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Sample records for repair mmr system

  1. Mismatch repair system (MMR) status correlates with response and survival in non-small cell lung cancer (NSCLC) patients.

    Science.gov (United States)

    Scartozzi, Mario; Franciosi, Vittorio; Campanini, Nicoletta; Benedetti, Giovanni; Barbieri, Fausto; Rossi, Giulio; Berardi, Rossana; Camisa, Roberta; Silva, Rosa Rita; Santinelli, Alfredo; Ardizzoni, Andrea; Crinò, Lucio; Rindi, Guido; Cascinu, Stefano

    2006-07-01

    Pre-clinical data suggested a relationship between inactivation of hMLH1 and hMSH2 and resistance to drugs like cisplatin and carboplatin, but not oxaliplatin. We then hypothesised that NSCLC showing loss of expression of the mismatch repair system (MMR), could be refractory to cisplatin-based, but not to oxaliplatin-based chemotherapy. Immunohistochemical expression of hMLH1 and hMSH2 was analysed on tumour samples from 93 advanced NSCLC, receiving chemotherapy with either cisplatin or oxaliplatin in combination with gemcitabine. Patients showing loss of hMLH1 or hMSH2 expression in > or = 50% of tumour cells were deemed MMR-negative (Group A), whereas cases with a normal hMLH1 or hMSH2 expression in > 50% of the tumour cells were defined MMR-positive (Group B). No differences in the response and progression rate were found in the whole patients population and in the gemcitabine/cisplatin group for both hMLH1 and hMSH2. In the gemcitabine/oxaliplatin group response rate was 38% and 0% (p=0.04) for patients with or without loss of hMSH2 expression. Median survival according to MMR status in Groups A and B, respectively was: 17 months versus 9 months for hMLH1 (p=0.031) and 10 months versus 9 months for hMSH2 (p=0.8330). Both the difference in response rate and in median survival observed according to MMR status seem to confirm what has been suggested by preclinical studies.

  2. The mismatch repair system modulates curcumin sensitivity through induction of DNA strand breaks and activation of G2-M checkpoint.

    Science.gov (United States)

    Jiang, Zhihua; Jin, ShunQian; Yalowich, Jack C; Brown, Kevin D; Rajasekaran, Baskaran

    2010-03-01

    The highly conserved mismatch (MMR) repair system corrects postreplicative errors and modulates cellular responses to genotoxic agents. Here, we show that the MMR system strongly influences cellular sensitivity to curcumin. Compared with MMR-proficient cells, isogenically matched MMR-deficient cells displayed enhanced sensitivity to curcumin. Similarly, cells suppressed for MLH1 or MSH2 expression by RNA interference displayed increased curcumin sensitivity. Curcumin treatment generated comparable levels of reactive oxygen species and the mutagenic adduct 8-oxo-guanine in MMR-proficient and MMR-deficient cells; however, accumulation of gammaH2AX foci, a marker for DNA double-strand breaks (DSB), occurred only in MMR-positive cells in response to curcumin treatment. Additionally, MMR-positive cells showed activation of Chk1 and induction of G(2)-M cell cycle checkpoint following curcumin treatment and inhibition of Chk1 by UCN-01 abrogated Chk1 activation and heightened apoptosis in MMR-proficient cells. These results indicate that curcumin triggers the accumulation of DNA DSB and induction of a checkpoint response through a MMR-dependent mechanism. Conversely, in MMR-compromised cells, curcumin-induced DSB is significantly blunted, and as a result, cells fail to undergo cell cycle arrest, enter mitosis, and die through mitotic catastrophe. The results have potential therapeutic value, especially in the treatment of tumors with compromised MMR function.

  3. Impact of DNA mismatch repair system alterations on human fertility and related treatments.

    Science.gov (United States)

    Hu, Min-hao; Liu, Shu-yuan; Wang, Ning; Wu, Yan; Jin, Fan

    2016-01-01

    DNA mismatch repair (MMR) is one of the biological pathways, which plays a critical role in DNA homeostasis, primarily by repairing base-pair mismatches and insertion/deletion loops that occur during DNA replication. MMR also takes part in other metabolic pathways and regulates cell cycle arrest. Defects in MMR are associated with genomic instability, predisposition to certain types of cancers and resistance to certain therapeutic drugs. Moreover, genetic and epigenetic alterations in the MMR system demonstrate a significant relationship with human fertility and related treatments, which helps us to understand the etiology and susceptibility of human infertility. Alterations in the MMR system may also influence the health of offspring conceived by assisted reproductive technology in humans. However, further studies are needed to explore the specific mechanisms by which the MMR system may affect human infertility. This review addresses the physiological mechanisms of the MMR system and associations between alterations of the MMR system and human fertility and related treatments, and potential effects on the next generation.

  4. MUTYH and the mismatch repair system: partners in crime?

    Science.gov (United States)

    Niessen, Renée C; Sijmons, Rolf H; Ou, J; Olthof, Sandra G M; Osinga, Jan; Ligtenberg, Marjolijn J; Hogervorst, Frans B L; Weiss, Marjan M; Tops, Carli M J; Hes, Frederik J; de Bock, Geertruida H; Buys, Charles H C M; Kleibeuker, Jan H; Hofstra, Robert M W

    2006-03-01

    Biallelic germline mutations of MUTYH-a gene encoding a base excision repair protein-are associated with an increased susceptibility of colorectal cancer. Whether monoallelic MUTYH mutations also increase cancer risk is not yet clear, although there is some evidence suggesting a slight increase of risk. As the MUTYH protein interacts with the mismatch repair (MMR) system, we hypothesised that the combination of a monoallelic MUTYH mutation with an MMR gene mutation increases cancer risk. We therefore investigated the prevalence of monoallelic MUTYH mutations in carriers of a germline MMR mutation: 40 carriers of a truncating mutation (group I) and 36 of a missense mutation (group II). These patients had been diagnosed with either colorectal or endometrial cancer. We compared their MUTYH mutation frequencies with those observed in a group of 134 Dutch colorectal and endometrial cancer patients without an MMR gene mutation (0.7%) and those reported for Caucasian controls (1.5%). In group I one monoallelic MUTYH mutation was found (2.5%). In group II five monoallelic germline MUTYH mutations were found (14%), four of them in MSH6 missense mutation carriers (20%). Of all patients with an MMR gene mutation, only those with a missense mutation showed a significantly higher frequency of (monoallelic) MUTYH mutations than the Dutch cancer patients without MMR gene mutations (P = 0.002) and the published controls (P = 0.001). These results warrant further study to test the hypothesis of mutations in MMR genes (in particular MSH6) and MUTYH acting together to increase cancer risk.

  5. Functions of the MMR system and special roles of mutL in bacterial evolution

    Institute of Scientific and Technical Information of China (English)

    JUN GONG; RU JING JIA

    2006-01-01

    DNA mismatch repair guards the integrity of the genome of almost all organisms by correcting DNA biosynthetic errors and by ensuring the fidelity of homologous genetic recombination. MutL is one of the important proteins involved in mismatch repair system. It has been suggested to function as a master coordinator or molecular matchmaker because it interacts physically with MutS, the endonuclease MutH, and DNA helicase UvrD. It also binds to DNA and has an ATPase activity. MutL defective bacteria strains have elevated mutation rates and it has been reported recently that MutL defect may have an important impact on bacterial evolution.

  6. A mononucleotide repeat in PRRT2 is an important, frequent target of mismatch repair deficiency in cancer

    NARCIS (Netherlands)

    I. Teles Alves (Inês); Cano, D. (David); R. Böttcher (René); H.A.G.M. van der Korput (Hetty); W.N.M. Dinjens (Winand); G.W. Jenster (Guido); J. Trapman (Hans)

    2017-01-01

    textabstractThe DNA mismatch repair (MMR) system corrects DNA replication mismatches thereby contributing to the maintenance of genomic stability. MMR deficiency has been observed in prostate cancer but its impact on the genomic landscape of these tumours is not known. In order to identify MMR assoc

  7. Measles, Mumps, Rubella (MMR)

    Science.gov (United States)

    ... at Each Vaccine: MMR (Measles, Mumps and Rubella) Vaccine Children's Hospital of Philadelphia (CHOP): Learn about measles, how ... Disease Control and Prevention AAP Urges Parents to Vaccinate Children to Protect Against Measles (1/23/15) American ...

  8. Grey Repairable System Analysis

    Institute of Scientific and Technical Information of China (English)

    Renkuan Guo; Charles Ernie Love

    2006-01-01

    In this paper, we systematically discuss the basic concepts of grey theory, particularly the grey differential equation and its mathematical foundation, which is essentially unknown in the reliability engineering community. Accordingly,we propose a small-sample based approach to estimate repair improvement effects by partitioning system stopping times into intrinsic functioning times and repair improvement times. An industrial data set is used for illustrative purposes in a stepwise manner.

  9. DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch Syndrome

    OpenAIRE

    Poulogiannis, George; Frayling, Ian; Arends, Mark

    2009-01-01

    Abstract DNA mismatch repair (MMR) deficiency is one of the best understood forms of genetic instability in colorectal cancer (CRC), and is characterised by the loss of function of the MMR pathway. Failure to repair replication-associated errors due to a defective MMR system allows persistence of mismatch mutations all over the genome, but especially in regions of repetitive DNA known as microsatellites, giving rise to the phenomenon of microsatellite instability (MSI). A high freq...

  10. Mammalian mismatch repair

    DEFF Research Database (Denmark)

    Pena Diaz, Javier; Jiricny, Josef

    2012-01-01

    A considerable surge of interest in the mismatch repair (MMR) system has been brought about by the discovery of a link between Lynch syndrome, an inherited predisposition to cancer of the colon and other organs, and malfunction of this key DNA metabolic pathway. This review focuses on recent...... advances in our understanding of the molecular mechanisms of canonical MMR, which improves replication fidelity by removing misincorporated nucleotides from the nascent DNA strand. We also discuss the involvement of MMR proteins in two other processes: trinucleotide repeat expansion and antibody maturation...

  11. Treating dynamical stability as an observable: a 5:2 MMR configuration for the extrasolar system HD 181433

    CERN Document Server

    Campanella, Giammarco

    2011-01-01

    The three-planet extrasolar system of HD 181433 has been detected with HARPS. The best-fit solution, announced by the discovery team, describes a highly unstable, self-disrupting configuration. In fact, a narrow observational window, only partially covering the longest orbital period, can lead to solutions representing unrealistic scenarios. Taking into account the dynamical stability as an additional observable while interpreting the RV data, we can analyse the phase space in a neighbourhood of the statistically best-fit and derive dynamically stable configurations that reproduce the observed RV signal. Our Newtonian stable best-fit model is capable of surviving for at least 250 Myrs. The two giant companions are found to be locked in the 5:2 MMR as Jupiter and Saturn in the Solar System. This mechanism does not allow close encounters even in case of highly eccentric orbits. Moreover, planets c and d are located in regions spanned by many other strong low-order MMRs. We study the dynamics of some plausible s...

  12. Mechanisms and functions of DNA mismatch repair

    Institute of Scientific and Technical Information of China (English)

    Guo MinLi

    2008-01-01

    DNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs generated dur-ing DNA replication and recombination. MMR also suppresses homeologous recombination and was recently shown to play a role in DNA damage signaling in eukaryotic cells. Escherichia coli MutS and MutL and their eukaryotic homo-logs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Many other protein components that participate in various DNA metabolic pathways, such as PCNA and RPA, are also essential for MMR. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including he-reditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.

  13. The origin and 9:7 MMR dynamics of the Kepler-29 system

    CERN Document Server

    Migaszewski, Cezary; Panichi, Federico

    2016-01-01

    We analyse the Transit Timing Variation (TTV) measurements of a~system of two super-Earths detected as Kepler-29, in order to constrain the planets' masses and orbital parameters. A dynamical analysis of the best-fitting configurations constrains the masses to be $\\sim 5$ and $\\sim 6$ Earth masses for the inner and the outer planets, respectively. The analysis also reveals that the system is likely locked in the 9:7~mean motion resonance. However, a variety of orbital architectures regarding eccentricities and the relative orientation of orbits is permitted by the observations as well as by stability constraints. We attempt to find configurations preferred by the planet formation scenarios as an additional, physical constraint. We show that configurations with low eccentricities and anti-aligned apsidal lines of the orbits are a natural and most likely outcome of the convergent migration. However, we show that librations of the critical angles are not necessary for the Kepler-29 system to be dynamically reson...

  14. The origin and 9:7 MMR dynamics of the Kepler-29 system

    Science.gov (United States)

    Migaszewski, Cezary; Goździewski, Krzysztof; Panichi, Federico

    2017-02-01

    We analyse the transit timing variation measurements of a system of two super-Earths detected as Kepler-29, in order to constrain the planets' masses and orbital parameters. A dynamical analysis of the best-fitting configurations constrains the masses to be ˜6 and ˜5 Earth masses for the inner and the outer planets, respectively. The analysis also reveals that the system is likely locked in the 9:7 mean motion resonance. However, a variety of orbital architectures regarding eccentricities and the relative orientation of orbits is permitted by the observations as well as by stability constraints. We attempt to find configurations preferred by the planet formation scenarios as an additional, physical constraint. We show that configurations with low eccentricities and anti-aligned apsidal lines of the orbits are a natural and most likely outcome of the convergent migration. However, we show that librations of the critical angles are not necessary for the Kepler-29 system to be dynamically resonant, and such configurations may be formed on the way of migration as well. We argue, on the other hand, that aligned configurations with e ≳ 0.03 may be not consistent with the migration scenario.

  15. MMR: risk, choice, chance.

    Science.gov (United States)

    Fitzpatrick, Michael

    2004-01-01

    The unfolding of the measles, mumps and rubella (MMR) controversy reveals some of the key features of the cultural climate affecting matters of health and illness in contemporary society. A high level of anxiety around issues of health is reflected in a heightened sense of individual vulnerability to environmental dangers (such as atmospheric pollution, electromagnetic fields, bioterrorism) and in a general aversion to risk, particularly in relation to children. This mood has proved responsive to views sceptical, if not hostile, towards science and medicine and associated professionals, particularly in the sphere of immunization. The result is that uptake of MMR vaccination in the UK has fallen, from a peak of 92% in the mid-1990s to a national level of 82% in 2003 (at the age of two); in London uptake is now less than 75%-much less in some areas-causing a significant risk of outbreaks of measles. In the USA too, the proportion of parents opting out of regulations requiring immunization as a condition of school entry has increased significantly in some areas, though these controversies appear to have had little impact so far in continental Europe.

  16. DNA Mismatch Repair System: Repercussions in Cellular Homeostasis and Relationship with Aging

    Directory of Open Access Journals (Sweden)

    Juan Cristóbal Conde-Pérezprina

    2012-01-01

    Full Text Available The mechanisms that concern DNA repair have been studied in the last years due to their consequences in cellular homeostasis. The diverse and damaging stimuli that affect DNA integrity, such as changes in the genetic sequence and modifications in gene expression, can disrupt the steady state of the cell and have serious repercussions to pathways that regulate apoptosis, senescence, and cancer. These altered pathways not only modify cellular and organism longevity, but quality of life (“health-span”. The DNA mismatch repair system (MMR is highly conserved between species; its role is paramount in the preservation of DNA integrity, placing it as a necessary focal point in the study of pathways that prolong lifespan, aging, and disease. Here, we review different insights concerning the malfunction or absence of the DNA-MMR and its impact on cellular homeostasis. In particular, we will focus on DNA-MMR mechanisms regulated by known repair proteins MSH2, MSH6, PMS2, and MHL1, among others.

  17. DNA Mismatch Repair System: Repercussions in Cellular Homeostasis and Relationship with Aging

    Science.gov (United States)

    Conde-Pérezprina, Juan Cristóbal; León-Galván, Miguel Ángel; Konigsberg, Mina

    2012-01-01

    The mechanisms that concern DNA repair have been studied in the last years due to their consequences in cellular homeostasis. The diverse and damaging stimuli that affect DNA integrity, such as changes in the genetic sequence and modifications in gene expression, can disrupt the steady state of the cell and have serious repercussions to pathways that regulate apoptosis, senescence, and cancer. These altered pathways not only modify cellular and organism longevity, but quality of life (“health-span”). The DNA mismatch repair system (MMR) is highly conserved between species; its role is paramount in the preservation of DNA integrity, placing it as a necessary focal point in the study of pathways that prolong lifespan, aging, and disease. Here, we review different insights concerning the malfunction or absence of the DNA-MMR and its impact on cellular homeostasis. In particular, we will focus on DNA-MMR mechanisms regulated by known repair proteins MSH2, MSH6, PMS2, and MHL1, among others. PMID:23213348

  18. [Comparison of geno- and cytotoxicity of methylnitrosourea on MMR-proficient and MMR-deficient human tumor cell lines].

    Science.gov (United States)

    Tronov, V A; Kramarenko, I I; Smirnova, T D; Terekhov, S M

    2006-01-01

    Deficient mismatch repair (MMR) is identified as a mutation of one of four major MMR genes and(or) microsatellite instability. These genomic changes are used as markers of MMR status of the heredity nonpolyposis colorectal cancer (HNPCC) spectrum tumors--familial and sporadic tumors of colon and extracolonic cancers fulfilling Amsterdam clinical criteria II. MMR-deficiency results in mutator phenotype and resistance to geno- and cytotoxicity of alkylating agents. The main cytotoxic damage to DNA in response to chemical methylation is O6-methylguanine (O6-mG). The secondary DNA strand breaks, which are formed during the MMR functioning, are proposed to be required for methylation induced cytotoxicity. We have assumed that the secondary double stand breaks (DSB) upon DNA methylation are able to represent functional efficiency of MMR in cells. The purpose of the paper was to test this assumption on human tumor cells differing in MMR-status and pulse-treated with methylnitrosourea (MNU). We used 3 cell lines: HeLa (MMR-competent endometrial tumor cells), HCT116 (MMR-deficient colorectal carcinoma cells), and Colo320 (sigmoid intestine tumor cells with uncharacterized MMR status). DSBs were evaluated with neutral comet assay. Cytotoxicity/viability was evaluated with MTT-asay and apoptotic index (frequency of morphologically determined apoptotic cells). We show that 1) cytotoxic effect of MNU (250 microM) on HeLa cells was exhibited 3 days after pulse-treatment of cells with MNU; 2) DSBs occurred 48 h after the drug treatment but prior to the onset of apoptosis of HeLa cells; 3) MMR-deficient HCT116 cells were resistant to the drug: no decreased viability, DSBs and apoptosis were observed during 3 days after cell treatment. Both cell lines exhibited high sensitivity to etoposide, classical inductor of unrepairable DSBs and p53. Etoposide has been found to induce DSBs in 6-12 h, which was followed by apoptosis (in 24 h). Colo320 cells exhibited intermediate position

  19. MMR Vaccination and Febrile Seizures

    DEFF Research Database (Denmark)

    Vestergaard, Mogens; Hviid, Anders; Madsen, Kreesten Meldgaard

    2004-01-01

    CONTEXT: The rate of febrile seizures increases following measles, mumps, and rubella (MMR) vaccination but it is unknown whether the rate varies according to personal or family history of seizures, perinatal factors, or socioeconomic status. Furthermore, little is known about the long-term outcome...... of febrile seizures following vaccination. OBJECTIVES: To estimate incidence rate ratios (RRs) and risk differences of febrile seizures following MMR vaccination within subgroups of children and to evaluate the clinical outcome of febrile seizures following vaccination. DESIGN, SETTING, AND PARTICIPANTS......: Incidence of first febrile seizure, recurrent febrile seizures, and subsequent epilepsy. RESULTS: A total of 439,251 children (82%) received MMR vaccination and 17,986 children developed febrile seizures at least once; 973 of these febrile seizures occurred within 2 weeks of MMR vaccination. The RR...

  20. 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.

  1. Integration of principles of systems biology and radiation biology: toward development of in silico models to optimize IUdR-mediated radiosensitization of DNA mismatch repair-deficient (damage tolerant human cancers

    Directory of Open Access Journals (Sweden)

    Timothy James Kinsella

    2011-08-01

    Full Text Available Over the last 7 years, we have focused our experimental and computational research efforts on improving our understanding of the biochemical, molecular, and cellular processing of iododeoxyuridine (IUdR and ionizing radiation (IR induced DNA base damage by DNA mismatch repair (MMR. These coordinated research efforts, sponsored by the National Cancer Institute Integrative Cancer Biology Program (ICBP, brought together system scientists with expertise in engineering, mathematics, and complex systems theory and translational cancer researchers with expertise in radiation biology. Our overall goal was to begin to develop computational models of IUdR- and/or IR- induced base damage processing by MMR that may provide new clinical strategies to optimize IUdR-mediated radiosensitiztion in MMR deficient (MMR- damage tolerant human cancers. Using multiple scales of experimental testing, ranging from purified protein systems to in vitro (cellular and to in vivo (human tumor xenografts in athymic mice models, we have begun to integrate and interpolate these experimental data with hybrid stochastic biochemical models of MMR damage processing and probabilistic cell cycle regulation models through a systems biology approach. In this article, we highlight the results and current status of our integration of radiation biology approaches and computational modeling to enhance IUdR-mediated radiosensitization in MMR- damage tolerant cancers.

  2. Kvitebjoern gas pipeline repair - baptism of remote pipeline repair system

    Energy Technology Data Exchange (ETDEWEB)

    Gjertveit, Erling

    2010-07-01

    On the 1st of November 2007, severe anchor damage was discovered on the 30 inch Kvitebjoern gas export pipeline. The damage constituted a localised dent and a 17deg buckle, but no leakage. Statoil has invested in building an effective repair contingency structure for the large pipeline network on the Norwegian Continental shelf, with particular focus on the large gas export pipelines. The repair method for the Kvitebjoern pipeline was remotely operated using two Morgrip couplings and a spool. The installation used the purpose built Pipeline Repair System stored at Killingoey and couplings produced and tested back in 2005. This presentation will cover the initial damage investigations, the temporary operational phase, the repair preparations, the actual repair and lessons learned. (Author)

  3. Construction of heteroduplex DNA and in vitro model for functional analysis of mismatch repair

    Institute of Scientific and Technical Information of China (English)

    WANG Yi; Clark Alan; WANG Jiaxun; SUN Menghong; SHI Daren

    2004-01-01

    Functional deficiency of mismatch repair (MMR) system is one of the mechanisms of tumorigenesis. With the development of the investigation and the requirement from the clinical diagnosis and treatment it is necessary to build up a method to evaluate the functional status of the whole MMR system in the concerned tumors. The original ssDNA and dsDNA from wild type (wt) bacteriophage M13mp2 and its three derivates with mutation points in the lacZα Gene have been used to construct two kinds of heteroduplex DNA molecules. One named del(2) has two bases deleted in the negative strand, the other has a G·G mismatch base pair in the negative strand too. Introducing this heteroduplex DNA into E. Coli NR9162 (mutS-) without the MMR ability on the indicator plate with x-gal and IPTG, there are three kinds of plaques, mixture plaque as the characteristic phenotype of heteroduplex DNA, blue and clear plaques. If the cell extract is mismatch repair competent the percentage of the mixture plaque will decrease after incubation with these heteroduplex DNA, the repair efficiency is expressed in percentage as 100× (1 minus the ratio of percentages of mixture plaque obtained from the extract-treated sample and untreated samples), which can imply the functional status of MMR system of certain samples. After large T-antigen-dependent SV-40 DNA replication assay cell extract from TK6, a human lymphoblastoid B-cell lymphoma cell line with MMR ability, and Lovo, a human colonic carcinoma cell line with MMR deficiency have incubated with these heteroduplex DNA. The repair efficiency of TK6 to del(2) is more than 60%, to G·G is more than 50%. The Lovo efficiency to del(2) is less than 10%, to G·G is less than 20%. Therefore, in this in vitro model used for functional analysis of mismatch repair of heteroduplex DNA as the repair target, TK6 can serve as the control for MMR proficiency and Lovo as the control for MMR deficiency. Using this model the tumor tissue from a case of hereditary

  4. Augmented Reality Repair Guidance System

    Directory of Open Access Journals (Sweden)

    Sidharth Bhatia

    2012-07-01

    Full Text Available The daily life of a common man revolves around various forms of appliances/gadgets he uses throughout the day such as a mobile phone, laptop, printer, microwave oven, washing machine, etc. Although these appliances/gadgets are taken by most of the people for granted, the problem occurs when any of these things do not work as they are expected to. Getting them to the repair shops for every small glitch is expensive as well as time consuming. Although most of the companies which produce these appliances/gadgets do supply them with basic manuals, which deal with how to solve these minor issues, but reading them and at the same time repairing the corresponding appliance/gadget can be a frustrating task at times. These problems can be reduced to a large extent if some kind of live guidance is available. In this paper we propose a method to do so with the help of an augmented reality based system that will guide the user to carry out small scale repair jobs on these gadgets. All that is required is a decent webcam and a computing device, with a processor of 1 GHz or more and a display screen.

  5. In vivo DNA mismatch repair measurement in zebrafish embryos and its use in screening of environmental carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yuanhong [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); Huang, Changjiang, E-mail: cjhuang5711@163.com [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); Bai, Chenglian; Du, Changchun; Liao, Junhua [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); Dong, Qiaoxiang, E-mail: dqxdong@163.com [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035 (China)

    2016-01-25

    Highlights: • We developed an in vivo DNA mismatch repair (MMR) measurement assay in zebrafish embryos. • This assay involves microinjection of homo- and heteroduplex EGFP plasmids into zebrafish embryos. • This novel assay was validated with embryos from the MMR-deficient mlh1 mutant fish. • We successfully applied this assay for detecting environmental chemicals with carcinogenic effect. • This novel assay can be used for screening of environmental carcinogens. - Abstract: Impairment of DNA mismatch repair (MMR) function leads to the development and progression of certain cancers. Many environmental contaminants can target DNA MMR system. Currently, measurement of MMR activity is limited to in vitro or in vivo methods at the cell line level, and reports on measurement of MMR activity at the live organism level are lacking. Here, we report an efficient method to measure DNA MMR activity in zebrafish embryos. A G-T mismatch was introduced into enhanced green fluorescent protein (EGFP) gene. Repair of the G-T mismatch to G-C in the heteroduplex plasmid generates a functional EGFP expression. The heteroduplex plasmid and a similarly constructed homoduplex plasmid were injected in parallel into the same batch of embryos at 1-cell stage and EGFP expression in EGFP positive embryos was quantified at 24 h after injection. MMR efficiency was calculated as the total fluorescence intensity of embryos injected with the heteroduplex construct divided by that of embryos injected with the homoduplex construct. Our results showed 73% reduction of MMR activity in embryos derived from MMR-deficient mlh1 mutant fish (positive control) when compared with embryos from MMR-competent wild type AB line fish, indicating feasibility of in vivo MMR activity measurement in zebrafish embryos. We further applied this novel assay for measurement of MMR efficiency in embryos exposed to environmental chemicals such as cadmium chloride (CdCl{sub 2}), benzo[a]pyrene (BaP), and

  6. Alkylation damage causes MMR-dependent chromosomal instability in vertebrate embryos.

    NARCIS (Netherlands)

    Feitsma, H.; Akay, A.; Cuppen, E.

    2008-01-01

    S(N)1-type alkylating agents, like N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU), are potent mutagens. Exposure to alkylating agents gives rise to O(6)-alkylguanine, a modified base that is recognized by DNA mismatch repair (MMR) proteins but is not repairable, resulting in

  7. The dual nature of mismatch repair as antimutator and mutator: for better or for worse

    Directory of Open Access Journals (Sweden)

    Sara Thornby Bak

    2014-08-01

    Full Text Available DNA is constantly under attack by a number of both exogenous and endogenous agents that challenge its integrity. Among the mechanisms that have evolved to counteract this deleterious action, mismatch repair (MMR has specialized in removing DNA biosynthetic errors that occur when replicating the genome. Malfunction or inactivation of this system results in an increase in spontaneous mutability and a strong predisposition to tumor development. Besides this key corrective role, MMR proteins are involved in other pathways of DNA metabolism such as mitotic and meiotic recombination and processing of oxidative damage. Surprisingly, MMR is also required for certain mutagenic processes. The mutagenic MMR has beneficial consequences contributing to the generation of a vast repertoire of antibodies through class switch recombination and somatic hypermutation processes. However, this non-canonical mutagenic MMR also has detrimental effects; it promotes repeat expansions associated with neuromuscular and neurodegenerative diseases and may contribute to cancer/disease-related aberrant mutations and translocations. The reaction responsible for replication error correction has been the most thoroughly studied and it is the subject to numerous reviews. This review describes briefly the biochemistry of MMR and focuses primarily on the non-canonical MMR activities described in mammals as well as emerging research implicating interplay of MMR and chromatin.

  8. Cross-calibration of the Siemens mMR

    DEFF Research Database (Denmark)

    Keller, Sune H; Jakoby, Björn; Svalling, Susanne;

    2016-01-01

    BACKGROUND: We present a quick and easy method to perform quantitatively accurate PET scans of typical water-filled PET plastic shell phantoms on the Siemens Biograph mMR PET/MR system. We perform regular cross-calibrations (Xcal) of our PET systems, including the PET/MR, using a Siemens mCT wate...

  9. Cross-calibration of the Siemens mMR

    DEFF Research Database (Denmark)

    Keller, Sune H; Jakoby, Björn; Svalling, Susanne

    2016-01-01

    BACKGROUND: We present a quick and easy method to perform quantitatively accurate PET scans of typical water-filled PET plastic shell phantoms on the Siemens Biograph mMR PET/MR system. We perform regular cross-calibrations (Xcal) of our PET systems, including the PET/MR, using a Siemens mCT water...

  10. 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.

  11. NIU's Kinder, Gentler, Housing Repair System.

    Science.gov (United States)

    Tillis, Linda; Montgomery, Rogene

    1999-01-01

    Explains the effective use of a centralized housing-repair request system at Northern Illinois University that has improved customer service and increased fiscal accountability. Describes the system and assesses of its effectiveness. (GR)

  12. A Two-Unit Cold Standby Repairable System with One Replaceable Repair Facility and Delay Repair:Some Reliability Problems

    Institute of Scientific and Technical Information of China (English)

    WEI Ying-yuan; TANG Ying-hui

    2004-01-01

    This paper considers a two-unit same cold standby repairable system with a replaceable repair facility and delay repair .The failure time of unit is assumed to follow exponential distribution , and the repair time and delay time of failed unit are assumed to follow arbitrary distributions , whereas the failure and replacement time distributions of the repair facility are exponential and arbitrary . By using the Markov renewal process theory, some primary reliability quantities of the system are obtained.

  13. Integrated Electrical Wire Insulation Repair System

    Science.gov (United States)

    Williams, Martha; Jolley, Scott; Gibson, Tracy; Parks, Steven

    2013-01-01

    An integrated system tool will allow a technician to easily and quickly repair damaged high-performance electrical wire insulation in the field. Low-melt polyimides have been developed that can be processed into thin films that work well in the repair of damaged polyimide or fluoropolymer insulated electrical wiring. Such thin films can be used in wire insulation repairs by affixing a film of this low-melt polyimide to the damaged wire, and heating the film to effect melting, flow, and cure of the film. The resulting repair is robust, lightweight, and small in volume. The heating of this repair film is accomplished with the use of a common electrical soldering tool that has been modified with a special head or tip that can accommodate the size of wire being repaired. This repair method can furthermore be simplified for the repair technician by providing replaceable or disposable soldering tool heads that have repair film already "loaded" and ready for use. The soldering tool heating device can also be equipped with a battery power supply that will allow its use in areas where plug-in current is not available

  14. Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 Expression.

    Science.gov (United States)

    Perazzoli, Gloria; Prados, Jose; Ortiz, Raul; Caba, Octavio; Cabeza, Laura; Berdasco, Maria; Gónzalez, Beatriz; Melguizo, Consolación

    2015-01-01

    The use of temozolomide (TMZ) has improved the prognosis for glioblastoma multiforme patients. However, TMZ resistance may be one of the main reasons why treatment fails. Although this resistance has frequently been linked to the expression of O6-methylguanine-DNA methyltransferase (MGMT) it seems that this enzyme is not the only molecular mechanism that may account for the appearance of drug resistance in glioblastoma multiforme patients as the mismatch repair (MMR) complex, P-glycoprotein, and/or the presence of cancer stem cells may also be implicated. Four nervous system tumor cell lines were used to analyze the modulation of MGMT expression and MGMT promoter methylation by TMZ treatment. Furthermore, 5-aza-2'-deoxycytidine was used to demethylate the MGMT promoter and O(6)-benzylguanine to block GMT activity. In addition, MMR complex and P-glycoprotein expression were studied before and after TMZ exposure and correlated with MGMT expression. Finally, the effect of TMZ exposure on CD133 expression was analyzed. Our results showed two clearly differentiated groups of tumor cells characterized by low (A172 and LN229) and high (SF268 and SK-N-SH) basal MGMT expression. Interestingly, cell lines with no MGMT expression and low TMZ IC50 showed a high MMR complex expression, whereas cell lines with high MGMT expression and high TMZ IC50 did not express the MMR complex. In addition, modulation of MGMT expression in A172 and LN229 cell lines was accompanied by a significant increase in the TMZ IC50, whereas no differences were observed in SF268 and SK-N-SH cell lines. In contrast, P-glycoprotein and CD133 was found to be unrelated to TMZ resistance in these cell lines. These results may be relevant in understanding the phenomenon of TMZ resistance, especially in glioblastoma multiforme patients laking MGMT expression, and may also aid in the design of new therapeutic strategies to improve the efficacy of TMZ in glioblastoma multiforme patients.

  15. 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)

  16. Evaluation of Lynch syndrome modifier genes in 748 MMR mutation carriers.

    Science.gov (United States)

    Houlle, Solene; Charbonnier, Françoise; Houivet, Estelle; Tinat, Julie; Buisine, Marie-Pierre; Caron, Olivier; Benichou, Jacques; Baert-Desurmont, Stéphanie; Frebourg, Thierry

    2011-08-01

    Several studies have reported that, in Lynch syndrome resulting from mutations of the mismatch repair (MMR) genes, a CA repeat ≤17 within the IGF1 promoter, SNPs within the xenobiotic metabolizing enzyme gene CYP1A1 and SNPs on 8q23.3 and 11q23.1 modify colorectal cancer (CRC) risk in MMR mutation carriers. We analysed the impact of these polymorphisms on CRC risk in 748 French MMR mutation carriers derived from 359 families. We also analysed the effect of the Novel 1 SNP (18q21), which has recently been shown to increase CRC risk in the general population. We observed a significant difference in the CRC-free survival time between males and females, between MSH2 and MSH6 mutation carriers and between MLH1 and MSH6, indicating that this series is representative of Lynch syndrome. In contrast, the univariate log-rank test, as well as multivariate Cox model analysis controlling for familial aggregation and mutated MMR gene, year of birth and gender showed that the polymorphic alleles tested were not associated with a significant CRC risk increase, neither on the entire sample nor among males and females. This discrepancy with previous reports might be explained both by the genetic heterogeneity between the different populations analysed and the allelic heterogeneity of the MMR mutations. We conclude that genotyping of these polymorphisms is not useful to evaluate CRC risk in MMR mutation carriers and to optimize their clinical follow-up.

  17. Evaluation of MMR Vaccination and Autism Link

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-11-01

    Full Text Available A retrospective cohort study of autism in all children born in Denmark from January 1991 through December 1998 and those receiving measles, mumps, and rubella (MMR vaccination is reported from the Danish Epidemiology Science Center, Aarhus, Denmark.

  18. 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.

  19. Loss of DNA mismatch repair imparts a selective advantage in planarian adult stem cells.

    Directory of Open Access Journals (Sweden)

    Jessica P Hollenbach

    Full Text Available Lynch syndrome (LS leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis.

  20. Loss of DNA mismatch repair imparts a selective advantage in planarian adult stem cells.

    Science.gov (United States)

    Hollenbach, Jessica P; Resch, Alissa M; Palakodeti, Dasaradhi; Graveley, Brenton R; Heinen, Christopher D

    2011-01-01

    Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis.

  1. Pregnancy outcome following M.MR vaccination

    Directory of Open Access Journals (Sweden)

    nahid Lorzadeh

    2007-09-01

    Full Text Available Lorzadeh N1, Ghafarzadeh M1, Vahabi S2, Lashgar-ara GhR3 1. Assistant professor, Department of gynecology, Faculty of medicine, Lorestan University of medical sciences 2. Assistant profwssor, Department of anesthesiology, Faculty of medicine, Lorestan University of medical sciences 3. General practitioner, Information and drugs center of Lorestan health department Abstract Background: In this study we evaluate the outcome of pregnancy in the patient that received M. MR vaccine during M.MR vaccination program on Lorestan of fall 2003. Materials and methods: This is a descriptive epidemiologic study, we evaluated all of women that vaccinated with M.MR vaccine during pre and post conception. We collected and analyzed all of information like prognosis of pregnancy, congenital rubella syndrome, gestational age weigh of newborn. Results: In 92 pregnancy women infected with MMR vaccine, the prognosis of pregnancy clearly seen 88 pregnant women (96% 73 (83% had normal and healthy newborn infant and 5 (6% had spontaneot abortion and 10 pregnant women (11% had legal abortion. Mean gestational age at birth was 39.5 ± 2.1 and weigh of newborn was 3257 ± 535 grams. None of the live born infants had not congenital rubella syndrome. Conclusion: In this study we showed M.MR vaccination during pregnancy had not any complication pregnancy. But pregnancy yet is an contraindication for M.MR vaccibnation, vecause this patient theories have risk of congenital rubella syndrome.

  2. Dual daughter strand incision is processive and increases the efficiency of DNA mismatch repair

    NARCIS (Netherlands)

    N. Hermans (Nicolaas); C. Laffeber; M. Cristovao (Michele); Artola-Borán, M. (Mariela); Mardenborough, Y. (Yannicka); P. Ikpa (Pauline); Jaddoe, A. (Aruna); H.H.K. Winterwerp (Herrie); C. Wyman (Claire); J. Jiricny (Josef); R. Kanaar (Roland); P. Friedhoff (Peter); J.H.G. Lebbink (Joyce)

    2016-01-01

    textabstractDNA mismatch repair (MMR) is an evolutionarily-conserved process responsible for the repair of replication errors. In Escherichia coli, MMR is initiated by MutS and MutL, which activate MutH to incise transiently-hemimethylated GATC sites. MMR efficiency depends on the distribution of th

  3. Diversity of the clinical presentation of the MMR gene biallelic mutations.

    Science.gov (United States)

    Bougeard, Gaëlle; Olivier-Faivre, Laurence; Baert-Desurmont, Stéphanie; Tinat, Julie; Martin, Cosette; Bouvignies, Emilie; Vasseur, Stéphanie; Huet, Frédéric; Couillault, Gérard; Vabres, Pierre; Le Pessot, Florence; Chapusot, Caroline; Malka, David; Bressac-de Paillerets, Brigitte; Tosi, Mario; Frebourg, Thierry

    2014-03-01

    Constitutional mismatch repair-deficiency, due to biallelic mutations of MMR genes, results in a tumour spectrum characterized by leukaemias, lymphomas, brain tumours and adenocarcinomas of the gastro-intestinal tract, occurring mostly in childhood. We report here two families illustrating the phenotypic diversity associated with biallelic MMR mutations. In the first family, two siblings developed six malignancies including glioblastoma, lymphoblastic T cell lymphoma, rectal and small bowel adenocarcinoma with onset as early as 6 years of age. We showed that this dramatic clinical presentation was due to the presence of two complex genomic PMS2 deletions in each patient predicted to result into complete PMS2 inactivation. In the second family, the index case presented with an early form of Lynch syndrome with colorectal adenocarcinomas at ages 17 and 20 years, and urinary tract tumours at the age of 25 years. We identified in this patient two MSH6 mutations corresponding to a frameshift deletion and an in frame deletion. The latter was not predicted to result into complete inactivation of MSH6. These reports show that the clinical expression of biallelic MMR mutations depends on the biological impact of the second MMR mutation and that, in clinical practice, the presence of a second MMR mutation located in trans should also be considered in patients suspected to present a Lynch syndrome with an unusual early-onset of tumours.

  4. Nuclear translocation contributes to regulation of DNA excision repair activities

    DEFF Research Database (Denmark)

    Knudsen, Nina Østergaard; Andersen, Sofie Dabros; Lützen, Anne;

    2009-01-01

    , it is evident that proteins from the different DNA repair pathways interact [Y. Wang, D. Cortez, P. Yazdi, N. Neff, S.J. Elledge, J. Qin, BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures, Genes Dev. 14 (2000) 927-939; M. Christmann, M......DNA mutations are circumvented by dedicated specialized excision repair systems, such as the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways. Although the individual repair pathways have distinct roles in suppressing changes in the nuclear DNA.......T. Tomicic, W.P. Roos, B. Kaina, Mechanisms of human DNA repair: an update, Toxicology 193 (2003) 3-34; N.B. Larsen, M. Rasmussen, L.J. Rasmussen, Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5 (2005) 89-108]. Protein interactions are not only important for function, but also...

  5. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina;

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

  6. Influencing factors in MMR immunisation decision making.

    Science.gov (United States)

    Hill, Marie C; Cox, Carol L

    Immunisation decision making is not a straightforward process for parents. Many factors influence parental decision making on whether they immunise their child with the measles, mumps and rubella (MMR) vaccine. The feasibility study described in this article provides insight into influencing factors associated with decisions regarding the immunisation of children by parents. The study findings suggest that the practice nurse is a credible source of information for parents seeking informed decision making. At a time when the incidence of measles and mumps is rising in the UK, the provision of appropriate information by the practice nurse has the potential to increase uptake of the MMR vaccine.

  7. Systems with randomly failing repairable components

    DEFF Research Database (Denmark)

    Der Kiureghian, Armen; Ditlevsen, Ove Dalager; Song, Junho

    2005-01-01

    Closed-form expressions are derived for the steady-state availability, mean rate of failure, mean duration of downtime and reliability of a general system with randomly and independently failing repairable components. Component failures are assumed to be homogeneous Poisson events in time and rep......, or reducing the mean duration of system downtime. Example applications to an electrical substation system demonstrate the use of the formulas developed in the paper....

  8. Risk of colorectal cancer for people with a mutation in both a MUTYH and a DNA mismatch repair gene

    Science.gov (United States)

    Win, Aung Ko; Reece, Jeanette C.; Buchanan, Daniel D.; Clendenning, Mark; Young, Joanne P.; Cleary, Sean P.; Kim, Hyeja; Cotterchio, Michelle; Dowty, James G.; MacInnis, Robert J.; Tucker, Katherine M.; Winship, Ingrid M.; Macrae, Finlay A.; Burnett, Terrilea; Le Marchand, Loïc; Casey, Graham; Haile, Robert W.; Newcomb, Polly A.; Thibodeau, Stephen N.; Lindor, Noralane M.; Hopper, John L.; Gallinger, Steven; Jenkins, Mark A.

    2015-01-01

    The base excision repair protein, MUTYH, functionally interacts with the DNA mismatch repair (MMR) system. As genetic testing moves from testing one gene at a time, to gene panel and whole exome next generation sequencing approaches, understanding the risk associated with co-existence of germline mutations in these genes will be important for clinical interpretation and management. From the Colon Cancer Family Registry, we identified 10 carriers who had both a MUTYH mutation (6 with c.1187G>A p.(Gly396Asp), 3 with c.821G>A p.(Arg274Gln), and 1 with c.536A>G p.(Tyr179Cys)) and a MMR gene mutation (3 in MLH1, 6 in MSH2, and 1 in PMS2), 375 carriers of a single (monoallelic) MUTYH mutation alone, and 469 carriers of a MMR gene mutation alone. Of the 10 carriers of both gene mutations, 8 were diagnosed with colorectal cancer. Using a weighted cohort analysis, we estimated that risk of colorectal cancer for carriers of both a MUTYH and a MMR gene mutation was substantially higher than that for carriers of a MUTYH mutation alone [hazard ratio (HR) 21.5, 95 % confidence interval (CI) 9.19–50.1; p colorectal cancer for carriers of a MMR gene mutation alone. Our finding suggests MUTYH mutation testing in MMR gene mutation carriers is not clinically informative. PMID:26202870

  9. DNA Mismatch Repair Interacts with CAF-1- and ASF1A-H3-H4-dependent Histone (H3-H4)2 Tetramer Deposition.

    Science.gov (United States)

    Rodriges Blanko, Elena; Kadyrova, Lyudmila Y; Kadyrov, Farid A

    2016-04-22

    DNA mismatch repair (MMR) is required for the maintenance of genome stability and protection of humans from several types of cancer. Human MMR occurs in the chromatin environment, but little is known about the interactions between MMR and the chromatin environment. Previous research has suggested that MMR coincides with replication-coupled assembly of the newly synthesized DNA into nucleosomes. The first step in replication-coupled nucleosome assembly is CAF-1-dependent histone (H3-H4)2 tetramer deposition, a process that involves ASF1A-H3-H4 complex. In this work we used reconstituted human systems to investigate interactions between MMR and CAF-1- and ASF1A-H3-H4-dependent histone (H3-H4)2 tetramer deposition. We have found that MutSα inhibits CAF-1- and ASF1A-H3-H4-dependent packaging of a DNA mismatch into a tetrasome. This finding supports the idea that MMR occurs before the DNA mismatch is packaged into the tetrasome. Our experiments have also revealed that CAF-1- and ASF1A-H3-H4-dependent deposition of the histone (H3-H4)2 tetramers does not interfere with MMR reactions. In addition, we have established that unnecessary degradation of the discontinuous strand that takes place in both DNA polymerase δ (Pol δ)- and DNA polymerase ϵ (Pol ϵ)-dependent MMR reactions is suppressed by CAF-1- and ASF1A-H3-H4-dependent deposition of the histone (H3-H4)2 tetramers. These data suggest that CAF-1- and ASF1A-H3-H4-dependent deposition of the histone (H3-H4)2 tetramers is compatible with MMR and protects the discontinuous daughter strand from unnecessary degradation by MMR machinery.

  10. Schedule Planning for Repairing Power Supply System

    OpenAIRE

    Kuo-Wei Lin; Chein-Jen Kang

    2012-01-01

    Problem statement: Taiwan is located in the tropical ocean areas. The strong typhoon in summer often causes the collapse of electric transmission towers and results in power outages that seriously affect peoples lives and industrial production. Approach: In light of this situation, this study aims to employ project management techniques of Theory of Constraints (TOC) to develop a practical TOC model to quickly repair the towers and restore power supplied system. Results: The actual applicatio...

  11. C-terminal fluorescent labeling impairs functionality of DNA mismatch repair proteins.

    Directory of Open Access Journals (Sweden)

    Angela Brieger

    Full Text Available The human DNA mismatch repair (MMR process is crucial to maintain the integrity of the genome and requires many different proteins which interact perfectly and coordinated. Germline mutations in MMR genes are responsible for the development of the hereditary form of colorectal cancer called Lynch syndrome. Various mutations mainly in two MMR proteins, MLH1 and MSH2, have been identified so far, whereas 55% are detected within MLH1, the essential component of the heterodimer MutLα (MLH1 and PMS2. Most of those MLH1 variants are pathogenic but the relevance of missense mutations often remains unclear. Many different recombinant systems are applied to filter out disease-associated proteins whereby fluorescent tagged proteins are frequently used. However, dye labeling might have deleterious effects on MutLα's functionality. Therefore, we analyzed the consequences of N- and C-terminal fluorescent labeling on expression level, cellular localization and MMR activity of MutLα. Besides significant influence of GFP- or Red-fusion on protein expression we detected incorrect shuttling of single expressed C-terminal GFP-tagged PMS2 into the nucleus and found that C-terminal dye labeling impaired MMR function of MutLα. In contrast, N-terminal tagged MutLαs retained correct functionality and can be recommended both for the analysis of cellular localization and MMR efficiency.

  12. Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 Expression.

    Directory of Open Access Journals (Sweden)

    Gloria Perazzoli

    Full Text Available The use of temozolomide (TMZ has improved the prognosis for glioblastoma multiforme patients. However, TMZ resistance may be one of the main reasons why treatment fails. Although this resistance has frequently been linked to the expression of O6-methylguanine-DNA methyltransferase (MGMT it seems that this enzyme is not the only molecular mechanism that may account for the appearance of drug resistance in glioblastoma multiforme patients as the mismatch repair (MMR complex, P-glycoprotein, and/or the presence of cancer stem cells may also be implicated.Four nervous system tumor cell lines were used to analyze the modulation of MGMT expression and MGMT promoter methylation by TMZ treatment. Furthermore, 5-aza-2'-deoxycytidine was used to demethylate the MGMT promoter and O(6-benzylguanine to block GMT activity. In addition, MMR complex and P-glycoprotein expression were studied before and after TMZ exposure and correlated with MGMT expression. Finally, the effect of TMZ exposure on CD133 expression was analyzed.Our results showed two clearly differentiated groups of tumor cells characterized by low (A172 and LN229 and high (SF268 and SK-N-SH basal MGMT expression. Interestingly, cell lines with no MGMT expression and low TMZ IC50 showed a high MMR complex expression, whereas cell lines with high MGMT expression and high TMZ IC50 did not express the MMR complex. In addition, modulation of MGMT expression in A172 and LN229 cell lines was accompanied by a significant increase in the TMZ IC50, whereas no differences were observed in SF268 and SK-N-SH cell lines. In contrast, P-glycoprotein and CD133 was found to be unrelated to TMZ resistance in these cell lines.These results may be relevant in understanding the phenomenon of TMZ resistance, especially in glioblastoma multiforme patients laking MGMT expression, and may also aid in the design of new therapeutic strategies to improve the efficacy of TMZ in glioblastoma multiforme patients.

  13. Proliferation rate but not mismatch repair affects the long-term response of colon carcinoma cells to 5FU treatment.

    Science.gov (United States)

    Choudhary, B; Hanski, M L; Zeitz, M; Hanski, C

    2012-07-01

    The role of mismatch repair (MMR) in the response of colon carcinoma cells to 5-fluorouracil (5FU) is not well understood. In most of the in vitro studies only short-term response was investigated. We focussed here on the influence of MMR status on the mechanism of the short- and long-term response to clinically relevant 5FU concentrations by using isogenic or semiisogenic cell line pairs expressing/nonexpressing the hMLH1 protein, an important component of the MMR system. We show that the lower survival of MMR-proficient than of MMR-deficient cells in the clonogenic survival assay is due to a more frequent early cell arrest and to subsequent senescence. By contrast, the long-term cell growth after treatment, which is also affected by long-term arrest and senescence, is independent from the MMR status. The overall effect on the long-term cell growth is a cumulative result of cell proliferation rate-dependent growth inhibition, apoptosis and necrotic cell death. The main long-term cytotoxic effect of 5FU is the inhibition of growth while apoptosis and the necrotic cell death are minor contributions.

  14. Association between perfluoroalkyl substance exposure and asthma and allergic disease in children as modified by MMR vaccination.

    Science.gov (United States)

    Timmermann, Clara Amalie Gade; Budtz-Jørgensen, Esben; Jensen, Tina Kold; Osuna, Christa Elyse; Petersen, Maria Skaalum; Steuerwald, Ulrike; Nielsen, Flemming; Poulsen, Lars K; Weihe, Pál; Grandjean, Philippe

    2017-12-01

    Perfluoroalkyl substances (PFASs) are highly persistent chemicals that might be associated with asthma and allergy, but the associations remain unclear. Therefore, this study examined whether pre- and postnatal PFAS exposure was associated with childhood asthma and allergy. Measles, mumps, and rubella (MMR) vaccination in early life may have a protective effect against asthma and allergy, and MMR vaccination is therefore taken into account when evaluating these associations. In a cohort of Faroese children whose mothers were recruited during pregnancy, serum concentrations of five PFASs - Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) - were measured at three timepoints (maternal serum in pregnancy week 34-36 and child serum at ages 5 and 13 years) and their association with immunoglobulin E (IgE) (cord blood and at age 7 years) and asthma/allergic diseases (questionnaires at ages 5 and 13 years and skin prick test at age 13 years) was determined. A total of 559 children were included in the analyses. Interactions with MMR vaccination were evaluated. Among 22 MMR-unvaccinated children, higher levels of the five PFASs at age 5 years were associated with increased odds of asthma at ages 5 and 13. The associations were reversed among MMR-vaccinated children. Prenatal PFAS exposure was not associated with childhood asthma or allergic diseases regardless of MMR vaccination status. In conclusion, PFAS exposure at age 5 was associated with increased risk of asthma among a small subgroup of MMR-unvaccinated children but not among MMR-vaccinated children. While PFAS exposure may impact immune system functions, this study suggests that MMR vaccination might be a potential effect-modifier.

  15. Optimal Strategy for Inspection and Repair of Structural Systems

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle; Sørensen, John Dalsgaard

    1987-01-01

    A new strategy for inspection and repair of structural elements and systems is presented. The total cost of inspection and repair is minimized with the constraints that the reliability of elements and/or of the structural system are acceptable. The design variables are the time intervals between...... inspections and the quality of the inspections. Numerical examples are presented to illustrate the performance of the strategy. The strategy can be used for any engineering system where inspection and repair are required....

  16. Schedule Planning for Repairing Power Supply System

    Directory of Open Access Journals (Sweden)

    Kuo-Wei Lin

    2012-01-01

    Full Text Available Problem statement: Taiwan is located in the tropical ocean areas. The strong typhoon in summer often causes the collapse of electric transmission towers and results in power outages that seriously affect peoples lives and industrial production. Approach: In light of this situation, this study aims to employ project management techniques of Theory of Constraints (TOC to develop a practical TOC model to quickly repair the towers and restore power supplied system. Results: The actual application had verified that the research model could not only shorten the duration of work but also save the manpower and material expenses. Conclusion: It once again proved the excellent results of reparation operations by applying TOC to project management.

  17. Distinct Clinicopathological Patterns of Mismatch Repair Status in Colorectal Cancer Stratified by KRAS Mutations.

    Directory of Open Access Journals (Sweden)

    Wenbin Li

    Full Text Available In sporadic colorectal cancer (CRC, the BRAFV600E mutation is associated with deficient mismatch repair (MMR status and inversely associated with to KRAS mutations. In contrast to deficient MMR (dMMR CRC, data on the presence of KRAS oncogenic mutations in proficient MMR (pMMR CRC and their relationship with tumor progression are scarce. We therefore examined the MMR status in combination with KRAS mutations in 913 Chinese patients and correlated the findings obtained with clinical and pathological features. The MMR status was determined based on detection of MLH1, MSH2, MSH6 and PMS2 expression. KRAS mutation and dMMR status were detected in 36.9% and 7.5% of cases, respectively. Four subtypes were determined by MMR and KRAS mutation status: KRAS (+/pMMR (34.0%, KRAS (+/dMMR (2.9%, KRAS (-/pMMR (58.5% and KRAS (-/dMMR (4.6%. A higher percentage of pMMR tumors with KRAS mutation were most likely to be female (49.0%, proximal located (45.5%, a mucinous histology (38.4%, and to have increased lymph node metastasis (60.3%, compared with pMMR tumors without BRAFV600E and KRAS mutations (36.0%, 29.3%, 29.4% and 50.7%, respectively; all P < 0.01. To the contrary, compared with those with KRAS(-/dMMR tumors, patients with KRAS(+/dMMR tumors demonstrated no statistically significant differences in gender, tumor location, pT depth of invasion, lymph node metastasis, pTNM stage, and histologic grade. This study revealed that specific epidemiologic and clinicopathologic characteristics are associated with MMR status stratified by KRAS mutation. Knowledge of MMR and KRAS mutation status may enhance molecular pathologic staging of CRC patients and metastatic progression in CRC can be estimated based on the combination of these biomarkers.

  18. Incidence of systemic inflammatory response syndrome after endovascular aortic repair

    DEFF Research Database (Denmark)

    De La Motte, L; Vogt, K; Jensen, Leif Panduro;

    2011-01-01

    The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair.......The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair....

  19. Closed loop two-echelon repairable item systems

    NARCIS (Netherlands)

    Spanjers, L.; van Ommeren, Jan C.W.; Zijm, Willem H.M.

    In this paper we consider closed loop two-echelon repairable item systems with repair facilities both at a number of local service centers (called bases) and at a central location (the depot). The goal of the system is to maintain a number of production facilities (one at each base) in optimal

  20. Unintended events following immunization with MMR: a systematic review.

    Science.gov (United States)

    Jefferson, Tom; Price, Deirdre; Demicheli, Vittorio; Bianco, Elvira

    2003-09-08

    Public debate over the safety of the trivalent measles, mumps and rubella (MMR) vaccine and the drop in vaccination rates in several countries persists despite its almost universal use and accepted effectiveness. We carried out a systematic review to assess the evidence of unintended effects (beneficial or harmful) associated with MMR and the applicability of systematic reviewing methods to the field of safety evaluation. Eligible studies were comparative prospective or retrospective on healthy individuals up to 15 years of age, carried out or published by 2003. We identified 120 articles satisfying our inclusion criteria and included 22. MMR is associated with a lower incidence of upper respiratory tract infections, a higher incidence of irritability, similar incidence of other adverse effects compared to placebo and is likely to be associated with benign thrombocytopenic purpura (TP), parotitis, joint and limb complaints and aseptic meningitis (mumps Urabe strain-containing MMR). Exposure to MMR is unlikely to be associated with Crohn's disease, ulcerative colitis, autism or aseptic meningitis (mumps Jeryl-Lynn strain-containing MMR). The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunization with MMR cannot be separated from its role in preventing the target diseases.

  1. MMR vaccination of children with egg allergy is safe

    DEFF Research Database (Denmark)

    Andersen, Dorthe Vestergård; Jørgensen, Inger Merete

    2013-01-01

    Measles, mumps and rubella (MMR) vaccination is part of the Danish Childhood Vaccination Programme. It is known that children may react with anaphylaxis to MMR vaccines containing traces of egg protein. In Denmark, national clinical guidelines recommend that children with egg allergy be referred...

  2. Quantitative comparison of PET performance—Siemens Biograph mCT and mMR

    Energy Technology Data Exchange (ETDEWEB)

    Karlberg, Anna M.; Sæther, Oddbjørn [Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Olav Kyrres gt 17, 7006 Trondheim (Norway); Eikenes, Live [Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Postbox 8905, 7491 Trondheim (Norway); Goa, Pål Erik [Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Olav Kyrres gt 17, 7006 Trondheim (Norway); Department of Physics, Norwegian University of Science and Technology, Trondheim (Norway)

    2016-02-25

    Integrated clinical whole-body PET/MR systems were introduced in 2010. In order to bring this technology into clinical usage, it is of great importance to compare the performance with the well-established PET/CT. The aim of this study was to evaluate PET performance, with focus on image quality, on Siemens Biograph mMR (PET/MR) and Siemens Biograph mCT (PET/CT). A direct quantitative comparison of the performance characteristics between the mMR and mCT system was performed according to National Electrical Manufacturers Association (NEMA) NU 2-2007 protocol. Spatial resolution, sensitivity, count rate and image quality were evaluated. The evaluation was supplemented with additional standardized uptake value (SUV) measurements. The spatial resolution was similar for the two systems. Average sensitivity was higher for the mMR (13.3 kcps/MBq) compared to the mCT system (10.0 kcps/MBq). Peak noise equivalent count rate (NECR) was slightly higher for the mMR (196 kcps @ 24.4 kBq/mL) compared to the mCT (186 kcps @ 30.1 kBq/mL). Scatter fractions in the clinical activity concentration range yielded lower values for the mCT (34.9 %) compared to those for the mMR (37.0 %). Best image quality of the systems resulted in approximately the same mean hot sphere contrast and a difference of 19 percentage points (pp) in mean cold contrast, in favour of the mCT. In general, point spread function (PSF) increased hot contrast and time of flight (TOF) increased both hot and cold contrast. Highest hot contrast for the smallest sphere (10 mm) was achieved with the combination of TOF and PSF on the mCT. Lung residual error was higher for the mMR (22 %) than that for the mCT (17 %), with no effect of PSF. With TOF, lung residual error was reduced to 8 % (mCT). SUV was accurate for both systems, but PSF caused overestimations for the 13-, 17- and 22-mm spheres. Both systems proved good performance characteristics, and the PET image quality of the mMR was close to that of the m

  3. Reliability analysis of two unit parallel repairable industrial system

    Directory of Open Access Journals (Sweden)

    Mohit Kumar Kakkar

    2015-09-01

    Full Text Available The aim of this work is to present a reliability and profit analysis of a two-dissimilar parallel unit system under the assumption that operative unit cannot fail after post repair inspection and replacement and there is only one repair facility. Failure and repair times of each unit are assumed to be uncorrelated. Using regenerative point technique various reliability characteristics are obtained which are useful to system designers and industrial managers. Graphical behaviors of mean time to system failure (MTSF and profit function have also been studied. In this paper, some important measures of reliability characteristics of a two non-identical unit standby system model with repair, inspection and post repair are obtained using regenerative point technique.

  4. Comparison Between helium cycle and Supercritical CO{sub 2} Cycle for MMR and AMR

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Seong Jun; Lee, Jeong Ik; Ahn, Yoon Han; Lee, Je Kyoung [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2013-05-15

    Korea Atomic Energy Research Institute (KAERI) started the development of Mobile Multi-Purpose Reactor (MMR), which is a 10MWth gas-cooled reactor. MMR is aiming for maximizing mobility, high performance, durability and safety. This is in order to use the MMR for many purposes such as ship propulsion, train engine and so on. MMR generally uses helium Brayton cycle as a power conversion system since it can obtain very simple system arrangement with direct cycle. However, some researchers have proposed that the supercritical carbon dioxide (S-CO{sub 2}) Brayton cycle can be more efficient energy converting cycle for the high temperature gas cooled reactor (HTGR) and the very high temperature reactor (VHTR) system as well. Thus, this paper is to compare helium Brayton cycle to the S-CO{sub 2} Brayton cycle in terms of the efficiency while varying turbine inlet temperature (T. I. T). A cascaded S-CO{sub 2} cycle which had been proposed by Argonne National laboratory (ANL) was used as the S-CO{sub 2} Brayton cycle configuration. This cycle is to overcome the mismatch of temperature drop between reactor coolant and CO{sub 2} through the reactor heat exchanger (RHX). Our research team reviewed the ANL research by using the in-house codes developed by the Korea Advanced institute of Science and Technology (KAIST) research team. The calculation error between the in-house code and previous result was -0.36%.

  5. Targeting DNA-repair systems brings hopes to cancer patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ CAS researchers have recently raised a hypothesis to circumvent tumor resistance to radio- and chemo-therapy and to enhance the efficacy of DNAdamaging agents by interfering with DNA repair. "There are emerging anticancer therapeutic opportunities in targeting DNA-repair systems," they asserted.

  6. Incidence of systemic inflammatory response syndrome after endovascular aortic repair

    DEFF Research Database (Denmark)

    De La Motte, L; Vogt, K; Jensen, Leif Panduro;

    2011-01-01

    AIM: The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair. METHODS: All patients, undergoing elective primary endovascular repair of an asymptomatic infrarenal abdominal aortic aneurysm...

  7. Capacitated two-indenture models for repairable item systems

    NARCIS (Netherlands)

    Zijm, Willem H.M.; Avsar, Zeynep Müge

    2003-01-01

    A two-indenture maintenance system is considered for a number of identical installations, in use at a single site. The installations are considered as assemblies that are made up of a number of repairable components. A component repair center and an assembly facility are both modeled as product form

  8. Capacitated two-indenture models for repairable item systems

    NARCIS (Netherlands)

    Zijm, Willem H.M.; Avsar, Z.M.; van Houtum, Geert-Jan

    2001-01-01

    A two-indenture maintenance system is considered for a number of identical installations, in use at a single site. The installations are considered as assemblies that are made up of a number of repairable components. A component repair center and an assembly facility are both modeled as product form

  9. Capacitated two-echelon inventory models for repairable item systems

    NARCIS (Netherlands)

    Avsar, Z.M.; Zijm, Willem H.M.; Gershwin, S.B.; Dallery, Y.; Papadopoulos, C.; Smith, J.M.

    2002-01-01

    In this paper, we consider two-echelon maintenance systems with repair facilities both at a number of local service centers (called bases) and at a central location. Each repair facility may be considered to be a job shop and is modeled as a (limited capacity) open queuing network, while any

  10. MMR vaccination of children with egg allergy is safe

    DEFF Research Database (Denmark)

    Andersen, Dorthe Vestergård; Jørgensen, Inger Merete

    2013-01-01

    Measles, mumps and rubella (MMR) vaccination is part of the Danish Childhood Vaccination Programme. It is known that children may react with anaphylaxis to MMR vaccines containing traces of egg protein. In Denmark, national clinical guidelines recommend that children with egg allergy be referred...... to vaccination at a paediatric ward despite changed recommendations in other countries. The purpose of this study was to determine whether children with egg allergy presented with anaphylactic/allergic reactions to MMR vaccination and to discuss whether Danish recommendations should be upheld....

  11. MMR vaccination of children with egg allergy is safe

    DEFF Research Database (Denmark)

    Andersen, Dorthe Vestergård; Jørgensen, Inger Merete

    2013-01-01

    Measles, mumps and rubella (MMR) vaccination is part of the Danish Childhood Vaccination Programme. It is known that children may react with anaphylaxis to MMR vaccines containing traces of egg protein. In Denmark, national clinical guidelines recommend that children with egg allergy be referred...... to vaccination at a paediatric ward despite changed recommendations in other countries. The purpose of this study was to determine whether children with egg allergy presented with anaphylactic/allergic reactions to MMR vaccination and to discuss whether Danish recommendations should be upheld....

  12. Reliability Analysis of Repairable Systems Using Stochastic Point Processes

    Institute of Scientific and Technical Information of China (English)

    TAN Fu-rong; JIANG Zhi-bin; BAI Tong-shuo

    2008-01-01

    In order to analyze the failure data from repairable systems, the homogeneous Poisson process(HPP) is usually used. In general, HPP cannot be applied to analyze the entire life cycle of a complex, re-pairable system because the rate of occurrence of failures (ROCOF) of the system changes over time rather thanremains stable. However, from a practical point of view, it is always preferred to apply the simplest methodto address problems and to obtain useful practical results. Therefore, we attempted to use the HPP model toanalyze the failure data from real repairable systems. A graphic method and the Laplace test were also usedin the analysis. Results of numerical applications show that the HPP model may be a useful tool for the entirelife cycle of repairable systems.

  13. Changes in DNA repair during aging

    Science.gov (United States)

    Gorbunova, Vera; Seluanov, Andrei; Mao, Zhiyong; Hine, Christpher

    2007-01-01

    DNA is a precious molecule. It encodes vital information about cellular content and function. There are only two copies of each chromosome in the cell, and once the sequence is lost no replacement is possible. The irreplaceable nature of the DNA sets it apart from other cellular molecules, and makes it a critical target for age-related deterioration. To prevent DNA damage cells have evolved elaborate DNA repair machinery. Paradoxically, DNA repair can itself be subject to age-related changes and deterioration. In this review we will discuss the changes in efficiency of mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER) and double-strand break (DSB) repair systems during aging, and potential changes in DSB repair pathway usage that occur with age. Mutations in DNA repair genes and premature aging phenotypes they cause have been reviewed extensively elsewhere, therefore the focus of this review is on the comparison of DNA repair mechanisms in young versus old. PMID:17913742

  14. Effect of surface roughness on amalgam repair using adhesive systems.

    Science.gov (United States)

    Giannini, Marcelo; Paulillo, Luis Alexandre Maffei Sartini; Ambrosano, Gláucia Maria Bovi

    2002-01-01

    The objective of this in vitro study was to evaluate the effect of three surface treatments and two adhesive systems on the shear bond strength of old and freshly placed amalgam. The results suggested that the intact amalgam showed a significantly higher strength than repaired groups and the strongest repaired specimens were made when the amalgam surfaces were roughened with a diamond bur or microetcher. The adhesive systems showed no significant differences on bond strength with the same superficial texture.

  15. Repair bond strength of resin composite to a novel CAD/CAM hybrid ceramic using different repair systems.

    Science.gov (United States)

    Elsaka, Shaymaa E

    2015-01-01

    This study evaluated the repair bond strength of a nanohybrid resin composite to a novel CAD/CAM hybrid ceramic based on four intraoral ceramic repair systems. Vita Enamic (VE) CAD/CAM hybrid ceramic was used in this study. Specimens were divided into five test groups according to the repair method performed on the ceramic surface: Gr C (No treatment; control); Gr CZ (Cimara Zircon); Gr PR (Porcelain Repair); Gr CR (Clearfil Repair); and Gr CS (CoJet system). Nanohybrid resin composite (GrandioSO) was packed onto treated ceramic surfaces for adhesion testing using microtensile bond strength test. Debonded specimens were examined with a stereomicroscope and SEM to determine the fracture mode. Data were analyzed using ANOVA and Tukey's HSD test. PR and CZ repair systems significantly enhanced the bond strength of nanohybrid resin composite to VE CAD/CAM hybrid ceramic when compared with the other tested repair systems.

  16. Comparative analysis of meiotic progression in female mice bearing mutations in genes of the DNA mismatch repair pathway.

    Science.gov (United States)

    Kan, Rui; Sun, Xianfei; Kolas, Nadine K; Avdievich, Elena; Kneitz, Burkhard; Edelmann, Winfried; Cohen, Paula E

    2008-03-01

    The DNA mismatch repair (MMR) family functions in a variety of contexts to preserve genome integrity in most eukaryotes. In particular, members of the MMR family are involved in the process of meiotic recombination in germ cells. MMR gene mutations in mice result in meiotic disruption during prophase I, but the extent of this disruption often differs between male and female meiocytes. To address the role of MMR proteins specifically in female meiosis, we explored the progression of oocytes through prophase I and the meiotic divisions in mice harboring deletions in members of the MMR pathway (Mlh1, Mlh3, Exo1, and an ATPase-deficient variant of Mlh1, Mlh1(G67R)). The colocalization of MLH1 and MLH3, key proteins involved in stabilization of nascent crossovers, was dependent on intact heterodimer formation and was highly correlated with the ability of oocytes to progress through to metaphase II. The exception was Exo1(-/-) oocytes, in which normal MLH1/MLH3 localization was observed followed by failure to proceed to metaphase II. All mutant oocytes were able to resume meiosis after dictyate arrest, but they showed a dramatic decline in chiasmata (to less than 25% of normal), accompanied by varied progression through metaphase I. Taken together, these results demonstrate that MMR function is required for the formation and stabilization of crossovers in mammalian oocytes and that, in the absence of a functional MMR system, the failure to maintain chiasmata results in a reduced ability to proceed normally through the first and second meiotic divisions, despite near-normal levels of meiotic resumption after dictyate arrest.

  17. DNA Repair Systems: Guardians of the Genome

    Indian Academy of Sciences (India)

    2016-10-01

    The 2015 Nobel Prize in Chemistry was awarded jointly to Tomas Lindahl, Paul Modrich and Aziz Sancar to honour their accomplishments in the field of DNA repair. Ever since the discovery of DNA structure and their importance in the storage of genetic information, questions about their stability became pertinent. A molecule which is crucial for the development and propagation of an organism must be closely monitored so that the genetic information is not corrupted. 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 in the fight against cancer and other debilitating diseases.

  18. Web-ADARE: A Web-Aided Data Repairing System

    KAUST Repository

    Gu, Binbin

    2017-03-08

    Data repairing aims at discovering and correcting erroneous data in databases. In this paper, we develop Web-ADARE, an end-to-end web-aided data repairing system, to provide a feasible way to involve the vast data sources on the Web in data repairing. Our main attention in developing Web-ADARE is paid on the interaction problem between web-aided repairing and rule-based repairing, in order to minimize the Web consultation cost while reaching predefined quality requirements. The same interaction problem also exists in crowd-based methods but this is not yet formally defined and addressed. We first prove in theory that the optimal interaction scheme is not feasible to be achieved, and then propose an algorithm to identify a scheme for efficient interaction by investigating the inconsistencies and the dependencies between values in the repairing process. Extensive experiments on three data collections demonstrate the high repairing precision and recall of Web-ADARE, and the efficiency of the generated interaction scheme over several baseline ones.

  19. ADHESIVE SYSTEM AFFECTS REPAIR BOND STRENGTH OF RESIN COMPOSITE

    Directory of Open Access Journals (Sweden)

    Özgür IRMAK

    2017-10-01

    Full Text Available Purpose: This study evaluated the effects of different adhesive systems on repair bond strength of aged resin composites. Materials and Methods: Ninety composite discs were built and half of them were subjected to thermal aging. Aged and non-aged specimens were repaired with resin composite using three different adhesive systems; a two-step self-etch adhesive, a two-step total-etch adhesive and a one-step self-etch adhesive; then they were subjected to shear forces. Data were analyzed statistically. Results: Adhesive type and aging significantly affected the repair bond strengths (p<0.0001. No statistical difference was found in aged composite groups repaired with two-step self- etch or two-step total-etch adhesive. One-step self-etch adhesive showed lower bond strength values in aged composite repair (p<0.0001. Conclusion: In the repair of aged resin composite, two-step self-etch and two-step total-etch adhesives exhibited higher shear bond strength values than that of one-step self-etch adhesive.

  20. Efficient and reproducible identification of mismatch repair deficient colon cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Bendahl, Pär-Ola; Halvarsson, Britta;

    2013-01-01

    BACKGROUND: The identification of mismatch-repair (MMR) defective colon cancer is clinically relevant for diagnostic, prognostic and potentially also for treatment predictive purposes. Preselection of tumors for MMR analysis can be obtained with predictive models, which need to demonstrate ease...... of application and favorable reproducibility. METHODS: We validated the MMR index for the identification of prognostically favorable MMR deficient colon cancers and compared performance to 5 other prediction models. In total, 474 colon cancers diagnosed ≥ age 50 were evaluated with correlation between...... and efficiently identifies MMR defective colon cancers with high sensitivity and specificity. The model shows stable performance with low inter-observer variability and favorable performance when compared to other MMR predictive models....

  1. [Characteristics and Outcomes of Treatment in Patients with Stage IV Colorectal Cancer with Mismatch Repair Deficiency].

    Science.gov (United States)

    Ishibashi, Keiichiro; Chika, Noriyasu; Suzuki, Okihide; Ito, Tetsuya; Amano, Kunihiko; Kumamoto, Kensuke; Fukuchi, Minoru; Kumagai, Youichi; Mochiki, Erito; Ishida, Hideyuki

    2016-11-01

    Mismatch repair(MMR)protein deficiency in colorectal cancer is well correlated with high-level microsatellite instability (MSI-H). There are little data on mismatch repair deficiency(dMMR)colorectal cancers in Japan. In addition, we have no available data on the therapeutic efficacy of oxaliplatin(oxa)-based chemotherapy, one of the standard treatment regimens for metastatic colorectal cancer, for patients with dMMR colorectal cancer. The subjects were 254 patients with Stage IV colorectal cancer whose tumors were immunohistochemically stained for MMR proteins, MLH1, MSH2, MSH6, and PMS2. Patients who underwent R0 resection were excluded. Clinicopathologic factors and the efficacy of oxa-based chemotherapy were compared between patients with dMMR colorectal cancer and those with mismatch repair proficient(pMMR)colorectal cancer. There were 7(2.8%)patients with dMMR. Four patients demonstrated both MLH1 and PMS2 loss, while 3 patients demonstrated both MSH2 and MSH6 loss. Though the dMMR had a higher frequency in female patients(p=0.02) and a lower frequency in those with liver metastasis(pcolorectal cancers was lower than those(4-11%)reported in Western countries. Therefore, the clinical significance of universal screeningfor dMMR in all colorectal cancer samples may not be valid. Concerningsurvival benefit, oxa-based chemotherapy seems to be an effective alternative in clinical practice for metastatic colorectal cancer patients with dMMR.

  2. Mismatch repair-deficient crypt foci in Lynch syndrome--molecular alterations and association with clinical parameters.

    Directory of Open Access Journals (Sweden)

    Laura Staffa

    Full Text Available Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR-DCF have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but very rarely progress to cancer. To shed light on molecular alterations and clinical associations of MMR-DCF, we systematically searched the intestinal mucosa from Lynch syndrome patients for MMR-DCF by immunohistochemistry. The identified lesions were characterised for alterations in microsatellite-bearing genes with proven or suspected role in malignant transformation. We demonstrate that the prevalence of MMR-DCF (mean 0.84 MMR-DCF per 1 cm2 mucosa in the colorectum of Lynch syndrome patients was significantly associated with patients' age, but not with patients' gender. No MMR-DCF were detectable in the mucosa of patients with sporadic MSI-H colorectal cancer (n = 12. Microsatellite instability of at least one tested marker was detected in 89% of the MMR-DCF examined, indicating an immediate onset of microsatellite instability after MMR gene inactivation. Coding microsatellite mutations were most frequent in the genes HT001 (ASTE1 with 33%, followed by AIM2 (17% and BAX (10%. Though MMR deficiency alone appears to be insufficient for malignant transformation, it leads to measurable microsatellite instability even in single MMR-deficient crypts. Our data indicate for the first time that the frequency of MMR-DCF increases with patients' age. Similar patterns of coding microsatellite instability in MMR-DCF and MMR-deficient cancers suggest that certain combinations of coding microsatellite mutations, including mutations of the HT001, AIM2 and BAX gene, may contribute to the progression of MMR-deficient lesions into MMR-deficient cancers.

  3. Analysis of contaminated field failure data for repairable systems

    DEFF Research Database (Denmark)

    Hansen, Christian Kornerup; Thyregod, Poul

    1991-01-01

    A simple model for electronic systems with repair, and a method for analyzing recorded field failure data for such systems are presented. The work performed has resulted in analytical results that may be used for assessing the product reliability. The method was originally developed for use under...

  4. Closed loop two-echelon repairable item systems

    NARCIS (Netherlands)

    Spanjers, L.; van Ommeren, Jan C.W.; Zijm, Willem H.M.; Liberopoulos, G.; Papadopoulos, C.T.; Tan, B.; MacGregor Smith, J.; Gershwin, S.B.

    2006-01-01

    In this paper we consider closed loop two-echelon epairable item systems with repair facilities both at a number of local service centers (called bases) and at a central location (the depot). The goal of the system is to maintain a number of production facilities (one at each base) in optimal

  5. Topoisomerase-1 and -2A gene copy numbers are elevated in mismatch repair-proficient colorectal cancers

    DEFF Research Database (Denmark)

    Sønderstrup, Ida Marie Heeholm; Nygård, Sune Boris; Poulsen, Tim Svenstrup

    2015-01-01

    (MMR) subtypes of CRC have been associated with benefit from adjuvant chemotherapy of primary CRC. Given the involvement of the topoisomerase enzymes in DNA replication and repair, we raised the hypothesis that an association may exist between TOP gene copy numbers and MMR proficiency/deficiency in CRC...... patients with deficient MMR (dMMR) CRC. TOP1 and TOP2A gene copy numbers and their ratios per nucleus were correlated with MMR status using the Mann-Whitney test. Validation cohort: FFPE samples from 154 patients with primary stage III CRC (originally included in the RANX05 study) were classified according...

  6. The Rate and Spectrum of Spontaneous Mutations in Mycobacterium smegmatis, a Bacterium Naturally Devoid of the Postreplicative Mismatch Repair Pathway

    Directory of Open Access Journals (Sweden)

    Sibel Kucukyildirim

    2016-07-01

    Full Text Available Mycobacterium smegmatis is a bacterium that is naturally devoid of known postreplicative DNA mismatch repair (MMR homologs, mutS and mutL, providing an opportunity to investigate how the mutation rate and spectrum has evolved in the absence of a highly conserved primary repair pathway. Mutation accumulation experiments of M. smegmatis yielded a base-substitution mutation rate of 5.27 × 10−10 per site per generation, or 0.0036 per genome per generation, which is surprisingly similar to the mutation rate in MMR-functional unicellular organisms. Transitions were found more frequently than transversions, with the A:T→G:C transition rate significantly higher than the G:C→A:T transition rate, opposite to what is observed in most studied bacteria. We also found that the transition-mutation rate of M. smegmatis is significantly lower than that of other naturally MMR-devoid or MMR-knockout organisms. Two possible candidates that could be responsible for maintaining high DNA fidelity in this MMR-deficient organism are the ancestral-like DNA polymerase DnaE1, which contains a highly efficient DNA proofreading histidinol phosphatase (PHP domain, and/or the existence of a uracil-DNA glycosylase B (UdgB homolog that might protect the GC-rich M. smegmatis genome against DNA damage arising from oxidation or deamination. Our results suggest that M. smegmatis has a noncanonical Dam (DNA adenine methylase methylation system, with target motifs differing from those previously reported. The mutation features of M. smegmatis provide further evidence that genomes harbor alternative routes for improving replication fidelity, even in the absence of major repair pathways.

  7. Eukaryotic Mismatch Repair in Relation to DNA Replication.

    Science.gov (United States)

    Kunkel, Thomas A; Erie, Dorothy A

    2015-01-01

    Three processes act in series to accurately replicate the eukaryotic nuclear genome. The major replicative DNA polymerases strongly prevent mismatch formation, occasional mismatches that do form are proofread during replication, and rare mismatches that escape proofreading are corrected by mismatch repair (MMR). This review focuses on MMR in light of increasing knowledge about nuclear DNA replication enzymology and the rate and specificity with which mismatches are generated during leading- and lagging-strand replication. We consider differences in MMR efficiency in relation to mismatch recognition, signaling to direct MMR to the nascent strand, mismatch removal, and the timing of MMR. These studies are refining our understanding of relationships between generating and repairing replication errors to achieve accurate replication of both DNA strands of the nuclear genome.

  8. Optimal inspection and Repair Strategies for Structural Systems

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Faber, Michael Havbro

    1992-01-01

    A model for reliability-based repair and maintenance strategies of structural systems is described. The total expected costs in the lifetime of the structure are minimized with the number of inspections, the number and positions of the inspected points, the inspection efforts, the repair criteria...... to be inspected and to select the location of the points to be inspected. It is shown how information obtained through inspections and through the periods of normal operating of the structure can be used to update the inspection and maintenance planning. Finally, a small example is given illustrating...

  9. Lubrication System. Teacher's Guide. Small Engine Repair Series. First Edition.

    Science.gov (United States)

    Hill, Pamela

    This teacher's guide accompanies three student manuals and together with them comprises an instructional package on the lubrication system in the Small Engine Repair Series for handicapped/special needs students. The first section, "Notes to the Instructor," covers equipment needs, preparation before teaching the instructional package,…

  10. UV Radiation Damage and Bacterial DNA Repair Systems

    Science.gov (United States)

    Zion, Michal; Guy, Daniel; Yarom, Ruth; Slesak, Michaela

    2006-01-01

    This paper reports on a simple hands-on laboratory procedure for high school students in studying both radiation damage and DNA repair systems in bacteria. The sensitivity to ultra-violet (UV) radiation of both "Escherichia coli" and "Serratia marcescens" is tested by radiating them for varying time periods. Two growth temperatures are used in…

  11. Approaches to diagnose DNA mismatch repair gene defects in cancer

    DEFF Research Database (Denmark)

    Peña-Diaz, Javier; Rasmussen, Lene Juel

    2016-01-01

    The DNA repair pathway mismatch repair (MMR) is responsible for the recognition and correction of DNA biosynthetic errors caused by inaccurate nucleotide incorporation during replication. Faulty MMR leads to failure to address the mispairs or insertion deletion loops (IDLs) left behind...... already been well defined and their pathogenicity assessed. Despite this substantial wealth of knowledge, the effects of a large number of alterations remain uncharacterized (variants of uncertain significance, VUSs). The advent of personalized genomics is likely to increase the list of VUSs found in MMR...

  12. Randomized trial comparing the Prolene Hernia System, mesh plug repair and Lichtenstein method for open inguinal hernia repair.

    NARCIS (Netherlands)

    Nienhuijs, S.W.; Oort, I.M. van; Keemers-Gels, M.E.; Strobbe, L.J.; Rosman, C.

    2005-01-01

    BACKGROUND: Most surgeons favour the use of a mesh for open inguinal hernia repair as it has a low recurrence rate. Procedures used most frequently are the Lichtenstein method, mesh plug repair and the Prolene Hernia System. The choice of technique may be influenced by the effects on postoperative p

  13. Effective Measurement of Reliability of Repairable USAF Systems

    Science.gov (United States)

    2012-09-01

    Hansen presented a course, Concepts and Models for Repairable Systems Reliability, at the 2009 Centro de Investigacion en Mathematicas (CIMAT). The...defines MTBF in Technical Order 00-2-2, Maintenance Documentation ., Mean Time Between Failure (Inherent). Inherent refers to a Type 1 failure or...The USAF uses maintenance data to document the system failures. There is no method within that data system to define specific failure modes

  14. Availability, reliability and downtime of systems with repairable components

    DEFF Research Database (Denmark)

    Kiureghian, Armen Der; Ditlevsen, Ove Dalager; Song, J.

    2007-01-01

    Closed-form expressions are derived for the steady-state availability, mean rate of failure, mean duration of downtime and lower bound reliability of a general system with randomly and independently failing repairable components. Component failures are assumed to be homogeneous Poisson events in ......, or reducing the mean duration of system downtime. Example applications to an electrical substation system demonstrate the use of the formulas developed in the paper....

  15. Measles, Mumps, Rubella and the MMR Vaccine during Pregnancy

    Science.gov (United States)

    ... in the U.S., but vaccination programs have greatly decreased their incidence. These viruses are still common in ... where a woman received the MMR vaccine during pregnancy. They did not experience adverse complications and there was no increased rate of birth defects. I have heard about a ...

  16. Danish MMR vaccination coverage is considerably higher than reported.

    Science.gov (United States)

    Holt, Nanna; Mygind, Anna; Bro, Flemming

    2017-02-01

    The Danish childhood vaccination programme offers protection against measles, mumps, and rubella (MMR). Nevertheless, many children appear to be unvaccinated according to the national registers. The aim of this study was to estimate the MMR1 vaccination coverage based on a medical record review of children whose vaccination status is negative according to the register-based data. We conducted a cross-sectional study of 19 randomly selected general practices in the Central Denmark Region including 1,712 children aged 18-42 months. The practices received a registration form listing children with a negative MMR1 vaccination status in the register-based data. The general practices then validated the children's vaccination status by medical record review. In total, 94% of the children had been vaccinated according to the medical records in general practice compared with 86% according to the register-based data. Of the 246 children who were unvaccinated according to the register-based data, 135 (55%) had been vaccinated according to the medical records. This discrepancy was due mainly to administrative reimbursement errors. The MMR1 vaccination coverage in Denmark seems to be considerably higher than reflected in national registers. Using medical record review to re-assess the vaccination status revealed that most of the supposedly unvaccinated children had, in fact, been vaccinated. The Danish Research Foundation for General Practice and the General Practitioners' Foundation for Education and Development. not relevant.

  17. DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer.

    Science.gov (United States)

    Ricker, Charité N; Hanna, Diana L; Peng, Cheng; Nguyen, Nathalie T; Stern, Mariana C; Schmit, Stephanie L; Idos, Greg E; Patel, Ravi; Tsai, Steven; Ramirez, Veronica; Lin, Sonia; Shamasunadara, Vinay; Barzi, Afsaneh; Lenz, Heinz-Josef; Figueiredo, Jane C

    2017-10-01

    The landscape of hereditary syndromes and clinicopathologic characteristics among US Latino/Hispanic individuals with colorectal cancer (CRC) remains poorly understood. A total of 265 patients with CRC who were enrolled in the Hispanic Colorectal Cancer Study were included in the current study. Information regarding CRC risk factors was elicited through interviews, and treatment and survival data were abstracted from clinical charts. Tumor studies and germline genetic testing results were collected from medical records or performed using standard molecular methods. The mean age of the patients at the time of diagnosis was 53.7 years (standard deviation, 10.3 years), and 48.3% were female. Overall, 21.2% of patients reported a first-degree or second-degree relative with CRC; 3.4% met Amsterdam I/II criteria. With respect to Bethesda guidelines, 38.5% of patients met at least 1 criterion. Of the 161 individuals who had immunohistochemistry and/or microsatellite instability testing performed, 21 (13.0%) had mismatch repair (MMR)-deficient (dMMR) tumors. dMMR tumors were associated with female sex (61.9%), earlier age at the time of diagnosis (50.4 ± 12.4 years), proximal location (61.9%), and first-degree (23.8%) or second-degree (9.5%) family history of CRC. Among individuals with dMMR tumors, 13 (61.9%) had a germline MMR mutation (MutL homolog 1 [MLH1] in 6 patients; MutS homolog 2 [MSH2] in 4 patients; MutS homolog 6 [MHS6] in 2 patients; and PMS1 homolog 2, mismatch repair system component [PMS2] in 1 patient). The authors identified 2 additional MLH1 mutation carriers by genetic testing who had not received immunohistochemistry/microsatellite instability testing. In total, 5.7% of the entire cohort were confirmed to have Lynch syndrome. In addition, 6 individuals (2.3%) had a polyposis phenotype. The percentage of dMMR tumors noted among Latino individuals (13%) is similar to estimates in non-Hispanic white individuals. In the current study, the majority of

  18. MMR (Measles, Mumps and Rubella) Vaccine: What You Need to Know

    Science.gov (United States)

    ... they would return. 2 Wanhdowshheonu?ld get MMR vaccine Children should get 2 doses of MMR vaccine: • First ... be given at the same time as other vaccines. Children between 1 and 12 years of age can ...

  19. Analysis of contaminated field failure data for repairable systems

    OpenAIRE

    Hansen, Christian Kornerup; Thyregod, Poul

    1991-01-01

    A simple model for electronic systems with repair, and a method for analyzing recorded field failure data for such systems are presented. The work performed has resulted in analytical results that may be used for assessing the product reliability. The method was originally developed for use under ideal circumstances, but it has been adapted for use with contaminated data (i.e., data where the failure times are observed embedded by noise). A simple model for the noise that enables an analytica...

  20. MMR-Vaccine and Regression in Autism Spectrum Disorders: Negative Results Presented from Japan

    Science.gov (United States)

    Uchiyama, Tokio; Kurosawa, Michiko; Inaba, Yutaka

    2007-01-01

    It has been suggested that the measles, mumps, and rubella vaccine (MMR) is a cause of regressive autism. As MMR was used in Japan only between 1989 and 1993, this time period affords a natural experiment to examine this hypothesis. Data on 904 patients with autism spectrum disorders (ASD) were analyzed. During the period of MMR usage no…

  1. Materials directed to implants for repairing Central Nervous System

    Energy Technology Data Exchange (ETDEWEB)

    Canillas, M.; Moreno-Burriel, B.; Chinarro, E.

    2014-07-01

    Central Nervous System (CNS) can be damaged by a wide range of injuries and disorders which entail permanent disability in some cases. Moreover, CNS repairing process presents some complications. The natural repair mechanism, which consists on the glial scar formation, is triggered by the inflammatory process. Molecules delivered during these processes, inflammation and glial scar formation as well as oxygen and glucose deficiencies due to the injury, create an inhibitory environment for axon regeneration and remyelination which is known as secondary injury. Biomaterials are taking up an even more important role in repairing CNS. Physicochemical properties of some ceramic materials have inspired different applications to repair CNS as substrates, electrodes or molecule vehicles. Based on their biocompatibility, capability to neutralize reactive species involved in the inflammatory processes and their versatile processing to obtain scaffolds with different shapes and sizes, ceramics are a succulent offer in nervous tissue engineering. Furthermore, their possibilities have been increased with polymeric-ceramics composites development, which have given rise to new interesting horizon. (Author)

  2. The news for MMR and clinical cancer%DNA错配修复和临床肿瘤新进展

    Institute of Scientific and Technical Information of China (English)

    马守成; 赵达

    2011-01-01

    DNA复制是一个严谨有序的过程,细胞分裂时,碱基错配的概率约为1/1010~1/109.错配修复系统(MMR)是一个从细菌到真核细胞皆保守的DNA修复途径,它负责修复DNA中错配的碱基,或者DNA聚合酶的校对功能失调而引起的复制错误,插入,遗失碱基,使DNA整体复制的保真度增加50~1000倍.MMR系统失控会导致DNA序列中微卫星序列的不稳定性(MSI)或编码功能蛋白的基因突变,改变正常细胞功能,从而引发肿瘤.%DNA replication is an extraordinarily faithful process, mutation occures at a frequency of 1/10 or 1/10 base pairs per cell division. The MMR pathway, a DNA repair pathway conserved from bacteria to humans, targets base substitution mismatches and insertion-deletion mismatches that arise as a result of replication errors that escape the proofreading function of DNA polymerases. In doing so, MMR contributes an additional 50 ~ 1000-fold to the o-verall fidelity of replication. Thus, inactivation of MMR confers a strong mutated phenotype in which the rate of spontaneous mutation is greatly elevated,such as microsatellite stability (MSI) , or mutated genes that code functional proteins, thus give rise to cancer.

  3. Reliability Analysis of Partially Repairable Systems%部分可修系统的可靠性分析

    Institute of Scientific and Technical Information of China (English)

    苏保河

    2005-01-01

    The reliability analysis of a system with repairable failures and non-repairable failures is presented. It is assumed that the system has n repairable failure modes and m non-repairable failure modes. As one repairable failure mode takes place, the system will be repaired after the failure mode is detected, otherwise, it would never work again when attaining one non-repairable failure mode. Thus, the system brings about new reliability indices for having both repairable failures and non-repairable failures. The definitions of the new reliability indices are given, and the calculating methods for them are derived by using probability analysis and the supplementary variable technique.

  4. Nonlinear Mixed-Effects Models for Repairable Systems Reliability

    Institute of Scientific and Technical Information of China (English)

    TAN Fu-rong; JIANG Zhi-bin; KUO Way; Suk Joo BAE

    2007-01-01

    Mixed-effects models, also called random-effects models, are a regression type of analysis which enables the analyst to not only describe the trend over time within each subject, but also to describe the variation among different subjects. Nonlinear mixed-effects models provide a powerful and flexible tool for handling the unbalanced count data. In this paper, nonlinear mixed-effects models are used to analyze the failure data from a repairable system with multiple copies. By using this type of models, statistical inferences about the population and all copies can be made when accounting for copy-to-copy variance. Results of fitting nonlinear mixed-effects models to nine failure-data sets show that the nonlinear mixed-effects models provide a useful tool for analyzing the failure data from multi-copy repairable systems.

  5. Noncanonical mismatch repair as a source of genomic instability in human cells

    DEFF Research Database (Denmark)

    Pena Diaz, Javier; Bregenhorn, Stephanie; Ghodgaonkar, Medini;

    2012-01-01

    Mismatch repair (MMR) is a key antimutagenic process that increases the fidelity of DNA replication and recombination. Yet genetic experiments showed that MMR is required for antibody maturation, a process during which the immunoglobulin loci of antigen-stimulated B cells undergo extensive mutage...

  6. Zebrafish with mutations in mismatch repair genes develop neurofibromas and other tumors.

    NARCIS (Netherlands)

    Feitsma, H.; Kuiper, R.V.; Korving, J.; Nijman, I.J.; Cuppen, E.

    2008-01-01

    Defective mismatch repair (MMR) in humans causes hereditary nonpolyposis colorectal cancer. This genetic predisposition to colon cancer is linked to heterozygous familial mutations, and loss-of-heterozygosity is necessary for tumor development. In contrast, the rare cases with biallelic MMR

  7. Antibody persistence in young adults 1 year after MMR immunization by aerosol or by subcutaneous route.

    Science.gov (United States)

    Díaz-Ortega, José Luis; Bennett, John V; Castañeda, D; Martinez, D; de Castro, J Fernandez

    2010-10-18

    Information on antibody persistence after aerosol revaccination with MMR components is limited. Thus, antibody titers were determined in 283 adult participants in a MMR vaccine trial 12 months after revaccination. One group had received aerosolized Triviraten vaccine while two other groups received either injected Triviraten or MMR II vaccine. Both MMR vaccines contained the same rubella strain, but different measles and mumps strains. Seropositivity to measles persisted in 98% of aerosolized vaccine recipients, 92% of injected Triviraten, and 95% of injected MMR II. All participants in the three groups retained seropositivity to rubella, while less than 50% remained seropositive to mumps. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. STRATOS™ system for the repair of pectus excavatum.

    Science.gov (United States)

    Stefani, Alessandro; Nesci, Jessica; Morandi, Uliano

    2013-12-01

    Open techniques represent a valid repair option for severe asymmetric pectus excavatum in adults. The use of metal supports is recommended to reduce the risk of recurrence. A wide variety of metal supports have been proposed, with pre-, trans- or retrosternal fixation. A novel open technique using titanium bars fixed to the ribs with clips has been recently introduced (STRATOS™ system) for chest wall reconstruction, rib fracture fixation and chest wall malformation repair. We employed this technique in two adult patients with severe asymmetric pectus excavatum: after sternal mobilization, one bar is passed below the body of the sternum and secured with clips bilaterally to two ribs. In the first case, the results remained excellent 5 years after surgery. In the second case, the initial results were satisfying but the bar ruptured after 30 months: removal of the bars and clips was performed and a subsequent recurrence of the deformity occurred. The experiences reported in literature are still too limited to draw firm conclusions about the use of the STRATOS™ system in pectus excavatum repair, but it seems that the use of two bars may reduce the risk of rupture. At present, we are the only ones who reported long-term results.

  9. Bone repair: Effects of physical exercise and LPS systemic exposition.

    Science.gov (United States)

    Nogueira, Jonatas E; Branco, Luiz G S; Issa, João Paulo M

    2016-08-01

    Bone repair can be facilitated by grafting, biochemical and physical stimulation. Conversely, it may be delayed lipopolysaccharide (LPS). Physical exercise exerts beneficial effects on the bone, but its effect on bone repair is not known. We investigated the effect of exercise on the LPS action on bone healing through bone densitometry, quantitative histological analysis for bone formation rate and immunohistochemical markers in sedentary and exercised animals. Rats ran on the treadmill for four weeks. After training the rats were submitted to a surgical procedure (bone defect in the right tibia) and 24h after the surgery LPS was administered at a dose of 100μg/kg i.p., whereas the control rats received a saline injection (1ml/kg, i.p.). Right tibias were obtained for analysis after 10days during which rats were not submitted to physical training. Physical exercise had a positive effect on bone repair, increasing bone mineral density, bone mineral content, bone formation rate, type I collagen and osteocalcin expression. These parameters were not affected by systemic administration of LPS. Our data indicate that physical exercise has an important osteogenic effect, which is maintained during acute systemic inflammation induced by exposure to a single dose of LPS.

  10. Evaluation of Precast Panels for Airfield Pavement Repair. Phase 1: System Optimization and Test Section Construction

    Science.gov (United States)

    2013-06-01

    panel repair system for repair of rigid airfield pavements in contingency situations. Design criteria were provided by AFCEC to assist with the...dimensions limit repair versatility, since they do not align with typical rigid airfield pavement slab sizes. The Air Force prototype system design consists...at the joint. The original Air Force panel design used 0.75-in.-wide joints that were backfilled with a rapid-setting rigid pavement repair material

  11. Detection of coding microsatellite frameshift mutations in DNA mismatch repair-deficient mouse intestinal tumors.

    Science.gov (United States)

    Woerner, Stefan M; Tosti, Elena; Yuan, Yan P; Kloor, Matthias; Bork, Peer; Edelmann, Winfried; Gebert, Johannes

    2015-11-01

    Different DNA mismatch repair (MMR)-deficient mouse strains have been developed as models for the inherited cancer predisposing Lynch syndrome. It is completely unresolved, whether coding mononucleotide repeat (cMNR) gene mutations in these mice can contribute to intestinal tumorigenesis and whether MMR-deficient mice are a suitable molecular model of human microsatellite instability (MSI)-associated intestinal tumorigenesis. A proof-of-principle study was performed to identify mouse cMNR-harboring genes affected by insertion/deletion mutations in MSI murine intestinal tumors. Bioinformatic algorithms were developed to establish a database of mouse cMNR-harboring genes. A panel of five mouse noncoding mononucleotide markers was used for MSI classification of intestinal matched normal/tumor tissues from MMR-deficient (Mlh1(-/-) , Msh2(-/-) , Msh2(LoxP/LoxP) ) mice. cMNR frameshift mutations of candidate genes were determined by DNA fragment analysis. Murine MSI intestinal tumors but not normal tissues from MMR-deficient mice showed cMNR frameshift mutations in six candidate genes (Elavl3, Tmem107, Glis2, Sdccag1, Senp6, Rfc3). cMNRs of mouse Rfc3 and Elavl3 are conserved in type and length in their human orthologs that are known to be mutated in human MSI colorectal, endometrial and gastric cancer. We provide evidence for the utility of a mononucleotide marker panel for detection of MSI in murine tumors, the existence of cMNR instability in MSI murine tumors, the utility of mouse subspecies DNA for identification of polymorphic repeats, and repeat conservation among some orthologous human/mouse genes, two of them showing instability in human and mouse MSI intestinal tumors. MMR-deficient mice hence are a useful molecular model system for analyzing MSI intestinal carcinogenesis.

  12. DNA错配修复蛋白多功能性的研究进展%Progress in the versatilities of DNA mismatch repair proteins

    Institute of Scientific and Technical Information of China (English)

    李正莉; 吴建新

    2010-01-01

    DNA Mismatch Repair (MMR) system is one of DNA damage repair pathways, existing in all organisms from bacteria, yeast to human. This system consists of a group of highly-conserved enzymatic proteins. The well-studied function of MMR proteins is to maintain the stability of the genomes by correcting basebase mismatches and insertion/deletion loops generated during DNA replication and recombination. Increasing numbers of researches have revealed that the MMR proteins have multiple roles, including regulation of DNA damage response, homologous recombination, meiotic chromosome pairing and segregation, diversification of antibody and tri-nucleotide repeat expansion. This review is about the resent progress in the study of the versatilities of DNA mismatch repair proteins.%DNA错配修复(mismatch repair,MMR)系统是DNA损伤修复的多种途径之一,存在于从细菌、酵母到人体的所有生物体,由一组高保守性酶蛋白组成.其通过校正DNA复制及重组中产生的碱基错配与插入/缺失环,维持所有生物基因组稳定性的功能已研究比较清楚.越来越多的研究还揭示了错配修复蛋白的其他功能:参与调控DNA损伤应答,同源重组,减数分裂的染色体配对和分离,抗体多样性产生及三核苷酸重复序列扩增等过程.本文将对错配修复蛋白多功能性的研究进展作一综述.

  13. A discounted model for a repairable system with continuous state space

    NARCIS (Netherlands)

    Bruns, P.B.

    2000-01-01

    We examine repairable systems with a continous state space and partial repair options, carried out at fixed times $n=1,2,...$. Every time interval $[n,n+1)$ there is a manufacturing cost and a repair cost. These cost functions are not restricted to the class of bounded functions in this study. Condi

  14. Bond strength durability of a resin composite on a reinforced ceramic using various repair systems

    NARCIS (Netherlands)

    Ozcan, Mutlu; Valandro, Luiz Felipe; Amaral, Regina; Leite, Fabiola; Bottino, Marco Antonio

    2009-01-01

    Objectives. This study compared the durability of repair bond strength of a resin composite to a reinforced ceramic after three repair systems. Methods. Alumina-reinforced feldspathic ceramic blocks (Vitadur-alpha(R)) (N=30) were randomly divided into three groups according to the repair method: PR-

  15. Alkylation damage in DNA and RNA--repair mechanisms and medical significance

    DEFF Research Database (Denmark)

    Drabløs, Finn; Feyzi, Emadoldin; Aas, Per Arne

    2004-01-01

    Alkylation lesions in DNA and RNA result from endogenous compounds, environmental agents and alkylating drugs. Simple methylating agents, e.g. methylnitrosourea, tobacco-specific nitrosamines and drugs like temozolomide or streptozotocin, form adducts at N- and O-atoms in DNA bases. These lesions...... are mainly repaired by direct base repair, base excision repair, and to some extent by nucleotide excision repair (NER). The identified carcinogenicity of O(6)-methylguanine (O(6)-meG) is largely caused by its miscoding properties. Mutations from this lesion are prevented by O(6)-alkylG-DNA alkyltransferase......, inactivation of the MMR system in an AGT-defective background causes resistance to the killing effects of O(6)-alkylating agents, but not to the mutagenic effect. Bifunctional alkylating agents, such as chlorambucil or carmustine (BCNU), are commonly used anti-cancer drugs. DNA lesions caused by these agents...

  16. Randomised cluster trial to support informed parental decision-making for the MMR vaccine

    Directory of Open Access Journals (Sweden)

    Bekker Hilary

    2011-06-01

    Full Text Available Abstract Background In the UK public concern about the safety of the combined measles, mumps and rubella [MMR] vaccine continues to impact on MMR coverage. Whilst the sharp decline in uptake has begun to level out, first and second dose uptake rates remain short of that required for population immunity. Furthermore, international research consistently shows that some parents lack confidence in making a decision about MMR vaccination for their children. Together, this work suggests that effective interventions are required to support parents to make informed decisions about MMR. This trial assessed the impact of a parent-centred, multi-component intervention (balanced information, group discussion, coaching exercise on informed parental decision-making for MMR. Methods This was a two arm, cluster randomised trial. One hundred and forty two UK parents of children eligible for MMR vaccination were recruited from six primary healthcare centres and six childcare organisations. The intervention arm received an MMR information leaflet and participated in the intervention (parent meeting. The control arm received the leaflet only. The primary outcome was decisional conflict. Secondary outcomes were actual and intended MMR choice, knowledge, attitude, concern and necessity beliefs about MMR and anxiety. Results Decisional conflict decreased for both arms to a level where an 'effective' MMR decision could be made one-week (effect estimate = -0.54, p Conclusions Whilst both the leaflet and the parent meeting reduced parents' decisional conflict, the parent meeting appeared to enable parents to act upon their decision leading to vaccination uptake.

  17. 基于INPGA的地下水污染治理多目标优化管理模型:Ⅱ——实例应用%INPGA-based Multiobjective Management Model for Optimal Design of Groundwater Remediation System: II. Application to the MMR Site

    Institute of Scientific and Technical Information of China (English)

    吴剑锋; 彭伟; 钱家忠; 吴吉春; 郑春苗

    2011-01-01

    简单算例研究表明改进的小生境Pareto遗传算法(INPGA)用于求解地下水系统的多目标优化管理模型时,求解过程简单,计算速度快,而且得到的Pareto解集跨度更为合理.本文以美国麻省军事保护区(Massachusetts Military Reservation,MMR)为实例,通过建立研究区复杂地下水污染治理的多目标优化管理模型,进一步对比NPGA和INPGA的求解结果,同时详细讨论和分析适应值库操作和MPI并行技术在实例中的应用效果.求解结果表明MPI并行技术在实例应用中能明显提高加速度和计算效率,而且同样能提供足够的选择方案供决策者权衡选择,由此证明基于INPGA的地下水污染治理多目标优化模型具有很好的应用前景.%The simple case study has shown that the improved niched Pareto genetic algorithm(INPGA) is applicable to multi-objective optimal design of groundwater remediation system due to thesimple procedure, the efficient computation, as well as the rational span of the Pareto solutions. However,the acceleration and efficiency of INPGA based on the message passing interface (MPI) is comparativelylow for the simple application. To further demonstrate the applicability and usefulness of INPGA coupledwith the MPI for parallel computing and the operation library of individual fitness under real fieldconditions, accordingly, an application project was conducted at the Massachusetts Military Reservation (MMR) in Cape Cod, Massachusetts, involving the multi-objective optimal design of a groundwater pump and treat system. The results of this study show that not only would it be possible using MPI to improve the parallel acceleration and efficiency, but also a near-Pareto-front trade-off curve could be achieved byproviding enough Pareto solutions to decision-makers. This field application clearly demonstrates the attractive prospect of MPI-based INPGA in identifying multi-objective optimal design of groundwater remediation systems.

  18. Successful repair of a ventricular assist system percutaneous lead.

    Science.gov (United States)

    Pantalos, G M; Marks, J D; Richardson, E E; Nelson, K E; Long, J W

    1999-01-01

    A patient with an implanted, electrically powered, ventricular assist device (Thermo Cardiosystems VE HeartMate) experienced a partial break of the percutaneous lead 5 months after implantation. The break (limited to the Silicone rubber tube) occurred at the junction of the lead with the Y-connector to the controller and vent, leaving approximately 5 cm of exposed lead from the skin exit site to the connector. Electronic and pumping functions of the pump continued, but the opening in the lead (which went more that half way around the circumference) prevented the use of pneumatic actuation as a back-up mode for pump operation, and placed the pump at risk for contamination. Repair of the lead without surgical intervention was desirable, with ease of repair and minimal risk to the patient being the top priorities. The use of multiple layers of heat-shrink tubing or external metal stents was ruled out in favor of a three stage repair procedure. The first stage involved the removal of the Dacron velour in-growth material from the lead to expose the underlying Silicone rubber tube. While the opening in the tube was held shut, a coating of medical grade Silicone rubber adhesive was applied to the tube, then wrapped with a woven Dacron mesh, followed by two layers of plastic wrapping material to protect the adhesive. This initial layer was secured by an external stent of tubing with cable ties. After several days to allow for complete curing of the adhesive, the adhesive coating with mesh was repeated. The final step involved a double layer wrap of a 1 mm thick Silicone rubber sheeting with mesh incorporation and adhesive secured in place with cable ties. After completion of the repair and verification of the ability to operate the device with pneumatic actuation, the patient was discharged with no recurrence of the problem after 8 months of weekly follow-up. This experience demonstrates the need to clinically anticipate component repair or replacement without total device

  19. Inducible repair system in Haemophilus influenzae unaccompanied by mutation. [uv

    Energy Technology Data Exchange (ETDEWEB)

    Notani, N.K.; Setlow, J.K.

    1980-07-01

    Weigle reactivation of ultraviolet-irradiated HPlc1 phage was observed after ultraviolet or mitomycin C treatment of Haemophilus influenzae cells. The amount of reactivation was considerably increased when the treated cells were incubated in growth medium before infection. The presence of chloramphenicol during this incubation abolished the reactivation. No mutation of this phage accompanied the reactivation. When cells were treated so as to produce a maximal reactivation of phage, neither reactivation nor mutation of cells was observed. It is concluded that H. influenzae has an inducible repair system that is not accompanied by mutation.

  20. Mechanism and Durability of Repair Systems in Polymer-Modified Cement Mortars

    Directory of Open Access Journals (Sweden)

    Ru Wang

    2015-01-01

    Full Text Available This paper investigated the mechanism and durability of repair systems made of ordinary cement-based repair mortar and three kinds of polymer-modified repair mortars with old concrete, SBR dispersion, SAE dispersion, and SAE powder. By comparing the bonding properties of mortars before and after erosion, it was found that polymers could effectively improve the durability of the repair system and SAE powder had the best improvement. Micromorphology study of the repair mortar and the interface of repair mortar with old concrete through SEM showed that the polymer film formed from SAE powder whatever in the mortar or at the interface was dense and tough, the film formed from SAE dispersion was loose and weak, while the film formed from SBR dispersion was in between them, which explained the difference in the tensile bond strength and the durability of the repair systems.

  1. Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents

    DEFF Research Database (Denmark)

    Bodo, Sahra; Colas, Chrystelle; Buhard, Olivier

    2015-01-01

    BACKGROUND & AIMS: Patients with bi-allelic germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) develop a rare but severe variant of Lynch syndrome called constitutional MMR deficiency (CMMRD). This syndrome is characterized by early-onset colorectal cancers, lymphomas o...

  2. Direct Self-Repairing Control for Quadrotor Helicopter Attitude Systems

    Directory of Open Access Journals (Sweden)

    Huiliao Yang

    2014-01-01

    Full Text Available A quadrotor helicopter with uncertain actuator faults, such as loss of effectiveness and lock-in-place, is studied in this paper. An adaptive fuzzy sliding mode controller based on direct self-repairing control is designed for such nonlinear system to track the desired output signal, when any actuator of this quadrotor helicopter is loss of effectiveness or stuck at some place. Moreover, using the Lyapunov stability theory, the stability of the whole system and the convergence of the tracking error can be guaranteed. Finally, the availability of the proposed method is verified by simulation on 3-DOF hover to ensure that the system performance under faulty conditions can be quickly recovered to its normal level. And this proposed method is also proved to be better than that of LQR through simulation.

  3. A deteriorating two-system with two repair modes and sojourn times phase-type distributed

    Energy Technology Data Exchange (ETDEWEB)

    Montoro-Cazorla, Delia [Departamento de Estadistica e I.O., Escuela Politecnica de Linares, Universidad de Jaen, 23700 Linares, Jaen (Spain); Perez-Ocon, Rafael [Departamento de Estadistica e I.O., Facultad de Ciencias, Universidad de Granada, Granada 18071 (Spain)]. E-mail: rperezo@ugr.es

    2006-01-01

    We study a two-unit cold standby system in steady-state. The online unit goes through a finite number of stages of successive degradation preceding the failure. The units are reparable, there is a repairman and two types of maintenance are considered, preventive and corrective. The preventive repair aims to improve the degradation of a unit being operative. The corrective repair is necessary when the unit fails. We will assume that the preventive repair will be interrupted in favour of a corrective repair in order to increase the availability of the system. The random operational and repair times follow phase-type distributions. For this system, the stationary probability vector, the replacement times, and the involved costs are calculated. An optimisation problem is illustrated by a numerical example. In this, the optimal degradation stage for the preventive repair of the online unit is determined by taking into account the system availability and the incurred costs.

  4. REPAIRABLE SYSTEM AVAILABILITY MODEL WITH RESPECT TO LIFE DISTRIBUTION OF SPARE PARTS

    Institute of Scientific and Technical Information of China (English)

    WU Yueming

    2008-01-01

    The failed components of repairable systems are replaced with spare parts that may have different failure distributions from those of the components that have failed. The spare parts may be either the same as new, better than new, or worse than new. This is the reality in maintenance engineering. Repair with better spare parts is defined as "super repair". The failure distributions of the spare parts affect the availability of the components and their systems. A novel model is proposed to describe the availability of repairable systems across their operating time, at the level of their components, on the assumption that the failed components are immediately replaced. The model functions with arbitrary failure distributions of spare parts. It can be used to compute the availability of components and systems not only under perfect and imperfect repair but also under super repair.

  5. Eliminating both canonical and short-patch mismatch repair in Drosophila melanogaster suggests a new meiotic recombination model.

    Science.gov (United States)

    Crown, K Nicole; McMahan, Susan; Sekelsky, Jeff

    2014-09-01

    In most meiotic systems, recombination is essential to form connections between homologs that ensure their accurate segregation from one another. Meiotic recombination is initiated by DNA double-strand breaks that are repaired using the homologous chromosome as a template. Studies of recombination in budding yeast have led to a model in which most early repair intermediates are disassembled to produce noncrossovers. Selected repair events are stabilized so they can proceed to form double-Holliday junction (dHJ) intermediates, which are subsequently resolved into crossovers. This model is supported in yeast by physical isolation of recombination intermediates, but the extent to which it pertains to animals is unknown. We sought to test this model in Drosophila melanogaster by analyzing patterns of heteroduplex DNA (hDNA) in recombination products. Previous attempts to do this have relied on knocking out the canonical mismatch repair (MMR) pathway, but in both yeast and Drosophila the resulting recombination products are complex and difficult to interpret. We show that, in Drosophila, this complexity results from a secondary, short-patch MMR pathway that requires nucleotide excision repair. Knocking out both canonical and short-patch MMR reveals hDNA patterns that reveal that many noncrossovers arise after both ends of the break have engaged with the homolog. Patterns of hDNA in crossovers could be explained by biased resolution of a dHJ; however, considering the noncrossover and crossover results together suggests a model in which a two-end engagement intermediate with unligated HJs can be disassembled by a helicase to a produce noncrossover or nicked by a nuclease to produce a crossover. While some aspects of this model are similar to the model from budding yeast, production of both noncrossovers and crossovers from a single, late intermediate is a fundamental difference that has important implications for crossover control.

  6. Eliminating both canonical and short-patch mismatch repair in Drosophila melanogaster suggests a new meiotic recombination model.

    Directory of Open Access Journals (Sweden)

    K Nicole Crown

    2014-09-01

    Full Text Available In most meiotic systems, recombination is essential to form connections between homologs that ensure their accurate segregation from one another. Meiotic recombination is initiated by DNA double-strand breaks that are repaired using the homologous chromosome as a template. Studies of recombination in budding yeast have led to a model in which most early repair intermediates are disassembled to produce noncrossovers. Selected repair events are stabilized so they can proceed to form double-Holliday junction (dHJ intermediates, which are subsequently resolved into crossovers. This model is supported in yeast by physical isolation of recombination intermediates, but the extent to which it pertains to animals is unknown. We sought to test this model in Drosophila melanogaster by analyzing patterns of heteroduplex DNA (hDNA in recombination products. Previous attempts to do this have relied on knocking out the canonical mismatch repair (MMR pathway, but in both yeast and Drosophila the resulting recombination products are complex and difficult to interpret. We show that, in Drosophila, this complexity results from a secondary, short-patch MMR pathway that requires nucleotide excision repair. Knocking out both canonical and short-patch MMR reveals hDNA patterns that reveal that many noncrossovers arise after both ends of the break have engaged with the homolog. Patterns of hDNA in crossovers could be explained by biased resolution of a dHJ; however, considering the noncrossover and crossover results together suggests a model in which a two-end engagement intermediate with unligated HJs can be disassembled by a helicase to a produce noncrossover or nicked by a nuclease to produce a crossover. While some aspects of this model are similar to the model from budding yeast, production of both noncrossovers and crossovers from a single, late intermediate is a fundamental difference that has important implications for crossover control.

  7. Loss of Thiol Repair Systems in Human Cataractous Lenses

    Science.gov (United States)

    Wei, Min; Xing, Kui-Yi; Fan, Yin-Chuan; Libondi, Teodosio; Lou, Marjorie F.

    2015-01-01

    Purpose. The purpose of this study was to investigate the thiol repair systems of thioltransferase (TTase) and thioredoxin (Trx) and oxidation-damaged proteins in human cataractous lenses. Methods. Cataractous lenses in humans (57–85 years of age) were classified into cortical, nuclear, mixed, mature, and hypermature cataract types by using a lens opacity classification system, and were obtained by extracapsular cataract extraction (ECCE) procedure. Cortical and nuclear cataracts were grouped by decreasing order of visual acuity into optical chart reading (R), counting fingers (CF), hand motion (HM), and light perception (LP). ECCE lens homogenate was analyzed for glutathione (GSH) level and enzyme activities of TTase, glutathione reductase (GR), Trx, and thioredoxin reductase (TR). Cortical and nuclear cataractous lenses (8 of each) with visual acuity better than HM were each dissected into cortical and nuclear portions for measurement of glyceraldehyde 3-phosphate dehydrogenase (G3PD) activity. Clear lenses (in humans 49–71 years of age) were used as control. Results. Compared with control, all cataractous lenses lost more than 80% GSH and 70% GR; TR and Trx activity; and 40% to 70% TTase activity, corroborated with the loss in visual acuity. Among cataracts with R and CF visual acuity, cortical cataract lost more cortical G3PD activity (18% of control) than that of nuclear cataract (50% of control), whereas GSH depletion and TTase inactivation were similar in both cataracts. Conclusions. Thiol repair systems were damaged in all types of cataracts. Cortical and nuclear cataracts showed differential G3PD inactivation in the cortex, implying those 2 type of cataracts might be formed through different mechanisms. PMID:25537203

  8. Repair and degradation systems in irradiated animal cells

    Energy Technology Data Exchange (ETDEWEB)

    Ivannik, B.P.; Proskuryakov, S.Ya.; Ryabchenko, N.I. (Akademiya Meditsinskikh Nauk SSSR, Obninsk. Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii)

    It was shown that primary radiosensitivity of DNA depends on the rate of DNA repair. In Zajdela hepatoma cells, cycloheximide administered immediately or 2 h before irradiation of animals does not influence DNA repair. Cycloheximide administered 4 h before irradiation of rats with a dose of 30 Gy arrests DNA repair in thymocytes and Zajdela hepatoma cells. At the same time, in cells of rat lymph nodes and spleen, under similar conditions, cycloheximide does not influence DNA repair and inhibits the secondary DNA degradation.

  9. MMR vaccine in 14 months old children, intramuscular versus subcutaneous administration

    NARCIS (Netherlands)

    Lafeber AF; Klis FRM van der; Marzec AHJO; Labadie J; Ommen R van; Strieder TG; Berbers GAM; Utrecht Stichting Thuiszorg; Amersfoort Stichting Thuiszorg Eemland (STE),; LVO

    2001-01-01

    In this study we compared the recommended subcutaneous administration of the RIVM MMR vaccine with the intramuscular administration for both safety and immunogenicity. Study subjects were 14 months old children, living in Amersfoort or Utrecht, who were eligible for their first MMR vaccination. The

  10. No Effect of MMR Withdrawal on the Incidence of Autism: A Total Population Study

    Science.gov (United States)

    Honda, Hideo; Shimizu, Yasuo; Rutter, Michael

    2005-01-01

    Background: A causal relationship between the measles, mumps, and rubella (MMR) vaccine and occurrence of autism spectrum disorders (ASD) has been claimed, based on an increase in ASD in the USA and the UK after introduction of the MMR vaccine. However, the possibility that this increase is coincidental has not been eliminated. The unique…

  11. Role of Cell Cycle Regulation and MLH1, A Key DNA Mismatch Repair Protein, In Adaptive Survival Responses. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    David A. Boothman

    1999-08-11

    Due to several interesting findings on both adaptive survival responses (ASRs) and DNA mismatch repair (MMR), this grant was separated into two discrete Specific Aim sets (each with their own discrete hypotheses). The described experiments were simultaneously performed.

  12. Effect of Moisture Exchange on Interface Formation in the Repair System Studied by X-ray Absorption

    NARCIS (Netherlands)

    Lukovic, M.; Ye, G.

    2015-01-01

    In concrete repair systems, material properties of the repair material and the interface are greatly influenced by the moisture exchange between the repair material and the substrate. If the substrate is dry, it can absorb water from the repair material and reduce its effective water-to-cement ratio

  13. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Buchanan DD

    2014-10-01

    Full Text Available Daniel D Buchanan,1,2 Christophe Rosty,1,3,4 Mark Clendenning,1 Amanda B Spurdle,5 Aung Ko Win2 1Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia; 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; 3Envoi Specialist Pathologists, Herston, QLD, Australia; 4School of Medicine, University of Queensland, Herston, QLD, Australia; 5Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaAbstract: Carriers of a germline mutation in one of the DNA mismatch repair (MMR genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome. MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the

  14. Mathematical model of MMR inversion for geophysical data

    Directory of Open Access Journals (Sweden)

    Suabsagun Yooyuanyong

    2007-09-01

    Full Text Available In this paper, we present an analysis of the solution to a number of geophysical inverse problems which are generally non-unique. The mathematical inverse problem that arises is commonly ill-posed in the sense that small changes in the data lead to large changes in the solution. We conduct the inversion algorithm to explore the conductivity for the ground structure. The algorithm uses the data in the form of magnetic field measurements for magnetometric resistivity (MMR. The inversion example is performed to investigate the conductivity ground profile that best fits the observed data. The result is compared with the true model and discussed to show the efficiency of the method. The model for the inversion example with the apparent conductivity and the true conductivity are plotted to show the convergence of the algorithm.

  15. DNA tandem repeat instability in the Escherichia coli chromosome is stimulated by mismatch repair at an adjacent CAG·CTG trinucleotide repeat

    Science.gov (United States)

    Blackwood, John K.; Okely, Ewa A.; Zahra, Rabaab; Eykelenboom, John K.; Leach, David R. F.

    2010-01-01

    Approximately half the human genome is composed of repetitive DNA sequences classified into microsatellites, minisatellites, tandem repeats, and dispersed repeats. These repetitive sequences have coevolved within the genome but little is known about their potential interactions. Trinucleotide repeats (TNRs) are a subclass of microsatellites that are implicated in human disease. Expansion of CAG·CTG TNRs is responsible for Huntington disease, myotonic dystrophy, and a number of spinocerebellar ataxias. In yeast DNA double-strand break (DSB) formation has been proposed to be associated with instability and chromosome fragility at these sites and replication fork reversal (RFR) to be involved either in promoting or in preventing instability. However, the molecular basis for chromosome fragility of repetitive DNA remains poorly understood. Here we show that a CAG·CTG TNR array stimulates instability at a 275-bp tandem repeat located 6.3 kb away on the Escherichia coli chromosome. Remarkably, this stimulation is independent of both DNA double-strand break repair (DSBR) and RFR but is dependent on a functional mismatch repair (MMR) system. Our results provide a demonstration, in a simple model system, that MMR at one type of repetitive DNA has the potential to influence the stability of another. Furthermore, the mechanism of this stimulation places a limit on the universality of DSBR or RFR models of instability and chromosome fragility at CAG·CTG TNR sequences. Instead, our data suggest that explanations of chromosome fragility should encompass the possibility of chromosome gaps formed during MMR. PMID:21149728

  16. Selenium compounds activate ATM-dependent DNA damage responses via the mismatch repair protein hMLH1 in colorectal cancer cells

    Science.gov (United States)

    Epidemiological and animal studies indicate that selenium supplementation suppresses risk of colorectal and other cancers. The majority of colorectal cancers are characterized by a defective DNA mismatch repair (MMR) process. Here, we have employed the MMR-deficient HCT 116 colorectal cancer cells ...

  17. Immunohistochemical expression of mismatch repair genes: A screening tool for predicting mutator phenotype in liver fluke infection-associated intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Upama Liengswangwong; Anant Karalak; Yukio Morishita; Masayuki Noguchi; Thiravud Khuhaprema; Petcharin Srivatanakul; Masanao Miwa

    2006-01-01

    AIM: To clarify possible contributions of DNA mismatch repair (MMR) system in carcinogenesis of liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) by using immunohistochemical assay.METHODS: A total of 29 ICC samples, which had been assessed for genomic instability by a PCR-based method, were used for study. They were examined immunohistochemically to demonstrate protein expression of two MMR genes, hMSH2 and hMLH1.Results obtained were compared with their mutator phenotype assessed previously.RESULTS: Either hMSH2or hMLH1 protein was obviously expressed in 28 of 29 (96.6%) ICC samples.Positive nuclear localization of hMSH2 or hMLH1 protein was observed in 86.2% (25/29) or 93.1% (27/29) ICC cases, respectively, while their negative nuclear reactivity was only detected in 13.8% (4/29) or 6.9% (2/29) ICC cases analyzed, respectively.CONCLUSION: Our study, probably for the first time,showed through immunohistochemical detection of hMSH2 and hMLH1 gene that DNA MMR system does not play a prominent role in liver fluke infection-associated cholangiocarcinogenesis. These results confirm previous findings on mutational status of these genes assessed through a PCR-based method. The immunohistochemical analysis has proven to be an effective and sensitive approach for screening MMR deficiency regardless of somatic inactivation or promoter hypermethylation of hMSH2 and/or hMLH1 gene. Furthermore,immunohistochemistry is more advantageous compared to mutator phenotyping assay in terms of simplicity,less time consuming and cost effectiveness for screening possible involvements of target MMR genes in tumorigenesis.

  18. Reliability analysis of repairable systems using system dynamics modeling and simulation

    Science.gov (United States)

    Srinivasa Rao, M.; Naikan, V. N. A.

    2014-07-01

    Repairable standby system's study and analysis is an important topic in reliability. Analytical techniques become very complicated and unrealistic especially for modern complex systems. There have been attempts in the literature to evolve more realistic techniques using simulation approach for reliability analysis of systems. This paper proposes a hybrid approach called as Markov system dynamics (MSD) approach which combines the Markov approach with system dynamics simulation approach for reliability analysis and to study the dynamic behavior of systems. This approach will have the advantages of both Markov as well as system dynamics methodologies. The proposed framework is illustrated for a standby system with repair. The results of the simulation when compared with that obtained by traditional Markov analysis clearly validate the MSD approach as an alternative approach for reliability analysis.

  19. Materials directed to implants for repairing Central Nervous System

    Directory of Open Access Journals (Sweden)

    Canillas, M.

    2014-12-01

    Full Text Available Central Nervous System (CNS can be damaged by a wide range of injuries and disorders which entail permanent disability in some cases. Moreover, CNS repairing process presents some complications. The natural repair mechanism, which consists on the glial scar formation, is triggered by the inflammatory process. Molecules delivered during these processes, inflammation and glial scar formation as well as oxygen and glucose deficiencies due to the injury, create an inhibitory environment for axon regeneration and remyelination which is known as “secondary injury”. Biomaterials are taking up an even more important role in repairing CNS. Physicochemical properties of some ceramic materials have inspired different applications to repair CNS as substrates, electrodes or molecule vehicles. Based on their biocompatibility, capability to neutralize reactive species involved in the inflammatory processes and their versatile processing to obtain scaffolds with different shapes and sizes, ceramics are a succulent offer in nervous tissue engineering. Furthermore, their possibilities have been increased with polymeric-ceramics composites development, which have given rise to new interesting horizon.Existen diferentes tipos de lesiones o desordenes del Sistema Nervioso Central (SNC que pueden provocar graves secuelas e incluso en algunos casos una discapacidad permanente. Además, el proceso de reparación del SNC tiene algunas complicaciones. El mecanismo natural de reacción a una lesión, el cual consiste en la formación de una cicatriz glial, es desencadenado por un proceso inflamatorio. Las moléculas liberadas durante estos procesos, la inflamación y formación de la cicatriz glial, así como la deficiencia en oxígeno y glucosa debidos a la lesión, crean un ambiente que inhibe la regeneración axonal creando la llamada “lesión secundaria”. Los biomateriales están adquiriendo un papel cada vez más importante en la reparación de SNC. Las

  20. Homologous and homeologous intermolecular gene conversion are not differentially affected by mutations in the DNA damage or the mismatch repair genes RAD1, RAD50, RAD51, RAD52, RAD54, PMS1 and MSH2

    Energy Technology Data Exchange (ETDEWEB)

    Porter, G.; Westmoreland, J.; Priebe, S. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)] [and others

    1996-06-01

    Mismatch repair (MMR) genes or genes involved in both DNA damage repair and homologous recombination might affect homeologous vs. homologous recombination differentially. Spontaneous mitotic gene conversion between a chromosome and a homologous or homeologous donor sequence (14% diverged) on a single copy plasmid was examined in wild-type Saccharomyces cerevisiae strains and in MMR or DNA damage repair mutants. Homologous recombination in rad51, rad52 and rad54 mutants was considerably reduced, while there was little effect of rad1, rad50, pms1 and msh2 null mutations. DNA divergence resulted in no differential effect on recombination rates in the wild type or the mutants; there was only a five- to 10-fold reduction in homeologous relative to homologous recombination regardless of background. Since DNA divergence is known to affect recombination in some systems, we propose that differences in the role of MMR depends on the mode of recombination and/or the level of divergence. Based on analysis of the recombination breakpoints, there is a minimum of three homologous bases required at a recombination junction. A comparison of Rad{sup +} vs. rad52 strains revealed that while all conversion tracts are continuous, elimination of RAD52 leads to the appearance of a novel class of very short conversion tracts. 67 refs., 5 figs., 4 tabs.

  1. A non-canonical mismatch repair pathway in prokaryotes

    Science.gov (United States)

    Castañeda-García, A.; Prieto, A. I.; Rodríguez-Beltrán, J.; Alonso, N.; Cantillon, D.; Costas, C.; Pérez-Lago, L.; Zegeye, E. D.; Herranz, M.; Plociński, P.; Tonjum, T.; García de Viedma, D.; Paget, M.; Waddell, S. J.; Rojas, A. M.; Doherty, A. J.; Blázquez, J.

    2017-01-01

    Mismatch repair (MMR) is a near ubiquitous pathway, essential for the maintenance of genome stability. Members of the MutS and MutL protein families perform key steps in mismatch correction. Despite the major importance of this repair pathway, MutS–MutL are absent in almost all Actinobacteria and many Archaea. However, these organisms exhibit rates and spectra of spontaneous mutations similar to MMR-bearing species, suggesting the existence of an alternative to the canonical MutS–MutL-based MMR. Here we report that Mycobacterium smegmatis NucS/EndoMS, a putative endonuclease with no structural homology to known MMR factors, is required for mutation avoidance and anti-recombination, hallmarks of the canonical MMR. Furthermore, phenotypic analysis of naturally occurring polymorphic NucS in a M. smegmatis surrogate model, suggests the existence of M. tuberculosis mutator strains. The phylogenetic analysis of NucS indicates a complex evolutionary process leading to a disperse distribution pattern in prokaryotes. Together, these findings indicate that distinct pathways for MMR have evolved at least twice in nature. PMID:28128207

  2. In-Space Repair and Refurbishment of Thermal Protection System Structures for Reusable Launch Vehicles

    Science.gov (United States)

    Singh, M.

    2007-01-01

    Advanced repair and refurbishment technologies are critically needed for the thermal protection system of current space transportation systems as well as for future launch and crew return vehicles. There is a history of damage to these systems from impact during ground handling or ice during launch. In addition, there exists the potential for in-orbit damage from micrometeoroid and orbital debris impact as well as different factors (weather, launch acoustics, shearing, etc.) during launch and re-entry. The GRC developed GRABER (Glenn Refractory Adhesive for Bonding and Exterior Repair) material has shown multiuse capability for repair of small cracks and damage in reinforced carbon-carbon (RCC) material. The concept consists of preparing an adhesive paste of desired ceramic with appropriate additives and then applying the paste to the damaged/cracked area of the RCC composites with an adhesive delivery system. The adhesive paste cures at 100-120 C and transforms into a high temperature ceramic during reentry conditions. A number of plasma torch and ArcJet tests were carried out to evaluate the crack repair capability of GRABER materials for Reinforced Carbon-Carbon (RCC) composites. For the large area repair applications, Integrated Systems for Tile and Leading Edge Repair (InSTALER) have been developed and evaluated under various ArcJet testing conditions. In this presentation, performance of the repair materials as applied to RCC is discussed. Additionally, critical in-space repair needs and technical challenges are reviewed.

  3. Higher occurrence of childhood cancer in families with germline mutations in BRCA2, MMR and CDKN2A genes

    DEFF Research Database (Denmark)

    Magnusson, S.; Borg, A.; Kristoffersson, U.

    2008-01-01

    The contribution of hereditary factors for development of childhood tumors is limited to some few known syndromes associated with predominance of tumors in childhood. Occurrence of childhood tumors in hereditary cancer syndromes such as BRCA1/2 associated breast and ovarian cancer, DNA-mismatch r......-mismatch repair (MMR) genes associated hereditary non polyposis colorectal cancer and CDKN2A associated familial malignant melanoma are very little studied. Herein we report the prevalence of childhood tumors (diagnosed......The contribution of hereditary factors for development of childhood tumors is limited to some few known syndromes associated with predominance of tumors in childhood. Occurrence of childhood tumors in hereditary cancer syndromes such as BRCA1/2 associated breast and ovarian cancer, DNA...

  4. Mismatch-mediated error prone repair at the immunoglobulin genes.

    Science.gov (United States)

    Chahwan, Richard; Edelmann, Winfried; Scharff, Matthew D; Roa, Sergio

    2011-12-01

    The generation of effective antibodies depends upon somatic hypermutation (SHM) and class-switch recombination (CSR) of antibody genes by activation induced cytidine deaminase (AID) and the subsequent recruitment of error prone base excision and mismatch repair. While AID initiates and is required for SHM, more than half of the base changes that accumulate in V regions are not due to the direct deamination of dC to dU by AID, but rather arise through the recruitment of the mismatch repair complex (MMR) to the U:G mismatch created by AID and the subsequent perversion of mismatch repair from a high fidelity process to one that is very error prone. In addition, the generation of double-strand breaks (DSBs) is essential during CSR, and the resolution of AID-generated mismatches by MMR to promote such DSBs is critical for the efficiency of the process. While a great deal has been learned about how AID and MMR cause hypermutations and DSBs, it is still unclear how the error prone aspect of these processes is largely restricted to antibody genes. The use of knockout models and mice expressing mismatch repair proteins with separation-of-function point mutations have been decisive in gaining a better understanding of the roles of each of the major MMR proteins and providing further insight into how mutation and repair are coordinated. Here, we review the cascade of MMR factors and repair signals that are diverted from their canonical error free role and hijacked by B cells to promote genetic diversification of the Ig locus. This error prone process involves AID as the inducer of enzymatically-mediated DNA mismatches, and a plethora of downstream MMR factors acting as sensors, adaptors and effectors of a complex and tightly regulated process from much of which is not yet well understood.

  5. THE OPTIMAL SYSTEM FOR SERIES SYSTEMS WITH WARM STANDBY COMPONENTS AND A REPAIRABLE SERVICE STATION

    Directory of Open Access Journals (Sweden)

    M. Salah EL-Sherbeny

    2009-01-01

    Full Text Available This paper deals with the reliability and availability characteristics of three different series system configurations with warm standby components and a repairable service station. The failure time of the primary and warm standby are assumed to be exponentially distributed with parameters and respectively. The repair time distribution of each server is also exponentially distributed with parameter . The breakdown time and the repair time of the service station are also assumed exponentially distributed with parameters and respectively. We derive the reliability dependent on time, availability dependent on time, the mean time to failure, , and the steady-state availability for three configurations and perform comparisons. Comparisons are made for specific values of distribution parameters and of the cost of the components. The three configurations are ranked based on: , and where is either or .

  6. A modelling study of drying shrinkage damage in concrete repair systems

    NARCIS (Netherlands)

    Lukovic, M.; Savija, B.; Schlangen, E.; Ye, G.; van Breugel, K.

    2014-01-01

    Differential shrinkage between repair material and concrete substrate is considered to be the main cause of premature failure of repair systems (Martinola, Sadouki et al. 2001, Beushausen and Alexander 2007). Magnitude of induced stresses depends on many factors, for example the amount of restraint,

  7. Low vaccine efficacy of mumps component among MMR vaccine recipients in Chennai, India

    Directory of Open Access Journals (Sweden)

    Jeevan Malaiyan

    2014-01-01

    Full Text Available Introduction of MMR vaccine was believed to have resulted in a decline in the incidence of measles, mumps and rubella infections. However, recent reports suggest the re-emergence of mumps infection worldwide in the vaccinated populations. It was proposed that the reason for this re-emergence was poor efficacy of MMR vaccine. The present study was aimed to investigate mumps infection in MMR vaccinated and non-vaccinated populations in Chennai, India. Blood samples were collected from acute mumps cases (n=74, 42<12 yr age, 54% males and investigated for IgM antibody against mumps, IgG antibody against measles, mumps and rubella viruses by ELISA. Sixty seven (91% patients had received MMR vaccine. All the 67 vaccinated cases were positive for parotitis, and mumps IgM. However, only 10 (15% were positive for IgG. All samples (100% were positive for rubella and measles IgG. These findings showed the occurrence of mumps infection among MMR vaccinated individuals in Chennai, India. The MMR vaccine failed to generate anti-mumps IgG. The reason may be low vaccine efficacy of the mumps component of the MMR vaccine used.

  8. Shear Bond Strength of Repair Systems to New CAD/CAM Restorative Materials.

    Science.gov (United States)

    Üstün, Özlem; Büyükhatipoğlu, Işıl Keçik; Seçilmiş, Aslı

    2016-11-23

    To evaluate the bond strength of repair systems (Ceramic Repair, Clearfil Repair) to computer-aided design/computer-assisted machining (CAD/CAM) restorative materials (IPS e.max CAD, Vita Suprinity, Vita Enamic, Lava Ultimate). Thermally aged CAD/CAM restorative material specimens (5000 cycles between 5°C and 55°C) were randomly divided into two groups according to the repair system: Ceramic Repair (37% phosphoric acid + Monobond-S + Heliobond + Tetric N Ceram) or Clearfil Repair (40% phosphoric acid + mixture of Clearfil Porcelain Bond Activator and Clearfil SE Bond Primer + Clearfil SE Bond + Filtek Z250). The resin composite was light-cured on conditioned specimens. All specimens were stored in distilled water at 37°C for 24 hours and then additionally aged for 5000 thermal cycles. The shear bond strength test was performed using a universal testing machine (0.5 mm/min). Two-way ANOVA was used to detect significance differences according to the CAD/CAM material and composite repair system factors. Subgroup analyses were conducted using the least significant difference post-hoc test. The results of two-way ANOVA indicated that bond strength values varied according to the restorative materials (p CAD/CAM restorative materials (p > 0.05), except in the Vita Suprinity group (p < 0.05). Moreover, no differences were observed between the repair systems. Both the Clearfil and Ceramic repair systems used in the study allow for successful repairs. © 2016 by the American College of Prosthodontists.

  9. Image reconstruction of mMR PET data using the open source software STIR

    Energy Technology Data Exchange (ETDEWEB)

    Markiewicz, Pawel [Centre for Medical Image Computing, University College London, London (United Kingdom); Thielemans, Kris [Institute of Nuclear Medicine, University College London, London (United Kingdom); Burgos, Ninon [Centre for Medical Image Computing, University College London, London (United Kingdom); Manber, Richard [Institute of Nuclear Medicine, University College London, London (United Kingdom); Jiao, Jieqing [Centre for Medical Image Computing, University College London, London (United Kingdom); Barnes, Anna [Institute of Nuclear Medicine, University College London, London (United Kingdom); Atkinson, David [Centre for Medical Imaging, University College London, London (United Kingdom); Arridge, Simon R [Centre for Medical Image Computing, University College London, London (United Kingdom); Hutton, Brian F [Institute of Nuclear Medicine, University College London, London (United Kingdom); Ourselin, Sébastien [Centre for Medical Image Computing, University College London, London (United Kingdom); Dementia Research Centre, University College London, London (United Kingdom)

    2014-07-29

    Simultaneous PET and MR acquisitions have now become possible with the new hybrid Biograph Molecular MR (mMR) scanner from Siemens. The purpose of this work is to create a platform for mMR 3D and 4D PET image reconstruction which would be freely accessible to the community as well as fully adjustable in order to obtain optimal images for a given research task in PET imaging. The proposed platform is envisaged to prove useful in developing novel and robust image bio-markers which could then be adapted for use on the mMR scanner.

  10. [Correlation between mismatch repair proteins status and clinicopathological characteristics in sporadic colorectal cancer patients].

    Science.gov (United States)

    Xiao, Z T; Zhang, R X; Zhao, Y; Peng, J H; Lu, S X; Zhang, H Z; Ding, P R; Wu, X J; Lu, Z H; Li, L R; Wan, D S; Pan, Z Z; Chen, G

    2017-04-25

    Objective: To explore the expression of mismatch repair (MMR) proteins in sporadic colorectal cancer (SCRC) patients, and its association with clinicopathological characteristics of SCRC. Methods: Patients with histologically confirmed colorectal cancer were consecutively recruited between December 2011 and June 2015 at Sun Yat-sen University Cancer Center. The exclusion criteria included multiple primary colorectal tumors, hereditary colorectal cancer (including Lynch syndrome, familial adenomatous polyposis), and the patients without the MMR proteins status tested. A total of 2 684 patients were included. Correlations of MMR proteins status and patients' demographics (including gender, age), tumor characteristics (site and differentiation) and TNM staging (excluding 315 SCRC patients receiving neoadjuvant therapy) were investigated. Results: The percentage of deficient MMR (dMMR) in these SCRC patients was 10.2%, and that of proficient MMR (pMMR) was 89.8%. The dMMR was more likely to be detected in younger (≤59 old years) SCRC patients compared to the elderly (>59 years) [12.7%(179/1 406)vs 7.5%(96/1 278), Pcolon cancer was significantly higher than that in left colon cancer and rectal cancer [22.7%(151/664)vs 7.2%(69/956)vs 5.2%(55/1 064), Pcolon mucinous adenocarcinoma among SCRC.

  11. Extravehicular Activity Probabilistic Risk Assessment Overview for Thermal Protection System Repair on the Hubble Space Telescope Servicing Mission

    Science.gov (United States)

    Bigler, Mark; Canga, Michael A.; Duncan, Gary

    2010-01-01

    The Shuttle Program initiated an Extravehicular Activity (EVA) Probabilistic Risk Assessment (PRA) to assess the risks associated with performing a Shuttle Thermal Protection System (TPS) repair during the Space Transportation System (STS)-125 Hubble repair mission as part of risk trades between TPS repair and crew rescue.

  12. Ultraviolet damage, DNA repair and vitamin D in nonmelanoma skin cancer and in malignant melanoma: an update.

    Science.gov (United States)

    Reichrath, Jörg; Rass, Knuth

    2014-01-01

    -induced tumorigenesis of melanoma and nonmelanoma skin cancer. An interesting new perspective in DNA damage and repair research lies in the participation of mammalian mismatch repair (MMR) in UV damage correction. As MMR enzyme hMSH2 displays a p53 target gene, is induced by UVB radiation and is involved in NER pathways, studies have now been initiated to elucidate the physiological and pathophysiological role of MMR in malignant melanoma and nonmelanoma skin cancer development. Interestingly, increasing evidence now demonstrates an important function of the vitamin D endocrine system (VDES) for prevention of BCC, SCC and melanoma, identifying the vitamin D receptor as a tumor suppressor in the skin.

  13. Modeling the induced mutation process in bacterial cells with defects in excision repair system

    Science.gov (United States)

    Bugay, A. N.; Vasilyeva, M. A.; Krasavin, E. A.; Parkhomenko, A. Yu.

    2015-12-01

    A mathematical model of the UV-induced mutation process in Escherichia coli cells with defects in the uvrA and polA genes has been developed. The model describes in detail the reaction kinetics for the excision repair system. The number of mismatches as a result of translesion synthesis is calculated for both wild-type and mutant cells. The effect of temporal modulation of the number of single-stranded DNA during postreplication repair has been predicted. A comparison of effectiveness of different repair systems has been conducted.

  14. On-Orbit Health Monitoring and Repair Assessment of Thermal Protection Systems Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR project delivers On-orbit health MoNItoring and repair assessment of THERMal protection systems (OMNI_THERM). OMNI_THERM features impedance-based...

  15. Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage

    NARCIS (Netherlands)

    Rutgers, M.; van Pelt, M.J.; Dhert, W.J.A.; Creemers, L.B.; Saris, D.B.F.

    2010-01-01

    Osteoarthritis and Cartilage Volume 18, Issue 1, January 2010, Pages 12-23 -------------------------------------------------------------------------------- Review Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage M. Rutgers†, M.J.P. van Pelt†, W.

  16. Current state in tracking and robotic navigation systems for application in endovascular aortic aneurysm repair

    NARCIS (Netherlands)

    De Ruiter, Quirina M B; Moll, Frans L.; Van Herwaarden, Joost A.

    2015-01-01

    Objective This study reviewed the current developments in manual tracking and robotic navigation technologies for application in endovascular aortic aneurysm repair (EVAR). Methods EMBASE and MEDLINE databases were searched for studies reporting manual tracking or robotic navigation systems that are

  17. Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage

    NARCIS (Netherlands)

    Rutgers, M.; van Pelt, M.J.; Dhert, W.J.A.; Creemers, L.B.; Saris, D.B.F.

    2010-01-01

    Osteoarthritis and Cartilage Volume 18, Issue 1, January 2010, Pages 12-23 -------------------------------------------------------------------------------- Review Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage M. Rutgers†, M.J.P. van Pelt†,

  18. Current state in tracking and robotic navigation systems for application in endovascular aortic aneurysm repair

    NARCIS (Netherlands)

    De Ruiter, Quirina M B; Moll, Frans L.|info:eu-repo/dai/nl/070246882; Van Herwaarden, Joost A.|info:eu-repo/dai/nl/304814733

    2015-01-01

    Objective This study reviewed the current developments in manual tracking and robotic navigation technologies for application in endovascular aortic aneurysm repair (EVAR). Methods EMBASE and MEDLINE databases were searched for studies reporting manual tracking or robotic navigation systems that are

  19. Self-Repairing Flight Control System for Online Health Monitoring and Recovery Project

    Data.gov (United States)

    National Aeronautics and Space Administration — In this SBIR project, a reliable self-repairing Flight Control System (FCS) will be developed. To achieve this goal, an artificial Neural Network based Sensor...

  20. WELL-POSEDNESS OF THE MODEL DESCRIBING A REPAIRABLE, STANDBY, HUMAN & MACHINE SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Geni Gupur

    2003-01-01

    By using the strong continuous semigroup theory of linear operators we prove the existence of a unique positive time-dependent solution of the model describing a repairable, standby, human & machine system.

  1. Is hospital based MMR vaccination for children with egg allergy here to stay?

    LENUS (Irish Health Repository)

    Hawkes, C P

    2010-01-01

    Egg allergy is incorrectly considered to constitute a contraindication to MMR in the community, despite a long history of its safe administration to egg allergic children. The product insert perpetuates this misinformation but the Irish guidelines from the RCPI are unequivocal. We reviewed all paediatric cases vaccinated in our hospital in 2007-2008. Forty seven of 91 children receiving vaccinations in hospital, had been referred for MMR due to concerns regarding egg allergy. In 32% (n=15), GP referral for vaccination was made despite correspondence from the clinic advising routine vaccination in the community. Nineteen were second MMR immunisations, which should all have occurred in the community. Unnecessary hospital referral for MMR vaccination is an extra burden on hospital resources, and causes unwarranted anxiety amongst parents of children with egg allergy. A change in practice seems difficult to achieve, as many referrals happen despite individualised correspondence to GPs and other referring clinicians outlining the current guidelines.

  2. MMR (measles, mumps, and rubella) vaccine - what you need to know

    Science.gov (United States)

    ... taken in its entirety from the CDC MMR (Measles, Mumps, & Rubella) Vaccine Information Statement (VIS): www.cdc. ... Why get vaccinated? Measles, mumps, and rubella are serious ... common, especially among children. Measles Measles virus causes ...

  3. A survey of UK parental attitudes to the MMR vaccine and trust in medical authority.

    Science.gov (United States)

    Casiday, Rachel; Cresswell, Tricia; Wilson, Deb; Panter-Brick, Catherine

    2006-01-12

    Contested reports associating the MMR vaccine with autism have resulted in diminished confidence and uptake of the vaccine in the UK. This postal survey of parent's decisions, attitudes and use of information about MMR immunisation was constructed from questions derived from in-depth qualitative work. The setting was a Primary Care Trust in northeast England (N=996). Both MMR-accepting and refusing parents were supportive of immunisation, yet the high level of concern about the safety of the vaccine expressed even by parents who had immunised their children is worrying in its implications for public confidence and trust in health care. The findings suggest that the ability of practitioners to provide effective professional advice about MMR vaccine could be undermined if a government were to directly promote the vaccine to parents. Practitioners should continue to provide parents with accurate information, while communicating respect for parents' intentions to protect their children's health.

  4. [The relationship between MMR vaccination level and the number of new cases of autism in children].

    Science.gov (United States)

    Mrozek-Budzyn, Dorota; Kiełtyka, Agnieszka

    2008-01-01

    The MMR vaccination coverage in Malopolskie voivodeship improved rapidly and finally reached a high level during last years. The number of new cases of autism spectrum disorders in children during that time revealed a slightly rising but not significant trend, while the number of childhood autism were stable. Ecological study showed no correlation between MMR vaccination and an increased risk of childhood autism and autism spectrum disorders in children.

  5. MUTYH and the mismatch repair system: partners in crime?

    NARCIS (Netherlands)

    Niessen, R.C.; Sijmons, R.H.; Ou, J.; Olthof, S.G.; Osinga, J.; Ligtenberg, M.J.L.; Hogervorst, F.B.L.; Weiss, M.M.; Tops, C.M.; Hes, F.J.; Bock, G.H. de; Buys, C.H.C.M.; Kleibeuker, J.H.; Hofstra, R.M.

    2006-01-01

    Biallelic germline mutations of MUTYH-a gene encoding a base excision repair protein-are associated with an increased susceptibility of colorectal cancer. Whether monoallelic MUTYH mutations also increase cancer risk is not yet clear, although there is some evidence suggesting a slight increase of r

  6. MUTYH and the mismatch repair system : partners in crime?

    NARCIS (Netherlands)

    Niessen, RC; Sijmons, RH; Ou, J; Olthof, SGM; Osinga, J; Ligtenberg, MJ; Hogervorst, FBL; Weiss, MM; Tops, CMJ; Hes, FJ; de Bock, GH; Buys, CHCM; Kleibeuker, JH; Hofstra, RMW

    2006-01-01

    Biallelic germline mutations of MUTYH-a gene encoding a base excision repair protein-are associated with an increased susceptibility of colorectal cancer. Whether monoallelic MUTYH mutations also increase cancer risk is not yet clear, although there is some evidence suggesting a slight increase of r

  7. Damage induced by continued corrosion in concrete repair systems

    NARCIS (Netherlands)

    Luckovic, M.; Savija, B.; Schlangen, E.

    2014-01-01

    Corrosion of steel reinforcement is the main cause of deterioration in reinforced concrete structures. After the repair, corrosion of the steel might continue and even accelerate. While the development of the corrosion cell depends on many parameters and is difficult to control, the occurrence of vi

  8. Mesenteric ischemia after abdominal aortic aneurysm repair : a systemic review

    NARCIS (Netherlands)

    Bruggink, J. L. M.; Tielliu, I. F. J.; Zeebregts, C. J.; Pol, R. A.

    2014-01-01

    Mesenteric ischemia after abdominal aneurysm repair is a devastating complication with mortality rates up to 70%. Incidence however is relatively low. The aim of this review was to provide an overview on current insights, diagnostic modalities and on mesenteric ischemia after abdominal aortic aneury

  9. Application of Interfacial Propagation and Kinking Crack Concept to ECC/Concrete Overlay Repair System

    Directory of Open Access Journals (Sweden)

    Yaw ChiaHwan

    2014-01-01

    Full Text Available Research on the application of ultraductile engineered cementitious composite (ECC as overlay in the repair of deteriorated concrete structures is performed in this paper. Also, interfacial crack kinking and trapping mechanism experimentally observed in ECC/concrete overlay repair system are described by comparison of toughness and energy release rate. The mechanism involves cycles of extension, kinking, and arrest of interfacial crack into the overlay. Experimental testing of overlay repair system reveals significant improvements in load carrying capacity and ductility over conventional concrete overlay. The commonly observed overlay system failure mode of delamination or spalling is eliminated when ECC is applied. These failure modes are suppressed when ECC is used as an ideal and durable candidate overlay repair material.

  10. Non-parametric estimation of the availability in a general repairable system

    Energy Technology Data Exchange (ETDEWEB)

    Gamiz, M.L. [Departamento de Estadistica e I.O., Facultad de Ciencias, Universidad de Granada, Granada 18071 (Spain)], E-mail: mgamiz@ugr.es; Roman, Y. [Departamento de Estadistica e I.O., Facultad de Ciencias, Universidad de Granada, Granada 18071 (Spain)

    2008-08-15

    This work deals with repairable systems with unknown failure and repair time distributions. We focus on the estimation of the instantaneous availability, that is, the probability that the system is functioning at a given time, which we consider as the most significant measure for evaluating the effectiveness of a repairable system. The estimation of the availability function is not, in general, an easy task, i.e., analytical techniques are difficult to apply. We propose a smooth estimation of the availability based on kernel estimator of the cumulative distribution functions (CDF) of the failure and repair times, for which the bandwidth parameters are obtained by bootstrap procedures. The consistency properties of the availability estimator are established by using techniques based on the Laplace transform.

  11. Role of the Mmr efflux pump in drug resistance in Mycobacterium tuberculosis.

    Science.gov (United States)

    Rodrigues, Liliana; Villellas, Cristina; Bailo, Rebeca; Viveiros, Miguel; Aínsa, José A

    2013-02-01

    Efflux pumps are membrane proteins capable of actively transporting a broad range of substrates from the cytoplasm to the exterior of the cell. Increased efflux activity in response to drug treatment may be the first step in the development of bacterial drug resistance. Previous studies showed that the efflux pump Mmr was significantly overexpressed in strains exposed to isoniazid. In the work to be described, we constructed mutants lacking or overexpressing Mmr in order to clarify the role of this efflux pump in the development of resistance to isoniazid and other drugs in M. tuberculosis. The mmr knockout mutant showed an increased susceptibility to ethidium bromide, tetraphenylphosphonium, and cetyltrimethylammonium bromide (CTAB). Overexpression of mmr caused a decreased susceptibility to ethidium bromide, acriflavine, and safranin O that was obliterated in the presence of the efflux inhibitors verapamil and carbonyl cyanide m-chlorophenylhydrazone. Isoniazid susceptibility was not affected by the absence or overexpression of mmr. The fluorometric method allowed the detection of a decreased efflux of ethidium bromide in the knockout mutant, whereas the overexpressed strain showed increased efflux of this dye. This increased efflux activity was inhibited in the presence of efflux inhibitors. Under our experimental conditions, we have found that efflux pump Mmr is mainly involved in the susceptibility to quaternary compounds such as ethidium bromide and disinfectants such as CTAB. The contribution of this efflux pump to isoniazid resistance in Mycobacterium tuberculosis still needs to be further elucidated.

  12. In Vitro Comparison of the Bond Strength between Ceramic Repair Systems and Ceramic Materials and Evaluation of the Wettability.

    Science.gov (United States)

    Kocaağaoğlu, Hasan; Manav, Taha; Albayrak, Haydar

    2017-04-01

    When fracture of an all-ceramic restoration occurs, it can be necessary to repair without removing the restoration. Although there are many studies about the repair of metal-ceramic restorations, there are few about all-ceramic restorations. The aim of this study was to evaluate the shear bond strength between ceramic repair systems and esthetic core materials and to evaluate the wettability of all-ceramic core materials. Disk-like specimens (N = 90) made of three dental ceramic infrastructure materials (zirconia ceramic, alumina ceramic, glass ceramic) were polished with silicon carbide paper, prepared for bonding (abrasion with 30 μm diamond rotary cutting instrument). Thirty specimens of each infrastructure were obtained. Each infrastructure group was divided into three subgroups; they were bonded using 3 repair systems: Bisco Intraoral Repair Kit, Cimara & Cimara Zircon Repair System, and Clearfil Repair System. After 1200 thermocycles, shear bond strength was measured in a universal testing machine at a 0.5 mm/min crosshead speed. In addition, the contact angle values of the infrastructures after surface treatments were examined for wettability. Data were analyzed by using ANOVA and Tukey post hoc tests. Although there were no significant differences among the repair systems (p > 0.05) in the glass ceramic and zirconia groups, a significant difference was found among the repair systems in alumina infrastructure (p 0.05); however, a statistically significant difference was found among the repair systems (p < 0.05). No difference was found among the infrastructures and repair systems in terms of contact angle values. Cimara & Cimara Zircon Repair System had higher bond strength values than the other repair systems. Although no difference was found among the infrastructures and repair systems, contact wettability angle was decreased by surface treatments compared with polished surfaces. © 2015 by the American College of Prosthodontists.

  13. Survey of unaffected BRCA and mismatch repair (MMR) mutation positive individuals.

    Science.gov (United States)

    McKinnon, Wendy; Banks, Kimberly C; Skelly, Joan; Kohlmann, Wendy; Bennett, Robin; Shannon, Kristen; Larson-Haidle, Joy; Ashakaga, Taka; Weitzel, Jeffrey N; Wood, Marie

    2009-01-01

    Many individuals do not proceed with cancer predisposition testing due to fears of genetic discrimination (GD). We report the results of a survey of 47 unaffected, mutation positive individuals regarding insurance outcomes. Participants recruited from six different Cancer Risk Programs across the country were queried about their experiences with health, life, and disability insurance, as well as employment issues. Eighty-seven percent of participants carried a BRCA mutation and 87% were part of a group insurance plan at the time of testing. Forty-seven percent of participants self-paid for testing. Less than 10% of participants reported that their results were placed in the general medical record, while 43% did not know where their results were placed. Due to concerns about GD, 13% of participants stated they avoided changing jobs. Thirteen percent stated that their at-risk relatives had not undergone testing for the familial mutation due to fears about GD. Adverse events following genetic testing included two denials from private health insurers, one denial for average life insurance coverage and one denial for additional disability insurance. There were no reports of job discrimination. Results suggest fear of GD is prevalent, yet data do not support evidence that GD exists.

  14. Stochastic behavior of a cold standby system with maximum repair time

    Directory of Open Access Journals (Sweden)

    Ashish Kumar

    2015-09-01

    Full Text Available The main aim of the present paper is to analyze the stochastic behavior of a cold standby system with concept of preventive maintenance, priority and maximum repair time. For this purpose, a stochastic model is developed in which initially one unit is operative and other is kept as cold standby. There is a single server who visits the system immediately as and when required. The server takes the unit under preventive maintenance after a maximum operation time at normal mode if one standby unit is available for operation. If the repair of the failed unit is not possible up to a maximum repair time, failed unit is replaced by new one. The failure time, maximum operation time and maximum repair time distributions of the unit are considered as exponentially distributed while repair and maintenance time distributions are considered as arbitrary. All random variables are statistically independent and repairs are perfect. Various measures of system effectiveness are obtained by using the technique of semi-Markov process and RPT. To highlight the importance of the study numerical results are also obtained for MTSF, availability and profit function.

  15. Mismatch repair balances leading and lagging strand DNA replication fidelity.

    Directory of Open Access Journals (Sweden)

    Scott A Lujan

    Full Text Available The two DNA strands of the nuclear genome are replicated asymmetrically using three DNA polymerases, α, δ, and ε. Current evidence suggests that DNA polymerase ε (Pol ε is the primary leading strand replicase, whereas Pols α and δ primarily perform lagging strand replication. The fact that these polymerases differ in fidelity and error specificity is interesting in light of the fact that the stability of the nuclear genome depends in part on the ability of mismatch repair (MMR to correct different mismatches generated in different contexts during replication. Here we provide the first comparison, to our knowledge, of the efficiency of MMR of leading and lagging strand replication errors. We first use the strand-biased ribonucleotide incorporation propensity of a Pol ε mutator variant to confirm that Pol ε is the primary leading strand replicase in Saccharomyces cerevisiae. We then use polymerase-specific error signatures to show that MMR efficiency in vivo strongly depends on the polymerase, the mismatch composition, and the location of the mismatch. An extreme case of variation by location is a T-T mismatch that is refractory to MMR. This mismatch is flanked by an AT-rich triplet repeat sequence that, when interrupted, restores MMR to > 95% efficiency. Thus this natural DNA sequence suppresses MMR, placing a nearby base pair at high risk of mutation due to leading strand replication infidelity. We find that, overall, MMR most efficiently corrects the most potentially deleterious errors (indels and then the most common substitution mismatches. In combination with earlier studies, the results suggest that significant differences exist in the generation and repair of Pol α, δ, and ε replication errors, but in a generally complementary manner that results in high-fidelity replication of both DNA strands of the yeast nuclear genome.

  16. Development of structural health monitoring systems for composite bonded repairs on aircraft structures

    Science.gov (United States)

    Galea, Stephen C.; Powlesland, Ian G.; Moss, Scott D.; Konak, Michael J.; van der Velden, Stephen P.; Stade, Bryan; Baker, Alan A.

    2001-08-01

    The application of bonded composite patches to repair or reinforce defective metallic structures is becoming recognized as a very effective versatile repair procedure for many types of problems. Immediate applications of bonded patches are in the fields of repair of cracking, localized reinforcement after removal of corrosion damage and for reduction of fatigue strain. However, bonded repairs to critical components are generally limited due to certification concerns. For certification and management of repairs to critical structure, the Smart Patch approach may be an acceptable solution from the airworthiness prospective and be cost effective for the operator and may even allow some relaxation of the certification requirements. In the most basic form of the Smart Patch in-situ sensors can be used as the nerve system to monitor in service the structural condition (health or well-being) of the patch system and the status of the remaining damage in the parent structure. This application would also allow the operator to move away from current costly time-based maintenance procedures toward real-time health condition monitoring of the bonded repair and the repaired structure. TO this end a stand-alone data logger device, for the real-time health monitoring of bonded repaired systems, which is in close proximity to sensors on a repair is being developed. The instrumentation will measure, process and store sensor measurements during flight and then allow this data to be up-loaded, after the flight, onto a PC, via remote (wireless) data access. This paper describes two in-situ health monitoring systems which will be used on a composite bonded patch applied to an F/A-18. The two systems being developed consists of a piezoelectric (PVDF) film-based and a conventional electrical-resistance foil strain gauge-based sensing system. The latter system uses a primary cell (Lithium- based battery) as the power source, which should enable an operating life of 1-2 years. The patch

  17. Diagnostic criteria for constitutional mismatch repair deficiency syndrome

    DEFF Research Database (Denmark)

    Wimmer, Katharina; Kratz, Christian P; Vasen, Hans F A;

    2014-01-01

    Constitutional mismatch repair deficiency (CMMRD) syndrome is a distinct childhood cancer predisposition syndrome that results from biallelic germline mutations in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2. The tumour spectrum is very broad, including mainly haematological, brain...

  18. Molecular Mechanisms of Ultraviolet Radiation-Induced DNA Damage and Repair

    Directory of Open Access Journals (Sweden)

    Rajesh P. Rastogi

    2010-01-01

    Full Text Available DNA is one of the prime molecules, and its stability is of utmost importance for proper functioning and existence of all living systems. Genotoxic chemicals and radiations exert adverse effects on genome stability. Ultraviolet radiation (UVR (mainly UV-B: 280–315 nm is one of the powerful agents that can alter the normal state of life by inducing a variety of mutagenic and cytotoxic DNA lesions such as cyclobutane-pyrimidine dimers (CPDs, 6-4 photoproducts (6-4PPs, and their Dewar valence isomers as well as DNA strand breaks by interfering the genome integrity. To counteract these lesions, organisms have developed a number of highly conserved repair mechanisms such as photoreactivation, base excision repair (BER, nucleotide excision repair (NER, and mismatch repair (MMR. Additionally, double-strand break repair (by homologous recombination and nonhomologous end joining, SOS response, cell-cycle checkpoints, and programmed cell death (apoptosis are also operative in various organisms with the expense of specific gene products. This review deals with UV-induced alterations in DNA and its maintenance by various repair mechanisms.

  19. Lubrication System. Introduction: Things for You to Know. Student Manual. Small Engine Repair Series. First Edition.

    Science.gov (United States)

    Hill, Pamela

    This student manual introducing the lubrication system is the first of three in an instructional package on the lubrication system in the Small Engine Repair Series for handicapped students. The stated purpose of the booklet is to help students learn about the lubrication system and safe and good work habits. Informative material and diagrams are…

  20. Parameter Interval Estimation of System Reliability for Repairable Multistate Series-Parallel System with Fuzzy Data

    Science.gov (United States)

    2014-01-01

    The purpose of this paper is to create an interval estimation of the fuzzy system reliability for the repairable multistate series–parallel system (RMSS). Two-sided fuzzy confidence interval for the fuzzy system reliability is constructed. The performance of fuzzy confidence interval is considered based on the coverage probability and the expected length. In order to obtain the fuzzy system reliability, the fuzzy sets theory is applied to the system reliability problem when dealing with uncertainties in the RMSS. The fuzzy number with a triangular membership function is used for constructing the fuzzy failure rate and the fuzzy repair rate in the fuzzy reliability for the RMSS. The result shows that the good interval estimator for the fuzzy confidence interval is the obtained coverage probabilities the expected confidence coefficient with the narrowest expected length. The model presented herein is an effective estimation method when the sample size is n ≥ 100. In addition, the optimal α-cut for the narrowest lower expected length and the narrowest upper expected length are considered. PMID:24987728

  1. [Effects of the MMR vaccination on the epidemiology of mumps in Germany].

    Science.gov (United States)

    Koch, J; Takla, A

    2013-09-01

    Mumps is an acute viral infectious disease characterized by fever and swelling and tenderness of one or more salivary glands, usually the parotid gland. Since 1976, the German Standing Committee on Vaccination (STIKO) has recommended a mumps vaccination as part of the routine immunization schedule in former West Germany. In East Germany, the vaccination was only introduced in 1991 after reunification. In the preceding decades, no comprehensive surveillance system existed in Germany. However, for East Germany and the successional federal states of former East Germany, data on mumps incidence are available from different Eastern surveillance systems for the time period 1968-2012. According to these data, the incidence of mumps has dropped from > 200 cases/100,000 annually in the pre-vaccine era to currently epidemiology and the increase of outbreaks among adolescents and young adults, the implementation of a nationwide mandatory notification was initiated and came into effect in March 2013. Mandatory notification enables the early detection of outbreaks and obtainment of comprehensive data for evaluation of the immunization program in place. Regarding the long-term prevention of mumps in Germany, it is hoped that--as part of the measles and rubella elimination effort--coverage rates for the second MMR dose among children will increase nationwide above 95% and existing vaccination gaps among adults will be closed.

  2. ALLOCATING REPAIRABLE SYSTEM'S RELIABILITY SUBJECT TO MINIMAL TOTAL COST - AN INTEGER PROGRAMMING APPROACH

    Institute of Scientific and Technical Information of China (English)

    Ahmad A. Moreb

    2007-01-01

    Reliability allocation problem is commonly treated using a closed-form expression relating the cost to reliability. A recent approach has introduced the use of discrete integer technique for un-repairable systems. This research addresses the allocation problem for repairable systems. It presents an integer formulation for finding the optimum selection of components based on the integer values of their Mean Time to Failure (MTTF) and Mean Time to Repair (MTTR). The objective is to minimize the total cost under a system reliability constraint, in addition to other physical constraints. Although, a closed-form expression relating the cost to reliability may not be a linear; however, in this research, the objective function will always be linear regardless of the shape of the equivalent continuous closed-form function. An example is solved using the proposed method and compared with the solution of the continuous closed-form version. The formulation for all possible system configurations, components and subsystems are also considered.

  3. Common variants associated with general and MMR vaccine-related febrile seizures

    Science.gov (United States)

    Feenstra, Bjarke; Pasternak, Björn; Geller, Frank; Carstensen, Lisbeth; Wang, Tongfei; Huang, Fen; Eitson, Jennifer L.; Hollegaard, Mads V.; Svanström, Henrik; Vestergaard, Mogens; Hougaard, David M.; Schoggins, John W.; Jan, Lily Yeh; Melbye, Mads; Hviid, Anders

    2014-01-01

    Febrile seizures represent a recognized serious adverse event following measles, mumps, and rubella (MMR) vaccination. We conducted a series of genome-wide association scans comparing children with MMR-related febrile seizures, children with febrile seizures unrelated to vaccination, and controls with no history of febrile seizures. Two loci were distinctly associated with MMR-related febrile seizures, harboring the interferon-stimulated gene IFI44L (rs273259; P = 5.9×10−12 vs. controls; P =1.2×10−9 vs. MMR-unrelated febrile seizures) and the measles virus receptor CD46 (rs1318653; P = 9.6×10−11 vs. controls; P = 1.6×10−9 vs. MMR-unrelated febrile seizures). Furthermore, four loci were associated with febrile seizures in general implicating the sodium channel genes SCN1A (rs6432860; P = 2.2×10−16) and SCN2A (rs3769955; P = 3.1×10−10), a TMEM16 family gene (TMEM16C; rs114444506; P = 3.7×10−20), and a region associated with magnesium levels (12q21.33; rs11105468; P = 3.4×10−11). Finally, functional relevance of TMEM16C was demonstrated with electrophysiological experiments in wild-type and knockout rats. PMID:25344690

  4. Inducible SOS Response System of DNA Repair and Mutagenesis in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Celina Janion

    2008-01-01

    Full Text Available Chromosomal DNA is exposed to continuous damage and repair. Cells contain a number of proteins and specific DNA repair systems that help maintain its correct structure. The SOS response was the first DNA repair system described in Escherichia coli induced upon treatment of bacteria with DNA damaging agents arrest DNA replication and cell division. Induction of the SOS response involves more than forty independent SOS genes, most of which encode proteins engaged in protection, repair, replication, mutagenesis and metabolism of DNA. Under normal growth conditions the SOS genes are expressed at a basal level, which increases distinctly upon induction of the SOS response. The SOS-response has been found in many bacterial species (e.g., Salmonella typhimurium, Caulobacter crescentus, Mycobacterium tuberculosis, but not in eukaryotic cells. However, species from all kingdoms contain some SOS-like proteins taking part in DNA repair that exhibit amino acid homology and enzymatic activities related to those found in E. coli. but are not organized in an SOS system. This paper presents a brief up-to-date review describing the discovery of the SOS system, the physiology of SOS induction, methods for its determination, and the role of some SOS-induced genes.

  5. Turbomachinery Performance Map Application for Analyzing Cycle Off-Design Behavior of KAIST MMR

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Seong Kuk; Lee, Jekyoung; Kim, Seong Gu; Lee, Jeong Ik [KAIST, Daejeon (Korea, Republic of)

    2015-05-15

    The steam Rankine cycle has been mainly applied in the Power Conversion Unit (PCU) of the existing SMRs. For this reason, modularization and downsizing of the nuclear power plant including PCU is difficult due to complexity and large volume. To solve these problems, KAIST research team proposed a new concept of SMR, called KAIST MMR (Micro Modular Reactor), which utilizes S-CO2 as the working fluid. Due to high density of S-CO2 and the development of heat exchanger technology, such as the printed circuit heat exchanger (PCHE), it can achieve small PCU and modularization of system. This paper describes the method of performance maps to predict the turbomachinery performance for different inlet conditions. One of the most well-known methods is equivalent conditions which include corrected mass flow, corrected total enthalpy rise, and corrected speed. Appropriate performance at any conditions which are different from the design condition can be calculated. As further works, the predicted data from KAIST{sub T}MD will be compared to other experimental data. Also turbine code will be validated.

  6. Parotid swelling due to Hoshino strain following MMR vac-cination in iranian immunization program

    Institute of Scientific and Technical Information of China (English)

    Majid Avijgan; Mandana Moghni; Seyyed Kamyar Mostafavi Zadeh; Masoud Hafizi

    2008-01-01

    This paper reports two seronegative cases of parotid swelling following MMR vaccination,which contains Hoshino strain of mumps virus.This study showed a high,(5%)potential reactogenicity induced by Hoshino strain of current MMR vaccine administered in Iranian EPI.The rate of complication of parotid swelling follow-ing national immunization against mumps is more than natural infection.Based on the results of this report, there is the first report of occurrence of parotid swelling 31 days following MMR vaccination.This reaction or complication may not be dependent on the vaccine dose,because one of cases presented parotid swelling fol-lowing taking one fifth of conventional dose of vaccine.It must be considered this strain may be with high rate of complication and be the subject of change of mumps strain of this vaccine in national immunization program of Iran.

  7. Effect of surface roughness and adhesive system on repair potential of silorane-based resin composite

    Directory of Open Access Journals (Sweden)

    Enas H. Mobarak

    2012-07-01

    Full Text Available This study was performed to evaluate the influence of surface roughness and adhesive system on the repair strength of silorane-based resin composite. Twenty-four substrate discs from silorane-based FiltekP90 were made and stored for 24 h. Half of the discs were roughened against 320 grit SiC paper while the other half was polished against 4000 grit SiC paper. All discs were etched with phosphoric acid. Repair resin composite, FiltekP90 or FiltekZ250, was bonded to the treated surfaces using their corresponding adhesive; P90 System Adhesive (SA or Adper Scotchbond Multipurpose (SBMP ending up with four repair groups. The groups were as follows: G1: Smooth + SA + FiltekP90; G2: Roughened + SA + FiltekP90; G3: Smooth + SBMP + FiltekZ250; G4: Roughened + SBMP + FiltekZ250. Additional six unrepaired discs from each resin composite (G5 and G6 were prepared to test the cohesive strength. After 24 h, discs (n = 6/group were serially sectioned to obtain sticks (n = 30/group for microtensile bond strength (μTBS testing. Scanning electron microscopic (SEM evaluation of substrates that received different treatments as well as representative substrate-repair sticks from each group were performed. Modes of failure were also determined. Two-way ANOVA with Repeated-Measures revealed that surface treatment and repair material had no significant effect on repair bond strength of silorane-based composite material. Paired t-test showed that all repair strength values were significantly lower than the cohesive strength of FiltekP90. Adhesive failure was the predominant mode of failure which was confirmed by SEM. Surface treated FiltekP90 composite showed different textures under SEM whereas phosphoric acid did not produce clear changes. An interaction layer between SBMP adhesive and FiltekZ250 repairing composite was detected. Repair of the silorane composite was successful irrespective of the surface roughness and chemistry of the repair

  8. Influence of very short patch mismatch repair on SOS inducing lesions after aminoglycoside treatment in Escherichia coli.

    Science.gov (United States)

    Baharoglu, Zeynep; Mazel, Didier

    2014-01-01

    Low concentrations of aminoglycosides induce the SOS response in Vibrio cholerae but not in Escherichia coli. In order to determine whether a specific factor present in E. coli prevents this induction, we developed a genetic screen where only SOS inducing mutants are viable. We identified the vsr gene coding for the Vsr protein of the very short patch mismatch repair (VSPR) pathway. The effect of mismatch repair (MMR) mutants was also studied. We propose that lesions formed upon aminoglycoside treatment are preferentially repaired by VSPR without SOS induction in E. coli and by MMR when VSPR is impaired.

  9. RESTART simulation of non-Markov consecutive-k-out-of-n: F repairable systems

    Energy Technology Data Exchange (ETDEWEB)

    Villen-Altamirano, Jose, E-mail: jvillen@eui.upm.e [Departamento de Matematica Aplicada (E.U. Informatica), Universidad Politecnica de Madrid, Calle Arboleda s/n, 28031 Madrid (Spain)

    2010-03-15

    The reliability of consecutive-k-out-of-n: F repairable systems and (k-1)-step Markov dependence is studied. The model analyzed in this paper is more general than those of previous studies given that repair time and component lifetimes are random variables that follow a general distribution. The system has one repair service which adopts a priority repair rule based on system failure risk. Since crude simulation has proved to be inefficient for highly dependable systems, the RESTART method was used for the estimation of steady-state unavailability, MTBF and unreliability. Probabilities up to the order of 10{sup -16} have been accurately estimated with little computational effort. In this method, a number of simulation retrials are performed when the process enters regions of the state space where the chance of occurrence of a rare event (e.g., a system failure) is higher. The main difficulty for the application of this method is to find a suitable function, called the importance function, to define the regions. Given the simplicity involved in changing some model assumptions with RESTART, the importance function used in this paper could be useful for dependability estimation of many systems.

  10. Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animals

    Directory of Open Access Journals (Sweden)

    van Roekel Henk S

    2008-10-01

    Full Text Available Abstract Background The laboratory rat (Rattus norvegicus is one of the preferred model organisms in physiological and pharmacological research, although the availability of specific genetic models, especially gene knockouts, is limited. N-ethyl-N-nitrosourea (ENU-driven target-selected mutagenesis is currently the most successful method in rats, although it is still very laborious and expensive. Results As ENU-induced DNA damage is normally recognized by the mismatch repair (MMR system, we hypothesized that the effectiveness of the target-selected mutagenesis approach could be improved by using a MMR-deficient genetic background. Indeed, Msh6 knockout rats were found to be more sensitive to ENU treatment and the germ line mutation rate was boosted more than two-fold to 1 mutation per 585 kb. In addition, the molecular mutation spectrum was found to be changed in favor of generating knockout-type alleles by ~20%, resulting in an overall increase in efficiency of ~2.5 fold. The improved effectiveness was demonstrated by high throughput mutation discovery in 70 Mb of sequence in a set of only 310 mutant F1 rats. This resulted in the identification of 89 mutations of which four introduced a premature stopcodon and 64 resulted in amino acid changes. Conclusion Taken together, we show that the use of a MMR-deficient background considerably improves ENU-driven target-selected mutagenesis in the rat, thereby reducing animal use as well as screening costs. The use of a mismatch repair-deficient genetic background for improving mutagenesis and target-selected knockout efficiency is in principle applicable to any organism of interest.

  11. Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animals

    Science.gov (United States)

    van Boxtel, Ruben; Toonen, Pim W; Verheul, Mark; van Roekel, Henk S; Nijman, Isaac J; Guryev, Victor; Cuppen, Edwin

    2008-01-01

    Background The laboratory rat (Rattus norvegicus) is one of the preferred model organisms in physiological and pharmacological research, although the availability of specific genetic models, especially gene knockouts, is limited. N-ethyl-N-nitrosourea (ENU)-driven target-selected mutagenesis is currently the most successful method in rats, although it is still very laborious and expensive. Results As ENU-induced DNA damage is normally recognized by the mismatch repair (MMR) system, we hypothesized that the effectiveness of the target-selected mutagenesis approach could be improved by using a MMR-deficient genetic background. Indeed, Msh6 knockout rats were found to be more sensitive to ENU treatment and the germ line mutation rate was boosted more than two-fold to 1 mutation per 585 kb. In addition, the molecular mutation spectrum was found to be changed in favor of generating knockout-type alleles by ~20%, resulting in an overall increase in efficiency of ~2.5 fold. The improved effectiveness was demonstrated by high throughput mutation discovery in 70 Mb of sequence in a set of only 310 mutant F1 rats. This resulted in the identification of 89 mutations of which four introduced a premature stopcodon and 64 resulted in amino acid changes. Conclusion Taken together, we show that the use of a MMR-deficient background considerably improves ENU-driven target-selected mutagenesis in the rat, thereby reducing animal use as well as screening costs. The use of a mismatch repair-deficient genetic background for improving mutagenesis and target-selected knockout efficiency is in principle applicable to any organism of interest. PMID:18840264

  12. Pattern recognition receptors and central nervous system repair.

    Science.gov (United States)

    Kigerl, Kristina A; de Rivero Vaccari, Juan Pablo; Dietrich, W Dalton; Popovich, Phillip G; Keane, Robert W

    2014-08-01

    Pattern recognition receptors (PRRs) are part of the innate immune response and were originally discovered for their role in recognizing pathogens by ligating specific pathogen associated molecular patterns (PAMPs) expressed by microbes. Now the role of PRRs in sterile inflammation is also appreciated, responding to endogenous stimuli referred to as "damage associated molecular patterns" (DAMPs) instead of PAMPs. The main families of PRRs include Toll-like receptors (TLRs), Nod-like receptors (NLRs), RIG-like receptors (RLRs), AIM2-like receptors (ALRs), and C-type lectin receptors. Broad expression of these PRRs in the CNS and the release of DAMPs in and around sites of injury suggest an important role for these receptor families in mediating post-injury inflammation. Considerable data now show that PRRs are among the first responders to CNS injury and activation of these receptors on microglia, neurons, and astrocytes triggers an innate immune response in the brain and spinal cord. Here we discuss how the various PRR families are activated and can influence injury and repair processes following CNS injury.

  13. Effect of Moisture Exchange on Interface Formation in the Repair System Studied by X-ray Absorption

    Directory of Open Access Journals (Sweden)

    Mladena Lukovic

    2015-12-01

    Full Text Available In concrete repair systems, material properties of the repair material and the interface are greatly influenced by the moisture exchange between the repair material and the substrate. If the substrate is dry, it can absorb water from the repair material and reduce its effective water-to-cement ratio (w/c. This further affects the hydration rate of cement based material. In addition to the change in hydration rate, void content at the interface between the two materials is also affected. In this research, the influence of moisture exchange on the void content in the repair system as a function of initial saturation level of the substrate is investigated. Repair systems with varying level of substrate saturation are made. Moisture exchange in these repair systems as a function of time is monitored by the X-ray absorption technique. After a specified curing age (3 d, the internal microstructure of the repair systems was captured by micro-computed X-ray tomography (CT-scanning. From reconstructed images, different phases in the repair system (repair material, substrate, voids can be distinguished. In order to quantify the void content, voids were thresholded and their percentage was calculated. It was found that significantly more voids form when the substrate is dry prior to application of the repair material. Air, initially filling voids and pores of the dry substrate, is being released due to the moisture exchange. As a result, air voids remain entrapped in the repair material close to the interface. These voids are found to form as a continuation of pre-existing surface voids in the substrate. Knowledge about moisture exchange and its effects provides engineers with the basis for recommendations about substrate preconditioning in practice.

  14. Determining the functional significance of mismatch repair gene missense variants using biochemical and cellular assays

    DEFF Research Database (Denmark)

    Heinen, Christopher D; Juel Rasmussen, Lene

    2012-01-01

    provided an important experimental tool for studying the functional consequences of VUS. However, beyond this repair assay, a number of other experimental methods have been developed that allow us to test the effect of a VUS on discrete biochemical steps or other aspects of MMR function. Here, we describe......ABSTRACT: With the discovery that the hereditary cancer susceptibility disease Lynch syndrome (LS) is caused by deleterious germline mutations in the DNA mismatch repair (MMR) genes nearly 20 years ago, genetic testing can now be used to diagnose this disorder in patients. A definitive diagnosis...

  15. Systemic Inflammatory Response and Severe Thrombocytopenia after Endovascular Thoracic Aortic Aneurysm Repair

    Directory of Open Access Journals (Sweden)

    Valentina Silvestrin

    2017-01-01

    Full Text Available After Endovascular repair of thoracic aortic aneurysm, a systemic inflammatory response, named postimplantation syndrome, can develop. This syndrome is characterized by fever, leukocytosis, and elevated CRP plasma levels and its pathogenetic mechanisms are still unknown. Although this syndrome generally resolves within few days, some patients develop a persisting severe inflammatory reaction leading to mild or severe complications. Here we describe the case of a male patient who developed postimplantation inflammatory syndrome and severe thrombocytopenia after endovascular repair of thoracic aortic aneurysm. Treatment with prednisone (50 mg/bid for two weeks did not improve the clinical and laboratory findings. We utilized danazol, a weak androgen that has been shown to be effective in the treatment of immune and idiopathic thrombocytopenic purpura, and after 12 days of treatment with danazol (200 mg/bid, the patient improved progressively and platelet number increased up to 53,000/μL. Patients undergoing endovascular repair of thoracic aortic aneurysm should be carefully monitored for the development of postimplantation syndrome. This clinical condition is relatively common after the endovascular repair of aortic aneurysm but is rarely observed after endovascular repair of thoracic aortic aneurysms. The different known therapeutical approaches are still empiric, with reported beneficial effects with the use of NSAID, corticosteroids, and danazol.

  16. Systemic Inflammatory Response and Severe Thrombocytopenia after Endovascular Thoracic Aortic Aneurysm Repair

    Science.gov (United States)

    Silvestrin, Valentina; Bonvini, Stefano; Antonello, Michele; Grego, Franco; Vettor, Roberto

    2017-01-01

    After Endovascular repair of thoracic aortic aneurysm, a systemic inflammatory response, named postimplantation syndrome, can develop. This syndrome is characterized by fever, leukocytosis, and elevated CRP plasma levels and its pathogenetic mechanisms are still unknown. Although this syndrome generally resolves within few days, some patients develop a persisting severe inflammatory reaction leading to mild or severe complications. Here we describe the case of a male patient who developed postimplantation inflammatory syndrome and severe thrombocytopenia after endovascular repair of thoracic aortic aneurysm. Treatment with prednisone (50 mg/bid) for two weeks did not improve the clinical and laboratory findings. We utilized danazol, a weak androgen that has been shown to be effective in the treatment of immune and idiopathic thrombocytopenic purpura, and after 12 days of treatment with danazol (200 mg/bid), the patient improved progressively and platelet number increased up to 53,000/μL. Patients undergoing endovascular repair of thoracic aortic aneurysm should be carefully monitored for the development of postimplantation syndrome. This clinical condition is relatively common after the endovascular repair of aortic aneurysm but is rarely observed after endovascular repair of thoracic aortic aneurysms. The different known therapeutical approaches are still empiric, with reported beneficial effects with the use of NSAID, corticosteroids, and danazol. PMID:28154580

  17. Prediction of Repair Work Duration for Gas Transport Systems Based on Small Data Samples

    DEFF Research Database (Denmark)

    Lesnykh, Valery; Litvin, Yuri; Kozin, Igor

    2016-01-01

    Prediction of the duration of a repair and maintenance project of a gas transport system is an important part of planning activities. There exist numerous sources of uncertainties that may result in time overruns possibly leading to multiple negative consequences. Our experience in planning...... this work suggests that accepting the stochastic nature of the project duration is a constructive step towards the preparedness to contingencies and defining penalties for repair companies. To support this approach, one needs to construct probability distributions of the durations of the projects...

  18. Things for You to Know. Fuel System. Student Manual--Introduction. Small Engine Repair Series. First Edition.

    Science.gov (United States)

    Hill, Pamela

    This student manual, part of a small-engine repair series on servicing fuel systems, is designed for use by special needs students in Texas. Information covered in this manual is considered to be the minimum that students need to know about fuel systems in order to get small-engine repair jobs. The manual introduces students to small-engine fuel…

  19. Lubrication System 2. Service the Crankcase Breather. Student Manual. Small Engine Repair Series. First Edition.

    Science.gov (United States)

    Hill, Pamela

    This student manual on servicing the crankcase breather is the third of three in an instructional package on the lubrication system in the Small Engine Repair Series for handicapped students. The stated purpose for the booklet is to help students learn what tools and equipment to use and all the steps of the job. Informative material and…

  20. Superficial fascial system repair: an abdominoplasty technique to reduce local complications after caesarean delivery.

    Science.gov (United States)

    Al-Benna, Sammy; Al-Ajam, Yazan; Tzakas, Elias

    2009-05-01

    Abdominal incision complications are a major source of morbidity after caesarean delivery. Repair of the superficial fascial system may avert local complications after caesarean delivery by minimising tension to the skin and increasing the initial biomechanical strength of wound which has the potential to decrease early wound dehiscence and as a by-product correct suprapubic bulging.

  1. Optimal Repair And Replacement Policy For A System With Multiple Components

    Science.gov (United States)

    2016-06-17

    probabilistic life-cycle maintenance mod- els for deteriorating civil infrastructure. Probabilistic Enginering Mechanics 19 345– 359. Zhang, Y.L. 2002. A...Repair, Replace, Multiple Component Models, Maintenance Models, Markov Decision Process 15. NUMBER OF PAGES 83 16. PRICE CODE 17. SECURITY...Parametric Analysis of the Fuel System . . . . . . . . . . . . . . 39 6 Conclusions and Future Work 45 6.1 Conclusions

  2. Semiconservative replication, genetic repair, and many-gened genomes: Extending the quasispecies paradigm to living systems

    Science.gov (United States)

    Tannenbaum, Emmanuel; Shakhnovich, Eugene I.

    2005-12-01

    Quasispecies theory has emerged as an important tool for modeling the evolutionary dynamics of biological systems. We review recent advances in the field, with an emphasis on the quasispecies dynamics of semiconservatively replicating genomes. Applications to cancer and adult stem cell growth are discussed. Additional topics, such as genetic repair and many-gene genomes, are covered as well.

  3. Bond strength durability of direct and indirect composite systems following surface conditioning for repair

    NARCIS (Netherlands)

    Passos, Sheila Pestana; Ozcan, Mutlu; Vanderlei, Aleska Dias; Leite, Fabiola Pessoa Pereira; Kimpara, Estevao Tomomitsu; Bottino, Marco Antonio

    2007-01-01

    Purpose: This study evaluated the effect of surface conditioning methods and thermocycling on the bond strength between a resin composite and an indirect composite system in order to test the repair bond strength. Materials and Methods: Eighteen blocks (5 x 5 x 4 mm) of indirect resin composite (Sin

  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 buff

  5. Simultaneous vaccination with MMR and DTaP-IPV-Hib and rate of hospital admissions with any infections

    DEFF Research Database (Denmark)

    Sørup, Signe; Benn, Christine S; Poulsen, Anja

    2016-01-01

    and inactivated vaccines may increase child mortality compared with the live vaccine alone. We examined the hypothesis that simultaneous administration of MMR and the inactivated DTaP-IPV-Hib vaccine compared with MMR alone is associated with higher incidence of infectious disease admissions. METHODS: Nationwide......BACKGROUND: In Denmark, live measles, mumps, and rubella vaccine (MMR) is associated with a reduced risk of infectious disease admissions, particularly for lower respiratory tract infections. In low-income countries, simultaneous vaccination (i.e. vaccination at the same visit) with live......, 4965 children had simultaneous MMR and DTaP-IPV-Hib as their most recent vaccination. Compared with MMR alone, simultaneous administration was associated with a higher rate of lower respiratory tract infections (adjusted incidence rate ratio (IRR), 1.27; 95% confidence interval (CI), 1...

  6. DNA repair. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    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. (HLW)

  7. Defective dental restorations: to repair or not to repair? Part 2: All-ceramics and porcelain fused to metal systems.

    Science.gov (United States)

    Blum, Igor R; Jagger, Daryll C; Wilson, Nairn H F

    2011-04-01

    With the increasing use of ceramics in restorative dentistry, and trends to extend restoration longevity through the use of minimal interventive techniques, dental practitioners should be familiar with the factors that may influence the decision either to repair or replace fractured metal-ceramic and all-ceramic restorations and, also, the materials and techniques available to repair these restorations. This second of two papers addresses the possible modes of failure of ceramic restorations and outlines indications and techniques in this developing aspect of restoration repair in clinical practice. The repair of metal-ceramic and all-ceramic restorations is a reliable low-cost, low-risk technique that may be of value for the management of loss or fracture of porcelain from a crown or bridge in clinical practice.

  8. DNA repair: Dynamic defenders against cancer and aging

    Energy Technology Data Exchange (ETDEWEB)

    Fuss, Jill O.; Cooper, Priscilla K.

    2006-04-01

    You probably weren't thinking about your body's cellular DNA repair systems the last time you sat on the beach in the bright sunshine. Fortunately, however, while you were subjecting your DNA to the harmful effects of ultraviolet light, your cells were busy repairing the damage. The idea that our genetic material could be damaged by the sun was not appreciated in the early days of molecular biology. When Watson and Crick discovered the structure of DNA in 1953 [1], it was assumed that DNA is fundamentally stable since it carries the blueprint of life. However, over 50 years of research have revealed that our DNA is under constant assault by sunlight, oxygen, radiation, various chemicals, and even our own cellular processes. Cleverly, evolution has provided our cells with a diverse set of tools to repair the damage that Mother Nature causes. DNA repair processes restore the normal nucleotide sequence and DNA structure of the genome after damage [2]. These responses are highly varied and exquisitely regulated. DNA repair mechanisms are traditionally characterized by the type of damage repaired. A large variety of chemical modifications can alter normal DNA bases and either lead to mutations or block transcription if not repaired, and three distinct pathways exist to remove base damage. Base excision repair (BER) corrects DNA base alterations that do not distort the overall structure of the DNA helix such as bases damaged by oxidation resulting from normal cellular metabolism. While BER removes single damaged bases, nucleotide excision repair (NER) removes short segments of nucleotides (called oligonucleotides) containing damaged bases. NER responds to any alteration that distorts the DNA helix and is the mechanism responsible for repairing bulky base damage caused by carcinogenic chemicals such as benzo [a]pyrene (found in cigarette smoke and automobile exhaust) as well as covalent linkages between adjacent pyrimidine bases resulting from the ultraviolet

  9. 3-Unit System Comprising Two Types of Units with First Come First Served Repair Pattern Except When Both Types of Units are Waiting for Repair

    Directory of Open Access Journals (Sweden)

    Amit Goyal

    2010-01-01

    Full Text Available Problem statement: In this study we investigated the probabilistic analysis of a three unit system working in a sugar Mill, wherein one unit is big and the other two units are small and identical, is examined. Upon failure of the big unit, both small units are made operative and failed unit is undertaken for repair immediately. Priority for operation is given to the big unit. Priority for repair is given to big unit if both types (i.e., big and small of units are in queue to get the repair done. System is able to work with full capacity only if big unit or both small units are in good condition. If only one small unit is operable, the system works at reduced capacity. The system under consideration goes to rest during the non-seasonal period. Approach: System was analyzed by making use of semi-Markov processes and regenerative point technique and various measures of the system effectiveness are obtained including the profit incurred to the system. Results: Graphs had been plotted to depict the behavior of the profit with respect to failure rate for different values of repair rate and with respect to revenue per unit up time for which system is working at full capacity for different values of cost for PM/CM. Conclusion: The profit increases with the decrease in the values of the failure rate and with the increase in the values of revenue per unit up time. It has lower (higher values on increasing the values of cost (repair rate. Cut-off points obtained for failure rate help decide about having the system with failure rate lesser than that the value at cut-off point. Also, the price of the product should be fixed in such a way so as to get the revenue greater than the value at cut-off point.

  10. ROLE OF MISMATCH REPAIR PROTEINS IN THE PROCESSING OF CISPLATIN INTERSTRAND CROSS-LINKS

    Science.gov (United States)

    Sawant, Akshada; Kothandapani, Anbarasi; Zhitkovich, Anatoly; Sobol, Robert W.; Patrick, Steve M.

    2015-01-01

    Mismatch repair (MMR) deficiency gives rise to cisplatin resistance and can lead to poor prognosis in cancers. Various models have been proposed to explain this low level of resistance caused due to loss of MMR proteins. We have shown that MMR proteins are required to maintain cisplatin interstrand cross-links (ICLs) on the DNA leading to increased cellular sensitivity. In our previous studies, we have shown that BER processing of the cisplatin ICLs is mutagenic. Polymerase β (Polβ) can generate mismatches which leads to the activation and the recruitment of mismatch repair proteins. In this paper, we distinguished between the requirement of different downstream MMR proteins for maintaining cisplatin sensitivity. We show that the MutSα (MSH2-MSH6) heterocomplex is required to maintain cisplatin sensitivity, whereas the Mutsβ complex has no effect. These results can be correlated with the increased repair of cisplatin ICLs and ICL induced DNA double strand breaks (DSBs) in the resistant cells. Moreover, we show that MLH1 proficient cells displayed a cisplatin sensitive phenotype when compared with the MLH1 deficient cells and the ATPase activity of MLH1 is essential to mediate this effect. Based on these results, we propose that MutSα as well as the downstream MMR pathway proteins are essential to maintain a cisplatin sensitive phenotype as a consequence of processing Polβ induced mismatches at sites flanking cisplatin ICLs. PMID:26519826

  11. Parents' champions vs. vested interests: Who do parents believe about MMR? A qualitative study

    Directory of Open Access Journals (Sweden)

    Petticrew Mark

    2007-03-01

    Full Text Available Abstract Background Despite the Government acting quickly to reassure parents about MMR safety following the publication of the 1998 paper by Wakefield and colleagues, MMR uptake declined. One of the reasons suggested for this decline is a loss of public trust in politicians and health professionals. The purpose of this analysis was to examine parents' views on the role the media, politicians and health professionals have played in providing credible evidence about MMR safety. Methods A qualitative focus group study conducted with parents living in Central Scotland. Eighteen focus groups were conducted with 72 parents (64 mothers and 8 fathers between November 2002 and March 2003. Purposive sampling was used to ensure maximum variation among parents. Results In the period after the MMR controversy, parents found it difficult to know who to trust to offer balanced and accurate information. The general consensus was that politicians were untrustworthy in matters of health. The motives of primary health care providers were suspected by some parents, who saw them as having a range of vested interests (including financial incentives. Among the sources of evidence seen by some parents as more credible were other parents, and Andrew Wakefield who was viewed as an important whistle-blower and champion of ordinary parents. Conclusion The provision of accurate information is only one aspect of helping parents make immunisation decisions. Establishing and maintaining trust in the information provided is also important. The MMR controversy may provide useful lessons for health professionals about trust and credibility that may be generalisable to future health controversies.

  12. Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children.

    Science.gov (United States)

    Strömbeck, Anna; Lundell, Anna-Carin; Nordström, Inger; Andersson, Kerstin; Adlerberth, Ingegerd; Wold, Agnes E; Rudin, Anna

    2016-04-01

    There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles-mumps-rubella (MMR) immunization relate to magnitudes of vaccine-specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-induced antibody titers were measured in plasma samples obtained at 36 months of age. Infants' blood samples obtained at birth, 3-5 days and at 4 and 18 months of age were analyzed for T- and B-cell numbers, proportions of naive and memory T and B cells, and fractions of putative regulatory T cells. Multivariate factor analyses show that higher anti-MMR antibody titers were associated with a lower degree of adaptive immune maturation, that is, lower proportions of memory T cells and a lower capacity of mononuclear cells to produce cytokines, but with higher proportions of putative regulatory T cells. Further, children born by cesarean section (CS) had significantly higher anti-measles titers than vaginally-born children; and CS was found to be associated with delayed adaptive immunity. Also, girls presented with significantly higher anti-mumps and anti-rubella antibody levels than boys at 36 months of age. These results indicate that delayed adaptive immune maturation before and in close proximity to immunization seems to be advantageous for the ability of children to respond with higher anti-MMR antibody levels after vaccination.

  13. 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…

  14. High prevalence of deficient mismatch repair phenotype and the V600E BRAF mutation in elderly patients with colorectal cancer.

    Science.gov (United States)

    Aparicio, Thomas; Schischmanoff, Olivier; Poupardin, Cecile; Mary, Florence; Soufir, Nadem; Barrat, Christophe; Bellaiche, Guy; Boubaya, Marouane; Choudat, Laurence; Cucherousset, Joel; DesGuetz, Gaetan; Wind, Philippe; Benamouzig, Robert

    2014-10-01

    Colorectal cancer (CRC) occurs mostly in the elderly. However, the biology of CRC in elderly has been poorly studied. This study examined the prevalence of deficient mismatch repair phenotype (dMMR) and BRAF mutations according to age. MMR phenotype was prospectively determined by molecular analysis in patients of all ages undergoing surgery for CRC. BRAF V600E mutation status was analysed in a subset of dMMR tumours. A total of 754 patients who underwent surgery between 2005 and 2008 were included in the study. Amongst them, 272 (36%) were ≥75years old. The proportion of women prevalence of dMMR was 19.4% in patients ≥75 and 10.7% in patients prevalence of dMMR was significantly higher in women than in men (27% vs 10.2%, respectively; p=0.003) but was similar in women and men prevalence of the BRAF V600E mutation according to sex (78% in women and 70% in men, p=0.9). The prevalence of dMMR in CRC is high in patients over 75. In elderly patients, dMMR tumours are significantly more frequent in women than in men. The BRAF mutation is frequent in elderly patients with CRC. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Quantifying the contributions of base selectivity, proofreading and mismatch repair to nuclear DNA replication in Saccharomyces cerevisiae.

    Science.gov (United States)

    St Charles, Jordan A; Liberti, Sascha E; Williams, Jessica S; Lujan, Scott A; Kunkel, Thomas A

    2015-07-01

    Mismatches generated during eukaryotic nuclear DNA replication are removed by two evolutionarily conserved error correction mechanisms acting in series, proofreading and mismatch repair (MMR). Defects in both processes are associated with increased susceptibility to cancer. To better understand these processes, we have quantified base selectivity, proofreading and MMR during nuclear DNA replication in Saccharomyces cerevisiae. In the absence of proofreading and MMR, the primary leading and lagging strand replicases, polymerase ɛ and polymerase δ respectively, synthesize DNA in vivo with somewhat different error rates and specificity, and with apparent base selectivity that is more than 100 times higher than measured in vitro. Moreover, leading and lagging strand replication fidelity rely on a different balance between proofreading and MMR. On average, proofreading contributes more to replication fidelity than does MMR, but their relative contributions vary from nearly all proofreading of some mismatches to mostly MMR of other mismatches. Thus accurate replication of the two DNA strands results from a non-uniform and variable balance between error prevention, proofreading and MMR.

  16. Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia: potential contribution to AML progression

    Institute of Scientific and Technical Information of China (English)

    Guogen Mao; Fenghua Yuan; Kimberly Absher; C Darrell Jennings; Dianna S Howard; Craig T Jordan; Liya Gu

    2008-01-01

    Acute myeloid leukemia (AML) is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AML development and relapse remain incompletely defined. To explore whether loss of DNA mismatch repair (MMR) function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls. We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter. In vitro functional MMR analysis revealed that almost all the mutations analyzed resulted in loss of MMR function. MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients. These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease pathogenesis.

  17. [The correlations between aging of the human body, oxidative stress and reduced efficiency of repair systems].

    Science.gov (United States)

    Michalak, Aleksandra; Krzeszowiak, Jakub; Markiewicz-Górka, Iwona

    2014-12-15

    The article presents an current knowledge overview about the importance of oxidative stress and reduced efficiency of repair processes during the aging process of the human body. Oxidative damage to cellular macromolecules (proteins, lipids, nucleic acids), are formed under the influence of reactive oxygen species (ROS). They are the part of important mechanism which is responsible for the process of aging and the development of many diseases. The most important effects result from DNA damage, due to the mutations formation, which can lead to the development of tumors. However, a well-functioning repair systems (i.a. homologous recombination) remove the damage and prevent harmful changes in the cells. Lipid peroxidation products also cause oxidative modification of nucleic acids (and proteins). Proteins and fats also have repair systems, but much simpler than those responsible for the repair of nucleic acids. Unfortunately, with increasing age, they are more weakened, which contributes to increase numbers of cell damage, and consequently development of diseases specific to old age: cancer, neurodegenerative diseases or atherosclerosis.

  18. A decision dependent stochastic process model for repairable systems with applications

    Directory of Open Access Journals (Sweden)

    Paul F. Zantek

    2015-12-01

    This paper mathematically formalizes the notion of how management actions impact the functioning of a repairable system over time by developing a new stochastic process model for such systems. The proposed model is illustrated using both simulated and real data. The proposed model compares favorably to other models for well-known data on Boeing airplanes. The model is further illustrated and compared to other models on failure time and maintenance data stemming from the South Texas Project nuclear power plant.

  19. Repair, Evaluation, Maintenance, and Rehabilitation Research Program: Elements of Floating-Debris Control Systems

    Science.gov (United States)

    1988-09-01

    a variety of materials from plastic bottles to sage brush, but it is t’quialy wood in soiw shape or form--from whole trees to lawn furniture. The...REPAIR, EVALUATION, MAINTENANCE, AND REHABILITATION’RESEARCH PROGRAM TECHNICAL REPORT REMVR-HY-3 ELEMENTS O F FLOATING- DEBRIS CONTROL SYSTEMS’ by...TITLE (Include Security Classification) Elements of Floating- Debris Control Systems 12. PERSONAL AUTHOR(S) Perham, Roscoe E. 13a. TYPE OF REPORT 13b TIME

  20. Inspection-Repair based Availability Optimization of Distribution Systems using Teaching Learning based Optimization

    Science.gov (United States)

    Tiwary, Aditya; Arya, L. D.; Arya, Rajesh; Choube, S. C.

    2016-09-01

    This paper describes a technique for optimizing inspection and repair based availability of distribution systems. Optimum duration between two inspections has been obtained for each feeder section with respect to cost function and subject to satisfaction of availability at each load point. Teaching learning based optimization has been used for availability optimization. The developed algorithm has been implemented on radial and meshed distribution systems. The result obtained has been compared with those obtained with differential evolution.

  1. Multisensor robotic system for autonomous space maintenance and repair

    Science.gov (United States)

    Abidi, M. A.; Green, W. L.; Chandra, T.; Spears, J.

    1988-01-01

    The feasibility of realistic autonomous space manipulation tasks using multisensory information is demonstrated. The system is capable of acquiring, integrating, and interpreting multisensory data to locate, mate, and demate a Fluid Interchange System (FIS) and a Module Interchange System (MIS). In both cases, autonomous location of a guiding light target, mating, and demating of the system are performed. Implemented visio-driven techniques are used to determine the arbitrary two-dimensional position and orientation of the mating elements as well as the arbitrary three-dimensional position and orientation of the light targets. A force/torque sensor continuously monitors the six components of force and torque exerted on the end-effector. Both FIS and MIS experiments were successfully accomplished on mock-ups built for this purpose. The method is immune to variations in the ambient light, in particular because of the 90-minute day-night shift in space.

  2. Service the Two-Piece Flo-Jet Carburetor. Fuel System. Student Manual 3. Small Engine Repair Series. First Edition.

    Science.gov (United States)

    Hill, Pamela

    This student manual, part of a small-engine repair series on servicing fuel systems, is designed for use by special needs students in Texas. The manual explains in pictures and short sentences, written on a low reading level, the job of servicing two-piece flo-jet carburetors. Along with the steps of this repair job, specific safety and caution…

  3. Homomorphic Self-repairing Codes for Agile Maintenance of Distributed Storage Systems

    CERN Document Server

    Oggier, Frederique

    2011-01-01

    Distributed data storage systems are essential to deal with the need to store massive volumes of data. In order to make such a system fault-tolerant, some form of redundancy becomes crucial, incurring various overheads - most prominently in terms of storage space and maintenance bandwidth requirements. Erasure codes, originally designed for communication over lossy channels, provide a storage efficient alternative to replication based redundancy, however entailing high communication overhead for maintenance, when some of the encoded fragments need to be replenished in news ones after failure of some storage devices. We propose as an alternative a new family of erasure codes called self-repairing codes (SRC) taking into account the peculiarities of distributed storage systems, specifically the maintenance process. SRC has the following salient features: (a) encoded fragments can be repaired directly from other subsets of encoded fragments by downloading less data than the size of the complete object, ensuring ...

  4. Corrosion inhibitors and other protective systems in concrete repair concepts or misconcepts

    Institute of Scientific and Technical Information of China (English)

    XuKe

    2009-01-01

    The paper concludes that as long as one continues to blindly use protection methods applicable for newly constructed structures for concrete repairs,the business of "repairing the repairs"will be on the rise.A broader understanding of the electrochemical differences between new and repaired concrete is necessary for effective protection of reinforcement in repaired structures.

  5. The Refrigeration System; Appliance Repair--Advanced: 9027.01.

    Science.gov (United States)

    Dade County Public Schools, Miami, FL.

    This course outline provides students with an understanding of the observation of basic refrigeration system components, the techniques used in working with copper tubing, and practice demonstrations to show what they have learned. Course content includes specific block objectives, orientation, refrigeration components (evaporator, compressor,…

  6. Rotator cuff repair in the Brazilian Unified Health System: Brazilian trends from 2003 to 2015.

    Science.gov (United States)

    Malavolta, Eduardo Angeli; Assunção, Jorge Henrique; Beraldo, Rodrigo Alves; Pinto, Gustavo de Mello Ribeiro; Gracitelli, Mauro Emilio Conforto; Ferreira Neto, Arnaldo Amado

    2017-01-01

    To assess the historical trend of rotator cuff repairs in Brazil between 2003 and 2015, using the database of the Brazilian Unified Health System's (Sistema Único de Saúde [SUS]) Department of Informatics (DataSUS). Historical series using DataSUS. Surgeries performed between 2003 and 2015 were included and data relating to cuff tear repair were assessed, including decompression procedures were included. The numerator was the total number of rotator cuff repair and the denominator, the total population of the assessed locality. Population data were based on information from the Instituto Brasileiro de Geografia e Estatística (IBGE). During the period, 50,207 surgeries were performed. The rate was presented as number of procedures per 100,000 inhabitants, and increased from 0.83 to 2.81, a growth of 238%. In 2015, the South region had the highest rate, 6.32, followed by the Southeast, 3.62, while the North had the lowest rate, 0.13. The growing trend can be observed in the Southeast, South, and Midwest, while the rate is stable in the North and Northeast. The rate of rotator cuff repairs in Brazil performed through the SUS increased from 0.83 to 2.81 between 2003 and 2015, representing a growth of 238%, but remains lower than that of developed countries. A trend of growth can be observed in the Southeast, South, and Midwest, while the rate is stable in the North and Northeast.

  7. Similar immunogenicity of measles-mumps-rubella (MMR) vaccine administrated at 8 months versus 12 months age in children.

    Science.gov (United States)

    He, Hanqing; Chen, Enfu; Chen, Haiping; Wang, Zhifang; Li, Qian; Yan, Rui; Guo, Jing; Zhou, Yang; Pan, Jinren; Xie, Shuyun

    2014-06-30

    Two doses of measles-mumps-rubella (MMR) strategy has been recommended by World Health Organization and is also widely adopted in many countries. In order to provide the evidence for perfecting the immunization strategy of MMR, this study evaluated the safety and immunogenicity of MMR with different two-dose schedule in infants. 280 participants were enrolled and randomly allocated to Group 1 (first dose at 8 months) or Group 2 (first dose at 12 months), and both groups administered the second dose at 10 months later. Solicited local and general symptoms after each vaccination with MMR were mild and infrequent in all participants of two groups. After administration of the first dose of MMR, seropositive rates were 100% in both groups for measles, 89.3% in Group 1 and 87.1% in Group 2 for mumps (P=0.578), 92.0% in Group 1 and 92.9% in Group 2 (P=0.393). The seropositive rates of mumps decreased significantly (from >86% to measles and rubella. All children get the positive titer for three vaccines in two groups after given the second dose MMR, higher seroconversion rate was found for mumps both in two groups (71.7% vs 77.2%, P=0.370). In conclusion, this study indicated that the MMR was well tolerated and immunogenic against measles, mumps and rubella with schedule of first dose both at 8 months and 12 months age. Our findings strongly supported that two doses of MMR can be introduced by replacing the first dose of MR in current EPI with MMR at 8 months age and the second dose at 18 months in China.

  8. Low velocity impact response and damage evolution in unreinforced resin systems and self-repairing polymer matrix composites

    Science.gov (United States)

    Motuku, Molefi

    The low velocity impact response and damage evolution in unreinforced polymer matrices, conventional polymer matrix composites, and self-repairing polymer matrix composites was investigated. The impact response study of unreinforced matrices and conventional laminates was undertaken because the failure initiation energies, threshold energy levels, failure characteristics and damage evolution in both the matrix material (unreinforced resin plaques) and the composite are intrinsic to proper design of a self-repairing composite. The self-repairing concept was investigated due to its attractive potential to alleviate damage problems in polymer matrix composites. Self-repairing composites, which fall under the category of passive smart polymer composites, have the potential to self repair both micro- and macro-damage resulting from impacts as well as non-impact loading. The self-repairing mechanism is achieved through the incorporation of hollow fibers in addition to the normal solid reinforcing fibers. The hollow fibers store the damage-repairing solution or chemicals that are released into the matrix or damaged zone upon fiber failure to repair and/or arrest damage progression. The room temperature low velocity impact response and damage evolution in DERAKANE 411-350 and 411-C50 vinyl ester unreinforced resin systems was investigated as a function of impact energy level, sample thickness, matrix material and catalyst system. The low velocity impact response of conventional and self-repairing glass reinforced polymer composites was investigated by addressing the fabrication and some of the parameters that influence their response to low velocity impact loading. Specific issues addressed by this study include developing a process to fabricate self-repairing laminates, processing quality; selection of storage material for the repairing solution; release and transportation of repairing solution; the effect of the number, type and spatial distribution of the repairing

  9. Uncertain multiobjective redundancy allocation problem of repairable systems based on artificial bee colony algorithm

    Institute of Scientific and Technical Information of China (English)

    Guo Jiansheng; Wang Zutong; Zheng Mingfa; Wang Ying

    2014-01-01

    Based on the uncertainty theory, this paper is devoted to the redundancy allocation problem in repairable parallel-series systems with uncertain factors, where the failure rate, repair rate and other relative coefficients involved are considered as uncertain variables. The availability of the system and the corresponding designing cost are considered as two optimization objectives. A crisp multiobjective optimization formulation is presented on the basis of uncertainty theory to solve this resultant problem. For solving this problem efficiently, a new multiobjective artificial bee colony algorithm is proposed to search the Pareto efficient set, which introduces rank value and crowding distance in the greedy selection strategy, applies fast non-dominated sort procedure in the exploitation search and inserts tournament selection in the onlooker bee phase. It shows that the proposed algorithm outperforms NSGA-II greatly and can solve multiobjective redundancy allocation problem efficiently. Finally, a numerical example is provided to illustrate this approach.

  10. Recommendations for optimised repair welding operations in steam systems exposed to creep; Rekommendationer foer optimering av svetsreparationer i kryppaakaenda aangsystem

    Energy Technology Data Exchange (ETDEWEB)

    Storesund, Jan; Samuelson, Aake; Klasen, Bjoern; Jensen, Carsten

    2002-03-01

    Recommendations for optimised repair welding in creep exposed steam systems have been produced on basis of different parts of the project which involve a literature survey, case studies, metallographical investigations and finite element simulations. The separate parts are compiled in the present report where the results also are coupled to each other. Two of the project parts are reported in appendices in the present report and the other ones in three separate work reports. The studies have shown evidence of the complexity associated with repair welding and many alternatives may be offered for a given situation. The importance of the factors which may influence the life time of the repair have been investigated and are described in order to facilitate the decision-making process for the given situation. From the obtained results there are also more general recommendations to be given: Make sure that system stresses not are acting at the repair. Avoid welding methods that could result in strongly creep soft HAZs. Select a weld metal for the repair which is slightly creep hard compared to the remaining aged material. Selection of a wide and 'medium' deep excavation geometry as well as a repair around the whole circumference is to be preferred. Repairs of welds that not include excavation of the whole width of the original weld should be avoided. Replica testing is recommended in addition to the common practice in the quality and condition-monitoring control of the repair.

  11. Genome Wide In silico Analysis of the Mismatch Repair Components of Plasmodium falciparum and Their Comparison with Human Host

    Science.gov (United States)

    Tarique, Mohammed; Ahmad, Moaz; Chauhan, Manish; Tuteja, Renu

    2017-01-01

    Malaria a major parasitic infection globally particularly in tropical and sub-tropical regions of the world is responsible for about 198 million cases and estimated deaths due to this disease are about 0.6 million. The emergence of drug resistance in the malaria parasite is alarming and it is necessary to understand its underlying cause and molecular mechanisms. It has been established that drug resistant malaria parasites have defective mismatch repair (MMR) therefore it is essential to study this pathway and its components in detail. Recently a number of non-synonymous Single Nucleotide Polymorphisms have been reported in genes involved in MMR pathways. PfMLH is an endonuclease essential to restore the MMR in drug resistant strains of Plasmodium falciparum. Considering all these facts about the role of MMR in emergence of drug resistant parasite, in this manuscript we report a genome wide analysis of the components of the MMR pathway such as MLH, Pms1, MSH2-1, MSH2-2, MSH6, and UvrD using in silico bioinformatics based approaches. The phylogenetic analysis revealed evolutionary closeness with the MMR components of various organisms. It is noteworthy that P. falciparum contains two homologs of MSH2, which are located on different chromosomes. The structural modeling of these components showed their similarity with the human/yeast MMR components. The docking studies reveal that PfUvrD and PfMLH interact with each other. The in silico identification of interacting partners of the major MMR components identified numerous P. falciparum specific proteins. In line with our previous studies the present study will also contribute significantly to understand the MMR pathway of malaria parasite. PMID:28232818

  12. Simple facet joint repair with dynamic pedicular system: Technical note and case series

    OpenAIRE

    Ali Fahir Ozer; Tuncer Suzer; Mehdi Sasani; Tunc Oktenoglu; Phillip Cezayirli; Hosein Jafari Marandi; Deniz Ufuk Erbulut

    2015-01-01

    Simple facet joint repair with dynamic pedicular system: Technical note and case series Ali Ozer, Tuncer Suzer, Mehdi Sasani, Tunc Oktenoglu, Phillip Cezayirli and Hosein Marandi Journal of Craniovertebral Junction and Spine. 6.2 (April-June 2015): p65. Copyright: COPYRIGHT 2015 Medknow Publications and Media Pvt. Ltd. http://www.jcvjs.com/ Full Text: Byline: Ali. Ozer, Tuncer. Suzer, Mehdi. Sasani, Tunc. Oktenoglu, Phillip. Cezayirli, Hosein. Marandi, Deniz. Erbulut Purpose: Facet joints are...

  13. Lack of DNA mismatch repair protein MSH6 in the rat results in hereditary non-polyposis colorectal cancer-like tumorigenesis.

    NARCIS (Netherlands)

    van Boxtel, R.; Toonen, P.W.; van Roekel, H.S.; Verheul, M.; Smits, B.M.; Korving, J.; de Bruin, A.; Cuppen, E.

    2008-01-01

    To understand genetic instability in relation to tumorigenesis, experimental animal models have proven very useful. The DNA mismatch repair (MMR) machinery safeguards genomic integrity by repairing mismatches, insertion or deletion loops and responding to genotoxic agents. Here, we describe the func

  14. Association of obesity with DNA mismatch repair status and clinical outcome in patients with stage II or III colon carcinoma participating in NCCTG and NSABP adjuvant chemotherapy trials.

    Science.gov (United States)

    Sinicrope, Frank A; Foster, Nathan R; Yoon, Harry H; Smyrk, Thomas C; Kim, George P; Allegra, Carmen J; Yothers, Greg; Nikcevich, Daniel A; Sargent, Daniel J

    2012-02-01

    Although the importance of obesity in colon cancer risk and outcome is recognized, the association of body mass index (BMI) with DNA mismatch repair (MMR) status is unknown. BMI (kg/m(2)) was determined in patients with TNM stage II or III colon carcinomas (n = 2,693) who participated in randomized trials of adjuvant chemotherapy. The association of BMI with MMR status and survival was analyzed by logistic regression and Cox models, respectively. Overall, 427 (16%) tumors showed deficient MMR (dMMR), and 630 patients (23%) were obese (BMI ≥ 30 kg/m(2)). Obesity was significantly associated with younger age (P = .021), distal tumor site (P = .012), and a lower rate of dMMR tumors (10% v 17%; P Obesity remained associated with lower rates of dMMR (odds ratio, 0.57; 95% CI, 0.41 to 0.79; P obese patients, rates of dMMR were lower in men compared with women (8% v 13%; P = .041). Obesity was associated with higher recurrence rates (P = .0034) and independently predicted worse disease-free survival (DFS; hazard ratio [HR], 1.37; 95% CI, 1.14 to 1.64; P = .0010) and overall survival (OS), whereas dMMR predicted better DFS (HR, 0.59; 95% CI, 0.47 to 0.74; P obese patients. Colon cancers from obese patients are less likely to show dMMR, suggesting obesity-related differences in the pathogenesis of colon cancer. Although obesity was independently associated with adverse outcome, the favorable prognostic impact of dMMR was maintained among obese patients.

  15. An application of modulated poisson processes to the reliability analysis of repairable systems

    Energy Technology Data Exchange (ETDEWEB)

    Saldanha, Pedro L.C. [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil). Coordenacao de Reatores]. E-mail: saldanha@cnen.gov.br; Melo, P.F. Frutuoso e [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia. Programa de Engenharia Nuclear]. E-mail: frutuoso@con.ufrj.br; Noriega, Hector C. [Universidad Austral de Chile (UACh), Valdivia (Chile). Faculdad de Ciencias de la Ingeniaria]. E-mail: hnoriega@uach.cl

    2005-07-01

    This paper discusses the application of the modulated power law process (MPLP) model to the rate of occurrence of failures of active repairable systems in reliability engineering. Traditionally, two ways of modeling repairable systems, in what concerns maintenance policies, are: a pessimistic approach (non-homogeneous process - NHPP), and a very optimistic approach (renewal processes - RP). It is important to build a generalized model that might consider characteristics and properties both of the NHPP and of the RP models as particular cases. In practice, by considering the pattern of times between failures, the MPLP appears to be more realistic to represent the occurrence of failures of repairable systems in order to define whether they can be modeled by a homogeneous or a non-homogeneous process. The study has shown that the model can be used to make decisions concerning the evaluation of the qualified life of plant equipment. By controlling and monitoring two of the three parameters of the MPLP model during the equipment operation, it is possible to check whether and how the equipment is following the basis of its qualification process, and so identify how the effects of time, degradation and operation modes are influencing the equipment performance. The discussion is illustrated by an application to the service water pumps of a typical PWR plant. (author)

  16. The blame frame: media attribution of culpability about the MMR-autism vaccination scare.

    Science.gov (United States)

    Holton, Avery; Weberling, Brooke; Clarke, Christopher E; Smith, Michael J

    2012-01-01

    Scholars have examined how news media frame events, including responsibility for causing and fixing problems, and how these frames inform public judgment. This study analyzed 281 newspaper articles about a controversial medical study linking the measles, mumps, and rubella (MMR) vaccination with autism. Given criticism of the study and its potential negative impact on vaccination rates across multiple countries, the current study examined actors to whom news media attributed blame for the MMR-vaccine association, sources used to support those attributions, and what solutions (e.g., mobilizing information), if any, were offered. This study provides unique insight by examining the evolution of these attributions over the lifetime of the controversy. Findings emphasize how news media may attribute blame in health risk communication and how that ascription plays a potentially vital role in shaping public behavior. Theoretical and practical implications are discussed.

  17. Expression of hMSH2 protein of the human DNA mismatch repair system in oral lichen planus

    Directory of Open Access Journals (Sweden)

    2004-08-01

    Full Text Available Lichen planus is a mucocutaneous disease of inflammatory nature and unknown etiology. It is characterized by a cell-mediated immunological response to induced antigenic change in skin and/or mucosa. The possible malignant transformation of lichen planus remains a subject of controversial discussions in the literature. hMSH2 is one of the human DNA mismatch repair (hMMR genes and it plays an important role in reducing mutation and maintaining genomic stability. hMSH2 alterations have been reported in oral squamous cell carcinoma and there are evidences suggesting the association between oral lichen planus and squamous cell carcinoma. In this study, we aim to investigate the immunolocalization of hMSH2 protein in oral lichen planus compared to oral normal mucosa epithelium. We examined the expression of hMSH2 protein by immunohistochemistry in twenty-six cases of oral lichen planus. Clinically, 12 of them were categorized into reticular subtype and 14 were atrophic/erosive. Ten cases of normal mucosa were added to the control group. Results showed that the percentage of positive cells to hMSH2 was smaller in reticular (46.54%; p=0,006 and atrophic/erosive (48.79%; p=0,028 subtypes of oral lichen planus compared to normal mucosa (61.29%. The reduced expression of hMSH2 protein in oral lichen planus suggests that this lesion is more susceptible to mutation and therefore facilitate the development of oral squamous cell carcinoma.

  18. What are parents' perspectives on psychological empowerment in the MMR vaccination decision? A focus group study

    OpenAIRE

    Fadda, Marta; Galimberti, Elisa; Carraro, Valter; Peter J Schulz

    2016-01-01

    Objectives Most developed countries do not have compulsory immunisation requirements, but instead issue recommendations. Although parents are expected to make an informed, autonomous (ie, empowered) decision regarding their children's vaccinations, there is no evidence about how parents' interpret this demand nor on the latitude of their decision-making. The goal of this study is to gain insights from parents residing in a low measles-mumps-rubella (MMR) uptake area on what constitutes feelin...

  19. Measles, the media, and MMR: Impact of the 2014-15 measles outbreak.

    Science.gov (United States)

    Cataldi, Jessica R; Dempsey, Amanda F; O'Leary, Sean T

    2016-12-07

    In late 2014, a measles outbreak beginning in California received significant media attention. To better understand the impact of this outbreak, we conducted a survey to assess and compare among vaccine hesitant and non-hesitant new mothers how this outbreak affected vaccine knowledge, attitudes, vaccination plans, and media use. A cross-sectional email survey of English-speaking women with a child ⩽1year old using a convenience sample of women from nine obstetrics and gynecology (OB/GYN) practices in Colorado assessed vaccine hesitancy, knowledge and attitudes about MMR vaccines and the outbreak, MMR vaccination plans before and after the outbreak, and use of and trust for media sources related to the outbreak. The response rate was 50% (351/701). Knowledge about the outbreak was high and vaccination attitudes were mostly favorable. Forty-eight percent of respondents thought MMR vaccine was more important after the outbreak. Online news (76%), television news (75%), and social media (68%) were the most frequently used media sources, yet were highly trusted by only 18%, 22%, and 1% of respondents respectively. Government websites (34%) and information from a doctor's office (34%) were infrequently used, but were highly trusted by 62% and 60% of respondents. Knowledge of the outbreak was lower among vaccine-hesitant respondents. Few mothers changed MMR vaccination plans after the outbreak. New mothers had high levels of knowledge and favorable attitudes about vaccination after the 2014-15 measles outbreak. Media sources used the most are not the most trusted. Communication about outbreaks of vaccine-preventable diseases should include spread of accurate information to new media sources and strengthening of existing trust in traditional media. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Operator Semi-group of Density Evolution Equation for a Repairable Redundnt System with Two Same Components

    Institute of Scientific and Technical Information of China (English)

    史定华; 徐洪; 等

    2002-01-01

    For a repairable redundant system consisting of two same components with exponential lifetime and general repair time distribution,the probability densities of the system in some state at time t were determined by a group of ordinary and partial differential equations,called density evolution equations.It was proved that the time-dependent solution of the density evolution equations uniquely exists and strongly converges to its steady state density solution by a semi-group method.In this proof,it is not necessary to suppose that the repair rate function is bounded.The technique of the proof is valuable for many density evolution equatons.

  1. A New Approach for Analyzing the Reliability of the Repair Facility in a Series System with Vacations

    Directory of Open Access Journals (Sweden)

    Renbin Liu

    2012-01-01

    Full Text Available Based on the renewal process theory we develop a decomposition method to analyze the reliability of the repair facility in an n-unit series system with vacations. Using this approach, we study the unavailability and the mean replacement number during (0,t] of the repair facility. The method proposed in this work is novel and concise, which can make us see clearly the structures of the facility indices of a series system with an unreliable repair facility, two convolution relations. Special cases and numerical examples are given to show the validity of our method.

  2. Association between perfluoroalkyl substance exposure and asthma and allergic disease in children as modified by MMR vaccination

    DEFF Research Database (Denmark)

    Timmermann, Clara Amalie Gade; Budtz-Jørgensen, Esben; Jensen, Tina Kold

    2017-01-01

    , and rubella (MMR) vaccination in early life may have a protective effect against asthma and allergy, and MMR vaccination is therefore taken into account when evaluating these associations. In a cohort of Faroese children whose mothers were recruited during pregnancy, serum concentrations of five PFASs...... – Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) – were measured at three timepoints (maternal serum in pregnancy week 34–36 and child serum at ages 5 and 13 years) and their association...... with immunoglobulin E (IgE) (cord blood and at age 7 years) and asthma/allergic diseases (questionnaires at ages 5 and 13 years and skin prick test at age 13 years) was determined. A total of 559 children were included in the analyses. Interactions with MMR vaccination were evaluated. Among 22 MMR...

  3. Association between perfluoroalkyl substance exposure and asthma and allergic disease in children as modified by MMR vaccination

    DEFF Research Database (Denmark)

    Timmermann, Clara Amalie Gade; Budtz-Jørgensen, Esben; Jensen, Tina Kold

    2017-01-01

    , and rubella (MMR) vaccination in early life may have a protective effect against asthma and allergy, and MMR vaccination is therefore taken into account when evaluating these associations. In a cohort of Faroese children whose mothers were recruited during pregnancy, serum concentrations of five PFASs...... - Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) - were measured at three timepoints (maternal serum in pregnancy week 34-36 and child serum at ages 5 and 13 years) and their association...... with immunoglobulin E (IgE) (cord blood and at age 7 years) and asthma/allergic diseases (questionnaires at ages 5 and 13 years and skin prick test at age 13 years) was determined. A total of 559 children were included in the analyses. Interactions with MMR vaccination were evaluated. Among 22 MMR...

  4. [Lack of association between MMR vaccination and the incidence of autism in children: a case-control study].

    Science.gov (United States)

    Mrozek-Budzyn, Dorota; Kiełtyka, Agnieszka; Majewska, Renata

    2009-01-01

    The matched case-control study has been undertook to investigate whether measles, mumps, and rubella (MMR) vaccine may be casually associated with autism in children. Cases were children to 14-year old with diagnosis of core autism or atypical autism. Controls were matched on age, sex and general practice. The 96 cases and 192 controls were included. The study provides strong evidence against association of autism with both MMR and a single measles individual vaccine. Additionally children vaccinated with MMR, regardless of age of vaccination (to 18th, 24th and 36th month of life), had risk equal half of that of single measles vaccinated (for vaccinated to 18th month OR=0.41 95%PU: 0.20-0.85). Our findings confirm that MMR vaccination is not associated with an increased risk of autism in children.

  5. THE WORK SIMULATION OF FLOW RATE FOR CARRIAGES' REPAIR AS A MULTIPHASE, MULTIPLEX AND MULTIDISCIPLINARY SYSTEM OF MASS SERVICE

    Directory of Open Access Journals (Sweden)

    V. V. Myamlin

    2011-04-01

    Full Text Available The algorithm of computer simulation of the flexible flow for repair of cars as a multiphase polychannel manyobject queuing system is presented. The basic operators of the model are given and their work is described.

  6. A Database to Support the Interpretation of Human Mismatch Repair Gene Variants

    NARCIS (Netherlands)

    Ou, Jianghua; Niessen, Renee C.; Vonk, Jan; Westers, Helga; Hofstra, Robert M. W.; Sijmons, Rolf H.

    2008-01-01

    Germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2 can cause Lynch syndrome. This syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominantly-inherited disorder predominantly characterized by colorectal and endometrial cancer. Tr

  7. Incisional, epigastric and umbilical hernia repair using the Prolene Hernia System: describing a novel technique.

    Science.gov (United States)

    Khera, Goldie; Berstock, David A

    2006-08-01

    The Prolene Hernia System (PHS) is already widely in use in the United Kingdom for inguinal hernias. We describe the novel technique of using the three-in-one design of the PHS (Ethicon Endo-Surgery, Bracknell, UK) for repairing incisional, epigastric and umbilical herniae. This is a three-dimensional device and consists of an onlay patch, a tubular connector and an underlay patch. We recommend a four 'corner' suturing of the underlay patch under vision (and then) through the full thickness of abdominal wall layers to ensure a flat underlay mesh. These four sutures flatten out the underlay patch and can be tied or removed with equal effect. The sutures are placed at 3, 6, 9 and 12 o'clock, which simplifies the procedure and ensures that the underlay lays correctly and is corrugation-free and tension-free, thereby providing a two-layer repair for those herniae with a high rate of recurrence.

  8. Prediction of Repair Work Duration for Gas Transport Systems Based on Small Data Samples

    DEFF Research Database (Denmark)

    Lesnykh, Valery; Litvin, Yuri; Kozin, Igor

    2016-01-01

    Prediction of the duration of a repair and maintenance project of a gas transport system is an important part of planning activities. There exist numerous sources of uncertainties that may result in time overruns possibly leading to multiple negative consequences. Our experience in planning...... this work suggests that accepting the stochastic nature of the project duration is a constructive step towards the preparedness to contingencies and defining penalties for repair companies. To support this approach, one needs to construct probability distributions of the durations of the projects...... of concurrently running subprojects. Following this, guidance is provided on how to decide about what duration should define the deadline for completion of the whole work. A simple example is provided....

  9. Intralesional tuberculin (PPD) versus measles, mumps, rubella (MMR) vaccine in treatment of multiple warts: a comparative clinical and immunological study.

    Science.gov (United States)

    Shaheen, Maha Adel; Salem, Samar Abdallah M; Fouad, Dina Adel; El-Fatah, Abeer Aly Abd

    2015-01-01

    Intralesional purified protein derivative (PPD) or mumps, measles, rubella (MMR) were not previously compared regarding their efficacy or mechanism of action in treatment of warts. We aimed to compare their efficacy in treatment of multiple warts and investigate their effect on serum interleukin (IL)-4 and IL-12. Thirty patients with multiple warts were included (10 treated with PPD, 10 with MMR, and 10 with normal saline (control)). Injection was done every 3 weeks until clearance or maximum of three treatments. Clinical response of target and distant warts was evaluated. Serum ILs-4 and -12 were assessed before and after treatment. A significantly higher rate of complete response was found in target and distant warts with PPD (60% each) and MMR (80%, 40%, respectively) compared with controls (0%), with no significant difference between both treatments. After treatment, the control group showed the lowest serum IL-12 and IL-4 levels compared with the MMR- and PPD-treated groups with statistically significant difference in between. MMR resulted in a significantly higher serum IL-12 than PPD. With PPD, IL-4 was increased with statistically significant change compared with pretreat-ment level. Intralesional PPD and MMR show comparable efficacy and safety in treatment of multiple warts. Serum ILs-4 and-12 increase following antigen injection. © 2015 Wiley Periodicals, Inc.

  10. Development of novel visual-plus quantitative analysis systems for studying DNA double-strand break repairs in zebrafish.

    Science.gov (United States)

    Liu, Jingang; Gong, Lu; Chang, Changqing; Liu, Cong; Peng, Jinrong; Chen, Jun

    2012-09-20

    The use of reporter systems to analyze DNA double-strand break (DSB) repairs, based on the enhanced green fluorescent protein (EGFP) and meganuclease such as I-Sce I, is usually carried out with cell lines. In this study, we developed three visual-plus quantitative assay systems for homologous recombination (HR), non-homologous end joining (NHEJ) and single-strand annealing (SSA) DSB repair pathways at the organismal level in zebrafish embryos. To initiate DNA DSB repair, we used two I-Sce I recognition sites in opposite orientation rather than the usual single site. The NHEJ, HR and SSA repair pathways were separately triggered by the injection of three corresponding I-Sce I-cut constructions, and the repair of DNA lesion caused by I-Sce I could be tracked by EGFP expression in the embryos. Apart from monitoring the intensity of green fluorescence, the repair frequencies could also be precisely measured by quantitative real-time polymerase chain reaction (qPCR). Analysis of DNA sequences at the DSB sites showed that NHEJ was predominant among these three repair pathways in zebrafish embryos. Furthermore, while HR and SSA reporter systems could be effectively decreased by the knockdown of rad51 and rad52, respectively, NHEJ could only be impaired by the knockdown of ligaseIV (lig4) when the NHEJ construct was cut by I-Sce I in vivo. More interestingly, blocking NHEJ with lig4-MO increased the frequency of HR, but decreased the frequency of SSA. Our studies demonstrate that the major mechanisms used to repair DNA DSBs are conserved from zebrafish to mammal, and zebrafish provides an excellent model for studying and manipulating DNA DSB repair at the organismal level.

  11. Development of Novel Visual-Plus Quantitative Analysis Systems for Studying DNA Double-Strand Break Repairs in Zebrafish

    Institute of Scientific and Technical Information of China (English)

    Jingang Liu; Lu Gong; Changqing Chang; Cong Liu; Jinrong Peng; Jun Chen

    2012-01-01

    The use of reporter systems to analyze DNA double-strand break (DSB) repairs,based on the enhanced green fluorescent protein (EGFP) and meganuclease such as I-Sce Ⅰ,is usually carried out with cell lines.In this study,we developed three visual-plus quantitative assay systems for homologous recombination (HR),non-homologous end joining (NHEJ) and single-strand annealing (SSA) DSB repair pathways at the organismal level in zebrafish embryos.To initiate DNA DSB repair,we used two I-Sce Ⅰ recognition sites in opposite orientation rather than the usual single site.The NHEJ,HR and SSA repair pathways were separately triggered by the injection of three corresponding I-Sce I-cut constructions,and the repair of DNA lesion caused by I-Sce Ⅰ could be tracked by EGFP expression in the embryos.Apart from monitoring the intensity of green fluorescence,the repair frequencies could also be precisely measured by quantitative real-time polymerase chain reaction (qPCR).Analysis of DNA sequences at the DSB sites showed that NHEJ was predominant among these three repair pathways in zebrafish embryos.Furthermore,while HR and SSA reporter systems could be effectively decreased by the knockdown of rad51 and rad52,respectively,NHEJ could only be impaired by the knockdown of ligaseⅣ (lig4) when the NHEJ construct was cut by I-Sce Ⅰ in vivo.More interestingly,blocking NHEJ with lig4-MO increased the frequency of HR,but decreased the frequency of SSA.Our studies demonstrate that the major mechanisms used to repair DNA DSBs are conserved from zebrafish to mammal,and zebrafish provides an excellent model for studying and manipulating DNA DSB repair at the organismal level.

  12. Oxidative DNA damage background estimated by a system model of base excision repair.

    Science.gov (United States)

    Sokhansanj, Bahrad A; Wilson, David M

    2004-08-01

    Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level, based on measuring 8-oxoguanine lesions as a biomarker, have led to estimates that vary over three to four orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parameters from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our findings show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.

  13. Targeting 14-3-3 adaptor protein-protein interactions to stimulate central nervous system repair

    Directory of Open Access Journals (Sweden)

    Andrew Kaplan

    2017-01-01

    Full Text Available The goal of developing treatments for central nervous system (CNS injuries is becoming more attainable with the recent identification of various drugs that can repair damaged axons. These discoveries have stemmed from screening efforts, large expression datasets and an improved understanding of the cellular and molecular biology underlying axon growth. It will be important to continue searching for new compounds that can induce axon repair. Here we describe how a family of adaptor proteins called 14-3-3s can be targeted using small molecule drugs to enhance axon outgrowth and regeneration. 14-3-3s bind to many functionally diverse client proteins to regulate their functions. We highlight the recent discovery of the axon-growth promoting activity of fusicoccin-A, a fungus-derived small molecule that stabilizes 14-3-3 interactions with their client proteins. Here we discuss how fusicoccin-A could serve as a starting point for the development of drugs to induce CNS repair.

  14. A Novel Repair Technique for the Internal Thermal Control System Dual-Membrane Gas Trap

    Science.gov (United States)

    Leimkuehler, Thomas O.; Patel, Vipul; Reeves, Daniel R.; Holt, James M.

    2005-01-01

    A dual-membrane gas trap is currently used to remove gas bubbles from the Internal Thermal Control System (ITCS) coolant on board the International Space Station (ISS). The gas trap consists of concentric tube membrane pairs, comprised of outer hydrophilic tubes and inner hydrophobic fibers. Liquid coolant passes through the outer hydrophilic membrane, which traps the gas bubbles. The inner hydrophobic fiber allows the trapped gas bubbles to pass through and vent to the ambient atmosphere in the cabin. The gas trap was designed to last for the entire lifetime of the ISS, and therefore was not designed to be repaired. However, repair of these gas traps is now a necessity due to contamination from the on-orbit ITCS fluid and other sources on the ground as well as a limited supply of flight gas traps. This paper describes a novel repair technique that has been developed that will allow the refurbishment of contaminated gas traps and their return to flight use.

  15. Oxidative DNA damage background estimated by a system model of base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Sokhansanj, B A; Wilson, III, D M

    2004-05-13

    Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level based on measuring 8-oxoguanine lesions as a biomarker have led to estimates varying over 3-4 orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parameters from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our results show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.

  16. Association between expression of DNA mismatch repair genes and clinical features and prognosis of patients with radical resection of colon cancer.

    Science.gov (United States)

    Wang, J B; Ma, D L; Li, J Y; Sun, Q D; Liu, Y E

    2016-08-19

    The aim of this study was to investigate the clinical significance of the expression of DNA mismatch repair (MMR) genes in patients subjected to radical surgical removal of colon cancer, as well as their correlation with disease prognosis. Ninety stage II and III colon cancer patients who received laparoscopic radical resection of colon cancer at our hospital were recruited in this study. The expression of hMLH1, hMSH2, hMSH6, and hPMS2 in the resected tumor tissues was examined by SP immunohistochemistry, in order to analyze the relationship between defective DNA MMR (dMMR) and the clinico-pathological features and prognosis of colon cancer. Patients were followed up over a period of 5-35 months, and the Kaplan-Meier survival curve was plotted. dMMR was confirmed in 27 subjects (30.0%), among whom recurrence with metastasis and death was reported in 5 (18.5%) and 2 (7.4%) patients, respectively. The remaining 63 subjects displayed proficient DNA MMR (pMMR); among these, 19 (30.2%) and 7 (11.1%) recurrences with metastasis and death were reported, respectively. dMMR showed no significant correlation with gender, age, or therapeutic modality (P > 0.05), but was significantly correlated with the degree of differentiation, tumor location, number of resected lymph nodes, presence of ileus, and TNM stage (P colon cancers.

  17. ANALYSIS OF A TWO UNIT STANDBY SYSTEM WITH CORRELATED FAILURE AND REPAIR AND RANDOM APPEARANCE AND DISAPPEARANCE OF REPAIRMAN

    Directory of Open Access Journals (Sweden)

    Rakesh Gupta

    2010-01-01

    Full Text Available The paper deals with the stochastic analysis of a two non-identical unit standbysystem model. The one unit is considered as priority (p unit and the other as ordinary (o unit.The p-unit gets priority in operation. A single repair facility appears in and disappears from thesystem randomly with constant rates. The repair discipline of units is FCFS. The joint distributionof failure and repair times for each unit is taken to be bivariate exponential. Using regenerativepoint technique various measures of system effectiveness useful to industrial managers areobtained.

  18. The neonate versus adult mammalian immune system in cardiac repair and regeneration.

    Science.gov (United States)

    Sattler, Susanne; Rosenthal, Nadia

    2016-07-01

    The immune system is a crucial player in tissue homeostasis and wound healing. A sophisticated cascade of events triggered upon injury ensures protection from infection and initiates and orchestrates healing. While the neonatal mammal can readily regenerate damaged tissues, adult regenerative capacity is limited to specific tissue types, and in organs such as the heart, adult wound healing results in fibrotic repair and loss of function. Growing evidence suggests that the immune system greatly influences the balance between regeneration and fibrotic repair. The neonate mammalian immune system has impaired pro-inflammatory function, is prone to T-helper type 2 responses and has an immature adaptive immune system skewed towards regulatory T cells. While these characteristics make infants susceptible to infection and prone to allergies, it may also provide an immunological environment permissive of regeneration. In this review we will give a comprehensive overview of the immune cells involved in healing and regeneration of the heart and explore differences between the adult and neonate immune system that may explain differences in regenerative ability. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  19. Efficacy of a novel IGS system in atrial septal defect repair

    Science.gov (United States)

    Mefleh, Fuad N.; Baker, G. Hamilton; Kwartowitz, David M.

    2013-03-01

    Congenital heart disease occurs in 107.6 out of 10,000 live births, with Atrial Septal Defects (ASD) accounting for 10% of these conditions. Historically, ASDs were treated with open heart surgery using cardiopulmonary bypass, allowing a patch to be sewn over the defect. In 1976, King et al. demonstrated use of a transcatheter occlusion procedure, thus reducing the invasiveness of ASD repair. Localization during these catheter based procedures traditionally has relied on bi-plane fluoroscopy; more recently trans-esophageal echocardiography (TEE) and intra-cardiac echocardiography (ICE) have been used to navigate these procedures. Although there is a high success rate using the transcatheter occlusion procedure, fluoroscopy poses radiation dose risk to both patient and clinician. The impact of this dose to the patients is important as many of those undergoing this procedure are children, who have an increased risk associated with radiation exposure. Their longer life expectancy than adults provides a larger window of opportunity for expressing the damaging effects of ionizing radiation. In addition, epidemiologic studies of exposed populations have demonstrated that children are considerably more sensitive to the carcinogenic effects radiation. Image-guided surgery (IGS) uses pre-operative and intra-operative images to guide surgery or an interventional procedure. Central to every IGS system is a software application capable of processing and displaying patient images, registration between multiple coordinate systems, and interfacing with a tool tracking system. We have developed a novel image-guided surgery framework called Kit for Navigation by Image Focused Exploration (KNIFE). In this work we assess the efficacy of this image-guided navigation system for ASD repair using a series of mock clinical experiments designed to simulate ASD repair device deployment.

  20. Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway.

    Directory of Open Access Journals (Sweden)

    Catherine E Smith

    2013-10-01

    Full Text Available Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.

  1. A Web-Based Rapid Prototyping Workflow Management Information System for Computer Repair and Maintenance

    Directory of Open Access Journals (Sweden)

    A. H. El-Mousa

    2008-01-01

    Full Text Available Problem statement: Response to paper-based requests for computer and peripheral repair and maintenance has become very troublesome and slow due to the large demand and expansion at the University of Jordan. The objectives of this study were to: (i investigate the current system processes associated with the paper-based workflow system. (ii design and implement, using a suitable workflow management approach, a totally electronic alterative to improve performance. Approach: The methodology followed in the transform of the business processes from the paper to the electronic-based was using the rapid prototyping workflow management approach. This approach is seen to be especially effective in such cases where there is direct continuous interaction and involvement between the different stakeholders during the lifecycle of the project. Results: The system had been implemented and tested with the result that efficiency, accountability and response time have greatly improved in handling repair and maintenance orders. The transform from paper to electronic resulted in greatly enhanced user satisfaction especially since the developed system provided automatic feedback regarding order status. Conclusion: The design process and results provide a working blueprint for easy and quick various similar university-based business processes to be transformed to electronic. This should highly motivate internal in-house restructuring of business process to utilize technology and IT to enhance performance and accountability.

  2. Reliability modelling of repairable systems using Petri nets and fuzzy Lambda-Tau methodology

    Energy Technology Data Exchange (ETDEWEB)

    Knezevic, J.; Odoom, E.R

    2001-07-01

    A methodology is developed which uses Petri nets instead of the fault tree methodology and solves for reliability indices utilising fuzzy Lambda-Tau method. Fuzzy set theory is used for representing the failure rate and repair time instead of the classical (crisp) set theory because fuzzy numbers allow expert opinions, linguistic variables, operating conditions, uncertainty and imprecision in reliability information to be incorporated into the system model. Petri nets are used because unlike the fault tree methodology, the use of Petri nets allows efficient simultaneous generation of minimal cut and path sets.

  3. A cell-free system for studying a priming factor involved in repair of bleomycin-damaged DNA.

    Directory of Open Access Journals (Sweden)

    Seki,Shuji

    1989-04-01

    Full Text Available A simple cell-free system for studying a priming factor involved in the repair of bleomycin-damaged DNA was established. The template-primer used for the repair DNA synthesis was prepared by treating the closed circular, superhelical form of pUC19 plasmid DNA with 2.2 microM bleomycin and 20 microM ferrous ions. Single-strand breaks were introduced into pUC19 DNA by the bleomycin treatment, and the DNA was consequently converted largely into the open circular form. A system for repair of this bleomycin-damaged DNA was constructed with a priming factor, DNA polymerase (DNA polymerase beta or Klenow fragment of DNA polymerase I, ATP, T4 DNA ligase and four deoxynucleoside triphosphates. After incubation, the conformation of the DNA was analyzed by agarose gel electrophoresis and electron microscopy. The open circular DNA was largely converted to the closed circular DNA, indicating that the single-strand breaks of DNA were repaired. When the priming factor was omitted, DNA repair did not occur. The present system seemed to be applicable to the study of priming factors involved in the repair of DNA with single-strand breaks caused not only by bleomycin but also by ionizing radiation or active oxygen.

  4. Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

    KAUST Repository

    Viterbo, David

    2016-03-16

    Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded.

  5. Mismatch repair status and synchronous metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Krarup, Peter-Martin; Morton, Dion

    2015-01-01

    The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis....... A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Group's database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial...... metastases (aOR = 0.69, 95% CI:0.26-1.29, p = 0.436) were unaffected by MMR. MMR in patients with SCCM had no impact on survival (Cox: adjusted Hazard Ratio (aHR) = 0.76, 95% CI: 0.54-1.06, p = 0.101; Proportional excess hazards: aHR = 0.73, 95% CI: 0.50-1.07, p = 0.111) when adjusting for other prognostic...

  6. Bond strength of the porcelain repair system to all-ceramic copings and porcelain.

    Science.gov (United States)

    Lee, Sang J; Cheong, Chan Wook; Wright, Robert F; Chang, Brian M

    2014-02-01

    The purpose of this study was to investigate the shear bond strength of the porcelain repair system on alumina and zirconia core ceramics, comparing this strength with that of veneering porcelain. Veneering ceramic (n = 12), alumina core (n = 24), and zirconia core (n = 24) blocks measuring 10 × 5 × 5 mm(3) were fabricated. Veneering ceramic blocks were used as the control. Alumina and zirconia core blocks were divided into 2 groups (n = 12 each), and a slot (2 × 2 × 4 mm(3)) filled with veneering ceramics was prepared into one of the alumina and zirconia core groups (n = 12). Followed by surface treatments of micro-abrasion with 30 μm alumina particles, etching with 35% phosphoric acid and silane primer and bond, composite resin blocks (2 × 2 × 2 mm(3)) were built up and light polymerized onto the treated surfaces by 3 configurations: (a) composite blocks bonded onto veneering ceramic surface alone, (b) composite blocks bonded onto alumina core or zirconia core surfaces, (c) a 50% surface area of the composite blocks bonded to veneering ceramics and the other 50% surface area of the composite blocks to alumina core or zirconia core surfaces. The shear bond strength of the composite to each specimen was tested by a universal testing machine at a 0.5 mm/min crosshead speed. The shear bond strength was analyzed by unpaired t-tests for within the configuration groups and ANOVA for among the different configuration groups. When the mean shear bond strength was compared within groups of the same configuration, there were no statistically significant differences. Comparison of the shear bond strength among groups of different configurations revealed statistically significant differences. The mean shear bond strength of composite onto 100% veneering ceramic surface and composite onto 50% veneering 50% all-ceramic cores was statistically higher than that of composite onto 100% all-ceramic cores; however, the differences of the shear bond strength of composite bonded

  7. Systemic inflammatory responses during laparoscopic and open inguinal hernia repair: a randomised prospective study

    DEFF Research Database (Denmark)

    Jess, P; Schultz, Karen; Bendtzen, K

    2000-01-01

    To see if the inflammatory responses during and after laparoscopic and open inguinal hernia repairs differed.......To see if the inflammatory responses during and after laparoscopic and open inguinal hernia repairs differed....

  8. Prolene Hernia System in the Tension-Free Repair of Primary Inguinal Hernias

    Directory of Open Access Journals (Sweden)

    Jayesh Gohel

    2012-06-01

    Full Text Available Objective: The aim of this study was to determine the feasibility of using the Prolene (polypropylene Hernia System for open tension-free repair on inguinal hernias, and study the results in terms of operation time, patient comfort, hospital stay, return to normal activity and postoperative complications. Material and Methods: From February 2002 through April 2003, we performed 50 open tension-free hernia repairs on 47 patients (46 men, 1 woman with a mean age of 55.8 years. There were 26 right and 18 left hernias, and 3 were bilateral. Of these, 39 were direct, 10 were indirect and 1 was femoral type. All were primary hernias. Results: The duration of surgery averaged 35 minutes (range 20 to 90 min. There was no perioperative mortality. Four patients developed mild self-limiting neuralgias. There were no subcutaneous wound infections, no haematomas, no seromas and no testicular atrophy. The average duration of postoperative hospitalisation was 3.5 days. The length of follow-up ranged from 1 month to 15 months (mean= 6.24 months. We have had no recurrences so far. Conclusion: The Prolene Hernia System is a novel approach in the management of inguinal hernias, with encouraging initial results. Its long-term efficacy needs to be studied with larger, prospective double-blind randomized trials, with longer follow-up. [National J of Med Res 2012; 2(3.000: 302-305

  9. Evaluation of ECHO PS Positioning System in a Porcine Model of Simulated Laparoscopic Ventral Hernia Repair.

    Science.gov (United States)

    Hanna, Erin M; Voeller, Guy R; Roth, J Scott; Scott, Jeffrey R; Gagne, Darcy H; Iannitti, David A

    2013-01-01

    Purpose. Operative efficiency improvements for laparoscopic ventral hernia repair (LVHR) have focused on reducing operative time while maintaining overall repair efficacy. Our objective was to evaluate procedure time and positioning accuracy of an inflatable mesh positioning device (Echo PS Positioning System), as compared to a standard transfascial suture technique, using a porcine model of simulated LVHR. Methods. The study population consisted of seventeen general surgeons (n = 17) that performed simulated LVHR on seventeen (n = 17) female Yorkshire pigs using two implantation techniques: (1) Ventralight ST Mesh + Echo PS Positioning System (Echo PS) and (2) Ventralight ST Mesh + transfascial sutures (TSs). Procedure time and mesh centering accuracy overtop of a simulated surgical defect were evaluated. Results. Echo PS demonstrated a 38.9% reduction in the overall procedure time, as compared to TS. During mesh preparation and positioning, Echo PS demonstrated a 60.5% reduction in procedure time (P Echo PS (16.2%), this was not significantly different than TS. Conclusions. Echo PS demonstrated a significant reduction in overall simulated LVHR procedure time, particularly during mesh preparation/positioning. These operative time savings may translate into reduced operating room costs and improved surgeon/operating room efficiency.

  10. Mismatch repair protein expression and colorectal cancer in Hispanics from Puerto Rico.

    Science.gov (United States)

    De Jesus-Monge, Wilfredo E; Gonzalez-Keelan, Carmen; Zhao, Ronghua; Hamilton, Stanley R; Rodriguez-Bigas, Miguel; Cruz-Correa, Marcia

    2010-06-01

    Colorectal cancer (CRC) is a leading cause of morbidity and mortality and alterations in mismatch repair (MMR) genes, leading to absent protein (negative) expression, are responsible for approximately 20% of CRC cases. Immunohistochemistry is a tool for prescreening of MMR protein expression in CRC but the literature on its use on Hispanics is scarce. However, Hispanics represent the second leading ethnicity in the United States (US) and CRC is a public health burden in this group. Our objectives were to determine the frequency of MMR protein-negative CRC and to evaluate its association with clinical and pathological characteristics among Hispanics from Puerto Rico, for the first time to our knowledge. A retrospective observational study of unselected CRC patients from the Puerto Rico Medical Center from 2001 to 2005 was done. MLH1 and MSH2, the most commonly altered MMR genes, protein expression was evaluated using immunohistochemistry, with microsatellite instability (MSI) and BRAF gene analyses in the absence of MLH1 protein expression. One-hundred sixty-four CRC patients were evaluated: the overall MMR protein-negative frequency was 4.3%, with 0.6% frequency of co-occurrence of MLH1-protein negative expression, MSI-high, and normal BRAF gene. MMR protein-negative expression was associated with proximal colon location (P = 0.02) and poor histological tumor differentiation (P = 0.001), but not with other characteristics. The frequency of MMR protein-negative CRC in Hispanics from Puerto Rico was lower than reported in other populations. This finding may explain the lower CRC incidence rate among US Hispanics as compared to US non-Hispanic whites and blacks.

  11. Gene expression of the mismatch repair gene MSH2 in primary colorectal cancer

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Kuramochi, Hidekazu; Crüger, Dorthe Gylling

    2011-01-01

    Microsatellite instability (MSI) is caused by defective mismatch repair (MMR) and is one of the very few molecular markers with proven clinical importance in colorectal cancer with respect to heredity, prognosis, and treatment effect. The gene expression of the MMR gene MSH2 may be a quantitative...... marker for the level of MMR and a potential molecular marker with clinical relevance. The aim was to investigate the gene expression of MSH2 in primary operable colorectal cancer in correlation with MSI, protein expression, and promoter hypermethylation. In a cohort of 210 patients, the primary tumor...... and lymphnode metastases were analyzed with immunohistochemistry, methylation and MSI analyses, and quantitative polymerase chain reaction (PCR). The median gene expression of MSH2 was 1.00 (range 0.16-11.2, quartiles 0.70-1.51) and there was good agreement between the gene expression in primary tumor and lymph...

  12. Attitudinal and Demographic Predictors of Measles-Mumps-Rubella Vaccine (MMR) Uptake during the UK Catch-Up Campaign 2008–09: Cross-Sectional Survey

    Science.gov (United States)

    Brown, Katrina; Fraser, Graham; Ramsay, Mary; Shanley, Ruth; Cowley, Noel; van Wijgerden, Johan; Toff, Penelope; Falconer, Michelle; Hudson, Michael; Green, John; Kroll, J. Simon; Vincent, Charles; Sevdalis, Nick

    2011-01-01

    Background and Objective Continued suboptimal measles-mumps-rubella (MMR) vaccine uptake has re-established measles epidemic risk, prompting a UK catch-up campaign in 2008–09 for children who missed MMR doses at scheduled age. Predictors of vaccine uptake during catch-ups are poorly understood, however evidence from routine schedule uptake suggests demographics and attitudes may be central. This work explored this hypothesis using a robust evidence-based measure. Design Cross-sectional self-administered questionnaire with objective behavioural outcome. Setting and Participants 365 UK parents, whose children were aged 5–18 years and had received <2 MMR doses before the 2008–09 UK catch-up started. Main Outcome Measures Parents' attitudes and demographics, parent-reported receipt of invitation to receive catch-up MMR dose(s), and catch-up MMR uptake according to child's medical record (receipt of MMR doses during year 1 of the catch-up). Results Perceived social desirability/benefit of MMR uptake (OR = 1.76, 95% CI = 1.09–2.87) and younger child age (OR = 0.78, 95% CI = 0.68–0.89) were the only independent predictors of catch-up MMR uptake in the sample overall. Uptake predictors differed by whether the child had received 0 MMR doses or 1 MMR dose before the catch-up. Receipt of catch-up invitation predicted uptake only in the 0 dose group (OR = 3.45, 95% CI = 1.18–10.05), whilst perceived social desirability/benefit of MMR uptake predicted uptake only in the 1 dose group (OR = 9.61, 95% CI = 2.57–35.97). Attitudes and demographics explained only 28% of MMR uptake in the 0 dose group compared with 61% in the 1 dose group. Conclusions Catch-up MMR invitations may effectively move children from 0 to 1 MMR doses (unimmunised to partially immunised), whilst attitudinal interventions highlighting social benefits of MMR may effectively move children from 1 to 2 MMR doses (partially to fully immunised). Older children may be

  13. Attitudinal and demographic predictors of measles-mumps-rubella vaccine (MMR uptake during the UK catch-up campaign 2008-09: cross-sectional survey.

    Directory of Open Access Journals (Sweden)

    Katrina Brown

    Full Text Available BACKGROUND AND OBJECTIVE: Continued suboptimal measles-mumps-rubella (MMR vaccine uptake has re-established measles epidemic risk, prompting a UK catch-up campaign in 2008-09 for children who missed MMR doses at scheduled age. Predictors of vaccine uptake during catch-ups are poorly understood, however evidence from routine schedule uptake suggests demographics and attitudes may be central. This work explored this hypothesis using a robust evidence-based measure. DESIGN: Cross-sectional self-administered questionnaire with objective behavioural outcome. SETTING AND PARTICIPANTS: 365 UK parents, whose children were aged 5-18 years and had received <2 MMR doses before the 2008-09 UK catch-up started. MAIN OUTCOME MEASURES: Parents' attitudes and demographics, parent-reported receipt of invitation to receive catch-up MMR dose(s, and catch-up MMR uptake according to child's medical record (receipt of MMR doses during year 1 of the catch-up. RESULTS: Perceived social desirability/benefit of MMR uptake (OR = 1.76, 95% CI = 1.09-2.87 and younger child age (OR = 0.78, 95% CI = 0.68-0.89 were the only independent predictors of catch-up MMR uptake in the sample overall. Uptake predictors differed by whether the child had received 0 MMR doses or 1 MMR dose before the catch-up. Receipt of catch-up invitation predicted uptake only in the 0 dose group (OR = 3.45, 95% CI = 1.18-10.05, whilst perceived social desirability/benefit of MMR uptake predicted uptake only in the 1 dose group (OR = 9.61, 95% CI = 2.57-35.97. Attitudes and demographics explained only 28% of MMR uptake in the 0 dose group compared with 61% in the 1 dose group. CONCLUSIONS: Catch-up MMR invitations may effectively move children from 0 to 1 MMR doses (unimmunised to partially immunised, whilst attitudinal interventions highlighting social benefits of MMR may effectively move children from 1 to 2 MMR doses (partially to fully immunised. Older children may be

  14. DNA repair mechanisms in eukaryotes: Special focus in Entamoeba histolytica and related protozoan parasites.

    Science.gov (United States)

    López-Camarillo, César; Lopez-Casamichana, Mavil; Weber, Christian; Guillen, Nancy; Orozco, Esther; Marchat, Laurence A

    2009-12-01

    Eukaryotic cell viability highly relies on genome stability and DNA integrity maintenance. The cellular response to DNA damage mainly consists of six biological conserved pathways known as homologous recombination repair (HRR), non-homologous end-joining (NHEJ), base excision repair (BER), mismatch repair (MMR), nucleotide excision repair (NER), and methyltransferase repair that operate in a concerted way to minimize genetic information loss due to a DNA lesion. Particularly, protozoan parasites survival depends on DNA repair mechanisms that constantly supervise chromosomes to correct damaged nucleotides generated by cytotoxic agents, host immune pressure or cellular processes. Here we reviewed the current knowledge about DNA repair mechanisms in the most relevant human protozoan pathogens. Additionally, we described the recent advances to understand DNA repair mechanisms in Entamoeba histolytica with special emphasis in the use of genomic approaches based on bioinformatic analysis of parasite genome sequence and microarrays technology.

  15. Completion of meiosis in male zebrafish (Danio rerio) despite lack of DNA mismatch repair gene mlh1

    NARCIS (Netherlands)

    Leal, M.C.; Feitsma, H.; Cuppen, E.; França, L.R.; Schulz, R.W.

    2008-01-01

    Mlh1 is a member of DNA mismatch repair (MMR) machinery and is also essential for the stabilization of crossovers during the first meiotic division. Recently, we have shown that zebrafish mlh1 mutant males are completely infertile because of a block in metaphase I, whereas females are fertile but ha

  16. Completion of meiosis in male zebrafish (Danio rerio) despite lack of DNA mismatch repair gene mlh1.

    NARCIS (Netherlands)

    Leal, M.C.; Feitsma, H.; Cuppen, E.; Franca, L.R.; Schulz, R.W.

    2008-01-01

    Mlh1 is a member of DNA mismatch repair (MMR) machinery and is also essential for the stabilization of crossovers during the first meiotic division. Recently, we have shown that zebrafish mlh1 mutant males are completely infertile because of a block in metaphase I, whereas females are fertile but

  17. A soft self-repairing for FBG sensor network in SHM system based on PSO-SVR model reconstruction

    Science.gov (United States)

    Zhang, Xiaoli; Wang, Peng; Liang, Dakai; Fan, Chunfeng; Li, Cailing

    2015-05-01

    Structural health monitoring (SHM) system takes advantage of an array of sensors to continuously monitor a structure and provide an early prediction such as the damage position and damage degree etc. Such a system requires monitoring the structure in any conditions including bad condition. Therefore, it must be robust and survivable, even has the self-repairing ability. In this study, a model reconstruction predicting algorithm based on particle swarm optimization-support vector regression (PSO-SVR) is proposed to achieve the self-repairing of the Fiber Bragg Grating (FBG) sensor network in SHM system. Furthermore, an eight-point FBG sensor SHM system is experimented in an aircraft wing box. For the damage loading position prediction on the aircraft wing box, six kinds of disabled modes are experimentally studied to verify the self-repairing ability of the FBG sensor network in the SHM system, and the predicting performance are compared with non-reconstruction based on PSO-SVR model. The research results indicate that the model reconstruction algorithm has more excellence than that of non-reconstruction model, if partial sensors are invalid in the FBG-based SHM system, the predicting performance of the model reconstruction algorithm is almost consistent with that no sensor is invalid in the SHM system. In this way, the self-repairing ability of the FBG sensor is achieved for the SHM system, such the reliability and survivability of the FBG-based SHM system is enhanced if partial FBG sensors are invalid.

  18. Bridge deck repair and protective systems: latex modified concrete topping. Interim report

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, H.N.

    1984-07-01

    Measures to reduce or eliminate bridge deck deterioration by the use of various protective systems have been the subject of a series of reports begun in 1976. This report presents current observations of latex-modified deck-topping concrete protective systems. Latex-modified concrete topping has not provided long-term protection for the ten structures under evaluation in Colorado. Cost comparisons are made between repair with latex-modified concrete and deck replacement. Over a 40-year period, replacement costs are slightly less than rehabilitation costs. Greater control of the curing of deck-topping materials may reduce shrinkage cracking. Nightime paving, cooler calmer weather and higher humidity would increase the probability of success on latex-modified concrete to rehabilitation projects. Asphalt membrane and asphalt overlay are also suggested to increase the probability of success.

  19. Evolution and Adaptation in Pseudomonas aeruginosa Biofilms Driven by Mismatch Repair System-Deficient Mutators

    DEFF Research Database (Denmark)

    Luján, Adela M.; Maciá, María D.; Yang, Liang

    2011-01-01

    Pseudomonas aeruginosa is an important opportunistic pathogen causing chronic airway infections, especially in cystic fibrosis (CF) patients. The majority of the CF patients acquire P. aeruginosa during early childhood, and most of them develop chronic infections resulting in severe lung disease......, which are rarely eradicated despite intensive antibiotic therapy. Current knowledge indicates that three major adaptive strategies, biofilm development, phenotypic diversification, and mutator phenotypes [driven by a defective mismatch repair system (MRS)], play important roles in P. aeruginosa chronic...... infections, but the relationship between these strategies is still poorly understood. We have used the flow-cell biofilm model system to investigate the impact of the mutS associated mutator phenotype on development, dynamics, diversification and adaptation of P. aeruginosa biofilms. Through competition...

  20. Dental pulp stem cells and their potential roles in central nervous system regeneration and repair.

    Science.gov (United States)

    Young, Fraser; Sloan, Alastair; Song, Bing

    2013-11-01

    Functional recovery from injuries to the brain or spinal cord represents a major clinical challenge. The transplantation of stem cells, traditionally isolated from embryonic tissue, may help to reduce damage following such events and promote regeneration and repair through both direct cell replacement and neurotrophic mechanisms. However, the therapeutic potential of using embryonic stem/progenitor cells is significantly restricted by the availability of embryonic tissues and associated ethical issues. Populations of stem cells reside within the dental pulp, representing an alternative source of cells that can be isolated with minimal invasiveness, and thus should illicit fewer moral objections, as a replacement for embryonic/fetal-derived stem cells. Here we discuss the similarities between dental pulp stem cells (DPSCs) and the endogenous stem cells of the central nervous system (CNS) and their ability to differentiate into neuronal cell types. We also consider in vitro and in vivo studies demonstrating the ability of DPSCs to help protect against and repair neuronal damage, suggesting that dental pulp may provide a viable alternative source of stem cells for replacement therapy following CNS damage.

  1. Space Transportation System (STS)-117 External Tank (ET)-124 Hail Damage Repair Assessment

    Science.gov (United States)

    Wilson, Timmy R.; Gentz, Steven J.; Barth, Timothy S.; Minute, Stephen A.; Flowers, Cody P.; Hamilton, David A.; Null, Cynthia H.; Schafer, Charles F.

    2009-01-01

    Severe thunderstorms with associated hail and high winds struck the STS-117 stack on February 26, 2007. Peak winds were recorded at 62 knots with hail sizes ranging from 0.3 inch to 0.8 inch in diameter. As a result of the storm, the North Carolina Foam Institute (NCFI) type 24-124 Thermal Protection System (TPS) foam on the liquid oxygen (LO2) ogive acreage incurred significant impact damage. The NCFI on the ET intertank and the liquid hydrogen (LH2) acreage sustained hail damage. The Polymer Development Laboratory (PDL)-1034 foam of the LO2 ice frost ramps (IFRs) and the Super-Lightweight Ablator (SLA) of the LO2 cable tray also suffered minor damage. NASA Engineering and Safety Center (NESC) was asked to assess the technical feasibility of repairing the ET TPS, the reasonableness of conducting those repairs with the vehicle in a vertical, integrated configuration at the Kennedy Space Center (KSC) Vehicle Assemble Building (VAB), and to address attendant human factors considerations including worker fatigue and the potential for error. The outcome of the assessment is recorded in this document.

  2. Recombinant Technology in the Development of Materials and Systems for Soft-Tissue Repair.

    Science.gov (United States)

    Girotti, Alessandra; Orbanic, Doriana; Ibáñez-Fonseca, Arturo; Gonzalez-Obeso, Constancio; Rodríguez-Cabello, José Carlos

    2015-11-18

    The field of biomedicine is constantly investing significant research efforts in order to gain a more in-depth understanding of the mechanisms that govern the function of body compartments and to develop creative solutions for the repair and regeneration of damaged tissues. The main overall goal is to develop relatively simple systems that are able to mimic naturally occurring constructs and can therefore be used in regenerative medicine. Recombinant technology, which is widely used to obtain new tailored synthetic genes that express polymeric protein-based structures, now offers a broad range of advantages for that purpose by permitting the tuning of biological and mechanical properties depending on the intended application while simultaneously ensuring adequate biocompatibility and biodegradability of the scaffold formed by the polymers. This Progress Report is focused on recombinant protein-based materials that resemble naturally occurring proteins of interest for use in soft tissue repair. An overview of recombinant biomaterials derived from elastin, silk, collagen and resilin is given, along with a description of their characteristics and suggested applications. Current endeavors in this field are continuously providing more-improved materials in comparison with conventional ones. As such, a great effort is being made to put these materials through clinical trials in order to favor their future use.

  3. The clinical value of the systemic inflammatory response syndrome (SIRS) in abdominal aortic aneurysm repair.

    Science.gov (United States)

    Norwood, M G; Bown, M J; Lloyd, G; Bell, P R F; Sayers, R D

    2004-03-01

    The systemic inflammatory response syndrome (SIRS) is common after major surgery. We examine the dynamics of SIRS in AAA patients, and assess the impact of the number of SIRS criteria on patient outcome. Prospective study of 151 consecutive patients with AAA, undergoing repair electively, urgently or with rupture. SIRS scores and organ failure scores were recorded prospectively each day for all patients. Outcome measures included length of stay, evidence of organ failure and mortality. The majority of patients developed SIRS postoperatively. Elective patients with a cumulative SIRS score of > or =10 during postoperative days 1-4 were more likely to die, compared to patients with a SIRS score of SIRS late in the postoperative period (day 5-10) was associated with adverse outcome (death) in elective patients (p=0.01). The actual number of SIRS criteria present did not significantly correlate with either outcome or the incidence of organ failure. SIRS is common in patients undergoing AAA repair. The SIRS score provides useful information regarding a patient's physiological state. High SIRS scores, and the development of SIRS late in the postoperative period are associated with adverse outcome in elective patients, and can therefore be used as an indicator of potential problems.

  4. 错配修复系统hMutS、hMutL的变异与结直肠癌的相关性研究进展%Recent Advances of Correlation of Mismatch Repair System hMutS, hMutL Variation and Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    段典榕; 汪旭; 周滔; 吴暇玉; 梁子卿; 倪娟

    2016-01-01

    DNA错配修复系统(mismatch repair system,MMR)是重要的复制后修复机制,修复各种类型的碱基错配和插入/缺失环.hMutS、hMutL是MMR中重要的两个子系统,它们的功能缺陷与多种肿瘤,尤其结直肠癌密切相关.hMutS、hMutL系统关键基因SNPs、启动子甲基化水平的变化,都会直接或间接影响MMR的功能,以及由此引起微卫星不稳定性增加,进而影响结直肠癌的发生、发展和预后.本文主要从hMutS、hMutL系统关键基因的SNPs、启动子甲基化和微卫星不稳定三个方面综述了hMutS、hMutL系统关键基因变异与结直肠癌相关性研究的进展.

  5. INTRALESIONAL MEASLES, MUMPS AND RUBELLA (MMR VACCINE-AN EFFECTIVE THERAPEUTIC TOOL IN THE TREATMENT OF WART

    Directory of Open Access Journals (Sweden)

    Raju

    2015-11-01

    Full Text Available BACKGROUND: Warts are common cutaneous viral infection. Various therapeutic modalities have been using in treatment of wart, but none of them are standardised. Immunotherapy is new current approach in the treatment of wart. AIMS: To know the efficacy and safety profile of Measles Mumps Rubella (MMR Vaccine in the treatment of wart. METHODS: MMR vaccine was injected into a largest single wart intralesionally and subsequent injections given every 2 weeks apart for about 3 to 5 times. Every month followup of patients was done to know the clearance of wart. RESULTS: Complete remission of warts seen in 70.4% of patients, partial remission seen in 22.2% and no response was seen in 7.4% of patients. No serious adverse side effects were seen in the current study. CONCLUSION: MMR vaccine can be considered as a safe, effective, inexpensive intralesional immunotherapeutic modality in the treatment of wart.

  6. Development of a rocking R/C shear wall system implementing repairable structural fuses

    Science.gov (United States)

    Parsafar, Saeed; Moghadam, Abdolreza S.

    2017-09-01

    In the last decades, the concept of earthquake resilient structural systems is becoming popular in which the rocking structure is considered as a viable option for buildings in regions of high seismicity. To this end, a novel wall-base connection based on the " repairable structure" approach is proposed and evaluated. The proposed system is made of several steel plates and high strength bolts act as a friction connection. To achieve the desired rocking motion in the proposed system, short-slotted holes are used in vertical directions for connecting the steel plates to the shear wall (SW). The experimental and numerical studies were performed using a series of displacement control quasi-static cyclic tests on a reference model and four different configurations of the proposed connection installed at the wall corners. The seismic response of the proposed system is compared to the conventional SW in terms of energy dissipation and damage accumulation. In terms of energy dissipation, the proposed system depicted better performance with 95% more energy dissipation capability compared to conventional SW. In terms of damage accumulation, the proposed SW system is nearly undamaged compared to the conventional wall system, which was severely damaged at the wall-base region. Overall, the introduced concept presents a feasible solution for R/C structures when a low-damage design is targeted, which can improve the seismic performance of the structural system significantly.

  7. Application of Petri nets to reliability prediction of occupant safety systems with partial detection and repair

    Energy Technology Data Exchange (ETDEWEB)

    Kleyner, Andre, E-mail: andre.v.kleyner@delphi.co [Delphi Corporation, Electronics and Safety Division, P.O. Box 9005, M.S. CTC 2E, Kokomo, IN 46904 (United States); Volovoi, Vitali, E-mail: vitali.volovoi@ae.gatech.ed [School of Aerospace Engineering, Georgia Institute of Technology, Atlanta, GA 30332 (United States)

    2010-06-15

    This paper presents an application of stochastic Petri nets (SPN) to calculate the availability of safety critical on-demand systems. Traditional methods of estimating system reliability include standards-based or field return-based reliability prediction methods. These methods do not take into account the effect of fault-detection capability and penalize the addition of detection circuitry due to the higher parts count. Therefore, calculating system availability, which can be linked to the system's probability of failure on demand (P{sub fd}), can be a better alternative to reliability prediction. The process of estimating the P{sub fd} of a safety system can be further complicated by the presence of system imperfections such as partial-fault detection by users and untimely or uncompleted repairs. Additionally, most system failures cannot be represented by Poisson process Markov chain methods, which are commonly utilized for the purposes of estimating P{sub fd}, as these methods are not well-suited for the analysis of non-Poisson failures. This paper suggests a methodology and presents a case study of SPN modeling adequately handling most of the above problems. The model will be illustrated with a case study of an automotive electronics airbag controller as an example of a safety critical on-demand system.

  8. Validation of the Algorithms for Depot Exchangeable Repair and Modification Costs for NSNS and Engines for the Component Support Cost System (D160B).

    Science.gov (United States)

    2014-09-26

    IDENTIFICATION OI 03 NOMENCLATURE . ITEM 012 03 PRICE. STANDARD INVENTORY 013 03 CODE. WEAPON SYSTEM SUPPORT 014 06 CODE. WEAPON SYSTEM SUPPORT. POSITIONS I TO...calculation of standard depot repair prices ( sales prices). Various knowledgeable Air Force personnel have noted that it is not unusual for an engine to be both...cost elements not used in calculation of standard depot repair prices (" sales prices"). ISI affirms the congruence of the definitions of repair prices as

  9. Sensitivity issues in the bayesian analysis of failures in repairable systems

    Energy Technology Data Exchange (ETDEWEB)

    Ruggero, F.

    2001-07-01

    The paper arises from a consulting project in which failures (gas escapes) are considered in the steel pipelines of an urban gas distribution network. The available data are the 33 failure times from 1978 to 1997 over a network of 275 kilometres. More details on the data can be found in (1). Steel pipelines are subject to ageing and the global system reliability is barely affected by one failure. Thus, we consider the network as a repairable system, since it keeps the same reliability when minimal repairs immediately follow failures. Failures of Such systems are often described by non-homogeneous Poisson processes (NHPP), which take in account the degradation of the components; see, e. g. (2). In the paper we model the failures pattern with a NHPP with logarithmic intensity and present different sensitivity analyses when relaxing the assumption on the parametric model. We operate in a robust Bayesian framework, see (3) for a thoroughly illustration of the approach. In the paper we do not focus on the commonly addressed issue of sensitivity to the prior, but we are interested in model sensitivity and consider two ways to build classes of models around the NHPP. In the first approach, we consider the NHPP as an element of a class of processes, defined through differential equations whose solutions are mean value functions of NHPPs. In the second, nonparametric approach, we consider processes whose mean value functions are distribution functions of random measures. In both cases, we compare the models with the baseline, logarithmic NHPP. In Section 2 we analyse the logarithmic NHPP and the class of parametric models, whereas comparison between parametric and nonparametric models is performed in Section 3. Some concluding remarks are presented in Section. (Author) 12 refs.

  10. Reliability Analysis of a Cold Standby System with Imperfect Repair and under Poisson Shocks

    Directory of Open Access Journals (Sweden)

    Yutian Chen

    2014-01-01

    Full Text Available This paper considers the reliability analysis of a two-component cold standby system with a repairman who may have vacation. The system may fail due to intrinsic factors like aging or deteriorating, or external factors such as Poisson shocks. The arrival time of the shocks follows a Poisson process with the intensity λ>0. Whenever the magnitude of a shock is larger than the prespecified threshold of the operating component, the operating component will fail. The paper assumes that the intrinsic lifetime and the repair time on the component are an extended Poisson process, the magnitude of the shock and the threshold of the operating component are nonnegative random variables, and the vacation time of the repairman obeys the general continuous probability distribution. By using the vector Markov process theory, the supplementary variable method, Laplace transform, and Tauberian theory, the paper derives a number of reliability indices: system availability, system reliability, the rate of occurrence of the system failure, and the mean time to the first failure of the system. Finally, a numerical example is given to validate the derived indices.

  11. How Trypanosoma cruzi deals with oxidative stress: Antioxidant defence and DNA repair pathways.

    Science.gov (United States)

    Machado-Silva, Alice; Cerqueira, Paula Gonçalves; Grazielle-Silva, Viviane; Gadelha, Fernanda Ramos; Peloso, Eduardo de Figueiredo; Teixeira, Santuza Maria Ribeiro; Machado, Carlos Renato

    2016-01-01

    Trypanosoma cruzi, the causative agent of Chagas disease, is an obligatory intracellular parasite with a digenetic life cycle. Due to the variety of host environments, it faces several sources of oxidative stress. In addition to reactive oxygen species (ROS) produced by its own metabolism, T. cruzi must deal with high ROS levels generated as part of the host's immune responses. Hence, the conclusion that T. cruzi has limited ability to deal with ROS (based on the lack of a few enzymes involved with oxidative stress responses) seems somewhat paradoxical. Actually, to withstand such variable sources of oxidative stress, T. cruzi has developed complex defence mechanisms. This includes ROS detoxification pathways that are distinct from the ones in the mammalian host, DNA repair pathways and specialized polymerases, which not only protect its genome from the resulting oxidative damage but also contribute to the generation of genetic diversity within the parasite population. Recent studies on T. cruzi's DNA repair pathways as mismatch repair (MMR) and GO system suggested that, besides a role associated with DNA repair, some proteins of these pathways may also be involved in signalling oxidative damage. Recent data also suggested that an oxidative environment might be beneficial for parasite survival within the host cell as it contributes to iron mobilization from the host's intracellular storages. Besides contributing to the understanding of basic aspects of T. cruzi biology, these studies are highly relevant since oxidative stress pathways are part of the poorly understood mechanisms behind the mode of action of drugs currently used against this parasite. By unveiling new peculiar aspects of T. cruzi biology, emerging data on DNA repair pathways and other antioxidant defences from this parasite have revealed potential new targets for a much needed boost in drug development efforts towards a better treatment for Chagas disease.

  12. Robot-assisted fenestrated endovascular aneurysm repair (FEVAR) using the Magellan system.

    Science.gov (United States)

    Riga, Celia V; Bicknell, Colin D; Rolls, Alexander; Cheshire, Nicholas J; Hamady, Mohamad S

    2013-02-01

    A 67-year-old man underwent robot-assisted three-vessel fenestrated endovascular aneurysm repair (FEVAR) for a 7.3-cm juxtarenal aneurysm. The 6-F robotic catheter was manipulated from a remote workstation, away from the radiation source. Robotic cannulation of the left renal artery was achieved within 3 minutes. System setup time was 5 minutes. There were no postoperative complications. Computed tomography angiography performed at discharge and at 4-month follow-up confirmed target vessel patency with no evidence of an endoleak. Selective cannulation of target vessels during FEVAR using this novel technology is feasible. Endovascular robotics may have a role in simplifying complex endovascular tasks and potentially reducing radiation exposure to the operator.

  13. [The putative link between the MMR vaccine and autism and refusal to vaccinate].

    Science.gov (United States)

    Segura Benedicto, Andreu

    2012-01-01

    The paper of Wakefield et al. in The Lancet, triggered a negative reaction to the MMR vaccine, even though it was just a series of cases and the association between vaccination and autism could well be anecdotal. However, it was found that this association was spurious, not only because of hidden biases but also to alterations of the data and other improper behavior of the two authors that they were expelled from medical council. Finally, the article was removed from the magazine. This episode invites to think about the credibility and trust in the authorities and professionals to the population, as well as the suspicions that may arise when there are potential conflicts of interest among professionals, industry magazines and the population. A special area of interest is on the distorted expectations of health interventions, including vaccination, particularly with regard to both individual and collective prevention.

  14. Lubrication System 1. Check and Change the Engine Oil. Student Manual. Small Engine Repair Series. First Edition.

    Science.gov (United States)

    Hill, Pamela

    This student manual on checking and changing the engine oil is the second of three in an instructional package on the lubrication system in the Small Engine Repair Series for handicapped students. The stated purpose for the booklet is to help students learn what tools and equipment to use and all the steps of the job. Informative material and…

  15. Early passage bone marrow stromal cells express genes involved in nervous system development supporting their relevance for neural repair

    NARCIS (Netherlands)

    Nandoe, R.D.S.; Bossers, K.; Ritfeld, G.J.; Blits, B.; Grotenhuis, J.A.; Verhaagen, J.; Oudega, M.

    2011-01-01

    PURPOSE: The assessment of the capacity of bone marrow stromal cells (BMSC) to repair the nervous system using gene expression profiling. The evaluation of effects of long-term culturing on the gene expression profile of BMSC. METHODS: Fourty four k whole genome rat microarrays were used to study

  16. Participatory Design Research as a Practice for Systemic Repair: Doing Hand-in-Hand Math Research with Families

    Science.gov (United States)

    Booker, Angela; Goldman, Shelley

    2016-01-01

    Success and failure in formal mathematics education has been used to legitimize stratification. We describe participatory design research as a methodology for systemic repair. The analysis describes epistemic authority--exercising the right or the power to know--as a form of agency in processes of mathematical problem solving and learning. We…

  17. Participatory Design Research as a Practice for Systemic Repair: Doing Hand-in-Hand Math Research with Families

    Science.gov (United States)

    Booker, Angela; Goldman, Shelley

    2016-01-01

    Success and failure in formal mathematics education has been used to legitimize stratification. We describe participatory design research as a methodology for systemic repair. The analysis describes epistemic authority--exercising the right or the power to know--as a form of agency in processes of mathematical problem solving and learning. We…

  18. Reliability and Functionality of Repairable Systems Using a Minimal Set of Metrics: Design and Maintenance of a Smart Charging Microgrid

    Science.gov (United States)

    2013-01-01

    DESIGN AND MAINTENANCE OF A SMART CHARGING MICROGRID Vijitashwa Pandey 1 pandey2@oakland.edu Annette Skowronska-Kurec 2...remote microgrid powering a military installation require a careful consideration of cost and repair strategies. This is because of logistical...value of the proposed approach using a US Army smart- charging microgrid installation. 1. INTRODUCTION Most real-life engineering systems are

  19. Study of the performance of four repairing material systems for hydraulic structures of concrete dams

    Directory of Open Access Journals (Sweden)

    Kormann A. C. M.

    2003-01-01

    Full Text Available Four types of repairing materials are studied as function of either a conventional concrete or a reference-concrete (RefC, these are: polymer-modified cement mortar (PMor, steel fiber concrete (SFco, epoxy mortar (EMor and silica fume mortar (SFmo, to be applied in hydraulic structures surfaces subjected to a high velocity water flow. Besides the mechanical requests and wearing resistance of hydraulic concrete dam structures, especially the spillway surfaces, the high solar radiation, the environmental temperature and wet and dry cycles, contribute significantly to the reduction of their lifespan. RefC and the SFco were developed based on a usual concrete mixture used in slabs of spillways. The average RefC mixture used was 1: 1.61: 2.99: 0.376, with Pozzolan-modified Portland cement consumption of 425 kg/m³. EMor and PMor mixtures followed the information given by the manufacturers and lab experience. Tests on concrete samples were carried out in laboratory simulating normally found environmental situations in order to control the mechanical resistance and the aging imposed conditions, such as solar radiation and humidity. Also, physicochemical characterizing tests were made for all used materials. From the analyzed results, two of them presented a higher performance: the EMor and SFmo. SFco presented good adherence to the RefC and good mechanical performance. However, it also presented apparent metal corrosion in humidity tests, being indicated for use, with caution, as an intermediate layer in underwater repairs. In a general classification, considering all tests, including their field applications, the better performance material systems were EMor- SFmo> SFco> PMor.

  20. Persistence of measles antibodies, following changes in the recommended age for the second dose of MMR-vaccine in Portugal.

    Science.gov (United States)

    Gonçalves, Guilherme; Frade, João; Nunes, Carla; Mesquita, João Rodrigo; Nascimento, Maria São José

    2015-09-22

    In populations vaccinated with two doses of combined measles-mumps-rubella vaccine (MMR), the serum levels of antibodies against measles depend on the vaccination schedule, time elapsed from the last dose and the area-specific epidemiological situation. Variables measuring "schedule" are age at first and second doses of MMR and intervals derived from that. Changes in vaccination schedules have been made in Portugal. The specific objectives of this study were to measure the association between those potential determinants and the concentration of measles-specific IgG antibodies, after the second dose of MMR. Convenience samples of three Portuguese birth cohorts were selected for this study (41, 66 and 60 born, respectively, in 2001-2003, 1990-1993 and 1994-1995). Geometric mean concentrations (GMC) for measles IgG were, respectively, 934, 251 and 144mIU/ml; pmeasles-IgG serum concentration decreased with time since last vaccination (waning immunity) and was not influenced by any other component of vaccination schedule, namely age at vaccination with the second dose of MMR. Waning levels of measles antibodies have been observed elsewhere but not as fast as it was observed in Portuguese birth cohorts in this study. Changes in the vaccination schedules might have to be considered in the future.

  1. Reasons for measles cases not being vaccinated with MMR: investigation into parents' and carers' views following a large measles outbreak.

    Science.gov (United States)

    McHale, P; Keenan, A; Ghebrehewet, S

    2016-03-01

    Uptake rates for the combined measles, mumps and rubella (MMR) vaccine have been below the required 95% in the UK since a retracted and discredited article linking the MMR vaccine with autism and inflammatory bowel disease was released in 1998. This study undertook semi-structured telephone interviews among parents or carers of 47 unvaccinated measles cases who were aged between 13 months and 9 years, during a large measles outbreak in Merseyside. Results showed that concerns over the specific links with autism remain an important cause of refusal to vaccinate, with over half of respondents stating this as a reason. A quarter stated child illness during scheduled vaccination time, while other reasons included general safety concerns and access issues. Over half of respondents felt that more information or a discussion with a health professional would help the decision-making process, while a third stated improved access. There was clear support for vaccination among respondents when asked about current opinions regarding MMR vaccine. The findings support the hypothesis that safety concerns remain a major barrier to MMR vaccination, and also support previous evidence that experience of measles is an important determinant in the decision to vaccinate.

  2. Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review.

    Science.gov (United States)

    Metcalf, Alexander M; Spurdle, Amanda B

    2014-03-01

    Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.

  3. Application of resin system for sand consolidation, mud-loss control, and channel repairing

    Energy Technology Data Exchange (ETDEWEB)

    Wasnik, A.; Mete, S.; Ghosh, B. [Maharashtra Inst. of Technology (India)

    2005-11-01

    Sand production is one of the major challenges facing oil well operators. A technique for sand consolidation and channel repairing with a resin system was described along with a methodology for placing a chemical casing during or after drilling a shale zone that is prone to caving. The methodology is intended to facilitate drilling with reduced mud weight, without reducing the hole size. The resin comprises a mixture of elastomers UF, MF and a suitable plasticizer to impart flexibility and impact resistance. The resin system includes both the resin and a hardener which is a mixture of 2 mild Lewis acids to control curing time. A special additive can be used to enhance surface bonding between the sand and resin. Experiments were then performed to examine the efficiency of resin (Asmid 603) with 7 different chemicals and resin Furmel 301 with Furmel catalyst as a curing modifier. The best combination for sand consolidation and chemical casing was found to be resin Asmid 603 with 0.6 per cent o-phosphoric acid at 80 degrees C and Furmel 301 with 2.5 per cent Furmel catalyst and CFNL with 0.6 per cent o-phosphoric acid. When this combination was used, the permeability was found to be nearly zero after consolidation of resin. The newly developed resin system costs one-third that of epoxy resins. Since it is water soluble, it is also easy to handle and environmentally sound. 15 refs., 2 tabs., 6 figs.

  4. Model System for Live Imaging of Neuronal Responses to Injury and Repair

    Directory of Open Access Journals (Sweden)

    Mathieu Gravel

    2011-11-01

    Full Text Available Although it has been well established that induction of growth-associated protein-43 (GAP-43 during development coincides with axonal outgrowth and early synapse formation, the existence of neuronal plasticity and neurite outgrowth in the adult central nervous system after injuries is more controversial. To visualize the processes of neuronal injury and repair in living animals, we generated reporter mice for bioluminescence and fluorescence imaging bearing the luc (luciferase and gfp (green fluorescent protein reporter genes under the control of the murine GAP-43 promoter. Reporter functionality was first observed during the development of transgenic embryos. Using in vivo bioluminescence and fluorescence imaging, we visualized induction of the GAP-43 signals from live embryos starting at E10.5, as well as neuronal responses to brain and peripheral nerve injuries (the signals peaked at 14 days postinjury. Moreover, three-dimensional analysis of the GAP-43 bioluminescent signal confirmed that it originated from brain structures affected by ischemic injury. The analysis of fluorescence signal at cellular level revealed colocalization between endogenous protein and the GAP-43-driven gfp transgene. Taken together, our results suggest that the GAP-43-luc/gfp reporter mouse represents a valid model system for real-time analysis of neurite outgrowth and the capacity of the adult nervous system to regenerate after injuries.

  5. The zebrafish as a gerontology model in nervous system aging, disease, and repair.

    Science.gov (United States)

    Van Houcke, Jessie; De Groef, Lies; Dekeyster, Eline; Moons, Lieve

    2015-11-01

    Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age-associated human pathologies through a survey of the functional deficits that arise as zebrafish age.

  6. Evolution and adaptation in Pseudomonas aeruginosa biofilms driven by mismatch repair system-deficient mutators.

    Directory of Open Access Journals (Sweden)

    Adela M Luján

    Full Text Available Pseudomonas aeruginosa is an important opportunistic pathogen causing chronic airway infections, especially in cystic fibrosis (CF patients. The majority of the CF patients acquire P. aeruginosa during early childhood, and most of them develop chronic infections resulting in severe lung disease, which are rarely eradicated despite intensive antibiotic therapy. Current knowledge indicates that three major adaptive strategies, biofilm development, phenotypic diversification, and mutator phenotypes [driven by a defective mismatch repair system (MRS], play important roles in P. aeruginosa chronic infections, but the relationship between these strategies is still poorly understood. We have used the flow-cell biofilm model system to investigate the impact of the mutS associated mutator phenotype on development, dynamics, diversification and adaptation of P. aeruginosa biofilms. Through competition experiments we demonstrate for the first time that P. aeruginosa MRS-deficient mutators had enhanced adaptability over wild-type strains when grown in structured biofilms but not as planktonic cells. This advantage was associated with enhanced micro-colony development and increased rates of phenotypic diversification, evidenced by biofilm architecture features and by a wider range and proportion of morphotypic colony variants, respectively. Additionally, morphotypic variants generated in mutator biofilms showed increased competitiveness, providing further evidence for mutator-driven adaptive evolution in the biofilm mode of growth. This work helps to understand the basis for the specific high proportion and role of mutators in chronic infections, where P. aeruginosa develops in biofilm communities.

  7. Evolution and adaptation in Pseudomonas aeruginosa biofilms driven by mismatch repair system-deficient mutators.

    Science.gov (United States)

    Luján, Adela M; Maciá, María D; Yang, Liang; Molin, Søren; Oliver, Antonio; Smania, Andrea M

    2011-01-01

    Pseudomonas aeruginosa is an important opportunistic pathogen causing chronic airway infections, especially in cystic fibrosis (CF) patients. The majority of the CF patients acquire P. aeruginosa during early childhood, and most of them develop chronic infections resulting in severe lung disease, which are rarely eradicated despite intensive antibiotic therapy. Current knowledge indicates that three major adaptive strategies, biofilm development, phenotypic diversification, and mutator phenotypes [driven by a defective mismatch repair system (MRS)], play important roles in P. aeruginosa chronic infections, but the relationship between these strategies is still poorly understood. We have used the flow-cell biofilm model system to investigate the impact of the mutS associated mutator phenotype on development, dynamics, diversification and adaptation of P. aeruginosa biofilms. Through competition experiments we demonstrate for the first time that P. aeruginosa MRS-deficient mutators had enhanced adaptability over wild-type strains when grown in structured biofilms but not as planktonic cells. This advantage was associated with enhanced micro-colony development and increased rates of phenotypic diversification, evidenced by biofilm architecture features and by a wider range and proportion of morphotypic colony variants, respectively. Additionally, morphotypic variants generated in mutator biofilms showed increased competitiveness, providing further evidence for mutator-driven adaptive evolution in the biofilm mode of growth. This work helps to understand the basis for the specific high proportion and role of mutators in chronic infections, where P. aeruginosa develops in biofilm communities.

  8. Microbial water quality before and after the repair of a failing onsite wastewater treatment system adjacent to coastal waters

    Science.gov (United States)

    Conn, K.E.; Habteselassie, M.Y.; Denene, Blackwood A.; Noble, R.T.

    2012-01-01

    Aims: The objective was to assess the impacts of repairing a failing onsite wastewater treatment system (OWTS, i.e., septic system) as related to coastal microbial water quality. Methods and Results: Wastewater, groundwater and surface water were monitored for environmental parameters, faecal indicator bacteria (total coliforms, Escherichia coli, enterococci) and the viral tracer MS2 before and after repairing a failing OWTS. MS2 results using plaque enumeration and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) often agreed, but inhibition limited the qRT-PCR assay sensitivity. Prerepair, MS2 persisted in groundwater and was detected in the nearby creek; postrepair, it was not detected. In groundwater, total coliform concentrations were lower and E.??coli was not detected, while enterococci concentrations were similar to prerepair levels. E.??coli and enterococci surface water concentrations were elevated both before and after the repair. Conclusions: Repairing the failing OWTS improved groundwater microbial water quality, although persistence of bacteria in surface water suggests that the OWTS was not the singular faecal contributor to adjacent coastal waters. A suite of tracers is needed to fully assess OWTS performance in treating microbial contaminants and related impacts on receiving waters. Molecular methods like qRT-PCR have potential but require optimization. Significance and Impact of Study: This is the first before and after study of a failing OWTS and provides guidance on selection of microbial tracers and methods. ?? 2011 The Authors. Journal of Applied Microbiology ?? 2011 The Society for Applied Microbiology.

  9. Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer

    NARCIS (Netherlands)

    Niessen, R C; Berends, M J W; Wu, Y; Sijmons, R H; Hollema, H; Ligtenberg, M J L; de Walle, H E K; de Vries, E G E; Karrenbeld, A; Buys, C H C M; van der Zee, A G J; Hofstra, R M W; Kleibeuker, J H

    2006-01-01

    Background: Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations. Aim: To analyse the value of family history,

  10. Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer.

    NARCIS (Netherlands)

    Niessen, R.C.; Berends, M.J.; Wu, Y.; Sijmons, R.H.; Hollema, H.; Ligtenberg, M.J.L.; Walle, H.E. de; Vries, E.G.F. de; Karrenbeld, A.; Buys, C.H.C.M.; Zee, A.G. van der; Hofstra, R.M.; Kleibeuker, J.H.

    2006-01-01

    BACKGROUND: Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations. AIM: To analyse the value of family history,

  11. Mismatch Repair Status and BRAF Mutation Status in Metastatic Colorectal Cancer Patients: A Pooled Analysis of the CAIRO, CAIRO2, COIN, and FOCUS Studies

    NARCIS (Netherlands)

    Venderbosch, S.; Nagtegaal, I.D.; Maughan, T.S.; Smith, C.G.; Cheadle, J.P.; Fisher, D.; Kaplan, R.; Quirke, P.; Seymour, M.T.; Richman, S.D.; Meijer, G.A.; Ylstra, B.; Heideman, D.A.; Haan, A.F.J. de; Punt, C.J.A.; Koopman, M.

    2014-01-01

    PURPOSE: To determine the prevalence and prognostic value of mismatch repair (MMR) status and its relation to BRAF mutation (BRAF(MT)) status in metastatic colorectal cancer (mCRC). EXPERIMENTAL DESIGN: A pooled analysis of four phase III studies in first-line treatment of mCRC (CAIRO, CAIRO2, COIN,

  12. Genetic characterization of cells of homocystinuria patients with disrupted DNA repair system

    Energy Technology Data Exchange (ETDEWEB)

    Sinel' shchikova, T.A.; L' vova, G.N.; Shoniya, N.N.; Zasukhina, G.D.

    1986-08-01

    Fibroblasts obtained from biopsy material and lymphocytes of patients with homocystinuria were investigated for repair activity according to the following criteria: rejoined DNA breaks, induced by 4-nitroquinoline-1-oxide and ..gamma..-radiation; indices of reactivation and induced mutagenesis of smallpox vaccine virus treated with these mutagens. In lymphocytes a defect of DNA repair was observed according to all criteria investigated. During passage of fibroblast cultures, inhibition of repair activity of cells was preserved according to ..gamma..-type. Increase in the number of spontaneous and ..gamma..-induced mutations of virus was noted according to degree of passage of fibroblasts.

  13. Minor Changes in Expression of the Mismatch Repair Protein MSH2 Exert a Major Impact on Glioblastoma Response to Temozolomide.

    Science.gov (United States)

    McFaline-Figueroa, José L; Braun, Christian J; Stanciu, Monica; Nagel, Zachary D; Mazzucato, Patrizia; Sangaraju, Dewakar; Cerniauskas, Edvinas; Barford, Kelly; Vargas, Amanda; Chen, Yimin; Tretyakova, Natalia; Lees, Jacqueline A; Hemann, Michael T; White, Forest M; Samson, Leona D

    2015-08-01

    Glioblastoma (GBM) is often treated with the cytotoxic drug temozolomide, but the disease inevitably recurs in a drug-resistant form after initial treatment. Here, we report that in GBM cells, even a modest decrease in the mismatch repair (MMR) components MSH2 and MSH6 have profound effects on temozolomide sensitivity. RNAi-mediated attenuation of MSH2 and MSH6 showed that such modest decreases provided an unexpectedly strong mechanism of temozolomide resistance. In a mouse xenograft model of human GBM, small changes in MSH2 were sufficient to suppress temozolomide-induced tumor regression. Using The Cancer Genome Atlas to analyze mRNA expression patterns in tumors from temozolomide-treated GBM patients, we found that MSH2 transcripts in primary GBM could predict patient responses to initial temozolomide therapy. In recurrent disease, the absence of microsatellite instability (the standard marker for MMR deficiency) suggests a lack of involvement of MMR in the resistant phenotype of recurrent disease. However, more recent studies reveal that decreased MMR protein levels occur often in recurrent GBM. In accordance with our findings, these reported decreases may constitute a mechanism by which GBM evades temozolomide sensitivity while maintaining microsatellite stability. Overall, our results highlight the powerful effects of MSH2 attenuation as a potent mediator of temozolomide resistance and argue that MMR activity offers a predictive marker for initial therapeutic response to temozolomide treatment.

  14. Comparison of a new braid fixation system to an interlocking intramedullary nail for tibial osteotomy repair in an ovine model.

    Science.gov (United States)

    Lu, Yan; Nemke, Brett; Lorang, Douglas M; Trip, Roel; Kobayashi, Hirohito; Markel, Mark D

    2009-06-01

    To compare bone healing of tibial osteotomy repaired with Nitinol wire braid and hardened steel rods (Braid system) and polymethylmethacrylate bone cement with an interlocking intramedullary (IM) nail fixation in an ovine model. In vitro and in vivo experimental study. Adult female sheep (n=22). Using sheep tibia, a middiaphyseal transverse osteotomy was performed in the right tibia, which were then randomly assigned to the Braid system group or IM nail group (n=5). The left tibia were used as controls. The torsional properties of tibial constructs were compared. The study was repeated in vivo in 12 sheep and mechanical properties and bone healing were evaluated at 12 weeks. In vitro, there was no significant difference in torsional stiffness between the groups. In vivo, operative time for the Braid system group was significantly shorter than the IM nail group. At 12 weeks, there were no significant differences in maximum torque and torsional stiffness between IM nail and Braid system groups nor were there significant radiographic or histologic differences between the groups. The Braid system might decrease operative time for repair of transverse middiaphyseal tibial fractures and result in similar bone healing at 12 weeks after surgery compared with an interlocking IM nail repair. A Nitinol Braid system may be a treatment option for transverse midshaft tibial fractures.

  15. Replace the Carburetor Diaphragm. Pulsa-Jet Style with Automatic Choke. Fuel System. Student Manual 2. Small Engine Repair Series. First Edition.

    Science.gov (United States)

    Hill, Pamela

    This student manual, part of a small-engine repair series on servicing fuel systems, is designed for use by special needs students in Texas. The manual explains in pictures and short sentences, written on a low reading level, the job of replacing carburetor diaphragms. Along with the steps of this repair job, specific safety and caution…

  16. Validation of the Algorithms for Base Exchangeable Repair Costs (Engine) and Base Exchangeable Modification Costs (Engine) for the Component Support Cost System (D160B).

    Science.gov (United States)

    2014-09-26

    REPORTING 010 03 NUMBER. ITEM IDENTIFICATION Oil 03 NOMENCLATURE . ITEM 012 03 PRICE. STANDARD INVENTORY 013 03 CODE, WEAPON SYSTEM SUPPORT 014 05 CODE...elements not used in calculation of standard depot repair prices (* sales prices"). ISI affirms the congruence of the definitions of repair prices as

  17. REPAIR OF GEAR-TYPE PUMPS FOR HYDRAULIC SYSTEMS OF CONSTRUCTION MACHINES

    OpenAIRE

    Posviatenko, Ye; Kropivniy, V.; Posviatenko, N.; Rousskykh, V.

    2007-01-01

    Investigation into resource-saving technology of repair of gear-type pumps by contact welding -on some wear-resistant composite sintered powders on the top of teeth with further thermal-cycle treatment has been described.

  18. The development of robotic system for inspecting and repairing NPP primary coolant system of high-level radioactive environment

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Ho; Kim, Ki Ho; Jung, Seung Ho; Kim, Byung Soo; Hwang, Suk Yeoung; Kim, Chang Hoi; Seo, Yong Chil; Lee, Young Kwang; Lee, Yong Bum; Cho, Jai Wan; Lee, Jae Kyung; Lee, Yong Deok

    1997-07-01

    This project aims at developing a robotic system to automatically handle inspection and maintenance of NPP safety-related facilities in high-level radioactive environment. This robotic system under development comprises two robots depending on application fields - a mobile robot and multi-functional robot. The mobile robot is designed to be used in the area of primary coolant system during the operation of NPP. This robot enables to overcome obstacles and perform specified tasks in unstructured environment. The multi-functional robot is designed for performing inspection and maintenance tasks of steam generator and nuclear reactor vessel during the overhaul periods of NPP. Nuclear facilities can be inspected and repaired all the time by use of both the mobile robot and the multi-functional robot. Human operator, by teleoperation, monitors the movements of such robots located at remote task environment via video cameras and controls those remotely generating desired commands via master manipulator. We summarize the technology relating to the application of the mobile robot to primary coolant system environment, the applicability of the mobile robot through 3D graphic simulation, the design of the mobile robot, the design of its radiation-hardened controller. We also describe the mechanical design, modeling, and control system of the multi-functional robot. Finally, we present the design of the force-reflecting master and the modeling of virtual task environment for a training simulator. (author). 47 refs., 16 tabs., 43 figs.

  19. Workshop on DNA repair.

    NARCIS (Netherlands)

    A.R. Lehmann (Alan); J.H.J. Hoeijmakers (Jan); A.A. van Zeeland (Albert); C.M.P. Backendorf (Claude); B.A. Bridges; A. Collins; R.P.D. Fuchs; G.P. Margison; R. Montesano; E. Moustacchi; A.T. Natarajan; M. Radman; A. Sarasin; E. Seeberg; C.A. Smith; M. Stefanini (Miria); L.H. Thompson; G.P. van der Schans; C.A. Weber (Christine); M.Z. Zdzienika

    1992-01-01

    textabstractA workshop on DNA repair with emphasis on eukaryotic systems was held, under the auspices of the EC Concerted Action on DNA Repair and Cancer, at Noordwijkerhout (The Netherlands) 14-19 April 1991. The local organization of the meeting was done under the auspices of the Medical Genetic C

  20. Energy-dissipating and self-repairing SMA-ECC composite material system

    Science.gov (United States)

    Li, Xiaopeng; Li, Mo; Song, Gangbing

    2015-02-01

    Structural component ductility and energy dissipation capacity are crucial factors for achieving reinforced concrete structures more resistant to dynamic loading such as earthquakes. Furthermore, limiting post-event residual damage and deformation allows for immediate re-operation or minimal repairs. These desirable characteristics for structural ‘resilience’, however, present significant challenges due to the brittle nature of concrete, its deformation incompatibility with ductile steel, and the plastic yielding of steel reinforcement. Here, we developed a new composite material system that integrates the unique ductile feature of engineered cementitious composites (ECC) with superelastic shape memory alloy (SMA). In contrast to steel reinforced concrete (RC) and SMA reinforced concrete (SMA-RC), the SMA-ECC beams studied in this research exhibited extraordinary energy dissipation capacity, minimal residual deformation, and full self-recovery of damage under cyclic flexural loading. We found that the tensile strain capacity of ECC, tailored up to 5.5% in this study, allows it to work compatibly with superelastic SMA. Furthermore, the distributed microcracking damage mechanism in ECC is critical for sufficient and reliable recovery of damage upon unloading. This research demonstrates the potential of SMA-ECC for improving resilience of concrete structures under extreme hazard events.

  1. The structure of the Lingo-1 ectodomain, a module implicated in central nervous system repair inhibition.

    Science.gov (United States)

    Mosyak, Lidia; Wood, Andrew; Dwyer, Brian; Buddha, Madhavan; Johnson, Mark; Aulabaugh, Ann; Zhong, Xiaotian; Presman, Eleonora; Benard, Susan; Kelleher, Kerry; Wilhelm, James; Stahl, Mark L; Kriz, Ron; Gao, Ying; Cao, Zixuan; Ling, Huai-Ping; Pangalos, Menelas N; Walsh, Frank S; Somers, William S

    2006-11-24

    Nogo receptor (NgR)-mediated control of axon growth relies on the central nervous system-specific type I transmembrane protein Lingo-1. Interactions between Lingo-1 and NgR, along with a complementary co-receptor, result in neurite and axonal collapse. In addition, the inhibitory role of Lingo-1 is particularly important in regulation of oligodendrocyte differentiation and myelination, suggesting that pharmacological modulation of Lingo-1 function could be a novel approach for nerve repair and remyelination therapies. Here we report on the crystal structure of the ligand-binding ectodomain of human Lingo-1 and show it has a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. The structure, together with biophysical analysis of its solution properties, reveals that in the crystals and in solution Lingo-1 persistently associates with itself to form a stable tetramer and that it is its LRR-Ig-composite fold that drives such assembly. Specifically, in the crystal structure protomers of Lingo-1 associate in a ring-shaped tetramer, with each LRR domain filling an open cleft in an adjacent protomer. The tetramer buries a large surface area (9,200 A2) and may serve as an efficient scaffold to simultaneously bind and assemble the NgR complex components during activation on a membrane. Potential functional binding sites that can be identified on the ectodomain surface, including the site of self-recognition, suggest a model for protein assembly on the membrane.

  2. Cell and biomolecule delivery for tissue repair and regeneration in the central nervous system.

    Science.gov (United States)

    Elliott Donaghue, Irja; Tam, Roger; Sefton, Michael V; Shoichet, Molly S

    2014-09-28

    Tissue engineering frequently involves cells and scaffolds to replace damaged or diseased tissue. It originated, in part, as a means of effecting the delivery of biomolecules such as insulin or neurotrophic factors, given that cells are constitutive producers of such therapeutic agents. Thus cell delivery is intrinsic to tissue engineering. Controlled release of biomolecules is also an important tool for enabling cell delivery since the biomolecules can enable cell engraftment, modulate inflammatory response or otherwise benefit the behavior of the delivered cells. We describe advances in cell and biomolecule delivery for tissue regeneration, with emphasis on the central nervous system (CNS). In the first section, the focus is on encapsulated cell therapy. In the second section, the focus is on biomolecule delivery in polymeric nano/microspheres and hydrogels for the nerve regeneration and endogenous cell stimulation. In the third section, the focus is on combination strategies of neural stem/progenitor cell or mesenchymal stem cell and biomolecule delivery for tissue regeneration and repair. In each section, the challenges and potential solutions associated with delivery to the CNS are highlighted.

  3. Cellular and molecular phenotypes depending upon the RNA repair system RtcAB of Escherichia coli

    Science.gov (United States)

    Engl, Christoph; Schaefer, Jorrit; Kotta-Loizou, Ioly; Buck, Martin

    2016-01-01

    RNA ligases function pervasively across the three kingdoms of life for RNA repair, splicing and can be stress induced. The RtcB protein (also HSPC117, C22orf28, FAAP and D10Wsu52e) is one such conserved ligase, involved in tRNA and mRNA splicing. However, its physiological role is poorly described, especially in bacteria. We now show in Escherichia coli bacteria that the RtcR activated rtcAB genes function for ribosome homeostasis involving rRNA stability. Expression of rtcAB is activated by agents and genetic lesions which impair the translation apparatus or may cause oxidative damage in the cell. Rtc helps the cell to survive challenges to the translation apparatus, including ribosome targeting antibiotics. Further, loss of Rtc causes profound changes in chemotaxis and motility. Together, our data suggest that the Rtc system is part of a previously unrecognized adaptive response linking ribosome homeostasis with basic cell physiology and behaviour. PMID:27402162

  4. Cellular and molecular phenotypes depending upon the RNA repair system RtcAB of Escherichia coli.

    Science.gov (United States)

    Engl, Christoph; Schaefer, Jorrit; Kotta-Loizou, Ioly; Buck, Martin

    2016-11-16

    RNA ligases function pervasively across the three kingdoms of life for RNA repair, splicing and can be stress induced. The RtcB protein (also HSPC117, C22orf28, FAAP and D10Wsu52e) is one such conserved ligase, involved in tRNA and mRNA splicing. However, its physiological role is poorly described, especially in bacteria. We now show in Escherichia coli bacteria that the RtcR activated rtcAB genes function for ribosome homeostasis involving rRNA stability. Expression of rtcAB is activated by agents and genetic lesions which impair the translation apparatus or may cause oxidative damage in the cell. Rtc helps the cell to survive challenges to the translation apparatus, including ribosome targeting antibiotics. Further, loss of Rtc causes profound changes in chemotaxis and motility. Together, our data suggest that the Rtc system is part of a previously unrecognized adaptive response linking ribosome homeostasis with basic cell physiology and behaviour. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. In-situ engineering of cartilage repair: a pre-clinical in-vivo exploration of a novel system.

    Science.gov (United States)

    Seedhom, B B; Luo, Z-J; Goldsmith, A J; Toyoda, T; Lorrison, J C; Guardamagna, L

    2007-07-01

    This investigation explores a new cartilage repair technique that uses a novel method to secure a non-woven multifilamentous scaffold in the defect site after microfracture. The hypothesis is that a scaffold provides a larger surface area for attachment and proliferation of the mesenchymal stem cells that migrate from the bone marrow. Two in-vivo studies were undertaken in an ovine model. The first study, which lasted for 8 weeks, aimed to compare the new technique with microfracture. Chondral defects, 7 mm in diameter, were created in both femoral medial condyles of five ewes. One defect was treated with the new technique while the contralateral knee was treated with microfracture alone. The results revealed that the quantity of repair tissue was significantly greater in the defects treated with the new system. The second study had two time points, 3 and 6 months, and used 13 ewes. In this study, both defects were treated with the new technique but one received additional subchondral drilling in order to stimulate extra tissue growth. The majority of the implants had good tissue induction, filling 50-100 per cent of the defect volume, while the compressive modulus of the repairs was in the range of 40-70 per cent of that for the surrounding cartilage. In addition, hyaline-like cartilage was seen in all the repairs which had the additional drilling of the subchondral bone.

  6. Detecting and Correcting Speech Repairs

    CERN Document Server

    Heeman, P A; Heeman, Peter; Allen, James

    1994-01-01

    Interactive spoken dialog provides many new challenges for spoken language systems. One of the most critical is the prevalence of speech repairs. This paper presents an algorithm that detects and corrects speech repairs based on finding the repair pattern. The repair pattern is built by finding word matches and word replacements, and identifying fragments and editing terms. Rather than using a set of prebuilt templates, we build the pattern on the fly. In a fair test, our method, when combined with a statistical model to filter possible repairs, was successful at detecting and correcting 80\\% of the repairs, without using prosodic information or a parser.

  7. Tendon repair

    Science.gov (United States)

    Repair of tendon ... Tendon repair can be performed using: Local anesthesia (the immediate area of the surgery is pain-free) ... a cut on the skin over the injured tendon. The damaged or torn ends of the tendon ...

  8. Effect of four different surface treatments on shear bond strength of three porcelain repair systems: An in vitro study

    Directory of Open Access Journals (Sweden)

    Ritesh Gourav

    2013-01-01

    Full Text Available Background: Ceramic fracture in metal ceramic restorations are serious and pose an aesthetic and functional dilemma both for the patients and the dentist. This has created a demand for the development of practical repair options which do not necessitate the removal and remake of entire restorations. Aim: To evaluate and compare the effect of four different surface treatments on shear bond strength of metal ceramic specimens with three commercially available porcelain repair systems. Materials and Methods: Specimens were fabricated with a base-metal ceramic alloy and divided into three groups, to evaluate three porcelain repair systems. Each group was divided into four subgroups based on surface treatment (A sandblasting, (B sandblasting followed by etching with 9% HF (Hydrofluoric acid on surrounding ceramic, (C Use of a diamond bur on exposed metal followed by etching with 37% H 3 PO 4 and (D Control groups (D 1 , D 2 , D 3 for three groups of porcelain repair system which was not subjected to further treatment after finishing with 240 grit silicon carbide paper grinding. Shear bond strength of each group of specimens based on surface treatment were evaluated with a universal testing machine after storing in distilled water for 7 days. One way ANOVA and Tukey-HSD procedure were used to compare the mean values between and among the groups. Results: The mean shear bond strength of group III (10.402 ± 1.055 were significantly higher than group I (8.647 ± 0.990 and group II (8.099 ± 0.600 for all surface treatments. However the mean values of shear bond strength of sub-group A were significantly higher than sub-group C and D but were not significantly higher than sub-group B. Conclusion: The results of this study suggest that in fractured metal ceramic restorations the exposed metal surface treated with sandblasting or sandblasting and etching the surrounding ceramic surface with HF can increase the shear bond strength of the repaired metal

  9. Ranking of small scale proposals for water system repair using the Rapid Impact Assessment Matrix (RIAM)

    Energy Technology Data Exchange (ETDEWEB)

    Shakib-Manesh, T.E.; Hirvonen, K.O.; Jalava, K.J.; Ålander, T.; Kuitunen, M.T., E-mail: markku.kuitunen@jyu.fi

    2014-11-15

    Environmental impacts of small scale projects are often assessed poorly, or not assessed at all. This paper examines the usability of the Rapid Impact Assessment Matrix (RIAM) as a tool to prioritize project proposals for small scale water restoration projects in relation to proposals' potential to improve the environment. The RIAM scoring system was used to assess and rank the proposals based on their environmental impacts, the costs of the projects to repair the harmful impacts, and the size of human population living around the sites. A four-member assessment group (The expert panel) gave the RIAM-scores to the proposals. The assumed impacts of the studied projects at the Eastern Finland water systems were divided into the ecological and social impacts. The more detailed assessment categories of the ecological impacts in this study were impacts on landscape, natural state, and limnology. The social impact categories were impacts to recreational use of the area, fishing, industry, population, and economy. These impacts were scored according to their geographical and social significance, their magnitude of change, their character, permanence, reversibility, and cumulativeness. The RIAM method proved to be an appropriate and recommendable method for the small-scale assessment and prioritizing of project proposals. If the assessments are well documented, the RIAM can be a method for easy assessing and comparison of the various kinds of projects. In the studied project proposals there were no big surprises in the results: the best ranks were received by the projects, which were assumed to return watersheds toward their original state.

  10. Dilemmas of a vitalizing vaccine market: lessons from the MMR vaccine/autism debate.

    Science.gov (United States)

    Bragesjö, Fredrik; Hallberg, Margareta

    2011-03-01

    A number of issues related to vaccines and vaccinations in society are discussed in this paper. Our purpose is to merge an analysis of some recent changes in the vaccine market with social science research on the relationship between citizens and authorities. The article has two empirical parts. The first shows how the vaccine market, which for many years has had immense financial problems, nowadays seems to becoming economically vitalized, mostly due to the production of new and profitable vaccines. However prosperous the future may appear, certain reactions from the public regarding vaccination initiatives offer insight into inherent problems of vaccine policies in many Western countries. In the second part of the article, these problems are exemplified with the recent controversy over the MMR (measles, mumps, and rubella) vaccine. We conclude that in spite of the improving profit-margins, the vaccine market remains vulnerable and insecure. Vaccines are permeated by society, even more so than pharmaceutics that are used to cure or alleviate illnesses. Radical changes in financial conditions with promises of a more profitable market will not, we argue, solve other even more fundamental problems.

  11. Timely MMR vaccination in infancy: influence of attitudes and medical advice on the willingness to vaccinate.

    Science.gov (United States)

    Schönberger, K; Ludwig, M-S; Wildner, M; Kalies, H

    2012-11-01

    In light of the failure to eliminate measles by 2010, the closure of any gaps in immunisation coverage is of paramount importance to interrupt transmission and to protect vulnerable individuals. Not only vaccination-critical attitudes of parents but furthermore the medical advice by physician in charge influence the vaccine uptake. 3 groups of factors which potentially influence parental decisions on child vaccination were analysed by univariable and multivariable logistic regression for the timely uptake of the first and the second dose of measles vaccination: parents' attitudes towards immunization, the influence of medical and laypersons and the influence of the advice of a medical doctor. A total of 3 041 children were eligible for the analysis. 53.0% of these received the first and 42.9% the second MMR dose in time. If parents considered that vaccinations are important and protective as well as the consulted physician advices towards vaccinations, children had significantly higher chances of a timely vaccination. Whereas, if parents were afraid of vaccinations or get advised by an alternative practitioner, the children had lower chances of being vaccinated in time. If medical providers help parents to reduce uncertainties about vaccination the chance for children to be vaccinated in time increased. It appeared that there still are unmet information needs after the medical consultation. By and large the medical advice plays an important role for vaccination uptake and its timing. In order to raise the vaccination rates further target-population specific approaches are needed.

  12. Using electronic mail to improve MMR uptake amongst third level students.

    LENUS (Irish Health Repository)

    Cooney, F

    2010-03-01

    This study assessed the usefulness of email in informing third level students about special MMR clinics being provided on campus during a mumps outbreak in the North West of Ireland. Email messages were sent directly to students, informing them of the clinics, inviting them to make a clinic appointment by email and providing details of walk-in clinics. At the clinics, all 177 attendees were asked to fill out a questionnaire and the response rate was 89% (n=158). Regarding the main sources of information about the vaccination clinics, email was selected by 117 (74%) students, word-of-mouth by 27 (17%), posters\\/leaflets by 8 (5%), and other sources by 6 (4%). Use of email as a source of information was rated as very good\\/excellent by 115 (73%), as good by 35 (22%) and poor\\/fair by 8 (5%). This study demonstrates that email is a useful and acceptable way of informing third level students about immunisation clinics in an outbreak situation.

  13. Using electronic mail to improve MMR uptake amongst third level students.

    Science.gov (United States)

    Cooney, F; Ryan, A; Schinaia, N; Breslin, A

    2010-03-01

    This study assessed the usefulness of email in informing third level students about special MMR clinics being provided on campus during a mumps outbreak in the North West of Ireland. Email messages were sent directly to students, informing them of the clinics, inviting them to make a clinic appointment by email and providing details of walk-in clinics. At the clinics, all 177 attendees were asked to fill out a questionnaire and the response rate was 89% (n=158). Regarding the main sources of information about the vaccination clinics, email was selected by 117 (74%) students, word-of-mouth by 27 (17%), posters/leaflets by 8 (5%), and other sources by 6 (4%). Use of email as a source of information was rated as very good/excellent by 115 (73%), as good by 35 (22%) and poor/fair by 8 (5%). This study demonstrates that email is a useful and acceptable way of informing third level students about immunisation clinics in an outbreak situation.

  14. Kinetic Metallization. Repair of IVD Al Coatings and Mg Alloys Aircraft Components Using Portable Kinetic Metallization Systems

    Science.gov (United States)

    2008-02-27

    person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number...aircraft carriers & depots Environmentally sustainable Meets Navy JTP-2003 Portable system & Handheld spray gun Robotic deployment for OEM Applications...Problem - Field & Depot Repair of Damaged IVD-Al & Mg Alloys NADEP Facilities PEO(T) F/A-18, EA-18G PMA -271 E-6B

  15. Healthcare workers and measles-mumps-rubella (MMR) status: how worried should we be about further outbreaks?

    Science.gov (United States)

    Basu, S; Giri, P; Adisesh, A; McNAUGHT, R

    2014-08-01

    Recently, a number of outbreaks of measles and mumps have occurred within the UK and Europe. Healthcare workers (HCWs) are at risk of contracting and transmitting disease to patients and staff. To examine this risk at the point of entry to healthcare, we assessed the serological results of new HCWs presenting for pre-placement clearance without evidence of measles-mumps-rubella (MMR) immunity between 1 April 2010 and 31 March 2012. Overall rates of serological positivity to MMR across all age groups were 88·2%, 68·8% and 93·9%, respectively. With regard to measles and mumps, there were statistically significant decreases in the percentage of HCWs born after 1980 that had positive serology (P outbreak within this cohort of HCWs appears low.

  16. Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age

    DEFF Research Database (Denmark)

    Møller, Pål; Seppälä, Toni; Bernstein, Inge

    2017-01-01

    : This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age. RESULTS: 3119 patients were followed for a total of 24 475 years. Cumulative incidences at 75 years (risks) for colorectal cancer were 46%, 43......% and 18%; and for brain tumours 1%, 5% and 1%, respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper gastrointestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder 93%, ureter 85......%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had lower risk for cancer. CONCLUSION: Carriers of different path_MMR variants exhibit distinct patterns of cancer risk and survival as they age. Risk estimates for counselling and planning of surveillance and treatment...

  17. FANCJ localization by mismatch repair is vital to maintain genomic integrity after UV irradiation.

    Science.gov (United States)

    Guillemette, Shawna; Branagan, Amy; Peng, Min; Dhruva, Aashana; Schärer, Orlando D; Cantor, Sharon B

    2014-02-01

    Nucleotide excision repair (NER) is critical for the repair of DNA lesions induced by UV radiation, but its contribution in replicating cells is less clear. Here, we show that dual incision by NER endonucleases, including XPF and XPG, promotes the S-phase accumulation of the BRCA1 and Fanconi anemia-associated DNA helicase FANCJ to sites of UV-induced damage. FANCJ promotes replication protein A phosphorylation and the arrest of DNA synthesis following UV irradiation. Interaction defective mutants of FANCJ reveal that BRCA1 binding is not required for FANCJ localization, whereas interaction with the mismatch repair (MMR) protein MLH1 is essential. Correspondingly, we find that FANCJ, its direct interaction with MLH1, and the MMR protein MSH2 function in a common pathway in response to UV irradiation. FANCJ-deficient cells are not sensitive to killing by UV irradiation, yet we find that DNA mutations are significantly enhanced. Thus, we considered that FANCJ deficiency could be associated with skin cancer. Along these lines, in melanoma we found several somatic mutations in FANCJ, some of which were previously identified in hereditary breast cancer and Fanconi anemia. Given that, mutations in XPF can also lead to Fanconi anemia, we propose collaborations between Fanconi anemia, NER, and MMR are necessary to initiate checkpoint activation in replicating human cells to limit genomic instability.

  18. Mutation mismatch repair gene deletions in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Couronné, Lucile; Ruminy, Philippe; Waultier-Rascalou, Agathe; Rainville, Vinciane; Cornic, Marie; Picquenot, Jean-Michel; Figeac, Martin; Bastard, Christian; Tilly, Hervé; Jardin, Fabrice

    2013-05-01

    To further unravel the molecular pathogenesis of diffuse large B-cell lymphoma (DLBCL), we performed high-resolution comparative genomic hybridization on lymph node biopsies from 70 patients. With this strategy, we identified microdeletions of genes involved in the mutation mismatch repair (MMR) pathway in two samples. The first patient presented with a homozygous deletion of MSH2-MSH6 due to duplication of an unbalanced pericentric inversion of chromosome 2. The other case showed a PMS2 heterozygous deletion. PMS2 and MSH2-MSH6 abnormalities, respectively, resulted in a decrease and complete loss of gene expression. However, unlike tumors associated with the hereditary non-polyposis colorectal cancer syndrome or immunodeficiency-related lymphomas, no microsatellite instability was detected. Mutational profiles revealed especially in one patient an aberrant hypermutation without a clear activation-induced cytidine deaminase signature, indicating a breakdown of the high-fidelity repair in favor of the error-prone repair pathway. Our findings suggest that in a rare subset of patients, inactivation of the genes of the MMR pathway is likely an important step in the molecular pathogenesis of DLBCL and does not involve the same molecular mechanisms as other common neoplasms with MMR deficiency.

  19. Stepwise deletions of polyA sequences in mismatch repair-deficient colorectal cancers.

    Science.gov (United States)

    Blake, C; Tsao, J L; Wu, A; Shibata, D

    2001-05-01

    PolyA simple repeat sequence deletions are common in tumors with microsatellite instability (MSI+). Such deletions occur one base at a time in DNA mismatch repair (MMR)-deficient yeast suggesting larger deletions in human MSI+ tumors represent multiple sequential stepwise losses. Sum total deletions in four polyA repeats were variable (between -17 to -45 bp) in 20 sporadic MSI+ colorectal cancers. Progressive but less extensive total deletions (maximum of -12 bp) occurred in similar polyA sequences in MMR-deficient mice (mlh1-/-) up to 478 days old. PolyA repeat lengths were relatively stable but already shortened in the MMR-deficient cell line HCT116. A transgene with 26 A's transfected into HCT116 shortened an average of 3.8 bases pairs after 469 days in culture, less than average deletions of BAT25 (-5.3) or BAT26 (-9.0) in MSI+ cancers. These findings further suggest that extensive polyA deletions common in MSI+ tumors likely reflect multiple stepwise smaller deletions that accumulate more than hundreds of divisions after loss of MMR.

  20. Antibody persistence in children aged 6-7years one year following booster immunization with two MMR vaccines applied by aerosol or by injection.

    Science.gov (United States)

    Díaz Ortega, José Luis; Castaneda, Deyanira; Arellano Quintanilla, Doris Ma; Martínez, David; Trumbo, Silas P; Fernández de Castro, Jorge

    2017-05-25

    In a previous study on booster vaccination, we reported that two aerosolized MMR vaccines were as safe and immunogenic as injectable vaccines containing the same antigens. We now present results of antibody persistence one year after immunization. To assess the antibody persistence for measles, mumps, and rubella one year following booster immunization. We performed clinical and serological follow-up of participants in a previous study of Mexican children aged 6-7years, in which participants were randomized to four groups receiving, by aerosolized or by injection, the MMR SII vaccine (Serum Institute of India), or the MMR II (Merck Sharp & Dhome). We evaluated the antibody persistence by PRN test for measles and by ELISA for rubella and mumps. The occurrence of clinical events was evaluated via periodic visits of a nurse team to children's schools and homes. Of the 260 initial participants, 241 completed one-year follow-up. There were only statistically significant differences in baseline seropositivity for mumps. One year after immunization, seropositivity in all groups was 100% for measles and rubella. The seropositivity rank for mumps was from 90.3% for the injected vaccine MMR II to 96.6% for vaccine MMR SII applied by aerosol; these differences were not statistically significant. With exception of the aerosolized vaccine MMR SII for the geometric mean titer (GMT) for measles, all study groups presented declination of GMT for the three viruses. The difference between the aerosolized vaccines MMR SII and MMR RII was statistically significant for mumps antibodies. Only mild clinical events were identified. Under conditions of no endemic transmission for measles and rubella, and of low circulation of mumps virus, school-aged children remained seropositive to the three viruses one year following booster immunization. The study was registered under CMN 2010-005 number at COFEPRIS (National Regulatory Authority). Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. 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...

  2. Bladder exstrophy repair

    Science.gov (United States)

    Bladder birth defect repair; Everted bladder repair; Exposed bladder repair; Repair of bladder exstrophy ... Bladder exstrophy repair involves two surgeries. The first surgery is to repair the bladder and the second one is to attach ...

  3. Complex DNA repair pathways as possible therapeutic targets to overcome temozolomide resistance in glioblastoma

    Directory of Open Access Journals (Sweden)

    Koji eYoshimoto

    2012-12-01

    Full Text Available Many conventional chemotherapeutic drugs exert their cytotoxic function by inducing DNA damage in the tumor cell. Therefore, a cell-inherent DNA repair pathway, which reverses the DNA-damaging effect of the cytotoxic drugs, can mediate therapeutic resistance to chemotherapy. The monofunctional DNA-alkylating agent temozolomide (TMZ is a commonly used chemotherapeutic drug and the gold standard treatment for glioblastoma. Although the activity of DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT has been described as the main modulator to determine the sensitivity of glioblastoma to TMZ, a subset of glioblastoma does not respond despite MGMT inactivation, suggesting that another DNA repair mechanism may also modulate the tolerance to TMZ. Considerable interest has focused on MGMT, mismatch repair (MMR, and the base-excision repair (BER pathway in the mechanism of mediating TMZ resistance, but emerging roles for the DNA strand-break repair pathway have been demonstrated. In the first part of this review article, we briefly review the significant role of MGMT, MMR, and the BER pathway in the tolerance to TMZ; in the last part, we review the recent publications that demonstrate possible roles of DNA strand-break repair pathways, such as single-strand break (SSB repair and double-strand break (DSB repair, as well as the Fanconi anemia pathway in the repair process after alkylating agent-based therapy. It is possible that all of these repair pathways have a potential to modulate the sensitivity to TMZ and aid in overcoming the therapeutic resistance in the clinic.

  4. DREMECELS: A Curated Database for Base Excision and Mismatch Repair Mechanisms Associated Human Malignancies.

    Directory of Open Access Journals (Sweden)

    Ankita Shukla

    Full Text Available DNA repair mechanisms act as a warrior combating various damaging processes that ensue critical malignancies. DREMECELS was designed considering the malignancies with frequent alterations in DNA repair pathways, that is, colorectal and endometrial cancers, associated with Lynch syndrome (also known as HNPCC. Since lynch syndrome carries high risk (~40-60% for both cancers, therefore we decided to cover all three diseases in this portal. Although a large population is presently affected by these malignancies, many resources are available for various cancer types but no database archives information on the genes specifically for only these cancers and disorders. The database contains 156 genes and two repair mechanisms, base excision repair (BER and mismatch repair (MMR. Other parameters include some of the regulatory processes that have roles in these disease progressions due to incompetent repair mechanisms, specifically BER and MMR. However, our unique database mainly provides qualitative and quantitative information on these cancer types along with methylation, drug sensitivity, miRNAs, copy number variation (CNV and somatic mutations data. This database would serve the scientific community by providing integrated information on these disease types, thus sustaining diagnostic and therapeutic processes. This repository would serve as an excellent accompaniment for researchers and biomedical professionals and facilitate in understanding such critical diseases. DREMECELS is publicly available at http://www.bioinfoindia.org/dremecels.

  5. Missed Opportunities for Measles, Mumps, and Rubella (MMR Immunization in Mesoamerica: Potential Impact on Coverage and Days at Risk.

    Directory of Open Access Journals (Sweden)

    Ali H Mokdad

    Full Text Available Recent outbreaks of measles in the Americas have received news and popular attention, noting the importance of vaccination to population health. To estimate the potential increase in immunization coverage and reduction in days at risk if every opportunity to vaccinate a child was used, we analyzed vaccination histories of children 11-59 months of age from large household surveys in Mesoamerica.Our study included 22,234 children aged less than 59 months in El Salvador, Guatemala, Honduras, Mexico, Nicaragua, and Panama. Child vaccination cards were used to calculate coverage of measles, mumps, and rubella (MMR and to compute the number of days lived at risk. A child had a missed opportunity for vaccination if their card indicated a visit for vaccinations at which the child was not caught up to schedule for MMR. A Cox proportional hazards model was used to compute the hazard ratio associated with the reduction in days at risk, accounting for missed opportunities.El Salvador had the highest proportion of children with a vaccine card (91.2% while Nicaragua had the lowest (76.5%. Card MMR coverage ranged from 44.6% in Mexico to 79.6% in Honduras while potential coverage accounting for missed opportunities ranged from 70.8% in Nicaragua to 96.4% in El Salvador. Younger children were less likely to have a missed opportunity. In Panama, children from households with higher expenditure were more likely to have a missed opportunity for MMR vaccination compared to the poorest (OR 1.62, 95% CI: 1.06-2.47. In Nicaragua, compared to children of mothers with no education, children of mothers with primary education and secondary education were less likely to have a missed opportunity (OR 0.46, 95% CI: 0.24-0.88 and OR 0.25, 95% CI: 0.096-0.65, respectively. Mean days at risk for MMR ranged from 158 in Panama to 483 in Mexico while potential days at risk ranged from 92 in Panama to 239 in El Salvador.Our study found high levels of missed opportunities for

  6. Missed Opportunities for Measles, Mumps, and Rubella (MMR) Immunization in Mesoamerica: Potential Impact on Coverage and Days at Risk.

    Science.gov (United States)

    Mokdad, Ali H; Gagnier, Marielle C; Colson, K Ellicott; Dansereau, Emily; Zúñiga-Brenes, Paola; Ríos-Zertuche, Diego; Haakenstad, Annie; Johanns, Casey K; Palmisano, Erin B; Hernandez, Bernardo; Iriarte, Emma

    2015-01-01

    Recent outbreaks of measles in the Americas have received news and popular attention, noting the importance of vaccination to population health. To estimate the potential increase in immunization coverage and reduction in days at risk if every opportunity to vaccinate a child was used, we analyzed vaccination histories of children 11-59 months of age from large household surveys in Mesoamerica. Our study included 22,234 children aged less than 59 months in El Salvador, Guatemala, Honduras, Mexico, Nicaragua, and Panama. Child vaccination cards were used to calculate coverage of measles, mumps, and rubella (MMR) and to compute the number of days lived at risk. A child had a missed opportunity for vaccination if their card indicated a visit for vaccinations at which the child was not caught up to schedule for MMR. A Cox proportional hazards model was used to compute the hazard ratio associated with the reduction in days at risk, accounting for missed opportunities. El Salvador had the highest proportion of children with a vaccine card (91.2%) while Nicaragua had the lowest (76.5%). Card MMR coverage ranged from 44.6% in Mexico to 79.6% in Honduras while potential coverage accounting for missed opportunities ranged from 70.8% in Nicaragua to 96.4% in El Salvador. Younger children were less likely to have a missed opportunity. In Panama, children from households with higher expenditure were more likely to have a missed opportunity for MMR vaccination compared to the poorest (OR 1.62, 95% CI: 1.06-2.47). In Nicaragua, compared to children of mothers with no education, children of mothers with primary education and secondary education were less likely to have a missed opportunity (OR 0.46, 95% CI: 0.24-0.88 and OR 0.25, 95% CI: 0.096-0.65, respectively). Mean days at risk for MMR ranged from 158 in Panama to 483 in Mexico while potential days at risk ranged from 92 in Panama to 239 in El Salvador. Our study found high levels of missed opportunities for immunizing

  7. Truncation of the MSH2 C-terminal 60 amino acids disrupts effective DNA mismatch repair and is causative for Lynch syndrome.

    Science.gov (United States)

    Wielders, Eva; Delzenne-Goette, Elly; Dekker, Rob; van der Valk, Martin; Te Riele, Hein

    2017-04-01

    Missense variants of DNA mismatch repair (MMR) genes pose a problem in clinical genetics as long as they cannot unambiguously be assigned as the cause of Lynch syndrome (LS). To study such variants of uncertain clinical significance, we have developed a functional assay based on direct measurement of MMR activity in mouse embryonic stem cells expressing mutant protein from the endogenous alleles. We have applied this protocol to a specific truncation mutant of MSH2 that removes 60 C-terminal amino acids and has been found in suspected LS families. We show that the stability of the MSH2/MSH6 heterodimer is severely perturbed, causing attenuated MMR in in vitro assays and cancer predisposition in mice. This mutation can therefore unambiguously be considered as deleterious and causative for LS.

  8. Optimum repair-level analysis (ORLA) and life cycle cost (LCC) models for the base and installation security system (BISS)

    Energy Technology Data Exchange (ETDEWEB)

    York, A.A.; Chipchak, J.S.

    1979-03-01

    Models for Optimum Repair-Level Analysis (ORLA) and Life Cycle Cost (LCC) analysis for Base and Installation Security System (BISS) equipment are described. The ORLA model determines the costs of alternative maintenance approaches for selection of the most economic maintenance approach. The LCC model determines the total cost to the Government for the development, acquisition, initial logistics support, and recurring support of a system over the projected inventory usage period. A unique feature of these models is the marriage of ORLA and ICC which enables LCC to utilize completely the most economic ORLA decision costs. This significantly reduces the overall LCC effort.

  9. ULTRAPRO Hernia System versus lichtenstein repair in treatment of primary inguinal hernias: a prospective randomized controlled study.

    Science.gov (United States)

    Karateke, Faruk; Ozyazici, Sefa; Menekse, Ebru; Özdogan, Hatice; Kunt, Mevlüt; Bozkurt, Hilmi; Bali, İlhan; Özdogan, Mehmet

    2014-01-01

    The Lichtenstein repair has been recommended as the gold standard for inguinal hernia repair. However, postoperative discomfort still constitutes a concern and an area for improvement. New mesh materials have been continuously introduced to achieve this goal. The goal of the present study was to investigate the outcomes of ULTRAPRO Hernia System (UHS) compared with Lichtenstein mesh repair. A total of 99 male patients with primary unilateral inguinal hernia were included in the study during the period of September 2010-January 2012. Patients with body mass index>30, comorbid diseases, and anesthetic risk of ASA-III and ASA-IV were excluded. The patients were randomly allocated to operation with the Lichtenstein technique (group L) or UHS. Demographics, operative and postoperative/recovery data, and short- and medium-term outcomes of the patients were recorded. A total of 50 patients in group L and 49 patients in group UHS were analyzed. The median follow-up time for the study was 33 months. There were no significant differences regarding demographics, complications, and rehabilitation between the groups. Overall, there was a prolonged operation time in the UHS group compared with the L group (UHS: 53.7±5.7 minutes; L: 44.5±5.5 minutes; Phernias regarding perioperative course, complications, recovery, and recurrence rates. However, because of reduced costs and the lack of need for the exploration of the preperitoneal space, we conclude that the Lichtenstein technique should be recommended as the first choice.

  10. High pulse pressure is not associated with abnormal activation of the renin-angiotensin-aldosterone system in repaired aortic coarctation.

    Science.gov (United States)

    Pedersen, T A L; Pedersen, E B; Munk, K; Hjortdal, V E; Emmertsen, K; Andersen, N H

    2015-04-01

    We investigated the relationship between pulse pressure (PP)--a surrogate marker of arterial stiffness-and activity of the renin-angiotensin-aldosterone system (RAAS) in adult patients with repaired coarctation and normal left ventricular (LV) function. A total of 114 patients (44 (26-74) years, 13 (0.1-40) years at repair) and 20 healthy controls were examined with 24-h ambulatory blood pressure monitoring, echocardiography, vasoactive hormone levels and magnetic resonance of the thoracic aorta. Forty-one patients (36%) were taking antihypertensives (28 RAAS inhibitors). Fifty-one had mean 24-h blood pressures >130/80 mm Hg. Hypertension was not associated with age at repair (P=0.257). Patients had higher PP and LV mass compared with controls (52±11 vs. 45±5 mm Hg and 221±71 vs. 154±55 g, respectively; both Pcoarctation have increased PP and LV mass compared with controls. PP increased with increasing recoarctation. Hypertension was present also in the absence of recoarctation. These changes could not be explained by abnormal activation of the RAAS.

  11. Endogenous bioelectric ifelds:a putative regulator of wound repair and regeneration in the central nervous system

    Institute of Scientific and Technical Information of China (English)

    Matthew L.Baer; Raymond J.Colello

    2016-01-01

    Studies on a variety of highly regenerative tissues, including the central nervous system (CNS) in non-mammalian vertebrates, have consistently demonstrated that tissue damage induces the formation of an ionic current at the site of injury. These injury currents generate electric ifelds (EF) that are 100-fold increased in intensity over that measured for uninjured tissue.In vitro and in vivo experiments have con-vincingly demonstrated that these electric ifelds (by their orientation, intensity and duration) can drive the migration, proliferation and differentiation of a host of cell types. These cellular behaviors are all necessary to facilitate regeneration as blocking these EFs at the site of injury inhibits tissue repair while enhancing their intensity promotes repair. Consequently, injury-induced currents, and the EFs they produce, represent a potent and crucial signal to drive tissue regeneration and repair. In this review, we will discuss how injury currents are generated, how cells detect these currents and what cellular responses they can induce. Addi-tionally, we will describe the growing evidence suggesting that EFs play a key role in regulating the cellular response to injury and may be a therapeutic target for inducing regeneration in the mammalian CNS.

  12. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Bill Bruce; Nancy Porter; George Ritter; Matt Boring; Mark Lozev; Ian Harris; Bill Mohr; Dennis Harwig; Robin Gordon; Chris Neary; Mike Sullivan

    2005-07-20

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  13. Multiobjective optimization of availability and cost in repairable systems design via genetic algorithms and discrete event simulation

    Directory of Open Access Journals (Sweden)

    Isis Didier Lins

    2009-04-01

    Full Text Available This paper attempts to provide a more realistic approach to the characterization of system reliability when handling redundancy allocation problems: it considers repairable series-parallel systems comprised of components subjected to corrective maintenance actions with failure-repair cycles modeled by renewal processes. A multiobjective optimization approach is applied since increasing the number of redundancies not only enlarges system reliability but also its associated costs. Then a multiobjective genetic algorithm is coupled with discrete event simulation and its solutions present the compromise between system reliability and cost. Two examples are provided. In the first one, the proposed algorithm is validated by comparison with results obtained from a system devised as to allow for analytical solutions of the objective functions. The second case analyzes a repairable system subjected to perfect repairs. Results from both examples show that the proposed method can be a valuable tool for the decision maker when choosing the system design.Esse artigo utiliza uma abordagem mais realista para a caracterização da confiabilidade de sistemas em problemas de alocação de redundâncias: são considerados sistemas série-paralelo formados por componentes sujeitos a ações de manutenção corretiva com ciclos de falha-reparo modelados por processos de renovação. É aplicada uma abordagem de otimização multiobjetivo, pois o aumento de redundâncias eleva a confiabilidade do sistema e também os seus custos. Assim, um algoritmo genético multiobjetivo é integrado com simulação discreta de eventos e suas soluções apresentam o compromisso entre confiabilidade e custo do sistema. Dois exemplos são fornecidos. No primeiro, o algoritmo proposto é validado através da comparação com resultados obtidos de um sistema criado de forma a permitir soluções analíticas das funções-objetivo. No segundo, analisa-se um sistema reparável sujeito a

  14. Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-deficient colorectal cancers

    Institute of Scientific and Technical Information of China (English)

    Marie-Pierre Buisine; Thècla Lesuffleur; Agnès Wacrenier; Christophe Mariette; Emmanuelle Leteurtre; Fabienne Escande; Sana Aissi; Amandine Ketele; Annette Leclercq; Nicole Porchet

    2008-01-01

    AIM:To investigate the polymorphic simple sequence repeat in intron 1 of the epidermal growth factor receptor gene(EGFR)(CA-SSR I),which is known to affect the efficiency of gene transcription as a putative target of the mismatch repair (MMR) machinery in colorectal tumors.METHODS:The CA-SSR I genotype was analyzed in a total of 86 primary colorectal tumors,selected upon their microsatellite instability (MSI) status [42 with high frequency MSI (MSI-H) and 44 microsatellite stable (MSS)]and their respective normal tissue.The effect of the CASSR I genotype on the expression of the EGFR gene was evaluated in 18 specimens using quantitative real-time reverse transcription PCR and immunohistochemistry.RESULTS:Mutations in CA-SSR I were detected in 86%(36 of 42) of MSI-H colorectal tumors and 0% (0 of 44) of MSS tumors,indicating the EGFR gene as a novel putative specific target of the defective MMR system (P<0.001).Impaired expression of EGFR was detected in most of the colorectal tumors analyzed [6/12 (50%) at the mRNA level and 15/18 (83%) at the peptide level].However,no association was apparent between EGFR expression and CA-SSR I status in tumors or normal tissues.CONCLUSION:Our results suggest that CA-SSR I sequence does not contribute to the regulation of EGFR transcription in colon,and should thus not be considered as a promising predictive marker for response to EGFR inhibitors in patients with colorectal cancer.

  15. Developing a bi-objective optimization model for solving the availability allocation problem in repairable series-parallel systems by NSGA II

    Science.gov (United States)

    Amiri, Maghsoud; Khajeh, Mostafa

    2016-11-01

    Bi-objective optimization of the availability allocation problem in a series-parallel system with repairable components is aimed in this paper. The two objectives of the problem are the availability of the system and the total cost of the system. Regarding the previous studies in series-parallel systems, the main contribution of this study is to expand the redundancy allocation problems to systems that have repairable components. Therefore, the considered systems in this paper are the systems that have repairable components in their configurations and subsystems. Due to the complexity of the model, a meta-heuristic method called as non-dominated sorting genetic algorithm is applied to find Pareto front. After finding the Pareto front, a procedure is used to select the best solution from the Pareto front.

  16. An Outline for a Manufacturing Planning and Control System for a Repair/ Overhaul/Rebuilding Environment

    Science.gov (United States)

    1992-03-01

    Air Force Institute of Technology (AU), Wright-Patterson AFB, OH, September 1988. Goldratt , Eliyahu M. and Jeff Cox. The Goal. A Process of Ongoing...of Constraints (ToC). The basic premise of ToC is that every manufacturing operation has a goal ( Goldratt , 1986). The C-141 Management Directorate...constraint is always operating at peak capacity ( Goldratt , 1986). This ensures that, in this instance, aircraft are not 42 waiting to be repaired

  17. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-12-31

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  18. Comparison of the tendon damage caused by four different anchor systems used in transtendon rotator cuff repair.

    Science.gov (United States)

    Zhang, Qing-Song; Liu, Sen; Zhang, Qiuyang; Xue, Yun; Ge, Dongxia; O'Brien, Michael J; Savoie, Felix H; You, Zongbing

    2012-01-01

    Objectives. The objective of this study was to compare the damage to the rotator cuff tendons caused by four different anchor systems. Methods. 20 cadaveric human shoulder joints were used for transtendon insertion of four anchor systems. The Healix Peek, Fastin RC, Bio-Corkscrew Suture, and Healix Transtend anchors were inserted through the tendons using standard transtendon procedures. The areas of tendon damage were measured. Results. The areas of tendon damage (mean ± standard deviation, n = 7) were 29.1 ± 4.3 mm(2) for the Healix Peek anchor, 20.4 ± 2.3 mm(2) for the Fastin RC anchor, 23.4 ± 1.2 mm(2) for the Bio-Corkscrew Suture anchor, 13.7 ± 3.2 mm(2) for the Healix Transtend anchor inserted directly, and 9.1 ± 2.1 mm(2) for the Healix Transtend anchor inserted through the Percannula system (P anchors). Conclusions. In a cadaver transtendon rotator cuff repair model, smaller anchors caused less damage to the tendon tissues. The Healix Transtend implant system caused the least damage to the tendon tissues. Our findings suggest that smaller anchors should be considered when performing transtendon procedures to repair partial rotator cuff tears.

  19. Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

    Science.gov (United States)

    An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

    2014-01-01

    Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

  20. Clinical Outcomes and Complications of Percutaneous Achilles Repair System Versus Open Technique for Acute Achilles Tendon Ruptures.

    Science.gov (United States)

    Hsu, Andrew R; Jones, Carroll P; Cohen, Bruce E; Davis, W Hodges; Ellington, J Kent; Anderson, Robert B

    2015-11-01

    Limited incision techniques for acute Achilles tendon ruptures have been developed in recent years to improve recovery and reduce postoperative complications compared with traditional open repair. The purpose of this retrospective cohort study was to analyze the clinical outcomes and postoperative complications between acute Achilles tendon ruptures treated using a percutaneous Achilles repair system (PARS [Arthrex, Inc, Naples, FL]) versus open repair and evaluate the overall outcomes for operatively treated Achilles ruptures. Between 2005 and 2014, 270 consecutive cases of operatively treated acute Achilles tendon ruptures were reviewed (101 PARS, 169 open). Patients with Achilles tendinopathy, insertional ruptures, chronic tears, or less than 3-month follow-up were excluded. Operative treatment consisted of a percutaneous technique (PARS) using a 2-cm transverse incision with FiberWire (Arthrex, Inc, Naples, FL) sutures or open repair using a 5- to 8-cm posteromedial incision with FiberWire in a Krackow fashion reinforced with absorbable sutures. Patient demographics were recorded along with medical comorbidities, activity at injury, time from injury to surgery, length of follow-up, return to baseline activities by 5 months, and postoperative complications. The most common activity during injury for both groups was basketball (PARS: 39%, open: 47%). A greater number of patients treated with PARS were able to return to baseline physical activities by 5 months compared with the open group (PARS: 98%, open: 82%; P = .0001). There were no significant differences (P > .05) between groups in rates of rerupture (P = 1.0), sural neuritis (P = .16), wound dehiscence (P = .74), superficial (P = .29) and/or deep infection (P = .29), or reoperation (P = .13). There were no deep vein thromboses (DVTs) or reruptures in either group. In the PARS group, there were no cases of sural neuritis, 3 cases (3%) of superficial wound dehiscence, and 2 reoperations (2%) for superficial

  1. Heteroduplex DNA mismatch repair system of Streptococcus pneumoniae: cloning and expression of the hexA gene.

    OpenAIRE

    Balganesh, T S; Lacks, S A

    1985-01-01

    Mutations affecting heteroduplex DNA mismatch repair in Streptococcus pneumoniae were localized in two genes, hexA and hexB, by fractionation of restriction fragments carrying mutant alleles. A fragment containing the hexA4 allele was cloned in the S. pneumoniae cloning system, and the hexA+ allele was introduced into the recombinant plasmid by chromosomal facilitation of plasmid transfer. Subcloning localized the functional hexA gene to a 3.5-kilobase segment of the cloned pneumococcal DNA. ...

  2. 'Failure limited' data and TTT-based trend tests in multiple repairable systems

    Energy Technology Data Exchange (ETDEWEB)

    Caroni, C., E-mail: ccar@math.ntua.g [Department of Mathematics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), 9 Iroon Polytechniou, Zografou 157 80, Athens (Greece)

    2010-06-15

    Tests for trend in multiple repairable systems based on the total time on test (introduced by Kvaloy and Lindqvist) are valid for data that end at a failure time only if data collection was planned to continue until a predetermined number of failures had occurred. They are not valid for a commoner form of data that end with the last of a random number of failures within a predetermined observation period. The necessary modification to the analysis is given here and appropriate terminology is suggested.

  3. Some Reliability Problems Arising in the Mx/G(M/G)/1 Repairable Queueing System with Single Delay Vacation

    Institute of Scientific and Technical Information of China (English)

    TANG Ying-hui

    2001-01-01

    On the basis of Ref. [1], the Mx/G(M/G)/1 repairable queueing system with single delay vacation is discussed again. The following reliability problems of the service station are studied: (a) The probability that it fails at time t, i.e. its unavailability; (b) The expected failure number during the time interval (0,t]; (c) The expected failure number during the "server busy period"; (d) The expected downtime during the time interval (0,t]. Some reliability results of the service station are obtained. These results would be interest to reliability analysts.

  4. Prognostic impact of mismatch repair genes germline defects in colorectal cancer patients: are all mutations equal?

    Science.gov (United States)

    Maccaroni, Elena; Bracci, Raffaella; Giampieri, Riccardo; Bianchi, Francesca; Belvederesi, Laura; Brugiati, Cristiana; Pagliaretta, Silvia; Del Prete, Michela; Scartozzi, Mario; Cascinu, Stefano

    2015-01-01

    Background Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by germline mutations in MisMatch Repair (MMR) genes, particularly in MLH1, MSH2 and MSH6. Patients with LS seem to have a more favourable prognosis than those with sporadic CRC, although the prognostic impact of different mutation types is unknown. Aim of our study is to compare survival outcomes of different types of MMR mutations in patients with LS-related CRC. Methods 302 CRC patients were prospectively selected on the basis of Amsterdam or Revised Bethesda criteria to undergo genetic testing: direct sequencing of DNA and MLPA were used to examine the entire MLH1, MSH2 and MSH6 coding sequence. Patients were classified as mutation-positive or negative according to the genetic testing result. Results A deleterious MMR mutation was found in 38/302 patients. Median overall survival (OS) was significantly higher in mutation-positive vs mutation-negative patients (102.6 vs 77.7 months, HR:0.63, 95%CI:0.46–0.89, p = 0.0083). Different types of mutation were significantly related with OS: missense or splicing-site mutations were associated with better OS compared with rearrangement, frameshift or non-sense mutations (132.5 vs 82.5 months, HR:0.46, 95%CI:0.16–0.82, p = 0.0153). Conclusions Our study confirms improved OS for LS-patients compared with mutation-negative CRC patients. In addition, not all mutations could be considered equal: the better prognosis in CRC patients with MMR pathogenic missense or splicing site mutation could be due to different functional activity of the encoded MMR protein. This matter should be investigated by use of functional assays in the future. PMID:26485756

  5. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-08-17

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without liners

  6. The Base Excision Repair system of Salmonella enterica serovar typhimurium counteracts DNA damage by host nitric oxide.

    Directory of Open Access Journals (Sweden)

    Anthony R Richardson

    2009-05-01

    Full Text Available Intracellular pathogens must withstand nitric oxide (NO. generated by host phagocytes. Salmonella enterica serovar Typhimurium interferes with intracellular trafficking of inducible nitric oxide synthase (iNOS and possesses multiple systems to detoxify NO.. Consequently, the level of NO. stress encountered by S. Typhimurium during infection in vivo has been unknown. The Base Excision Repair (BER system recognizes and repairs damaged DNA bases including cytosine and guanine residues modified by reactive nitrogen species. Apurinic/apyrimidinic (AP sites generated by BER glycosylases require subsequent processing by AP endonucleases. S. Typhimurium xth nfo mutants lacking AP endonuclease activity exhibit increased NO. sensitivity resulting from chromosomal fragmentation at unprocessed AP sites. BER mutant strains were thus used to probe the nature and extent of nitrosative damage sustained by intracellular bacteria during infection. Here we show that an xth nfo S. Typhimurium mutant is attenuated for virulence in C3H/HeN mice, and virulence can be completely restored by the iNOS inhibitor L-NIL. Inactivation of the ung or fpg glycosylase genes partially restores virulence to xth nfo mutant S. Typhimurium, demonstrating that NO. fluxes in vivo are sufficient to modify cytosine and guanine bases, respectively. Mutants lacking ung or fpg exhibit NO.-dependent hypermutability during infection, underscoring the importance of BER in protecting Salmonella from the genotoxic effects of host NO.. These observations demonstrate that host-derived NO. damages Salmonella DNA in vivo, and the BER system is required to maintain bacterial genomic integrity.

  7. Tegaserod Mimics the Neurostimulatory Glycan Polysialic Acid and Promotes Nervous System Repair

    Science.gov (United States)

    2014-01-01

    transplanted Schwann cells over- expressing PSA augment repair in both spinal cord (Luo et al., 2011; Papastefanaki et al., 2007) and peripheral nerve...NCAM/ 14-day-old (E14) mouse embryos as described (Simova et al., 2006). In brief, 48-well plates were coated with 0.01% poly-L-lysine (PLL) or...of polysialic acid as part of tissue-engineered nerve transplants . Tissue Eng. Part A 16, 3085e3098. Haile, Y., Berski, S., Drager, G., Nobre, A

  8. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; Nancy Porter; Mike Sullivan; Chris Neary

    2004-04-12

    The two broad categories of deposited weld metal repair and fiber-reinforced composite liner repair technologies were reviewed for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Preliminary test programs were developed for both deposited weld metal repair and for fiber-reinforced composite liner repair. Evaluation trials have been conducted using a modified fiber-reinforced composite liner provided by RolaTube and pipe sections without liners. All pipe section specimens failed in areas of simulated damage. Pipe sections containing fiber-reinforced composite liners failed at pressures marginally greater than the pipe sections without liners. The next step is to evaluate a liner material with a modulus of elasticity approximately 95% of the modulus of elasticity for steel. Preliminary welding parameters were developed for deposited weld metal repair in preparation of the receipt of Pacific Gas & Electric's internal pipeline welding repair system (that was designed specifically for 559 mm (22 in.) diameter pipe) and the receipt of 559 mm (22 in.) pipe sections from Panhandle Eastern. The next steps are to transfer welding parameters to the PG&E system and to pressure test repaired pipe sections to failure. A survey of pipeline operators was conducted to better understand the needs and performance requirements of the natural gas transmission industry regarding internal repair. Completed surveys contained the following principal conclusions: (1) Use of internal weld repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling (HDD) when a new bore must be created

  9. One strategy for arthroscopic suture fixation of tibial intercondylar eminence fractures using the Meniscal Viper Repair System

    Directory of Open Access Journals (Sweden)

    Ochiai Satoshi

    2011-08-01

    Full Text Available Abstract Background Principles for the treatment of tibial intercondylar eminence fracture are early reduction and stable fixation. Numerous ways to treatment of this fracture have been invented. We designed a simple, low-invasive, and arthroscopic surgical strategy for tibial intercondylar eminence fracture utilizing the Meniscal Viper Repair System used for arthroscopic meniscal suture. Methods We studied 5 patients, who underwent arthroscopic suture fixation that we modified. The present technique utilized the Meniscal Viper Repair System for arthroscopic suture of the meniscus. With one handling, a high-strength ultra-high molecular weight polyethylene(UHMWPE suture can be passed through the anterior cruciate ligament (ACL and the loops for suture retrieval placed at both sides of ACL. Surgical results were evaluated by the presence or absence of bone union on plain radiographs, postoperative range of motion of the knee joint, the side-to-side differences measured by Telos SE, and Lysholm scores. Results The reduced position achieved after surgery was maintained and good function was obtained in all cases. The mean distance of tibia anterior displacement and assessment by Lysholm score showed good surgical results. Conclusion This method simplified the conventional arthroscopic suture fixation and increased its precision, and was applicable to Type II fractures that could be reduced, as well as surgically indicated Types III and IV. The present series suggested that our surgical approach was a useful surgical intervention for tibial intercondylar eminence fracture.

  10. DNA replication, repair, and repair tests. [Rat; human leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lambert, B.

    1980-09-01

    The rate of inhibition and recovery of DNA synthesis can be used in a rapid assay system to detect genotoxic potentials of chemicals. Also, the observation that an agent stimulates DNA repair in a test system indicates its ability to cause damage in DNA. Different experimental approaches to the study of repair synthesis are discussed.

  11. Role of APC and DNA mismatch repair genes in the development of colorectal cancers

    Directory of Open Access Journals (Sweden)

    Roy Deodutta

    2003-12-01

    Full Text Available Abstract Colorectal cancer is the third most common cause of cancer-related death in both men and women in the western hemisphere. According to the American Cancer Society, an estimated 105,500 new cases of colon cancer with 57,100 deaths will occur in the U.S. in 2003, accounting for about 10% of cancer deaths. Among the colon cancer patients, hereditary risk contributes approximately 20%. The main inherited colorectal cancers are the familial adenomatous polyposis (FAP and the hereditary nonpolyposis colorectal cancers (HNPCC. The FAP and HNPCC are caused due to mutations in the adenomatous polyposis coli (APC and DNA mismatch repair (MMR genes. The focus of this review is to summarize the functions of APC and MMR gene products in the development of colorectal cancers.

  12. Harnessing neural activity to promote repair of the damaged corticospinal system after spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    John H. Martin

    2016-01-01

    As most spinal cord injuries (SCIs) are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract (CST) is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paraly-sis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST—which establishes connectional speci-ifcity through axon pruning, axon outgrowth, and synaptic competition among CST terminals—informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spi-nal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C4 contusion rat model.

  13. Harnessing neural activity to promote repair of the damaged corticospinal system after spinal cord injury

    Directory of Open Access Journals (Sweden)

    John H Martin

    2016-01-01

    Full Text Available As most spinal cord injuries (SCIs are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract (CST is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paralysis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST-which establishes connectional specificity through axon pruning, axon outgrowth, and synaptic competition among CST terminals-informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spinal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C 4 contusion rat model.

  14. Systemic neutrophil depletion modulates the migration and fate of transplanted human neural stem cells to rescue functional repair.

    Science.gov (United States)

    Nguyen, Hal X; Hooshmand, Mitra J; Saiwai, Hirokazu; Maddox, Jake; Salehi, Arjang; Lakatos, Anita; Nishi, Rebecca; Salazar, Desiree; Uchida, Nobuko; Anderson, Aileen J

    2017-08-28

    The interaction of transplanted stem cells with local cellular and molecular cues in the host central nervous system (CNS) microenvironment may affect the potential for repair by therapeutic cell populations. In this regard, spinal cord injury (SCI), Alzheimer's disease, and other neurological injuries and diseases all exhibit dramatic and dynamic changes to the host microenvironment over time. Previously, we reported that delayed transplantation of CNS-derived human neural stem cells (hCNS-SCns) at 9 or 30 days post-SCI (dpi) resulted in extensive donor cell migration, predominantly neuronal and oligodendrocytic donor cell differentiation, and functional locomotor improvements. Here, we report that acute transplantation of hCNS-SCns at 0 dpi resulted in localized astroglial differentiation of donor cells near the lesion epicenter, and failure to produce functional improvement in an all-female immunodeficient mouse model. Critically, specific immunodepletion of neutrophils (polymorphonuclear leukocytes, PMN) blocked hCNS-SCns astroglial differentiation near the lesion epicenter and rescued the capacity of these cells to restore function. These data represent novel evidence that a host immune cell population can block the potential for functional repair derived from a therapeutic donor cell population, and support targeting the inflammatory microenvironment in combination with cell transplantation after SCI.SIGNIFICANCE STATEMENTThe interaction of transplanted cells with local cellular and molecular cues in the host microenvironment is a key variable that may shape the translation of neurotransplantation research to the clinical SCI human population, and few studies have investigated these events. We show that the specific immunodepletion of PMN neutrophils using anti-Ly6G inhibits donor cell astrogliosis and rescues the capacity of a donor cell population to promote locomotor improvement after SCI. Critically, our data demonstrate novel evidence that a specific

  15. Endovascular repair of arterial iliac vessel wall lesions with a self-expandable nitinol stent graft system.

    Directory of Open Access Journals (Sweden)

    Birger Mensel

    Full Text Available OBJECTIVE: To assess the therapeutic outcome after endovascular repair of iliac arterial lesions (IALs using a self-expandable Nitinol stent graft system. METHODS: Between July 2006 and March 2013, 16 patients (13 males, mean age: 68 years with a self-expandable Nitinol stent graft. A total of 19 lesions were treated: nine true aneurysms, two anastomotic aneurysms, two dissections, one arteriovenous fistula, two type 1B endoleaks after endovascular aneurysm repair, one pseudoaneurysm, and two perforations after angioplasty. Pre-, intra-, and postinterventional imaging studies and the medical records were analyzed for technical and clinical success and postinterventional complications. RESULTS: The primary technical and clinical success rate was 81.3% (13/16 patients and 75.0% (12/16, respectively. Two patients had technical failure due to persistent type 1A endoleak and another patient due to acute stent graft thrombosis. One patient showed severe stent graft kinking on the first postinterventional day. In two patients, a second intervention was performed. The secondary technical and clinical success rate was 87.5% (14/16 and 93.8% (15/16. The minor complication rate was 6.3% (patient with painful hematoma at the access site. The major complication rate was 6.3% (patient with ipsilateral deep vein thrombosis. During median follow-up of 22.4 months, an infection of the aneurysm sac in one patient and a stent graft thrombosis in another patient were observed. CONCLUSION: Endovascular repair of various IALs with a self-expandable Nitinol stent graft is safe and effective.

  16. Hypospadias repair

    Science.gov (United States)

    ... the problem. If the repair is not done, problems may occur later on such as: Difficulty controlling and directing urine stream A curve in the penis during erection Decreased fertility Embarrassment about appearance of penis Surgery ...

  17. MTBF evaluation for 2-out-of-3 redundant repairable systems with common cause and cascade failures considering fuzzy rates for failures and repair: a case study of a centrifugal water pumping system

    Science.gov (United States)

    Mortazavi, Seyed Mohammad; Mohamadi, Maryam; Jouzdani, Javid

    2017-08-01

    In many cases, redundant systems are beset by both independent and dependent failures. Ignoring dependent variables in MTBF evaluation of redundant systems hastens the occurrence of failure, causing it to take place before the expected time, hence decreasing safety and creating irreversible damages. Common cause failure (CCF) and cascading failure are two varieties of dependent failures, both leading to a considerable decrease in the MTBF of redundant systems. In this paper, the alpha-factor model and the capacity flow model are combined so as to incorporate CCF and cascading failure in the evaluation of MTBF of a 2-out-of-3 repairable redundant system. Then, using a transposed matrix, the MTBF function of the system is determined. Due to the fact that it is difficult to estimate the independent and dependent failure rates, industries are interested in considering uncertain failure rates. Therefore, fuzzy theory is used to incorporate uncertainty into the model presented in this study, and a nonlinear programming model is used to determine system's MTBF. Finally, in order to validate the proposed model, evaluation of MTBF of the redundant system of a centrifugal water pumping system is presented as a practical example.

  18. Lichtenstein, prolene hernia system, and UltraPro Hernia System for primary inguinal hernia repair: one-year outcome of a prospective randomized controlled trial.

    Science.gov (United States)

    Magnusson, J; Nygren, J; Thorell, A

    2012-06-01

    The optimal technique for open inguinal hernia repair is yet to be determined. Three hundred and nine male patients [median of 60 years (range, 31-75)] undergoing primary open inguinal hernia repair in local anesthesia and day-care surgery were randomly allocated to operation with the Lichtenstein technique (L), Prolene Hernia System (PHS), or UltraPro Hernia System (UHS). [Median (IQR)] There were no differences in operating time [47 (40-58) vs. 50 (40-57) and 50 (42-56) min in groups L, PHS, and UHS, respectively], intra- or postoperative complications, time until return to normal workload (8 (4-14) vs. 9 (4-14), and 8 (4-14) days) or occurrence of chronic pain at 12 months (15 vs. 12, and 13 patients). Self-reported physical quality of life (SF-36) was reduced compared to matched controls preoperatively and increased similarly to levels not different from controls in all groups at 12 months postoperatively. There was one recurrence in each group during the follow-up period. The Lichtenstein technique, PHS, and UHS seem all acceptable approaches for open inguinal hernia repair in local anesthesia and day-care surgery regarding perioperative course, rehabilitation, complications, recurrence rates, development of chronic groin pain, and improvement in quality of life after 12 months. However, due to reduced costs and lack of need for the exploration of the preperitoneal space, the Lichtenstein technique should be recommended as first choice.

  19. Brh2 and Rad51 promote telomere maintenance in Ustilago maydis, a new model system of DNA repair proteins at telomeres.

    Science.gov (United States)

    Yu, Eun Young; Kojic, Milorad; Holloman, William K; Lue, Neal F

    2013-07-01

    Recent studies implicate a number of DNA repair proteins in mammalian telomere maintenance. However, because several key repair proteins in mammals are missing from the well-studied budding and fission yeast, their roles at telomeres cannot be modeled in standard fungi. In this report, we explored the dimorphic fungus Ustilago maydis as an alternative model for telomere research. This fungus, which belongs to the phylum Basidiomycota, has a telomere repeat unit that is identical to the mammalian repeat, as well as a constellation of DNA repair proteins that more closely mimic the mammalian collection. We showed that the two core components of homology-directed repair (HDR) in U. maydis, namely Brh2 and Rad51, both promote telomere maintenance in telomerase positive cells, just like in mammals. In addition, we found that Brh2 is localized to telomeres in vivo, suggesting that it acts directly at chromosome ends. We surveyed a series of mutants with DNA repair defects, and found many of them to have short telomeres. Our results indicate that factors involved in DNA repair are probably also needed for optimal telomere maintenance in U. maydis, and that this fungus is a useful alternative model system for telomere research.

  20. The Mre11/Rad50/Nbs1 complex interacts with the mismatch repair system and contributes to temozolomide-induced G2 arrest and cytotoxicity.

    Science.gov (United States)

    Mirzoeva, Olga K; Kawaguchi, Tomohiro; Pieper, Russell O

    2006-11-01

    The chemotherapeutic agent temozolomide produces O(6)-methylguanine (O6MG) in DNA, which triggers futile DNA mismatch repair, DNA double-strand breaks (DSB), G(2) arrest, and ultimately cell death. Because the protein complex consisting of Mre11/Rad50/Nbs1 (MRN complex) plays a key role in DNA damage detection and signaling, we asked if this complex also played a role in the cellular response to temozolomide. Temozolomide exposure triggered the assembly of MRN complex into chromatin-associated nuclear foci. MRN foci formed significantly earlier than gamma-H2AX and 53BP1 foci that assembled in response to temozolomide-induced DNA DSBs. MRN foci formation was suppressed in cells that incurred lower levels of temozolomide-induced O6MG lesions and/or had decreased mismatch repair capabilities, suggesting that the MRN foci formed not in response to temozolomide-induced DSB but rather in response to mismatch repair processing of mispaired temozolomide-induced O6MG lesions. Consistent with this idea, the MRN foci colocalized with those of proliferating cell nuclear antigen (a component of the mismatch repair complex), and the MRN complex component Nbs1 coimmunoprecipitated with the mismatch repair protein Mlh1 specifically in response to temozolomide treatment. Furthermore, small inhibitory RNA-mediated suppression of Mre11 levels decreased temozolomide-induced G(2) arrest and cytotoxicity in a manner comparable to that achieved by suppression of mismatch repair. These data show that temozolomide-induced O6MG lesions, acted upon by the mismatch repair system, drive formation of the MRN complex foci and the interaction of this complex with the mismatch repair machinery. The MRN complex in turn contributes to the control of temozolomide-induced G(2) arrest and cytotoxicity, and as such is an additional determining factor in glioma sensitivity to DNA methylating chemotherapeutic drugs such as temozolomide.

  1. Production of truncated MBD4 protein by frameshift mutation in DNA mismatch repair-deficient cells enhances 5-fluorouracil sensitivity that is independent of hMLH1 status.

    Science.gov (United States)

    Suzuki, Satoshi; Iwaizumi, Moriya; Tseng-Rogenski, Stephanie; Hamaya, Yasushi; Miyajima, Hiroaki; Kanaoka, Shigeru; Sugimoto, Ken; Carethers, John M

    2016-07-02

    Methyl-CpG binding domain protein 4 (MBD4) is a DNA glycosylase that can remove 5-fluorodeoxyuracil from DNA as well as repair T:G or U:G mismatches. MBD4 is a target for frameshift mutation with DNA mismatch repair (MMR) deficiency, creating a truncated MBD4 protein (TruMBD4) that lacks its glycosylase domain. Here we show that TruMBD4 plays an important role for enhancing 5-fluorouracil (5FU) sensitivity in MMR-deficient colorectal cancer cells. We found biochemically that TruMBD4 binds to 5FU incorporated into DNA with higher affinity than MBD4. TruMBD4 reduced the 5FU affinity of the MMR recognition complexes that determined 5FU sensitivity by previous reports, suggesting other mechanisms might be operative to trigger cytotoxicity. To analyze overall 5FU sensitivity with TruMBD4, we established TruMBD4 overexpression in hMLH1-proficient or -deficient colorectal cancer cells followed by treatment with 5FU. 5FU-treated TruMBD4 cells demonstrated diminished growth characteristics compared to controls, independently of hMLH1 status. Flow cytometry revealed more 5FU-treated TruMBD4 cells in S phase than controls. We conclude that patients with MMR-deficient cancers, which show characteristic resistance to 5FU therapy, may be increased for 5FU sensitivity via secondary frameshift mutation of the base excision repair gene MBD4.

  2. 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.

  3. Exonuclease 1 and its versatile roles in DNA repair

    DEFF Research Database (Denmark)

    Keijzers, Guido; Liu, Dekang; Rasmussen, Lene Juel

    2016-01-01

    Exonuclease 1 (EXO1) is a multifunctional 5' → 3' exonuclease and a DNA structure-specific DNA endonuclease. EXO1 plays roles in DNA replication, DNA mismatch repair (MMR) and DNA double-stranded break repair (DSBR) in lower and higher eukaryotes and contributes to meiosis, immunoglobulin...... maturation, and micro-mediated end-joining in higher eukaryotes. In human cells, EXO1 is also thought to play a role in telomere maintenance. Mutations in the human EXO1 gene correlate with increased susceptibility to some cancers. This review summarizes recent studies on the enzymatic functions...... and biological roles of EXO1, its possible protective role against cancer and aging, and regulation of EXO1 by posttranslational modification....

  4. DNA polymerase delta, RFC and PCNA are required for repair synthesis of large looped heteroduplexes in Saccharomyces cerevisiae.

    Science.gov (United States)

    Corrette-Bennett, Stephanie E; Borgeson, Claudia; Sommer, Debbie; Burgers, Peter M J; Lahue, Robert S

    2004-01-01

    Small looped mispairs are corrected by DNA mismatch repair (MMR). In addition, a distinct process called large loop repair (LLR) corrects loops up to several hundred nucleotides in extracts of bacteria, yeast or human cells. Although LLR activity can be readily demonstrated, there has been little progress in identifying its protein components. This study identified some of the yeast proteins responsible for DNA repair synthesis during LLR. Polyclonal antisera to either Pol31 or Pol32 subunits of polymerase delta efficiently inhibited LLR in extracts by blocking repair just prior to gap filling. Gap filling was inhibited regardless of whether the loop was retained or removed. These experiments suggest polymerase delta is uniquely required in yeast extracts for LLR-associated synthesis. Similar results were obtained with antisera to the clamp loader proteins Rfc3 and Rfc4, and to PCNA, i.e. LLR was inhibited just prior to gap filling for both loop removal and loop retention. Thus PCNA and RFC seem to act in LLR only during repair synthesis, in contrast to their roles at both pre- and post-excision steps of MMR. These biochemical experiments support the idea that yeast polymerase delta, RFC and PCNA are required for large loop DNA repair synthesis.

  5. TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver

    Science.gov (United States)

    Du, Zhongkun; Zhang, Yan; Wang, Guowei; Peng, Jianbiao; Wang, Zunyao; Gao, Shixiang

    2016-02-01

    Triphenyl phosphate is a high production volume organophosphate flame retardant that has been detected in multiple environmental media at increasing concentrations. The environmental and health risks of triphenyl phosphate have drawn attention because of the multiplex toxicity of this chemical compound. However, few studies have paid close attention to the impacts of triphenyl phosphate on liver metabolism. We investigated hepatic histopathological, metabolomic and transcriptomic responses of zebrafish after exposure to 0.050 mg/L and 0.300 mg/L triphenyl phosphate for 7 days. Metabolomic analysis revealed significant changes in the contents of glucose, UDP-glucose, lactate, succinate, fumarate, choline, acetylcarnitine, and several fatty acids. Transcriptomic analysis revealed that related pathways, such as the glycosphingolipid biosynthesis, PPAR signaling pathway and fatty acid elongation, were significantly affected. These results suggest that triphenyl phosphate exposure markedly disturbs hepatic carbohydrate and lipid metabolism in zebrafish. Moreover, DNA replication, the cell cycle, and non-homologous end-joining and base excision repair were strongly affected, thus indicating that triphenyl phosphate hinders the DNA damage repair system in zebrafish liver cells. The present study provides a systematic analysis of the triphenyl phosphate-induced toxic effects in zebrafish liver and demonstrates that low concentrations of triphenyl phosphate affect normal metabolism and cell cycle.

  6. Ultrapro hernia system for inguinal hernia repair%腹股沟疝 UHS 手术

    Institute of Scientific and Technical Information of China (English)

    陈吉彩; 陈晓曦

    2014-01-01

    Ultrapro hernia dystem ( UHS) is a bilayer polypropylene mesh which is composed of an anterior layer , a posterior layer and a connector .The posterior layer is placed between the transversalis fascia and peritoneum ( preperitoneal space ) and covers the myopectineal orifice , for repairing the preperitoneal space.By fixing of the anterior layer between the inguinal ligament and pubic tubercle , the posterior wall of the inguinal canal could be strengthened .The connector , which filled the abdominal wall defect and fixed layers, could prevent from recurrence caused by displacement of mesh .Double repairment of the posterior wall of the inguinal canal and the preperitoneal space by using UHS could significantly reduce the recurrence of inguinal hernia maximally .%超普疝修补装置( ULTRAPRO Hernia System, UHS)由上片、下片和中间连接柱构成。下片位于腹膜与腹横筋膜之间(腹膜前间隙),覆盖整个肌耻骨孔,起到了腹膜前间隙修补的作用;将上片分别固定于腹股沟韧带和耻骨结节,加强腹股沟管后壁;中间连接柱既充填了疝环缺损,又连接和稳定了上、下片,可防止网片移位造成的复发。 UHS同时对腹膜前间隙和腹股沟管后壁进行双重修补,理论上最大限度地减少了腹股沟疝的复发。

  7. A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy.

    Science.gov (United States)

    Owens, Daniel J; Sharples, Adam P; Polydorou, Ioanna; Alwan, Nura; Donovan, Timothy; Tang, Jonathan; Fraser, William D; Cooper, Robert G; Morton, James P; Stewart, Claire; Close, Graeme L

    2015-12-15

    Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be established. To address this gap in knowledge in relation to damage repair, a randomised, placebo-controlled trial was performed in 20 males with insufficient concentrations of serum 25(OH)D (45 ± 25 nmol/l). Prior to and following 6 wk of supplemental vitamin D3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 × 10 damaging eccentric contractions of the knee extensors, with peak torque measured over the following 7 days of recovery. Parallel experimentation using isolated human skeletal muscle-derived myoblast cells from biopsies of 14 males with low serum 25(OH)D (37 ± 11 nmol/l) were subjected to mechanical wound injury, which enabled corresponding in vitro studies of muscle repair, regeneration, and hypertrophy in the presence and absence of 10 or 100 nmol 1α,25(OH)2D3. Supplemental vitamin D3 increased serum 25(OH)D and improved recovery of peak torque at 48 h and 7 days postexercise. In vitro, 10 nmol 1α,25(OH)2D3 improved muscle cell migration dynamics and resulted in improved myotube fusion/differentiation at the biochemical, morphological, and molecular level together with increased myotube hypertrophy at 7 and 10 days postdamage. Together, these preliminary data are the first to characterize a role for vitamin D in human skeletal muscle regeneration and suggest that maintaining serum 25(OH)D may be beneficial for enhancing reparative processes and potentially for facilitating subsequent hypertrophy. Copyright © 2015 the American Physiological Society.

  8. CDX2 downregulation is associated with poor differentiation and MMR deficiency in colon cancer

    DEFF Research Database (Denmark)

    Olsen, J.; Eiholm, Susanne; Kirkeby, L T

    2016-01-01

    , and migration. In this study, we investigated CDX2 mRNA and protein expression in relation to the clinicopathological characteristics of colon cancer, including mismatch repair status and recurrence risk. METHODS: Tumor samples were obtained from colon cancer patients. Biopsies from tumor tissue and normal......BACKGROUND: Homeobox genes are often deregulated in cancer and can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. CDX2 has been implicated in differentiation, proliferation, cell adhesion...

  9. 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)

  10. A non-regenerative model of a redundant repairable system: bounds for the unavailability and asymptotical insensitivity to the lifetime distribution

    Directory of Open Access Journals (Sweden)

    Igor N. Kovalenko

    1996-01-01

    Full Text Available In this paper we investigate steady state reliability parameters of an F:r-out-of-N redundant repairable system with m(1≤m≤r−1 repair channels in light traffic conditions. Such a system can also be treated as a closed queueing network of a simple kind. It includes two nodes, with infinite number of channels and m channels, respectively. Each of the N customers pass cyclically from one node to the other; the service time distributions are of a general form for both the nodes.

  11. Parasympathetic nervous system activity predicts mood repair use and its effectiveness among adolescents with and without histories of major depression.

    Science.gov (United States)

    Yaroslavsky, Ilya; Rottenberg, Jonathan; Bylsma, Lauren M; Jennings, J Richard; George, Charles; Baji, Ildikó; Benák, István; Dochnal, Roberta; Halas, Kitti; Kapornai, Krisztina; Kiss, Enikő; Makai, Attila; Varga, Hedvig; Vetró, Ágnes; Kovacs, Maria

    2016-04-01

    Depressive disorders that onset in the juvenile years have been linked to far-reaching adverse consequences, making it imperative to elucidate key mechanisms and contributory factors. Excessive use of regulatory responses that exacerbate sadness (maladaptive mood repair) or insufficient use of regulatory responses that reduce it (adaptive mood repair) may reflect behavioral mechanisms of depression risk. Cardiac vagal control, indexed by patterns of respiratory sinus arrhythmia (RSA), has received attention as a putative physiological risk factor for depression. Although mood repair and RSA are related, the nature of this relationship is not well characterized in the context of depression risk. Therefore, we tested alternative models of the relationships between RSA patterns (at rest and in response to a sad film), trait mood repair, and the effectiveness of a mood repair response in the laboratory (state mood repair) among adolescents with depression histories (n = 210) and emotionally healthy peers (n = 161). In our data, a mediation model best explained the association between the key constructs: Adolescents with normative RSA patterns exhibited lower levels of depression and trait maladaptive mood repair, and benefited more from instructed (state) mood repair in the laboratory. By contrast, adolescents with atypical RSA patterns exhibited higher levels of depression and dispositional maladaptive mood repair, which, in turn, mediated the relations of RSA patterns and depression symptoms. Atypical RSA patterns also predicted reduced benefits from laboratory mood repair.

  12. Femoral hernia repair

    Science.gov (United States)

    Femorocele repair; Herniorrhaphy; Hernioplasty - femoral ... During surgery to repair the hernia, the bulging tissue is pushed back in. The weakened area is sewn closed or strengthened. This repair ...

  13. Undescended testicle repair

    Science.gov (United States)

    Orchidopexy; Inguinal orchidopexy; Orchiopexy; Repair of undescended testicle; Cryptorchidism repair ... first year of life without treatment. Undescended testicle repair surgery is recommended for patients whose testicles do ...

  14. Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine.

    Science.gov (United States)

    Stritzelberger, J; Distel, L; Buslei, R; Fietkau, R; Putz, F

    2017-08-20

    Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. While the alkylating agent temozolomide (TMZ) has prolonged overall survival, resistance evolution represents an important clinical problem. Therefore, we studied the effectiveness of radiotherapy and CCNU in an in vitro model of acquired TMZ resistance. We studied the MGMT-methylated GBM cell line U251 and its in vitro derived TMZ-resistant subline, U251/TMZ-R. Cytotoxicity of TMZ, CCNU, and radiation was tested. Both cell lines were analyzed for MGMT promotor status and expression of mismatch repair genes (MMR). The influence of MMR inhibition by cadmium chloride (CdCl2) on the effects of both drugs was evaluated. During the resistance evolution process in vitro, U251/TMZ-R developed MMR deficiency, but MGMT status did not change. U251/TMZ-R cells were more resistant to TMZ than parental U251 cells (cell viability: 92.0% in U251/TMZ-R/69.2% in U251; p = 0.032) yet more sensitive to CCNU (56.4%/80.8%; p = 0.023). The effectiveness of radiotherapy was not reduced in the TMZ-resistant cell line. Combination of CCNU and TMZ showed promising results for both cell lines and overcame resistance. CdCl2-induced MMR deficiency increased cytotoxicity of CCNU. Our results confirm MMR deficiency as a crucial process for resistance evolution to TMZ. MMR-deficient TMZ-resistant GBM cells were particularly sensitive to CCNU and to combined CCNU/TMZ. Effectiveness of radiotherapy was preserved in TMZ-resistant cells. Consequently, CCNU might be preferentially considered as a treatment option for recurrent MGMT-methylated GBM and may even be suitable for prevention of resistance evolution in primary treatment.

  15. Studying repair of a single protein-bound nick in vivo using the Flp-nick system

    DEFF Research Database (Denmark)

    2012-01-01

    damage mimics a stabilized topoisomerase I-DNA cleavage complex. DNA topoisomerases are ubiquitous enzymes that relieve topological stress in the DNA arising during DNA replication or transcription. During this process, they make transient enzyme-DNA cleavage complexes, which normally are reversed...... by a rapid ligation step. However, aberrant long-lived enzyme-DNA complexes may occur frequently due to either endogenous or exogenous damage, and the cellular repair machinery therefore needs to be able to eliminate this type of damage. This chapter describes how to establish the Flp-nick system in S....... cerevisiae, how to detect FlpH305L at the FRT site using a modified chromatin immunoprecipitation assay where formaldehyde fixation is omitted, and how to monitor nicking at the FRT site by alkaline denaturing gel analysis...

  16. Repair of segmental bone defect using Totally Vitalized tissue engineered bone graft by a combined perfusion seeding and culture system.

    Directory of Open Access Journals (Sweden)

    Lin Wang

    Full Text Available BACKGROUND: The basic strategy to construct tissue engineered bone graft (TEBG is to combine osteoblastic cells with three dimensional (3D scaffold. Based on this strategy, we proposed the "Totally Vitalized TEBG" (TV-TEBG which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect. METHODS: In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP scaffold fabricated by Rapid Prototyping (RP technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC method, static seeding and perfusion culture (SSPC method, and static seeding and static culture (SSSC method for their in vitro performance and bone defect healing efficacy with a rabbit model. RESULTS: Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation. CONCLUSION: This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and

  17. Research on Replacement Model for Queuing System with Deteriorative Repairable Service Station Including Delay Repair%带延迟修理的退化服务台排队系统更换模型研究

    Institute of Scientific and Technical Information of China (English)

    贾积身; 侯江华

    2011-01-01

    针对带有延迟修理的退化可修服务台的排队系统,提出了一种新的维修更换模型。假定服务台逐次故障后的维修时间构成随机递增的几何过程,工作时间构成随机递增的几何过程,在服务台每次故障以概率P需要延迟修理和延迟修理时间为随机变量的情况下,选取被服务的顾客数N为其更换策略,以系统长期运行单位时间内的期望效益为目标函数,通过更新过程和几何过程理论建立数学模型,导出了目标函数的解析表达式。并根据目标函数情况,通过最大化目标函数来获取系统最优的更换策略N^*,最后还对结果进行了讨论。%To study queueing system with deteriorative repairable service station including delay repair, this paper proposes a kind of new maintenance and replacement model. Supposing that the successive survival time of the system constitute a decreasing geometric process stochastically, while the consecutive repair time of the system constitute an increasing geometric process, under the conditions that the delay repair time is random variable and the failure service station needs delay repair with probability , we take the number N of the customer that have been serv- iced at the service station as its replacement policy and choose the long - run expected profit per unit time as objec- tive function. By using renewal process and geometric process theory, mathematic model is established and the ex- plicit expressions of the objective function is derived. According objective function, the optimal replacement policy is obtained by maximizing the objective function. Finally, we discuss the result also.

  18. Enhancement of Achilles tendon repair mediated by matrix metalloproteinase inhibition via systemic administration of doxycycline.

    Science.gov (United States)

    Kessler, Michael W; Barr, Jerome; Greenwald, Robert; Lane, Lewis B; Dines, Joshua S; Dines, David M; Drakos, Mark C; Grande, Daniel A; Chahine, Nadeen O

    2014-04-01

    Collagenases or matrix metalloproteinases (MMPs) have been shown to play an important role in the matrix degradation cascade associated with Achilles tendon rupture and disease. The goal of this study was to examine the effects of daily administration of doxycycline (Doxy) through oral gavage on MMP activity and on the repair quality of Achilles tendons in vivo. Our findings indicate that Achilles tendon transection resulted in increasing MMP-8 activity from 2 to 6 weeks post-injury, with peak increases in activity occurring at 4 weeks post-injury. Doxy adiministration at clinically relevant serum concentrations was found to significantly inhibit MMP activity after continuous treatment for 4 weeks, but not for continuous administration for shorter durations (96 h or 2 weeks). Extended doxy administration was also associated with improved collagen fibril organization, and enhanced biomechanical properties (stiffness, ultimate tensile strength, maximum load to failure, and elastic toughness). Our findings indicate that a temporal delay exists between Achilles tendon transection and associated increases in MMP-8 activity in situ. Our findings suggest that inhibition of MMP-8 at its peak activity levels ameliorates fibrosis development and improves biomechanical properties of the Achilles tendon. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  19. Intestinal obstruction repair

    Science.gov (United States)

    Repair of volvulus; Intestinal volvulus - repair; Bowel obstruction - repair ... Intestinal obstruction repair is done while you are under general anesthesia . This means you are asleep and DO NOT feel pain. ...

  20. Aortic aneurysm repair - endovascular

    Science.gov (United States)

    EVAR; Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... Endovascular aortic repair is done because your aneurysm is very large, growing quickly, or is leaking or bleeding. You may have ...

  1. Matrix metalloproteinase-2 and -9 as promising benefactors in development, plasticity and repair of the nervous system.

    Science.gov (United States)

    Verslegers, Mieke; Lemmens, Kim; Van Hove, Inge; Moons, Lieve

    2013-06-01

    It has been 50 years since Gross and Lapiere discovered collagenolytic activity during tadpole tail metamorphosis, which was later on revealed as MMP-1, the founding member of the matrix metalloproteinases (MMPs). Currently, MMPs constitute a large group of endoproteases that are not only able to cleave all protein components of the extracellular matrix, but also to activate or inactivate many other signaling molecules, such as receptors, adhesion molecules and growth factors. Elevated MMP levels are associated with an increasing number of injuries and disorders, such as cancer, inflammation and auto-immune diseases. Yet, MMP upregulation has also been implicated in many physiological functions such as embryonic development, wound healing and angiogenesis and therefore, these proteinases are considered to be crucial mediators in many biological processes. Over the past decennia, MMP research has gained considerable attention in several pathologies, most prominently in the field of cancer metastasis, and more recent investigations also focus on the nervous system, with a striking emphasis on the gelatinases, MMP-2 and MMP-9. Unfortunately, the contribution of these gelatinases to neuropathological disorders, like multiple sclerosis and Alzheimer's disease, has overshadowed their potential as modulators of fundamental nervous system functions. Within this review, we wish to highlight the currently known or suggested actions of MMP-2 and MMP-9 in the developing and adult nervous system and their potential to improve repair or regeneration after nervous system injury.

  2. Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair

    Science.gov (United States)

    Zhu, Kai; Lai, Hao; Guo, Changfa; Li, Jun; Wang, Yulin; Wang, Lingyan; Wang, Chunsheng

    2014-01-01

    Mesenchymal stem cell (MSC) transplantation has attracted much attention in myocardial infarction therapy. One of the limitations is the poor survival of grafted cells in the ischemic microenvironment. Small interfering RNA-mediated prolyl hydroxylase domain protein 2 (PHD2) silencing in MSCs holds tremendous potential to enhance their survival and paracrine effect after transplantation. However, an efficient and biocompatible PHD2 silencing system for clinical application is lacking. Herein, we developed a novel PHD2 silencing system based on arginine-terminated generation 4 poly(amidoamine) (Arg-G4) nanoparticles. The system exhibited effective and biocompatible small interfering RNA delivery and PHD2 silencing in MSCs in vitro. After genetically modified MSC transplantation in myocardial infarction models, MSC survival and paracrine function of IGF-1 were enhanced significantly in vivo. As a result, we observed decreased cardiomyocyte apoptosis, scar size, and interstitial fibrosis, and increased angiogenesis in the diseased myocardium, which ultimately attenuated ventricular remodeling and improved heart function. This work demonstrated that an Arg-G4 nanovector-based PHD2 silencing system could enhance the efficiency of MSC transplantation for infarcted myocardium repair. PMID:25429216

  3. Impact of APEX Ile64val Gene Polymorphisms of DNA Repair Ber System on Modulation of the Risk of Colorectal Cancer in the Polish Population

    Directory of Open Access Journals (Sweden)

    Kabziński Jacek

    2015-03-01

    Full Text Available Colorectal cancer (CRC is one of the deadliest cancers which lie in the incidence of morbidity in second place. Intensive research is to determine and confirm the genetic basis of this disease, which is believed may have a direct relationship with the reduced efficiency of DNA repair systems.

  4. Resident adult neural stem cells in Parkinson's disease--the brain's own repair system?

    Science.gov (United States)

    van den Berge, Simone A; van Strien, Miriam E; Hol, Elly M

    2013-11-05

    One important pathological process in the brain of Parkinson disease (PD) patients is the degeneration of the dopaminergic neurons in the substantia nigra, which leads to a decline in striatal dopamine levels and motor dysfunction. A major clinical problem is that this degenerative process currently cannot be stopped or reversed. Expectations from the restorative capacity of neural stem cells (NSCs) are high, as these cells can potentially replace the degenerating neurons. The discovery of the presence of NSCs in the adult human brain has instigated research into the potential of these cells as a resource to promote brain repair in neurodegenerative diseases. Neural stem and progenitor cells reside in the subventricular zone (SVZ), which is closely situated to the striatum, which is affected in PD. Therefore, restoring the dopamine levels in the striatum of PD patients through stimulating endogenous NSCs in the nearby SVZ to migrate into the striatum and differentiate into dopaminergic neurons might thus be an attractive future therapeutic approach. We will review the reported changes in NSCs in the SVZ of PD animal models and PD patients, which are due to a lack of striatal dopamine. Furthermore, we will summarise the reports that describe efforts to stimulate NSCs to replace dopaminergic cells in the SN and restore striatal dopamine levels. In our opinion, mobilizing the endogenous SVZ NSCs to replenish striatal dopamine is an attractive approach to alleviate the motor symptoms in PD patients, without the ethical and immunological challenges of transplantation of NSCs and foetal brain tissue. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Targeting Insulin-Like Growth Factor-1 Signaling into the Central Nervous System for Promoting Myelin Repair

    Directory of Open Access Journals (Sweden)

    Nadine Wilczak

    2008-01-01

    Full Text Available Multiple sclerosis (MS is the most common demyelinating disease of the central nervous system (CNS. Without myelin, nerve impulses in the CNS are slowed or stopped, leading to a constellation of neurological symptoms. Demyelination also provides a permitting condition for irreversible axonal damage. Remyelination of MS lesions largely fails, although oligodendrocyte precursors and premyelinating oligodendrocytes (myelin forming cells are present in many demyelinated plaques. Insulin-like growth factor (IGF-1 is a growth factor that should provide the appropriate signals to promote repair of MS lesions, because it acts as a survival factor for cells of the oligodendrocyte lineage and stimulates myelin synthesis. In a pilot study on MS patients, no detectable remyelinating effects in the CNS were observed following subcutaneous administration of IGF-1. A number of reasons might explain a lack of beneficial effects: a it is unlikely that subcutaneous administration of IGF-1 provides sufficient passage across the blood-brain-barrier and into the CNS, b the biological actions of IGF-1 are tightly regulated by several insulin-like growth factor binding proteins (IGFBPs, which become upregulated in the demyelinated lesions and may prevent access of IGF-1 to its receptor, c IGF-1 not only acts on oligodendrocytes, but also stimulates the proliferation of astrocytes, which form the glial scar that impedes repair processes. In this review, we will discuss strategies to enhance IGF-1 signaling in the CNS utilizing a alternative routes of administration, b IGF analogues that displace IGF-1 from regulatory IGFBPs and c strategies to selectively target IGF-1 to oligodendrocytes.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Component-Level Electronic-Assembly Repair (CLEAR) Analysis of the Problem Reporting and Corrective Action (PRACA) Database of the International Space Station On-Orbit Electrical Systems

    Science.gov (United States)

    Oeftering, Richard C.; Bradish, Martin A.; Juergens, Jeffrey R.; Lewis, Michael J.

    2011-01-01

    The NASA Constellation Program is investigating and developing technologies to support human exploration of the Moon and Mars. The Component-Level Electronic-Assembly Repair (CLEAR) task is part of the Supportability Project managed by the Exploration Technology Development Program. CLEAR is aimed at enabling a flight crew to diagnose and repair electronic circuits in space yet minimize logistics spares, equipment, and crew time and training. For insight into actual space repair needs, in early 2008 the project examined the operational experience of the International Space Station (ISS) program. CLEAR examined the ISS on-orbit Problem Reporting and Corrective Action database for electrical and electronic system problems. The ISS has higher than predicted reliability yet, as expected, it has persistent problems. A goal was to identify which on-orbit electrical problems could be resolved by a component-level replacement. A further goal was to identify problems that could benefit from the additional diagnostic and test capability that a component-level repair capability could provide. The study indicated that many problems stem from a small set of root causes that also represent distinct component problems. The study also determined that there are certain recurring problems where the current telemetry instrumentation and built-in tests are unable to completely resolve the problem. As a result, the root cause is listed as unknown. Overall, roughly 42 percent of on-orbit electrical problems on ISS could be addressed with a component-level repair. Furthermore, 63 percent of on-orbit electrical problems on ISS could benefit from additional external diagnostic and test capability. These results indicate that in situ component-level repair in combination with diagnostic and test capability can be expected to increase system availability and reduce logistics. The CLEAR approach can increase the flight crew s ability to act decisively to resolve problems while reducing

  8. Genome-wide analysis of heteroduplex DNA in mismatch repair-deficient yeast cells reveals novel properties of meiotic recombination pathways.

    Directory of Open Access Journals (Sweden)

    Emmanuelle Martini

    2011-09-01

    Full Text Available Meiotic DNA double-strand breaks (DSBs initiate crossover (CO recombination, which is necessary for accurate chromosome segregation, but DSBs may also repair as non-crossovers (NCOs. Multiple recombination pathways with specific intermediates are expected to lead to COs and NCOs. We revisited the mechanisms of meiotic DSB repair and the regulation of CO formation, by conducting a genome-wide analysis of strand-transfer intermediates associated with recombination events. We performed this analysis in a SK1 × S288C Saccharomyces cerevisiae hybrid lacking the mismatch repair (MMR protein Msh2, to allow efficient detection of heteroduplex DNAs (hDNAs. First, we observed that the anti-recombinogenic activity of MMR is responsible for a 20% drop in CO number, suggesting that in MMR-proficient cells some DSBs are repaired using the sister chromatid as a template when polymorphisms are present. Second, we observed that a large fraction of NCOs were associated with trans-hDNA tracts constrained to a single chromatid. This unexpected finding is compatible with dissolution of double Holliday junctions (dHJs during repair, and it suggests the existence of a novel control point for CO formation at the level of the dHJ intermediate, in addition to the previously described control point before the dHJ formation step. Finally, we observed that COs are associated with complex hDNA patterns, confirming that the canonical double-strand break repair model is not sufficient to explain the formation of most COs. We propose that multiple factors contribute to the complexity of recombination intermediates. These factors include repair of nicks and double-stranded gaps, template switches between non-sister and sister chromatids, and HJ branch migration. Finally, the good correlation between the strand transfer properties observed in the absence of and in the presence of Msh2 suggests that the intermediates detected in the absence of Msh2 reflect normal intermediates.

  9. Reliability measures of a computer system with priority to PM over the H/W repair activities subject to MOT and MRT

    Directory of Open Access Journals (Sweden)

    Ashish Kumar

    2015-01-01

    Full Text Available This paper concentrates on the evaluation of reliability measures of a computer system of two-identical units having independent failure of h/w and s/w components. Initially one unit is operative and the other is kept as spare in cold standby. There is a single server visiting the system immediately whenever needed. The server conducts preventive maintenance of the unit after a maximum operation time. If server is unable to repair the h/w components in maximum repair time, then components in the unit are replaced immediately by new one. However, only replacement of the s/w components has been made at their failure. The priority is given to the preventive maintenance over repair activities of the h/w. The time to failure of the components follows negative exponential distribution whereas the distribution of preventive maintenance, repair and replacement time are taken as arbitrary. The expressions for some important reliability measures of system effectiveness have been derived using semi-Markov process and regenerative point technique. The graphical behavior of the results has also been shown for a particular case.

  10. Augmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma.

    Science.gov (United States)

    Gil Del Alcazar, Carlos Rodrigo; Todorova, Pavlina Krasimirova; Habib, Amyn A; Mukherjee, Bipasha; Burma, Sandeep

    2016-10-01

    Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults and is universally fatal. The DNA alkylating agent temozolomide is part of the standard-of-care for GBM. However, these tumors eventually develop therapy-driven resistance and inevitably recur. While loss of mismatch repair (MMR) and re-expression of MGMT have been shown to underlie chemoresistance in a fraction of GBMs, resistance mechanisms operating in the remaining GBMs are not well understood. To better understand the molecular basis for therapy-driven temozolomide resistance, mice bearing orthotopic GBM xenografts were subjected to protracted temozolomide treatment, and cell lines were generated from the primary (untreated) and recurrent (temozolomide-treated) tumors. As expected, the cells derived from primary tumors were sensitive to temozolomide, whereas the cells from the recurrent tumors were significantly resistant to the drug. Importantly, the acquired resistance to temozolomide in the recurrent lines was not driven by re-expression of MGMT or loss of MMR but was due to accelerated repair of temozolomide-induced DNA double-strand breaks (DSB). Temozolomide induces DNA replication-associated DSBs that are primarily repaired by the homologous recombination (HR) pathway. Augmented HR appears to underpin temozolomide resistance in the recurrent lines, as these cells were cross-resistant to other agents that induced replication-associated DSBs, exhibited faster resolution of damage-induced Rad51 foci, and displayed higher levels of sister chromatid exchanges (SCE). Furthermore, in light of recent studies demonstrating that CDK1 and CDK2 promote HR, it was found that CDK1/2 inhibitors countered the heightened HR in recurrent tumors and sensitized these therapy-resistant tumor cells to temozolomide.

  11. Nuclear localization of human DNA mismatch repair protein exonuclease 1 (hEXO1)

    DEFF Research Database (Denmark)

    Knudsen, Nina Østergaard; Nielsen, Finn Cilius; Vinther, Lena

    2007-01-01

    localization signals (NLSs) in hEXO1. Using fluorescent fusion proteins, we show that the sequence 418KRPR421, which exhibit strong homology to other monopartite NLS sequences, is responsible for correct nuclear localization of hEXO1. This NLS sequence is located in a region that is also required for hEXO1......Human exonuclease 1 (hEXO1) is implicated in DNA mismatch repair (MMR) and mutations in hEXO1 may be associated with hereditary nonpolyposis colorectal cancer (HNPCC). Since the subcellular localization of MMR proteins is essential for proper MMR function, we characterized possible nuclear...... interaction with hMLH1 and we show that defective nuclear localization of hEXO1 mutant proteins could be rescued by hMLH1 or hMSH2. Both hEXO1 and hMLH1 form complexes with the nuclear import factors importin beta/alpha1,3,7 whereas hMSH2 specifically recognizes importin beta/alpha3. Taken together, we infer...

  12. Stability Analysis of a Repairable System with Warning Device and Repairman Vacation

    Directory of Open Access Journals (Sweden)

    Yangli Ren

    2013-01-01

    probability analysis method, the system is first transformed into a group of integrodifferential equations. Then, the existence and uniqueness as well as regularity of the system dynamic solution are discussed with the functional analysis method. Further, the asymptotic stability, especially the exponential stability of the system dynamic solution, is studied by using the strongly continuous semigroup theory or C0 semigroup theory. The reliability indices and some applications (such as the comparisons of indices and profit of systems with and without warning device, as well as numerical examples, are presented at the end of the paper.

  13. RELIABILITY ANALYSIS FOR A REPAIRABLE PARALLEL SYSTEM WITH TIME-VARYING FAILURE RATES

    Institute of Scientific and Technical Information of China (English)

    TangShengdao; WangFengquan

    2005-01-01

    To solve a real problem :how to calculate the reliability of a system with time-varying failure rates in industry systems,this paper studies a model for the load-sharing parallel system with time-varying failure rates,and obtains calculating formulas of reliability and availability of the system by solving differential equations. In this paper, the failure rates are expressed in polynomial configuration. The constant,linear and Weibull failure rate are in their special form. The polynomial failure rates provide flexibility in modeling the practical time-varying failure rates.

  14. Neural Network Enhanced Structure Determination of Osteoporosis, Immune System, and Radiation Repair Proteins Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation will utilize self learning neural network technology to determine the structure of osteoporosis, immune system disease, and excess radiation...

  15. A new possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system.

    Science.gov (United States)

    Katsui, Renta; Kojima, Yu; Kuniyasu, Hiroki; Shimizu, Juichiro; Koyama, Fumikazu; Fujii, Hisao; Nakajima, Yoshiyuki; Takaki, Miyako

    2008-04-01

    Moderate rectal distension elicits recto-rectal reflex contractions and simultaneous recto-internal anal sphincter reflex relaxations that together comprise the defecation reflex. Both reflexes are controlled by 1) pelvic nerves, 2) lumbar colonic nerves, and 3) enteric nervous system. The aim of the present study was to explore a novel approach to repairing the defecation reflex dysfunction by using the plasticity of enteric nervous pathways. Experiments were performed in anesthetized guinea pigs with ethyl carbamate. The rectum 30 mm oral from the anal verge was transected without damage to extrinsic nerves, and subsequent end-to-end one-layer anastomosis was performed. Recovery of the defecation reflex and associated reflex pathways were evaluated. Eight weeks after sectioning of intrinsic reflex nerve pathways in the rectum, the defecation reflex recovered to the control level, accompanied with regeneration of reflex pathways. The 5-HT(4)-receptor agonist mosapride (0.5 and 1.0 mg/kg) significantly (P nervous system with local application of BDNF.

  16. The CREB Coactivator CRTC2 is a Lymphoma Tumor Suppressor that Preserves Genome Integrity Through Transcription of DNA Mismatch Repair Genes

    Science.gov (United States)

    Fang, Minggang; Pak, Magnolia L.; Chamberlain, Lynn; Xing, Wei; Yu, Hongbo; Green, Michael R.

    2015-01-01

    SUMMARY The CREB-regulated transcription coactivator CRTC2 stimulates CREB target gene expression and has a well-established role in modulating glucose and lipid metabolism. Here we find, unexpectedly, that loss of CRTC2, as well as CREB1 and its coactivator CREB-binding protein (CBP), results in a deficiency in DNA mismatch repair (MMR) and a resultant increased mutation frequency. We show that CRTC2, CREB1 and CBP are transcriptional activators of well-established MMR genes, including EXO1, MSH6, PMS1 and POLD2. Mining of expression profiling databases and analysis of patient samples reveal that CRTC2 and its target MMR genes are down-regulated in specific T-cell lymphoma subtypes, which are microsatellite unstable. The levels of acetylated histone H3 on the CRTC2 promoter are significantly reduced in lymphoma compared to normal tissue, explaining the decreased CRTC2 expression. Our results establish a role for CRTC2 as a lymphoma tumor suppressor gene that preserves genome integrity by stimulating transcription of MMR genes. PMID:26004186

  17. Fusion tyrosine kinase NPM-ALK Deregulates MSH2 and suppresses DNA mismatch repair function novel insights into a potent oncoprotein.

    Science.gov (United States)

    Young, Leah C; Bone, Kathleen M; Wang, Peng; Wu, Fang; Adam, Benjamin A; Hegazy, Samar; Gelebart, Pascal; Holovati, Jelena; Li, Liang; Andrew, Susan E; Lai, Raymond

    2011-07-01

    The fusion tyrosine kinase NPM-ALK is central to the pathogenesis of ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL). We recently identified that MSH2, a key DNA mismatch repair (MMR) protein integral to the suppression of tumorigenesis, is an NPM-ALK-interacting protein. In this study, we found in vitro evidence that enforced expression of NPM-ALK in HEK293 cells suppressed MMR function. Correlating with these findings, six of nine ALK(+)ALCL tumors displayed evidence of microsatellite instability, as opposed to none of the eight normal DNA control samples (P = 0.007, Student's t-test). Using co-immunoprecipitation, we found that increasing levels of NPM-ALK expression in HEK293 cells resulted in decreased levels of MSH6 bound to MSH2, whereas MSH2·NPM-ALK binding was increased. The NPM-ALK·MSH2 interaction was dependent on the activation/autophosphorylation of NPM-ALK, and the Y191 residue of NPM-ALK was a crucial site for this interaction and NPM-ALK-mediated MMR suppression. MSH2 was found to be tyrosine phosphorylated in the presence of NPM-ALK. Finally, NPM-ALK impeded the expected DNA damage-induced translocation of MSH2 out of the cytoplasm. To conclude, our data support a model in which the suppression of MMR by NPM-ALK is attributed to its ability to interfere with normal MSH2 biochemistry and function.

  18. Evaluating the performance of clinical criteria for predicting mismatch repair gene mutations in Lynch syndrome: a comprehensive analysis of 3,671 families.

    Science.gov (United States)

    Steinke, Verena; Holzapfel, Stefanie; Loeffler, Markus; Holinski-Feder, Elke; Morak, Monika; Schackert, Hans K; Görgens, Heike; Pox, Christian; Royer-Pokora, Brigitte; von Knebel-Doeberitz, Magnus; Büttner, Reinhard; Propping, Peter; Engel, Christoph

    2014-07-01

    Carriers of mismatch repair (MMR) gene mutations have a high lifetime risk for colorectal and endometrial cancers, as well as other malignancies. As mutation analysis to detect these patients is expensive and time-consuming, clinical criteria and tumor-tissue analysis are widely used as pre-screening methods. The aim of our study was to evaluate the performance of commonly applied clinical criteria (the Amsterdam I and II Criteria, and the original and revised Bethesda Guidelines) and the results of tumor-tissue analysis in predicting MMR gene mutations. We analyzed 3,671 families from the German HNPCC Registry and divided them into nine mutually exclusive groups with different clinical criteria. A total of 680 families (18.5%) were found to have a pathogenic MMR gene mutation. Among all 1,284 families with microsatellite instability-high (MSI-H) colorectal cancer, the overall mutation detection rate was 53.0%. Mutation frequencies and their distribution between the four MMR genes differed significantly between clinical groups (p small-bowel cancer (p small-bowel cancer were clinically relevant predictors for Lynch syndrome. © 2013 UICC.

  19. Experimental assessment of concrete damage due to exposure to high temperature and efficacy of the repair system

    Directory of Open Access Journals (Sweden)

    Guruprasad Y.K.

    2013-09-01

    Full Text Available The present study experimentally evaluates the performance of control (standard cylinder specimen, damaged (mechanical loading after thermal exposure and repaired / retrofitted normal plain concrete cylinders using different repair schemes such as on use of FRP wraps, Geo-polymers, etc., to restore the capacity of damaged structural concrete elements. The control-companion specimen in the series provides the reference frame against which both, specimen damage levels were quantified and the benefits of a specimen repaired subsequent to damage were assessed.

  20. Reliability optimization of binary state non-repairable systems: A state of the art survey

    Directory of Open Access Journals (Sweden)

    Roya Soltani

    2014-06-01

    Full Text Available IThe purpose of this paper is to discuss the state of the art on models and methods for reliability optimization problems (ROPs including reliability allocation, redundancy allocation and reliability-redundancy allocation. There are literally few surveys for reviewing the literature of the ROPs. Tillman et al. (1980 classified the related papers by system structure, problem type, and solution methods, separately. In another work, Tzafestas (1980 reviewed system reliability optimization models and the optimization techniques. Yearout (1986 reviewed the literature related to standby redundancy. Kuo (2000 studied the system reliability optimization based on system structure and solution methods. Kuo and Prasad (2004 overviewed system reliability optimization methods. Later, Kuo (2007 reviewed recent advances in optimal reliability allocation problems. The present study adds to the previous literature surveys and focuses mainly on papers after year 2000 but with a quick review on the previous works so that the readers become familiar with the existing approaches. This research investigates the literature from system structure, system performance, uncertainty state and solution approach standpoints, simultaneously.

  1. Complementary analysis of microsatellite tumor profile and mismatch repair defects in colorectal carcinomas

    Institute of Scientific and Technical Information of China (English)

    Alfredo Blanes; Salvador J Diaz-Cano

    2006-01-01

    Microsatellite instability (MSI) is a prognostic factor and a marker of deficient mismatch repair (MMR) in colorectal adenocarcinomas (CRC). However, a proper application of this marker requires understanding the following: (1)The MSI concept: The PCR approach must amplify the correct locus and accurately identify the microsatellite pattern in the patient's normal tissue. MSI is demonstrated when the length of DNA sequences in a tumor differs from that of nontumor tissue. Any anomalous expansion or reduction of tandem repeats results in extra-bands normally located in the expected size range (100 bp,above or below the expected product), differ from the germline pattern by some multiple of the repeating unit,and must show appropriate stutter. (2) MSI mechanisms:MMR gene inactivation (by either mutation or protein down-regulation as frequently present in deep CRC compartments) leads to mutation accumulation in a cell with every cellular division, resulting in malignant transformation. These mechanisms can express tumor progression and result in a decreased prevalence of aneuploid cells and loss of the physiologic cell kinetic correlations in the deep CRC compartments. MSI molecular mechanisms are not necessarily independent from chromosomal instability and may coexist in a given CRC. (3) Because of intratumoural heterogeneity, at least two samples from each CRC should be screened, preferably from the superficial (tumor cells above the muscularis propria) and deep (tumor cells infiltrating the muscularis propria) CRC compartments to cover the topographic tumor heterogeneity. (4) Pathologists play a critical role in identifying microsatellite-unstable CRC, such as occur in young patients with synchronous or metachronous tumors or with tumors showing classic histologic features. In these cases, MSI testing and/or MMR immunohistochemistry are advisable, along with gene sequencing and genetic counseling if appropriate. MSI is an excellent functional and prognostically

  2. Both microsatellite length and sequence context determine frameshift mutation rates in defective DNA mismatch repair.

    Science.gov (United States)

    Chung, Heekyung; Lopez, Claudia G; Holmstrom, Joy; Young, Dennis J; Lai, Jenny F; Ream-Robinson, Deena; Carethers, John M

    2010-07-01

    It is generally accepted that longer microsatellites mutate more frequently in defective DNA mismatch repair (MMR) than shorter microsatellites. Indeed, we have previously observed that the A10 microsatellite of transforming growth factor beta type II receptor (TGFBR2) frameshifts -1 bp at a faster rate than the A8 microsatellite of activin type II receptor (ACVR2), although both genes become frameshift-mutated in >80% of MMR-defective colorectal cancers. To experimentally determine the effect of microsatellite length upon frameshift mutation in gene-specific sequence contexts, we altered the microsatellite length within TGFBR2 exon 3 and ACVR2 exon 10, generating A7, A10 and A13 constructs. These constructs were cloned 1 bp out of frame of EGFP, allowing a -1 bp frameshift to drive EGFP expression, and stably transfected into MMR-deficient cells. Subsequent non-fluorescent cells were sorted, cultured for 7-35 days and harvested for EGFP analysis and DNA sequencing. Longer microsatellites within TGFBR2 and ACVR2 showed significantly higher mutation rates than shorter ones, with TGFBR2 A13, A10 and A7 frameshifts measured at 22.38x10(-4), 2.17x10(-4) and 0.13x10(-4), respectively. Surprisingly, shorter ACVR2 constructs showed three times higher mutation rates at A7 and A10 lengths than identical length TGFBR2 constructs but comparably lower at the A13 length, suggesting influences from both microsatellite length as well as the sequence context. Furthermore, the TGFBR2 A13 construct mutated into 33% A11 sequences (-2 bp) in addition to expected A12 (-1 bp), indicating that this construct undergoes continual subsequent frameshift mutation. These data demonstrate experimentally that both the length of a mononucleotide microsatellite and its sequence context influence mutation rate in defective DNA MMR.

  3. Both hMutSα and hMutSß DNA mismatch repair complexes participate in 5-fluorouracil cytotoxicity.

    Directory of Open Access Journals (Sweden)

    Akihiro Tajima

    Full Text Available BACKGROUND: Patients with advanced microsatellite unstable colorectal cancers do not show a survival benefit from 5-fluorouracil (5-FU-based chemotherapy. We and others have shown that the DNA mismatch repair (MMR complex hMutSα binds 5-FU incorporated into DNA. Although hMutSß is known to interact with interstrand crosslinks (ICLs induced by drugs such as cisplatin and psoralen, it has not been demonstrated to interact with 5-FU incorporated into DNA. Our aim was to examine if hMutSß plays a role in 5-FU recognition. METHODS: We compared the normalized growth of 5-FU treated cells containing either or both mismatch repair complexes using MTT and clonogenic assays. We utilized oligonucleotides containing 5-FU and purified baculovirus-synthesized hMutSα and hMutSß in electromobility shift assays (EMSA and further analyzed binding using surface plasmon resonance. RESULTS: MTT and clonogenic assays after 5-FU treatment demonstrated the most cytotoxicity in cells with both hMutSα and hMutSß, intermediate cytotoxicity in cells with hMutSα alone, and the least cytotoxicity in cells with hMutSß alone, hMutSß binds 5-FU-modified DNA, but its relative binding is less than the binding of 5-FU-modified DNA by hMutSα. CONCLUSION: Cytotoxicity induced by 5-FU is dependent on intact DNA MMR, with relative cell death correlating directly with hMutSα and/or hMutSß 5-FU binding ability (hMutSα>hMutSß. The MMR complexes provide a hierarchical chemosensitivity for 5-FU cell death, and may have implications for treatment of patients with certain MMR-deficient tumors.

  4. Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair

    Directory of Open Access Journals (Sweden)

    Zhu K

    2014-11-01

    Full Text Available Kai Zhu,1,2 Hao Lai,1,2 Changfa Guo,1,2 Jun Li,1,2 Yulin Wang,1,2 Lingyan Wang,3 Chunsheng Wang1,2 1Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Institute of Cardiovascular Disease, Shanghai, People’s Republic of China; 3Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China Abstract: Mesenchymal stem cell (MSC transplantation has attracted much attention in myocardial infarction therapy. One of the limitations is the poor survival of grafted cells in the ischemic microenvironment. Small interfering RNA-mediated prolyl hydroxylase domain protein 2 (PHD2 silencing in MSCs holds tremendous potential to enhance their survival and paracrine effect after transplantation. However, an efficient and biocompatible PHD2 silencing system for clinical application is lacking. Herein, we developed a novel PHD2 silencing system based on arginine-terminated generation 4 poly(amidoamine (Arg-G4 nanoparticles. The system exhibited effective and biocompatible small interfering RNA delivery and PHD2 silencing in MSCs in vitro. After genetically modified MSC transplantation in myocardial infarction models, MSC survival and paracrine function of IGF-1 were enhanced significantly in vivo. As a result, we observed decreased cardiomyocyte apoptosis, scar size, and interstitial fibrosis, and increased angiogenesis in the diseased myocardium, which ultimately attenuated ventricular remodeling and improved heart function. This work demonstrated that an Arg-G4 nanovector-based PHD2 silencing system could enhance the efficiency of MSC transplantation for infarcted myocardium repair. Keywords: nanoparticles, PHD2, siRNA delivery, mesenchymal stem cells, myocardial infarction

  5. Final Environmental Assessment Airfield Storm Drainage System Repair Joint Base Andrews-Naval Air Facility Washington, MD

    Science.gov (United States)

    2015-06-01

    eastern cottontail (Sylvilagus floridanus). Reptiles occasionally found on the airfield include the eastern garter snake (Thamnophis sirtalis...and Noise Control. Acoustical Society of America . Sewickley, PA. HDR (HDR Engineering, Inc.). 2014. Design Analysis. Design for Repair/Replacement of

  6. The Proposal of Demand Estimation of Repairable Items for the Weapon Systems During the Initial Support Period: F-16 Case Study

    Directory of Open Access Journals (Sweden)

    Bahtiyar Eren

    2012-02-01

    Full Text Available Every country that has military systems such as aircraft, radar, warship or tank has to meet the operational needs of those military systems in order to keep them ready for military operations. Logistics support needs are defined basically either before or after procurement. If they are defined before procurement, they are called "initial support requirement", otherwise called "sustainment support requirement". Due to the fact that new system will be added into the Turkish military inventory, it is focused on the initial support requirement phase. In addition to that, it is focused on repairable items since most of the material acquisition cost within the initial support budget is allocated to repairable items. In this study, within the scope of initial support requirements,the method that produces much better results in terms of quantity and cost perspective than the ones used in Turkey and USA is established and demonstrated by using real data set of F-16.

  7. Therapy and progression – induced O6-methylguanine-DNA methyltransferase and mismatch repair alterations in recurrent glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    S Agarwal

    2015-01-01

    Full Text Available Despite multimodality treatment protocol including surgical resection, radiotherapy, and chemotherapy in patients with glioblastoma multiforme (GBM, most suffer from treatment failure and tumor recurrence within a few months of initial surgery. The effectiveness of temozolomide (TMZ, the most commonly used chemotherapeutic agent, is largely dependent on the methylation status of the promoter of the gene O6-methylguanine-DNA methyltransferase (MGMT and the integrity of the mismatch repair (MMR system. Changes in these regulatory mechanisms at the time of recurrence may influence response to therapy. Deciphering the molecular mechanisms of resistance to these drugs may in future lead to improvised patient management. In this article, we provide an update of the spectrum of molecular changes that occur in recurrent GBMs, and thus may have an impact on patient survival and treatment response. For review, electronic search for the keywords “Recurrent GBM”, “Recurrent GBM AND MGMT” “Recurrent glioma AND MGMT”, “Recurrent GBM AND MMR” and “Recurrent glioma AND MMR”, “Recurrent GBM AND MMR” and “Recurrent glioma AND MMR” was done on PubMed and relevant citations were screened including cross-references.

  8. Assessment of the functionality of bacteria-based repair system for concrete through ESEM analysis

    NARCIS (Netherlands)

    Wiktor, V.; Jonkers, H.M.

    2015-01-01

    Biodeposition, a method by which calcium carbonate (CaCO3) precipitation is induced by bacteria, has been proposed as an interesting approach to protect building materials. The liquid-based system presented in this paper aims at the sealing of cracks and decrease of the porosity due to the productio

  9. 3D bioprinting of neural stem cell-laden thermoresponsive biodegradable polyurethane hydrogel and potential in central nervous system repair.

    Science.gov (United States)

    Hsieh, Fu-Yu; Lin, Hsin-Hua; Hsu, Shan-Hui

    2015-12-01

    The 3D bioprinting technology serves as a powerful tool for building tissue in the field of tissue engineering. Traditional 3D printing methods involve the use of heat, toxic organic solvents, or toxic photoinitiators for fabrication of synthetic scaffolds. In this study, two thermoresponsive water-based biodegradable polyurethane dispersions (PU1 and PU2) were synthesized which may form gel near 37 °C without any crosslinker. The stiffness of the hydrogel could be easily fine-tuned by the solid content of the dispersion. Neural stem cells (NSCs) were embedded into the polyurethane dispersions before gelation. The dispersions containing NSCs were subsequently printed and maintained at 37 °C. The NSCs in 25-30% PU2 hydrogels (∼680-2400 Pa) had excellent proliferation and differentiation but not in 25-30% PU1 hydrogels. Moreover, NSC-laden 25-30% PU2 hydrogels injected into the zebrafish embryo neural injury model could rescue the function of impaired nervous system. However, NSC-laden 25-30% PU1 hydrogels only showed a minor repair effect in the zebrafish model. In addition, the function of adult zebrafish with traumatic brain injury was rescued after implantation of the 3D-printed NSC-laden 25% PU2 constructs. Therefore, the newly developed 3D bioprinting technique involving NSCs embedded in the thermoresponsive biodegradable polyurethane ink offers new possibilities for future applications of 3D bioprinting in neural tissue engineering.

  10. 36. Anesthesia for high risk patients undergoing percutaneous mitral valve repair with the mitraclip system in the catheterization laboratory

    Directory of Open Access Journals (Sweden)

    R. Soliman

    2016-07-01

    Full Text Available MitraClip system implantation is used inhigh-risk patients with severe mitral regurgitation.anesthetic management for mitral clip implantation. The study included 34patients scheduled for MitraClip implantations in the catheterization laboratory. An arterial line and central venous line were inserted under local anesthesia before induction. Epinephrine was started before induction and milrinone infusion was started after induction. The anesthetic technique for induction and maintenance was the same for all patients. All patients were hemodynamically stable intra- and postoperatively. The intervention was successful in 33 cases and aborted in one case because of severe posteromedial leaflet tethering. The epinephrine and milrinone were weaned and all patients were extubated, except, one case mortality happened within the first 8 hours postoperatively. Percutaneous mitral valve repair with MitraClip implantation is a successful alternative in high-risk patients with symptomatic severe mitral regurgitation. Starting epinephrine before anesthetic induction and milrinone infusion induction resulted in decreased pulmonary artery pressure, increased ejection fraction and maintained arterial blood pressure during procedure inspite of worse preoperative conditions.

  11. Single-stage implantation in the atrophic alveolar ridge of the mandible with the Norian skeletal repair system.

    Science.gov (United States)

    Hölzle, Frank; Bauer, Florian; Kesting, Marco R; Mücke, Thomas; Deppe, Herbert; Wolff, Klaus-Dietrich; Swaid, Sami

    2011-10-01

    Dental implants have played a part in rehabilitation of the jaws for more than 40 years, but in some cases they alone are inadequate because of extreme alveolar resorption. Correction may necessitate a two-stage procedure with additional interventions. We have made a preliminary study of the use of the Norian skeletal repair system (SRS), a carbonated calcium phosphate bone cement used to augment the alveolar ridge as a single-stage procedure, with the placement of implants. Ten edentulous patients with insufficient vertical bone in the interforaminal area were treated. After a horizontal osteotomy and crestal mobilisation of the alveolar ridge, implants were placed through the crestal part and fixed in the basal part of the mandible. Norian SRS was used to fill the gap created. The prostheses were inserted 3 months later. Forty implants were inserted. The follow up period was 60 months, and no fractures or dislocations developed. One of the implants was lost and there was one wound dehiscence, but no surgical intervention or revision was necessary. Radiographs showed good consolidation of the bony structure in all cases. We have described a reliable, single-stage procedure for augmentation and implantation in a highly atrophic alveolar crest. A 98% survival is comparable with those of other techniques. Further clinical trials are necessary to replicate these promising results.

  12. The nucleotide excision repair (NER system of Helicobacter pylori: Role in mutation prevention and chromosomal import patterns after natural transformation

    Directory of Open Access Journals (Sweden)

    Moccia Claudia

    2012-05-01

    Full Text Available Abstract Background Extensive genetic diversity and rapid allelic diversification are characteristics of the human gastric pathogen Helicobacter pylori, and are believed to contribute to its ability to cause chronic infections. Both a high mutation rate and frequent imports of short fragments of exogenous DNA during mixed infections play important roles in generating this allelic diversity. In this study, we used a genetic approach to investigate the roles of nucleotide excision repair (NER pathway components in H. pylori mutation and recombination. Results Inactivation of any of the four uvr genes strongly increased the susceptibility of H. pylori to DNA damage by ultraviolet light. Inactivation of uvrA and uvrB significantly decreased mutation frequencies whereas only the uvrA deficient mutant exhibited a significant decrease of the recombination frequency after natural transformation. A uvrC mutant did not show significant changes in mutation or recombination rates; however, inactivation of uvrC promoted the incorporation of significantly longer fragments of donor DNA (2.2-fold increase into the recipient chromosome. A deletion of uvrD induced a hyper-recombinational phenotype. Conclusions Our data suggest that the NER system has multiple functions in the genetic diversification of H. pylori, by contributing to its high mutation rate, and by controlling the incorporation of imported DNA fragments after natural transformation.

  13. Research on Evolvable Repairing Ability of Bio-inspired Fault-tolerance System%仿生容错系统演化修复能力研究

    Institute of Scientific and Technical Information of China (English)

    巨政权; 满梦华; 褚杰; 常小龙

    2012-01-01

    基于演化硬件技术构建一种仿生容错系统,通过不同模式、数量的故障注入对其演化修复能力进行研究,得到系统故障状况与演化修复能力间的关系:(1)随着故障数量的增加,系统演化修复能力的主要影响因素从演化算法的效率逐步向演化修复过程中的故障“躲避”概率转移;(2)系统的演化修复能力与故障数量符合指数衰减规律.%Based on the Evolvable Hardware EH W) technique, a bio-inspired fault-tolerance system is design and constructed, and the evolvable repairing ability is researched under the different fault modes and quantities. This paper obtains some relations between the faults and the evolvable repairing ability through analyzing the measured data. And there are two most valuable results: (l)With the increase of the quantity of faults, the main influence factors of the evolvable repairing ability are shift from the efficiency of evolution strategy to the probability of the fault avoided; (2)The evolvable repairing ability and the fault quantity are in accord with the exponential decay law.

  14. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    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 DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of 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. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  15. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    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 DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of 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. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  16. Advanced biomaterials for repairing the nervous system: what can hydrogels do for the brain?

    Directory of Open Access Journals (Sweden)

    Zin Z. Khaing

    2014-09-01

    Full Text Available Newly developed hydrogels are likely to play significant roles in future therapeutic strategies for the nervous system. In this review, unique features of the central nervous system (i.e., the brain and spinal cord that are important to consider in developing engineered biomaterials for therapeutic applications are discussed. This review focuses on recent findings in hydrogels as biomaterials for use as (1 drug delivery devices, specifically focusing on how the material can change the delivery rate of small molecules, (2 scaffolds that can modify the post-injury environment, including preformed and injectable scaffolds, (3 cell delivery vehicles, discussing cellular response to natural and synthetic polymers as well as structured and amorphous materials, and (4 scaffolds for tissue regeneration, describing micro- and macro-architectural constructs that have been designed for neural applications. In addition, key features in each category that are likely to contribute to the translational success of these biomaterials are highlighted.

  17. The Challenges of Sensing and Repairing Software Defects in Autonomous Systems

    Science.gov (United States)

    2014-05-09

    designing accurate anomaly detection systems.” IFIP/ACM Latin American Networking Conference, San Jose, Costa Rica , 2007. 14  Approved for public...loss-to-computer-bugs-18122012.htm, 2012. [9] Mike Mount, Quijano Elaine. “Iraqi insurgents hacked Predator drone feeds, U.S. official indicates...CNN.com, URL: http: // www. cnn. com/ 2009/ US/ 12/ 17/ drone . video. hacked/ index. html , Dec. 17, 2009. [10] B. Cox, D. Evans, A. Filipi, J

  18. Delivery Systems for Bone Morphogenetic Protein (BMP) for Repair of Battle Incurred Bone Injuries.

    Science.gov (United States)

    1987-11-01

    infections, congenital malformations that fail to heal are eligible for BMP treatment. I (my child/my ward) will be one of 50 patients to be treated with...Fusions in Dogs 6. Craniotomy Defects in Sheep t0 7. Craniotomy Defects in Monkeys 10 8. BMP Delivery System of Bone Matrix Non Collagenous 11 Proteins...effects. The most important and indispensptle substitutes for experiments in human beings are adult mongrel dogs, monkeys, and sheep . Experimental .S

  19. DNA repair in neurons: So if they don't divide what's to repair?

    Energy Technology Data Exchange (ETDEWEB)

    Fishel, Melissa L. [Department of Pediatrics (Section of Hematology/Oncology), Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut, Room 302C, Indianapolis, IN 46202 (United States); Vasko, Michael R. [Department of Pharmacology and Toxicology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202 (United States); Kelley, Mark R. [Department of Pediatrics (Section of Hematology/Oncology), Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut, Room 302C, Indianapolis, IN 46202 (United States) and Department of Pharmacology and Toxicology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202 (United States) and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 1044 W. Walnut, Room 302C, Indianapolis, IN 46202 (United States)]. E-mail: mkelley@iupui.edu

    2007-01-03

    Neuronal DNA repair remains one of the most exciting areas for investigation, particularly as a means to compare the DNA repair response in mitotic (cancer) vs. post-mitotic (neuronal) cells. In addition, the role of DNA repair in neuronal cell survival and response to aging and environmental insults is of particular interest. DNA damage caused by reactive oxygen species (ROS) such as generated by mitochondrial respiration includes altered bases, abasic sites, and single- and double-strand breaks which can be prevented by the DNA base excision repair (BER) pathway. Oxidative stress accumulates in the DNA of the human brain over time especially in the mitochondrial DNA (mtDNA) and is proposed to play a critical role in aging and in the pathogenesis of several neurological disorders including Parkinson's disease, ALS, and Alzheimer's diseases. Because DNA damage accumulates in the mtDNA more than nuclear DNA, there is increased interest in DNA repair pathways and the consequence of DNA damage in the mitochondria of neurons. The type of damage that is most likely to occur in neuronal cells is oxidative DNA damage which is primarily removed by the BER pathway. Following the notion that the bulk of neuronal DNA damage is acquired by oxidative DNA damage and ROS, the BER pathway is a likely area of focus for neuronal studies of DNA repair. BER variations in brain aging and pathology in various brain regions and tissues are presented. Therefore, the BER pathway is discussed in greater detail in this review than other repair pathways. Other repair pathways including direct reversal, nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination and non-homologous end joining are also discussed. Finally, there is a growing interest in the role that DNA repair pathways play in the clinical arena as they relate to the neurotoxicity and neuropathy associated with cancer treatments. Among the numerous side effects of cancer treatments, major

  20. Aircraft Propeller Hub Repair

    Energy Technology Data Exchange (ETDEWEB)

    Muth, Thomas R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Peter, William H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    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.

  1. A Combined Brazing and Aluminizing Process for Repairing Turbine Blades by Thermal Spraying Using the Coating System NiCrSi/NiCoCrAlY/Al

    Science.gov (United States)

    Nicolaus, M.; Möhwald, K.; Maier, H. J.

    2017-08-01

    The repair and maintenance of components in the aerospace industry play an increasingly important role due to rising manufacturing costs. Besides welding, vacuum brazing is a well-established repair process for turbine blades made of nickel-based alloys. After the coating of the worn turbine blade has been removed, the manual application of the nickel-based filler metal follows. Subsequently, the hot gas corrosion-protective coating is applied by thermal spraying. The brazed turbine blade is aluminized to increase the hot gas corrosion resistance. The thermal spray technology is used to develop a two-stage hybrid technology that allows shortening the process chain for repair brazing turbine blades and is described in the present paper. In the first step, the coating is applied on the base material. Specifically, the coating system employed here is a layer system consisting of nickel filler metal, NiCoCrAlY and aluminum. The second step represents the combination of brazing and aluminizing of the coating system which is subjected to a heat treatment. The microstructure, which results from the combined brazing and aluminizing process, is characterized and the relevant diffusion processes in the coating system are illustrated. The properties of the coating and the ramifications with respect to actual applications will be discussed.

  2. Nuclear power plant steam pipes repairing with Tirant 3 Robot system

    Energy Technology Data Exchange (ETDEWEB)

    Soto, M.; Curiel, M. [Logistica y Acondicionamientos Industriales SAU, Sorolla Center, local 10, Av. de las Cortes Valencianas No. 58, 46015 Valencia (Spain); Lazaro, F. [Revestimientos Anticorrosivos Industriales, S. L. U., Sorolla Center, local 10, Av. de las Cortes Valencianas No. 58, 46015 Valencia (Spain); Arnaldos, A., E-mail: m.soto@lainsa.co [TITANIA Servicios Tecnologicos SL, Sorolla Center, local 10, Av. de las Cortes Valencianas No. 58, 46015 Valencia (Spain)

    2010-10-15

    The metallization arc spray process is based on the projection of molten metal, supplied by means of different stainless alloys wire, over a surface of carbon steel usually, with the object of serving as protection against erosion-corrosion, increasing resistance to abrasion and detrition. A typical application functions covering the steam pipes inner surface in coal-fired power station and nuclear power plants. The results of this process are spectacular in terms of protection against corrosion and abrasion, but its application has conditioning factors, such as: Severe application conditions for workers. Due to the worker's postural position (usually kneeling) in 32 diameter pipes and working with fireproof clothing and masks with outdoor air supplying, due to fumes, sparks and molten metal particles, radiological contamination, confined space, poor lighting, ... Coating uniformity. As metallization is a manual process, the carried out measurements show small variations in the thickness of the coating, always within the tolerance limits established by the applicable regulations and quality assurance. An increase in the uniformity of the projected coating, increase the resistance and give a better surface protection. For all these reasons, Lainsa has developed the Tirant 3 robot, a worldwide innovative system, for metallization of steam pipes inner surface. Tirant 3 robot is tele operated from outside of the pipe, so that human intervention is reduced to the operations of robot positioning and change of metallization wire. As it is an independent system of the human factor, metallization process performance is significantly increased by reducing rest periods due only to the robot maintenance. Likewise, Tirant 3 system permits to increase resulting coating uniformity and thus its resistance, keeping selected parameters constant (forward speed, rotation speed and inner surface distance) depending on required type and thickness of wire. (Author)

  3. 40 CFR 60.692-6 - Standards: Delay of repair.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Standards: Delay of repair. 60.692-6... From Petroleum Refinery Wastewater Systems § 60.692-6 Standards: Delay of repair. (a) Delay of repair of facilities that are subject to the provisions of this subpart will be allowed if the repair...

  4. 48 CFR 1371.118 - Changes-ship repair.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Changes-ship repair. 1371... SUPPLEMENTAL REGULATIONS ACQUISITIONS INVOLVING SHIP CONSTRUCTION AND SHIP REPAIR Provisions and Clauses 1371.118 Changes—ship repair. Insert clause 1352.271-87, Changes—Ship Repair, in all solicitations...

  5. 48 CFR 252.247-7025 - Reflagging or repair work.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Reflagging or repair work... of Provisions And Clauses 252.247-7025 Reflagging or repair work. As prescribed in 247.574(d), use the following clause: Reflagging or Repair Work (JUN 2005) (a) Definition. Reflagging or repair...

  6. The therapeutic potential of microRNAs in nervous system damage, degeneration, and repair.

    Science.gov (United States)

    Hutchison, Emmette R; Okun, Eitan; Mattson, Mark P

    2009-01-01

    MicroRNAS (miRNAs) have been suggested to play important roles in the central nervous system during development as well as disease. miRNAs appear to be dysregulated in a number of neurodegenerative diseases, developmental disorders, and as a result of stroke. Each miRNA has the ability to regulate hundreds of messenger RNA transcripts, both by causing degradation of the mRNA and by inhibition of protein translation. Recent findings suggest that it may eventually be possible to treat some neurological disorders by restoring or inhibiting miRNAs altered by disease pathology. Both viral delivery and administration of modified oligonucleotides mimicking or inhibiting specific miRNAs have been effective in model systems. Artificial miRNAs have also been generated for the repression of specific transcripts. Alteration of miRNA expression by disease and insult also holds the potential for improved diagnostic tools. Finally, miRNAs have been shown to control cellular proliferation and specification, suggesting that manipulation of miRNAs in cultured cells could result in more convenient generation of pure cell populations for transplantation.

  7. Simple facet joint repair with dynamic pedicular system: Technical note and case series

    Directory of Open Access Journals (Sweden)

    Ali Fahir Ozer

    2015-01-01

    Full Text Available Purpose: Facet joints are important anatomical structures for the stability of spine. Surgical or degenerative damage to a facet joint may lead to spinal instability and causes clinical problems. This article explains the importance of facet joints, reviews facet replacement systems, and describes a simple and effective method for facet replacement after surgical removal of facet joints. Materials and Methods: Ten patients were operated with the diagnosis of unilateral nerve root compression secondary to facet degeneration. The hypertrophic facet joints were removed with microsurgical techniques and the roots were decompressed. Then, a unilateral artificial facet joint was created using two hinged screws and a dynamic rod. Results: The clinical outcome of all the patients was determined good or excellent at second and last follow-up (mean 13.3 months controls using visual analog scale (VAS and Oswestry Disability Index (ODI scores. Radiological evaluations also demonstrated no implant-related complications. Conclusions: The authors suggest that, if removal of a facet joint is necessary to decompress the nerve roots, the joint can be replaced by a construct composed of two hinged screws connected by a dynamic rod. This simple system mimics the function of a normal facet joint and is an effective technique for unilateral facet joint replacement.

  8. Sensors systems for the automation of operations in the ship repair industry.

    Science.gov (United States)

    Navarro, Pedro Javier; Muro, Juan Suardíaz; Alcover, Pedro María; Fernández-Isla, Carlos

    2013-09-13

    Hull cleaning before repainting is a key operation in the maintenance of ships. For years, a method to improve such operation has been sought by means of the robotization of techniques such as grit blasting and ultra high pressure water jetting. Despite this, it continues to be standard practice in shipyards that this process is carried out manually because the developed robotized systems are too expensive to be widely accepted by shipyards. We have chosen to apply a more conservative and realistic approach to this problem, which has resulted in the development of several solutions that have been designed with different automation and operation range degrees. These solutions are fitted with most of the elements already available in many shipyards, so the installation of additional machinery in the workplace would not be necessary. This paper describes the evolutionary development of sensor systems for the automation of the preparation process of ship hull surfaces before the painting process is performed. Such evolution has given rise to the development of new technologies for coating removal.

  9. Information is in the eye of the beholder: Seeking information on the MMR vaccine through an Internet search engine.

    Science.gov (United States)

    Yom-Tov, Elad; Fernandez-Luque, Luis

    2014-01-01

    Vaccination campaigns are one of the most important and successful public health programs ever undertaken. People who want to learn about vaccines in order to make an informed decision on whether to vaccinate are faced with a wealth of information on the Internet, both for and against vaccinations. In this paper we develop an automated way to score Internet search queries and web pages as to the likelihood that a person making these queries or reading those pages would decide to vaccinate. We apply this method to data from a major Internet search engine, while people seek information about the Measles, Mumps and Rubella (MMR) vaccine. We show that our method is accurate, and use it to learn about the information acquisition process of people. Our results show that people who are pro-vaccination as well as people who are anti-vaccination seek similar information, but browsing this information has differing effect on their future browsing. These findings demonstrate the need for health authorities to tailor their information according to the current stance of users.

  10. The efficiency of homologous recombination and non-homologous end joining systems in repairing double-strand breaks during cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Leonardo Bee

    Full Text Available This study investigated the efficiency of Non-Homologous End Joining (NHEJ and Homologous Recombination (HR repair systems in rejoining DNA double-strand breaks (DSB induced in CCD-34Lu cells by different γ-ray doses. The kinetics of DNA repair was assessed by analyzing the fluorescence decrease of γ-H2AX foci measured by SOID (Sum Of Integrated Density parameter and counting foci number in the time-interval 0.5-24 hours after irradiation. Comparison of the two methods showed that the SOID parameter was useful in determining the amount and the persistence of DNA damage signal after exposure to high or low doses of ionizing radiation. The efficiency of DSB rejoining during the cell cycle was assessed by distinguishing G1, S, and G2 phase cells on the basis of nuclear fluorescence of the CENP-F protein. Six hours after irradiation, γ-H2AX foci resolution was higher in G2 compared to G1 cells in which both NHEJ and HR can cooperate. The rejoining of γ-H2AX foci in G2 phase cells was, moreover, decreased by RI-1, the chemical inhibitor of HR, demonstrating that homologous recombination is at work early after irradiation. The relevance of HR in DSB repair was assessed in DNA-PK-deficient M059J cells and in CCD-34Lu treated with the DNA-PKcs inhibitor, NU7026. In both conditions, the kinetics of γ-H2AX demonstrated that DSBs repair was markedly affected when NHEJ was absent or impaired, even in G2 phase cells in which HR should be at work. The recruitment of RAD51 at DSB sites was, moreover, delayed in M059J and in NU7026 treated-CCD-34Lu, with respect to DNA-PKcs proficient cells and continued for 24 hours despite the decrease in DNA repair. The impairment of NHEJ affected the efficiency of the HR system and significantly decreased cell survival after ionizing radiation, confirming that DSB rejoining is strictly dependent on the integrity of the NHEJ repair system.

  11. Addressing issues of vaccination literacy and psychological empowerment in the measles-mumps-rubella (MMR) vaccination decision-making: a qualitative study.

    Science.gov (United States)

    Fadda, Marta; Depping, Miriam K; Schulz, Peter J

    2015-09-02

    Whether or not to vaccinate one's child is one of the first health-related decisions parents have to make after their child's birth. For the past 20 years, the share of parents choosing not to immunize their children has increased in many countries, for various reasons. Among these, rumors affirming that vaccinations contain dangerous chemicals or might trigger severe chronic diseases have negatively affected parental attitudes towards pediatric immunizations, particularly the vaccination against measles, mumps and rubella (MMR), raising a number of public health concerns. The primary aim of this qualitative study is to understand what drives parents' decision, giving special attention to vaccination literacy and psychological empowerment in such a context. Twenty individual semi-structured interviews were conducted in the Canton of Ticino (Switzerland) between January and June 2014. Participants were either mothers or fathers of children less than 1 year old living in Switzerland. An inductive thematic analysis was performed to identify the main themes with regard to vaccination literacy and psychological empowerment in the MMR vaccination decision-making. Parents' reports yielded four main themes: (a) the paradox of the free choice, referring to the misinterpretation of current vaccination policies; (b) giving up the power, pointing at the outcomes of a low perceived competence; (c) a far-reaching decision, reflecting the importance attributed to the MMR choice and the different levels of impact the decision can have; (d) the demand for shared-decision making, referring to the parental needs in relation to the child's healthcare provider. Understanding what drives parents' management of their children's immunization schedule in terms of vaccination literacy and psychological empowerment can help health professionals to communicate more effectively with parents in order to facilitate an informed decision, and stakeholders to design tailored health education

  12. Eye muscle repair - discharge

    Science.gov (United States)

    ... Lazy eye repair - discharge; Strabismus repair - discharge; Extraocular muscle surgery - discharge ... You or your child had eye muscle repair surgery to correct eye muscle ... term for crossed eyes is strabismus. Children most often ...

  13. Ventral hernia repair

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/007661.htm Ventral hernia repair To use the sharing features on this page, please enable JavaScript. Ventral hernia repair is surgery to repair a ventral hernia. ...

  14. 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 ...

  15. TRAFFIC SENSITIVE AND TRAFFIC LOAD AWARE PATH SELECTION ALGORITHM FOR MMR WIMAX NETWORKS

    Directory of Open Access Journals (Sweden)

    Sandhya Kulkarni

    2011-08-01

    Full Text Available The recent developments in the broadband wireless access (BWA communication systems haveintroduced several major changes to the existing systems. Legacy IEEE 802.16j is one such amendment tothe existing IEEE 802.16 WiMAX family. The key modification introduced by 802.16j system is theconcept of relay station (RS, which may be used to enhance the system coverage or to make systemthroughput optimal. The end terminals, subscriber stations (SS are unchanged in the standard. Theoverall change pertinent to the system has raised many unresolved issues related to RS and multi-hoprelay base station (MR-BS. The selection of path from a SS to MR-BS via a RS is also one of the issues,need to be addressed. The path selection of a SS in both uplink and downlink directions is left open in thestandard. It is very significant to satisfy the traffics of stringent quality of service (QoS requirements andto appropriately manage the resources of a cell under different circumstances. This paper proposes apath selection algorithm to achieve the aforementioned qualities in the network. The path selectionmetrics include traffic load of the transparent relay station and traffic sensitivity factor of the SS. Anextensive simulation work discusses the performance evaluation of the proposed work using QualNetsimulator.

  16. Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair.

    Science.gov (United States)

    Sharma, Aruna; Menon, Preeti; Muresanu, Dafin F; Ozkizilcik, Asya; Tian, Z Ryan; Lafuente, José V; Sharma, Hari S

    2016-01-01

    The blood-brain barrier (BBB) is a physiological regulator of transport of essential items from blood to brain for the maintenance of homeostasis of the central nervous system (CNS) within narrow limits. The BBB is also responsible for export of harmful or metabolic products from brain to blood to keep the CNS fluid microenvironment healthy. However, noxious insults to the brain caused by trauma, ischemia or environmental/chemical toxins alter the BBB function to small as well as large molecules e.g., proteins. When proteins enter the CNS fluid microenvironment, development of brain edema occurs due to altered osmotic balance between blood and brain. On the other hand, almost all neurodegenerative diseases and traumatic insults to the CNS and subsequent BBB dysfunction lead to edema formation and cell injury. To treat these brain disorders suitable drug therapy reaching their brain targets is needed. However, due to edema formation or only a focal disruption of the BBB e.g., around brain tumors, many drugs are unable to reach their CNS targets in sufficient quantity. This results in poor therapeutic outcome. Thus, new technology such as nanodelivery is needed for drugs to reach their CNS targets and be effective. In this review, use of nanowires as a possible novel tool to enhance drug delivery into the CNS in various disease models is discussed based on our investigations. These data show that nanowired delivery of drugs may have superior neuroprotective ability to treat several CNS diseases effectively indicating their role in future therapeutic strategies.

  17. Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system

    Science.gov (United States)

    Gonzalez, Ginez A.; Hofer, Matthias P.; Syed, Yasir A.; Amaral, Ana I.; Rundle, Jon; Rahman, Saifur; Zhao, Chao; Kotter, Mark R. N.

    2016-01-01

    Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models. PMID:27554391

  18. Immune response to the mumps component of the MMR vaccine in the routine of immunisation services in the Brazilian National Immunisation Program

    Directory of Open Access Journals (Sweden)

    Eliane Matos dos Santos

    2014-06-01

    Full Text Available A non-controlled longitudinal study was conducted to evaluate the combined vaccine against measles, mumps and rubella (MMR immunogenicity in 150 children vaccinated in the routine of three health units in the city of Rio de Janeiro, Brazil, 2008-2009, without other vaccines administered during the period from 30 days before to 30 days after vaccination. A previous study conducted in Brazil in 2007, in 1,769 children ranging from 12-15 months of age vaccinated against yellow fever and MMR simultaneously or at intervals of 30 days or more between doses, had shown low seroconversion for mumps regardless of the interval between administration of the two vaccines. The current study showed 89.5% (95% confidence interval: 83.3; 94.0 seroconversion rate for mumps. All children seroconverted for measles and rubella. After revaccination, high antibody titres and seroconversion rates were achieved against mumps. The results of this study and others suggest that two MMR doses confer optimal immunoresponses for all three antigens and the possible need for additional doses should be studied taking into account not only serological, but also epidemiological data, as there is no serological correlate of protection for mumps.

  19. Anterior cruciate ligament repair with LARS (ligament advanced reinforcement system: a systematic review

    Directory of Open Access Journals (Sweden)

    Machotka Zuzana

    2010-12-01

    Full Text Available Abstract Background Injury to the anterior cruciate ligament (ACL of the knee is common. Following complete rupture of the ACL, insufficient re-vascularization of the ligament prevents it from healing completely, creating a need for reconstruction. A variety of grafts are available for use in ACL reconstruction surgery, including synthetic grafts. Over the last two decades new types of synthetic ligaments have been developed. One of these synthetic ligaments, the Ligament Advanced Reinforcement System (LARS, has recently gained popularity. The aim of this systematic review was to assess the current best available evidence for the effectiveness of the LARS as a surgical option for symptomatic, anterior cruciate ligament rupture in terms of graft stability, rehabilitation time and return to pre-injury function. Method This systematic review included studies using subjects with symptomatic, ACL ruptures undergoing LARS reconstruction. A range of electronic databases were searched in May 2010. The methodological quality of studies was appraised with a modified version of the Law critical appraisal tool. Data relating to study characteristics, surgical times, complication rates, outcomes related to knee stability, quality of life, function, and return to sport as well as details of rehabilitation programs and timeframes were collected. Results This review identified four studies of various designs, of a moderate methodological quality. Only one case of knee synovitis was reported. Patient satisfaction with LARS was high. Graft stability outcomes were found to be inconsistent both at post operative and at follow up periods. The time frames of rehabilitation periods were poorly reported and at times omitted. Return to pre-injury function and activity was often discussed but not reported in results. Conclusions There is an emerging body of evidence for LARS with comparable complication rates to traditional surgical techniques, and high patient

  20. DNA repair in Chromobacterium violaceum.

    Science.gov (United States)

    Duarte, Fábio Teixeira; Carvalho, Fabíola Marques de; Bezerra e Silva, Uaska; Scortecci, Kátia Castanho; Blaha, Carlos Alfredo Galindo; Agnez-Lima, Lucymara Fassarella; Batistuzzo de Medeiros, Silvia Regina

    2004-03-31

    Chromobacterium violaceum is a Gram-negative beta-proteobacterium that inhabits a variety of ecosystems in tropical and subtropical regions, including the water and banks of the Negro River in the Brazilian Amazon. This bacterium has been the subject of extensive study over the last three decades, due to its biotechnological properties, including the characteristic violacein pigment, which has antimicrobial and anti-tumoral activities. C. violaceum promotes the solubilization of gold in a mercury-free process, and has been used in the synthesis of homopolyesters suitable for the production of biodegradable polymers. The complete genome sequence of this organism has been completed by the Brazilian National Genome Project Consortium. The aim of our group was to study the DNA repair genes in this organism, due to their importance in the maintenance of genomic integrity. We identified DNA repair genes involved in different pathways in C. violaceum through a similarity search against known sequences deposited in databases. The phylogenetic analyses were done using programs of the PHILYP package. This analysis revealed various metabolic pathways, including photoreactivation, base excision repair, nucleotide excision repair, mismatch repair, recombinational repair, and the SOS system. The similarity between the C. violaceum sequences and those of Neisserie miningitidis and Ralstonia solanacearum was greater than that between the C. violaceum and Escherichia coli sequences. The peculiarities found in the C. violaceum genome were the absence of LexA, some horizontal transfer events and a large number of repair genes involved with alkyl and oxidative DNA damage.

  1. Efficacy and safety of Elevate® system on apical and anterior compartment prolapse repair with personal technique modification.

    Science.gov (United States)

    Castellani, Daniele; Galica, Vikiela; Saldutto, Pietro; Galatioto, Giuseppe Paradiso; Vicentini, Carlo

    2017-03-07

    To evaluate the effectiveness and safety of Anterior Elevate® mesh kit system (AES) in woman with symptomatic stage 3 or 4 anterior and/or apical pelvic organ prolapse (POP). This retrospective, monocentric, single surgeon study enrolled between May 2010 and January 2013 fifty-six woman experiencing symptomatic anterior vaginal prolapse with or without apical descent (POP-Q stage 3 or 4). All women received a AES and 7 (12.5%) received a concomitant transvaginal hysterectomy. Primary endpoint was anatomic correction of prolapse; success was defined as POP-Q stage ≤ 1 or asymptomatic stage 2. Secondary endpoints were quality-of-life (QOL) results and patients' safety outcomes, which were assessed by 3 validated self-reporting questionnaires at baseline and annually: ICIQ-UI short form, ICIQ-VS and P-QOL. All patients completed 2-years and 28 women 3-years of follow-up. Surgical approach was modified in women with uterus, moving the two-propylene strips anteriorly around the cervix itself crossing one another, so the left will take place in the right side and the right on the opposite. This modification was made in order to better support the uterus. Vaginal mesh exposure was present in 3 (5,3%) patients. Very good anatomical outcomes were seen, with one (1,8%) failure at 6-months, 4 (7,1%) at 1-year, 6 at 2-years (10,7%). Statistically significant improvements were seen in the ICIQ-VS and P-QOL questionnaires throughout follow-up. Our data suggest that AES is a minimally-invasive transvaginal procedure to repair anterior and apical POP, with good evidence related to mid-term safety and efficacy. Copyright® by the International Brazilian Journal of Urology.

  2. Operator Semi-group of Density Evolution Equation for a Repairable Redundant System with Two Same Components%可修冗余系统密度演化方程的算子半群

    Institute of Scientific and Technical Information of China (English)

    史定华; 徐洪; 熊勇; 王远第

    2002-01-01

    For a repairable redundant system consisting of two same components with exponential lifetime and general repair time distribution, the probability densities of the system in some state at time t were determined by a group of ordinary and partial differential equations, called density evolution equations. It was proved that the time-dependent solution of the density evolution equations uniquely exists and strongly converges to its steady state density solution by a semi-group method. In this proof, it is not necessary to suppose that the repair rate function is bounded. The technique of the proof is valuable for many density evolution equations.

  3. Minimally disruptive schedule repair for MCM missions

    Science.gov (United States)

    Molineaux, Matthew; Auslander, Bryan; Moore, Philip G.; Gupta, Kalyan M.

    2015-05-01

    Mine countermeasures (MCM) missions entail planning and operations in very dynamic and uncertain operating environments, which pose considerable risk to personnel and equipment. Frequent schedule repairs are needed that consider the latest operating conditions to keep mission on target. Presently no decision support tools are available for the challenging task of MCM mission rescheduling. To address this capability gap, we have developed the CARPE system to assist operation planners. CARPE constantly monitors the operational environment for changes and recommends alternative repaired schedules in response. It includes a novel schedule repair algorithm called Case-Based Local Schedule Repair (CLOSR) that automatically repairs broken schedules while satisfying the requirement of minimal operational disruption. It uses a case-based approach to represent repair strategies and apply them to new situations. Evaluation of CLOSR on simulated MCM operations demonstrates the effectiveness of case-based strategy. Schedule repairs are generated rapidly, ensure the elimination of all mines, and achieve required levels of clearance.

  4. On a Batch Arrival Queuing System Equipped with a Stand-by Server during Vacation Periods or the Repairs Times of the Main Server

    Directory of Open Access Journals (Sweden)

    Rehab F. Khalaf

    2011-01-01

    Full Text Available We study a queuing system which is equipped with a stand-by server in addition to the main server. The stand-by server provides service to customers only during the period of absence of the main server when either the main server is on a vacation or it is in the state of repairs due to a sudden failure from time to time. The service times, vacation times, and repair times are assumed to follow general arbitrary distributions while the stand-by service times follow exponential distribution. Supplementary variables technique has been used to obtain steady state results in explicit and closed form in terms of the probability generating functions for the number of customers in the queue, the average number of customers, and the average waiting time in the queue while the MathCad software has been used to illustrate the numerical results in this work.

  5. The development of a quantitative scoring system to predict whether a large-to-massive rotator cuff tear can be arthroscopically repaired.

    Science.gov (United States)

    Kim, S-J; Park, J-S; Lee, K-H; Lee, B-G

    2016-12-01

    The aim of the study was to develop a quantitative scoring system to predict whether a large-to-massive rotator cuff tear was arthroscopically reparable prior to surgery. We conducted a retrospective review of the pre-operative MR imaging and surgical records of 87 patients (87 shoulders) who underwent arthroscopic repair of a large-to-massive rotator cuff tear. Patients were divided into two groups, based on the surgical outcome of the repair. Of the 87 patients, 53 underwent complete repair (Group I) and 34 an incomplete repair (Group II). Pre-operative MR images were reviewed to quantify several variables. Between-group differences were evaluated and multiple logistic regression analysis was used to calculate the predictive value of significant variables. The reparability index (RI) was constructed using the odds ratios of significant variables and a receiver operating characteristic curve analysis performed to identify the optimal RI cutoff to differentiate between the two groups. The following variables were identified as independent predictors of arthroscopic reparability: the size of the defect with medial-lateral diameter (cutoff, 4.2 cm) and anterior-posterior diameter (cutoff, 3.7cm); Patte's grade of muscle atrophy (cutoff, grade 3) and Goutallier grade of fatty degeneration (cutoff, grade 3). An RI cutoff value of 2.5 provided the highest differentiation between groups I and II, with an area under the curve of 0.964, and a sensitivity of 73.5% and specificity of 96.2%. The RI developed in our study may prove to be an efficient clinical scoring system to predict whether a large-to-massive rotator cuff tear is arthroscopically reparable. Cite this article: Bone Joint J 2016;98-B:1656-61. ©2016 The British Editorial Society of Bone & Joint Surgery.

  6. A study of molecular signals deregulating mismatch repair genes in prostate cancer compared to benign prostatic hyperplasia.

    Science.gov (United States)

    Basu, Sanmitra; Majumder, Subhadipa; Bhowal, Ankur; Ghosh, Alip; Naskar, Sukla; Nandy, Sumit; Mukherjee, Subhabrata; Sinha, Rajan Kumar; Basu, Keya; Karmakar, Dilip; Banerjee, Soma; Sengupta, Sanghamitra

    2015-01-01

    Prostate cancer is one of the leading causes of mortality among aging males. There is an unmet requirement of clinically useful biomarkers for early detection of prostate cancer to reduce the liabilities of overtreatment and accompanying morbidity. The present population-based study investigates the factors disrupting expression of multiple functionally related genes of DNA mismatch repair pathway in prostate cancer patients to identify molecular attributes distinguishing adenocarcinoma from benign hyperplasia of prostate. Gene expression was compared between tissue samples from prostate cancer and benign prostatic hyperplasia using real-time-PCR, western blot and immunohistochemistry. Assessment of genotypes of seven single-nucleotide-polymorphisms of three MMR genes was conducted using PCR-coupled RFLP and sequencing. Promoter methylation was interrogated by methylation-specific-PCR and bisulfite-sequencing. Interaction between microRNAs and MMR genes was verified by 3'UTR-based dual luciferase assays. Concurrent reduction of three MMR genes namely hMLH1, hMSH6 and hMSH2 (34-85%, Pprostate cancer tissues. hMSH6 polymorphism rs1800932(Pro92Pro) conferred a borderline protection in cancer patients (OR = 0.33, 95% CI = 0.15-0.75). Relative transcript level of hMLH1 was inversely related (r = -0.59, Pprostate cancer. This comparative study reflects that microRNA expression level, particularly hsa-miR-155, exhibits predictive signature of prostate adenocarcinoma.

  7. Sebaceous neoplasms and the immunoprofile of mismatch-repair proteins as a screening target for syndromic cases

    DEFF Research Database (Denmark)

    Boennelycke, Marie; Thomsen, Birthe M; Holck, Susanne

    2015-01-01

    16-negativity in MLH1-deficient cases may denote methylation rather than mutation. The prime aim of this study was to evaluate the mismatch-repair (MMR)-protein deficiency and the p16 status among sebaceous neoplasms. MATERIAL AND METHOD: From January 1990 through October 2012, 26 sebaceous adenomas...... (SAs) and 6 sebaceous carcinomas (SCs) were accrued. The expression of MLH1, MSH2, MSH6, and PMS2 was recorded. MLH1-deficient cases were tested for p16 status. RESULTS: Eighteen (56%) of the 32 specimens with SA or SC displayed MMR-protein deficiency, comprising 17 (65.4%) SAs (MSH2/MSH6 loss in 12......, MLH1/PMS2 loss in 3, MSH6 loss only in 2 cases) and 1 (16.7%) SC (MLH1/PMS2 loss). All 4 MLH1 deficient cases were p16-positive. CONCLUSION: A substantial proportion of sebaceous neoplasms were MMR-protein deficient and thus likely MTS candidates. Given the low prevalence of sebaceous neoplasms...

  8. Aseptic meningitis in a large MMR vaccine campaign (590,609 people in Curitiba, Paraná, Brazil, 1998

    Directory of Open Access Journals (Sweden)

    ARRUDA Walter Oleschko

    2001-01-01

    Full Text Available The aseptic meningitis after Measles-Mumps-Rubella vaccine (MMR is a well recognized complication, and different incidences have been observed in several studies. We retrospectively analyzed forty cases of aseptic meningitis, during a large public immunization campaign (1998 in Curitiba, Southern Brazil (590,609 people, admitted in our Service. The vaccine utilized was Leningrad-3-Zagreb mumps strain, Edmonston-Zagreb measles strain, and RA 27#3 rubella strain. In all county, a total number of 87 cases were reported, resulting in a incidence of 1.7 cases per 10,000 given doses . The mean age was 23.7 ± 12.8 years. The female:male ratio was 1.35:1. Severe headache with meningismus (92.5%, fever (87.5%, nausea/vomiting (82.5% were the most common clinical findings. Three cases (7.5% developed mild mumps. All patients underwent cerebrospinal fluid (CSF tap with the following findings: mononuclear pleocytosis from 100 to 500 cells/mm³ in 17 cases (42.5%; 257.5 ± 260.6 cells/mm³; increased protein 28 cases (67.5%; 92.1 ± 76.9 mg/dL; glucose was normal in all cases (56.8 ± 11.2 mg/dL except in 4 (10% cases, which presented less than 44 mg/dL. All serological tests (latex to bacterial meningitis, Cryptococcus, cysticercosis, VDRL and bacteriological cultures were negative. Virus identification were also negative in 8 samples. None of the patients had neurological deficits or related symptoms after one year of onset. We believe the benefit of vaccination clearly outweights the incidence of benign vaccine-associated meningitis.

  9. Systemic biomarkers of neutrophilic inflammation, tissue injury and repair in COPD patients with differing levels of disease severity.

    Directory of Open Access Journals (Sweden)

    Debra A Cockayne

    Full Text Available The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research. The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls. Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-α and HB-EGF showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups. Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV(1, FEV(1/FVC and DLCO. Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin predicted 21% of the variability in DLCO values. To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile. While analytes related to neutrophil function (EN-RAGE, NGAL, MPO grouped together to form a cluster associated with FEV(1 related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-α formed another cluster associated with both DLCO and FEV(1 related parameters. Associations of Fibrinogen with DLCO and MPO with FEV(1/FVC were stronger in patients without metabolic syndrome (r  =  -0.52, p  =  0.005 and r  =  -0.61, p =  0.023, respectively compared to patients with coexisting metabolic syndrome (r  =  -0.25, p  =  0.47 and r  =  -0.15, p  =  0.96, respectively, and may be driving overall associations in the general cohort. In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV(1, FEV(1/FVC and DLCO. These data highlight systemic

  10. Mutation rates of TGFBR2 and ACVR2 coding microsatellites in human cells with defective DNA mismatch repair.

    Directory of Open Access Journals (Sweden)

    Heekyung Chung

    Full Text Available Microsatellite instability promotes colonic tumorigenesis through generating frameshift mutations at coding microsatellites of tumor suppressor genes, such as TGFBR2 and ACVR2. As a consequence, signaling through these TGFbeta family receptors is abrogated in DNA Mismatch repair (MMR-deficient tumors. How these mutations occur in real time and mutational rates of these human coding sequences have not previously been studied. We utilized cell lines with different MMR deficiencies (hMLH1-/-, hMSH6-/-, hMSH3-/-, and MMR-proficient to determine mutation rates. Plasmids were constructed in which exon 3 of TGFBR2 and exon 10 of ACVR2 were cloned +1 bp out of frame, immediately after the translation initiation codon of an enhanced GFP (EGFP gene, allowing a -1 bp frameshift mutation to drive EGFP expression. Mutation-resistant plasmids were constructed by interrupting the coding microsatellite sequences, preventing frameshift mutation. Stable cell lines were established containing portions of TGFBR2 and ACVR2, and nonfluorescent cells were sorted, cultured for 7-35 days, and harvested for flow cytometric mutation detection and DNA sequencing at specific time points. DNA sequencing revealed a -1 bp frameshift mutation (A9 in TGFBR2 and A7 in ACVR2 in the fluorescent cells. Two distinct fluorescent populations, M1 (dim, representing heteroduplexes and M2 (bright, representing full mutants were identified, with the M2 fraction accumulating over time. hMLH1 deficiency revealed 11 (5.91 x 10(-4 and 15 (2.18 x 10(-4 times higher mutation rates for the TGFBR2 and ACVR2 microsatellites compared to hMSH6 deficiency, respectively. The mutation rate of the TGFBR2 microsatellite was approximately 3 times higher in both hMLH1 and hMSH6 deficiencies than the ACVR2 microsatellite. The -1 bp frameshift mutation rates of TGFBR2 and ACVR2 microsatellite sequences are dependent upon the human MMR background.

  11. 供电急修故障分析系统应用研究%Application Study on Power Supply Urgent Repair Failure Analysis System

    Institute of Scientific and Technical Information of China (English)

    何坚

    2014-01-01

    供电急修故障分析系统对历史急修数据进行提取整合,并利用配电网生产管理系统的设备台账数据、营销系统的低压用户数据,对95598接报停电事件发生的故障情况作出科学的分析,为急修作业人员进行抢修工作和答复用户复电时间提供有效依据。该系统由停电判断、故障字典查询、分类汇总查询、历史故障台区查询四大功能模块组成,主要完成故障类型、故障原因、解决方式、平均复电时间等功能,能更准确合理地判断故障和解决故障。供电急修故障分析系统为供电企业建立起一套实用、科学、快速的故障决策系统。%The power supply urgent repair failure analysis system is used for extracting and integrating historical urgent repair data and making scientific analysis on power cut failures reported by 95598 according to equipment standing book data of production management system of power distribution network and low voltage customer data of marketing system which is a-ble to provide efficient basis for operating personnel to carry on urgent repairs and reply customers power recovery time.This system is consisted of four function modules including power cut predication,failure dictionary inquiry,classification collec-tion inquiry and historical failure district inquiry.It is mainly applied for finishing functions of failure types,failure reasons, solutions and average power recovery time which may more correctly and reasonably judge and solve failures.The power sup-ply urgent repair failure analysis system is useful to establish a set of practical,scientific and rapid failure decision system for power supply enterprises.

  12. Reinforcement of dented pipeline through composite sleeve repair systems subjected to fatigue by internal pressure; Reparos de dutos com amassamento atraves de luvas de materiais compositos submetidos a fadiga por pressao interna

    Energy Technology Data Exchange (ETDEWEB)

    Perrut, Valber Azevedo; Meniconi, Luiz Claudio de Marco [Centro de Pesquisas da Petrobras (CENPES). Gerencia de Tecnologia de Materiais, Equipamentos e Corrosao (Brazil)], e-mails: vperrut@petrobras.com.br, meniconi@petrobras.com.br; Souza Filho, Byron Goncalvez de [Transpetro (Brazil)], e-mail: byron.souza@petrobras.com.br

    2008-12-15

    Composite sleeve repair systems, now of widespread use in the market, were originally developed for the reinforcement of corroded pipelines. TRANSPETRO, the Brazilian pipeline operator, requested PETROBRAS/CENPES to address the behavior of sleeves when applied to dented pipelines. Simple verification experiments were carried out, in which both the dent filler material and the sleeve material were varied. Artificial dents with depths of 19% OD were imposed to 22 in. OD, 0.5 in. thick, API 5L X60 tubular specimens. Concrete and polymeric materials were tested for dent filler, whereas glass and carbon fiber composites, in two different thicknesses, were tried as the sleeve structural material. The main purpose of the repair sleeve in this case is to provide a repair procedure installed at low temperature and capable of reducing the stress range at the hot spot in the dent. The goal is to improve the fatigue resistance of the repaired pipeline. Low cycle fatigue tests were performed, both using non-repaired specimens (to serve as the basis for comparison) and specimens repaired using different schemes. The tests were fully instrumented to analyze strains in each specimen. After the fatigue tests, each specimen was pressurized until collapse, in order to quantify their ultimate strength. This paper reports the main results of the tests and the strain analysis for each repaired specimen, with the purpose of defining parameters which will serve to the design of future cases. (author)

  13. Online Repair of Office Equipment System Based on UML Modeling%基于UML的办公设备网上报修系统的建模

    Institute of Scientific and Technical Information of China (English)

    崔文

    2014-01-01

    the Hospital since the beginning of 2006 enabled OA system which brings implementa-tion of paperless office .Automated Office systems provides us with the preparation of documents ,publi-cation of notices ,send and receive messages ,wage management ,features such as short message service , cost savings ,and increased productivity .For the further implementation of the paperless office concept , we will embrace OA office equipment repair system ,repair systems analysis and design process are de-scribed in this paper ,highlights the modeling process .%我院自2006年开始启用OA系统,初步实现了无纸化办公。自动化办公系统为我们提供了编制文件、发布通知、收发内部邮件、工资管理,短信息服务等功能,既节约了办公成本,又提高了办公效率。为进一步落实无纸化办公的理念,我们将办公设备报修系统融入了 OA中,本文叙述了报修系统的分析与设计流程,重点突出了建模过程。

  14. Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts.

    Science.gov (United States)

    Fang, Rui; Qiao, Shupei; Liu, Yi; Meng, Qingyuan; Chen, Xiongbiao; Song, Bing; Hou, Xiaolu; Tian, Weiming

    2015-01-01

    Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.

  15. Bond strength of repaired amalgam restorations.

    Science.gov (United States)

    Rey, Rosalia; Mondragon, Eduardo; Shen, Chiayi

    2015-01-01

    This in vitro study investigated the interfacial flexural strength (FS) of amalgam repairs and the optimal combination of repair materials and mechanical retention required for a consistent and durable repair bond. Amalgam bricks were created, each with 1 end roughened to expose a fresh surface before repair. Four groups followed separate repair protocols: group 1, bonding agent with amalgam; group 2, bonding agent with composite resin; group 3, mechanical retention (slot) with amalgam; and group 4, slot with bonding agent and amalgam. Repaired specimens were stored in artificial saliva for 1, 10, 30, 120, or 360 days before being loaded to failure in a 3-point bending test. Statistical analysis showed significant changes in median FS over time in groups 2 and 4. The effect of the repair method on the FS values after each storage period was significant for most groups except the 30-day storage groups. Amalgam-amalgam repair with adequate condensation yielded the most consistent and durable bond. An amalgam bonding agent could be beneficial when firm condensation on the repair surface cannot be achieved or when tooth structure is involved. Composite resin can be a viable option for amalgam repair in an esthetically demanding region, but proper mechanical modification of the amalgam surface and selection of the proper bonding system are essential.

  16. Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

    Directory of Open Access Journals (Sweden)

    Pina Julieta

    2009-09-01

    Full Text Available Abstract Background MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. Methods We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH. Results Using unconditional logistic regression we found that MLH3 (L844P, G>A polymorphism GA (Leu/Pro and AA (Pro/Pro genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95 (p = 0.03 and OR = 0.62 (0.41-0.94 (p = 0.03, respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83, p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49, p = 0.01], GG/AA [OR = 2.11 (1.12-3,98, p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15, p = 0.02] all associated with an increased risk for breast cancer. Conclusion It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results.

  17. 48 CFR 1352.271-87 - Changes-ship repair.

    Science.gov (United States)

    2010-10-01

    ...—ship repair. As prescribed in 48 CFR 1371.118, insert the following clause: Changes—Ship Repair (APR... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Changes-ship repair. 1352.271-87 Section 1352.271-87 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE CLAUSES...

  18. Repair mechanisms inducible to the DNA in I.M.M.S. biological systems; Mecanismos de reparacion inducible del ADN en sistemas biologicos I.M.M.S

    Energy Technology Data Exchange (ETDEWEB)

    Guzman, J.; Arceo, C.; Cortinas, C.; Rosa, M.E. De la; Olvera, O.; Cruces, M.; Pimentel, E

    1990-03-15

    Given the characteristics of the MMS and the relative antecedents to the repair mechanisms in eucariontes are sought to determine the effect of the MMS on the genetic material and their repair in Drosophila melanogaster. (Author)

  19. Effect of gender on results of percutaneous edge-to-edge mitral valve repair with MitraClip system

    DEFF Research Database (Denmark)

    Estévez-Loureiro, Rodrigo; Settergren, Magnus; Winter, Reidar

    2015-01-01

    Knowledge regarding gender-specific results of percutaneous edge-to-edge mitral valve repair is scarce. The aim of this study was to investigate gender differences in outcomes in a cohort of patients treated with MitraClip implantation. A multicenter registry of 173 patients treated with Mitra......Clip prostheses from 2009 to 2012 at 3 experienced centers was performed. One hundred nine patients (63%) were men. Men were younger (mean age 73 ± 10 vs 79 ± 9 years, p = 0.001) and had a higher prevalence of previous coronary bypass graft surgery (34% vs 13%, p = 0.002), previous myocardial infarction (46% vs...

  20. Targeted gene repair – in the arena

    OpenAIRE

    2003-01-01

    The development of targeted gene repair is under way and, despite some setbacks, shows promise as an alternative form of gene therapy. This approach uses synthetic DNA molecules to activate and direct the cell’s inherent DNA repair systems to correct inborn errors. The progress of this technique and its therapeutic potential are discussed in relation to the treatment of genetic diseases.

  1. Repairs the added value of being wrong

    CERN Document Server

    Brandt, Patrick

    2013-01-01

    Grammatical structures connect systems of thought and articulation, the conditions of which hardly seem to fit each other. Repairs are productive mechanisms that solve translation problems between modules or levels by adapting derivations or representations to requirements that have to be met unconditionally. Compensating for derivational and interpretive defects, repairs

  2. Flight-testing of the self-repairing flight control system using the F-15 highly integrated digital electronic control flight research facility

    Science.gov (United States)

    Stewart, James F.; Shuck, Thomas L.

    1990-01-01

    Flight tests conducted with the self-repairing flight control system (SRFCS) installed on the NASA F-15 highly integrated digital electronic control aircraft are described. The development leading to the current SRFCS configuration is highlighted. Key objectives of the program are outlined: (1) to flight-evaluate a control reconfiguration strategy with three types of control surface failure; (2) to evaluate a cockpit display that will inform the pilot of the maneuvering capacity of the damage aircraft; and (3) to flight-evaluate the onboard expert system maintenance diagnostics process using representative faults set to occur only under maneuvering conditions. Preliminary flight results addressing the operation of the overall system, as well as the individual technologies, are included.

  3. Pectus excavatum repair

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002949.htm Pectus excavatum repair To use the sharing features on this page, please enable JavaScript. Pectus excavatum repair is surgery to correct pectus excavatum . This ...

  4. Persistence of antibodies in 4-8 year old Austrian children after vaccination with hexavalent DTaP-HBV-IPV/Hib and MMR vaccines.

    Science.gov (United States)

    Paulke-Korinek, Maria; Fischmeister, Gustav; Grac, Ana; Rendi-Wagner, Pamela; Kundi, Michael; Mohsenzadeh-Rabbani, Afsaneh; Moritz, Katharina; Fenninger, Beate; Jarisch, Reinhart; Jasinska, Joanna; Holzmann, Heidemarie; Wiedermann, Ursula; Kollaritsch, Herwig

    2011-07-18

    To determine the proficiency of the Austrian childhood vaccination schedule to induce long lasting seroprotection against vaccine preventable diseases a seroepidemiological study in 348 children between four and eight years of age was conducted. Antibodies against diphtheria, tetanus, pertussis, hepatitis B, measles, mumps and rubella antigens were assessed in children, who had been vaccinated with hexavalent DTaP-HBV-IPV/Hib vaccines at three, four, five months and in the second year of life and/or MMR vaccines in the second year of life at least once, but mostly twice. High seroprotection rates (SPRs) were detected for tetanus (96%) and measles (90%). SPRs regarding diphtheria and mumps were 81% and 72%, respectively. Rubella-SPRs were 68% in females and 58% in males. Hepatitis B-antibody levels ≥10 mIU/mL were present in 52%; antibodies against pertussis were detected in 27% of the children. SPRs for measles and rubella depended on the interval since last vaccination; mumps-antibodies were significantly lower after one MMR-vaccination only. Antibodies against diphtheria, tetanus and pertussis depended on the interval since last vaccination while HBs-antibodies did not. The low levels of antibodies 1-7 years after vaccination against pertussis, rubella and mumps after only one vaccination should be considered when recommending new vaccination schedules.

  5. Fabrication and Characterization of Multi-Walled Carbon Nanotube (MWCNT) and Ni-Coated Multi-Walled Carbon Nanotube (Ni-MWCNT) Repair Patches for Carbon Fiber Reinforced Composite Systems

    Science.gov (United States)

    Johnson, Brienne; Caraccio, Anne; Tate, LaNetra; Jackson, Dionne

    2011-01-01

    Multi-walled carbon nanotube (MWCNT)/epoxy and nickel-coated multi-walled carbon nanotube (Ni-MWCNT)/epoxy systems were fabricated into carbon fiber composite repair patches via vacuum resin infusion. Two 4 ply patches were manufactured with fiber orientations of [90/ 90/ 4590] and [0/90/ +45/ -45]. Prior to resin infusion, the MWCNT/Epoxy system and NiMWCNT/ epoxy systems were optimized for dispersion quality. Scanning electron microscopy (SEM) and optical microscopy (OM) were used to determine the presence ofcarbon nanotubes and assess dispersion quality. Decomposition temperatures were determined via thermogravametric analysis (TGA). SEM and TGA were also used to evaluate the composite repair patches.

  6. When "Other" Initiate Repair.

    Science.gov (United States)

    Schegloff, Emanuel A.

    2000-01-01

    Elaborates on the locus of other-initiated repair, and reports on a number of environments in which others initiate repair turns later than the one directly following the trouble-source turn. Describes several ways that other initiation of repair, which occurs in next-turn position, may be delayed within that position. (Author/VWL)

  7. A Geometry-Based Cycle Slip Detection and Repair Method with Time-Differenced Carrier Phase (TDCP for a Single Frequency Global Position System (GPS + BeiDou Navigation Satellite System (BDS Receiver

    Directory of Open Access Journals (Sweden)

    Chuang Qian

    2016-12-01

    Full Text Available As the field of high-precision applications based on carriers continues to expand, the development of low-cost, small, modular receivers and their application in diverse scenarios and situations with complex data quality has increased the requirements of carrier-phase data preprocessing. A new geometry-based cycle slip detection and repair method based on Global Position System (GPS + BeiDou Navigation Satellite System (BDS is proposed. The method uses a Time-differenced Carrier Phase (TDCP model, which eliminates the Inner-System Bias (ISB between GPS and BDS, and it is conducive to the effective combination of GPS and BDS. It avoids the interference of the noise of the pseudo-range with cycle slip detection, while the cycle slips are preserved as integers. This method does not limit the receiver frequency number, and it is applicable to single-frequency data. The process is divided into two steps to detect and repair cycle slip. The first step is cycle slip detection, using the Improved Local Analysis Method (ILAM to find satellites that have cycle slips; The second step is to repair the cycle slips, including estimating the float solution of changes in ambiguities at the satellites that have cycle slips with the least squares method and the integer solution of the cycle slips by rounding. In the process of rounding, in addition to the success probability, a decimal test is carried out to validate the result. Finally, experiments with filed test data are carried out to prove the effectiveness of this method. The results show that the detectable cycle slips number with GPS + BDS is much greater than that with GPS. The method can also detect the non-integer outliers while fixing the cycle slip. The maximum decimal bias in repair is less than that with GPS. It implies that this method takes full advantages of multi-system.

  8. A Geometry-Based Cycle Slip Detection and Repair Method with Time-Differenced Carrier Phase (TDCP) for a Single Frequency Global Position System (GPS) + BeiDou Navigation Satellite System (BDS) Receiver.

    Science.gov (United States)

    Qian, Chuang; Liu, Hui; Zhang, Ming; Shu, Bao; Xu, Longwei; Zhang, Rufei

    2016-12-05

    As the field of high-precision applications based on carriers continues to expand, the development of low-cost, small, modular receivers and their application in diverse scenarios and situations with complex data quality has increased the requirements of carrier-phase data preprocessing. A new geometry-based cycle slip detection and repair method based on Global Position System (GPS) + BeiDou Navigation Satellite System (BDS) is proposed. The method uses a Time-differenced Carrier Phase (TDCP) model, which eliminates the Inner-System Bias (ISB) between GPS and BDS, and it is conducive to the effective combination of GPS and BDS. It avoids the interference of the noise of the pseudo-range with cycle slip detection, while the cycle slips are preserved as integers. This method does not limit the receiver frequency number, and it is applicable to single-frequency data. The process is divided into two steps to detect and repair cycle slip. The first step is cycle slip detection, using the Improved Local Analysis Method (ILAM) to find satellites that have cycle slips; The second step is to repair the cycle slips, including estimating the float solution of changes in ambiguities at the satellites that have cycle slips with the least squares method and the integer solution of the cycle slips by rounding. In the process of rounding, in addition to the success probability, a decimal test is carried out to validate the result. Finally, experiments with filed test data are carried out to prove the effectiveness of this method. The results show that the detectable cycle slips number with GPS + BDS is much greater than that with GPS. The method can also detect the non-integer outliers while fixing the cycle slip. The maximum decimal bias in repair is less than that with GPS. It implies that this method takes full advantages of multi-system.

  9. Double-strand break repair based on short-homology regions is suppressed under terminal deoxynucleotidyltransferase expression, as revealed by a novel vector system for analysing DNA repair by nonhomologous end joining.

    Science.gov (United States)

    Maezawa, So; Nakano, Saori; Kuniya, Takaaki; Koiwai, Osamu; Koiwai, Kotaro

    2016-01-01

    We have constructed a novel, nonhomologous end-joining (NHEJ) assay vector (NAV), containing mKate2, Venus and ccdB genes. Cotransfection of NAV with a construct expressing the restriction enzyme I-SceI generated a double-strand break (DSB) in NAV that excised mKate2 and ccdB. Repair of this DSB produced an intact vector that expressed Venus, a green fluorescent protein. Because cells bearing the repaired NAV lacked the ccdB gene which slows cell proliferation, the cultures were enriched in cells containing repaired DSBs. DNA sequence analysis of the DSB junctions indicated that the repair was carried out mainly by using the closest homology sequence. Use of the NAV yielded rapid results within 3 days after transfection. We then used the NAV to analyse NHEJ in cells overexpressing terminal deoxynucleotidyltransferase (TdT). The results indicated that TdT suppresses DNA repair that is based on short (one- or two-base) homology regions, to efficiently add deoxynucleotides during VDJ recombination in lymphoid cells.

  10. Databases and Bioinformatics Tools for the Study of DNA Repair

    Directory of Open Access Journals (Sweden)

    Kaja Milanowska

    2011-01-01

    Full Text Available DNA is continuously exposed to many different damaging agents such as environmental chemicals, UV light, ionizing radiation, and reactive cellular metabolites. DNA lesions can result in different phenotypical consequences ranging from a number of diseases, including cancer, to cellular malfunction, cell death, or aging. To counteract the deleterious effects of DNA damage, cells have developed various repair systems, including biochemical pathways responsible for the removal of single-strand lesions such as base excision repair (BER and nucleotide excision repair (NER or specialized polymerases temporarily taking over lesion-arrested DNA polymerases during the S phase in translesion synthesis (TLS. There are also other mechanisms of DNA repair such as homologous recombination repair (HRR, nonhomologous end-joining repair (NHEJ, or DNA damage response system (DDR. This paper reviews bioinformatics resources specialized in disseminating information about DNA repair pathways, proteins involved in repair mechanisms, damaging agents, and DNA lesions.

  11. Construction of a three-dimensional bionic nerve conduit containing two neurotrophic factors with separate delivery systems for the repair of sciatic nerve defects

    Institute of Scientific and Technical Information of China (English)

    Zhiyue Li; Qun Zhao; Ran Bi; Yong Zhuang; Siyin Feng

    2011-01-01

    Previous studies of nerve conduits have investigated numerous properties, such as conduit luminal structure and neurotrophic factor incorporation, for the regeneration of nerve defects. The present study used a poly(lactic-co-glycolic acid) (PLGA) copolymer to construct a three-dimensional (3D) bionic nerve conduit, with two channels and multiple microtubule lumens, and incorporating two neurotrophic factors, each with their own delivery system, as a novel environment for peripheral nerve regeneration. The efficacy of this conduit in repairing a 1.5 cm sciatic nerve defect was compared with PLGA-alone and PLGA-microfilament conduits, and autologous nerve transplantation. Results showed that compared with the other groups, the 3D bionic nerve conduit had the fastest nerve conduction velocity, largest electromyogram amplitude, and shortest electromyogram latency. In addition, the nerve fiber density, myelin sheath thickness and axon diameter were significantly increased, and the recovery rate of the triceps surae muscle wet weight was lowest. These findings suggest that 3D bionic nerve conduits can provide a suitable microenvironment for peripheral nerve regeneration to efficiently repair sciatic nerve defects.

  12. Compassionate use of the PASCAL transcatheter mitral valve repair system for patients with severe mitral regurgitation: a multicentre, prospective, observational, first-in-man study.

    Science.gov (United States)

    Praz, Fabien; Spargias, Konstantinos; Chrissoheris, Michael; Büllesfeld, Lutz; Nickenig, Georg; Deuschl, Florian; Schueler, Robert; Fam, Neil P; Moss, Robert; Makar, Moody; Boone, Robert; Edwards, Jeremy; Moschovitis, Aris; Kar, Saibal; Webb, John; Schäfer, Ulrich; Feldman, Ted; Windecker, Stephan

    2017-08-19

    Severe mitral regurgitation is associated with impaired prognosis if left untreated. Using the devices currently available, transcatheter mitral valve repair (TMVr) remains challenging in complex anatomical situations. We report the procedural and 30-day results of the first-in-man study of the Edwards PASCAL TMVr system. In this multicentre, prospective, observational, first-in-man study, we collected data from seven tertiary care hospitals in five countries that had a compassionate use programme in which patients underwent transcatheter mitral valve repair using the Edwards PASCAL TMVr system. Eligible patients were those with symptomatic, severe functional, degenerative, or mixed mitral regurgitation deemed at high risk or inoperable. Safety and efficacy of the procedure were prospectively assessed at device implantation, discharge, and 30 days after device implantation. The key study endpoints were technical success assessed at the end of the procedure and device success 30 days after implantation using the Mitral Valve Academic Research Consortium definitions. Between Sept 1, 2016, and March 31, 2017, 23 patients (median age 75 years [IQR 61-82]) had treatment for moderate-to-severe (grade 3+) or severe (grade 4+) mitral regurgitation using the Edwards PASCAL TMVr system. At baseline, the median EuroScore II score was 7·1% (IQR 3·6-12·8) and the median Society of Thoracic Surgeons predicted risk of mortality for mitral valve repair was 4·8% (2·1-9·0) and 6·8% (2·9-10·1) for mitral valve replacement. 22 (96%) of 23 patients were New York Heart Association (NYHA) class III or IV at baseline. The implantation of at least one device was successful in all patients, resulting in procedural residual mitral regurgitation of grade 2+ or less in 22 (96%) patients. Six (26%) of 23 patients had two implants. Periprocedural complications occurred in two (9%) of 23 patients (one minor bleeding event and one transient ischaemic attack). Despite the anatomical

  13. Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis.

    Science.gov (United States)

    Takeda, Takashi; Banno, Kouji; Yanokura, Megumi; Adachi, Masataka; Iijima, Moito; Kunitomi, Haruko; Nakamura, Kanako; Iida, Miho; Nogami, Yuya; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Yamagami, Wataru; Hirasawa, Akira; Tominaga, Eiichiro; Susumu, Nobuyuki; Aoki, Daisuke

    2016-10-14

    Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1, MSH2, and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP). Germline mutation of MMR genes, microsatellite instability (MSI), and immunohistochemistry (IHC) were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%)-1 out of 58 (1.72%) with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes.

  14. 40 CFR 1033.815 - Maintenance, operation, and repair.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Maintenance, operation, and repair... Maintenance, operation, and repair. All persons who own, operate, or maintain locomotives are subject to this... components of the diagnostics system itself. For most repairs, this paragraph (b) requires that...

  15. 21 CFR 872.3570 - OTC denture repair kit.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false OTC denture repair kit. 872.3570 Section 872.3570...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3570 OTC denture repair kit. (a) Identification. An OTC denture repair kit is a device consisting of a material, such as a resin monomer system...

  16. Performance of shcc with bacteria for concrete patch repair

    NARCIS (Netherlands)

    Sierra Beltran, M.G.; Jonkers, H.M.; Schlangen, E.

    2014-01-01

    The overall performance of concrete patch repair systems depends on the durability of and compatibility between the concrete substrate and the repair material. This paper investigates the performance of a new type of SHCC material with embedded bacteria as a repair material. The bacteria are a

  17. A heart team's perspective on interventional mitral valve repair

    DEFF Research Database (Denmark)

    Treede, Hendrik; Schirmer, Johannes; Rudolph, Volker

    2012-01-01

    Surgical mitral valve repair carries an elevated perioperative risk in the presence of severely reduced ventricular function and relevant comorbidities. We sought to assess the feasibility of catheter-based mitral valve repair using a clip-based percutaneous edge-to-edge repair system in selected...

  18. Percutaneous mitral valve repair.

    Science.gov (United States)

    Gillinov, A Marc; Liddicoat, John R

    2006-01-01

    Surgical mitral valve repair is the procedure of choice to treat mitral regurgitation of all etiologies. Whereas annuloplasty is the cornerstone of mitral valve repair, a variety of other surgical techniques are utilized to correct dysfunction of the leaflets and subvalvular apparatus; in most cases, surgical repair entails application of multiple repair techniques in each patient. Preclinical studies and early human experience have demonstrated that some of these surgical repair techniques can be performed using percutaneous approaches. Specifically, there has been great progress in the development of novel technology to facilitate percutaneous annuloplasty and percutaneous edge-to-edge repair. The objectives of this report were to (1) discuss the surgical foundations for these percutaneous approaches; (2) review device design and experimental and clinical results of percutaneous valve repair; and (3) address future directions, including the key challenges of patient selection and clinical trial design.

  19. A study of molecular signals deregulating mismatch repair genes in prostate cancer compared to benign prostatic hyperplasia.

    Directory of Open Access Journals (Sweden)

    Sanmitra Basu

    Full Text Available Prostate cancer is one of the leading causes of mortality among aging males. There is an unmet requirement of clinically useful biomarkers for early detection of prostate cancer to reduce the liabilities of overtreatment and accompanying morbidity. The present population-based study investigates the factors disrupting expression of multiple functionally related genes of DNA mismatch repair pathway in prostate cancer patients to identify molecular attributes distinguishing adenocarcinoma from benign hyperplasia of prostate. Gene expression was compared between tissue samples from prostate cancer and benign prostatic hyperplasia using real-time-PCR, western blot and immunohistochemistry. Assessment of genotypes of seven single-nucleotide-polymorphisms of three MMR genes was conducted using PCR-coupled RFLP and sequencing. Promoter methylation was interrogated by methylation-specific-PCR and bisulfite-sequencing. Interaction between microRNAs and MMR genes was verified by 3'UTR-based dual luciferase assays. Concurrent reduction of three MMR genes namely hMLH1, hMSH6 and hMSH2 (34-85%, P<0.05 was observed in prostate cancer tissues. hMSH6 polymorphism rs1800932(Pro92Pro conferred a borderline protection in cancer patients (OR = 0.33, 95% CI = 0.15-0.75. Relative transcript level of hMLH1 was inversely related (r = -0.59, P<0.05 with methylation quotient of its promoter which showed a significantly higher methylation density (P = 0.008, Z = -2.649 in cancer patients. hsa-miR-155, hsa-miR-141 and hsa-miR-21 gene expressions were significantly elevated (66-85%, P<0.05 in tumor specimens and negatively correlated (r = -0.602 to -0.527, P<0.05 with that of MMR genes. hsa-miR-155 & hsa-miR-141 and hsa-miR-155 & hsa-miR-21 were demonstrated to bind to their putative seed sequences in hMLH1 and hMSH6 3'UTRs respectively. Relatively higher expression of DNA methyl-transferases (DNMT1 and DNMT3b and HIF-1α genes (34-50%, P<0.05 were also detected in tumor

  20. Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks

    DEFF Research Database (Denmark)

    Liberti, Sascha E; Andersen, Sofie Dabros; Wang, Jing

    2011-01-01

    Human exonuclease 1 (hEXO1) is implicated in DNA metabolism, including replication, recombination and repair, substantiated by its interactions with PCNA, DNA helicases BLM and WRN, and several DNA mismatch repair (MMR) proteins. We investigated the sub-nuclear localization of hEXO1 during S......-phase progression and in response to laser-induced DNA double strand breaks (DSBs). We show that hEXO1 and PCNA co-localize in replication foci. This apparent interaction is sustained throughout S-phase. We also demonstrate that hEXO1 is rapidly recruited to DNA DSBs. We have identified a PCNA interacting protein...... (PIP-box) region on hEXO1 located in its COOH-terminal ((788)QIKLNELW(795)). This motif is essential for PCNA binding and co-localization during S-phase. Recruitment of hEXO1 to DNA DSB sites is dependent on the MMR protein hMLH1. We show that two distinct hMLH1 interaction regions of hEXO1 (residues...