi; Huang, Yiran; Li, Zheng; Kan, Lixin; Hu, Hongliang

    2014-10-28

    Indian hedgehog (Ihh) signaling pathway is known to play key roles in various aspects of normal endochondral bone development. This study tested the potential roles of high Ihh signaling in the context of injury-induced bone regeneration. A rabbit tibia defect model was established to test the effects of the implant of Ihh/mesenchymal stem cells (MSCs)/scaffold complex. Computed tomography (CT), gross observation, and standard histological and immunohistological techniques were used to evaluate the effectiveness of the treatment. In vitro studies with MSCs and C3H10T1/2 cells were also employed to further understand the cellular and molecular mechanisms. We found that the implanted Ihh/MSCs/scaffold complex promoted bone repair. Consistently, in vitro study found that Ihh induced the upregulation of chondrocytic, osteogenic, and vascular cell markers, both in C3H10T1/2 cells and MSCs. Our study has demonstrated that high Ihh signaling in a complex with MSCs enhanced bone regeneration effectively in a clinically relevant acute injury model. Even though the exact underlying mechanisms are still far from clear, our primary data suggested that enhanced chondrogenesis, osteogenesis, and angiogenesis of MSCs at least partially contribute to the process. This study not only has implications for basic research of MSCs and Ihh signaling pathway but also points to the possibility of direct application of this specific paradigm to clinical bone repair.

  13. Fibronectin Extra Domain A Promotes Liver Sinusoid Repair following Hepatectomy.

    Directory of Open Access Journals (Sweden)

    Bridget Sackey-Aboagye

    Full Text Available Liver sinusoidal endothelial cells (LSECs are the main endothelial cells in the liver and are important for maintaining liver homeostasis as well as responding to injury. LSECs express cellular fibronectin containing the alternatively spliced extra domain A (EIIIA-cFN and increase expression of this isoform after liver injury, although its function is not well understood. Here, we examined the role of EIIIA-cFN in liver regeneration following partial hepatectomy. We carried out two-thirds partial hepatectomies in mice lacking EIIIA-cFN and in their wild type littermates, studied liver endothelial cell adhesion on decellularized, EIIIA-cFN-containing matrices and investigated the role of cellular fibronectins in liver endothelial cell tubulogenesis. We found that liver weight recovery following hepatectomy was significantly delayed and that sinusoidal repair was impaired in EIIIA-cFN null mice, especially females, as was the lipid accumulation typical of the post-hepatectomy liver. In vitro, we found that liver endothelial cells were more adhesive to cell-deposited matrices containing the EIIIA domain and that cellular fibronectin enhanced tubulogenesis and vascular cord formation. The integrin α9β1, which specifically binds EIIIA-cFN, promoted tubulogenesis and adhesion of liver endothelial cells to EIIIA-cFN. Our findings identify a role for EIIIA-cFN in liver regeneration and tubulogenesis. We suggest that sinusoidal repair is enhanced by increased LSEC adhesion, which is mediated by EIIIA-cFN.

  14. The effect of caffeine on repair systems in oocytes of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Mendelson, D.

    1976-01-01

    Irradiated males were mated to females that had received treatment with caffeine or honey (by feeding), and the frequencies of sex-chromosome losses and chromosome rearrangements induced in mature spermatozoa of the males were compared. Caffeine treatment led to an enhancement of the frequencies of sex-chromosome loss and a decrease in those of rearrangements. These findings can be interpreted on the assumption that caffeine inhibits repair and misrepair processes that are active in the oocytes. Caffeine treatment administered to one of the female stocks used in these studies was without any effect, presumably because of the absence of a caffeine-sensitive repair mechanism in the oocytes

  15. Electrospun composites of PHBV/pearl powder for bone repairing

    Directory of Open Access Journals (Sweden)

    Jingjing Bai

    2015-08-01

    Full Text Available Electrospun fiber has highly structural similarity with natural bone extracelluar matrix (ECM. Many researches about fabricating organic–inorganic composite materials have been carried out in order to mimic the natural composition of bone and enhance the biocompatibility of materials. In this work, pearl powder was added to the poly (3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV and the composite nanofiber scaffold was prepared by electrospinning. Mineralization ability of the composite scaffolds can be evaluated by analyzing hydroxyapatite (HA formation on the surface of nanofiber scaffolds. The obtained composite nanofiber scaffolds showed an enhanced mineralization capacity due to incorporation of pearl powder. The HA formed amount of the composite scaffolds was raised as the increase of pearl powder in composite scaffolds. Therefore, the prepared PHBV/pearl composite nanofiber scaffolds would be a promising candidate as an osteoconductive composite material for bone repairing.

  16. Long-term successful arthroscopic repair of large and massive rotator cuff tears with a functional and degradable reinforcement device.

    Science.gov (United States)

    Proctor, Christopher S

    2014-10-01

    Rotator cuff repair is a procedure with varying outcomes, and there has been subsequent interest in devices that reinforce the repair and enhance structural and functional outcomes. The objective of this study was to determine these outcomes for arthroscopic repair of large and massive rotator cuff tears augmented with a synthetic absorbable mesh designed specifically for reinforcement of tendon repair by imaging and clinical assessments. Consecutive arthroscopic repairs were performed on 18 patients with large to massive rotator cuff tears by use of a poly-l-lactic acid synthetic patch as a reinforcement device and fixation with 4 sutures. Patients were assessed preoperatively and at 6 months, 12 months, and a mean of 42 months after surgery by the American Shoulder and Elbow Surgeons (ASES) shoulder score to evaluate clinical performance and at 12 months by ultrasound to assess structural repair. Ultrasound showed that 15 of 18 patients had intact rotator cuff repair at 12 months; at 42 months, an additional patient had a failed repair. Patients showed improvement in the ASES shoulder score from 25 preoperatively to 71 at 12 months and 70 at 42 months after surgery. Patients with intact rotator cuff (n = 14) at 42 months had an ASES shoulder score of 82. The poly-l-lactic acid bioabsorbable patch designed specifically to reinforce the surgical repair of tendons supported successful repair of large to massive rotator cuff tears in 83% of patients at 12 months after surgery and 78% of patients at 42 months after surgery, with substantial functional improvement. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  17. Cytogenetic Response to Ionizing Radiation Exposure in Human Fibroblasts with Suppressed Expression of Non-DSB Repair Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Hammond, Dianne; Mehta, Satish K.; Jeevarajan, Antony S.; Pierson, Duane L.; Wu, Honglu

    2009-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in radiation-induced chromosome aberrations and micronuclei formation. In the study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequencies of micronuclei (MN) formation and chromosome aberrations were measured to determine the efficiency of cytogenetic repair, and the fraction of bi-nucleated cells in the MN analysis was used as a marker for cell cycle progression. In response to gamma radiation, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR

  18. DNA repair in proteus mirabilis. 5

    International Nuclear Information System (INIS)

    Hofemeister, J.; Boehme, H.; Fleischhacker, M.; Adler, B.; Eitner, G.; Steinborn, G.

    1979-01-01

    Inducible cell lysis in UV-irradiated cultures of Proteus mirabilis PG VI rec + derivatives is due to the induction of a defective prophage dP VI. This lytic response is found to account for the extraordinary high UV sensitivity of P. mirabilis rec + strains. Lysis of cells after UV or mitomycin C treatment is accompanied by the release of various defective phage particles including head-tail, tail and polysheath structures. Survival of P. mirabilis is shown to be strongly affected by the plating procedure. It is supposed that plating of UV-irradiated rec + cells after a distinct time of growth in liquid medium some how enhances the efficiency of repair activities rather than to prevent inducible cell lysis in P. mirabilis from occurring. The resident defective prophage interferes with the multiplication of infectious temperate phages (π1) as indicated by the efficiency of plating and plaque size. The extent of host-controlled reactivation of UV-irradiated phages, however, was not influenced by the lysogenic state of the host bacteria. The derepression of the resident prophage is thought to correlate with the appearence after UV exposure of a distinct and relatively stable low molecular weight DNA which is assumed to originate from enzymatic fragmentation rather than postmortal nicking of chromosomal DNA in P. mirabilis. Mutants are described which lost the inducible cell lysis response and, in case of PG 1300- also lost the immunity for bacteriolytic activities formed by PG VI strains after lysogenic induction. Whilst this derivative of P. mirabilis might either be cured for the defective prophage or rendered noninducible by mutation this substrain lost also both the extrasensitivity against UV and the chromosomal DNA fragmentation. The extent of the UV-induced DNA degradation response seems not to be markedly affected by these DNA fragmentations. (author)

  19. A history of the DNA repair and mutagenesis field: The discovery of base excision repair.

    Science.gov (United States)

    Friedberg, Errol C

    2016-01-01

    This article reviews the early history of the discovery of an DNA repair pathway designated as base excision repair (BER), since in contrast to the enzyme-catalyzed removal of damaged bases from DNA as nucleotides [called nucleotide excision repair (NER)], BER involves the removal of damaged or inappropriate bases, such as the presence of uracil instead of thymine, from DNA as free bases. Copyright © 2015. Published by Elsevier B.V.

  20. Pulpal progenitors and dentin repair.

    Science.gov (United States)

    Harichane, Y; Hirata, A; Dimitrova-Nakov, S; Granja, I; Goldberg, A; Kellermann, O; Poliard, A

    2011-07-01

    Mesenchymal stem cells are present in the dental pulp. They have been shown to contribute to dentin-like tissue formation in vitro and to participate in bone repair after a mandibular lesion. However, their capacity to contribute efficiently to reparative dentin formation after pulp lesion has never been explored. After pulp exposure, we have identified proliferative cells within 3 zones. In the crown, zone I is near the cavity, and zone II corresponds to the isthmus between the mesial and central pulp. In the root, zone III, near the apex, at a distance from the inflammatory site, contains mitotic stromal cells which may represent a source of progenitor cells. Stem-cell-based strategies are promising treatments for tissue injury in dentistry. Our experiments focused on (1) location of stem cells induced to leave their quiescent state early after pulp injury and (2) implantation of pulp progenitors, a substitute for classic endodontic treatments, paving the way for pulp stem-cell-based therapies.