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Sample records for repair mmr system

  1. Evaluation of possible occurrence of mutation in MMR repair system genes in resistant and sensitiveclinical strains of Mycobacterium tuberculosisby using sequencing method

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    AmirPoyan Afzali

    2016-07-01

    Full Text Available Background:during recent years, the incidence and spread of drug resistance in Mycobacterium tuberculosis, the bacterium causing tuberculosis, has set this disease in World Health Organizationpriorities alignment of diseases like AIDS and hepatitis. Study of close examination of resistant and susceptible clinical strains genotypes is necessary to overcome drug resistance. Among the numerous repair systems, only there are limited number of encoding genes of DNA repair enzymes in Mycobacterium tuberculosis. Commonly these genes have been conserved and any changes among them likely increasethe mutation occurance due to the impossibility of correctionof spontaneous mutations insensitive strains of this bacteria.mut genes encodeDNA repairable enzymes.This study investigated the mutations in these genes and the effect of these mutations on tuberculosis drug resistance. Materials&Methods: In this study,of 29 available specimens,we were selected 8 susceptible strains and 21 resistantstrains andafter ordering appropriate primers and performing the proliferation reaction two types of amplicons produced which includingfragments of genes mut T2 and mut T4 and they were sent inorder to sequencing. Results:The results of chain reactionprimer represents an appropriate choice of primerswhich were investigated. Sequencing results showed that overall 73% of resistant strains that had been selected for study of mutT4gene, have no mutations in codons 48of mutT4 gene, and 70% of resistant strains have no GGA >>> CGA mutation at codon 58 of mutT2 gene. Conclusion: One of the strategies to overcome tuberculosis drug resistance is a close examination of genotypes of resistant and susceptible clinical strains. Results of this study was performedby examining changes in mut T2 and mut T4 gene sequence. The mutation in mut T2 always associated with mutation in mut T4, in this way, the first mutation may occurs in mut T4and after that, the second mutationmay occurs in mut T

  2. Constitutional Mismatch Repair Deficiency in Israel: High Proportion of Founder Mutations in MMR Genes and Consanguinity.

    Science.gov (United States)

    Baris, Hagit N; Barnes-Kedar, Inbal; Toledano, Helen; Halpern, Marisa; Hershkovitz, Dov; Lossos, Alexander; Lerer, Israela; Peretz, Tamar; Kariv, Revital; Cohen, Shlomi; Half, Elizabeth E; Magal, Nurit; Drasinover, Valerie; Wimmer, Katharina; Goldberg, Yael; Bercovich, Dani; Levi, Zohar

    2016-03-01

    Heterozygous germline mutations in any of the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2, cause Lynch syndrome (LS), an autosomal dominant cancer predisposition syndrome conferring a high risk of colorectal, endometrial, and other cancers in adulthood. Offspring of couples where both spouses have LS have a 1:4 risk of inheriting biallelic MMR gene mutations. These cause constitutional MMR deficiency (CMMRD) syndrome, a severe recessively inherited cancer syndrome with a broad tumor spectrum including mainly hematological malignancies, brain tumors, and colon cancer in childhood and adolescence. Many CMMRD children also present with café au lait spots and axillary freckling mimicking neurofibromatosis type 1. We describe our experience in seven CMMRD families demonstrating the role and importance of founder mutations and consanguinity on its prevalence. Clinical presentations included brain tumors, colon cancer, lymphoma, and small bowel cancer. In children from two nonconsanguineous Ashkenazi Jewish (AJ) families, the common Ashkenazi founder mutations were detected; these were homozygous in one family and compound heterozygous in the other. In four consanguineous families of various ancestries, different homozygous mutations were identified. In a nonconsanguineous Caucasus/AJ family, lack of PMS2 was demonstrated in tumor and normal tissues; however, mutations were not identified. CMMRD is rare, but, especially in areas where founder mutations for LS and consanguinity are common, pediatricians should be aware of it since they are the first to encounter these children. Early diagnosis will enable tailored cancer surveillance in the entire family and a discussion regarding prenatal genetic diagnosis. © 2015 Wiley Periodicals, Inc.

  3. Integrated analysis of mismatch repair system in malignant astrocytomas.

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    Irene Rodríguez-Hernández

    Full Text Available Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed protein expression and promoter methylation of MLH1, MSH2 and MSH6 as well as microsatellite instability (MSI and MMR gene mutations in a set of 96 low- and high-grade astrocytomas. Forty-one astrocytomas failed to express at least one MMR protein. Loss of MSH2 expression was more frequent in low-grade astrocytomas. Loss of MLH1 expression was associated with MLH1 promoter hypermethylation and MLH1-93G>A promoter polymorphism. However, MSI was not related with MMR protein expression and only 5% of tumors were MSI-High. Furthermore, the incidence of tumors carrying germline mutations in MMR genes was low and only one glioblastoma was associated with Lynch syndrome. Interestingly, survival analysis identified that tumors lacking MSH6 expression presented longer overall survival in high-grade astrocytoma patients treated only with radiotherapy while MSH6 expression did not modify the prognosis of those patients treated with both radiotherapy and chemotherapy. Our findings suggest that MMR system alterations are a frequent event in malignant astrocytomas and might help to define a subgroup of patients with different outcome.

  4. An Inducible, Isogenic Cancer Cell Line System for Targeting the State of Mismatch Repair Deficiency

    Science.gov (United States)

    Bailis, Julie M.; Gordon, Marcia L.; Gurgel, Jesse L.; Komor, Alexis C.; Barton, Jacqueline K.; Kirsch, Ilan R.

    2013-01-01

    The DNA mismatch repair system (MMR) maintains genome stability through recognition and repair of single-base mismatches and small insertion-deletion loops. Inactivation of the MMR pathway causes microsatellite instability and the accumulation of genomic mutations that can cause or contribute to cancer. In fact, 10-20% of certain solid and hematologic cancers are MMR-deficient. MMR-deficient cancers do not respond to some standard of care chemotherapeutics because of presumed increased tolerance of DNA damage, highlighting the need for novel therapeutic drugs. Toward this goal, we generated isogenic cancer cell lines for direct comparison of MMR-proficient and MMR-deficient cells. We engineered NCI-H23 lung adenocarcinoma cells to contain a doxycycline-inducible shRNA designed to suppress the expression of the mismatch repair gene MLH1, and compared single cell subclones that were uninduced (MLH1-proficient) versus induced for the MLH1 shRNA (MLH1-deficient). Here we present the characterization of these MMR-inducible cell lines and validate a novel class of rhodium metalloinsertor compounds that differentially inhibit the proliferation of MMR-deficient cancer cells. PMID:24205301

  5. 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.

  6. Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rudolph, Christiane; Melau, Cecilie; Nielsen, John E.

    2017-01-01

    in the majority of tumours, although the underlying mechanism largely remains to be elucidated. The aim of this study was to investigate the role of the DNA mismatch repair (MMR) system in the cisplatin sensitivity of TGCT. MethodsThe expression pattern of key MMR proteins, including MSH2, MSH6, MLH1 and PMS2...... proteins, in particular MSH2 and MLH1, which are involved in the recognition of cisplatin adducts and in activation of the DNA damage response pathway to initiate apoptosis....

  7. 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...

  8. Composite Repair System, Phase I

    Data.gov (United States)

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

  9. DNA Repair Systems

    Indian Academy of Sciences (India)

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

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

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    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.

  11. Café-au-lait macules and pediatric malignancy caused by biallelic mutations in the DNA mismatch repair (MMR) gene PMS2.

    Science.gov (United States)

    Jackson, Carl-Christian; Holter, Spring; Pollett, Aaron; Clendenning, Mark; Chou, Shirley; Senter, Leigha; Ramphal, Raveena; Gallinger, Steven; Boycott, Kym

    2008-06-01

    A 14-year-old male presented with a T4 sigmoid adenocarcinoma, PMS2 protein and high frequency microsatellite instability. Germline analysis identified biallelic PMS2 missense mutations. A new cancer syndrome caused by biallelic mutations in the mismatch repair genes, including PMS2, is now emerging and is characterized by café-au-lait macules, colonic polyps and a distinctive tumor spectrum. (c) 2007 Wiley-Liss, Inc.

  12. DNA Repair Systems

    Indian Academy of Sciences (India)

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

  13. 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.

  14. Reward optimization of a repairable system

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  15. Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours.

    Science.gov (United States)

    Rudolph, Christiane; Melau, Cecilie; Nielsen, John E; Vile Jensen, Kristina; Liu, Dekang; Pena-Diaz, Javier; Rajpert-De Meyts, Ewa; Rasmussen, Lene Juel; Jørgensen, Anne

    2017-08-01

    Testicular germ cell tumours (TGCT) are highly sensitive to cisplatin-based chemotherapy, but patients with tumours containing differentiated teratoma components are less responsive to this treatment. The cisplatin sensitivity in TGCT has previously been linked to the embryonic phenotype in the majority of tumours, although the underlying mechanism largely remains to be elucidated. The aim of this study was to investigate the role of the DNA mismatch repair (MMR) system in the cisplatin sensitivity of TGCT. The expression pattern of key MMR proteins, including MSH2, MSH6, MLH1 and PMS2, were investigated during testis development and in the pathogenesis of TGCT, including germ cell neoplasia in situ (GCNIS). The TGCT-derived cell line NTera2 was differentiated using retinoic acid (10 μM, 6 days) after which MMR protein expression and activity, as well as cisplatin sensitivity, were investigated in both undifferentiated and differentiated cells. Finally, the expression of MSH2 was knocked down by siRNA in NTera2 cells after which the effect on cisplatin sensitivity was examined. MMR proteins were expressed in proliferating cells in the testes, while in malignant germ cells MMR protein expression was found to coincide with the expression of the pluripotency factor OCT4, with no or low expression in the more differentiated yolk sac tumours, choriocarcinomas and teratomas. In differentiated NTera2 cells we found a significantly (p cisplatin sensitivity, compared to undifferentiated NTera2 cells. Also, we found that partial knockdown of MSH2 expression in undifferentiated NTera2 cells resulted in a significantly (p cisplatin sensitivity. This study reports, for the first time, expression of the MMR system in fetal gonocytes, from which GCNIS cells are derived. Our findings in primary TGCT specimens and TGCT-derived cells suggest that a reduced sensitivity to cisplatin in differentiated TGCT components could result from a reduced expression of MMR proteins, in

  16. Comparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry

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    Jiyoon Jung

    2017-03-01

    Full Text Available Background Colorectal cancer (CRC is one of the most common malignancies worldwide. Approximately 10%–15% of the CRC cases have defective DNA mismatch repair (MMR genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2 has emerged as a useful technique to complement polymerase chain reaction (PCR analyses. Methods In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined. Results Based on IHC, 7/61 primary tumors (11.4% showed deficient MMR systems, while 13/61 secondary tumors (21.3% showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor. Conclusions Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61. These data are in agreement with the previous microsatellite detection studies that used PCR and IHC.

  17. 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

    International Nuclear Information System (INIS)

    Kinsella, Timothy J.; Gurkan-Cavusoglu, Evren; Du, Weinan; Loparo, Kenneth A.

    2011-01-01

    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 radiosensitization 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.

  18. Long-term stability of the BDNPF/BDNPA nitroplaticizer system: an MMR analysis. Progress report, October--December 1975

    International Nuclear Information System (INIS)

    Clink, G.L.

    1976-01-01

    NMR analysis of the BDNPF/BDNPA eutectic system reaffirms the molecular integrity of the constituents, the stability of their molar ratios, and the effective retardant effect of the phenyl-beta-napthylamine antioxidant. Additional work on the analysis of the PBX 9501 system is underway at the present time

  19. TumorNext-Lynch-MMR: a comprehensive next generation sequencing assay for the detection of germline and somatic mutations in genes associated with mismatch repair deficiency and Lynch syndrome.

    Science.gov (United States)

    Gray, Phillip N; Tsai, Pei; Chen, Daniel; Wu, Sitao; Hoo, Jayne; Mu, Wenbo; Li, Bing; Vuong, Huy; Lu, Hsiao-Mei; Batth, Navanjot; Willett, Sara; Uyeda, Lisa; Shah, Swati; Gau, Chia-Ling; Umali, Monalyn; Espenschied, Carin; Janicek, Mike; Brown, Sandra; Margileth, David; Dobrea, Lavinia; Wagman, Lawrence; Rana, Huma; Hall, Michael J; Ross, Theodora; Terdiman, Jonathan; Cullinane, Carey; Ries, Savita; Totten, Ellen; Elliott, Aaron M

    2018-04-17

    The current algorithm for Lynch syndrome diagnosis is highly complex with multiple steps which can result in an extended time to diagnosis while depleting precious tumor specimens. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext-Lynch-MMR, which generates a comprehensive genetic profile of both germline and somatic mutations that can accelerate and streamline the time to diagnosis and preserve specimen. TumorNext-Lynch-MMR can detect single nucleotide variants, small insertions and deletions in 39 genes that are frequently mutated in Lynch syndrome and colorectal cancer. Moreover, the panel provides microsatellite instability status and detects loss of heterozygosity in the five Lynch genes; MSH2 , MSH6 , MLH1 , PMS2 and EPCAM . Clinical cases are described that highlight the assays ability to differentiate between somatic and germline mutations, precisely classify variants and resolve discordant cases.

  20. Using repair priorities in systems with redundacies

    NARCIS (Netherlands)

    Sleptchenko, A.V.; Adan, I.J.B.F.; Van Houtum, G.-J.

    2014-01-01

    In this paper, we present and analyze a mathematical model for the computation of the system availability for a system of parallel machines with redundancies and repair priorities. Using the presented models, we show that the repair priorities have a strong effect on the performance of the system.

  1. Znaczenie mechanizmu naprawy DNA błędnie sparowanych zasad azotowych (MMR w raku piersi

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    Hanna Romanowicz

    2010-04-01

    Full Text Available Background: Microsatellite instability (MSI is due to defective DNA mismatch repair. Defects in DNA mismatch-repair (MMR genes lead to replication errors revealed as instability in microsatellite markers. Studieshave shown that breast cancer may be associated with mutations in mismatch repair genes, such as MSH2,MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH. Aim: Results from studies that assayed MMR in sporadic breast cancer are reviewed. Conclusion: Several data suggest that microsatellite instability seems to be a risk factor for breast cancerin subjects belonging to HNPCC (hereditary non-polyposis colorectal cancer families with high incidence of thiscancer and sporadic breast cancer.

  2. 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

  3. 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

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

    International Nuclear Information System (INIS)

    Chen, Yuanhong; Huang, Changjiang; Bai, Chenglian; Du, Changchun; Liao, Junhua; Dong, Qiaoxiang

    2016-01-01

    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_2), benzo[a]pyrene (BaP), and

  5. 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.

  6. 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...

  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. Radiotherapy Results of Midline Malignant Reticulosis (MMR)

    International Nuclear Information System (INIS)

    Yun, Sang Mo; Kim, Jae Cheol

    1996-01-01

    Purpose : This study was performed to evaluate survival, failure patterns, and prognositc factors of MMR patients after radiation therapy. We also discussed the need for chemotherapy. Materials and Methods : A retrospective analysis was done for 23 patients with MMR who were treated with radiation therapy form June 1985 to November 1992. There were 19 male and 4 female patients. The patients age ranged from 17 to 71 years(median 39 years). Systemic symptoms including fever, weight loss, or malaise were found in 30% of the patients. He nasal cavity was most frequently involved. No patients had nodal involvement at diagnosis. There were 2 patients with distant metastasis at presentation. Radiation therapy was delivered five times a week, 1.8 Gy daily, total 45∼54 Gy(median 50.4 Gy) using 6 MV X-ray. No patients received chemotherapy as initial treatment. Results : Overall 5-year and 10-year survival rates were 52.4% and 44.1%, respectively. Seventy percent(12/17) of the patients achieved complete response to radiotherapy., and 29.4%(5/17) achieved partial response. The patients with complete response showed a better 5-year survival rate than those with partial response (66.9% vs. 20%, p-0.004). Symptom duration before diagnosis, the presence of systemic symptom, ad the number of primary sites had no influence on survival. The patterns of failure were as flows: local failure(1), failure in adjacent site(1), local and distant failure(1), distant metastasis(2), and conversion to malignant lymphoma(1). W could not find factors associated with the patterns of failure. Conclusion : The most important factor associated with survival was the response to radiotherapy. Seventeen percent of the patients had distant metastasis, and the salvage after distant metastasis was not successful. However, about 50% of the patients could achieve long-term survival with local radiation therapy alone. Therefore, chemotherapy of MMR should be done after a prospective randomized study for

  9. 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)

  10. Regression Models for Repairable Systems

    Czech Academy of Sciences Publication Activity Database

    Novák, Petr

    2015-01-01

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

  11. 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.

  12. Activation of Saccharomyces cerevisiae Mlh1-Pms1 Endonuclease in a Reconstituted Mismatch Repair System*

    Science.gov (United States)

    Smith, Catherine E.; Bowen, Nikki; Graham, William J.; Goellner, Eva M.; Srivatsan, Anjana; Kolodner, Richard D.

    2015-01-01

    Previous studies reported the reconstitution of an Mlh1-Pms1-independent 5′ nick-directed mismatch repair (MMR) reaction using Saccharomyces cerevisiae proteins. Here we describe the reconstitution of a mispair-dependent Mlh1-Pms1 endonuclease activation reaction requiring Msh2-Msh6 (or Msh2-Msh3), proliferating cell nuclear antigen (PCNA), and replication factor C (RFC) and a reconstituted Mlh1-Pms1-dependent 3′ nick-directed MMR reaction requiring Msh2-Msh6 (or Msh2-Msh3), exonuclease 1 (Exo1), replication protein A (RPA), RFC, PCNA, and DNA polymerase δ. Both reactions required Mg2+ and Mn2+ for optimal activity. The MMR reaction also required two reaction stages in which the first stage required incubation of Mlh1-Pms1 with substrate DNA, with or without Msh2-Msh6 (or Msh2-Msh3), PCNA, and RFC but did not require nicking of the substrate, followed by a second stage in which other proteins were added. Analysis of different mutant proteins demonstrated that both reactions required a functional Mlh1-Pms1 endonuclease active site, as well as mispair recognition and Mlh1-Pms1 recruitment by Msh2-Msh6 but not sliding clamp formation. Mutant Mlh1-Pms1 and PCNA proteins that were defective for Exo1-independent but not Exo1-dependent MMR in vivo were partially defective in the Mlh1-Pms1 endonuclease and MMR reactions, suggesting that both reactions reflect the activation of Mlh1-Pms1 seen in Exo1-independent MMR in vivo. The availability of this reconstituted MMR reaction should now make it possible to better study both Exo1-independent and Exo1-dependent MMR. PMID:26170454

  13. Activation of Saccharomyces cerevisiae Mlh1-Pms1 Endonuclease in a Reconstituted Mismatch Repair System.

    Science.gov (United States)

    Smith, Catherine E; Bowen, Nikki; Graham, William J; Goellner, Eva M; Srivatsan, Anjana; Kolodner, Richard D

    2015-08-28

    Previous studies reported the reconstitution of an Mlh1-Pms1-independent 5' nick-directed mismatch repair (MMR) reaction using Saccharomyces cerevisiae proteins. Here we describe the reconstitution of a mispair-dependent Mlh1-Pms1 endonuclease activation reaction requiring Msh2-Msh6 (or Msh2-Msh3), proliferating cell nuclear antigen (PCNA), and replication factor C (RFC) and a reconstituted Mlh1-Pms1-dependent 3' nick-directed MMR reaction requiring Msh2-Msh6 (or Msh2-Msh3), exonuclease 1 (Exo1), replication protein A (RPA), RFC, PCNA, and DNA polymerase δ. Both reactions required Mg(2+) and Mn(2+) for optimal activity. The MMR reaction also required two reaction stages in which the first stage required incubation of Mlh1-Pms1 with substrate DNA, with or without Msh2-Msh6 (or Msh2-Msh3), PCNA, and RFC but did not require nicking of the substrate, followed by a second stage in which other proteins were added. Analysis of different mutant proteins demonstrated that both reactions required a functional Mlh1-Pms1 endonuclease active site, as well as mispair recognition and Mlh1-Pms1 recruitment by Msh2-Msh6 but not sliding clamp formation. Mutant Mlh1-Pms1 and PCNA proteins that were defective for Exo1-independent but not Exo1-dependent MMR in vivo were partially defective in the Mlh1-Pms1 endonuclease and MMR reactions, suggesting that both reactions reflect the activation of Mlh1-Pms1 seen in Exo1-independent MMR in vivo. The availability of this reconstituted MMR reaction should now make it possible to better study both Exo1-independent and Exo1-dependent MMR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. 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.

  15. 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.

  16. 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...

  17. Self-repair of cracks in brittle material systems

    Science.gov (United States)

    Dry, Carolyn M.

    2016-04-01

    One of the most effective uses for self repair is in material systems that crack because the cracks can allow the repair chemical to flow into the crack damage sites in all three dimensions. In order for the repair chemical to stay in the damage site and flow along to all the crack and repair there must be enough chemical to fill the entire crack. The repair chemical must be designed appropriately for the particular crack size and total volume of cracks. In each of the three examples of self repair in crackable brittle systems, the viscosity and chemical makeup and volume of the repair chemicals used is different for each system. Further the chemical delivery system has to be designed for each application also. Test results from self repair of three brittle systems are discussed. In "Self Repair of Concrete Bridges and Infrastructure" two chemicals were used due to different placements in bridges to repair different types of cracks- surface shrinkage and shear cracks, In "Airplane Wings and Fuselage, in Graphite" the composite has very different properties than the concrete bridges. In the graphite for airplane components the chemical also had to survive the high processing temperatures. In this composite the cracks were so definite and deep and thin that the repair chemical could flow easily and repair in all layers of the composite. In "Ceramic/Composite Demonstrating Self Repair" the self repair system not only repaired the broken ceramic but also rebounded the composite to the ceramic layer

  18. A model system for DNA repair studies

    International Nuclear Information System (INIS)

    Lange, C.S.; Perlmutter, E.

    1984-01-01

    The search for the ''lethal lesion:'' which would yield a molecular explanation of biological survival curves led to attempts to correlate unrepaired DNA lesions with loss of reproductive integrity. Such studies have shown the crucial importance of DNA repair systems. The unrepaired DSB has been sought for such correlation, but in such study the DNA was too large, polydisperse, and/or structurally complex to permit precise measurement of break induction and repair. Therefore, an analog of higher order systems but with a genome of readily measurable size, is needed. Bacteriophage T4 is such an analog. Both its biological (PFU) and molecular (DNA) survival curves are exponentials. Its aerobic /sub PFU/D/sub 37///sub DNA/D/sub 37/ ratio, (410 +- 4.5Gy/540 +- 25 Gy) indicates that 76 +- 4% of lethality at low multiplicity infection (moi 1) the survival is greater than can be explained if the assumption of no parental DSB repair were valid. Both T4 and its host have DSB repair systems which can be studied by the infectious center method. Results of such studies are discussed

  19. 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

    for regulation of nuclear import that is necessary for proper localization of the repair proteins. This review summarizes the current knowledge on nuclear import mechanisms of DNA excision repair proteins and provides a model that categorizes the import by different mechanisms, including classical nuclear import......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......, 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...

  20. GLI1 interferes with the DNA mismatch repair system in pancreatic cancer through BHLHE41-mediated suppression of MLH1.

    Science.gov (United States)

    Inaguma, Shingo; Riku, Miho; Hashimoto, Mitsuyoshi; Murakami, Hideki; Saga, Shinsuke; Ikeda, Hiroshi; Kasai, Kenji

    2013-12-15

    The mismatch repair (MMR) system is indispensable for the fidelity of DNA replication, the impairment of which predisposes to the development and progression of many types of cancers. To date, GLI1 transcription factor, a key molecule of the Hedgehog signaling pathway, has been shown to regulate the expression of several genes crucial for a variety of cancer cell properties in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), but whether GLI1 could control the MMR system was not known. Here, we showed that GLI1 and GLI2 indirectly suppressed the expression of MLH1 in PDAC cells. Through GLI1 target gene screening, we found that GLI1 and GLI2 activated the expression of a basic helix-loop-helix type suppressor BHLHE41/DEC2/SHARP1 through a GLI-binding site in the promoter. Consistent with a previous report that BHLHE41 suppresses the MLH1 promoter activity, we found that the activation of GLI1 led to the BHLHE41-dependent suppression of MLH1, and a double knockdown of GLI1 and GLI2 conversely increased the MLH1 protein in PDAC cells. Using TALEN-based modification of the MLH1 gene, we further showed that GLI1 expression was indeed associated with an increased tolerance to a methylating agent, methylnitrosourea cooperatively with a lower copy number status of MLH1. Finally, GLI1 expression was immunohistochemically related positively with BHLHE41 and inversely with MLH1 in PDAC cells and precancerous lesions of the pancreas. On the basis of these results, we propose that GLI1 depresses the MMR activity and might contribute to the development and progression of PDAC. ©2013 AACR.

  1. DNA Damage Induced by Alkylating Agents and Repair Pathways

    Science.gov (United States)

    Kondo, Natsuko; Takahashi, Akihisa; Ono, Koji; Ohnishi, Takeo

    2010-01-01

    The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O6-methylguanine-DNA methyltransferase, and O6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O6MeG/T mispairs, which eventually lead to double-strand breaks. Bifunctional alkylating agents form interstrand cross-links (ICLs) which are more complex and highly cytotoxic. ICLs are repaired by complex of NER factors (e.g., endnuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1), Fanconi anemia repair, and homologous recombination. A detailed understanding of how cells cope with DNA damage caused by alkylating agents is therefore potentially useful in clinical medicine. PMID:21113301

  2. A geometric process repair model for a repairable cold standby system with priority in use and repair

    International Nuclear Information System (INIS)

    Zhang Yuanlin; Wang Guanjun

    2009-01-01

    In this paper, a deteriorating cold standby repairable system consisting of two dissimilar components and one repairman is studied. For each component, assume that the successive working times form a decreasing geometric process while the consecutive repair times constitute an increasing geometric process, and component 1 has priority in use and repair. Under these assumptions, we consider a replacement policy N based on the number of repairs of component 1 under which the system is replaced when the number of repairs of component 1 reaches N. Our problem is to determine an optimal policy N* such that the average cost rate (i.e. the long-run average cost per unit time) of the system is minimized. The explicit equation of the average cost rate of the system is derived and the corresponding optimal replacement policy N* can be determined analytically or numerically. Finally, a numerical example with Weibull distribution is given to illustrate some theoretical results in this paper.

  3. 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...

  4. Analysis for a two-dissimilar-component cold standby repairable system with repair priority

    International Nuclear Information System (INIS)

    Leung, Kit Nam Francis; Zhang Yuanlin; Lai, Kin Keung

    2011-01-01

    In this paper, a cold standby repairable system consisting of two dissimilar components and one repairman is studied. Assume that working time distributions and repair time distributions of the two components are both exponential, and Component 1 has repair priority when both components are broken down. After repair, Component 1 follows a geometric process repair while Component 2 obeys a perfect repair. Under these assumptions, using the perfect repair model, the geometric process repair model and the supplementary variable technique, we not only study some important reliability indices, but also consider a replacement policy T, under which the system is replaced when the working age of Component 1 reaches T. Our problem is to determine an optimal policy T* such that the long-run average loss per unit time (i.e. average loss rate) of the system is minimized. The explicit expression for the average loss rate of the system is derived, and the corresponding optimal replacement policy T* can be found numerically. Finally, a numerical example for replacement policy T is given to illustrate some theoretical results and the model's applicability. - Highlights: → A two-dissimilar-component cold standby system with repair priority is formulated. → The successive up/repair times of Component 1 form a decreasing/increasing geometric process. → Not only some reliability indices but also a replacement policy are studied.

  5. 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

  6. Failure Modes in Concrete Repair Systems due to Ongoing Corrosion

    Directory of Open Access Journals (Sweden)

    Mladena Luković

    2017-01-01

    Full Text Available Corrosion of steel reinforcement is the main cause of deterioration in reinforced concrete structures. It can result in cracking and spalling of the concrete cover. After the damaged cover is repaired, reinforcement corrosion might continue and even accelerate. While the development of the corrosion cell is difficult to control, the damage can be possibly delayed and controlled by use of a suitable repair material. The lattice fracture model is used in this paper to investigate the performance of strain hardening cementitious composite (SHCC in concrete repair systems exposed to ongoing corrosion. Numerical results were verified by experimental tests when SHCC, nonreinforced material (repair mortar, and commercial repair mortar are used as repair materials. In experiments, reinforcement bars (surrounded by a repair material were exposed to accelerated corrosion tests. The influence of the substrate surface preparation, the type of repair material, the interface, and the substrate strength on the resulting damage and failure mode of repair systems are discussed. In general, SHCC repair enables distributed cracking with small crack widths, up to several times smaller compared to repair mortar. Furthermore, more warning signs prior to the final failure are present in the SHCC repair system.

  7. Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures

    OpenAIRE

    Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

    2014-01-01

    OBJECTIVE: Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50-60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC ac...

  8. C-Terminal Fluorescent Labeling Impairs Functionality of DNA Mismatch Repair Proteins

    Science.gov (United States)

    Brieger, Angela; Plotz, Guido; Hinrichsen, Inga; Passmann, Sandra; Adam, Ronja; Zeuzem, Stefan

    2012-01-01

    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. PMID:22348133

  9. 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.

  10. Microsatellites in the Eukaryotic DNA Mismatch Repair Genes as Modulators of Evolutionary Mutation Rate

    Science.gov (United States)

    Chang, Dong Kyung; Metzgar, David; Wills, Christopher; Boland, C. Richard

    2003-01-01

    All "minor" components of the human DNA mismatch repair (MMR) system-MSH3, MSH6, PMS2, and the recently discovered MLH3-contain mononucleotide microsatellites in their coding sequences. This intriguing finding contrasts with the situation found in the major components of the DNA MMR system-MSH2 and MLH1-and, in fact, most human genes. Although eukaryotic genomes are rich in microsatellites, non-triplet microsatellites are rare in coding regions. The recurring presence of exonal mononucleotide repeat sequences within a single family of human genes would therefore be considered exceptional.

  11. MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils

    Science.gov (United States)

    Campo, Vanina A.; Patenaude, Anne-Marie; Kaden, Svenja; Horb, Lori; Firka, Daniel; Jiricny, Josef; Di Noia, Javier M.

    2013-01-01

    The mammalian antibody repertoire is shaped by somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) loci of B lymphocytes. SHM and CSR are triggered by non-canonical, error-prone processing of G/U mismatches generated by activation-induced deaminase (AID). In birds, AID does not trigger SHM, but it triggers Ig gene conversion (GC), a ‘homeologous’ recombination process involving the Ig variable region and proximal pseudogenes. Because recombination fidelity is controlled by the mismatch repair (MMR) system, we investigated whether MMR affects GC in the chicken B cell line DT40. We show here that Msh6−/− and Pms2−/− DT40 cells display cell cycle defects, including genomic re-replication. However, although IgVλ GC tracts in MMR-deficient cells were slightly longer than in normal cells, Ig GC frequency, donor choice or the number of mutations per sequence remained unaltered. The finding that the avian MMR system, unlike that of mammals, does not seem to contribute towards the processing of G/U mismatches in vitro could explain why MMR is unable to initiate Ig GC in this species, despite initiating SHM and CSR in mammalian cells. Moreover, as MMR does not counteract or govern Ig GC, we report a rare example of ‘homeologous’ recombination insensitive to MMR. PMID:23314153

  12. DNA repair systems as targets of cadmium toxicity

    International Nuclear Information System (INIS)

    Giaginis, Constantinos; Gatzidou, Elisavet; Theocharis, Stamatios

    2006-01-01

    Cadmium (Cd) is a heavy metal and a potent carcinogen implicated in tumor development through occupational and environmental exposure. Recent evidence suggests that proteins participating in the DNA repair systems, especially in excision and mismatch repair, are sensitive targets of Cd toxicity. Cd by interfering and inhibiting these DNA repair processes might contribute to increased risk for tumor formation in humans. In the present review, the information available on the interference of Cd with DNA repair systems and their inhibition is summarized. These actions could possibly explain the indirect contribution of Cd to mutagenic effects and/or carcinogenicity

  13. Human mismatch repair protein hMutLα is required to repair short slipped-DNAs of trinucleotide repeats.

    Science.gov (United States)

    Panigrahi, Gagan B; Slean, Meghan M; Simard, Jodie P; Pearson, Christopher E

    2012-12-07

    Mismatch repair (MMR) is required for proper maintenance of the genome by protecting against mutations. The mismatch repair system has also been implicated as a driver of certain mutations, including disease-associated trinucleotide repeat instability. We recently revealed a requirement of hMutSβ in the repair of short slip-outs containing a single CTG repeat unit (1). The involvement of other MMR proteins in short trinucleotide repeat slip-out repair is unknown. Here we show that hMutLα is required for the highly efficient in vitro repair of single CTG repeat slip-outs, to the same degree as hMutSβ. HEK293T cell extracts, deficient in hMLH1, are unable to process single-repeat slip-outs, but are functional when complemented with hMutLα. The MMR-deficient hMLH1 mutant, T117M, which has a point mutation proximal to the ATP-binding domain, is defective in slip-out repair, further supporting a requirement for hMLH1 in the processing of short slip-outs and possibly the involvement of hMHL1 ATPase activity. Extracts of hPMS2-deficient HEC-1-A cells, which express hMLH1, hMLH3, and hPMS1, are only functional when complemented with hMutLα, indicating that neither hMutLβ nor hMutLγ is sufficient to repair short slip-outs. The resolution of clustered short slip-outs, which are poorly repaired, was partially dependent upon a functional hMutLα. The joint involvement of hMutSβ and hMutLα suggests that repeat instability may be the result of aberrant outcomes of repair attempts.

  14. Mountain Plains Learning Experience Guide: Automotive Repair. Course: Brake Systems.

    Science.gov (United States)

    Schramm, C.; Osland, Walt

    One of twelve individualized courses included in an automotive repair curriculum, this course covers theory, operation, and repair of drum brakes, disc brakes, and brake system components. The course is comprised of six units: (1) Fundamentals of Brake Systems, (2) Master Cylinder, (3) Drum Brakes, (4) Disc Brakes, (5) Power Brakes, and (6)…

  15. 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

  16. Closed-loop two-echelon repairable item systems

    NARCIS (Netherlands)

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

    2003-01-01

    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

  17. Reducing costs of repairable inventory supply systems via dynamic scheduling

    NARCIS (Netherlands)

    Tiemessen, H.G.H.; Houtum, van G.J.J.A.N.

    2013-01-01

    We study a system consisting of one repair shop and one stockpoint, where spare parts of multiple critical repairables are kept on stock to serve an installed base of technical systems. Part requests are met from stock if possible, and backordered otherwise. The objective is to minimize aggregate

  18. Component-Level Electronic-Assembly Repair (CLEAR) System Architecture

    Science.gov (United States)

    Oeftering, Richard C.; Bradish, Martin A.; Juergens, Jeffrey R.; Lewis, Michael J.; Vrnak, Daniel R.

    2011-01-01

    This document captures the system architecture for a Component-Level Electronic-Assembly Repair (CLEAR) capability needed for electronics maintenance and repair of the Constellation Program (CxP). CLEAR is intended to improve flight system supportability and reduce the mass of spares required to maintain the electronics of human rated spacecraft on long duration missions. By necessity it allows the crew to make repairs that would otherwise be performed by Earth based repair depots. Because of practical knowledge and skill limitations of small spaceflight crews they must be augmented by Earth based support crews and automated repair equipment. This system architecture covers the complete system from ground-user to flight hardware and flight crew and defines an Earth segment and a Space segment. The Earth Segment involves database management, operational planning, and remote equipment programming and validation processes. The Space Segment involves the automated diagnostic, test and repair equipment required for a complete repair process. This document defines three major subsystems including, tele-operations that links the flight hardware to ground support, highly reconfigurable diagnostics and test instruments, and a CLEAR Repair Apparatus that automates the physical repair process.

  19. 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.

  20. Autogenous Metallic Pipe Leak Repair in Potable Water Systems.

    Science.gov (United States)

    Tang, Min; Triantafyllidou, Simoni; Edwards, Marc A

    2015-07-21

    Copper and iron pipes have a remarkable capability for autogenous repair (self-repair) of leaks in potable water systems. Field studies revealed exemplars that metallic pipe leaks caused by nails, rocks, and erosion corrosion autogenously repaired, as confirmed in the laboratory experiments. This work demonstrated that 100% (N = 26) of 150 μm leaks contacting representative bulk potable water in copper pipes sealed autogenously via formation of corrosion precipitates at 20-40 psi, pH 3.0-11.0, and with upward and downward leak orientations. Similar leaks in carbon steel pipes at 20 psi self-repaired at pH 5.5 and 8.5, but two leaks did not self-repair permanently at pH 11.0 suggesting that water chemistry may control the durability of materials that seal the leaks and therefore the permanence of repair. Larger 400 μm holes in copper pipes had much lower (0-33%) success of self-repair at pH 3.0-11.0, whereas all 400 μm holes in carbon steel pipes at 20 psi self-repaired at pH 4.0-11.0. Pressure tests indicated that some of the repairs created at 20-40 psi ambient pressure could withstand more than 100 psi without failure. Autogenous repair has implications for understanding patterns of pipe failures, extending the lifetime of decaying infrastructure, and developing new plumbing materials.

  1. Repairing method for reactor primary system pipeline

    International Nuclear Information System (INIS)

    Hosokawa, Hideyuki; Uetake, Naoto; Hara, Teruo.

    1997-01-01

    Pipelines after decontamination of radioactive nuclides deposited on the pipelines in a nuclear power plant during operation or pipelines to replace pipelines deposited with radioactive nuclide are connected to each system of the nuclear power plant. They are heated in a gas phase containing oxygen to form an oxide film on the surface of the pipelines. The thickness of the oxide film formed in the gas phase is 1nm or greater, preferably 100nm. The concentration of oxygen in the gas phase containing oxygen must be 0.1% or greater. The heating is conducted by circulating a heated gas to the inside of the pipelines or disposing a movable heater such as a high frequency induction heater inside of the pipelines to form the oxide film. Then, redeposition of radioactive nuclide can be suppressed and since the oxide film is formed in the gas phase, a large scaled facilities are not necessary, thereby enabling to repair pipelines of reactor primary system at low cost. (N.H.)

  2. 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

  3. Immunotherapy holds the key to cancer treatment and prevention in constitutional mismatch repair deficiency (CMMRD) syndrome.

    Science.gov (United States)

    Westdorp, Harm; Kolders, Sigrid; Hoogerbrugge, Nicoline; de Vries, I Jolanda M; Jongmans, Marjolijn C J; Schreibelt, Gerty

    2017-09-10

    Monoallelic germline mutations in one of the DNA mismatch repair (MMR) genes cause Lynch syndrome, with a high lifetime risks of colorectal and endometrial cancer at adult age. Less well known, is the constitutional mismatch repair deficiency (CMMRD) syndrome caused by biallelic germline mutations in MMR genes. This syndrome is characterized by the development of childhood cancer. Patients with CMMRD are at extremely high risk of developing multiple cancers including hematological, brain and intestinal tumors. Mutations in MMR genes impair DNA repair and therefore most tumors of patients with CMMRD are hypermutated. These mutations lead to changes in the translational reading frame, which consequently result in neoantigen formation. Neoantigens are recognized as foreign by the immune system and can induce specific immune responses. The growing evidence on the clinical efficacy of immunotherapies, such as immune checkpoint inhibitors, offers the prospect for treatment of patients with CMMRD. Combining neoantigen-based vaccination strategies and immune checkpoint inhibitors could be an effective way to conquer CMMRD-related tumors. Neoantigen-based vaccines might also be a preventive treatment option in healthy biallelic MMR mutation carriers. Future studies need to reveal the safety and efficacy of immunotherapies for patients with CMMRD. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  4. 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.

  5. Calibration of Multiple In Silico Tools for Predicting Pathogenicity of Mismatch Repair Gene Missense Substitutions

    Science.gov (United States)

    Thompson, Bryony A.; Greenblatt, Marc S.; Vallee, Maxime P.; Herkert, Johanna C.; Tessereau, Chloe; Young, Erin L.; Adzhubey, Ivan A.; Li, Biao; Bell, Russell; Feng, Bingjian; Mooney, Sean D.; Radivojac, Predrag; Sunyaev, Shamil R.; Frebourg, Thierry; Hofstra, Robert M.W.; Sijmons, Rolf H.; Boucher, Ken; Thomas, Alun; Goldgar, David E.; Spurdle, Amanda B.; Tavtigian, Sean V.

    2015-01-01

    Classification of rare missense substitutions observed during genetic testing for patient management is a considerable problem in clinical genetics. The Bayesian integrated evaluation of unclassified variants is a solution originally developed for BRCA1/2. Here, we take a step toward an analogous system for the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) that confer colon cancer susceptibility in Lynch syndrome by calibrating in silico tools to estimate prior probabilities of pathogenicity for MMR gene missense substitutions. A qualitative five-class classification system was developed and applied to 143 MMR missense variants. This identified 74 missense substitutions suitable for calibration. These substitutions were scored using six different in silico tools (Align-Grantham Variation Grantham Deviation, multivariate analysis of protein polymorphisms [MAPP], Mut-Pred, PolyPhen-2.1, Sorting Intolerant From Tolerant, and Xvar), using curated MMR multiple sequence alignments where possible. The output from each tool was calibrated by regression against the classifications of the 74 missense substitutions; these calibrated outputs are interpretable as prior probabilities of pathogenicity. MAPP was the most accurate tool and MAPP + PolyPhen-2.1 provided the best-combined model (R2 = 0.62 and area under receiver operating characteristic = 0.93). The MAPP + PolyPhen-2.1 output is sufficiently predictive to feed as a continuous variable into the quantitative Bayesian integrated evaluation for clinical classification of MMR gene missense substitutions. PMID:22949387

  6. 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

  7. Repair systems for deteriorated bridge piles : final report.

    Science.gov (United States)

    2017-04-01

    The objective of this research project is to develop a durable repair system for deteriorated steel bridge piles that : can be implemented without the need for dewatering. A rigorous survey of the relevant practice nationwide was : conducted to infor...

  8. Dacryoscintigraph evaluation of the repaired lacrimal drainage system

    International Nuclear Information System (INIS)

    Hoehn, J.G.; Vitale, P.; Elliott, R.A. Jr.

    1976-01-01

    We have used dacryoscintigraphy to study the efficiency of the lacrimal system following the repair of a divided lower canaliculus in 4 children. This test has been reliable in evaluating lacrimal function and suggests that a canaliculus can be repaired and splinted satisfactorily. Our experience with dacryoscintigraphy confirms that it is a safe comfortable, and reliable method for studying the patency of the lacrimal drainage system

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

    Science.gov (United States)

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

    2008-07-01

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

  10. Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures.

    Directory of Open Access Journals (Sweden)

    Mehdi Shakibaei

    Full Text Available OBJECTIVE: Treatment of colorectal cancer (CRC remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50-60%. Cancer stem cells (CSC are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin in context of DNA mismatch repair (MMR status and CSC activity in 3D cultures of CRC cells. METHODS: High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3 and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. RESULTS: Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. CONCLUSION: Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract.

  11. Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures.

    Science.gov (United States)

    Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

    2014-01-01

    Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50-60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells. High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract).

  12. 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....

  13. 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.

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

    KAUST Repository

    Gu, Binbin; Li, Zhixu; Yang, Qiang; Xie, Qing; Liu, An; Liu, Guanfeng; Zheng, Kai; Zhang, Xiangliang

    2017-01-01

    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.

  15. 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...

  16. Distinct effects of the recurrent Mlh1G67R mutation on MMR functions, cancer, and meiosis

    OpenAIRE

    Avdievich, Elena; Reiss, Cora; Scherer, Stefan J.; Zhang, Yongwei; Maier, Sandra M.; Jin, Bo; Hou, Harry; Rosenwald, Andreas; Riedmiller, Hubertus; Kucherlapati, Raju; Cohen, Paula E.; Edelmann, Winfried; Kneitz, Burkhard

    2008-01-01

    Mutations in the human DNA mismatch repair (MMR) gene MLH1 are associated with hereditary nonpolyposis colorectal cancer (Lynch syndrome, HNPCC) and a significant proportion of sporadic colorectal cancer. The inactivation of MLH1 results in the accumulation of somatic mutations in the genome of tumor cells and resistance to the genotoxic effects of a variety of DNA damaging agents. To study the effect of MLH1 missense mutations on cancer susceptibility, we generated a mouse line carrying the ...

  17. A bivariate optimal replacement policy for a multistate repairable system

    International Nuclear Information System (INIS)

    Zhang Yuanlin; Yam, Richard C.M.; Zuo, Ming J.

    2007-01-01

    In this paper, a deteriorating simple repairable system with k+1 states, including k failure states and one working state, is studied. It is assumed that the system after repair is not 'as good as new' and the deterioration of the system is stochastic. We consider a bivariate replacement policy, denoted by (T,N), in which the system is replaced when its working age has reached T or the number of failures it has experienced has reached N, whichever occurs first. The objective is to determine the optimal replacement policy (T,N)* such that the long-run expected profit per unit time is maximized. The explicit expression of the long-run expected profit per unit time is derived and the corresponding optimal replacement policy can be determined analytically or numerically. We prove that the optimal policy (T,N)* is better than the optimal policy N* for a multistate simple repairable system. We also show that a general monotone process model for a multistate simple repairable system is equivalent to a geometric process model for a two-state simple repairable system in the sense that they have the same structure for the long-run expected profit (or cost) per unit time and the same optimal policy. Finally, a numerical example is given to illustrate the theoretical results

  18. Measles, Mumps, and Rubella (MMR) Vaccination: What Everyone Should Know

    Science.gov (United States)

    ... information, see State Vaccination Requirements . How Can Parents Pay For MMR Vaccine? Most health insurance plans cover ... Word file Microsoft Excel file Audio/Video file Apple Quicktime file RealPlayer file Text file Zip Archive ...

  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. Cross calibration of the Siemens mMR: easily acquired accurate PET phantom measurements, long term stability and reproducibility

    Energy Technology Data Exchange (ETDEWEB)

    Keller, Sune H [Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Jakoby, Bjorn [University of Surrey, Guildford (United Kingdom); Hansen, Adam Espe; Svalling, Susanne; Klausen, Thomas L [Rigshospitalet, University of Copenhagen, Copenhagen (Denmark)

    2015-05-18

    We present a quick and easy method to perform quantitatively accurate PET scans of typical water-filled PET plastic shell phantoms on the Siemens mMR PET/MR scanner. We perform regular cross calibrations (Xcals) of our PET scanners, including the Siemens mMR PET/MR, with a Siemens mCT water phantom. We evaluate the mMR cross calibration stability over a 3-year period. Recently, the mMR software (VB20P) offered the option of using predefined μ-maps. We evaluated this option by using either the predefined μ-map of the long mMR water phantom or a system-integrated user defined CT-based μ-map of the mCT water phantom used for Xcal. On 54 cross calibrations that were acquired over 3 years, the mMR on average underestimated the concentration by 16% due to the use of MR-based μ-maps. The mMR produced the narrowest range and lowest standard deviation of the Xcal ratios, implying it and is the most stable of the 6 scanners included in this study over a 3 year period. With correctly segmented μ-maps, the mMR produced Xcal ratios of 1.00-1.02, well within the acceptance range [0.95-1.05]. Measuring the concentration in a centrally placed cylindrical VOI allows for some robustness against misregistration of the μ-maps but it should be no more than a few millimeters in the x-y plane, while the tolerance is larger on the z-axis (when, as always with PET, keeping clear of the axial edges of the FOV). The mMR is the most stable scanner in this study and the mean underestimation is no longer an issue with the easily accessible μ-map, which in all 7 tests resulted in correct Xcal ratios. We will share the user defined μ-map of the mCT phantom and the protocol with interested mMR users.

  1. Cross calibration of the Siemens mMR: easily acquired accurate PET phantom measurements, long term stability and reproducibility

    International Nuclear Information System (INIS)

    Keller, Sune H; Jakoby, Bjorn; Hansen, Adam Espe; Svalling, Susanne; Klausen, Thomas L

    2015-01-01

    We present a quick and easy method to perform quantitatively accurate PET scans of typical water-filled PET plastic shell phantoms on the Siemens mMR PET/MR scanner. We perform regular cross calibrations (Xcals) of our PET scanners, including the Siemens mMR PET/MR, with a Siemens mCT water phantom. We evaluate the mMR cross calibration stability over a 3-year period. Recently, the mMR software (VB20P) offered the option of using predefined μ-maps. We evaluated this option by using either the predefined μ-map of the long mMR water phantom or a system-integrated user defined CT-based μ-map of the mCT water phantom used for Xcal. On 54 cross calibrations that were acquired over 3 years, the mMR on average underestimated the concentration by 16% due to the use of MR-based μ-maps. The mMR produced the narrowest range and lowest standard deviation of the Xcal ratios, implying it and is the most stable of the 6 scanners included in this study over a 3 year period. With correctly segmented μ-maps, the mMR produced Xcal ratios of 1.00-1.02, well within the acceptance range [0.95-1.05]. Measuring the concentration in a centrally placed cylindrical VOI allows for some robustness against misregistration of the μ-maps but it should be no more than a few millimeters in the x-y plane, while the tolerance is larger on the z-axis (when, as always with PET, keeping clear of the axial edges of the FOV). The mMR is the most stable scanner in this study and the mean underestimation is no longer an issue with the easily accessible μ-map, which in all 7 tests resulted in correct Xcal ratios. We will share the user defined μ-map of the mCT phantom and the protocol with interested mMR users.

  2. Cold standby repairable system with working vacations and vacation interruption

    Institute of Scientific and Technical Information of China (English)

    Baoliang Liu; Lirong Cui; Yanqing Wen

    2015-01-01

    This paper studies a cold standby repairable system with working vacations and vacation interruption. The repairman’s multiple vacations policy, the working vacations policy and the vacation interruption are considered simultaneously. The lifetime of components fol ows a phase-type (PH) distribution. The repair time in the regular repair period and the working vacation period fol ow other two PH distributions at different rates. For this sys-tem, the vector-valued Markov process governing the system is constructed. We obtain several important performance measures for the system in transient and stationary regimes applying matrix-analytic methods. Final y, a numerical example is given to il ustrate the results obtained.

  3. The role of mismatch repair in small-cell lung cancer cells

    DEFF Research Database (Denmark)

    Hansen, L T; Thykjaer, T; Ørntoft, T F

    2003-01-01

    The role of mismatch repair (MMR) in small-cell lung cancer (SCLC) is controversial, as the phenotype of a MMR-deficiency, microsatellite instability (MSI), has been reported to range from 0 to 76%. We studied the MMR pathway in a panel of 21 SCLC cell lines and observed a highly heterogeneous...... pattern of MMR gene expression. A significant correlation between the mRNA and protein levels was found. We demonstrate that low hMLH1 gene expression was not linked to promoter CpG methylation. One cell line (86MI) was found to be deficient in MMR and exhibited resistance to the alkylating agent MNNG...

  4. Inducible DNA-repair systems in yeast: competition for lesions.

    Science.gov (United States)

    Mitchel, R E; Morrison, D P

    1987-03-01

    DNA lesions may be recognized and repaired by more than one DNA-repair process. If two repair systems with different error frequencies have overlapping lesion specificity and one or both is inducible, the resulting variable competition for the lesions can change the biological consequences of these lesions. This concept was demonstrated by observing mutation in yeast cells (Saccharomyces cerevisiae) exposed to combinations of mutagens under conditions which influenced the induction of error-free recombinational repair or error-prone repair. Total mutation frequency was reduced in a manner proportional to the dose of 60Co-gamma- or 254 nm UV radiation delivered prior to or subsequent to an MNNG exposure. Suppression was greater per unit radiation dose in cells gamma-irradiated in O2 as compared to N2. A rad3 (excision-repair) mutant gave results similar to wild-type but mutation in a rad52 (rec-) mutant exposed to MNNG was not suppressed by radiation. Protein-synthesis inhibition with heat shock or cycloheximide indicated that it was the mutation due to MNNG and not that due to radiation which had changed. These results indicate that MNNG lesions are recognized by both the recombinational repair system and the inducible error-prone system, but that gamma-radiation induction of error-free recombinational repair resulted in increased competition for the lesions, thereby reducing mutation. Similarly, gamma-radiation exposure resulted in a radiation dose-dependent reduction in mutation due to MNU, EMS, ENU and 8-MOP + UVA, but no reduction in mutation due to MMS. These results suggest that the number of mutational MMS lesions recognizable by the recombinational repair system must be very small relative to those produced by the other agents. MNNG induction of the inducible error-prone systems however, did not alter mutation frequencies due to ENU or MMS exposure but, in contrast to radiation, increased the mutagenic effectiveness of EMS. These experiments demonstrate

  5. Service water system repair/replacement guidelines: Planning and implementation

    International Nuclear Information System (INIS)

    Frederick, G.J.; Gandy, D.W.; Peterson, A.G. Jr.; Findlan, S.J.

    1993-11-01

    Service water system failures have prompted concerns related to extended power plant operating life and plant availability. Selection and procurement of materials for repair or replacement of piping and components may be the most important factors in improving service water system reliability. The authors examined factors that contribute to reduced SWS reliability. The factors include material selection inadequacies, water treatment problems, operational/maintenance practices, fabrication procedures, environmental degradation mechanisms, and coating problems. The authors investigated material selection for replacement and repair, taking into account fabrication practices, environmental concerns, and cost comparisons of materials. They examined specific components such as piping, pumps, valves, and heat exchangers with regard to material selection and fabrication practice. Although proper material selection is essential in upgrading and maintaining the designed functions of a SWS, it is critical to address SWS repair/replacement activities with a systemwide approach. Degradation of materials in SWS applications are plant specific, depending on factors unique to each site such as geographic location, existing materials, operating procedures, and environment. All these characteristics must be addressed in making repair/replacement decisions. Criteria that must be integrated for successful long-term operation of SWS include the following: Materials selection (upgrade or in-kind replacement), Evaluation of root cause or nature of the failure mechanism, Scope of the repair/replacement activities, Material compatibility of the existing materials, Operational and maintenance procedures, Code or jurisdictional requirements, Economic considerations, Water treatment programs, System design improvements or modifications

  6. Balancing flexibility and inventory in repair inventory systems

    NARCIS (Netherlands)

    Haas, de H.F.M.; Martin, H.H.

    1995-01-01

    In repair inventory systems, failed units are exchanged for serviceable units upon failure. The probability that serviceable units are available to support the exchange process can be used as a measure for the performance of the system. This measure is commonly called the expected fill rate. The

  7. Effective Measurement of Reliability of Repairable USAF Systems

    Science.gov (United States)

    2012-09-01

    ix I. Introduction ...RELIABILITY OF REPAIRABLE USAF SYSTEMS I. Introduction General Issue The United States relies on complex systems to protect and project the national...Under Secretary of Defense for Acquisition, Technology, and Logistics, Implementing a Lifecycle Mangement Framework, Washington DC, DC: DoD, 2008

  8. 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

  9. Mountain Plains Learning Experience Guide: Automotive Repair. Course: Emission Systems.

    Science.gov (United States)

    Schramm, C.; Osland, Walt

    One of twelve individualized courses included in an automotive repair curriculum, this course covers the theory, testing, and servicing of automotive emission control systems. The course is comprised of one unit, Fundamentals of Emission Systems. The unit begins with a Unit Learning Experience Guide that gives directions for unit completion. The…

  10. Pathological assessment of mismatch repair gene variants in Lynch syndrome

    DEFF Research Database (Denmark)

    Rasmussen, Lene Juel; Heinen, Christopher D; Royer-Pokora, Brigitte

    2012-01-01

    Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose...

  11. DNA mismatch repair and its many roles in eukaryotic cells

    DEFF Research Database (Denmark)

    Liu, Dekang; Keijzers, Guido; Rasmussen, Lene Juel

    2017-01-01

    in the clinic, and as a biomarker of cancer susceptibility in animal model systems. Prokaryotic MMR is well-characterized at the molecular and mechanistic level; however, MMR is considerably more complex in eukaryotic cells than in prokaryotic cells, and in recent years, it has become evident that MMR plays...... novel roles in eukaryotic cells, several of which are not yet well-defined or understood. Many MMR-deficient human cancer cells lack mutations in known human MMR genes, which strongly suggests that essential eukaryotic MMR components/cofactors remain unidentified and uncharacterized. Furthermore......, the mechanism by which the eukaryotic MMR machinery discriminates between the parental (template) and the daughter (nascent) DNA strand is incompletely understood and how cells choose between the EXO1-dependent and the EXO1–independent subpathways of MMR is not known. This review summarizes recent literature...

  12. Human Postmeiotic Segregation 2 Exhibits Biased Repair at Tetranucleotide Microsatellite Sequences

    OpenAIRE

    Shah, Sandeep N.; Eckert, Kristin A.

    2009-01-01

    The mismatch repair (MMR) system plays a major role in removing DNA polymerization errors, and loss of this pathway results in hereditary cancers characterized by microsatellite instability. We investigated microsatellite stability during DNA replication within human postmeiotic segregation 2 (hPMS2)–deficient and proficient human lymphoblastoid cell lines. Using a shuttle vector assay, we measured mutation rates at reporter cassettes containing defined mononucleotide, dinucleotide, and tetra...

  13. Iterative Repair Planning for Spacecraft Operations Using the Aspen System

    Science.gov (United States)

    Rabideau, G.; Knight, R.; Chien, S.; Fukunaga, A.; Govindjee, A.

    2000-01-01

    This paper describes the Automated Scheduling and Planning Environment (ASPEN). ASPEN encodes complex spacecraft knowledge of operability constraints, flight rules, spacecraft hardware, science experiments and operations procedures to allow for automated generation of low level spacecraft sequences. Using a technique called iterative repair, ASPEN classifies constraint violations (i.e., conflicts) and attempts to repair each by performing a planning or scheduling operation. It must reason about which conflict to resolve first and what repair method to try for the given conflict. ASPEN is currently being utilized in the development of automated planner/scheduler systems for several spacecraft, including the UFO-1 naval communications satellite and the Citizen Explorer (CX1) satellite, as well as for planetary rover operations and antenna ground systems automation. This paper focuses on the algorithm and search strategies employed by ASPEN to resolve spacecraft operations constraints, as well as the data structures for representing these constraints.

  14. Repair of uv damaged DNA in systemic lupus erythematosus. [Mice

    Energy Technology Data Exchange (ETDEWEB)

    Beighlie, D J; Teplitz, R L

    1975-06-01

    The NZB NZW hybrid mouse is an animal model of human systemic lupus erythematosus (SLE). Two breeding schemes were devised using NZB, NZW, B/W, and CBA mice, which permit definitive decisions regarding genetic and/or viral origin of the disease. It is proposed that at least two factors must be involved: a genetic abnormality producing hyper-responsiveness to nucleic acid antigens, and a DNA repair defect which results in liberation of DNA and RNA when cells are lethally injured. Evidence is presented for a DNA repair deficit in human SLE lymphocytes following in vitro irradiation with ultraviolet (uv) light. Lymphocytes from adult New Zealand and control mice were found to lack normal amounts of endonuclease necessary for repairing uv damage.

  15. Interdependence of DNA mismatch repair proteins MLH1 and MSH2 in apoptosis in human colorectal carcinoma cell lines.

    Science.gov (United States)

    Hassen, Samar; Ali, Akhtar A; Kilaparty, Surya P; Al-Anbaky, Qudes A; Majeed, Waqar; Boman, Bruce M; Fields, Jeremy Z; Ali, Nawab

    2016-01-01

    The mammalian DNA mismatch repair (MMR) system consists of a number of proteins that play important roles in repair of base pair mismatch mutations and in maintenance of genomic integrity. A defect in this system can cause genetic instability, which can lead to carcinogenesis. For instance, a germline mutation in one of the mismatch repair proteins, especially MLH1 or MSH2, is responsible for hereditary non-polyposis colorectal cancer. These MMR proteins also play an important role in the induction of apoptosis. Accordingly, altered expression of or a defect in MLH1 or MSH2 may confer resistance to anti-cancer drugs used in chemotherapy. We hypothesized that the ability of these two MMR proteins to regulate apoptosis are interdependent. Moreover, a defect in either one may confer resistance to chemotherapy by an inability to trigger apoptosis. To this end, we studied three cell lines-SW480, LoVo, and HTC116. These cell lines were selected based on their differential expression of MLH1 and MSH2 proteins. SW480 expresses both MLH1 and MSH2; LoVo expresses only MLH1 but not MSH2; HCT116 expresses only MSH2 but not MLH1 protein. MTT assays, a measure of cytotoxicity, showed that there were different cytotoxic effects of an anti-cancer drug, etoposide, on these cell lines, effects that were correlated with the MMR status of the cells. Cells that are deficient in MLH1 protein (HCT116 cells) were resistant to the drug. Cells that express both MLH1 and MSH2 proteins (SW480 cells) showed caspase-3 cleavage, an indicator of apoptosis. Cells that lack MLH1 (HCT116 cells) did not show any caspase-3 cleavage. Expression of full-length MLH1 protein was decreased in MMR proficient (SW480) cells during apoptosis; it remained unchanged in cells that lack MSH2 (LoVo cells). The expression of MSH2 protein remained unchanged during apoptosis both in MMR proficient (SW480) and deficient (HCT116) cells. Studies on translocation of MLH1 protein from nucleus to cytosolic fraction, an

  16. 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 ...

  17. Microsatellite Instability Use in Mismatch Repair Gene Sequence Variant Classification

    Directory of Open Access Journals (Sweden)

    Bryony A. Thompson

    2015-03-01

    Full Text Available Inherited mutations in the DNA mismatch repair genes (MMR can cause MMR deficiency and increased susceptibility to colorectal and endometrial cancer. Microsatellite instability (MSI is the defining molecular signature of MMR deficiency. The clinical classification of identified MMR gene sequence variants has a direct impact on the management of patients and their families. For a significant proportion of cases sequence variants of uncertain clinical significance (also known as unclassified variants are identified, constituting a challenge for genetic counselling and clinical management of families. The effect on protein function of these variants is difficult to interpret. The presence or absence of MSI in tumours can aid in determining the pathogenicity of associated unclassified MMR gene variants. However, there are some considerations that need to be taken into account when using MSI for variant interpretation. The use of MSI and other tumour characteristics in MMR gene sequence variant classification will be explored in this review.

  18. 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...... clinicopathologic variables and immunohistochemical MMR protein expression. RESULTS: Female sex, age ≥60 years, proximal tumor location, expanding growth pattern, lack of dirty necrosis, mucinous differentiation and presence of tumor-infiltrating lymphocytes significantly correlated with MMR deficiency. Presence...

  19. DNA Damage Repair System in Plants: A Worldwide Research Update.

    Science.gov (United States)

    Gimenez, Estela; Manzano-Agugliaro, Francisco

    2017-10-30

    Living organisms are usually exposed to various DNA damaging agents so the mechanisms to detect and repair diverse DNA lesions have developed in all organisms with the result of maintaining genome integrity. Defects in DNA repair machinery contribute to cancer, certain diseases, and aging. Therefore, conserving the genomic sequence in organisms is key for the perpetuation of life. The machinery of DNA damage repair (DDR) in prokaryotes and eukaryotes is similar. Plants also share mechanisms for DNA repair with animals, although they differ in other important details. Plants have, surprisingly, been less investigated than other living organisms in this context, despite the fact that numerous lethal mutations in animals are viable in plants. In this manuscript, a worldwide bibliometric analysis of DDR systems and DDR research in plants was made. A comparison between both subjects was accomplished. The bibliometric analyses prove that the first study about DDR systems in plants (1987) was published thirteen years later than that for other living organisms (1975). Despite the increase in the number of papers about DDR mechanisms in plants in recent decades, nowadays the number of articles published each year about DDR systems in plants only represents 10% of the total number of articles about DDR. The DDR research field was done by 74 countries while the number of countries involved in the DDR & Plant field is 44. This indicates the great influence that DDR research in the plant field currently has, worldwide. As expected, the percentage of studies published about DDR systems in plants has increased in the subject area of agricultural and biological sciences and has diminished in medicine with respect to DDR studies in other living organisms. In short, bibliometric results highlight the current interest in DDR research in plants among DDR studies and can open new perspectives in the research field of DNA damage repair.

  20. 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...

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

    Science.gov (United States)

    Kucukyildirim, Sibel; Long, Hongan; Sung, Way; Miller, Samuel F; Doak, Thomas G; Lynch, Michael

    2016-07-07

    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. Copyright © 2016 Kucukyildirim et al.

  2. 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.

  3. Optimal Inspection and Repair Strategies for Structural Systems

    DEFF Research Database (Denmark)

    Sommer, A. M.; Nowak, A. S.; Thoft-Christensen, Palle

    1992-01-01

    and a design variable as optimization variables. A model for estimating the total expected costs for structural systems is given including the costs associated with the loss of individual structural members as well as the costs associated with the loss of at least one element of a particular group......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...... of structural members and the costs associated with the simultaneous loss of all members of a specific group of structural members. The approach is based on the pre-posteriori analysis from the classical decision theory. Special emphasis is given to the problem of selecting the number of points in the structure...

  4. Development of management system for plant repairing work

    International Nuclear Information System (INIS)

    Terauchi, Makoto

    1999-01-01

    In the fast breeder reactor, ''Monju'', in order to conduct nuclear plant repairing works securely and effectively, development of a computer system to assist management business on plant repairing work was begun on 1993. The system has been applied to about 5,000 times of operational management through past four times of plant inspection and to daily inspections and maintenance, and is daily used at working places of ''Monju'' such as issue/management of about 110,000 times of operational prohibition tag in isolated management. And, by automation of issue/management on working sheets and operational prohibition tag and others conducted hitherto by hand, the management business has been largely rationalized. (G.K.)

  5. Reporting of MMR evidence in professional publications: 1988–2007

    Science.gov (United States)

    Hilton, S; Hunt, K; Langan, M; Hamilton, V; Petticrew, M

    2009-01-01

    Objective: To examine how journals and magazines disseminate research evidence and guidance on best practice to health professionals by aligning commentaries on measles, mumps, and rubella vaccine (MMR) evidence in journals with key events in the MMR controversy. Design: Content analysis. Data sources: Comment articles in six commonly read UK publications. Main outcome measures: Number of comment pieces by publication, year and article type; trends in the focus, tone and inclusion of recommendations on MMR. Results: 860 articles met the inclusion criteria (BMJ n = 104, Community Practitioner n = 45, Health Visitor n = 24, Practice Nurse n = 61, Nursing Standard n = 61 and Pulse n = 565). Of these 860 comment pieces, 264 made some reference to evidence endorsing the safety of MMR. Around one in 10 were rated as negative (10.9%, n = 29) or neutral (11.3%, n = 30) in relation to MMR safety, and nearly a quarter (22.7%, n = 60) were rated as mixed. Following the publication of Wakefield et al’s 1998 paper there was a period of neutrality. In 2000, despite growing public concerns and widespread media coverage, fewer than 20 comment pieces were published. Less than a quarter of comment pieces (n = 196, 22.7%) included recommendations. Conclusion: While a period of neutrality may reflect a professional response to uncertainty by holding back until consensus emerges, it may also represent a missed opportunity to promote evidence-based practice. PMID:19414434

  6. On some steady-state characteristics of systems with gradual repair

    International Nuclear Information System (INIS)

    Finkelstein, Maxim; Ludick, Zani

    2014-01-01

    We consider a repairable system with continuous output that alternates between states of operation and repair. The output of the system in the operating state is represented by a continuous, decreasing function of time. We assume that during the repair state, the system can produce output that is modelled by an increasing stochastic process. The repair action gradually restores the output of the system to its initial level and it returns to the operating state. We obtain and analyse expressions for the generalized availability and related characteristics of systems with gradual repair and consider several meaningful examples

  7. Moisture movement in cement-based repair systems monitored by X-ray absorption

    NARCIS (Netherlands)

    Lukovic, M.; Ye, G.; Schlangen, H.E.J.G.; van Breugel, K.

    2017-01-01

    In concrete repair systems, material properties in the repair material and interface are greatly influenced by the initial moisture content of the concrete (or mortar) substrate. In order to quantify moisture profiles inside the repair system, X-ray absorption was used. Preliminary studies are

  8. 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

  9. The development of a remote repair system for deep water pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Frazer, Ian; Giles, John [Stolt Offshore MS Ltd., Aberdeen (United Kingdom)

    2000-07-01

    The ability to maintain a high level of flexibility within the contingency plans for sub sea pipeline repair is a critical issue normally achieved by basing the repair plans on diver intervention. This allows the pipeline operator flexibility to respond to particular repair situations as they occur, minimize up front planning and optimize the investment in repair equipment and stock. However for deep water pipelines all intervention must be performed by remote methods, which require the development of suitable equipment and more detailed repair procedures. This paper describes the development of a remotely operated pipeline repair system capable of working down to 3000 m and allowing a relatively high level of flexibility with minimum investment in repair stock. The repair system is based upon the Modular Advanced Tie-In System (MATIS) which has been successfully developed for the tie-in of deep water flow lines. The MATIS repair system is based on the use of standard flanges to replace a damaged section of pipe with a spool piece in a similar manner to a hyperbaric welded repair. Various repair scenarios are discussed in the paper together with the equipment and the procedures used to perform the repair. The paper will also discuss the other remote repair options such as hot tapping and friction stitch welding. (author)

  10. Mismatch repair proficiency is not required for radioenhancement by gemcitabine

    International Nuclear Information System (INIS)

    Bree, Chris van; Rodermond, Hans M.; Vos, Judith de; Haveman, Jaap; Franken, Nicolaas

    2005-01-01

    Purpose: Mismatch repair (MMR) proficiency has been reported to either increase or decrease radioenhancement by 24-h incubations with gemcitabine. This study aimed to establish the importance of MMR for radioenhancement by gemcitabine after short-exposure, high-dose treatment and long-exposure, low-dose treatment. Methods and Materials: Survival of MMR-deficient HCT116 and MMR-proficient HCT116 + 3 cells was analyzed by clonogenic assays. Mild, equitoxic gemcitabine treatments (4 h, 0.1 μM vs. 24 h, 6 nM) were combined with γ-irradiation to determine the radioenhancement with or without recovery. Gemcitabine metabolism and cell-cycle effects were evaluated by high-performance liquid chromatography analysis and bivariate flow cytometry. Results: Radioenhancement after 4 h of 0.1 μM of gemcitabine was similar in both cell lines, but the radioenhancement after 24 h of 6 nM of gemcitabine was reduced in MMR-proficient cells. No significant differences between both cell lines were observed in the gemcitabine metabolism or cell-cycle effects after these treatments. Gemcitabine radioenhancement after recovery was also lower in MMR-proficient cells than in MMR-deficient cells. Conclusion: Mismatch repair proficiency decreases radioenhancement by long incubations of gemcitabine but does not affect radioenhancement by short exposures to a clinically relevant gemcitabine dose. Our data suggest that MMR contributes to the recovery from gemcitabine treatment

  11. Reliable pipeline repair system for very large pipe size

    Energy Technology Data Exchange (ETDEWEB)

    Charalambides, John N.; Sousa, Alexandre Barreto de [Oceaneering International, Inc., Houston, TX (United States)

    2004-07-01

    The oil and gas industry worldwide has been mainly depending on the long-term reliability of rigid pipelines to ensure the transportation of hydrocarbons, crude oil, gas, fuel, etc. Many other methods are also utilized onshore and offshore (e.g. flexible lines, FPSO's, etc.), but when it comes to the underwater transportation of very high volumes of oil and gas, the industry commonly uses large size rigid pipelines (i.e. steel pipes). Oil and gas operators learned to depend on the long-lasting integrity of these very large pipelines and many times they forget or disregard that even steel pipelines degrade over time and more often that that, they are also susceptible to various forms of damage (minor or major, environmental or external, etc.). Over the recent years the industry had recognized the need of implementing an 'emergency repair plan' to account for such unforeseen events and the oil and gas operators have become 'smarter' by being 'pro-active' in order to ensure 'flow assurance'. When we consider very large diameter steel pipelines such as 42' and 48' nominal pipe size (NPS), the industry worldwide does not provide 'ready-made', 'off-the-shelf' repair hardware that can be easily shipped to the offshore location and effect a major repair within acceptable time frames and avoid substantial profit losses due to 'down-time' in production. The typical time required to establish a solid repair system for large pipe diameters could be as long as six or more months (depending on the availability of raw materials). This paper will present in detail the Emergency Pipeline Repair Systems (EPRS) that Oceaneering successfully designed, manufactured, tested and provided to two major oil and gas operators, located in two different continents (Gulf of Mexico, U.S.A. and Arabian Gulf, U.A.E.), for two different very large pipe sizes (42'' and 48'' Nominal Pipe Sizes

  12. DNA repair

    International Nuclear Information System (INIS)

    Setlow, R.

    1978-01-01

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

  13. Availability estimation of repairable systems using reliability graph with general gates (RGGG)

    International Nuclear Information System (INIS)

    Goh, Gyoung Tae

    2009-02-01

    By performing risk analysis, we may obtain sufficient information about the system to redesign it and lower the probability of the occurrence of an accident or mitigate the ensuing consequences. The concept of reliability is widely used to express risk of systems. The reliability is used for non-repairable systems. But nuclear power plant systems are repairable systems. With repairable systems, repairable components can improve the availability of a system because faults that are generated in components can be recovered. Hence, the availability of the system is more proper concept in case of repairable systems. Reliability graph with general gate (RGGG) is one of the system reliability analysis methods. The RGGG is a very intuitiveness method as compared with other methods. But the RGGG has not been applied to repairable systems yet. The objective of this study is to extend the RGGG in order to enable one to analyze repairable system. Determining the probability table for each node is a critical process to calculate the system availability in the RGGG method. Therefore finding the proper algorithms and making probability tables in various situations are the major a part of this study. The other part is an example of applying RGGG method to a real system. We find the proper algorithms and probability tables for independent repairable systems, dependent series repairable systems, and k-out-of-m (K/M) redundant parallel repairable systems in this study. We can evaluate the availability of real system using these probability tables. An example for a real system is shown in the latter part of this study. For the purpose of this analysis, the charging pumps subsystem of the chemical and volume control system (CVCS) was selected. The RGGG method extended for repairable systems has the same characteristic of intuitiveness as the original RGGG method and we can confirm that the availability analysis result from the repairable RGGG method is exact

  14. Reliability analysis for a circular consecutive-2-out-of-n:F repairable system with priority in repair

    International Nuclear Information System (INIS)

    Zhang Yuanlin; Zuo, Ming J.; Yam, Richard C.M.

    2000-01-01

    A circular consecutive-2-out-of-n:F repairable system with one repairman is studied in this paper. When there are more than one failed component, priorities are assigned to the failed components. Both the working time and the repair time of each component is assumed to be exponentially distributed. Every component after repair is as good as new. By using the definition of generalized transition probability and the concept of critical component, we derive the state transition probability matrix of the system. Methodologies are then presented for the derivation of system reliability indexes such as availability, rate of occurrence of failure, mean time between failures, reliability, and mean time to first failure

  15. 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.

  16. 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...

  17. Evaluation of Uniform Cost Accounting System to Fully Capture Depot Level Repair Costs.

    Science.gov (United States)

    1985-12-01

    RD-RI65 522 EVALUATION OF UNIFORM COST ACCOUNTING SYSTEM TO FULLY i/I CAPTURE DEPOT LEVEL REPAIR COSTS (U) NAVAL POSTGRADUATE SCHOOL MONTEREY CA D R...8217.LECTE B ,- THESIS EVALUATION OF UNIFORM COST ACCOUNTING SYSTEM 0TO FULLY CAPTURE DEPOT LEVEL REPAIR COSTS Jby __jDavid Richmond O’Brien lj,,, December...Include Security Classification) EVALUATION OF UNIFORM COST ACCOUNTING SYSTEM TO FULLY CAPTURE DEPOT LEVEL REPAIR COSTS 12 PERSONAL AUTHOR(S) O’Brien- David

  18. 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.

  19. The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance

    Directory of Open Access Journals (Sweden)

    Feng YC

    2018-01-01

    .8% were associated with dMMR. PD-L1 in cancer cells, PD-L1 in TILs, and PD-1 in TILs took up 59.1%, 47.0%, and 60.6%, respectively. The data indicated that both dMMR and PD-L1 overexpression resulted from lower cancer differentiation, more incidences of childbearing, and a history of abortion. Abortion could significantly increase PD-1 expression levels in TILs. Additionally, more incidence of childbearing or older age (35–55 years was able to upregulate PD-L1 expression in TILs. Statistical difference of PD-L1 in cancer cells could be observed between dMMR and pMMR subgroups. In the dMMR group, PD-L1 in cancer cells and PD-1 in TILs had no correlation (rs=0.161, p=0.537, but in the pMMR group, they had good correlation (rs=0.645, p<0.001. Conclusion: According to prior studies and our own experiments, PD-L1 in both cancer cells and TILs and PD-1 in TILs are widely observed in cervical cancer patients, indicating that there may be potential to apply PD-1/PD-L1 antibody drugs in cervical cancer. dMMR patients are associated with higher PD-L1 expression compared with pMMR ones, which suggested that PD-1/PD-L1 antibody drugs may work well in dMMR cervical cancer patients. Moreover, in patients with more incidences of childbearing or abortion, dMMR may be a molecular detection target for clinical application of PD-1/PD-L1 antibody drugs. Keywords: programmed cell death 1, programmed cell death 1 ligand 1, DNA mismatch repair system, cervical cancer

  20. Guardians of the mycobacterial genome: A review on DNA repair systems in Mycobacterium tuberculosis.

    Science.gov (United States)

    Singh, Amandeep

    2017-12-01

    The genomic integrity of Mycobacterium tuberculosis is continuously threatened by the harsh survival conditions inside host macrophages, due to immune and antibiotic stresses. Faithful genome maintenance and repair must be accomplished under stress for the bacillus to survive in the host, necessitating a robust DNA repair system. The importance of DNA repair systems in pathogenesis is well established. Previous examination of the M. tuberculosis genome revealed homologues of almost all the major DNA repair systems, i.e. nucleotide excision repair (NER), base excision repair (BER), homologous recombination (HR) and non-homologous end joining (NHEJ). However, recent developments in the field have pointed to the presence of novel proteins and pathways in mycobacteria. Homologues of archeal mismatch repair proteins were recently reported in mycobacteria, a pathway previously thought to be absent. RecBCD, the major nuclease-helicase enzymes involved in HR in E. coli, were implicated in the single-strand annealing (SSA) pathway. Novel roles of archeo-eukaryotic primase (AEP) polymerases, previously thought to be exclusive to NHEJ, have been reported in BER. Many new proteins with a probable role in DNA repair have also been discovered. It is now realized that the DNA repair systems in M. tuberculosis are highly evolved and have redundant backup mechanisms to mend the damage. This review is an attempt to summarize our current understanding of the DNA repair systems in M. tuberculosis.

  1. Injectable systems and implantable conduits for peripheral nerve repair

    International Nuclear Information System (INIS)

    Lin, Yen-Chih; Marra, Kacey G

    2012-01-01

    Acute sensory problems following peripheral nerve injury include pain and loss of sensation. Approximately 360 000 people in the United States suffer from upper extremity paralytic syndromes every year. Restoration of sufficient functional recovery after long-gap peripheral nerve damage remains a clinical challenge. Potential nerve repair therapies have increased in the past decade as the field of tissue engineering expands. The following review describes the use of biomaterials in nerve tissue engineering. Namely, the use of both synthetic and natural biomaterials, including non-degradable and degradable nerve grafts, is addressed. The enhancement of axonal regeneration can be achieved by further modification of the nerve guides. These approaches include injectable hydrogel fillers, controlled drug delivery systems, and cell incorporation. Hydrogels are a class of liquid–gel biomaterials with high water content. Injectable and gelling hydrogels can serve as growth factor delivery vehicles and cell carriers for tissue engineering applications. While natural hydrogels and polymers are suitable for short gap nerve repair, the use of polymers for relatively long gaps remains a clinical challenge. (paper)

  2. Inequity in Timeliness of MMR Vaccination in Children Living in the Suburbs of Iranian Cities.

    Science.gov (United States)

    Jadidi, Rahmatollah; Mohammadbeigi, Abolfazl; Mohammadsalehi, Narges; Ansari, Hossein; Ghaderi, Ebrahim

    2015-06-01

    High coverage of immunization is one of the indicators of good performance of health system but timely vaccination is another indicator which is associated with protective effect of vaccines. The present study aimed at evaluating the inequity in timely vaccination with a focus on inequities in timeliness by gender, birth order, parents' education and place of residence (rural or urban). A historical cohort study was conducted on children of 24-47 months of age who were living in the suburbs of big cities in Iran and were selected through stratified proportional sampling method. Only children who had vaccine cards -i.e. 3610 children -were included in data analysis. The primary outcome was age-appropriate vaccination of MMR1. Inequity was measured by Concentration Index (C) and Relative Index of Inequity (RII). Inequity indexes were calculated according to the mother and father's education, child birth order, child's sex and the family's place of residence at the time of vaccination. The overall on-time MMR1 vaccination was 70% and 54.4% for Iranians and Non-Iranians, respectively. The C index of mother and father's education for timely MMR vaccination was 0.023 and was 0.029 in Iranian children as well as 0.044 and 0.019 for non-Iranians, respectively. The C index according to child order in Iranians and Non-Iranians was 0.025 and C=0.078. With regard to children who lived in cities, the on-time vaccination was 0.36% and 0.29% higher than that in rural areas . In male children it was 0.12% and 0.14% higher than that in female children for Iranians and Non-Iranians, respectively. Timeliness MMR vaccination in Iranian children is higher than that in non-Iranian children. Regarding the existence of differences in timely vaccination rate in all Iranian and Non-Iranian children, no evidence was observed for inequity by focusing on parents' education, birth order, gender or place of residence. So, increasing timeliness of vaccination for enhancing the protective effect

  3. Extending minimal repair models for repairable systems: A comparison of dynamic and heterogeneous extensions of a nonhomogeneous Poisson process

    International Nuclear Information System (INIS)

    Asfaw, Zeytu Gashaw; Lindqvist, Bo Henry

    2015-01-01

    For many applications of repairable systems, the minimal repair assumption, which leads to nonhomogeneous Poisson processes (NHPP), is not adequate. We review and study two extensions of the NHPP, the dynamic NHPP and the heterogeneous NHPP. Both extensions are motivated by specific aspects of potential applications. It has long been known, however, that the two paradigms are essentially indistinguishable in an analysis of failure data. We investigate the connection between the two approaches for extending NHPP models, both theoretically and numerically in a data example and a simulation study. - Highlights: • Review of dynamic extension of a minimal repair model (LEYP), introduced by Le Gat. • Derivation of likelihood function and comparison to NHPP model with heterogeneity. • Likelihood functions and conditional intensities are similar for the models. • ML estimation is considered for both models using a power law baseline. • A simulation study illustrates and confirms findings of the theoretical study

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

    International Nuclear Information System (INIS)

    Montoro-Cazorla, Delia; Perez-Ocon, Rafael

    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

  5. 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.

  6. DNA repair systems and the pathogenesis of Mycobacterium tuberculosis: varying activities at different stages of infection.

    Science.gov (United States)

    Gorna, Alina E; Bowater, Richard P; Dziadek, Jaroslaw

    2010-05-25

    Mycobacteria, including most of all MTB (Mycobacterium tuberculosis), cause pathogenic infections in humans and, during the infectious process, are exposed to a range of environmental insults, including the host's immune response. From the moment MTB is exhaled by infected individuals, through an active and latent phase in the body of the new host, until the time they reach the reactivation stage, MTB is exposed to many types of DNA-damaging agents. Like all cellular organisms, MTB has efficient DNA repair systems, and these are believed to play essential roles in mycobacterial pathogenesis. As different stages of infection have great variation in the conditions in which mycobacteria reside, it is possible that different repair systems are essential for progression to specific phases of infection. MTB possesses homologues of DNA repair systems that are found widely in other species of bacteria, such as nucleotide excision repair, base excision repair and repair by homologous recombination. MTB also possesses a system for non-homologous end-joining of DNA breaks, which appears to be widespread in prokaryotes, although its presence is sporadic within different species within a genus. However, MTB does not possess homologues of the typical mismatch repair system that is found in most bacteria. Recent studies have demonstrated that DNA repair genes are expressed differentially at each stage of infection. In the present review, we focus on different DNA repair systems from mycobacteria and identify questions that remain in our understanding of how these systems have an impact upon the infection processes of these important pathogens.

  7. DNA repair in B. subtilis: an inducible dimer-specific W-reactivation system

    International Nuclear Information System (INIS)

    Fields, P.I.; Yasbin, R.E.

    1982-01-01

    The W-reactivation system of Bacillus subtilis can repair pyrimidine dimers in bacteriophage DNA. This inducible repair system can be activated by treatment of the bacteria with uv, alkylating agents, cross-linking agents and gamma irradiation. However, bacteriophage treated with agents other than those that cause pyrimidine dimers to be produced was not repaired by this unique form of W-reactivation. In contrast, the W-reactivation system of Escherichia coli can repair a variety of damages placed in the bacteriophage DNA

  8. Performance Estimation of Supercritical Co2 Micro Modular Reactor (MMR) for Varying Cooling Air Temperature

    International Nuclear Information System (INIS)

    Ahn, Yoonhan; Kim, Seong Gu; Cho, Seong Kuk; Lee, Jeong Ik

    2015-01-01

    A Small Modular Reactor (SMR) receives interests for the various application such as electricity co-generation, small-scale power generation, seawater desalination, district heating and propulsion. As a part of SMR development, supercritical CO2 Micro Modular Reactor (MMR) of 36.2MWth in power is under development by the KAIST research team. To enhance the mobility, the entire system including the power conversion system is designed for the full modularization. Based on the preliminary design, the thermal efficiency is 31.5% when CO2 is sufficiently cooled to the design temperature. A supercritical CO2 MMR is designed to supply electricity to the remote regions. The ambient temperature of the area can influence the compressor inlet temperature as the reactor is cooled with the atmospheric air. To estimate the S-CO2 cycle performance for various environmental conditions, A quasi-static analysis code is developed. For the off design performance of S-CO2 turbomachineries, the experimental result of Sandia National Lab (SNL) is utilized

  9. Mismatch repair deficiency commonly precedes adenoma formation in Lynch Syndrome-Associated colorectal tumorigenesis.

    Science.gov (United States)

    Sekine, Shigeki; Mori, Taisuke; Ogawa, Reiko; Tanaka, Masahiro; Yoshida, Hiroshi; Taniguchi, Hirokazu; Nakajima, Takeshi; Sugano, Kokichi; Yoshida, Teruhiko; Kato, Mamoru; Furukawa, Eisaku; Ochiai, Atsushi; Hiraoka, Nobuyoshi

    2017-08-01

    Lynch syndrome is a cancer predisposition syndrome caused by germline mutations in mismatch repair (MMR) genes. MMR deficiency is a ubiquitous feature of Lynch syndrome-associated colorectal adenocarcinomas; however, it remains unclear when the MMR-deficient phenotype is acquired during tumorigenesis. To probe this issue, the present study examined genetic alterations and MMR statuses in Lynch syndrome-associated colorectal adenomas and adenocarcinomas, in comparison with sporadic adenomas. Among the Lynch syndrome-associated colorectal tumors, 68 of 86 adenomas (79%) and all adenocarcinomas were MMR-deficient, whereas all the sporadic adenomas were MMR-proficient, as determined by microsatellite instability testing and immunohistochemistry for MMR proteins. Sequencing analyses identified APC or CTNNB1 mutations in the majority of sporadic adenomas (58/84, 69%) and MMR-proficient Lynch syndrome-associated adenomas (13/18, 72%). However, MMR-deficient Lynch syndrome-associated adenomas had less APC or CTNNB1 mutations (25/68, 37%) and frequent frameshift RNF43 mutations involving mononucleotide repeats (45/68, 66%). Furthermore, frameshift mutations affecting repeat sequences constituted 14 of 26 APC mutations (54%) in MMR-deficient adenomas whereas these frameshift mutations were rare in MMR-proficient adenomas in patients with Lynch syndrome (1/12, 8%) and in sporadic adenomas (3/52, 6%). Lynch syndrome-associated adenocarcinomas exhibited mutation profiles similar to those of MMR-deficient adenomas. Considering that WNT pathway activation sufficiently drives colorectal adenoma formation, the distinct mutation profiles of WNT pathway genes in Lynch syndrome-associated adenomas suggest that MMR deficiency commonly precedes adenoma formation.

  10. ARCHER-Advanced System for RPVH Inspection and Repair

    International Nuclear Information System (INIS)

    Tomasic, Tomislav; Vukovic, Igor; Bakic, Ante

    2014-01-01

    The reactor pressure vessel head (RPVH) is an integral part of the reactor coolant pressure boundary. Its integrity is important for the safe and reliable operation of the nuclear power plant (NPP). After detection of the leakage and cracks in French NPP, followed by another that occurred in NPP in USA, methods and frequency of inspection were defined, and are strictly regulated by the US NRC Order EA-03-009 (substituted lately by ASME Code Case N-791-1) since 2003. Usual scope of inspection from inner side of RPVH comprises of visual inspection of the surface, ultrasonic testing (UT) and eddy current testing (ET) of the penetration nozzle and ET of the J-groove weld and nozzle outside surface below the weld. ARCHER, new INETEC's manipulator, is designed to provide full scope inspection of the RPVH, by use of various test modules and by performing the surface repair action on J-groove weld. It is adjustable to work with different types of penetration nozzles and thermal sleeves on both VVER and PWR type of NPP. Due to complex geometry each module is specially designed for particular type of examination. Modules are exchanged through the docking system without need for personnel to enter under the head region, thus reducing the personnel's exposure to the ionizing radiation. The end effectors are used to determine the surface flaws or cracks on inner diameter surface of penetration nozzle gap. It guides a slim sword-like probe which carries a pair of TOFD transducers for detection and sizing of circumferential and axial cracks, an eddy current cross-wounded coil, and a zero-degree UT probe through a gap between the penetration nozzle and thermal sleeve. In case of a non-sleeved penetration nozzle, an open housing module is used. J-groove module is designed to fit geometry of the J-groove weld of penetration nozzle, vent pipe and funnel guide. The whole weld area (2' mm on shell side and 1/2' on nozzle side) is covered by two specially designed

  11. Repairable system analysis in presence of covariates and random effects

    International Nuclear Information System (INIS)

    Giorgio, M.; Guida, M.; Pulcini, G.

    2014-01-01

    This paper aims to model the failure pattern of repairable systems in presence of explained and unexplained heterogeneity. The failure pattern of each system is described by a Power Law Process. Part of the heterogeneity among the patterns is explained through the use of a covariate, and the residual unexplained heterogeneity (random effects) is modeled via a joint probability distribution on the PLP parameters. The proposed approach is applied to a real set of failure time data of powertrain systems mounted on 33 buses employed in urban and suburban routes. Moreover, the joint probability distribution on the PLP parameters estimated from the data is used as an informative prior to make Bayesian inference on the future failure process of a generic system belonging to the same population and employed in an urban or suburban route under randomly chosen working conditions. - Highlights: • We describe the failure process of buses powertrain system subject to heterogeneity. • Heterogeneity due to different service types is explained by a covariate. • Random effect is modeled through a joint pdf on failure process parameters. • The powertrain reliability under new future operating conditions is estimated

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

    Directory of Open Access Journals (Sweden)

    Hong-Yu LIU

    2014-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Samuel L Collins

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

  14. 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

  15. Repair systems with exchangeable items and the longest queue mechanism

    NARCIS (Netherlands)

    Ravid, R.; Boxma, O.J.; Perry, D.

    2013-01-01

    We consider a repair facility consisting of one repairman and two arrival streams of failed items, from bases 1 and 2. The arrival processes are independent Poisson processes, and the repair times are independent and identically exponentially distributed. The item types are exchangeable, and a

  16. Repair systems with exchangeable items and the longest queue mechanism

    NARCIS (Netherlands)

    Ravid, R.; Boxma, O.J.; Perry, D.

    2011-01-01

    We consider a repair facility consisting of one repairman and two arrival streams of failed items, from bases 1 and 2. The arrival processes are independent Poisson processes, and the repair times are independent and identically exponentially distributed. The item types are exchangeable, and a

  17. Life forms employ different repair strategies of repair single- and double strand DNA breaks caused by different qualities of radiation: criticality of RecA mediated repair system

    International Nuclear Information System (INIS)

    Sharan, R.N.

    2013-01-01

    Different qualities of radiation, either through direct or indirect pathway, induce qualitative different spectrum of damages in DNA, which are also different in in vitro and in vivo systems. The single- and double strand breaks of DNA are of special interest as they lead to serious biological consequences. The implications of such damage to DNA and their processing by various inherent repair pathways together decide the fate of the living form

  18. 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...... or leukemias, and brain tumors. There is no satisfactory method for diagnosis of CMMRD because screens for mutations in MMR genes are noninformative for 30% of patients. MMR-deficient cancer cells are resistant to genotoxic agents and have microsatellite instability (MSI), due to accumulation of errors...

  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. 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.

  1. Analysis of a carbon composite overwrap pipeline repair system

    Energy Technology Data Exchange (ETDEWEB)

    Duell, J.M.; Wilson, J.M. [Department of Mechanical Engineering, University of Tulsa, Tulsa, OK 74104 (United States); Kessler, M.R. [Department of Materials Science and Engineering, Iowa State University, Ames, IA 50011 (United States)], E-mail: mkessler@iastate.edu

    2008-11-15

    A relatively new method has been developed to stop external corrosion and structurally reinforce steel pipes by external wrapping of damaged sections using fibre reinforced polymer (FRP) materials. Several different defect geometries representing corrosion patches on steel pipe were characterized using finite-element analysis, by changing the circumferential length of the defect. Pipe vessels containing these defects along with the composite structural repairs were modeled and the results were compared to field tests to determine the effectiveness of the repairs. It was found that the defect width around the circumference had little impact on the ultimate rupture pressure of the repaired vessel, but influenced the stress state in the underlying pipe substrate.

  2. An optimal replacement policy for a repairable system based on its repairman having vacations

    Energy Technology Data Exchange (ETDEWEB)

    Yuan Li [School of Aerospace Engineering and Applied Mechanics, Tongji University, Shanghai 200092 (China); Xu Jian, E-mail: xujian@tongji.edu.c [School of Aerospace Engineering and Applied Mechanics, Tongji University, Shanghai 200092 (China)

    2011-07-15

    This paper studies a cold standby repairable system with two different components and one repairman who can take multiple vacations. If there is a component which fails and the repairman is on vacation, the failed component will wait for repair until the repairman is available. In the system, assume that component 1 has priority in use. After repair, component 1 follows a geometric process repair, while component 2 can be repaired as good as new after failures. Under these assumptions, a replacement policy N based on the failed times of component 1 is studied. The system will be replaced if the failure times of component 1 reach N. The explicit expression of the expected cost rate is given, so that the optimal replacement time N{sup *} is determined. Finally, a numerical example is given to illustrate the theoretical results of the model.

  3. Modeling imperfectly repaired system data via grey differential equations with unequal-gapped times

    International Nuclear Information System (INIS)

    Guo Renkuan

    2007-01-01

    In this paper, we argue that grey differential equation models are useful in repairable system modeling. The arguments starts with the review on GM(1,1) model with equal- and unequal-spaced stopping time sequence. In terms of two-stage GM(1,1) filtering, system stopping time can be partitioned into system intrinsic function and repair effect. Furthermore, we propose an approach to use grey differential equation to specify a semi-statistical membership function for system intrinsic function times. Also, we engage an effort to use GM(1,N) model to model system stopping times and the associated operating covariates and propose an unequal-gapped GM(1,N) model for such analysis. Finally, we investigate the GM(1,1)-embed systematic grey equation system modeling of imperfectly repaired system operating data. Practical examples are given in step-by-step manner to illustrate the grey differential equation modeling of repairable system data

  4. In-Space Repair of Reinforced Carbon-Carbon Thermal Protection System Structures

    Science.gov (United States)

    Singh, Mrityunjay

    2006-01-01

    Advanced repair and refurbishment technologies are critically needed for the thermal protection system of current space transportation system as well as for future Crew Exploration Vehicles (CEV). The damage to these components could be caused by impact during ground handling or due to falling of ice or other objects during launch. In addition, in-orbit damage includes 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 adhesive delivery system. The adhesive paste cures at 100-120 C and transforms into a high temperature ceramic during simulated entry 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 system for tile and leading edge repair (InSTALER) have been developed. In this presentation, critical in-space repair needs and technical challenges as well as various issues and complexities will be discussed along with the plasma performance and post test characterization of repaired RCC materials.

  5. 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,

  6. A 3D Lattice Modelling Study of Drying Shrinkage Damage in Concrete Repair Systems

    NARCIS (Netherlands)

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

    2016-01-01

    Differential shrinkage between repair material and concrete substrate is considered to be the main cause of premature failure of repair systems. The magnitude of induced stresses depends on many factors, for example the degree of restraint, moisture gradients caused by curing and drying conditions,

  7. 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.

  8. DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

    Science.gov (United States)

    Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

    2018-06-08

    Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

  9. Single-Molecule Methods for Nucleotide Excision Repair: Building a System to Watch Repair in Real Time.

    Science.gov (United States)

    Kong, Muwen; Beckwitt, Emily C; Springall, Luke; Kad, Neil M; Van Houten, Bennett

    2017-01-01

    Single-molecule approaches to solving biophysical problems are powerful tools that allow static and dynamic real-time observations of specific molecular interactions of interest in the absence of ensemble-averaging effects. Here, we provide detailed protocols for building an experimental system that employs atomic force microscopy and a single-molecule DNA tightrope assay based on oblique angle illumination fluorescence microscopy. Together with approaches for engineering site-specific lesions into DNA substrates, these complementary biophysical techniques are well suited for investigating protein-DNA interactions that involve target-specific DNA-binding proteins, such as those engaged in a variety of DNA repair pathways. In this chapter, we demonstrate the utility of the platform by applying these techniques in the studies of proteins participating in nucleotide excision repair. © 2017 Elsevier Inc. All rights reserved.

  10. 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.

  11. Availability and mean life time prediction of multistage degraded system with partial repairs

    International Nuclear Information System (INIS)

    Pham, Hoang; Suprasad, A.; Misra, R.B.

    1997-01-01

    In some environments, components might not always fail fully, but can degrade, and there can be multiple stages of degradation. In such cases, the efficiency of the system may decrease. After a certain stage of degradation the efficiency of the system may decrease to an unacceptable limit and can be considered as a total failure. However, the system can fail randomly from any stage. and can be repaired. Further, the repair action cannot bring the system to the good stage, but can make it operational and the failure rate of the system will, therefore, remain the same as before the failure. In this study, we present a model for predicting the reliability, availability, mean life time, and mean time to first failure of multistage degraded systems with partial repairs. In the analysis, state dependent transition rates for the degradation process, as well as repair processes, are considered. A numerical example is provided to illustrate the results

  12. ICAM (Conceptual Design for Computer-Integrated Manufacturing. Volume 2. Part 6. Task B - Establishment of the Factory of the Future Conceptual Framework Conceptual Framework Document, (MMR)

    Science.gov (United States)

    1984-06-29

    to an area where the chips may be accumulated for recycle or destroyed. This subsystem also involves cleaning and recycling of fluids. o Tool...information and trivia . 5-28 MMR110512000 10 February 1984 Thus, managers interacting with an elementary data processinq system often become

  13. Reliability analysis of repairable safety systems of a reprocessing plant allowing for tolerable system downtimes

    International Nuclear Information System (INIS)

    Schaefer, H.

    1987-01-01

    GRS has been engaged in safety analysises of the German Reprocessing Plant for several years. The development and verification of appropriate reliability analysis methods, the generation of data as well as the search for an adequate structural presentation of the results to form a basis of recommendations for technical or administrative measures or contributions to risk oriented evaluations have been or are in the process of being established. In contrast to NPP-studies, the reliability assessment of safety systems of a reprocessing plant is applied to repairable and often relatively small systems allowing for tolerable system downtimes. A sketch of the diverse cooling systems of a vessel containing a selfheating solution is given. The interruption of the cooling function for about one day might be tolerable before boiling will be reached. This interval is suitable for transfer of the solution to a spare vessel or for repairing the failed components, thus restoring the cooling function

  14. Immunogenicity and safety of a novel MMR vaccine (live, freeze-dried) containing the Edmonston-Zagreb measles strain, the Hoshino mumps strain, and the RA 27/3 rubella strain: Results of a randomized, comparative, active controlled phase III clinical trial.

    Science.gov (United States)

    Sood, Ashwani; Mitra, Monjori; Joshi, Himanshu Arvind; Nayak, Uma Siddhartha; Siddaiah, Prashanth; Babu, T Ramesh; Mahapatro, Samarendra; Sanmukhani, Jayesh; Gupta, Gaurav; Mittal, Ravindra; Glueck, Reinhard

    2017-07-03

    This phase III clinical trial was conducted to evaluate the immunogenicity and safety of the single-dose and multi-dose formulations of a novel MMR vaccine (live, freeze-dried) developed by M/s Cadila Healthcare Limited, India (Cadila MMR vaccine), containing the Hoshino mumps strain, compared to that of an existing MMR vaccine (live, freeze-dried) developed by M/s Serum Institute of India Limited, India (Serum MMR vaccine). These two vaccines have similar measles and rubella strains, but different mumps strains (Hoshino in Cadila MMR vaccine, and L-Zagreb in Serum MMR vaccine). Three hundred and twenty-eight subjects of either sex, aged 15-18 months, were randomized in a 2:1 ratio to receive either the Cadila or Serum MMR vaccine. Immunogenicity assessments (IgG antibodies against measles, mumps, and rubella viruses) were done at baseline and 42 d after vaccination. Solicited (local and systemic) and unsolicited adverse events were recorded for up to 42 d following vaccination. The Cadila MMR vaccine was found to be non-inferior to the Serum MMR vaccine in terms of end-of-study proportion of subjects seropositive for anti-measles antibodies (100.0% in both groups), anti-mumps antibodies (94.5% vs. 94.0%), and anti-rubella antibodies (95.5% vs. 91.0%). Both vaccines were well tolerated by all study participants; the most common adverse event reported in both groups was fever, followed by rash. The results of this phase III clinical trial show that the novel Cadila MMR vaccine is non-inferior to the Serum MMR vaccine.

  15. Targeting DNA repair systems in antitubercular drug development.

    Science.gov (United States)

    Minias, Alina; Brzostek, Anna; Dziadek, Jaroslaw

    2018-01-28

    Infections with Mycobacterium tuberculosis, the causative agent of tuberculosis, are difficult to treat using currently available chemotherapeutics. Clinicians agree on the urgent need for novel drugs to treat tuberculosis. In this mini review, we summarize data that prompts the consideration of DNA repair-associated proteins as targets for the development of new antitubercular compounds. We discuss data, including gene expression data, that highlight the importance of DNA repair genes during the pathogenic cycle as well as after exposure to antimicrobials currently in use. Specifically, we report experiments on determining the essentiality of DNA repair-related genes. We report the availability of protein crystal structures and summarize discovered protein inhibitors. Further, we describe phenotypes of available gene mutants of M. tuberculosis and model organisms Mycobacterium bovis and Mycobacterium smegmatis. We summarize experiments regarding the role of DNA repair-related proteins in pathogenesis and virulence performed both in vitro and in vivo during the infection of macrophages and animals. We detail the role of DNA repair genes in acquiring mutations, which influence the rate of drug resistance acquisition. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. A massive parallel sequencing workflow for diagnostic genetic testing of mismatch repair genes

    Science.gov (United States)

    Hansen, Maren F; Neckmann, Ulrike; Lavik, Liss A S; Vold, Trine; Gilde, Bodil; Toft, Ragnhild K; Sjursen, Wenche

    2014-01-01

    The purpose of this study was to develop a massive parallel sequencing (MPS) workflow for diagnostic analysis of mismatch repair (MMR) genes using the GS Junior system (Roche). A pathogenic variant in one of four MMR genes, (MLH1, PMS2, MSH6, and MSH2), is the cause of Lynch Syndrome (LS), which mainly predispose to colorectal cancer. We used an amplicon-based sequencing method allowing specific and preferential amplification of the MMR genes including PMS2, of which several pseudogenes exist. The amplicons were pooled at different ratios to obtain coverage uniformity and maximize the throughput of a single-GS Junior run. In total, 60 previously identified and distinct variants (substitutions and indels), were sequenced by MPS and successfully detected. The heterozygote detection range was from 19% to 63% and dependent on sequence context and coverage. We were able to distinguish between false-positive and true-positive calls in homopolymeric regions by cross-sample comparison and evaluation of flow signal distributions. In addition, we filtered variants according to a predefined status, which facilitated variant annotation. Our study shows that implementation of MPS in routine diagnostics of LS can accelerate sample throughput and reduce costs without compromising sensitivity, compared to Sanger sequencing. PMID:24689082

  17. Planets around the evolved stars 24 Boötis and γ Libra: A 30 d-period planet and a double giant-planet system in possible 7:3 MMR

    Science.gov (United States)

    Takarada, Takuya; Sato, Bun'ei; Omiya, Masashi; Harakawa, Hiroki; Nagasawa, Makiko; Izumiura, Hideyuki; Kambe, Eiji; Takeda, Yoichi; Yoshida, Michitoshi; Itoh, Yoichi; Ando, Hiroyasu; Kokubo, Eiichiro; Ida, Shigeru

    2018-05-01

    We report the detection of planets around two evolved giant stars from radial velocity measurements at Okayama Astrophysical observatory. 24 Boo (G3 IV) has a mass of 0.99 M_{⊙}, a radius of 10.64 R_{⊙}, and a metallicity of [Fe/H] = -0.77. The star hosts one planet with a minimum mass of 0.91 MJup and an orbital period of 30.35 d. The planet has one of the shortest orbital periods among those ever found around evolved stars using radial-velocity methods. The stellar radial velocities show additional periodicity with 150 d, which can probably be attributed to stellar activity. The star is one of the lowest-metallicity stars orbited by planets currently known. γ Lib (K0 III) is also a metal-poor giant with a mass of 1.47 M_{⊙}, a radius of 11.1 R_{⊙}, and [Fe/H] = -0.30. The star hosts two planets with minimum masses of 1.02 MJup and 4.58 MJup, and periods of 415 d and 964 d, respectively. The star has the second-lowest metallicity among the giant stars hosting more than two planets. Dynamical stability analysis for the γ Lib system sets the minimum orbital inclination angle to be about 70° and suggests that the planets are in 7:3 mean-motion resonance, though the current best-fitting orbits for the radial-velocity data are not totally regular.

  18. Somatic mutations in mismatch repair genes in sporadic gastric carcinomas are not a cause but a consequence of the mutator phenotype

    NARCIS (Netherlands)

    Pinto, Mafalda; Wub, Ying; Mensink, Rob G. J.; Cirnes, Luis; Seruca, Raquel; Hofstra, Robert M. W.

    2008-01-01

    In hereditary nonpolyposis colorectal cancer (HNPCC), patients' mismatch repair (MMR) gene mutations cause MMR deficiency, leading to microsatellite instability (MSI-H). MSI-H is also found in a substantial fraction of sporadic gastric carcinomas (SGC), mainly due to MLH1 promoter hypermethylation,

  19. 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

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

    Science.gov (United States)

    Buchanan, Daniel D; Rosty, Christophe; Clendenning, Mark; Spurdle, Amanda B; Win, Aung Ko

    2014-01-01

    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 data from published studies are combined, 59% (95% confidence interval [CI]: 55% to 64%) of colorectal cancers and 52% (95% CI: 41% to 62%) of endometrial cancers with MMR deficiency were identified as suspected Lynch syndrome. Recent studies estimated that colorectal cancer risk for relatives of suspected Lynch syndrome cases is lower than for relatives of those with MMR gene mutations, but higher than for relatives of those with tumor MMR deficiency resulting from methylation of the MLH1 gene promoter. The cause of tumor MMR deficiency in suspected Lynch syndrome cases is likely due to either unidentified germline MMR gene mutations, somatic cell mosaicism, or biallelic somatic

  1. Reliability analysis of Markov history-dependent repairable systems with neglected failures

    International Nuclear Information System (INIS)

    Du, Shijia; Zeng, Zhiguo; Cui, Lirong; Kang, Rui

    2017-01-01

    Markov history-dependent repairable systems refer to the Markov repairable systems in which some states are changeable and dependent on recent evolutional history of the system. In practice, many Markov history-dependent repairable systems are subjected to neglected failures, i.e., some failures do not affect system performances if they can be repaired promptly. In this paper, we develop a model based on the theory of aggregated stochastic processes to describe the history-dependent behavior and the effect of neglected failures on the Markov history-dependent repairable systems. Based on the developed model, instantaneous and steady-state availabilities are derived to characterize the reliability of the system. Four reliability-related time distributions, i.e., distribution for the k th working period, distribution for the k th failure period, distribution for the real working time in an effective working period, distribution for the neglected failure time in an effective working period, are also derived to provide a more comprehensive description of the system's reliability. Thanks to the power of the theory of aggregated stochastic processes, closed-form expressions are obtained for all the reliability indexes and time distributions. Finally, the developed indexes and analysis methods are demonstrated by a numerical example. - Highlights: • Markovian history-dependent repairable systems with neglected failures is modeled. • Aggregated stochastic processes are used to derive reliability indexes and time distributions. • Closed-form expressions are derived for the considered indexes and distributions.

  2. A multifactorial likelihood model for MMR gene variant classification incorporating probabilities based on sequence bioinformatics and tumor characteristics: a report from the Colon Cancer Family Registry.

    Science.gov (United States)

    Thompson, Bryony A; Goldgar, David E; Paterson, Carol; Clendenning, Mark; Walters, Rhiannon; Arnold, Sven; Parsons, Michael T; Michael D, Walsh; Gallinger, Steven; Haile, Robert W; Hopper, John L; Jenkins, Mark A; Lemarchand, Loic; Lindor, Noralane M; Newcomb, Polly A; Thibodeau, Stephen N; Young, Joanne P; Buchanan, Daniel D; Tavtigian, Sean V; Spurdle, Amanda B

    2013-01-01

    Mismatch repair (MMR) gene sequence variants of uncertain clinical significance are often identified in suspected Lynch syndrome families, and this constitutes a challenge for both researchers and clinicians. Multifactorial likelihood model approaches provide a quantitative measure of MMR variant pathogenicity, but first require input of likelihood ratios (LRs) for different MMR variation-associated characteristics from appropriate, well-characterized reference datasets. Microsatellite instability (MSI) and somatic BRAF tumor data for unselected colorectal cancer probands of known pathogenic variant status were used to derive LRs for tumor characteristics using the Colon Cancer Family Registry (CFR) resource. These tumor LRs were combined with variant segregation within families, and estimates of prior probability of pathogenicity based on sequence conservation and position, to analyze 44 unclassified variants identified initially in Australasian Colon CFR families. In addition, in vitro splicing analyses were conducted on the subset of variants based on bioinformatic splicing predictions. The LR in favor of pathogenicity was estimated to be ~12-fold for a colorectal tumor with a BRAF mutation-negative MSI-H phenotype. For 31 of the 44 variants, the posterior probabilities of pathogenicity were such that altered clinical management would be indicated. Our findings provide a working multifactorial likelihood model for classification that carefully considers mode of ascertainment for gene testing. © 2012 Wiley Periodicals, Inc.

  3. On-Orbit Health Monitoring and Repair Assessment of Thermal Protection Systems, Phase II

    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...

  4. Self-Repairing Flight Control System for Online Health Monitoring and Recovery, Phase I

    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...

  5. 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†,

  6. Systemic EP4 Inhibition Increases Adhesion Formation in a Murine Model of Flexor Tendon Repair.

    Directory of Open Access Journals (Sweden)

    Michael B Geary

    Full Text Available Flexor tendon injuries are a common clinical problem, and repairs are frequently complicated by post-operative adhesions forming between the tendon and surrounding soft tissue. Prostaglandin E2 and the EP4 receptor have been implicated in this process following tendon injury; thus, we hypothesized that inhibiting EP4 after tendon injury would attenuate adhesion formation. A model of flexor tendon laceration and repair was utilized in C57BL/6J female mice to evaluate the effects of EP4 inhibition on adhesion formation and matrix deposition during flexor tendon repair. Systemic EP4 antagonist or vehicle control was given by intraperitoneal injection during the late proliferative phase of healing, and outcomes were analyzed for range of motion, biomechanics, histology, and genetic changes. Repairs treated with an EP4 antagonist demonstrated significant decreases in range of motion with increased resistance to gliding within the first three weeks after injury, suggesting greater adhesion formation. Histologic analysis of the repair site revealed a more robust granulation zone in the EP4 antagonist treated repairs, with early polarization for type III collagen by picrosirius red staining, findings consistent with functional outcomes. RT-PCR analysis demonstrated accelerated peaks in F4/80 and type III collagen (Col3a1 expression in the antagonist group, along with decreases in type I collagen (Col1a1. Mmp9 expression was significantly increased after discontinuing the antagonist, consistent with its role in mediating adhesion formation. Mmp2, which contributes to repair site remodeling, increases steadily between 10 and 28 days post-repair in the EP4 antagonist group, consistent with the increased matrix and granulation zones requiring remodeling in these repairs. These findings suggest that systemic EP4 antagonism leads to increased adhesion formation and matrix deposition during flexor tendon healing. Counter to our hypothesis that EP4 antagonism

  7. A 3D Lattice Modelling Study of Drying Shrinkage Damage in Concrete Repair Systems

    Directory of Open Access Journals (Sweden)

    Mladena Luković

    2016-07-01

    Full Text Available Differential shrinkage between repair material and concrete substrate is considered to be the main cause of premature failure of repair systems. The magnitude of induced stresses depends on many factors, for example the degree of restraint, moisture gradients caused by curing and drying conditions, type of repair material, etc. Numerical simulations combined with experimental observations can be of great use when determining the influence of these parameters on the performance of repair systems. In this work, a lattice type model was used to simulate first the moisture transport inside a repair system and then the resulting damage as a function of time. 3D simulations were performed, and damage patterns were qualitatively verified with experimental results and cracking tendencies in different brittle and ductile materials. The influence of substrate surface preparation, bond strength between the two materials, and thickness of the repair material were investigated. Benefits of using a specially tailored fibre reinforced material, namely strain hardening cementitious composite (SHCC, for controlling the damage development due to drying shrinkage in concrete repairs was also examined.

  8. Shear Bond Strength of a Novel Porcelain Repair System for ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... Each fracture type was examined under a stereomicroscope .... fracture types. Statistical analysis. The normal distribution of data was examined using the Kolmogorov–Smirnov test. Shear bond strength data of repaired CAD/CAM .... adhesives to enamel, dentine, and porcelain surfaces can be compared.

  9. 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

  10. Failure Modes in Concrete Repair Systems due to Ongoing Corrosion

    NARCIS (Netherlands)

    Lukovic, M.; Šavija, B.; Ye, G.; Schlangen, H.E.J.G.; van Breugel, K.

    2017-01-01

    Corrosion of steel reinforcement is the main cause of deterioration in reinforced concrete structures. It can result in cracking and spalling of the concrete cover. After the damaged cover is repaired, reinforcement corrosion might continue and even accelerate. While the development of the corrosion

  11. Mismatch repair and treatment resistance in ovarian cancer

    International Nuclear Information System (INIS)

    Helleman, Jozien; Staveren, Iris L van; Dinjens, Winand NM; Kuijk, Patricia F van; Ritstier, Kirsten; Ewing, Patricia C; Burg, Maria EL van der; Stoter, Gerrit; Berns, Els MJJ

    2006-01-01

    The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation

  12. Mismatch repair and treatment resistance in ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Helleman, Jozien; Staveren, Iris L van [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Dinjens, Winand NM [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Kuijk, Patricia F van; Ritstier, Kirsten [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Ewing, Patricia C [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Burg, Maria EL van der; Stoter, Gerrit [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Berns, Els MJJ [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Erasmus MC, Department of Medical Oncology, Josephine Nefkens Institute, Room Be424, P.O. Box 1738, 3000 DR (Netherlands)

    2006-07-31

    The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

  13. Mismatch repair and treatment resistance in ovarian cancer

    Directory of Open Access Journals (Sweden)

    van der Burg Maria EL

    2006-07-01

    Full Text Available Abstract Background The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. Methods We determined, microsatellite instability (MSI as a marker for MMR inactivation (analysis of BAT25 and BAT26, MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR in 75 ovarian carcinomas and eight ovarian cancer cell lines Results MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation, SKOV3 (no MLH1 mRNA expression and 2774 (no altered expression of MMR genes. Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response. The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. Conclusion No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

  14. Evaluating Mismatch Repair Deficiency in Pancreatic Adenocarcinoma: Challenges and Recommendations.

    Science.gov (United States)

    Hu, Zishuo I; Shia, Jinru; Stadler, Zsofia K; Varghese, Anna M; Capanu, Marinela; Salo-Mullen, Erin; Lowery, Maeve A; Diaz, Luis A; Mandelker, Diana; Yu, Kenneth H; Zervoudakis, Alice; Kelsen, David P; Iacobuzio-Donahue, Christine A; Klimstra, David S; Saltz, Leonard B; Sahin, Ibrahim H; O'Reilly, Eileen M

    2018-03-15

    Purpose: Immune checkpoint inhibition has been shown to generate profound and durable responses in mismatch repair deficient (MMR-D) solid tumors and has elicited interest in detection tools and strategies to guide therapeutic decision-making. Herein we address questions on the appropriate screening, detection methods, patient selection, and initiation of therapy for MMR-D pancreatic ductal adenocarcinoma (PDAC) and assess the utility of next-generation sequencing (NGS) in providing additional prognostic and predictive information for MMR-D PDAC. Experimental Design: Archival and prospectively acquired samples and matched normal DNA from N = 833 PDAC cases were analyzed using a hybridization capture-based, NGS assay designed to perform targeted deep sequencing of all exons and selected introns of 341 to 468 cancer-associated genes. A computational program using NGS data derived the MSI status from the tumor-normal paired genome sequencing data. Available germline testing, IHC, and microsatellite instability (MSI) PCR results were reviewed to assess and confirm MMR-D and MSI status. Results: MMR-D in PDAC is a rare event among PDAC patients (7/833), occurring at a frequency of 0.8%. Loss of MMR protein expression by IHC, high mutational load, and elevated MSIsensor scores were correlated with MMR-D PDAC. All 7 MMR-D PDAC patients in the study were found to have Lynch syndrome. Four (57%) of the MMR-D patients treated with immune checkpoint blockade had treatment benefit (1 complete response, 2 partial responses, 1 stable disease). Conclusions: An integrated approach of germline testing and somatic analyses of tumor tissues in advanced PDAC using NGS may help guide future development of immune and molecularly directed therapies in PDAC patients. Clin Cancer Res; 24(6); 1326-36. ©2018 AACR . ©2018 American Association for Cancer Research.

  15. 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.

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

    International Nuclear Information System (INIS)

    Markiewicz, Pawel; Thielemans, Kris; Burgos, Ninon; Manber, Richard; Jiao, Jieqing; Barnes, Anna; Atkinson, David; Arridge, Simon R; Hutton, Brian F; Ourselin, Sébastien

    2014-01-01

    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.

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

    International Nuclear Information System (INIS)

    Gamiz, M.L.; Roman, Y.

    2008-01-01

    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

  18. 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.

  19. 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.

  20. 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.

  1. Control and repair system for radioactive nuclear fuel elements

    International Nuclear Information System (INIS)

    Shallenberger, J.M.; Hornak, L.P.; Desmarchais, W.E.

    1975-01-01

    Irradiated fuel, especially such containing Pu-239, are put in a shielding container for inspection or repair. This container consists of an inner and outer tube of, for example, stainless steel, between which there is a gap filled with water, mineral oil, or polyethylene. At the upper end of the shielding container a rotating sleeve is positioned, by means of a bearing. It contains, for instance, an access opening and an inspection opening which are shielded by means of plexiglass. The access hole is opened only for repair work. In oder to prevent radiation from escaping to the environment during withdrawal and inspection of the fuel elements a second shielding container or shielding tube may be put over the sleeve. (DG/PB) [de

  2. Spectrum of mismatch repair gene mutations and clinical presentation of Hispanic individuals with Lynch syndrome.

    Science.gov (United States)

    Sunga, Annette Y; Ricker, Charité; Espenschied, Carin R; Castillo, Danielle; Melas, Marilena; Herzog, Josef; Bannon, Sarah; Cruz-Correa, Marcia; Lynch, Patrick; Solomon, Ilana; Gruber, Stephen B; Weitzel, Jeffrey N

    2017-04-01

    Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is caused by mismatch repair (MMR) gene mutations. However, data about MMR mutations in Hispanics are limited. This study aims to describe the spectrum of MMR mutations in Hispanics with LS and explore ancestral origins. This case series involved an IRB-approved retrospective chart review of self-identified Hispanic patients (n = 397) seen for genetic cancer risk assessment at four collaborating academic institutions in California, Texas, and Puerto Rico who were evaluated by MMR genotyping and/or tumor analysis. A literature review was conducted for all mutations identified. Of those who underwent clinical genetic testing (n = 176), 71 had MMR gene mutations. Nine mutations were observed more than once. One third (3/9) of recurrent mutations and two additional mutations (seen only once) were previously reported in Spain, confirming the influence of Spanish ancestry on MMR mutations in Hispanic populations. The recurrent mutations identified (n = 9) included both previously reported mutations as well as unique mutations not in the literature. This is the largest report of Hispanic MMR mutations in North America; however, a larger sample and haplotype analyses are needed to better understand recurrent MMR mutations in Hispanic populations. Copyright © 2017. Published by Elsevier Inc.

  3. 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 viral diseases that can ... Before vaccines, these diseases were very common in ...

  4. 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.

  5. The role of message framing in promoting MMR vaccination: evidence of a loss-frame advantage.

    Science.gov (United States)

    Abhyankar, Purva; O'Connor, Daryl B; Lawton, Rebecca

    2008-01-01

    This study examined the effects of message framing on intentions to obtain the measles, mumps and rubella (MMR) vaccine for one's child and investigated whether Theory of Planned Behaviour (TPB) and perceived outcome efficacy variables mediate and/or moderate message framing effects. One hundred and forty women read either a loss-framed or gain-framed message and then completed measures assessing their intentions to obtain the MMR vaccine for their child, and TPB and outcome efficacy variables. Exposure to the loss frame increased intentions to obtain the MMR vaccine and influenced perceptions of outcome efficacy. This suggests that outcome efficacy, but not other TPB variables may mediate framing effects within the context of MMR vaccination. Message frame, in addition to TPB variables, significantly predicted unique variance in behavioural intentions. These findings are discussed within the context of Prospect Theory, perceived risk and prevention/detection behaviours.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-03-15

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  8. 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.

  9. [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.

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

    International Nuclear Information System (INIS)

    David A. Boothman

    1999-01-01

    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

  11. Inactivation of DNA mismatch repair by variants of uncertain significance in the PMS2 gene.

    Science.gov (United States)

    Drost, Mark; Koppejan, Hester; de Wind, Niels

    2013-11-01

    Lynch syndrome (LS) is a common cancer predisposition caused by an inactivating mutation in one of four DNA mismatch repair (MMR) genes. Frequently a variant of uncertain significance (VUS), rather than an obviously pathogenic mutation, is identified in one of these genes. The inability to define pathogenicity of such variants precludes targeted healthcare. Here, we have modified a cell-free assay to test VUS in the MMR gene PMS2 for functional activity. We have analyzed nearly all VUS in PMS2 found thus far and describe loss of MMR activity for five, suggesting the applicability of the assay for diagnosis of LS. © 2013 WILEY PERIODICALS, INC.

  12. Selecting patients with young-onset colorectal cancer for mismatch repair gene analysis

    DEFF Research Database (Denmark)

    Walker, M; O'Sullivan, B; Perakath, B

    2007-01-01

    BACKGROUND: Young patients with colorectal cancer are at increased risk of carrying a germline mutation in mismatch repair (MMR) genes. This study investigated the role of clinical criteria and immunohistochemistry for MMR proteins in selecting young patients for mutation testing. METHODS: A cohort...... of 56 consecutive patients with colorectal cancer aged less than 45 years were stratified into three groups based on clinical criteria: 'Amsterdam criteria', 'high risk' and 'young onset only'. Immunohistochemistry for four MMR proteins was carried out and the rate of compliance with clinical guidelines...

  13. Reliability analysis of a repairable k-out-of-n system with some components being suspended when the system is down

    International Nuclear Information System (INIS)

    Li Xiaohu; Zuo, Ming J.; Yam, Richard C.M.

    2006-01-01

    A k-out-of-n system with independent exponential components is investigated. It is assumed that some working components are suspended as soon as the system is down, repair starts immediately when a component fails and repair times are independent and exponentially distributed. Formulas for various reliability indices of the system including mean time between failures, mean working time in a failure-repair cycle, and mean down time in a failure-repair cycle are derived

  14. Control of a maintenance system when failure and repair times have phase type distributions

    Science.gov (United States)

    Decassiamenesesrodrigues, Rita

    1990-09-01

    In the model of machine repair discussed there are M + R identical machines, M operating, and R spares. All machines are independent of one another. When an operating machine fails, it is sent to a single server repair station and immediately replaced by a spare machine, if one is available. The server has two available service types to choose from. There are waiting costs, repair costs, lost production costs, and switch-over costs. The following decision problem is treated: to obtain a stationary policy which determines the service type as a function of the state of the system in order to minimize the long-run average cost when failure and repair times have second-order Coxian distribution. This control problem is represented by a semi-Markov decision process. The policy-iteration algorithm and the value-iteration algorithm are used to obtain the optimal policy. Numerical results are given for these two optimization methods.

  15. Reliability analysis of repairable multi-state system with common bus performance sharing

    International Nuclear Information System (INIS)

    Yu, Huan; Yang, Jun; Mo, Huadong

    2014-01-01

    In this paper, an instantaneous availability model for repairable multi-state system (MSS) with common bus performance sharing is proposed. The repairable MSS consists of some multi-state units and a common bus performance redistribution system. Each unit in the system has several performance levels and must satisfy its individual random demand. A unit can transmit the surplus performance to other units in real time through the common bus performance redistribution system, if it has a performance that exceeds its demand. The entire system fails if the demand of any unit is not satisfied. A new method based on the combination of the stochastic process method and the universal generating function technique is suggested to evaluate the instantaneous availability and the mean instantaneous performance deficiency of the proposed repairable MSS. Two examples are given for applications in the end

  16. Optimal preventive maintenance and repair policies for multi-state systems

    International Nuclear Information System (INIS)

    Sheu, Shey-Huei; Chang, Chin-Chih; Chen, Yen-Luan; George Zhang, Zhe

    2015-01-01

    This paper studies the optimal preventive maintenance (PM) policies for multi-state systems. The scheduled PMs can be either imperfect or perfect type. The improved effective age is utilized to model the effect of an imperfect PM. The system is considered as in a failure state (unacceptable state) once its performance level falls below a given customer demand level. If the system fails before a scheduled PM, it is repaired and becomes operational again. We consider three types of major, minimal, and imperfect repair actions, respectively. The deterioration of the system is assumed to follow a non-homogeneous continuous time Markov process (NHCTMP) with finite state space. A recursive approach is proposed to efficiently compute the time-dependent distribution of the multi-state system. For each repair type, we find the optimal PM schedule that minimizes the average cost rate. The main implication of our results is that in determining the optimal scheduled PM, choosing the right repair type will significantly improve the efficiency of the system maintenance. Thus PM and repair decisions must be made jointly to achieve the best performance

  17. Repair system and mitomycin mutagenesis in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Otsuji, N; Murayama, I [Kyushu Univ., Fukuoka (Japan). Faculty of Pharmaceutical Sciences

    1974-03-01

    Ultraviolet light sensitive mutants of E. coli defective at the uvrA, uvrB or uvrC locus showed increased sensitivity to the lethal effects of monofunctional mitomycin, 7-methoxymitosene (7-MMT) or decarbamoyl mitomycin C (DCMTC), as well as mitomycin C (MTC). (1) Treatment of wild type bacteria with these monofunctional mitomycins resulted in the production of single-strand breaks in DNA, which were repaired upon incubation in a growth medium. Such breaks in DNA were not produced in the UvrA and the UvrB mutants. In the UvrC mutant, single-strand breaks were produced by 7-MMT or by DCMTC, but these breaks were not repaired upon incubation. (2) Exposure of E. coli to MTC caused cross-linkage between DNA strands, which converted to a normally denaturable form during further incubation after treatment. This was not occurred in the UvrB strain. In the UvrC mutant, a portion of the cross-links was removed upon incubation. (3) 7-MMT and DCMTC induced mutation in UV sensitive UvrB and UvrC mutants with much higher frequency than in wild type bacteria, while MTC did not induce mutation in these Uvr-strains.

  18. Repair system and mitomycin mutagenesis in Escherichia coli

    International Nuclear Information System (INIS)

    Otsuji, Nozomu; Murayama, Ichiko

    1974-01-01

    Ultraviolet light sensitive mutants of E. coli defective at the uvrA, uvrB or uvrC locus showed increased sensitivity to the lethal effects of monofunctional mitomycin, 7-methoxymitosene (7-MMT) or decarbamoyl mitomycin C (DCMTC), as well as mitomycin C (MTC). (1) Treatment of wild type bacteria with these monofunctional mitomycins resulted in the production of single-strand breaks in DNA, which were repaired upon incubation in a growth medium. Such breaks in DNA were not produced in the UvrA and the UvrB mutants. In the UvrC mutant, single-strand breaks were produced by 7-MMT or by DCMTC, but these breaks were not repaired upon incubation. (2) Exposure of E. coli to MTC caused cross-linkage between DNA strands, which converted to a normally denaturable form during further incubation after treatment. This was not occurred in the UvrB strain. In the UvrC mutant, a portion of the cross-links was removed upon incubation. (3) 7-MMT and DCMTC induced mutation in UV sensitive UvrB and UvrC mutants with much higher frequency than in wild type bacteria, while MTC did not induce mutation in these Uvr-strains. (author)

  19. Flexible Software Solution for Information System of Maintenance and Repair in Armenian NPP Medzamor

    International Nuclear Information System (INIS)

    Stoilova Yordanova, V.; Manchev, B.

    2016-01-01

    Achieving high performance in maintenance and repair activities in nuclear facilities and good results in this area is not possible without proper planning. This includes long-term, medium-term and annual planning. A computerized information maintenance management system is a tool widely used by nuclear operators to achieve safe, reliable, stable and predictable plant operation. Development and implementation of such a system in the Armenian NPP Medzamor (ANPP) was initiated by the European Commission (EC) in August 2013 based on the decision of ANPP management to improve practice in terms of planning and carrying out maintenance and repair of plant structures, systems and components (SSCs). The main purpose for the development and deployment of information maintenance management system in ANPP is creation of a systematic approach to the distribution of tasks between the maintenance personnel as well as the timing and methods of their implementation - on which systems, structures and components, maintenance frequency, while the ultimate goal is to optimize the use of resources for maintenance and to ensure plant safe operation and reliability. In November 2013 a contract between European Commission and consortium Risk Engineering -David Holding was signed, including the following supplies: Hardware for the information system of ANPP (called us Archimed MRO); Specification, design and development of the software of Archimed MRO, installation of the system, data migration, training of ANPP staff operating the system, and 9 months trial operation. In the process of specifying the functionality of the system the main purpose was to provide modern information tools to help improve the work of ANPP personnel in the following areas: Optimization of ANPP maintenance program; Planning of maintenance, repair and overhaul (MRO) activities; Effective management of the processes of MRO; Analysis of the MRO results (trend analysis, recurrence of repairs, quality of the repairs

  20. Immunotherapy holds the key to cancer treatment and prevention in constitutional mismatch repair deficiency (CMMRD) syndrome

    NARCIS (Netherlands)

    Westdorp, Harm; Kolders, Sigrid; Hoogerbrugge, Nicoline; de Vries, I Jolanda M; Jongmans, Marjolijn C.J.; Schreibelt, Gerty

    2017-01-01

    Monoallelic germline mutations in one of the DNA mismatch repair (MMR) genes cause Lynch syndrome, with a high lifetime risks of colorectal and endometrial cancer at adult age. Less well known, is the constitutional mismatch repair deficiency (CMMRD) syndrome caused by biallelic germline mutations

  1. Human DNA polymerase delta double-mutant D316A;E318A interferes with DNA mismatch repair in vitro

    DEFF Research Database (Denmark)

    Liu, Dekang; Frederiksen, Jane H.; Liberti, Sascha Emilie

    2017-01-01

    DNA mismatch repair (MMR) is a highly-conserved DNA repair mechanism, whose primary role is to remove DNA replication errors preventing them from manifesting as mutations, thereby increasing the overall genome stability. Defects in MMR are associated with increased cancer risk in humans and other...... organisms. Here, we characterize the interaction between MMR and a proofreading-deficient allele of the human replicative DNA polymerase delta, PolδD316A;E318A, which has a higher capacity for strand displacement DNA synthesis than wild type Polδ. Human cell lines overexpressing PolδD316A;E318A display...

  2. Self-repair in a Bidirectionally Coupled Astrocyte-Neuron (AN System based on Retrograde Signaling

    Directory of Open Access Journals (Sweden)

    John eWade

    2012-09-01

    Full Text Available In this paper we demonstrate that retrograde signaling via astrocytes may underpin self-repair in the brain. Faults manifest themselves in silent or near silent neurons caused by low transmission probability synapses; the enhancement of the transmission probability of a healthy neighbouring synapse by retrograde signaling can enhance the transmission probability of the faulty synapse (repair. Our model of self-repair is based on recent research showing that retrograde signaling via astrocytes can increase the probability of neurotransmitter release at damaged or low transmission probability synapses. The model demonstrates that astrocytes are capable of bidirectional communication with neurons which leads to modulation of synaptic activity, and that indirect signaling through retrograde messengers such as endocannabinoids leads to modulation of synaptic transmission probability. Although our model operates at the level of cells, it provides a new research direction on brain-like self-repair which can be extended to networks of astrocytes and neurons. It also provides a biologically inspired basis for developing highly adaptive, distributed computing systems that can, at fine levels of granularity, fault detect, diagnose and self-repair autonomously, without the traditional constraint of a central fault detect/repair unit.

  3. Performance evaluation of multi-state degraded systems with minimal repairs and imperfect preventive maintenance

    International Nuclear Information System (INIS)

    Soro, Isaac W.; Nourelfath, Mustapha; Ait-Kadi, Daoud

    2010-01-01

    In this paper, we develop a model for evaluating the availability, the production rate and the reliability function of multi-state degraded systems subjected to minimal repairs and imperfect preventive maintenance. The status of the system is considered to degrade with use. These degradations may lead to decrease in the system efficiency. It is assumed that the system can consecutively degrade into several discrete states, which are characterized by different performance rates, ranging from perfect functioning to complete failure. The latter is observed when the degradation level reaches a certain critical threshold such as the system efficiency may decrease to an unacceptable limit. In addition, the system can fail randomly from any operational or acceptable state and can be repaired. This repair action brings the system to its previous operational state without affecting its failure rate (i.e., minimal repair). The used preventive maintenance policy suggests that if the system reaches the last acceptable degraded state, it is brought back to one of the states with higher efficiency. Considering customer demand as constant, the system is modeled as a continuous-time Markov process to assess its instantaneous and stationary performance measures. A numerical example is given to illustrate the proposed model.

  4. Effects of caffeine or maternal repair systems in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Osgood, C.; Zimmering, S.

    1979-01-01

    Drosophila melanogaster females were treated with 1% caffeine, mated with X-rayed males and the frequencies of induced sex-chromosome loss, translocations between the major autosomes and between the Y-chromosome and the major autosomes determined. In a reversal of the results obtained previously with 0.2% caffeine by Mendelson and Sobels, treatment of females with 1% caffeine led to a decrease in sex-chromosome loss, confirming preliminary data of Zimmering and Osgood and in increase in autosome-autosome translocations. It is suggested that the higher concentration of caffeine inhibits replication permitting more time available for chromosome-type restitutions by means of caffeine-insensitive repair mechanisms. In contrast with results for autosome-autosome translocation, the fequency of Y-autosome translocations was depressed below controls suggesting an isolation (by any one of several means) of Y-chromosome breaks from those in the autosomes. (Auth.)

  5. Bayesian analysis of repairable systems showing a bounded failure intensity

    International Nuclear Information System (INIS)

    Guida, Maurizio; Pulcini, Gianpaolo

    2006-01-01

    The failure pattern of repairable mechanical equipment subject to deterioration phenomena sometimes shows a finite bound for the increasing failure intensity. A non-homogeneous Poisson process with bounded increasing failure intensity is then illustrated and its characteristics are discussed. A Bayesian procedure, based on prior information on model-free quantities, is developed in order to allow technical information on the failure process to be incorporated into the inferential procedure and to improve the inference accuracy. Posterior estimation of the model-free quantities and of other quantities of interest (such as the optimal replacement interval) is provided, as well as prediction on the waiting time to the next failure and on the number of failures in a future time interval is given. Finally, numerical examples are given to illustrate the proposed inferential procedure

  6. The role of the bacterial mismatch repair system in SOS-induced mutagenesis: a theoretical background

    International Nuclear Information System (INIS)

    Belov, O.V.; Kapralov, M.I.; Chuluunbaatar, O.; Sweilam, N.H.

    2012-01-01

    A theoretical study is performed of the possible role of the methyl-directed mismatch repair system in the ultraviolet-induced mutagenesis of Escherichia coli bacterial cells. For this purpose, a mathematical model of the bacterial mismatch repair system is developed. Within this model, the key pathways of this type of repair are simulated on the basis of modern experimental data related to its mechanisms. Here we have modelled in detail five main pathways of DNA misincorporation removal with different DNA exonucleases. Using our calculations, we have tested the hypothesis that the bacterial mismatch repair system is responsible for the removal of the nucleotides misincorporated by DNA polymerase V (the UmuD' 2 C complex) during ultraviolet-induced SOS response. For the theoretical analysis of the mutation frequency, we have combined the proposed mathematical approach with the model of SOS-induced mutagenesis in the E.coli bacterial cell developed earlier. Our calculations support the hypothesis that methyl-directed mismatch repair influences the mutagenic effect of ultraviolet radiation

  7. Robotics in the nuclear environment-inspection and repairs inside the primary coolant system

    International Nuclear Information System (INIS)

    Guillet, J.; Marcel Tortolano

    2005-01-01

    The increase in the lifetime of the power plants and the ageing of materials require the intervention inside the components to carry out controls and possibly repairs in the event of discovered defects. Within this framework, EDF is investigating the feasibility of robotized repairs of the components and pipes of the main primary coolant system of a nuclear power plant. For several years, EDF R and D has engaged projects whose subject of study is the possibility of repairing components such as the main vessel; the pressurizer or the primary coolant pipes with the help of robots and dedicated tools. INTERVENTIONS INSIDE PRIMARY COOLANT PIPES: Studies undertaken by EDF highlighted that certain zones, particularly in pipe connections, can be affected by thermal fatigue which causes crackling defects or crackings. In anticipation of this phenomenon which would affect primary pipes and to avoid their replacements, EDF R and D has been studying the feasibility of examining and repairing these zones using robots. Robotized repair consists in introducing into the pipe while passing by the vessel, a 6 degrees of freedom manipulator mounted on a mobile carrier. This robot implements and carries out the trajectories of the different processes of repair: - Precise localization of the defects, - Elimination (possibly sampling) of the defects by machining, - Control that the defects were eliminated, - Weld metal buildup if the repair cavity is too deep, - Grinding followed by a new control of the surface. These studies and tests were conducted in the laboratory of EDF R and D in Chatou. The sequence of operations included machining by grinding and milling, profilometric control, dye penetrant testing, TIG welding and ultrasonic examinations. The results of the tests, executed on full scale models of components, are satisfactory and show the advantages of robotics compared with classical methods. ROBOTIZED INTERVENTIONS IN THE REACTOR VESSEL: Another difficult issue is the

  8. 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....... They include multiple hyperpigmented and hypopigmented skin areas, brain malformations, pilomatricomas, a second childhood malignancy, a Lynch syndrome (LS)-associated tumour in a relative and parental consanguinity. According to the scoring system, CMMRD should be suspected in any cancer patient who reaches...... patient. Tumours highly specific for CMMRD syndrome are assigned three points, malignancies overrepresented in CMMRD two points and all other malignancies one point. According to their specificity for CMMRD and their frequency in the general population, additional features are weighted with 1-2 points...

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

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

    International Nuclear Information System (INIS)

    Villen-Altamirano, Jose

    2010-01-01

    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 -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.

  11. 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.

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

    Science.gov (United States)

    Lukovic, Mladena; Ye, Guang

    2015-12-22

    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.

  13. Evaluation of temporary non-code repairs in safety class 3 piping systems

    International Nuclear Information System (INIS)

    Godha, P.C.; Kupinski, M.; Azevedo, N.F.

    1996-01-01

    Temporary non-ASME Code repairs in safety class 3 pipe and piping components are permissible during plant operation in accordance with Nuclear Regulatory Commission Generic Letter 90-05. However, regulatory acceptance of such repairs requires the licensee to undertake several timely actions. Consistent with the requirements of GL 90-05, this paper presents an overview of the detailed evaluation and relief request process. The technical criteria encompasses both ductile and brittle piping materials. It also lists appropriate evaluation methods that a utility engineer can select to perform a structural integrity assessment for design basis loading conditions to support the use of temporary non-Code repair for degraded piping components. Most use of temporary non-code repairs at a nuclear generating station is in the service water system which is an essential safety related system providing the ultimate heat sink for various plant systems. Depending on the plant siting, the service water system may use fresh water or salt water as the cooling medium. Various degradation mechanisms including general corrosion, erosion/corrosion, pitting, microbiological corrosion, galvanic corrosion, under-deposit corrosion or a combination thereof continually challenge the pressure boundary structural integrity. A good source for description of corrosion degradation in cooling water systems is provided in a cited reference

  14. [Studies on the repair of damaged DNA in bacteriophage, bacterial and mammalian systems]: Final report

    International Nuclear Information System (INIS)

    Friedberg, E.C.

    1987-08-01

    This study sought to exploit the use of uv radiation as a source of genomic damage. We explored the molecular mechanism of the repair of DNA damage at a number of different levels of biological organization, by investigating bacteriophage, bacterial, yeast and mammalian cells. Not only have observations obtained in one biological system suggested specific experimental approaches in others, but we have also learned that some biochemical pathways for DNA repair are unique to specific organisms. Our studies are summarized in terms of 4 major areas of research activity that span the past 16 years. 86 refs

  15. 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...

  16. A new technique for repair of a dislocated sternoclavicular joint using a sternal tension cable system.

    Science.gov (United States)

    Janson, Jacques T; Rossouw, Gawie J

    2013-02-01

    An unstable anterior or posterior sternoclavicular joint dislocation can cause severe morbidity with poor shoulder movement and strength. These dislocations need to be repaired, which can be challenging. Many different procedures have been described to obtain a stable joint fixation with varying results. We report a new technique for repairing a sternoclavicular joint dislocation by using a figure-of-eight sternal cable system. This procedure is relatively simple and reproducible to create a stable and functional sternoclavicular joint. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Telomeres and genomic damage repair. Their implication in human pathology

    International Nuclear Information System (INIS)

    Perez, Maria del R.; Dubner, Diana; Michelin, Severino; Gisone, Pablo; Carosella, Edgardo D.

    2002-01-01

    Telomeres, functional complexed that protect eukaryotic chromosome ends, participate in the regulation of cell proliferation and could play a role in the stabilization of genomic regions in response to genotoxic stress. Their significance in human pathology becomes evident in several diseases sharing genomic instability as a common trait, in which alterations of the telomere metabolism have been demonstrated. Many of them are also associated with hypersensitivity to ionizing radiation and cancer susceptibility. Besides the specific proteins belonging to the telomeric complex, other proteins involved in the DNA repair machinery, such as ATM, BRCA1, BRCA2, PARP/tankyrase system, DNA-PK and RAD50-MRE11-NBS1 complexes, are closely related with the telomere. This suggests that the telomere sequesters DNA repair proteins for its own structure maintenance, with could also be released toward damaged sites in the genomic DNA. This communication describes essential aspects of telomere structure and function and their links with homologous recombination, non-homologous end-joining (NHEJ), V(D)J system and mismatch-repair (MMR). Several pathological conditions exhibiting alterations in some of these mechanisms are also considered. The cell response to ionizing radiation and its relationship with the telomeric metabolism is particularly taken into account as a model for studying genotoxicity. (author)

  18. 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

  19. Rhodium metalloinsertor binding generates a lesion with selective cytotoxicity for mismatch repair-deficient cells.

    Science.gov (United States)

    Bailis, Julie M; Weidmann, Alyson G; Mariano, Natalie F; Barton, Jacqueline K

    2017-07-03

    The DNA mismatch repair (MMR) pathway recognizes and repairs errors in base pairing and acts to maintain genome stability. Cancers that have lost MMR function are common and comprise an important clinical subtype that is resistant to many standard of care chemotherapeutics such as cisplatin. We have identified a family of rhodium metalloinsertors that bind DNA mismatches with high specificity and are preferentially cytotoxic to MMR-deficient cells. Here, we characterize the cellular mechanism of action of the most potent and selective complex in this family, [Rh(chrysi)(phen)(PPO)] 2+ (Rh-PPO). We find that Rh-PPO binding induces a lesion that triggers the DNA damage response (DDR). DDR activation results in cell-cycle blockade and inhibition of DNA replication and transcription. Significantly, the lesion induced by Rh-PPO is not repaired in MMR-deficient cells, resulting in selective cytotoxicity. The Rh-PPO mechanism is reminiscent of DNA repair enzymes that displace mismatched bases, and is differentiated from other DNA-targeted chemotherapeutics such as cisplatin by its potency, cellular mechanism, and selectivity for MMR-deficient cells.

  20. Six types Monte Carlo for estimating the current unavailability of Markov system with dependent repair

    International Nuclear Information System (INIS)

    Xiao Gang; Li Zhizhong

    2004-01-01

    Based on integral equaiton describing the life-history of Markov system, six types of estimators of the current unavailability of Markov system with dependent repair are propounded. Combining with the biased sampling of state transition time of system, six types of Monte Carlo for estimating the current unavailability are given. Two numerical examples are given to deal with the variances and efficiencies of the six types of Monte Carlo methods. (authors)

  1. An artificial neural network for modeling reliability, availability and maintainability of a repairable system

    International Nuclear Information System (INIS)

    Rajpal, P.S.; Shishodia, K.S.; Sekhon, G.S.

    2006-01-01

    The paper explores the application of artificial neural networks to model the behaviour of a complex, repairable system. A composite measure of reliability, availability and maintainability parameters has been proposed for measuring the system performance. The artificial neural network has been trained using past data of a helicopter transportation facility. It is used to simulate behaviour of the facility under various constraints. The insights obtained from results of simulation are useful in formulating strategies for optimal operation of the system

  2. 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...

  3. Planning of Maintenance and Repair of Complicated Technical Systems

    Directory of Open Access Journals (Sweden)

    N. I. Liseychikov

    2004-01-01

    Full Text Available It is expedient to use mathematical models for substantiation of operational material consumption at maintenance of complicated technical systems. The appropriate tasks have been considered: minimization of operational material consumption; determination of maximum scope of work to be executed while maintaining one system; optimization of operational material consumption while organizing maintenance of a system group; planning of technical maintenance and determination of a number of systems to be maintained. Formalization and solution of the above problems have been accomplished.

  4. The necessity of a theory of biology for tissue engineering: metabolism-repair systems.

    Science.gov (United States)

    Ganguli, Suman; Hunt, C Anthony

    2004-01-01

    Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering.

  5. 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. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  6. 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…

  7. Present status of DNA repair mechanisms in uv irradiated yeast taken as a model eukaryotic system

    International Nuclear Information System (INIS)

    Moustacchi, E.; Waters, R.; Heude, M.; Chanet, R.

    1975-01-01

    The repair mechanisms of altered DNA are generally less well understood for eukaryotes than they are for prokaryotes and bacteriophages. For mammalian cell lines cultured in vitro the specific labelling of DNA has allowed the biochemical analysis of some of the steps of the repair processes whereas the determination of their genetic controls is, with a few exceptions, obviously difficult. On the other hand, with fungi and more specifically with yeast taken as a model unicellular eukaryotic system, the genetic approach has been extensively explored: radiosensitive mutants are readily detected and genetically analyzed, double and multiple mutants can be constructed and from their responses to irradiation the number of repair pathways involved can be suggested. The lack of thymidine kinase in these organisms has hampered for a certain time the biochemical analysis of repair. However, the recent isolation of yeast strains capable of taking up and incorporating thymidine 5'-monophosphate into their DNA opens new possibilities for the future. In spite of this difficulty, attempts to measure the induction and removal of uv-induced pyrimidine dimers were performed by several groups during the last three years. The two main repair pathways described for E. coli, i.e., the excision-resynthesis and post-replicative recombinational repair pathways, do exist in yeast. The existence of the former pathway is supported not only by indirect evidence but also by biochemical analysis. The rad 1 and rad 2 mutants for instance have been shown to be blocked in the excision of uv-induced pyrimidine dimers. Other loci are epistatic to rad 1 and rad 2 (rad 3 , rad 4 ) and are likely to act on this excision pathway. The genetic control of the mitochondrial response to a uv treatment involves nuclear genes and mitochondrial determinants

  8. Selective Cytotoxicity of Rhodium Metalloinsertors in Mismatch Repair-Deficient Cells†

    Science.gov (United States)

    Ernst, Russell J.; Komor, Alexis C.; Barton, Jacqueline K.

    2011-01-01

    Mismatches in DNA occur naturally during replication and as a result of endogenous DNA damaging agents, but the mismatch repair (MMR) pathway acts to correct mismatches before subsequent rounds of replication. Rhodium metalloinsertors bind to DNA mismatches with high affinity and specificity and represent a promising strategy to target mismatches in cells. Here we examine the biological fate of rhodium metalloinsertors bearing dipyridylamine ancillary ligands in cells deficient in MMR versus those that are MMR-proficient. These complexes are shown to exhibit accelerated cellular uptake which permits the observation of various cellular responses, including disruption of the cell cycle, monitored by flow cytometry assays, and induction of necrosis, monitored by dye exclusion and caspase inhibition assays, that occur preferentially in the MMR-deficient cell line. These cellular responses provide insight into the mechanisms underlying the selective activity of this novel class of targeted anti-cancer agents. PMID:22103240

  9. Statistical evaluation of failures and repairs of the V-1 measuring and control system

    International Nuclear Information System (INIS)

    Laurinec, R.; Korec, J.; Mitosinka, J.; Zarnovican, V.

    1984-01-01

    A failure record card system was introduced for evaluating the reliability of the measurement and control equipment of the V-1 nuclear power plant. The SPU-800 microcomputer system is used for recording data on magnetic tape and their transmission to the central data processing department. The data are used for evaluating the reliability of components and circuits and a selection is made of the most failure-prone components, and the causes of failures are evaluated as are failure identification, repair and causes of outages. The system provides monthly, annual and total assessment data since the system was commissioned. The results of the statistical evaluation of failures are used for planning preventive maintenance and for determining optimal repair intervals. (E.S.)

  10. [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.

  11. Modelling open pit shovel-truck systems using the Machine Repair Model

    Energy Technology Data Exchange (ETDEWEB)

    Krause, A.; Musingwini, C. [CBH Resources Ltd., Sydney, NSW (Australia). Endeaver Mine

    2007-08-15

    Shovel-truck systems for loading and hauling material in open pit mines are now routinely analysed using simulation models or off-the-shelf simulation software packages, which can be very expensive for once-off or occasional use. The simulation models invariably produce different estimations of fleet sizes due to their differing estimations of cycle time. No single model or package can accurately estimate the required fleet size because the fleet operating parameters are characteristically random and dynamic. In order to improve confidence in sizing the fleet for a mining project, at least two estimation models should be used. This paper demonstrates that the Machine Repair Model can be modified and used as a model for estimating truck fleet size in an open pit shovel-truck system. The modified Machine Repair Model is first applied to a virtual open pit mine case study. The results compare favourably to output from other estimation models using the same input parameters for the virtual mine. The modified Machine Repair Model is further applied to an existing open pit coal operation, the Kwagga Section of Optimum Colliery as a case study. Again the results confirm those obtained from the virtual mine case study. It is concluded that the Machine Repair Model can be an affordable model compared to off-the-shelf generic software because it is easily modelled in Microsoft Excel, a software platform that most mines already use.

  12. Formal definition of coherency and computation of minimal cut sequences for binary dynamic and repairable systems

    International Nuclear Information System (INIS)

    Chaux, Pierre-Yves

    2013-01-01

    Preventive risk assessment of a complex system rely on a dynamic models which describe the link between the system failure and the scenarios of failure and repair events from its components. The qualitative analyses of a binary dynamic and repairable system is aiming at computing and analyse the scenarios that lead to the system failure. Since such systems describe a large set of those, only the most representative ones, called Minimal Cut Sequences (MCS), are of interest for the safety engineer. The lack of a formal definition for the MCS has generated multiple definitions either specific to a given model (and thus not generic) or informal. This work proposes i) a formal framework and definition for the MCS while staying independent of the reliability model used, ii) the methodology to compute them using property extracted from their formal definition, iii) an extension of the formal framework for multi-states components in order to perform the qualitative analyses of Boolean logic Driven Markov Processes (BDMP) models. Under the hypothesis that the scenarios implicitly described by any reliability model can always be represented by a finite automaton, this work is defining the coherency for dynamic and repairable systems as the way to give a minimal representation of all scenarios that are leading to the system failure. (author)

  13. RNA damage in biological conflicts and the diversity of responding RNA repair systems

    Science.gov (United States)

    Burroughs, A. Maxwell; Aravind, L.

    2016-01-01

    RNA is targeted in biological conflicts by enzymatic toxins or effectors. A vast diversity of systems which repair or ‘heal’ this damage has only recently become apparent. Here, we summarize the known effectors, their modes of action, and RNA targets before surveying the diverse systems which counter this damage from a comparative genomics viewpoint. RNA-repair systems show a modular organization with extensive shuffling and displacement of the constituent domains; however, a general ‘syntax’ is strongly maintained whereby systems typically contain: a RNA ligase (either ATP-grasp or RtcB superfamilies), nucleotidyltransferases, enzymes modifying RNA-termini for ligation (phosphatases and kinases) or protection (methylases), and scaffold or cofactor proteins. We highlight poorly-understood or previously-uncharacterized repair systems and components, e.g. potential scaffolding cofactors (Rot/TROVE and SPFH/Band-7 modules) with their respective cognate non-coding RNAs (YRNAs and a novel tRNA-like molecule) and a novel nucleotidyltransferase associating with diverse ligases. These systems have been extensively disseminated by lateral transfer between distant prokaryotic and microbial eukaryotic lineages consistent with intense inter-organismal conflict. Components have also often been ‘institutionalized’ for non-conflict roles, e.g. in RNA-splicing and in RNAi systems (e.g. in kinetoplastids) which combine a distinct family of RNA-acting prim-pol domains with DICER-like proteins. PMID:27536007

  14. 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

  15. Generalized renewal process for repairable systems based on finite Weibull mixture

    International Nuclear Information System (INIS)

    Veber, B.; Nagode, M.; Fajdiga, M.

    2008-01-01

    Repairable systems can be brought to one of possible states following a repair. These states are: 'as good as new', 'as bad as old' and 'better than old but worse than new'. The probabilistic models traditionally used to estimate the expected number of failures account for the first two states, but they do not properly apply to the last one, which is more realistic in practice. In this paper, a probabilistic model that is applicable to all of the three after-repair states, called generalized renewal process (GRP), is applied. Simplistically, GRP addresses the repair assumption by introducing the concept of virtual age into the stochastic point processes to enable them to represent the full spectrum of repair assumptions. The shape of measured or design life distributions of systems can vary considerably, and therefore frequently cannot be approximated by simple distribution functions. The scope of the paper is to prove that a finite Weibull mixture, with positive component weights only, can be used as underlying distribution of the time to first failure (TTFF) of the GRP model, on condition that the unknown parameters can be estimated. To support the main idea, three examples are presented. In order to estimate the unknown parameters of the GRP model with m-fold Weibull mixture, the EM algorithm is applied. The GRP model with m mixture components distributions is compared to the standard GRP model based on two-parameter Weibull distribution by calculating the expected number of failures. It can be concluded that the suggested GRP model with Weibull mixture with an arbitrary but finite number of components is suitable for predicting failures based on the past performance of the system

  16. 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.

  17. Multi-echelon Repair Inventory Systems: Select Issues in Modular Electronic Equipment

    OpenAIRE

    Amik Garg; S. G. Deshmukh

    2010-01-01

    Flow of modules/printed circuit boards (PCBs) in a multi-echelon repair inventory system pertaining to modular electronic equipment for large maintenance organisations having large inventory in range and depth, like defence has been critically examined using a case study. Desirable features of the proposed system are identified and a general framework suggested for examining its feasibility and implementation in an organisation. An analytical model with an objective to reduce number of echelo...

  18. A Conceptual Study of Using an Isothermal Compressor on an S-CO{sub 2} Cooled KAIST Micro Modular Reactor (KAIST-MMR)

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Jin Young; Ahn, Yoonhan; Lee, Jeong Ik [KAIST, Daejeon (Korea, Republic of)

    2016-05-15

    Although the isothermal compressor technology is not fully matured for commercialization, its potential to reduce the compressor work and the cycle physical size due to the merging of the compressor and the precooler into one turbomachine can be utilized well especially in a concept such as the KAIST-MMR. Future works include optimization of the cycle layout and parameters to enhance performance, calculation of the heat exchanger sizes, and turbomachinery design of components. The development of small modular reactors (SMR) has been gathering attention due to factory manufacturing, but the power system required for a steam cycle in a water-cooled SMR is significantly large. A new concept called the KAIST Micro Modular Reactor (MMR) has been designed previously to make use of the supercritical CO{sub 2} (S-CO{sub 2}) cycle to significantly decrease the size and to improve its cycle efficiency. To further enhance the advantages of the KAIST-MMR concept, the conventional compressor is replaced with an isothermal compressor in the S-CO{sub 2} cycle.

  19. Non-periodic preventive maintenance with reliability thresholds for complex repairable systems

    International Nuclear Information System (INIS)

    Lin, Zu-Liang; Huang, Yeu-Shiang; Fang, Chih-Chiang

    2015-01-01

    In general, a non-periodic condition-based PM policy with different condition variables is often more effective than a periodic age-based policy for deteriorating complex repairable systems. In this study, system reliability is estimated and used as the condition variable, and three reliability-based PM models are then developed with consideration of different scenarios which can assist in evaluating the maintenance cost for each scenario. The proposed approach provides the optimal reliability thresholds and PM schedules in advance by which the system availability and quality can be ensured and the organizational resources can be well prepared and managed. The results of the sensitivity anlysis indicate that PM activities performed at a high reliability threshold can not only significantly improve the system availability but also efficiently extend the system lifetime, although such a PM strategy is more costly than that for a low reliabiltiy threshold. The optimal reliability threshold increases along with the number of PM activities to prevent future breakdowns caused by severe deterioration, and thus substantially reduces repair costs. - Highlights: • The PM problems for repairable deteriorating systems are formulated. • The structural properties of the proposed PM models are investigated. • The corresponding algorithms to find the optimal PM strategies are provided. • Imperfect PM activities are allowed to reduce the occurences of breakdowns. • Provide managers with insights about the critical factors in the planning stage

  20. Knowledge, attitudes and opinions towards measles and the MMR vaccine across two NSW cohorts.

    Science.gov (United States)

    Brieger, Daniel; Edwards, Matthew; Mudgil, Poonam; Whitehall, John

    2017-12-01

    Although the number of national measles cases has greatly decreased since 1980s, there has been resurgence in disease incidence in recent years. While parental knowledge and attitudes toward both disease and vaccinations are known to influence vaccine uptake, the contribution of these factors toward vaccination rates in NSW populations has not been studied. The aim of this study was to investigate the knowledge and opinions on measles and MMR vaccine in NSW Central and North Coast regions. Parents (n=201) of children <12 years were surveyed with a purpose design survey at public beaches at the Central Coast and community markets at the North Coast. Eight per cent of respondents reported not immunising their child with MMR vaccine. Most respondents recognised that measles is a highly contagious disease. Non-immunisers were found to be older, had a lower perceived severity of measles, were less likely to agree with the efficacy and safety of the vaccine, and were more likely to have encountered someone who had suffered side-effects of the vaccine. There is considerable concern over safety of MMR vaccine among non-immunisers. Implications for public health: Improving confidence in MMR vaccine should be a target of future public health interventions. © 2017 The Authors.

  1. Parental decision-making in uptake of the MMR vaccination: a systematic review of qualitative literature.

    Science.gov (United States)

    Allan, N; Harden, J

    2015-12-01

    Controversy has surrounded MMR vaccination in the aftermath of Wakefield's 1998 paper suggesting links between MMR and the development of pervasive developmental disorder in children. The paper sparked off media debate and contributed to a lack of parental trust in health-care providers and reduction in MMR uptake. This review aims to identify and evaluate research on the subject, with a view to present the reasons behind, and influences on parental decision-making in relation to MMR. Systematic search strategy identified 14 relevant papers on which thematic analysis was performed. Themes identified were categorized as follows: perceptions of risk; roles and responsibility; experience and knowledge. There were limited changes in parental decision-making factors over the time period despite an increase in uptake. Many studies fail to differentiate between accepters and rejecters, making it difficult to draw out clear conclusions. Policymakers need to adapt information provided to address these concerns. Future research should focus more on distinguishing between accepters and rejecters to determine which factors can alter outcome. © The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Reliability Analysis of 6-Component Star Markov Repairable System with Spatial Dependence

    Directory of Open Access Journals (Sweden)

    Liying Wang

    2017-01-01

    Full Text Available Star repairable systems with spatial dependence consist of a center component and several peripheral components. The peripheral components are arranged around the center component, and the performance of each component depends on its spatial “neighbors.” Vector-Markov process is adapted to describe the performance of the system. The state space and transition rate matrix corresponding to the 6-component star Markov repairable system with spatial dependence are presented via probability analysis method. Several reliability indices, such as the availability, the probabilities of visiting the safety, the degradation, the alert, and the failed state sets, are obtained by Laplace transform method and a numerical example is provided to illustrate the results.

  3. Development of laser cladding system to repair wall thinning of 1-inch heat exchanger tube

    International Nuclear Information System (INIS)

    Terada, Takaya

    2013-01-01

    We developed a laser cladding system to repair the inner wall wastage of heat exchanger tubes. Our system, which is designed to repair thinning tube walls within 100 mm from the edge of a heat exchanger tube, consists of a fiber laser, a composite-type optical fiberscope, a coupling device, a laser processing head, and a wire-feeding device. All of these components were reconfigured from the technologies of FBR maintenance. The laser processing head, which has a 15-mm outer diameter, was designed to be inserted into a 1-inch heat exchanger tube. We mounted a heatproof broadband mirror for laser cladding and fiberscope observation with visible light inside the laser processing head. The wire-feeding device continuously supplied 0.4-mm wire to the laser irradiation spot with variable feeding speeds from 0.5 to 20 mm/s. We are planning to apply our proposed system to the maintenance of aging industrial plants. (author)

  4. A shock and wear system under environmental conditions subject to internal failures, repair, and replacement

    International Nuclear Information System (INIS)

    Montoro-Cazorla, Delia; Pérez-Ocón, Rafael

    2012-01-01

    A system in a random environment is considered. The influence of the external conditions is governed by a Markovian arrival process. The internal structure of failure and repair are governed by phase-type distributions. The maintenance is performed by policy N. Under these assumptions, the Markov process governing the system is constructed, and it is studied in transient and stationary regime, calculating the availability and the rate of occurrence of failures. The renewal process due to the replacements of the system is studied, and expressions for the number of replacements and for the number of repairs between replacements are calculated. This paper extends other previously published since it incorporates a shock arrival process with dependence among the interarrival times and the renewal process associated to the replacements. A numerical application illustrates the calculations.

  5. Rare event simulation for highly dependable systems with fast repairs

    NARCIS (Netherlands)

    Reijsbergen, D.P.; de Boer, Pieter-Tjerk; Scheinhardt, Willem R.W.; Haverkort, Boudewijn R.H.M.

    2010-01-01

    Stochastic model checking has been used recently to assess, among others, dependability measures for a variety of systems. However, the employed numerical methods, as, e.g., supported by model checking tools such as PRISM and MRMC, suffer from the state-space explosion problem. The main alternative

  6. Rare event simulation for highly dependable systems with fast repairs

    NARCIS (Netherlands)

    Reijsbergen, D.P.; de Boer, Pieter-Tjerk; Scheinhardt, Willem R.W.; Haverkort, Boudewijn R.H.M.

    Probabilistic model checking has been used recently to assess, among others, dependability measures for a variety of systems. However, the numerical methods employed, such as those supported by model checking tools such as PRISM and MRMC, suffer from the state-space explosion problem. The main

  7. Automated TIG welding system with visual sensor for repairing nuclear plants

    International Nuclear Information System (INIS)

    Inoue, Katsunori; Watanabe, Hiroshi; Kondoh, Yoshihide.

    1986-01-01

    An automated TIG welding system has been developed. This system is to be used for repairing nuclear plants, whose work environment is highly radioactive, so should have the automatic self control function and the remote controllable function. For this purpose, the visual sensor, a TV camera and an image processor, is installed and the image processing technique is applied to the all-position TIG welding system. In this system, all controls are made with microprocessors and every necessary information is displayed on the screen of the remote control unit. The excellent performance was obtained as the application of this system to the practical field. (author)

  8. 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.

  9. 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.

  10. A systems approach to inventory management of repairables in the Navy

    OpenAIRE

    Apple, Chris Leon

    1985-01-01

    Approved for public release; distribution is unlimited This thesis develops an inventory model for repairable items which integrates the shipboard protection level into the wholesale stock level computations. It uses mean supply response time (MSRT) as its measure of effectiveness and provides methods for computing either the required wholesale stock level given a MSRT goal or for minimizing the system MSRT subject to budgetary constraints. Examples are provided which demons...

  11. Novel Combinatory Approaches to Repair Visual System after Optic Nerve Damage

    Science.gov (United States)

    2014-09-01

    Novel Combinatory Approaches to Repair Visual System After Optic Nerve Damage 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...biological functions such as metabolism, growth, cell cycle, and survival ( Cardone et al., 1998; Diehl, Cheng, Roussel, & Sherr, 1998; Hers, Vincent...of injured adult sensory neurons. The Journal of Neuroscience, 21, 7161–7170. Cardone , M. H., Roy, N., Stennicke, H. R., Salvesen, G. S., Franke, T. F

  12. 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)

  13. Involvement of DNA mismatch repair in the maintenance of heterochromatic DNA stability in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Basanta K Dahal

    2017-10-01

    Full Text Available Heterochromatin contains a significant part of nuclear DNA. Little is known about the mechanisms that govern heterochromatic DNA stability. We show here that in the yeast Saccharomyces cerevisiae (i DNA mismatch repair (MMR is required for the maintenance of heterochromatic DNA stability, (ii MutLα (Mlh1-Pms1 heterodimer, MutSα (Msh2-Msh6 heterodimer, MutSβ (Msh2-Msh3 heterodimer, and Exo1 are involved in MMR at heterochromatin, (iii Exo1-independent MMR at heterochromatin frequently leads to the formation of Pol ζ-dependent mutations, (iv MMR cooperates with the proofreading activity of Pol ε and the histone acetyltransferase Rtt109 in the maintenance of heterochromatic DNA stability, (v repair of base-base mismatches at heterochromatin is less efficient than repair of base-base mismatches at euchromatin, and (vi the efficiency of repair of 1-nt insertion/deletion loops at heterochromatin is similar to the efficiency of repair of 1-nt insertion/deletion loops at euchromatin.

  14. 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.

  15. Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods

    Science.gov (United States)

    Arora, Sanjeevani; Huwe, Peter J.; Sikder, Rahmat; Shah, Manali; Browne, Amanda J.; Lesh, Randy; Nicolas, Emmanuelle; Deshpande, Sanat; Hall, Michael J.; Dunbrack, Roland L.; Golemis, Erica A.

    2017-01-01

    ABSTRACT The cancer-predisposing Lynch Syndrome (LS) arises from germline mutations in DNA mismatch repair (MMR) genes, predominantly MLH1, MSH2, MSH6, and PMS2. A major challenge for clinical diagnosis of LS is the frequent identification of variants of uncertain significance (VUS) in these genes, as it is often difficult to determine variant pathogenicity, particularly for missense variants. Generic programs such as SIFT and PolyPhen-2, and MMR gene-specific programs such as PON-MMR and MAPP-MMR, are often used to predict deleterious or neutral effects of VUS in MMR genes. We evaluated the performance of multiple predictive programs in the context of functional biologic data for 15 VUS in MLH1, MSH2, and PMS2. Using cell line models, we characterized VUS predicted to range from neutral to pathogenic on mRNA and protein expression, basal cellular viability, viability following treatment with a panel of DNA-damaging agents, and functionality in DNA damage response (DDR) signaling, benchmarking to wild-type MMR proteins. Our results suggest that the MMR gene-specific classifiers do not always align with the experimental phenotypes related to DDR. Our study highlights the importance of complementary experimental and computational assessment to develop future predictors for the assessment of VUS. PMID:28494185

  16. Interactions of radiation repair systems in escherichia colt with antineoplastic anthracyclines

    International Nuclear Information System (INIS)

    Kacinski, B.M.; Rupp, W.D.

    1984-01-01

    The authors have studied the interactions of several anthracylines with the UVR DN*a repair system of E. coli. The authors found that doxorubicin is quite toxic for uvr- but not for uvr+strains. They also found that exposure of cells carrying a multicopy plasmid to this agent yielded plasmid DNA molecules with lesions which were recognized and cleaved by purified E. coli UVRABC DNA repair endonuclease. A derivative of doxorubicin was not measurably toxic for either uvr+ or uvr- strains but nevertheless produced lesions which were substrates for the UVRABC endonuclease. The authors propose that anthracycline toxicity in uvr- E. coli may correlate with clinical toxicity while anthracylcine antineopolastic activity may correlate with their ability to produce UVRABC endonuclease-sensitive DNA damage

  17. Bioactive Molecule-loaded Drug Delivery Systems to Optimize Bone Tissue Repair.

    Science.gov (United States)

    Oshiro, Joao Augusto; Sato, Mariana Rillo; Scardueli, Cassio Rocha; Lopes de Oliveira, Guilherme Jose Pimentel; Abucafy, Marina Paiva; Chorilli, Marlus

    2017-01-01

    Bioactive molecules such as peptides and proteins can optimize the repair of bone tissue; however, the results are often unpredictable when administered alone, owing to their short biological half-life and instability. Thus, the development of bioactive molecule-loaded drug delivery systems (DDS) to repair bone tissue has been the subject of intense research. DDS can optimize the repair of bone tissue owing to their physicochemical properties, which improve cellular interactions and enable the incorporation and prolonged release of bioactive molecules. These characteristics are fundamental to favor bone tissue homeostasis, since the biological activity of these factors depends on how accessible they are to the cell. Considering the importance of these DDS, this review aims to present relevant information on DDS when loaded with osteogenic growth peptide and bone morphogenetic protein. These are bioactive molecules that are capable of modulating the differentiation and proliferation of mesenchymal cells in bone tissue cells. Moreover, we will present different approaches using these peptide and protein-loaded DDS, such as synthetic membranes and scaffolds for bone regeneration, synthetic grafts, bone cements, liposomes, and micelles, which aim at improving the therapeutic effectiveness, and we will compare their advantages with commercial systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. 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.

  19. Space Shuttle Thermal Protection System Repair Flight Experiment Induced Contamination Impacts

    Science.gov (United States)

    Smith, Kendall A.; Soares, Carlos E.; Mikatarian, Ron; Schmidl, Danny; Campbell, Colin; Koontz, Steven; Engle, Michael; McCroskey, Doug; Garrett, Jeff

    2006-01-01

    NASA s activities to prepare for Flight LF1 (STS-114) included development of a method to repair the Thermal Protection System (TPS) of the Orbiter s leading edge should it be damaged during ascent by impacts from foam, ice, etc . Reinforced Carbon-Carbon (RCC) is used for the leading edge TPS. The repair material that was developed is named Non- Oxide Adhesive eXperimental (NOAX). NOAX is an uncured adhesive material that acts as an ablative repair material. NOAX completes curing during the Orbiter s descent. The Thermal Protection System (TPS) Detailed Test Objective 848 (DTO 848) performed on Flight LF1 (STS-114) characterized the working life, porosity void size in a micro-gravity environment, and the on-orbit performance of the repairs to pre-damaged samples. DTO 848 is also scheduled for Flight ULF1.1 (STS-121) for further characterization of NOAX on-orbit performance. Due to the high material outgassing rates of the NOAX material and concerns with contamination impacts to optically sensitive surfaces, ASTM E 1559 outgassing tests were performed to determine NOAX condensable outgassing rates as a function of time and temperature. Sensitive surfaces of concern include the Extravehicular Mobility Unit (EMU) visor, cameras, and other sensors in proximity to the experiment during the initial time after application. This paper discusses NOAX outgassing characteristics, how the amount of deposition on optically sensitive surfaces while the NOAX is being manipulated on the pre-damaged RCC samples was determined by analysis, and how flight rules were developed to protect those optically sensitive surfaces from excessive contamination where necessary.

  20. Role of the immune system in cardiac tissue damage and repair following myocardial infarction.

    Science.gov (United States)

    Saparov, Arman; Ogay, Vyacheslav; Nurgozhin, Talgat; Chen, William C W; Mansurov, Nurlan; Issabekova, Assel; Zhakupova, Jamilya

    2017-09-01

    The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

  1. Molecular mechanism of short-patch repair of radiation-damaged DNA by in vitro reconstituted systems

    International Nuclear Information System (INIS)

    Matsumoto, Y.; Kim, K.; Biade, S.

    1995-01-01

    Objective: Short-patch excision repair is the major pathway to correct DNA damage such as modified bases, apurinic/apyrimidinic (AP) sites and single-strand breaks. Recently this repair reaction was demonstrated to proceed by two alternative pathways: DNA polymerase β (pol β)-dependent pathway and proliferating cell nuclear antigen (PCNA)-dependent pathway. In this work, we focused to compare substrate specificity of these two repair pathways and elucidate their roles in cellular responses to radiation damage. Materials and Methods: Three protein fractions, AP endonuclease, pol β, and BE-1B, which are required for the pol β-dependent pathway, and five protein fractions, AP endonuclease, BE-1B (these two are common to the pol β-dependent pathway), PCNA, pol δ, and BE-2, which are essential for the PCNA-dependent pathway were obtained from Xenopus laevis ovaries through column chromatography. The circular DNA containing either one of the following three lesions: a natural AP site, its synthetic analog, 3-hydroxy-2-hydroxymethyltetrahydrofuran (tetrahydrofuran), and 5-iododeoxyuridine (IdU), was prepared by in vitro ligation of oligonucleotides to a gapped circular DNA. The IdU-containing DNA was irradiated with 312 nm UV light prior to repair reaction. In addition, DNA carrying a single-strand break was obtained by Cs-137 irradiation. Repair reactions of these substrate DNAs were conducted with either the reconstituted system for the pol β-dependent pathway or the one for the PCNA-dependent pathway. After the reaction, repaired and unrepaired DNAs were separated by gel electrophoresis and quantitated. Results: The pol β-dependent reconstituted system was able to repair natural AP sites but not tetrahydrofuran sites or UV-irradiated IdU. The single-strand breaks generated by γ-irradiation were partially repaired by thepol β-dependent pathway. The PCNA-dependent system was able to repair natural AP sites, tetrahydrofuran sites, and most of the single

  2. Calcium Carbonate Formation in Water Distribution Systems and Autogenous Repair of Leaks by Inert Particle Clogging

    OpenAIRE

    Richards, Colin Scott

    2016-01-01

    The formation of calcium carbonate (CaCO3) (i.e. scale) in potable water systems has long been a concern in water treatment and distribution. A literature review reveals that CaCO3 scaling issues are re-emerging due to climate change, temperature increases in hot water systems and lower use of scaling and corrosion inhibitors. Moreover, we have gathered insights that suggest CaCO3 coatings can be beneficial and stop pipeline leaks via self-repair or clogging. Ironically, the actions we are ta...

  3. Low frequency of defective mismatch repair in a population-based series of upper urothelial carcinoma

    International Nuclear Information System (INIS)

    Ericson, Kajsa M; Isinger, Anna P; Isfoss, Björn L; Nilbert, Mef C

    2005-01-01

    Upper urothelial cancer (UUC), i.e. transitional cell carcinomas of the renal pelvis and the ureter, occur at an increased frequency in patients with hereditary nonpolyposis colorectal cancer (HNPCC). Defective mismatch repair (MMR) specifically characterizes HNPCC-associated tumors, but also occurs in subsets of some sporadic tumors, e.g. in gastrointestinal cancer and endometrial cancer. We assessed the contribution of defective MMR to the development of UUC in a population-based series from the southern Swedish Cancer Registry, through microsatellite instability (MSI) analysis and immunohistochemical evaluation of expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6. A MSI-high phenotype was identified in 9/216 (4%) successfully analyzed patients and a MSI-low phenotype in 5/216 (2%). Loss of MMR protein immunostaining was found in 11/216 (5%) tumors, and affected most commonly MSH2 and MSH6. This population-based series indicates that somatic MMR inactivation is a minor pathway in the development of UUC, but tumors that display defective MMR are, based on the immunohistochemical expression pattern, likely to be associated with HNPCC

  4. Low frequency of defective mismatch repair in a population-based series of upper urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Isfoss Björn L

    2005-03-01

    Full Text Available Abstract Background Upper urothelial cancer (UUC, i.e. transitional cell carcinomas of the renal pelvis and the ureter, occur at an increased frequency in patients with hereditary nonpolyposis colorectal cancer (HNPCC. Defective mismatch repair (MMR specifically characterizes HNPCC-associated tumors, but also occurs in subsets of some sporadic tumors, e.g. in gastrointestinal cancer and endometrial cancer. Methods We assessed the contribution of defective MMR to the development of UUC in a population-based series from the southern Swedish Cancer Registry, through microsatellite instability (MSI analysis and immunohistochemical evaluation of expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6. Results A MSI-high phenotype was identified in 9/216 (4% successfully analyzed patients and a MSI-low phenotype in 5/216 (2%. Loss of MMR protein immunostaining was found in 11/216 (5% tumors, and affected most commonly MSH2 and MSH6. Conclusion This population-based series indicates that somatic MMR inactivation is a minor pathway in the development of UUC, but tumors that display defective MMR are, based on the immunohistochemical expression pattern, likely to be associated with HNPCC.

  5. Low frequency of defective mismatch repair in a population-based series of upper urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ericson, Kajsa M; Isinger, Anna P [Departments of Oncology, University Hospital, Lund (Sweden); Isfoss, Björn L [Departments of Pathology, University Hospital, Lund (Sweden); Nilbert, Mef C [Departments of Oncology, University Hospital, Lund (Sweden)

    2005-01-01

    Upper urothelial cancer (UUC), i.e. transitional cell carcinomas of the renal pelvis and the ureter, occur at an increased frequency in patients with hereditary nonpolyposis colorectal cancer (HNPCC). Defective mismatch repair (MMR) specifically characterizes HNPCC-associated tumors, but also occurs in subsets of some sporadic tumors, e.g. in gastrointestinal cancer and endometrial cancer. We assessed the contribution of defective MMR to the development of UUC in a population-based series from the southern Swedish Cancer Registry, through microsatellite instability (MSI) analysis and immunohistochemical evaluation of expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6. A MSI-high phenotype was identified in 9/216 (4%) successfully analyzed patients and a MSI-low phenotype in 5/216 (2%). Loss of MMR protein immunostaining was found in 11/216 (5%) tumors, and affected most commonly MSH2 and MSH6. This population-based series indicates that somatic MMR inactivation is a minor pathway in the development of UUC, but tumors that display defective MMR are, based on the immunohistochemical expression pattern, likely to be associated with HNPCC.

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

    Directory of Open Access Journals (Sweden)

    Eduardo Angeli Malavolta

    Full Text Available ABSTRACT OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. Dynamic and Control Analysis of Modular Multi-Parallel Rectifiers (MMR)

    DEFF Research Database (Denmark)

    Zare, Firuz; Ghosh, Arindam; Davari, Pooya

    2017-01-01

    This paper presents dynamic analysis of a Modular Multi-Parallel Rectifier (MMR) based on state-space modelling and analysis. The proposed topology is suitable for high power application which can reduce line current harmonics emissions significantly. However, a proper controller is required...... to share and control current through each rectifier. Mathematical analysis and preliminary simulations have been carried out to verify the proposed controller under different operating conditions....

  8. Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR

    Science.gov (United States)

    2012-01-01

    The imidazotetrazine ring is an acid-stable precursor and prodrug of highly reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of Temozolomide. PMID:24900418

  9. Information, education, and health behaviors: Evidence from the MMR vaccine autism controversy.

    Science.gov (United States)

    Chang, Lenisa V

    2018-05-02

    In the wake of strong, although later refuted, claims of a link between autism and the measles-mumps-rubella (MMR) vaccine, I examine whether fewer parents immunized or delayed vaccinations for their children and if there was a differential response by mother's education level. Using various controls and a differencing strategy that compares in MMR take-up with other vaccines, I find that the MMR-autism controversy led to a decline in the immediate years and that there were negative spillovers onto other vaccines. I also find evidence that more highly educated mothers responded more strongly to the controversy either by not immunizing their children altogether or, to a lesser degree, delaying vaccination. Moreover, the educational gap was greater in states where there was greater media attention devoted to the controversy. This is consistent with the health allocative efficiency hypothesis whereby part of the education gradient in health outcomes is due to more-educated individuals absorbing and responding to health information more quickly. However, unlike in the United Kingdom, where previous studies find that the gap was eliminated after the link was refuted, the evidence for the United States suggests that the educational gap persisted. Copyright © 2018 John Wiley & Sons, Ltd.

  10. DEVELOPMENT AND DEPLOYMENT ASSESSMENT OF A MELT-DOWN PROOF MODULAR MICRO REACTOR (MDP-MMR)

    Energy Technology Data Exchange (ETDEWEB)

    Hawari, Ayman I.; Venneri, Francesco

    2018-04-02

    The objective of this project is to perform feasibility assessment and technology gap analysis and establish a development roadmap for an innovative and highly compact Micro Modular Reactor (MMR) concept that integrates power production, power conversion and electricity generation in a single unit. The MMR is envisioned to use fully ceramic micro-encapsulated (FCM) fuel, a particularly robust form of TRISO fuel, and to be gas-cooled (e.g., He or CO2) and capable of generating power in the range of 10 to 40 MW-thermal. It is designed to be absolutely melt-down proof (MDP) under all circumstances including complete loss of coolant scenarios with no possible release of radioactive material, to be factory produced, to have a cycle length of greater than 20 years, and to be highly proliferation resistant. In addition, it will be transportable, retrievable and suitable for use in remote areas. As such, the MDP-MMR will represent a versatile reactor concept that is suitable for use in various applications including electricity generation, process heat utilization and propulsion.

  11. Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing.

    Science.gov (United States)

    Buchanan, Daniel D; Tan, Yen Y; Walsh, Michael D; Clendenning, Mark; Metcalf, Alexander M; Ferguson, Kaltin; Arnold, Sven T; Thompson, Bryony A; Lose, Felicity A; Parsons, Michael T; Walters, Rhiannon J; Pearson, Sally-Ann; Cummings, Margaret; Oehler, Martin K; Blomfield, Penelope B; Quinn, Michael A; Kirk, Judy A; Stewart, Colin J; Obermair, Andreas; Young, Joanne P; Webb, Penelope M; Spurdle, Amanda B

    2014-01-10

    Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered. Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation.

  12. Ability of Bacillus subtilis protoplasts to repair irradiated bacteriophage deoxyribonucleic acid via acquired and natural enzymatic systems

    International Nuclear Information System (INIS)

    Yasbin, R.E.; Andersen, B.J.; Sutherland, B.M.

    1981-01-01

    A novel form of enzyme therapy was achieved by utilizing protoplasts of Bacillus subtilis. Photoreactivating enzyme of Escherichia coli was successfully inserted into the protoplasts of B. subtilis treated with polyethylene glycol. This enzyme was used to photoreactivate ultraviolet-damaged bacteriophage deoxyribonucleic acid (DNA). Furthermore, in polyethylene glycol-treated protoplasts, ultraviolet-irradiated transfecting bacteriophage DNA was shown to be a functional substrate for the host DNA excision repair system. Previous results (R.E. Yasbin, J.D. Fernwalt, and P.I. Fields, J. Bacteriol.; 137: 391-396) showed that ultraviolet-irradiated bacteriophage DNA could not be repaired via the excision repair system of competent cells. Therefore, the processing of bacteriophage DNA by protoplasts and by competent cells must be different. This sensitive protoplast assay can be used to identify and to isolate various types of DNA repair enzymes

  13. Influence of oxidized purine processing on strand directionality of mismatch repair.

    Science.gov (United States)

    Repmann, Simone; Olivera-Harris, Maite; Jiricny, Josef

    2015-04-17

    Replicative DNA polymerases are high fidelity enzymes that misincorporate nucleotides into nascent DNA with a frequency lower than [1/10(5)], and this precision is improved to about [1/10(7)] by their proofreading activity. Because this fidelity is insufficient to replicate most genomes without error, nature evolved postreplicative mismatch repair (MMR), which improves the fidelity of DNA replication by up to 3 orders of magnitude through correcting biosynthetic errors that escaped proofreading. MMR must be able to recognize non-Watson-Crick base pairs and excise the misincorporated nucleotides from the nascent DNA strand, which carries by definition the erroneous genetic information. In eukaryotes, MMR is believed to be directed to the nascent strand by preexisting discontinuities such as gaps between Okazaki fragments in the lagging strand or breaks in the leading strand generated by the mismatch-activated endonuclease of the MutL homologs PMS1 in yeast and PMS2 in vertebrates. We recently demonstrated that the eukaryotic MMR machinery can make use also of strand breaks arising during excision of uracils or ribonucleotides from DNA. We now show that intermediates of MutY homolog-dependent excision of adenines mispaired with 8-oxoguanine (G(O)) also act as MMR initiation sites in extracts of human cells or Xenopus laevis eggs. Unexpectedly, G(O)/C pairs were not processed in these extracts and failed to affect MMR directionality, but extracts supplemented with exogenous 8-oxoguanine DNA glycosylase (OGG1) did so. Because OGG1-mediated excision of G(O) might misdirect MMR to the template strand, our findings suggest that OGG1 activity might be inhibited during MMR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. 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

    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...... 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...

  15. Intentions to use a novel Zika vaccine: the effects of misbeliefs about the MMR vaccine and perceptions about Zika.

    Science.gov (United States)

    Ophir, Yotam; Jamieson, Kathleen Hall

    2018-03-15

    People's intentions to use vaccines are influenced by their beliefs about both the specific vaccine and the disease it prevents. In the absence of firm beliefs about Zika virus (ZIKV), individuals may base their intentions to vaccinate against it on beliefs about other vaccines, and specifically the misbelief that MMR causes autism. A survey of 3337 Americans, using a random-digit-dialing sample of landline telephone households and cell-phones. Intentions to use a Zika vaccine were influenced by beliefs about Zika, science in general, and MMR. Intentions were positively influenced by perceived severity of and vulnerability to Zika, as well as belief in science's efficacy. However, intentions were negatively influenced by the belief that MMR causes autism in children. The misbelief about MMR and autism may reduce people's intentions to use a new Zika vaccine. However, perceptions of severity of and vulnerability to Zika may increase intentions. Implications for science educators and public health officials are discussed.

  16. [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.

  17. DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics.

    Science.gov (United States)

    de Rosa, Nicole; Rodriguez-Bigas, Miguel A; Chang, George J; Veerapong, Jula; Borras, Ester; Krishnan, Sunil; Bednarski, Brian; Messick, Craig A; Skibber, John M; Feig, Barry W; Lynch, Patrick M; Vilar, Eduardo; You, Y Nancy

    2016-09-01

    DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer-specific survival were calculated by the Kaplan-Meier method. The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer-specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions. © 2016 by American Society of Clinical Oncology.

  18. 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.

    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.

  19. Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors

    DEFF Research Database (Denmark)

    Saydam, Nurten; Kanagaraj, Radhakrishnan; Dietschy, Tobias

    2007-01-01

    is poorly understood. Here we show that WRN physically interacts with the MSH2/MSH6 (MutSalpha), MSH2/MSH3 (MutSbeta) and MLH1/PMS2 (MutLalpha) heterodimers that are involved in the initiation of mismatch repair (MMR) and the rejection of homeologous recombination. MutSalpha and MutSbeta can strongly...

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  1. 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

    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...

  2. The two-dose measles, mumps, and rubella (MMR) immunisation schedule: factors affecting maternal intention to vaccinate.

    OpenAIRE

    Pareek, M; Pattison, H M

    2000-01-01

    BACKGROUND: In the light of sub-optimal uptake of the measles, mumps, and rubella (MMR) vaccination, we investigated the factors that influence the intentions of mothers to vaccinate. METHOD: A cross-sectional survey of 300 mothers in Birmingham with children approaching a routine MMR vaccination was conducted using a postal questionnaire to measure: intention to vaccinate, psychological variables, knowledge of the vaccine, and socioeconomic status. The vaccination status of the children was ...

  3. Systematic immunohistochemical screening for mismatch repair and ERCC1 gene expression from colorectal cancers in China: Clinicopathological characteristics and effects on survival.

    Directory of Open Access Journals (Sweden)

    Pan Li

    Full Text Available We performed a systematic screening of colorectal cancer (CRC tissues to investigate whether mismatch repair (MMR status and ERCC1 protein expression could be predictive of clinical outcomes for these patients following the recommendation of The Evaluation of Genomic Applications in Practice of Prevention (EGAPP.The expression of four MMR genes and ERCC1 were assessed by immunohistochemistry (IHC from cancer tissue samples of 2233 consecutive CRC patients.We observed that most CRC patients with a proficient MMR (pMMR status tended to have simultaneous ERCC1 protein expression (P< 0.001. Stage III CRC patients with deficient MMR (dMMR had higher prognoses than the same stage patients with pMMR (DFS: 74% vs 65%, P = 0.04; OS: 79% vs 69%, P = 0.04. Here, dMMR is also associated with poorer survival for stage II patients after chemotherapy (DFS: 66% vs 78%, P = 0.04. Stage II and III patients that were shown to express ERCC1 protein had higher DFS and OS than those that were deficient in expression (stage II, DFS: 83% vs 70%, P = 0.006; OS 85% vs 73%, P = 0.02. Stage III, DFS: 67% vs56%, P = 0.03; OS: 71% vs 57%, P = 0.04.Our results indicate that dMMR appeared to predictive of a survival benefit for stage III CRC patients. We also found the determination of ERCC1 expression to be useful for predicting DFS or OS for stage II and III CRC patients. In addition, the expression of MMR genes and ERCC1 showed a significant relationship.

  4. Heterogenous mismatch-repair status in colorectal cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Veurink, Nynke; Holck, Susanne

    2014-01-01

    BACKGROUND: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative......, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. METHODS: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative....... CONCLUSIONS: Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. VIRTUAL SLIDES: The virtual slide(s) for this article...

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

    International Nuclear Information System (INIS)

    Knezevic, J.; Odoom, E.R.

    2001-01-01

    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

  6. Autism occurrence by MMR vaccine status among US children with older siblings with and without autism.

    Science.gov (United States)

    Jain, Anjali; Marshall, Jaclyn; Buikema, Ami; Bancroft, Tim; Kelly, Jonathan P; Newschaffer, Craig J

    2015-04-21

    Despite research showing no link between the measles-mumps-rubella (MMR) vaccine and autism spectrum disorders (ASD), beliefs that the vaccine causes autism persist, leading to lower vaccination levels. Parents who already have a child with ASD may be especially wary of vaccinations. To report ASD occurrence by MMR vaccine status in a large sample of US children who have older siblings with and without ASD. A retrospective cohort study using an administrative claims database associated with a large commercial health plan. Participants included children continuously enrolled in the health plan from birth to at least 5 years of age during 2001-2012 who also had an older sibling continuously enrolled for at least 6 months between 1997 and 2012. MMR vaccine receipt (0, 1, 2 doses) between birth and 5 years of age. ASD status defined as 2 claims with a diagnosis code in any position for autistic disorder or other specified pervasive developmental disorder (PDD) including Asperger syndrome, or unspecified PDD (International Classification of Diseases, Ninth Revision, Clinical Modification 299.0x, 299.8x, 299.9x). Of 95,727 children with older siblings, 994 (1.04%) were diagnosed with ASD and 1929 (2.01%) had an older sibling with ASD. Of those with older siblings with ASD, 134 (6.9%) had ASD, vs 860 (0.9%) children with unaffected siblings (P siblings, vs 73% (n = 1409) at age 2 years and 86% (n = 1660) at age 5 years for children with affected siblings. MMR vaccine receipt was not associated with an increased risk of ASD at any age. For children with older siblings with ASD, at age 2, the adjusted relative risk (RR) of ASD for 1 dose of MMR vaccine vs no vaccine was 0.76 (95% CI, 0.49-1.18; P = .22), and at age 5, the RR of ASD for 2 doses compared with no vaccine was 0.56 (95% CI, 0.31-1.01; P = .052). For children whose older siblings did not have ASD, at age 2, the adjusted RR of ASD for 1 dose was 0.91 (95% CI, 0.67-1.20; P = .50) and at age 5

  7. 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.

  8. 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

  9. Repair mechanisms inducible to the DNA in I.M.M.S. biological systems

    International Nuclear Information System (INIS)

    Guzman, J.; Arceo, C.; Cortinas, C.; Rosa, M.E. De la; Olvera, O.; Cruces, M.; Pimentel, E.

    1990-03-01

    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)

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

    International Nuclear Information System (INIS)

    Yoshimoto, Koji; Mizoguchi, Masahiro; Hata, Nobuhiro; Murata, Hideki; Hatae, Ryusuke; Amano, Toshiyuki; Nakamizo, Akira; Sasaki, Tomio

    2012-01-01

    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 (GBM). Although the activity of DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) has been described as the main modulator to determine the sensitivity of GBM to TMZ, a subset of GBM 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 repair and double-strand break 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Yoshimoto, Koji; Mizoguchi, Masahiro; Hata, Nobuhiro; Murata, Hideki; Hatae, Ryusuke; Amano, Toshiyuki; Nakamizo, Akira; Sasaki, Tomio, E-mail: kyoshimo@ns.med.kyushu-u.ac.jp [Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan)

    2012-12-05

    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 (GBM). Although the activity of DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) has been described as the main modulator to determine the sensitivity of GBM to TMZ, a subset of GBM 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 repair and double-strand break 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.

  12. [The quality of patient care under the German DRG system using as example the inguinal hernia repair].

    Science.gov (United States)

    Rudroff, C; Schweins, M; Heiss, M M

    2008-02-01

    The DRG system in Germany was introduced to improve and at the same time simplify the reimbursement of costs in German hospitals. Cost effectiveness and economic efficiency were the declared goals. Structural changes and increased competition among different hospitals were the consequences. The effect on the qualitiy of patient care has been discussed with some concern. Furthermore, doubts have been expressed about the correct representation of the various diagnoses and treatments in the coding system and the financial revenue. Inguinal hernia repair serves as an example to illustrate some common problems with the reimbursement in the DRG system. Virtual patients were grouped using a "Web Grouper" and analysed using the cost accounting from the G-DRG-Browser of the InEK. Additionally, the reimbursement for ambulant hernia repair was estimated. The DRG coding did not differentiate the various operative procedures for inguinal hernia repair. They all generated the same revenues. For example, the increased costs for bilateral inguinal hernia repair are not represented in the payment. Furthermore, no difference is made between primary and recurrent inguinal hernia. In the case of a short-term hospital stay, part of the revenue is retained. In the case of ambulatory treatment of inguinal hernia, the reimbursement is by far not a real compensation for the actual costs. The ideal patient in the DRG system suffers from a primary inguinal hernia, undergoes an open hernia repair without mesh, and remains for 2-3 days in hospital. Minimally invasive procedures, repair of bilateral inguinal hernia and ambulant operation are by far less profitable--if at all. The current revenues for inguinal hernia repair require improvement and adjustment to reality in order to accomplish the goals which the DRG system in Germany aims at.

  13. A Mobile Robotic System for the Inspection and Repair of SG Tubes in NPPs

    Directory of Open Access Journals (Sweden)

    Yong-Chil Seo

    2016-04-01

    Full Text Available The reliability and performance of a steam generator (SG is one of the serious concerns in the operation of pressurized water nuclear power plants. Because of high levels of radiation, robotic systems have been used to inspect and repair SG tubes. In this paper, we present a mobile robotic system that positions the inspection and repair tools while hanging down from the tube sheets where the tubes are fixed. All of the driving mechanisms of the mobile robot are actuated by electric motors to start its works, providing that the electric power is prepared without the additional need for an on-site air services. A special tube-holding mechanism with a high holding force has been developed to prevent falling from the tube sheets, even in the case of an electric power failure. We have also developed a quick installation guide device that guides the mobile robot to desired initial positions in the tube sheet exactly and quickly, which helps to reduce the radiation exposure of human workers during the installation work. This paper also provides on-site experimental results and lessons learned.

  14. Balancing repair and tolerance of DNA damage caused by alkylating agents

    OpenAIRE

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D.

    2012-01-01

    Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial ...

  15. SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

    OpenAIRE

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

    2012-01-01

    Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial fo...

  16. Stripped-down DNA repair in a highly reduced parasite

    Directory of Open Access Journals (Sweden)

    Fast Naomi M

    2007-03-01

    Full Text Available Abstract Background Encephalitozoon cuniculi is a member of a distinctive group of single-celled parasitic eukaryotes called microsporidia, which are closely related to fungi. Some of these organisms, including E. cuniculi, also have uniquely small genomes that are within the prokaryotic range. Thus, E. cuniculi has undergone a massive genome reduction which has resulted in a loss of genes from diverse biological pathways, including those that act in DNA repair. DNA repair is essential to any living cell. A loss of these mechanisms invariably results in accumulation of mutations and/or cell death. Six major pathways of DNA repair in eukaryotes include: non-homologous end joining (NHEJ, homologous recombination repair (HRR, mismatch repair (MMR, nucleotide excision repair (NER, base excision repair (BER and methyltransferase repair. DNA polymerases are also critical players in DNA repair processes. Given the close relationship between microsporidia and fungi, the repair mechanisms present in E. cuniculi were compared to those of the yeast Saccharomyces cerevisiae to ascertain how the process of genome reduction has affected the DNA repair pathways. Results E. cuniculi lacks 16 (plus another 6 potential absences of the 56 DNA repair genes sought via BLASTP and PSI-BLAST searches. Six of 14 DNA polymerases or polymerase subunits are also absent in E. cuniculi. All of these genes are relatively well conserved within eukaryotes. The absence of genes is not distributed equally among the different repair pathways; some pathways lack only one protein, while there is a striking absence of many proteins that are components of both double strand break repair pathways. All specialized repair polymerases are also absent. Conclusion Given the large number of DNA repair genes that are absent from the double strand break repair pathways, E. cuniculi is a prime candidate for the study of double strand break repair with minimal machinery. Strikingly, all of the

  17. An assessment of composite repair system in offshore platform for corroded circumferential welds in super duplex steel pipe

    Directory of Open Access Journals (Sweden)

    Silvio de Barros

    2018-04-01

    Full Text Available The main aim of this study is to assess the effectiveness of a composite repair system in severely corroded circumferential welds in super duplex stainless steel pipes as a preventive measure against the premature corrosion damage at the welds. Artificial defects were fabricated on the super duplex steel tube in order to reproduce the localized corrosion damage defects found in real welded joints. Three kinds of through thickness defects were considered: 25%, 50% and 96% of the perimeter of the pipe. The performance of the repaired pipe was assessed by hydrostatic tests as per ISO 24817 standard. The results showed that the composite repair system can sustain the designed failure pressure even for the pipe damaged with through-wall defect up to 96% of the perimeter of the pipe. Hence, the composite repair system can be used as a preliminary tool to protect the unexpected or premature failure at the welds and maintain an adequate level of mechanical strength for a given operating pressure. This composite repair system can assure that the pipe will not leak until a planned maintenance of the line. Nevertheless, further work is still desirable to improve the confidence in the long-term performance of bonded composite

  18. Atucha I nuclear power plant: repair works in QK02W01 moderator system heat exchanger

    International Nuclear Information System (INIS)

    Olivieri, Luis E.; Zanni, Pablo A.

    2000-01-01

    Atucha I nuclear power plant moderator system operates with highly radioactive heavy water, a pressure of 115 Bar and temperatures of about 200 C degrees. In March 2000, an increasing leakage of heavy water to the conventional thermal circuit was detected, conducting the plant to a shut down. The development of a number of actions and measures were taken, in order to plug this leakage. The leakage was found in a heat exchanger, which is located in a place of difficult access, with a high radiological yield and which, according to design, it was not considered to be mechanically repaired. It is a U bend tubes heat exchanger, weighting about 20 tons, and with a heavy water flow of 800 tons/h on the primary circuit, and 950 tons/h of ordinary water on the secondary side. Foreseeing this event, it had been designed and constructed special equipment and procedures, by means of a contract, with the Company INVAP SA. Repair works were carried out within a period of eighty-six (86) days, from which, forty five days were used to repair the component itself. A considerable amount of time was used to prepare simulators and the training of personnel. Due to the high radiological yield and the strict care of radiological standards, it was necessary the participation of 300 persons, integrating a collective dose of 4,86 Sv-m. It was necessary the construction of platforms and auxiliary stairs so as to make the work place accessible, as well as lifting and movement devices for heavy components, since this area does not have such kind of facilities. Welding and cutting machines remote controlled as well as manipulators which operated in front of the exchanger tube sheet were used. The aim was the reduction of dose values as much as possible. Special shielding were developed and in some cases it was necessary the adoption of drastic measures such as the cutting of bolts or pipes. The failure was detected and the tube was plugged. Also were plugged those tubes with wall thickness

  19. 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.

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

    KAUST Repository

    Viterbo, David; Michoud, Gregoire; Mosbach, Valentine; Dujon, Bernard; Richard, Guy-Franck

    2016-01-01

    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.

  1. A method for the calculation of the cumulative failure probability distribution of complex repairable systems

    International Nuclear Information System (INIS)

    Caldarola, L.

    1976-01-01

    A method is proposed for the analytical evaluation of the cumulative failure probability distribution of complex repairable systems. The method is based on a set of integral equations each one referring to a specific minimal cut set of the system. Each integral equation links the unavailability of a minimal cut set to its failure probability density distribution and to the probability that the minimal cut set is down at the time t under the condition that it was down at time t'(t'<=t). The limitations for the applicability of the method are also discussed. It has been concluded that the method is applicable if the process describing the failure of a minimal cut set is a 'delayed semi-regenerative process'. (Auth.)

  2. A real-time expert system for self-repairing flight control

    Science.gov (United States)

    Gaither, S. A.; Agarwal, A. K.; Shah, S. C.; Duke, E. L.

    1989-01-01

    An integrated environment for specifying, prototyping, and implementing a self-repairing flight-control (SRFC) strategy is described. At an interactive workstation, the user can select paradigms such as rule-based expert systems, state-transition diagrams, and signal-flow graphs and hierarchically nest them, assign timing and priority attributes, establish blackboard-type communication, and specify concurrent execution on single or multiple processors. High-fidelity nonlinear simulations of aircraft and SRFC systems can be performed off-line, with the possibility of changing SRFC rules, inference strategies, and other heuristics to correct for control deficiencies. Finally, the off-line-generated SRFC can be transformed into highly optimized application-specific real-time C-language code. An application of this environment to the design of aircraft fault detection, isolation, and accommodation algorithms is presented in detail.

  3. 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

    , 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...... 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...

  4. Building an adaptive agent to monitor and repair the electrical power system of an orbital satellite

    Science.gov (United States)

    Tecuci, Gheorghe; Hieb, Michael R.; Dybala, Tomasz

    1995-01-01

    Over several years we have developed a multistrategy apprenticeship learning methodology for building knowledge-based systems. Recently we have developed and applied our methodology to building intelligent agents. This methodology allows a subject matter expert to build an agent in the same way in which the expert would teach a human apprentice. The expert will give the agent specific examples of problems and solutions, explanations of these solutions, or supervise the agent as it solves new problems. During such interactions, the agent learns general rules and concepts, continuously extending and improving its knowledge base. In this paper we present initial results on applying this methodology to build an intelligent adaptive agent for monitoring and repair of the electrical power system of an orbital satellite, stressing the interaction with the expert during apprenticeship learning.

  5. Sensitivity analysis of repairable redundant system with switching failure and geometric reneging

    Directory of Open Access Journals (Sweden)

    Chandra Shekhar

    2017-09-01

    Full Text Available This study deals with the performance modeling and reliability analysis of a redundant machining system composed of several functional machines. To analyze the more realistic scenarios, the concepts of switching failure and geometric reneging are included. The time-to-breakdown and repair time of operating and standby machines are assumed to follow the exponential distribution. For the quantitative assessment of the machine interference problem, various performance measures such as mean-time-to-failure, reliability, reneging rate, etc. have been formulated. To show the practicability of the developed model, a numerical illustration has been presented. For the practical justification and validity of the results established, the sensitivity analysis of reliability indices has been presented by varying different system descriptors.

  6. Lethal effects of solar radiation in proficient and deficient bacteria in repair systems

    International Nuclear Information System (INIS)

    Sousa Neto, A. de.

    1980-01-01

    A study of the lethal action of solar radiation on strains of E.coli K12, proficient or deficient in repair systems, as well as the wild type strain gene products are involved in repair of damage induced by solar radiation. The inactivation of the various bacterial strains (normalized to a dose equivalent to radiation at a wavelength 254 nm) suggests that the more energetic wavelengths of the solar spectrum (290-320 nm) could be responsible for the primary damage that occurs in the DNA. The reduction in the shoulder of the survival curve in wild type strains in indicative of induction of sub-lethal damage in this region of the curve. Analysing solar inactivation curves of the bacterial strains (normalised by spore dosimetry) together with those of the same strains irradiated with UV at 254 nm, it was evident that 254 nm is not the ideal wavelength for comparison. This analysis also indicated that in addition to damage to DNA, other factors are involved in the solar radiation inactivation of wild type strains. (author)

  7. An Injury Paradigm to Investigate Central Nervous System Repair in Drosophila

    Science.gov (United States)

    Kato, Kentaro; Hidalgo, Alicia

    2013-01-01

    An experimental method has been developed to investigate the cellular responses to central nervous system (CNS) injury using the fruit-fly Drosophila. Understanding repair and regeneration in animals is a key question in biology. The damaged human CNS does not regenerate, and understanding how to promote the regeneration is one of main goals of medical neuroscience. The powerful genetic toolkit of Drosophila can be used to tackle the problem of CNS regeneration. A lesion to the CNS ventral nerve cord (VNC, equivalent to the vertebrate spinal cord) is applied manually with a tungsten needle. The VNC can subsequently be filmed in time-lapse using laser scanning confocal microscopy for up to 24 hr to follow the development of the lesion over time. Alternatively, it can be cultured, then fixed and stained using immunofluorescence to visualize neuron and glial cells with confocal microscopy. Using appropriate markers, changes in cell morphology and cell state as a result of injury can be visualized. With ImageJ and purposely developed plug-ins, quantitative and statistical analyses can be carried out to measure changes in wound size over time and the effects of injury in cell proliferation and cell death. These methods allow the analysis of large sample sizes. They can be combined with the powerful genetics of Drosophila to investigate the molecular mechanisms underlying CNS regeneration and repair. PMID:23567253

  8. 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.

  9. Availability of K-out-of-N:G systems with non-identical components subject to repair priorities

    International Nuclear Information System (INIS)

    Khatab, A.; Nahas, N.; Nourelfath, M.

    2009-01-01

    In this paper, a K-out-of-N:G system with N categories of components is studied. Each component category is characterized by its own failure and repair rates. There are R repair facilities, and repair priorities are specified between the N non-identical components. An algorithm for automatic construction of the system state transition diagram is presented. The stationary availability of each component and that of the system are evaluated by using a multi-dimensional Markov model. We show how this model can be represented as a network of stochastic automata with state-dependent transitions that can be implemented via generalized tensor (or Kronecker) algebra. For the efficiency assessment, an analog Monte Carlo simulation model is developed. Experiments are then conducted and simulation results are compared to those obtained by the proposed approach

  10. Dynamic reliability assessment and prediction for repairable systems with interval-censored data

    International Nuclear Information System (INIS)

    Peng, Yizhen; Wang, Yu; Zi, YanYang; Tsui, Kwok-Leung; Zhang, Chuhua

    2017-01-01

    The ‘Test, Analyze and Fix’ process is widely applied to improve the reliability of a repairable system. In this process, dynamic reliability assessment for the system has been paid a great deal of attention. Due to instrument malfunctions, staff omissions and imperfect inspection strategies, field reliability data are often subject to interval censoring, making dynamic reliability assessment become a difficult task. Most traditional methods assume this kind of data as multiple normal distributed variables or the missing mechanism as missing at random, which may cause a large bias in parameter estimation. This paper proposes a novel method to evaluate and predict the dynamic reliability of a repairable system subject to interval-censored problem. First, a multiple imputation strategy based on the assumption that the reliability growth trend follows a nonhomogeneous Poisson process is developed to derive the distributions of missing data. Second, a new order statistic model that can transfer the dependent variables into independent variables is developed to simplify the imputation procedure. The unknown parameters of the model are iteratively inferred by the Monte Carlo expectation maximization (MCEM) algorithm. Finally, to verify the effectiveness of the proposed method, a simulation and a real case study for gas pipeline compressor system are implemented. - Highlights: • A new multiple imputation strategy was developed to derive the PDF of missing data. • A new order statistic model was developed to simplify the imputation procedure. • The parameters of the order statistic model were iteratively inferred by MCEM. • A real cases study was conducted to verify the effectiveness of the proposed method.

  11. 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.

  12. Joint optimisation of spare part inventory, maintenance frequency and repair capacity for k-out-of-N systems

    NARCIS (Netherlands)

    de Smidt-Destombes, Karin S.; van der Heijden, Matthijs C.; van Harten, Aart

    2009-01-01

    To achieve a high system availability at minimal costs, relevant decisions include the choice of preventive maintenance frequency, spare part inventory levels and spare part repair capacity. We develop heuristics for the joint optimisation of these variables for (a) a single k-out-of-N system under

  13. 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.

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

    Science.gov (United States)

    Smith, Catherine E; Mendillo, Marc L; Bowen, Nikki; Hombauer, Hans; Campbell, Christopher S; Desai, Arshad; Putnam, Christopher D; Kolodner, Richard D

    2013-10-01

    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.

  15. Left cardiac chambers reverse remodeling after percutaneous mitral valve repair with the MitraClip system.

    Science.gov (United States)

    Scandura, Salvatore; Ussia, Gian Paolo; Capranzano, Piera; Caggegi, Anna; Sarkar, Kunal; Cammalleri, Valeria; Mangiafico, Sarah; Chiarandà, Marta; Immè, Sebastiano; Di Pasqua, Fabio; Pistritto, Anna Maria; Millan, Giovanni; Tamburino, Corrado

    2012-10-01

    Successful mitral valve surgical repair, decreasing volume overload, has been shown to provide reverse left ventricular (LV) and/or left atrial remodeling in most patients. Percutaneous mitral valve repair with the MitraClip system (Abbott, Abbott Park, IL) has been associated with favorable clinical outcomes in patients with mitral regurgitation at high risk of surgery. However, specific data on left cardiac chambers reverse remodeling after such procedures are limited. This was a prospective observational study of consecutive patients at high risk of surgery, with moderate-to-severe or severe mitral regurgitation undergoing MitraClip system implantation. Follow-up echocardiography was performed at 6 months. The evaluated parameters were the LV end-diastolic and end-systolic volume indexes, LV sphericity index, LV ejection fraction, and left atrial volume index. Reverse LV remodeling was defined as a decrease of 10% in the LV end-diastolic volume index. The study population included 44 patients: 14 with degenerative and 30 with functional mitral regurgitation. At 6 months of follow-up, significant reductions in the median and interquartile range of the sphericity index (from 0.57 [interquartile range 0.54-0.62] to 0.54 [interquartile range 0.50-0.58]; P interquartile range 63.0-102.2] to 60.7 mL/m(2) [50.8-84.4]; P interquartile range 28.2-70.5] to 28.9 mL/m(2) [interquartile range 22.2-55.8]; P interquartile range 30.0-55.0%] to 46.0% [interquartile range 35.0-58.0%]; P < .001) from baseline to 6 months. Minor differences in the left atrial volume index were observed. Reverse remodeling, according to the specified definition, was observed in 77.3% of the patients. The present study reports positive LV reshape effects after mitral valve repair with the MitraClip system, showing significant improvements in LV size and function. Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

  16. Failure mechanism dependence and reliability evaluation of non-repairable system

    International Nuclear Information System (INIS)

    Chen, Ying; Yang, Liu; Ye, Cui; Kang, Rui

    2015-01-01

    Reliability study of electronic system with the physics-of-failure method has been promoted due to the increase knowledge of electronic failure mechanisms. System failure initiates from independent failure mechanisms, have effect on or affect by other failure mechanisms and finally result in system failure. Failure mechanisms in a non-repairable system have many kinds of correlation. One failure mechanism developing to a certain degree will trigger, accelerate or inhibit another or many other failure mechanisms, some kind of failure mechanisms may have the same effect on the failure site, component or system. The destructive effect will be accumulated and result in early failure. This paper presents a reliability evaluation method considering correlativity among failure mechanisms, which includes trigger, acceleration, inhibition, accumulation, and competition. Based on fundamental rule of physics of failure, decoupling methods of these correlations are discussed. With a case, reliability of electronic system is evaluated considering failure mechanism dependence. - Highlights: • Five types of failure mechanism correlations are described. • Decoupling methods of these correlations are discussed. • A reliability evaluation method considering mechanism dependence is proposed. • Results are quite different to results under failure independence assumption

  17. 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.

  18. Propagated failure analysis for non-repairable systems considering both global and selective effects

    International Nuclear Information System (INIS)

    Wang Chaonan; Xing Liudong; Levitin, Gregory

    2012-01-01

    This paper proposes an algorithm for the reliability analysis of non-repairable binary systems subject to competing failure propagation and failure isolation events with both global and selective failure effects. A propagated failure that originates from a system component causes extensive damage to the rest of the system. Global effect happens when the propagated failure causes the entire system to fail; whereas selective effect happens when the propagated failure causes only failure of a subset of system components. In both cases, the failure propagation that originates from some system components (referred to as dependent components) can be isolated because of functional dependence between the dependent components and a component that prevents the failure propagation (trigger components) when the failure of the trigger component happens before the occurrence of the propagated failure. Most existing studies focus on the analysis of propagated failures with global effect. However, in many cases, propagated failures affect only a subset of system components not the entire system. Existing approaches for analyzing propagated failures with selective effect are limited to series-parallel systems. This paper proposes a combinatorial method for the propagated failure analysis considering both global and selective effects as well as the competition with the failure isolation in the time domain. The proposed method is not limited to series-parallel systems and has no limitation on the type of time-to-failure distributions for the system components. The method is verified using the Markov-based method. An example of computer memory systems is analyzed to demonstrate the application of the proposed method.

  19. Peritumoral granulomatous reaction in endometrial carcinoma: association with DNA mismatch repair protein deficiency, particularly loss of PMS2 expression.

    Science.gov (United States)

    Stewart, Colin J R; Pearn, Amy; Pachter, Nicholas; Tan, Adeline

    2018-04-30

    The observation of peritumoral granulomatous reactions (PGRs) in two endometrial carcinomas (ECs) with a PMS2-deficient/MLH1-intact expression pattern led us to investigate whether PGRs in EC were specifically associated with DNA mismatch repair (MMR) protein deficiency, particularly PMS2 loss. Hysterectomy specimens from 22 MMR protein-intact and 54 MMR protein-deficient ECs were reviewed with specific attention to the presence of a PGR and a tumour-associated lymphoid reaction [including tumour-infiltrating lymphocytes (TILs) and stromal lymphoid infiltrates]. The MMR protein-deficient ECs included 22 cases with combined MLH1/PMS2 loss, 11 with combined MSH2/MSH6 loss, 11 with isolated MSH6 loss, and 10 with PMS2 loss but intact MLH1 staining (including the two 'index' cases). Overall, PGRs were identified in seven of 54 (13%) MMR protein-deficient ECs, five of which showed a PMS2-deficient/MLH1-intact immunophenotype; three of these patients had germline PMS2 mutations and one additional patient had a germline MSH6 mutation. None of the MMR protein-intact tumours showed a PGR. Although five of the seven PGR-positive ECs had a high-grade histological component, six were stage I. Most ECs with PGRs also showed TILs and stromal lymphoid reactions, similarly to MMR protein-deficient ECs in general. MMR protein-deficient ECs, particularly those with PMS2 loss, occasionally show PGRs in addition to stromal lymphoid infiltrates and TILs. Therefore, PGRs could be considered to constitute a histological prompt for consideration of Lynch syndrome. The potential prognostic significance of PGRs in EC requires further study. © 2018 John Wiley & Sons Ltd.

  20. 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...

  1. The on-line repair, improvement and expansion of a working multicomputer control system for the CERN SPS accelerator

    International Nuclear Information System (INIS)

    Altaber, J.; Beck, F.; Collins, M.; Crowley-Milling, M.C.; Rausch, R.

    1979-01-01

    The 400 GeV proton synchrotron at CERN was first commissioned in 1976. Those of its features which are pertinent to the design of the control system are summarized. The paper then proceeds as follows: changes to the control system (changes to applications programs, equipment handling routines, system software changes); hardware increases and repairs; changes to the character of the system (hardware changes, microprocessors); conclusions. (U.K.)

  2. A novel measles outbreak control strategy in the Netherlands in 2013-2014 using a national electronic immunization register: A study of early MMR uptake and its determinants.

    Science.gov (United States)

    Nic Lochlainn, Laura M; Woudenberg, Tom; van Lier, Alies; Zonnenberg, Irmgard; Philippi, Marvin; de Melker, Hester E; Hahné, Susan J M

    2017-10-13

    During a large measles outbreak in the Netherlands in 2013-2014, infants aged 6-14months living in municipalities with low (<90%) measles-mumps-rubella (MMR) coverage were individually invited for an early MMR using the national electronic immunization register, Præventis. We estimated uptake of early MMR prior to and during the 2013-2014 outbreak and assessed determinants for early MMR vaccination. We obtained vaccination records from Præventis, and defined early MMR as vaccination before 415days (13months) of age. A multi-level multivariable logistic regression model, restricted to infants with three diphtheria-pertussis-tetanus-polio (DPTP) vaccinations was used to examine the association between early MMR uptake and sex, parents' country of birth, socioeconomic status (SES; at postcode level) and voting proportions for the Reformed Political Party (SGP; at municipal level), used as a proxy for religious objections towards vaccination. In the 29 municipalities with low MMR coverage, uptake of early MMR was 0.5-2.2% prior to the outbreak. Between July 2013 and March 2014, 5,800 (57%) invited infants received an early MMR. Among infants with three DPTP, 70% received an early MMR. Only 1% of infants without prior DPTP received an early MMR. Lower early MMR uptake was associated with a higher SGP voter-ship (OR 0.89 per 5% increase, 95%CI 0.83-0.96), parents' with unknown country of birth (OR 0.66 95%CI 0.47-0.93) and compared with very high SES, high SES had significantly lower early MMR uptake (OR 0.66 95%CI 0.50-0.87). This is the first study describing use of Præventis during an outbreak and to assess determinants of early MMR uptake. More than half of invited infants obtained an early MMR. SES, parents' with unknown country of birth and religious objections towards vaccination were found to be associated with lower early MMR uptake. In future outbreaks, these determinants could be used to tailor intervention strategies. Copyright © 2017. Published by

  3. 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

  4. In vitro Repair of Oxidative DNA Damage by Human Nucleotide Excision Repair System: Possible Explanation for Neurodegeneration in Xeroderma Pigmentosum Patients

    Science.gov (United States)

    Reardon, Joyce T.; Bessho, Tadayoshi; Kung, Hsiang Chuan; Bolton, Philip H.; Sancar, Aziz

    1997-08-01

    Xeroderma pigmentosum (XP) patients fail to remove pyrimidine dimers caused by sunlight and, as a consequence, develop multiple cancers in areas exposed to light. The second most common sign, present in 20-30% of XP patients, is a set of neurological abnormalities caused by neuronal death in the central and peripheral nervous systems. Neural tissue is shielded from sunlight-induced DNA damage, so the cause of neurodegeneration in XP patients remains unexplained. In this study, we show that two major oxidative DNA lesions, 8-oxoguanine and thymine glycol, are excised from DNA in vitro by the same enzyme system responsible for removing pyrimidine dimers and other bulky DNA adducts. Our results suggest that XP neurological disease may be caused by defective repair of lesions that are produced in nerve cells by reactive oxygen species generated as by-products of an active oxidative metabolism.

  5. Inhibition of colorectal cancer genomic copy number alterations and chromosomal fragile site tumor suppressor FHIT and WWOX deletions by DNA mismatch repair

    Science.gov (United States)

    Gelincik, Ozkan; Blecua, Pedro; Edelmann, Winfried; Kucherlapati, Raju; Zhou, Kathy; Jasin, Maria; Gümüş, Zeynep H.; Lipkin, Steven M.

    2017-01-01

    Homologous recombination (HR) enables precise DNA repair after DNA double strand breaks (DSBs) using identical sequence templates, whereas homeologous recombination (HeR) uses only partially homologous sequences. Homeologous recombination introduces mutations through gene conversion and genomic deletions through single-strand annealing (SSA). DNA mismatch repair (MMR) inhibits HeR, but the roles of mammalian MMR MutL homologues (MLH1, PMS2 and MLH3) proteins in HeR suppression are poorly characterized. Here, we demonstrate that mouse embryonic fibroblasts (MEFs) carrying Mlh1, Pms2, and Mlh3 mutations have higher HeR rates, by using 7,863 uniquely mapping paired direct repeat sequences (DRs) in the mouse genome as endogenous gene conversion and SSA reporters. Additionally, when DSBs are induced by gamma-radiation, Mlh1, Pms2 and Mlh3 mutant MEFs have higher DR copy number alterations (CNAs), including DR CNA hotspots previously identified in mouse MMR-deficient colorectal cancer (dMMR CRC). Analysis of The Cancer Genome Atlas CRC data revealed that dMMR CRCs have higher genome-wide DR HeR rates than MMR proficient CRCs, and that dMMR CRCs have deletion hotspots in tumor suppressors FHIT/WWOX at chromosomal fragile sites FRA3B and FRA16D (which have elevated DSB rates) flanked by paired homologous DRs and inverted repeats (IR). Overall, these data provide novel insights into the MMR-dependent HeR inhibition mechanism and its role in tumor suppression. PMID:29069730

  6. 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

  7. 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

  8. Mismatch repair deficiency: a temozolomide resistance factor in medulloblastoma cell lines that is uncommon in primary medulloblastoma tumours

    NARCIS (Netherlands)

    von Bueren, A. O.; Bacolod, M. D.; Hagel, C.; Heinimann, K.; Fedier, A.; Kordes, U.; Pietsch, T.; Koster, J.; Grotzer, M. A.; Friedman, H. S.; Marra, G.; Kool, M.; Rutkowski, S.

    2012-01-01

    BACKGROUND: Tumours are responsive to temozolomide (TMZ) if they are deficient in O-6-methylguanine-DNA methyltransferase (MGMT), and mismatch repair (MMR) proficient. METHODS: The effect of TMZ on medulloblastoma (MB) cell killing was analysed with clonogenic survival assays. Expression of DNA

  9. Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer.

    Science.gov (United States)

    Wilczak, Waldemar; Rashed, Semin; Hube-Magg, Claudia; Kluth, Martina; Simon, Ronald; Büscheck, Franziska; Clauditz, Till Sebastian; Grupp, Katharina; Minner, Sarah; Tsourlakis, Maria Christina; Möller-Koop, Christina; Graefen, Markus; Adam, Meike; Haese, Alexander; Wittmer, Corinna; Sauter, Guido; Izbicki, Jakob Robert; Huland, Hartwig; Schlomm, Thorsten; Steurer, Stefan; Krech, Till; Lebok, Patrick

    2017-01-01

    DNA mismatch repair (MMR) is integral to the maintenance of genetic stability. We aimed to evaluate the clinical impact of MMR gene expression in prostate cancer. The MMR genes MSH6, MLH1 and PMS2 were analyzed by immunohistochemistry on a tissue microarray containing 11152 prostate cancer specimens. Results were compared with ETS-related gene status and deletions of PTEN, 3p13, 5q21 and 6q15. MSH6, MLH1 and PMS2 expression was detectable in 89.5%, 85.4% and 85.0% of cancers and was particularly strong in cancers with advanced pathological tumor stage (P < 0.0001 each), high Gleason grade (P < 0.0001 each), nodal metastasis (P ≤ 0.0083) and early biochemical recurrence (P < 0.0001). High levels of MMR gene expression paralleled features of genetic instability, such as the number of genomic deletions per cancer; strong expression of all three MMR genes was found in 24%, 29%, 30%, 33% and 42% of cancers with no, one, two, three or four to five deletions (P < 0.0001). The prognostic value of the analyzed MMR genes was largely driven by the subset of cancers lacking ERG fusion (P < 0.0001), while the prognostic impact of MMR gene overexpression was only marginal in ERG-positive cancers. Multivariate analyses suggested an independent prognostic relevance of MMR genes in ERG-negative prostate cancers when compared with prognostic parameters available at the time of initial biopsy. In conclusion, MMR overexpression is common in prostate cancer and is linked to poor outcome as well as features indicating genetic instability. ERG fusion should be analyzed along with MMR gene expression in potential clinical tests. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. 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.

  11. Real-Time Multifault Rush Repairing Strategy Based on Utility Theory and Multiagent System in Distribution Networks

    Directory of Open Access Journals (Sweden)

    Zhao Hao

    2016-01-01

    Full Text Available The problem of multifault rush repair in distribution networks (DNs is a multiobjective dynamic combinatorial problem with topology constraints. The problem consists of archiving an optimal faults’ allocation strategy to squads and an admissible multifault rush repairing strategy with coordinating switch operations. In this article, the utility theory is introduced to solve the first problem and a new discrete bacterial colony chemotaxis (DBCC algorithm is proposed for the second problem to determine the optimal sequence for each squad to repair faults and the corresponding switch operations. The above solution is called the two-stage approach. Additionally, a double mathematical optimization model based on the fault level is proposed in the second stage to minimize the outage loss and total repairing time. The real-time adjustment multiagent system (RA-MAS is proposed to provide facility to achieve online multifault rush repairing strategy in DNs when there are emergencies after natural disasters. The two-stage approach is illustrated with an example from a real urban distribution network and the simulation results show the effectiveness of the two-stage approach.

  12. DNA Mismatch Repair Deficiency Promotes Genomic Instability in a Subset of Papillary Thyroid Cancers.

    Science.gov (United States)

    Javid, Mahsa; Sasanakietkul, Thanyawat; Nicolson, Norman G; Gibson, Courtney E; Callender, Glenda G; Korah, Reju; Carling, Tobias

    2018-02-01

    Efficient DNA damage repair by MutL-homolog DNA mismatch repair (MMR) enzymes, MLH1, MLH3, PMS1 and PMS2, are required to maintain thyrocyte genomic integrity. We hypothesized that persistent oxidative stress and consequent transcriptional dysregulation observed in thyroid follicles will lead to MMR deficiency and potentiate papillary thyroid tumorigenesis. MMR gene expression was analyzed by targeted microarray in 18 papillary thyroid cancer (PTC), 9 paracarcinoma normal thyroid (PCNT) and 10 normal thyroid (NT) samples. The findings were validated by qRT-PCR, and in follicular thyroid cancers (FTC) and follicular thyroid adenomas (FTA) for comparison. FOXO transcription factor expression was also analyzed. Protein expression was assessed by immunohistochemistry. Genomic integrity was evaluated by whole-exome sequencing-derived read-depth analysis and Mann-Whitney U test. Clinical correlations were assessed using Fisher's exact and t tests. Microarray and qRT-PCR revealed reduced expression of all four MMR genes in PTC compared with PCNT and of PMS2 compared with NT. FTC and FTA showed upregulation in MLH1, MLH3 and PMS2. PMS2 protein expression correlated with the mRNA expression pattern. FOXO1 showed lower expression in PMS2-deficient PTCs (log2-fold change -1.72 vs. -0.55, U = 11, p clinical characteristics. MMR deficiency, potentially promoted by FOXO1 suppression, may explain the etiology for PTC development in some patients. FTC and FTA retain MMR activity and are likely caused by a different tumorigenic pathway.

  13. On the interaction between maintenance, spare part inventories and repair capacity for a k-out-of-N-system with wear-out

    NARCIS (Netherlands)

    de Smidt-Destombes, Karin S.; van der Heijden, Matthijs C.; van Harten, Aart

    2006-01-01

    In this paper we consider a k-out-of-N system with identical, repairable components under a condition-based maintenance policy. Maintenance consists of replacing all failed and/or aged components. Next, the replaced components have to be repaired. The system availability can be controlled by the

  14. On the interaction between maintenance, spare part inventories and repair capacity for a k-out-of-N system with wear-out

    NARCIS (Netherlands)

    Smidt-Destombes, K.S. de; Heijden, M.C. van der; Harten, A. van

    2006-01-01

    In this paper we consider a k-out-of-N system with identical, repairable components under a condition-based maintenance policy. Maintenance consists of replacing all failed and/or aged components. Next, the replaced components have to be repaired. The system availability can be controlled by the

  15. 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…

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

    NARCIS (Netherlands)

    Nandoe Tewarie, 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

  17. 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.

  18. Elevated levels of the mismatch repair protein PMS2 are associated with prostate cancer.

    Science.gov (United States)

    Norris, Alixanna M; Woodruff, R D; D'Agostino, Ralph B; Clodfelter, Jill E; Scarpinato, Karin Drotschmann

    2007-02-01

    Defects in mismatch repair (MMR) proteins have been identified in various types of cancer. However, an association with prostate cancer has been controversial. Defective MMR results in genome instability with detrimental consequences that significantly contribute to tumorigenesis. This study determined alterations in key MMR protein levels in prostate cancer with the goal to identify prognostic markers. Prostatectomy samples were immunohistochemically stained and the relative presence or absence of key proteins MSH2, MLH1, and PMS2 determined. Cancer tissue of distinct grades was compared with the normal surrounding tissue. Microsatellite instability (MSI) in altered tissues was determined according to NCI guidelines. In contrast to reports that associate a lack of individual MMR proteins with tumorigenesis, a significant increase in PMS2 levels was identified in PIN lesions and prostate cancer tissue. This elevation in PMS2 was independent of changes in levels in its heterodimeric partner, MLH1. Prostate tumors with elevated levels of PMS2 were genetically unstable, which was corrected by MLH1 co-elevation. This is the first documentation of detrimental consequences associated with the increase in a MMR protein in human cancer. This study recognizes PMS2 elevation as a prognostic marker in pre-neoplastic and prostate cancer lesions. This result has significant implications for future diagnostic and treatment measures. (c) 2006 Wiley-Liss, Inc.

  19. MULTI-AGENT APPROACH TO BUILDING AN INTELLIGENT VEHICLE MAINTENANCE AND REPAIR SYSTEM

    Directory of Open Access Journals (Sweden)

    V. Pavlenko

    2017-12-01

    Full Text Available To ensure the reliability of the car, early detection and prevention of the occurrence and development of failures is required in order to reduce the costs of maintenance and repair. Multi-agent technologies make it possible to raise the level of technical reliability of cars and minimize the costs of performing repair and maintenance operations.

  20. 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

    BACKGROUND: Most patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival. OBJECTIVE AND DESIGN......%, 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...

  1. Multipurpose expert-robot system model for control, diagnosis, maintenance, and repairs at the steam generators of the NPP

    International Nuclear Information System (INIS)

    Popa, I.

    1994-01-01

    The paper presents the model concept for a multipurpose expert-robot system for control, diagnosis, forecast, maintenance, and repairs at the steam generators of CANDU type nuclear power plants. The system has two separate parts: the expert system and the robot (manipulator) system. These parts compose a hierarchic structure with the expert system on the upper level. The expert system has a blackboard architecture, to which tree interfaces with the robot system, with the control system of the NPP and with the methods and techniques of control, maintenance and repairs system of the steam generator are added. Due to complex nature of its activities the expert-robot system model combines the deterministic type reasons with probabilistic, fuzzy, and neural-networks type ones. The information that enter the expert system comes from the robot system, from process, from user, and human expert. The information that enter robot system comes from the expert system, from the human operator (when connected) and from process. Control maintenance and repair operations take place by means of the robot system that can be monitored either directly by the expert system or by the human operator who follows its activity. All these activities are performed in parallel with the adequate information of the expert system directly, by the human operator, about the status parameters and, possibly, operating parameters of the steam generator components. The expert-robot system can work independently, but it can be connected and integrated in the control system of NPP, to take over and develop some of its functions. The activities concerning diagnosis and characterization of the state of steam generator components subsequent to control, as well as the forecast of their future behavior, are performed by means of the expert system. Due to these characteristics the expert-robot system can be used successfully in personnel training activities. (Author)

  2. 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.

  3. Single-Molecule Methods for Nucleotide Excision Repair: Building a System to Watch Repair in Real Time

    OpenAIRE

    Kong, Muwen; Beckwitt, Emily C.; Springall, Luke; Kad, Neil M.; Van Houten, Bennett

    2017-01-01

    Single-molecule approaches to solving biophysical problems are powerful tools that allow static and dynamic real-time observations of specific molecular interactions of interest in the absence of ensemble-averaging effects. Here, we provide detailed protocols for building an experimental system that employs atomic force microscopy and a single-molecule DNA tightrope assay based on oblique angle illumination fluorescence microscopy. Together with approaches for engineering site-specific lesion...

  4. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1978-01-01

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

  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. NAXE Mutations Disrupt the Cellular NAD(P)HX Repair System and Cause a Lethal Neurometabolic Disorder of Early Childhood.

    Science.gov (United States)

    Kremer, Laura S; Danhauser, Katharina; Herebian, Diran; Petkovic Ramadža, Danijela; Piekutowska-Abramczuk, Dorota; Seibt, Annette; Müller-Felber, Wolfgang; Haack, Tobias B; Płoski, Rafał; Lohmeier, Klaus; Schneider, Dominik; Klee, Dirk; Rokicki, Dariusz; Mayatepek, Ertan; Strom, Tim M; Meitinger, Thomas; Klopstock, Thomas; Pronicka, Ewa; Mayr, Johannes A; Baric, Ivo; Distelmaier, Felix; Prokisch, Holger

    2016-10-06

    To safeguard the cell from the accumulation of potentially harmful metabolic intermediates, specific repair mechanisms have evolved. APOA1BP, now renamed NAXE, encodes an epimerase essential in the cellular metabolite repair for NADHX and NADPHX. The enzyme catalyzes the epimerization of NAD(P)HX, thereby avoiding the accumulation of toxic metabolites. The clinical importance of the NAD(P)HX repair system has been unknown. Exome sequencing revealed pathogenic biallelic mutations in NAXE in children from four families with (sub-) acute-onset ataxia, cerebellar edema, spinal myelopathy, and skin lesions. Lactate was elevated in cerebrospinal fluid of all affected individuals. Disease onset was during the second year of life and clinical signs as well as episodes of deterioration were triggered by febrile infections. Disease course was rapidly progressive, leading to coma, global brain atrophy, and finally to death in all affected individuals. NAXE levels were undetectable in fibroblasts from affected individuals of two families. In these fibroblasts we measured highly elevated concentrations of the toxic metabolite cyclic-NADHX, confirming a deficiency of the mitochondrial NAD(P)HX repair system. Finally, NAD or nicotinic acid (vitamin B3) supplementation might have therapeutic implications for this fatal disorder. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    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 γ-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 γ-type. Increase in the number of spontaneous and γ-induced mutations of virus was noted according to degree of passage of fibroblasts

  9. Application of a System-Based Inventory Model to Marine Corps Repairable Parts

    National Research Council Canada - National Science Library

    Barnett, Craig

    2001-01-01

    ... isolation of the inventories and because of mathematical flaws in the Marine Corps' sparing methodology The Marine Corps is seeking to centralize the management of secondary repairables and is considering...

  10. The effect of caffeine on repair systems in oocytes of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Mendelson, D.

    1976-01-01

    Genetic analysis was performed to locate the factors involved in the defective repair mechanism in the oocytes of Ubx e 4 /Payne ca females. The results demonstrate that at least three third-chromosome factors may be involved in the control of maternal repair, the two most effective ones being located on the right arm of the third chromosome, one near the Ubx locus and the other near the ca locus

  11. DNA repair genes

    International Nuclear Information System (INIS)

    Morimyo, Mitsuoki

    1995-01-01

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

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

    International Nuclear Information System (INIS)

    Li, Xiaopeng; Li, Mo; Song, Gangbing

    2015-01-01

    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. (paper)

  13. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. 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.

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

    International Nuclear Information System (INIS)

    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

  16. Immunohistochemical null-phenotype for mismatch repair proteins in colonic carcinoma associated with concurrent MLH1 hypermethylation and MSH2 somatic mutations.

    Science.gov (United States)

    Wang, Tao; Stadler, Zsofia K; Zhang, Liying; Weiser, Martin R; Basturk, Olca; Hechtman, Jaclyn F; Vakiani, Efsevia; Saltz, Lenard B; Klimstra, David S; Shia, Jinru

    2018-04-01

    Microsatellite instability, a well-established driver pathway in colorectal carcinogenesis, can develop in both sporadic and hereditary conditions via different molecular alterations in the DNA mismatch repair (MMR) genes. MMR protein immunohistochemistry (IHC) is currently widely used for the detection of MMR deficiency in solid tumors. The IHC test, however, can show varied staining patterns, posing challenges in the interpretation of the staining results in some cases. Here we report a case of an 80-year-old female with a colonic adenocarcinoma that exhibited an unusual "null" IHC staining pattern with complete loss of all four MMR proteins (MLH1, MSH2, MSH6, and PMS2). This led to subsequent MLH1 methylation testing and next generation sequencing which demonstrated that the loss of all MMR proteins was associated with concurrent promoter hypermethylation of MLH1 and double somatic truncating mutations in MSH2. These molecular findings, in conjunction with the patient's age being 80 years and the fact that the patient had no personal or family cancer history, indicated that the MMR deficiency was highly likely sporadic in nature. Thus, the stringent Lynch syndrome type surveillance programs were not recommended to the patient and her family members. This case illustrates a rare but important scenario where a null IHC phenotype signifies complex underlying molecular alternations that bear clinical management implications, highlighting the need for recognition and awareness of such unusual IHC staining patterns.

  17. Improving the Repair Planning System for Mining Equipment on the Basis of Non-destructive Evaluation Data

    Science.gov (United States)

    Drygin, Michael; Kuryshkin, Nicholas

    2017-11-01

    The article tells about forming a new concept of scheduled preventive repair system of the equipment at coal mining enterprises, based on the use of modem non-destructive evaluation methods. The approach to the solution for this task is based on the system-oriented analysis of the regulatory documentation, non-destructive evaluation methods and means, experimental studies with compilation of statistics and subsequent grapho-analytical analysis. The main result of the work is a feasible explanation of using non-destructive evaluation methods within the current scheduled preventive repair system, their high efficiency and the potential of gradual transition to condition-based maintenance. In practice wide use of nondestructive evaluation means w;ill allow to reduce significantly the number of equipment failures and to repair only the nodes in pre-accident condition. Considering the import phase-out policy, the solution for this task will allow to adapt the SPR system to Russian market economy conditions and give the opportunity of commercial move by reducing the expenses for maintenance of Russian-made and imported equipment.

  18. Dependability estimation for non-Markov consecutive-k-out-of-n: F repairable systems by fast simulation

    International Nuclear Information System (INIS)

    Xiao Gang; Li Zhizhong; Li Ting

    2007-01-01

    A model of consecutive-k-out-of-n: F repairable system with non-exponential repair time distribution and (k-1)-step Markov dependence is introduced in this paper along with algorithms of three Monte Carlo methods, i.e. importance sampling, conditional expectation estimation and combination of the two methods, to estimate dependability of the non-Markov model including reliability, transient unavailability, MTTF, and MTBF. A numerical example is presented to demonstrate the efficiencies of above methods. The results show that combinational method has the highest efficiency for estimation of unreliability and unavailability, while conditional expectation estimation is the most efficient method for estimation of MTTF and MTBF. Conditional expectation estimation seems to have overall higher speedups in estimating dependability of such systems

  19. 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.

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

    International Nuclear Information System (INIS)

    Shakib-Manesh, T.E.; Hirvonen, K.O.; Jalava, K.J.; Ålander, T.; Kuitunen, M.T.

    2014-01-01

    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

  1. Selected technological problems of repair of hydraulic drive systems for shearer loaders with the example of A2V-107 pumps and SHT-630W motors

    Energy Technology Data Exchange (ETDEWEB)

    Kusak, E.; Paluch, J.

    1983-07-01

    Major elements of hydraulic drive systems as well as their wear and repair characteristics are described. Types of wear and standardized repair methods are comparatively evaluated. The evaluations are aimed at development of standardized procedures for use in large repair shops. The following stages of repair operations of A2V-107 pumps and SHT-630W motors are analyzed: disassembling hydraulic systems, washing and cleaning, classification of equipment elements (elements for scrapping and for regeneration), regeneration, assembling and final tests. The following regeneration methods are discussed: cutting, burnishing, bushing (e.g. the Heli Coil method), regeneration using copper, tin or zinc dusts and a temperature from 950 to 1,000 K under inert atmosphere, heat treatments. Methods are reviewed for comparative evaluations of repair efficiency and repair quality as well as documents used for recording repair in the shops. Economic aspects of using standardized procedures for repair of hydraulic equipment for shearer loaders are discussed and recommendations are made. (6 refs.)

  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. PMS2 gene mutation results in DNA mismatch repair system failure in a case of adult granulosa cell tumor

    OpenAIRE

    Wang, Wen-Chung; Lee, Ya-Ting; Lai, Yen-Chein

    2017-01-01

    Background Granulosa cell tumors are rare ovarian malignancies. Their characteristics include unpredictable indolent growth with malignant potential and late recurrence. Approximately 95% are of adult type. Recent molecular studies have characterized the FOXL2 402C?>?G mutation in adult granulosa cell tumor. Our previous case report showed that unique FOXL2 402C?>?G mutation and defective DNA mismatch repair system are associated with the development of adult granulosa cell tumor. Findings In...

  4. The human cyclin B1 protein modulates sensitivity of DNA mismatch repair deficient prostate cancer cell lines to alkylating agents.

    Science.gov (United States)

    Rasmussen, L J; Rasmussen, M; Lützen, A; Bisgaard, H C; Singh, K K

    2000-05-25

    DNA damage caused by alkylating agents results in a G2 checkpoint arrest. DNA mismatch repair (MMR) deficient cells are resistant to killing by alkylating agents and are unable to arrest the cell cycle in G2 phase after alkylation damage. We investigated the response of two MMR-deficient prostate cancer cell lines DU145 and LNCaP to the alkylating agent MNNG. Our studies reveal that DU145 cancer cells are more sensitive to killing by MNNG than LNCaP. Investigation of the underlying reasons for lower resistance revealed that the DU145 cells contain low endogenous levels of cyclin B1. We provide direct evidence that the endogenous level of cyclin B1 modulates the sensitivity of MMR-deficient prostate cancer cells to alkylating agents.

  5. Repair of X-ray-induced single-strand breaks by a cell-free system

    International Nuclear Information System (INIS)

    Seki, Shuji; Ikeda, Shogo; Tsutui, Ken; Teraoka, Hirobumi

    1990-01-01

    Repair of X-ray-induced single-strand breaks of DNA was studied in vitro using an exonuclease purified from mouse ascites sarcoma (SR-C3H/He) cells. X-ray-dose-dependent unscheduled DNA synthesis was primed by the exonuclease. Repair of X-ray-induced single-strand breaks in pUC19 plasmid DNA was demonstrated by agarose gel electrophoresis after incubating the damaged DNA with the exonuclease, DNA polymerase (Klenow fragment of DNA polymerase I or DNA polymerase β purified from SR-C3H/He cells), four deoxynucleoside triphosphates, ATP and DNA ligase (T4 DNA ligase or DNA ligase I purified from calf thymus). The present results suggested that the exonuclease is involved in the initiation of repair of X-ray-induced single-strand breaks in removing 3' ends of X-ray-damaged DNA. (author)

  6. Role for cER and Mmr1p in anchorage of mitochondria at sites of polarized surface growth in budding yeast.

    Science.gov (United States)

    Swayne, Theresa C; Zhou, Chun; Boldogh, Istvan R; Charalel, Joseph K; McFaline-Figueroa, José Ricardo; Thoms, Sven; Yang, Christine; Leung, Galen; McInnes, Joseph; Erdmann, Ralf; Pon, Liza A

    2011-12-06

    Mitochondria accumulate at neuronal and immunological synapses and yeast bud tips and associate with the ER during phospholipid biosynthesis, calcium homeostasis, and mitochondrial fission. Here we show that mitochondria are associated with cortical ER (cER) sheets underlying the plasma membrane in the bud tip and confirm that a deletion in YPT11, which inhibits cER accumulation in the bud tip, also inhibits bud tip anchorage of mitochondria. Time-lapse imaging reveals that mitochondria are anchored at specific sites in the bud tip. Mmr1p, a member of the DSL1 family of tethering proteins, localizes to punctate structures on opposing surfaces of mitochondria and cER sheets underlying the bud tip and is recovered with isolated mitochondria and ER. Deletion of MMR1 impairs bud tip anchorage of mitochondria without affecting mitochondrial velocity or cER distribution. Deletion of the phosphatase PTC1 results in increased Mmr1p phosphorylation, mislocalization of Mmr1p, defects in association of Mmr1p with mitochondria and ER, and defects in bud tip anchorage of mitochondria. These findings indicate that Mmr1p contributes to mitochondrial inheritance as a mediator of anchorage of mitochondria to cER sheets in the yeast bud tip and that Ptc1p regulates Mmr1p phosphorylation, localization, and function. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Outcomes of Endovascular Aneurysm Repair using the Ovation Stent Graft System in Adverse Anatomy.

    Science.gov (United States)

    Greaves, Nicholas S; Moore, Aiden; Seriki, Dare; Ghosh, Jonathan

    2018-04-01

    The aim was the evaluation of mid-term efficacy and safety outcome measures for the Ovation (Endologix, Santa Rosa, CA, USA) stent graft system in the management of infrarenal abdominal aortic aneurysms (iAAA) with adverse anatomy. A retrospective observational study of all patients undergoing elective iAAA repair was carried out from 2012 to 2017 using Ovation Prime or iX stent grafts with a minimum of 3 months follow-up at a single UK vascular centre. Post-operative surveillance involved computed tomography scans at 3 months and 1 year, with duplex ultrasound yearly thereafter. Outcome measures were established with retrospective analysis of pre- and post-operative imaging, and included peri-operative mortality, major adverse events, limb complications, aneurysm diameter change, and endoleak rates. All patients were within Ovation instructions for use (IFU), and assessment was made to determine whether aneurysms had anatomical features considered adverse for other commonly used stent graft platforms. Ovation stent grafts were implanted in 52 patients (79% male, mean age 75.7 years) with a mean aneurysm diameter of 62.5 mm (range 55-107 mm). There was 100% technical deployment success. The 30 day mortality was 0% and there was no aneurysm related mortality during follow-up (median 24 months, range 3-48 months). There were no type I or III endoleaks, but 19% developed type II endoleaks with one patient requiring re-intervention. No iliac limb occlusions were identified but one case required relining for limb kinking. All 52 cases were within the IFU for Ovation but only 12% met the IFU criteria for the Cook and Medtronic devices. The mid-term experience with Ovation demonstrates safe, durable treatment of iAAAs, including those with unfavourable anatomy, frequently off IFU for other commonly used devices. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

  8. The effect of caffeine on repair systems in oocytes of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Mendelson, D.

    1976-01-01

    Irradiated males were mated to females that had received treatment with caffeine or honey (by feeding), and the frequencies of sex-chromosome losses and chromosome rearrangements induced in mature spermatozoa of the males were compared. Caffeine treatment led to an enhancement of the frequencies of sex-chromosome loss and a decrease in those of rearrangements. These findings can be interpreted on the assumption that caffeine inhibits repair and misrepair processes that are active in the oocytes. Caffeine treatment administered to one of the female stocks used in these studies was without any effect, presumably because of the absence of a caffeine-sensitive repair mechanism in the oocytes

  9. Pitfalls in molecular analysis for mismatch repair deficiency in a family with biallelic pms2 germline mutations.

    Science.gov (United States)

    Leenen, C H M; Geurts-Giele, W R R; Dubbink, H J; Reddingius, R; van den Ouweland, A M; Tops, C M J; van de Klift, H M; Kuipers, E J; van Leerdam, M E; Dinjens, W N M; Wagner, A

    2011-12-01

    Heterozygous germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause Lynch syndrome. Biallelic mutations in the MMR genes are associated with a childhood cancer syndrome [constitutional mismatch repair deficiency (CMMR-D)]. This is predominantly characterized by hematological malignancies and tumors of the bowel and brain, often associated with signs of neurofibromatosis type 1 (NF1). Diagnostic strategies for selection of patients for MMR gene analysis include analysis of microsatellite instability (MSI) and immunohistochemical (IHC) analysis of MMR proteins in tumor tissue. We report the clinical characterization and molecular analyses of tumor specimens from a family with biallelic PMS2 germline mutations. This illustrates the pitfalls of present molecular screening strategies. Tumor tissues of five family members were analyzed for MSI and IHC. MSI was observed in only one of the analyzed tissues. However, IHC analysis of brain tumor tissue of the index patient and his sister showed absence of PMS2 expression, and germline mutation analyses showed biallelic mutations in PMS2: p.Ser46IIe and p.Pro246fs. The same heterozygous mutations were confirmed in the father and mother, respectively. These data support the conclusion that in case of a clinical phenotype of CMMR-D, it is advisable to routinely combine MSI analysis with IHC analysis for the expression of MMR proteins. With inconclusive or conflicting results, germline mutation analysis of the MMR genes should be considered after thorough counselling of the patients and/or their relatives. © 2011 John Wiley & Sons A/S.

  10. Simulation based analysis and an application to an offshore oil and gas production system of the Natvig measures of component importance in repairable systems

    International Nuclear Information System (INIS)

    Natvig, Bent; Eide, Kristina A.; Gasemyr, Jorund; Huseby, Arne B.; Isaksen, Stefan L.

    2009-01-01

    In the present paper the Natvig measures of component importance for repairable systems, and its extended version are analyzed for two three-component systems and a bridge system. The measures are also applied to an offshore oil and gas production system. According to the extended version of the Natvig measure a component is important if both by failing it strongly reduces the expected system uptime and by being repaired it strongly reduces the expected system downtime. The results include a study of how different distributions affect the ranking of the components. All numerical results are computed using discrete event simulation. In a companion paper [Huseby AB, Eide KA, Isaksen SL, Natvig B, Gasemyr, J. Advanced discrete event simulation methods with application to importance measure estimation. 2009, submitted for publication] the advanced simulation methods needed in these calculations are described.

  11. 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...

  12. PMS2 gene mutation results in DNA mismatch repair system failure in a case of adult granulosa cell tumor.

    Science.gov (United States)

    Wang, Wen-Chung; Lee, Ya-Ting; Lai, Yen-Chein

    2017-03-27

    Granulosa cell tumors are rare ovarian malignancies. Their characteristics include unpredictable indolent growth with malignant potential and late recurrence. Approximately 95% are of adult type. Recent molecular studies have characterized the FOXL2 402C > G mutation in adult granulosa cell tumor. Our previous case report showed that unique FOXL2 402C > G mutation and defective DNA mismatch repair system are associated with the development of adult granulosa cell tumor. In this study, the DNA sequences of four genes, MSH2, MLH1, MSH6, and PMS2, in the DNA mismatch repair system were determined via direct sequencing to elucidate the exact mechanism for the development of this granulosa cell tumor. The results showed that two missense germline mutations, T485K and N775L, inactivate the PMS2 gene. The results of this case study indicated that although FOXL2 402C > G mutation determines the development of granulosa cell tumor, PMS2 mutation may be the initial driver of carcinogenesis. Immunohistochemistry-based tumor testing for mismatch repair gene expression may be necessary for granulosa cell tumors to determine their malignant potential or if they are part of Lynch syndrome.

  13. Endoscopic augmentation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease: Multicenter study of the gatekeeper reflux repair system

    NARCIS (Netherlands)

    Fockens, P.; Bruno, M. J.; Gabbrielli, A.; Odegaard, S.; Hatlebakk, J.; Allescher, H. D.; Rösch, T.; Rhodes, M.; Bastid, C.; Rey, J.; Boyer, J.; Muehldorffer, S.; van den Hombergh, U.; Costamagna, G.

    2004-01-01

    Background and Study Aims: The safety and effectiveness of the Gatekeeper Reflux Repair System (Medtronic Europe, Tolochenaz, Switzerland) in the treatment of gastroesophageal reflux disease (GERD) was evaluated. This new, reversible treatment modality involves the endoscopic introduction of

  14. 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.

  15. 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.

  16. Analysis of CO2 draining in the supercritical subchannel of an MMR reactor using CFD techniques

    International Nuclear Information System (INIS)

    Dutra, Carolina S.B.; Ribeiro, Felipe P.; Su, Jian

    2017-01-01

    This work aims to analyze the steady state thermal hydraulic behavior of the supercritical CO 2 by means of the computational modeling of the triangular arrangement subchannel of the KAIST MMR (Korea Advanced Institute of Science and Technology). The mathematical model is composed of Navier-Stokes equations of Reynolds average (RANS), with the model of turbulence k-omega SST (Shear Stress Transport) for the fluid refrigerant in the subchannel and the heat conduction equation for the fuel and coating. The thermodynamic properties of CO 2 are implemented from National Institute of Standards and Technology (NIST) data. The transport equations were solved using a commercial CFD (Fluid Dynamics) tool, ANSYS FLUENT. Initially, a geometric model was constructed, using the ICEM software, composed of fuel, interstice, coating, refrigerant and two adiabatic regions of the fuel rod. The numerical solution used was validated by simulation of a simpler vertical circular tube and by comparisons with numerical and experimental results available in the literature. Using these results, we performed the mesh convergence study and initialized the simulations in the subchannel

  17. Clustered DNA lesions containing 5-formyluracil and AP site: repair via the BER system.

    Directory of Open Access Journals (Sweden)

    Ekaterina A Belousova

    Full Text Available Lesions in the DNA arise under ionizing irradiation conditions or various chemical oxidants as a single damage or as part of a multiply damaged site within 1-2 helical turns (clustered lesion. Here, we explored the repair opportunity of the apurinic/apyrimidinic site (AP site composed of the clustered lesion with 5-formyluracil (5-foU by the base excision repair (BER proteins. We found, that if the AP site is shifted relative to the 5-foU of the opposite strand, it could be repaired primarily via the short-patch BER pathway. In this case, the cleavage efficiency of the AP site-containing DNA strand catalyzed by human apurinic/apyrimidinic endonuclease 1 (hAPE1 decreased under AP site excursion to the 3'-side relative to the lesion in the other DNA strand. DNA synthesis catalyzed by DNA polymerase lambda was more accurate in comparison to the one catalyzed by DNA polymerase beta. If the AP site was located exactly opposite 5-foU it was expected to switch the repair to the long-patch BER pathway. In this situation, human processivity factor hPCNA stimulates the process.

  18. Complex catalysts from self-repairing ensembles to highly reactive air-based oxidation systems

    Science.gov (United States)

    Craig L. Hill; Laurent Delannoy; Dean C. Duncan; Ira A. Weinstock; Roman F. Renneke; Richard S. Reiner; Rajai H. Atalla; Jong Woo Han; Daniel A. Hillesheim; Rui Cao; Travis M. Anderson; Nelya M. Okun; Djamaladdin G. Musaev; Yurii V. Geletii

    2007-01-01

    Progress in four interrelated catalysis research efforts in our laboratory are summarized: (1) catalytic photochemical functionalization of unactivated CeH bonds by polyoxometalates (POMs); (2) self-repairing catalysts; (3) catalysts for air-based oxidations under ambient conditions; and (4) terminal oxo complexes of the late-transition metal elements and their...

  19. The development of remote repairing system, decontamination and in-cell remote inspection equipment

    International Nuclear Information System (INIS)

    Ishibashi, Yuzo; Toyoda, Osamu; Haginoya, Isao; Yamamoto, Ryuichi; Tanaka, Yasumasa

    1993-01-01

    PNC has been developing remote repair and inspection technologies for in-cell components in reprocessing Plants. In this report, several remote technologies such as remote dismantling and removal, decontamination, remote pipe maintenance and remote in-cell inspection equipment are described. (author)

  20. Crystal structure and DNA-binding property of the ATPase domain of bacterial mismatch repair endonuclease MutL from Aquifex aeolicus.

    Science.gov (United States)

    Fukui, Kenji; Iino, Hitoshi; Baba, Seiki; Kumasaka, Takashi; Kuramitsu, Seiki; Yano, Takato

    2017-09-01

    DNA mismatch repair (MMR) system corrects mismatched bases that are generated mainly by DNA replication errors. The repair system excises the error-containing single-stranded region and enables the re-synthesis of the strand. In the early reactions of MMR, MutL endonuclease incises the newly-synthesized/error-containing strand of the duplex to initiate the downstream excision reaction. MutL endonuclease consists of the N-terminal ATPase and C-terminal endonuclease domains. In this study, we report the crystal structure of the ATPase domain of MutL endonuclease from Aquifex aeolicus. The overall structure of the domain was similar to those of human MutL homologs and Escherichia coli MutL, although E. coli MutL has no endonuclease activity. The ATPase domain was comprised of two subdomains: the N-terminal ATP-binding subdomain and the C-terminal α-β sandwich subdomain. Site-directed mutagenesis experiment identified DNA-interacting eight basic amino acid residues, which were distributed across both the two subdomains and formed a DNA-binding cleft. Docking simulation between the structures of the ATPase and endonuclease domains generated a reliable model structure for the full-length A. aeolicus MutL, which satisfies our previous result of small-angle X-ray scattering analysis. On the basis of the model structure and further experimental results, we concluded that the two separate DNA-binding sites in the full-length A. aeolicus MutL simultaneously bind a dsDNA molecule. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. DNA repair in human cells

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  2. Reflex test reminders in required cancer synoptic templates decrease order entry error: An analysis of mismatch repair immunohistochemical orders to screen for Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Mark R Kilgore

    2016-01-01

    Full Text Available Background: Endometrial carcinoma (EC is the most common extracolonic malignant neoplasm associated with Lynch syndrome (LS. LS is caused by autosomal dominant germline mutations in DNA mismatch repair (MMR genes. Screening for LS in EC is often evaluated by loss of immunohistochemical (IHC expression of DNA MMR enzymes MLH1, MSH2, MSH6, and PMS2 (MMR IHC. In July 2013, our clinicians asked that we screen all EC in patients ≤60 for loss of MMR IHC expression. Despite this policy, several cases were not screened or screening was delayed. We implemented an informatics-based approach to ensure that all women who met criteria would have timely screening. Subjects and Methods: Reports are created in PowerPath (Sunquest Information Systems, Tucson, AZ with custom synoptic templates. We implemented an algorithm on March 6, 2014 requiring pathologists to address MMR IHC in patients ≤60 with EC before sign out (S/O. Pathologists must answer these questions: is patient ≤60 (yes/no, if yes, follow-up questions (IHC done previously, ordered with addendum to follow, results included in report, N/A, or not ordered, if not ordered, one must explain. We analyzed cases from July 18, 2013 to August 31, 2016 preimplementation (PreImp and postimplementation (PostImp that met criteria. Data analysis was performed using the standard data package included with GraphPad Prism® 7.00 (GraphPad Software, Inc., La Jolla, CA, USA. Results: There were 147 patients who met criteria (29 PreImp and 118 PostImp. IHC was ordered in a more complete and timely fashion PostImp than PreImp. PreImp, 4/29 (13.8% cases did not get any IHC, but PostImp, only 4/118 (3.39% were missed (P = 0.0448. Of cases with IHC ordered, 60.0% (15/25 were ordered before or at S/O PreImp versus 91.2% (104/114 PostImp (P = 0.0004. Relative to day of S/O, the mean days of order delay were longer and more variable PreImp versus PostImp (12.9 ± 40.7 vs. -0.660 ± 1.15; P = 0.0227, with the average

  3. Reflex test reminders in required cancer synoptic templates decrease order entry error: An analysis of mismatch repair immunohistochemical orders to screen for Lynch syndrome.

    Science.gov (United States)

    Kilgore, Mark R; McIlwain, Carrie A; Schmidt, Rodney A; Norquist, Barbara M; Swisher, Elizabeth M; Garcia, Rochelle L; Rendi, Mara H

    2016-01-01

    Endometrial carcinoma (EC) is the most common extracolonic malignant neoplasm associated with Lynch syndrome (LS). LS is caused by autosomal dominant germline mutations in DNA mismatch repair (MMR) genes. Screening for LS in EC is often evaluated by loss of immunohistochemical (IHC) expression of DNA MMR enzymes MLH1, MSH2, MSH6, and PMS2 (MMR IHC). In July 2013, our clinicians asked that we screen all EC in patients ≤60 for loss of MMR IHC expression. Despite this policy, several cases were not screened or screening was delayed. We implemented an informatics-based approach to ensure that all women who met criteria would have timely screening. Reports are created in PowerPath (Sunquest Information Systems, Tucson, AZ) with custom synoptic templates. We implemented an algorithm on March 6, 2014 requiring pathologists to address MMR IHC in patients ≤60 with EC before sign out (S/O). Pathologists must answer these questions: is patient ≤60 (yes/no), if yes, follow-up questions (IHC done previously, ordered with addendum to follow, results included in report, N/A, or not ordered), if not ordered, one must explain. We analyzed cases from July 18, 2013 to August 31, 2016 preimplementation (PreImp) and postimplementation (PostImp) that met criteria. Data analysis was performed using the standard data package included with GraphPad Prism ® 7.00 (GraphPad Software, Inc., La Jolla, CA, USA). There were 147 patients who met criteria (29 PreImp and 118 PostImp). IHC was ordered in a more complete and timely fashion PostImp than PreImp. PreImp, 4/29 (13.8%) cases did not get any IHC, but PostImp, only 4/118 (3.39%) were missed ( P = 0.0448). Of cases with IHC ordered, 60.0% (15/25) were ordered before or at S/O PreImp versus 91.2% (104/114) PostImp ( P = 0.0004). Relative to day of S/O, the mean days of order delay were longer and more variable PreImp versus PostImp (12.9 ± 40.7 vs. -0.660 ± 1.15; P = 0.0227), with the average being before S/O PostImp. This algorithm

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

    Science.gov (United States)

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

    2017-03-01

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

  5. Development and applications of Bacillus subtilis test systems for mutagens, involving DNA-repair deficiency and suppressible auxotrophic mutations

    International Nuclear Information System (INIS)

    Tanooka, H.

    1977-01-01

    A mutagen-tester of Bacillus subtilis was constructed and tested with known carcinogens. The parental strain HA101 of Okubo and Yanagida carrying suppressible nonsense mutations in his and met genes was transformed to carry an excision-repair deficiency mutation. The constructed strain TKJ5211 showed a 20-30-fold higher sensitivity for His + reversion than the parental strain when treated with UV and UV-mimetic chemicals but unchanged mutation frequency with X-rays and methyl methanesulfonate. The tester strain was used in a spot test of 30 selected chemicals and also for testing with liver homogenate activation. The results showed an almost equivalent but somewhat broader detection spectrum than the Salmonella typhimurium TA100 system. Another test method used a pair of B. subtilis strains differing in their DNA-repair capacity, i.e. the most UV-sensitive mutant HJ-15 and a wild-type strain, to detect repair-dependent DNA damage produced by chemicals. Spores could be used in either test

  6. The Influence of Hepatitis C Virus Therapy on the DNA Base Excision Repair System of Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    Czarny, Piotr; Merecz-Sadowska, Anna; Majchrzak, Kinga; Jabłkowski, Maciej; Szemraj, Janusz; Śliwiński, Tomasz; Karwowski, Bolesław

    2017-07-01

    Hepatitis C virus (HCV) can infect extrahepatic tissues, including lymphocytes, creating reservoir of the virus. Moreover, HCV proteins can interact with DNA damage response proteins of infected cells. In this article we investigated the influence of the virus infection and a new ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) anti-HCV therapy on the PBMCs (peripheral blood mononuclear cells, mainly lymphocytes) DNA base excision repair (BER) system. BER protein activity was analyzed in the nuclear and mitochondrial extracts (NE and ME) of PBMC isolated from patients before and after therapy, and from subjects without HCV, using modeled double-strand DNA, with 2'-deoxyuridine substitution as the DNA damage. The NE and ME obtained from patients before therapy demonstrated lower efficacy of 2'-deoxyuridine removal and DNA repair polymerization than those of the control group or patients after therapy. Moreover, the extracts from the patients after therapy had similar activity to those from the control group. However, the efficacy of apurinic/apyrimidinic site excision in NE did not differ between the studied groups. We postulate that infection of lymphocytes by the HCV can lead to a decrease in the activity of BER enzymes. However, the use of novel therapy results in the improvement of glycosylase activity as well as the regeneration of endonuclease and other crucial repair enzymes.

  7. Discrete event simulation methods applied to advanced importance measures of repairable components in multistate network flow systems

    International Nuclear Information System (INIS)

    Huseby, Arne B.; Natvig, Bent

    2013-01-01

    Discrete event models are frequently used in simulation studies to model and analyze pure jump processes. A discrete event model can be viewed as a system consisting of a collection of stochastic processes, where the states of the individual processes change as results of various kinds of events occurring at random points of time. We always assume that each event only affects one of the processes. Between these events the states of the processes are considered to be constant. In the present paper we use discrete event simulation in order to analyze a multistate network flow system of repairable components. In order to study how the different components contribute to the system, it is necessary to describe the often complicated interaction between component processes and processes at the system level. While analytical considerations may throw some light on this, a simulation study often allows the analyst to explore more details. By producing stable curve estimates for the development of the various processes, one gets a much better insight in how such systems develop over time. These methods are particulary useful in the study of advanced importancez measures of repairable components. Such measures can be very complicated, and thus impossible to calculate analytically. By using discrete event simulations, however, this can be done in a very natural and intuitive way. In particular significant differences between the Barlow–Proschan measure and the Natvig measure in multistate network flow systems can be explored

  8. Autism Narratives in Media Coverage of the MMR Vaccine-Autism Controversy under a Crip Futurism Framework.

    Science.gov (United States)

    Mann, Benjamin W

    2018-03-09

    While previous studies in health communication have examined online news media regarding autism, there is a lack of research that critically examines how such media representations may stigmatize autism and seeks to eliminate the condition, particularly in the context of the resurging measles, mumps, and rubella (MMR) vaccine-autism controversy. To address this gap in the literature, this study analyzes 153 articles that engage the MMR vaccine-autism controversy from the top 10 online news sources in the U.S. from September 2015 through July 2017. It draws from Kafer's (2013) work in Feminist, Crip, Queer, using a lens of crip futurism to interpret three major narrative themes: a death and survival narrative that purports autism as a worst-case scenario, a societal problem narrative, and a preventative narrative that seeks to eliminate the condition. These themes suggest that online news media narratives about autism surrounding the autism-MMR controversy play into stereotypes about autism, including stigmatization and prioritization of preventive behaviors and cures over supporting the lived experiences of autistic individuals. Continued research on the impact of online media portrayals of autism specifically, and disability in health contexts generally, is called for.

  9. 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

  10. Prevalence of adenomas and hyperplastic polyps in mismatch repair mutation carriers among CAPP2 participants: report by the colorectal adenoma/carcinoma prevention programme 2

    DEFF Research Database (Denmark)

    Liljegren, Annelie; Barker, Gail; Elliott, Faye

    2008-01-01

    PURPOSE: To determine the prevalence of adenomatous and hyperplastic polyps in a large cohort of individuals with a germline mutation in a mismatch repair (MMR) gene, the major genetic determinant of hereditary nonpolyposis colorectal cancer (HNPCC). These prevalences have been estimated previously...... in smaller studies, and the results have been found to be variable. PATIENTS AND METHODS: Colorectal Adenoma/Carcinoma Prevention Programme 2 trial is a chemoprevention trial in people classified as having HNPCC. The 695 patients with a proven germline MMR mutation and documented screening history before...

  11. Frameshift mutational target gene analysis identifies similarities and differences in constitutional mismatch repair-deficiency and Lynch syndrome.

    Science.gov (United States)

    Maletzki, Claudia; Huehns, Maja; Bauer, Ingrid; Ripperger, Tim; Mork, Maureen M; Vilar, Eduardo; Klöcking, Sabine; Zettl, Heike; Prall, Friedrich; Linnebacher, Michael

    2017-07-01

    Mismatch-repair deficient (MMR-D) malignancies include Lynch Syndrome (LS), which is secondary to germline mutations in one of the MMR genes, and the rare childhood-form of constitutional mismatch repair-deficiency (CMMR-D); caused by bi-allelic MMR gene mutations. A hallmark of LS-associated cancers is microsatellite instability (MSI), characterized by coding frameshift mutations (cFSM) in target genes. By contrast, tumors arising in CMMR-D patients are thought to display a somatic mutation pattern differing from LS. This study has the main goal to identify cFSM in MSI target genes relevant in CMMR-D and to compare the spectrum of common somatic mutations, including alterations in DNA polymerases POLE and D1 between LS and CMMR-D. CMMR-D-associated tumors harbored more somatic mutations compared to LS cases, especially in the TP53 gene and in POLE and POLD1, where novel mutations were additionally identified. Strikingly, MSI in classical mononucleotide markers BAT40 and CAT25 was frequent in CMMR-D cases. MSI-target gene analysis revealed mutations in CMMR-D-associated tumors, some of them known to be frequently hit in LS, such as RNaseT2, HT001, and TGFβR2. Our results imply a general role for these cFSM as potential new drivers of MMR-D tumorigenesis. © 2017 Wiley Periodicals, Inc.

  12. The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA during mismatch repair

    Science.gov (United States)

    Plys, Aaron J.; Rogacheva, Maria V.; Greene, Eric C.; Alani, Eric

    2012-01-01

    DNA mismatch repair (MMR) models have proposed that MSH proteins identify DNA polymerase errors while interacting with the DNA replication fork. MLH proteins (primarily Mlh1-Pms1 in baker’s yeast) then survey the genome for lesion-bound MSH proteins. The resulting MSH-MLH complex formed at a DNA lesion initiates downstream steps in repair. MLH proteins act as dimers and contain long (20 – 30 nanometers) unstructured arms that connect two terminal globular domains. These arms can vary between 100 to 300 amino acids in length, are highly divergent between organisms, and are resistant to amino acid substitutions. To test the roles of the linker arms in MMR, we engineered a protease cleavage site into the Mlh1 linker arm domain of baker’s yeast Mlh1-Pms1. Cleavage of the Mlh1 linker arm in vitro resulted in a defect in Mlh1-Pms1 DNA binding activity, and in vivo proteolytic cleavage resulted in a complete defect in MMR. We then generated a series of truncation mutants bearing Mlh1 and Pms1 linker arms of varying lengths. This work revealed that MMR is greatly compromised when portions of the Mlh1 linker are removed, whereas repair is less sensitive to truncation of the Pms1 linker arm. Purified complexes containing truncations in Mlh1 and Pms1 linker arms were analyzed and found to have differential defects in DNA binding that also correlated with the ability to form a ternary complex with Msh2-Msh6 and mismatch DNA. These observations are consistent with the unstructured linker domains of MLH proteins providing distinct interactions with DNA during MMR. PMID:22659005

  13. Disparities in health system input between minority and non-minority counties and their effects on maternal mortality in Sichuan province of western China.

    Science.gov (United States)

    Ren, Yan; Qian, Ping; Duan, Zhanqi; Zhao, Ziling; Pan, Jay; Yang, Min

    2017-09-29

    The maternal mortality rate (MMR) markedly decreased in China, but there has been a significant imbalance among different geographic regions (east, central and west regions), and the mortality in the western region remains high. This study aims to examine how much disparity in the health system and MMR between ethnic minority and non-minority counties exists in Sichuan province of western China and measures conceivable commitments of the health system determinants of the disparity in MMR. The MMR and health system data of 67 minority and 116 non-minority counties were taken from Sichuan provincial official sources. The 2-level Poisson regression model was used to identify health system determinants. A series of nested models with different health system factors were fitted to decide contribution of each factor to the disparity in MMR. The MMR decreased over the last decade, with the fastest declining rate from 2006 to 2010. The minority counties experienced higher raw MMR in 2002 than non-minority counties (94.4 VS. 58.2), which still remained higher in 2014 (35.7 VS. 14.3), but the disparity of raw MMR between minority and non-minority counties decreased from 36.2 to 21.4. The better socio-economic condition, more health human resources and higher maternal health care services rate were associated with lower MMR. Hospital delivery rate alone explained 74.5% of the difference in MMR between minority and non-minority counties. All health system indicators together explained 97.6% of the ethnic difference in MMR, 59.8% in the change trend, and 66.3% county level variation respectively. Hospital delivery rate mainly determined disparity in MMR between minority and non-minority counties in Sichuan province. Increasing hospital birth rates among ethnic minority counties may narrow the disparity in MMR by more than two-thirds of the current level.

  14. 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.

  15. Functional role of DNA mismatch repair gene PMS2 in prostate cancer cells.

    Science.gov (United States)

    Fukuhara, Shinichiro; Chang, Inik; Mitsui, Yozo; Chiyomaru, Takeshi; Yamamura, Soichiro; Majid, Shahana; Saini, Sharanjot; Deng, Guoren; Gill, Ankurpreet; Wong, Darryn K; Shiina, Hiroaki; Nonomura, Norio; Lau, Yun-Fai C; Dahiya, Rajvir; Tanaka, Yuichiro

    2015-06-30

    DNA mismatch repair (MMR) enzymes act as proofreading complexes that maintains genomic integrity and MMR-deficient cells show an increased mutation rate. MMR has also been shown to influence cell signaling and the regulation of tumor development. MMR consists of various genes and includes post-meiotic segregation (PMS) 2 which is a vital component of mutL-alpha. In prostate, the functional role of this gene has never been reported and in this study, our aim was to investigate the effect of PMS2 on growth properties of prostate cancer (PCa) cells. Previous studies have shown PMS2 to be deficient in DU145 cells and this lack of expression was confirmed by Western blotting whereas normal prostatic PWR-1E and RWPE-1 cells expressed this gene. PMS2 effects on various growth properties of DU145 were then determined by creating stable gene transfectants. Interestingly, PMS2 caused decreased cell proliferation, migration, invasion, and in vivo growth; and increased apoptosis as compared to vector control. We further analyzed genes affected by PMS2 expression and observe the apoptosis-related TMS1 gene to be significantly upregulated whereas anti-apoptotic BCL2A1 was downregulated. These results demonstrate a functional role for PMS2 to protect against PCa progression by enhancing apoptosis of PCa cells.

  16. Complex relationship between mismatch repair proteins and MBD4 during immunoglobulin class switch recombination.

    Science.gov (United States)

    Grigera, Fernando; Bellacosa, Alfonso; Kenter, Amy L

    2013-01-01

    Mismatch repair (MMR) safeguards against genomic instability and is required for efficient Ig class switch recombination (CSR). Methyl CpG binding domain protein 4 (MBD4) binds to MutL homologue 1 (MLH1) and controls the post-transcriptional level of several MMR proteins, including MutS homologue 2 (MSH2). We show that in WT B cells activated for CSR, MBD4 is induced and interacts with MMR proteins, thereby implying a role for MBD4 in CSR. However, CSR is in the normal range in Mbd4 deficient mice deleted for exons 2-5 despite concomitant reduction of MSH2. We show by comparison in Msh2(+/-) B cells that a two-fold reduction of MSH2 and MBD4 proteins is correlated with impaired CSR. It is therefore surprising that CSR occurs at normal frequencies in the Mbd4 deficient B cells where MSH2 is reduced. We find that a variant Mbd4 transcript spanning exons 1,6-8 is expressed in Mbd4 deficient B cells. This transcript can be ectopically expressed and produces a truncated MBD4 peptide. Thus, the 3' end of the Mbd4 locus is not silent in Mbd4 deficient B cells and may contribute to CSR. Our findings highlight a complex relationship between MBD4 and MMR proteins in B cells and a potential reconsideration of their role in CSR.

  17. 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

  18. Molecular dialogs 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

    2014-04-01

    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 dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke. Published by Elsevier Ltd.

  19. 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

  20. Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudia Maletzki

    Full Text Available BACKGROUND: Colorectal cancer (CRC represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs. Pre-clinical in vitro models representing molecular features of MMR-D tumors are thus mandatory for identifying biomarkers that finally help to predict responses towards new cytostatic drugs. Here, we describe the successful establishment and characterization of three patient-derived MMR-D cell lines (HROC24, HROC87, and HROC113 along with their corresponding xenografts. METHODOLOGY: MMR-D cell lines (HROC24, HROC87, and HROC113 were established from a total of ten clinicopathological well-defined MMR-D cases (120 CRC cases in total. Cells were comprehensively characterized by phenotype, morphology, growth kinetics, invasiveness, and molecular profile. Additionally, response to clinically relevant chemotherapeutics was examined in vitro and in vivo. PRINCIPAL FINDINGS: Two MMR-D lines showing CIMP-H derived from sporadic CRC (HROC24: K-ras(wt, B-raf(mut, HROC87: K-ras(wt, B-raf(mut, whereas the HROC113 cell line (K-ras(mut, B-raf(wt was HNPCC-associated. A diploid DNA-status could be verified by flow cytometry and SNP Array analysis. All cell lines were characterized as epithelial (EpCAM(+ tumor cells, showing surface tumor marker expression (CEACAM(+. MHC-class II was inducible by Interferon-γ stimulation. Growth kinetics as well as invasive potential was quite heterogeneous between individual lines. Besides, MMR-D cell lines exhibited distinct responsiveness towards chemotherapeutics, even when comparing in vitro and in vivo sensitivity. CONCLUSIONS: These newly established and well-characterized, low-passage MMR-D cell lines provide a useful tool for future investigations on the

  1. Application of Rapid Prototyping Technique and Intraoperative Navigation System for the Repair and Reconstruction of Orbital Wall Fractures

    Science.gov (United States)

    Cha, Jong Hyun; Lee, Yong Hae; Ruy, Wan Chul; Roe, Young; Moon, Myung Ho

    2016-01-01

    Background Restoring the orbital cavity in large blow out fractures is a challenge for surgeons due to the anatomical complexity. This study evaluated the clinical outcomes and orbital volume after orbital wall fracture repair using a rapid prototyping (RP) technique and intraoperative navigation system. Methods This prospective study was conducted on the medical records and radiology records of 12 patients who had undergone a unilateral blow out fracture reconstruction using a RP technique and an intraoperative navigation system from November 2014 to March 2015. The surgical results were assessed by an ophthalmic examination and a comparison of the preoperative and postoperative orbital volume ratio (OVR) values. Results All patients had a successful treatment outcome without complications. Volumetric analysis revealed a significant decrease in the mean OVR from 1.0952±0.0662 (ranging from 0.9917 to 1.2509) preoperatively to 0.9942±0.0427 (ranging from 0.9394 to 1.0680) postoperatively. Conclusion The application of a RP technique for the repair of orbital wall fractures is a useful tool that may help improve the clinical outcomes by understanding the individual anatomy, determining the operability, and restoring the orbital cavity volume through optimal implant positioning along with an intraoperative navigation system. PMID:28913272

  2. SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

    Science.gov (United States)

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

    2013-01-01

    Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for an organism's favorable response to alkylating agents. Furthermore, an individual's response to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity. PMID:22237395

  3. Meningocele repair

    Science.gov (United States)

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

  4. Incorrect modeling of the failure process of minimally repaired systems under random conditions: The effect on the maintenance costs

    International Nuclear Information System (INIS)

    Pulcini, Gianpaolo

    2015-01-01

    This note investigates the effect of the incorrect modeling of the failure process of minimally repaired systems that operates under random environmental conditions on the costs of a periodic replacement maintenance. The motivation of this paper is given by a recently published paper, where a wrong formulation of the expected cost for unit time under a periodic replacement policy is obtained. This wrong formulation is due to the incorrect assumption that the intensity function of minimally repaired systems that operate under random conditions has the same functional form as the failure rate of the first failure time. This produced an incorrect optimization of the replacement maintenance. Thus, in this note the conceptual differences between the intensity function and the failure rate of the first failure time are first highlighted. Then, the correct expressions of the expected cost and of the optimal replacement period are provided. Finally, a real application is used to measure how severe can be the economical consequences caused by the incorrect modeling of the failure process.

  5. 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 To assess the therapeutic outcome after endovascular repair of iliac arterial lesions (IALs using a self-expandable Nitinol stent graft system.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.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.Endovascular repair of various IALs with a self-expandable Nitinol stent graft is safe and effective.

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

    Science.gov (United States)

    Bodo, Sahra; Colas, Chrystelle; Buhard, Olivier; Collura, Ada; Tinat, Julie; Lavoine, Noémie; Guilloux, Agathe; Chalastanis, Alexandra; Lafitte, Philippe; Coulet, Florence; Buisine, Marie-Pierre; Ilencikova, Denisa; Ruiz-Ponte, Clara; Kinzel, Miriam; Grandjouan, Sophie; Brems, Hilde; Lejeune, Sophie; Blanché, Hélène; Wang, Qing; Caron, Olivier; Cabaret, Odile; Svrcek, Magali; Vidaud, Dominique; Parfait, Béatrice; Verloes, Alain; Knappe, Ulrich J; Soubrier, Florent; Mortemousque, Isabelle; Leis, Alexander; Auclair-Perrossier, Jessie; Frébourg, Thierry; Fléjou, Jean-François; Entz-Werle, Natacha; Leclerc, Julie; Malka, David; Cohen-Haguenauer, Odile; Goldberg, Yael; Gerdes, Anne-Marie; Fedhila, Faten; Mathieu-Dramard, Michèle; Hamelin, Richard; Wafaa, Badre; Gauthier-Villars, Marion; Bourdeaut, Franck; Sheridan, Eamonn; Vasen, Hans; Brugières, Laurence; Wimmer, Katharina; Muleris, Martine; Duval, Alex

    2015-10-01

    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 or leukemias, and brain tumors. There is no satisfactory method for diagnosis of CMMRD because screens for mutations in MMR genes are noninformative for 30% of patients. MMR-deficient cancer cells are resistant to genotoxic agents and have microsatellite instability (MSI), due to accumulation of errors in repetitive DNA sequences. We investigated whether these features could be used to identify patients with CMMRD. We examined MSI by PCR analysis and tolerance to methylating or thiopurine agents (functional characteristics of MMR-deficient tumor cells) in lymphoblastoid cells (LCs) from 3 patients with CMMRD and 5 individuals with MMR-proficient LCs (controls). Using these assays, we defined experimental parameters that allowed discrimination of a series of 14 patients with CMMRD from 52 controls (training set). We then used the same parameters to assess 23 patients with clinical but not genetic features of CMMRD. In the training set, we identified parameters, based on MSI and LC tolerance to methylation, that detected patients with CMMRD vs controls with 100% sensitivity and 100% specificity. Among 23 patients suspected of having CMMRD, 6 had MSI and LC tolerance to methylation (CMMRD highly probable), 15 had neither MSI nor LC tolerance to methylation (unlikely to have CMMRD), and 2 were considered doubtful for CMMRD based on having only 1 of the 2 features. The presence of MSI and tolerance to methylation in LCs identified patients with CMMRD with 100% sensitivity and specificity. These features could be used in diagnosis of patients. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  7. Evaluation of Heat Removal Performance of Passive Decay Heat Removal system for S-CO{sub 2} Cooled Micro Modular Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Jangsik; Lee, Jeong Ik; Jeong, Yong Hoon [KAIST, Daejeon (Korea, Republic of)

    2015-05-15

    The modular systems is able to be transported by large trailer. Moreover, dry cooling system is applied for waste heat removal. The characteristics of MMR takes wide range of construction area from coast to desert, isolated area and disaster area. In MMR, Passive decay heat removal system (PDHRS) is necessary for taking the advantage on selection of construction area where external support cannot be offered. The PDHRS guarantees to protect MMR without external support. In this research, PDHRS of MMR is introduced and decay heat removal performance is analyzed. The PDHRS guarantees integrity of reactor coolant system. The high level of decay heat (2 MW) can be removed by PDHRS without offsite power.

  8. Passive Decay Heat Removal System Options for S-CO2 Cooled Micro Modular Reactor

    International Nuclear Information System (INIS)

    Moon, Jangsik; Jeong, Yong Hoon; Lee, Jeong Ik

    2014-01-01

    To achieve modularization of whole reactor system, Micro Modular Reactor (MMR) which has been being developed in KAIST took S-CO 2 Brayton power cycle. The S-CO 2 power cycle is suitable for SMR due to high cycle efficiency, simple layout, small turbine and small heat exchanger. These characteristics of S-CO 2 power cycle enable modular reactor system and make reduced system size. The reduced size and modular system motived MMR to have mobility by large trailer. Due to minimized on-site construction by modular system, MMR can be deployed in any electricity demand, even in isolated area. To achieve the objective, fully passive safety systems of MMR were designed to have high reliability when any offsite power is unavailable. In this research, the basic concept about MMR and Passive Decay Heat Removal (PDHR) system options for MMR are presented. LOCA, LOFA, LOHS and SBO are considered as DBAs of MMR. To cope with the DBAs, passive decay heat removal system is designed. Water cooled PDHR system shows simple layout, but has CCF with reactor systems and cannot cover all DBAs. On the other hand, air cooled PDHR system with two-phase closed thermosyphon shows high reliability due to minimized CCF and is able to cope with all DBAs. Therefore, the PDHR system of MMR will follows the air-cooled PDHR system and the air cooled system will be explored

  9. 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.

  10. Radiometric calibration of the reflective bands of NS001-Thematic Mapper Simulator (TMS) and modular multispectral radiometers (MMR)

    Science.gov (United States)

    Markham, Brian L.; Wood, Frank M., Jr.; Ahmad, Suraiya P.

    1988-01-01

    The NS001 Thematic Mapper Simulator scanner (TMS) and several modular multispectral radiometers (MMRs) are among the primary instruments used in the First ISLSCP (International Satellite Land Surface Climatology Project) Field Experiment (FIFE). The NS001 has a continuously variable gain setting. Calibration of the NS001 data is influenced by drift in the dark current level of up to six counts during a mirror scan at typical gain settings. The MMR instruments are being used in their 1 deg FOV configuration on the helicopter and 15 deg FOV on the ground.

  11. Dilemma Program MDGS in Maternal Mortality (MMR and Infant Mortality (IMR Reduction through Jampersal in the District Tuban

    Directory of Open Access Journals (Sweden)

    M. Amir. HT

    2014-03-01

    Full Text Available This study is an implementation program designed Jampersal Mixing Methods approach which is a qualitative study, guided by quantitative figures, to examine in depth a phenomenon that exists in society by not manipulate variables (ex post facto, concerning the events that have been occurred, associated with the present condition of the Jampersal users who switch to JKN implementation managed by BPJS since the beginning of 2014. The goal is to examine the implementation Jampersal program, whether the program is to reach the target with existing funds, as expected Millennium Development Goals (MDGs, in reducing the MMR and IMR in the district Tuban, which will expire in 2015.

  12. DNA repair in neurons: So if they don't divide what's to repair?

    International Nuclear Information System (INIS)

    Fishel, Melissa L.; Vasko, Michael R.; Kelley, Mark R.

    2007-01-01

    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 clinical effects

  13. DNA repair

    International Nuclear Information System (INIS)

    Van Zeeland, A.A.

    1984-01-01

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

  14. Method and apparatus for in-system redundant array repair on integrated circuits

    Science.gov (United States)

    Bright, Arthur A.; Crumley, Paul G.; Dombrowa, Marc B.; Douskey, Steven M.; Haring, Rudolf A.; Oakland, Steven F.; Ouellette, Michael R.; Strissel, Scott A.

    2007-12-18

    Disclosed is a method of repairing an integrated circuit of the type comprising of a multitude of memory arrays and a fuse box holding control data for controlling redundancy logic of the arrays. The method comprises the steps of providing the integrated circuit with a control data selector for passing the control data from the fuse box to the memory arrays; providing a source of alternate control data, external of the integrated circuit; and connecting the source of alternate control data to the control data selector. The method comprises the further step of, at a given time, passing the alternate control data from the source thereof, through the control data selector and to the memory arrays to control the redundancy logic of the memory arrays.

  15. Design structure for in-system redundant array repair in integrated circuits

    Science.gov (United States)

    Bright, Arthur A.; Crumley, Paul G.; Dombrowa, Marc; Douskey, Steven M.; Haring, Rudolf A.; Oakland, Steven F.; Quellette, Michael R.; Strissel, Scott A.

    2008-11-25

    A design structure for repairing an integrated circuit during operation of the integrated circuit. The integrated circuit comprising of a multitude of memory arrays and a fuse box holding control data for controlling redundancy logic of the arrays. The design structure provides the integrated circuit with a control data selector for passing the control data from the fuse box to the memory arrays; providing a source of alternate control data, external of the integrated circuit; and connecting the source of alternate control data to the control data selector. The design structure further passes the alternate control data from the source thereof, through the control data selector and to the memory arrays to control the redundancy logic of the memory arrays.

  16. Method and apparatus for in-system redundant array repair on integrated circuits

    Science.gov (United States)

    Bright, Arthur A [Croton-on-Hudson, NY; Crumley, Paul G [Yorktown Heights, NY; Dombrowa, Marc B [Bronx, NY; Douskey, Steven M [Rochester, MN; Haring, Rudolf A [Cortlandt Manor, NY; Oakland, Steven F [Colchester, VT; Ouellette, Michael R [Westford, VT; Strissel, Scott A [Byron, MN

    2008-07-29

    Disclosed is a method of repairing an integrated circuit of the type comprising of a multitude of memory arrays and a fuse box holding control data for controlling redundancy logic of the arrays. The method comprises the steps of providing the integrated circuit with a control data selector for passing the control data from the fuse box to the memory arrays; providing a source of alternate control data, external of the integrated circuit; and connecting the source of alternate control data to the control data selector. The method comprises the further step of, at a given time, passing the alternate control data from the source thereof, through the control data selector and to the memory arrays to control the redundancy logic of the memory arrays.

  17. 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.

  18. Overexpression of the DNA mismatch repair factor, PMS2, confers hypermutability and DNA damage tolerance.

    Science.gov (United States)

    Gibson, Shannon L; Narayanan, Latha; Hegan, Denise Campisi; Buermeyer, Andrew B; Liskay, R Michael; Glazer, Peter M

    2006-12-08

    Inherited defects in genes associated with DNA mismatch repair (MMR) have been linked to familial colorectal cancer. Cells deficient in MMR are genetically unstable and demonstrate a tolerance phenotype in response to certain classes of DNA damage. Some sporadic human cancers also show abnormalities in MMR gene function, typically due to diminished expression of one of the MutL homologs, MLH1. Here, we report that overexpression of the MutL homolog, human PMS2, can also cause a disruption of the MMR pathway in mammalian cells, resulting in hypermutability and DNA damage tolerance. A mouse fibroblast cell line carrying a recoverable lambda phage shuttle vector for mutation detection was transfected with either a vector designed to express hPMS2 or with an empty vector control. Cells overexpressing hPMS2 were found to have elevated spontaneous mutation frequencies at the cII reporter gene locus. They also showed an increase in the level of mutations induced by the alkylating agent, methynitrosourea (MNU). Clonogenic survival assays demonstrated increased survival of the PMS2-overexpressing cells following exposure to MNU, consistent with the induction of a damage tolerance phenotype. Similar results were seen in cells expressing a mutant PMS2 gene, containing a premature stop codon at position 134 and representing a variant found in an individual with familial colon cancer. These results show that dysregulation of PMS2 gene expression can disrupt MMR function in mammalian cells and establish an additional carcinogenic mechanism by which cells can develop genetic instability and acquire resistance to cytotoxic cancer therapies.

  19. [Direct repair of adolescent lumbar spondylolysis using a pedicle screw-laminar hook system by paramedian approach].

    Science.gov (United States)

    Wang, Bin; Tang, Yong-hua; Tang, Hong-chao; Jin, Cai-yi

    2011-08-01

    To discuss the indication and clinical effect of direct repair of adolescent lumbar spondylolysis by screw-laminar hook system. From August 2003 to December 2008, 28 patients (13 males and 15 females,ranging in age from 15 and 26 years, averaged 21.6 years) with lumbar spondylolysis were treated with isthmic bone grafting and internal fixation with a pedicle screw-laminar hook system. Three patients had spondylolysis at L3, L4; 5 patients had spondylolysis at L4, L5; 8 patients had spondylolysis at L4; and 12 patients had spondylolysis at L5. All the patients had low back pain and lasted over 6 months. According to preoperative and postoperative plain radiograph, CT scan and Macnab criteria, the fusion rate and clinical effect of this technique were evaluated. All the patients were followed up with a mean period of 14.9 months, ranging from 9 to 24 months. All the patients had bony union according to the X-rays and CT scan. According to the calculation results of Macnab criteria, 22 patients got an excellent result, 5 good and 1 fair. The direct repair of adolescent lumbar spondylolysis with pedicle screw-laminar hook system can shorten length of operation,decrease blood loss, preserve more posterior structures of spine and avoid iatrogenic instability of spine. The postoperative immediate stability of vertebral segment is acquired and the mobility of adjacent intervertebral discs is reserved. The screw-laminar hook system for the treatment of adolescent spondylolisthesis can get satisfactory clinical results.

  20. 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)

  1. International congress on DNA damage and repair: Book of abstracts

    International Nuclear Information System (INIS)

    1987-01-01

    This document contains the abstracts of 105 papers presented at the Congress. Topics covered include the Escherichia coli nucleotide excision repair system, DNA repair in malignant transformations, defective DNA repair, and gene regulation

  2. Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: report from the constitutional mismatch repair deficiency consortium.

    Science.gov (United States)

    Bakry, Doua; Aronson, Melyssa; Durno, Carol; Rimawi, Hala; Farah, Roula; Alharbi, Qasim Kholaif; Alharbi, Musa; Shamvil, Ashraf; Ben-Shachar, Shay; Mistry, Matthew; Constantini, Shlomi; Dvir, Rina; Qaddoumi, Ibrahim; Gallinger, Steven; Lerner-Ellis, Jordan; Pollett, Aaron; Stephens, Derek; Kelies, Steve; Chao, Elizabeth; Malkin, David; Bouffet, Eric; Hawkins, Cynthia; Tabori, Uri

    2014-03-01

    Constitutional mismatch repair deficiency (CMMRD) is a devastating cancer predisposition syndrome for which data regarding clinical manifestations, molecular screening tools and management are limited. We established an international CMMRD consortium and collected comprehensive clinical and genetic data. Molecular diagnosis of tumour and germline biospecimens was performed. A surveillance protocol was developed and implemented. Overall, 22/23 (96%) of children with CMMRD developed 40 different tumours. While childhood CMMRD related tumours were observed in all families, Lynch related tumours in adults were observed in only 2/14 families (p=0.0007). All children with CMMRD had café-au-lait spots and 11/14 came from consanguineous families. Brain tumours were the most common cancers reported (48%) followed by gastrointestinal (32%) and haematological malignancies (15%). Importantly, 12 (30%) of these were low grade and resectable cancers. Tumour immunohistochemistry was 100% sensitive and specific in diagnosing mismatch repair (MMR) deficiency of the corresponding gene while microsatellite instability was neither sensitive nor specific as a diagnostic tool (psyndrome where family history of cancer may not be contributory. Screening tumours and normal tissues using immunohistochemistry for abnormal expression of MMR gene products may help in diagnosis and early implementation of surveillance for these children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. The food-borne pathogen Campylobacter jejuni depends on the AddAB DNA repair system to defend against bile in the intestinal environment.

    Science.gov (United States)

    Gourley, Christopher R; Negretti, Nicholas M; Konkel, Michael E

    2017-10-31

    Accurate repair of DNA damage is crucial to ensure genome stability and cell survival of all organisms. Bile functions as a defensive barrier against intestinal colonization by pathogenic microbes. Campylobacter jejuni, a leading bacterial cause of foodborne illness, possess strategies to mitigate the toxic components of bile. We recently found that growth of C. jejuni in medium with deoxycholate, a component of bile, caused DNA damage consistent with the exposure to reactive oxygen species. We hypothesized that C. jejuni must repair DNA damage caused by reactive oxygen species to restore chromosomal integrity. Our efforts focused on determining the importance of the putative AddAB DNA repair proteins. A C. jejuni addAB mutant demonstrated enhanced sensitivity to deoxycholate and was impaired in DNA double strand break repair. Complementation of the addAB mutant restored resistance to deoxycholate, as well as function of the DNA double strand break repair system. The importance of these findings translated to the natural host, where the AddAB system was found to be required for efficient C. jejuni colonization of the chicken intestine. This research provides new insight into the molecular mechanism utilized by C. jejuni, and possibly other intestinal pathogens, to survive in the presence of bile.

  4. Minimal access direct spondylolysis repair using a pedicle screw-rod system: a case series

    Directory of Open Access Journals (Sweden)

    Mohi Eldin Mohamed

    2012-11-01

    Full Text Available Abstract Introduction Symptomatic spondylolysis is always challenging to treat because the pars defect causing the instability needs to be stabilized while segmental fusion needs to be avoided. Direct repair of the pars defect is ideal in cases of spondylolysis in which posterior decompression is not necessary. We report clinical results using segmental pedicle-screw-rod fixation with bone grafting in patients with symptomatic spondylolysis, a modification of a technique first reported by Tokuhashi and Matsuzaki in 1996. We also describe the surgical technique, assess the fusion and analyze the outcomes of patients. Case presentation At Cairo University Hospital, eight out of twelve Egyptian patients’ acute pars fractures healed after conservative management. Of those, two young male patients underwent an operative procedure for chronic low back pain secondary to pars defect. Case one was a 25-year-old Egyptian man who presented with a one-year history of axial low back pain, not radiating to the lower limbs, after falling from height. Case two was a 29-year-old Egyptian man who presented with a one-year history of axial low back pain and a one-year history of mild claudication and infrequent radiation to the leg, never below the knee. Utilizing a standardized mini-access fluoroscopically-guided surgical protocol, fixation was established with two titanium pedicle screws place into both pedicles, at the same level as the pars defect, without violating the facet joint. The cleaned pars defect was grafted; a curved titanium rod was then passed under the base of the spinous process of the affected vertebra, bridging the loose fragment, and attached to the pedicle screw heads, to uplift the spinal process, followed by compression of the defect. The patients were discharged three days after the procedure, with successful fusion at one-year follow-up. No rod breakage or implant-related complications were reported. Conclusions Where there is no

  5. 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.

  6. Some areas of reliability technique which have been neglected to some extent - maintainability - human reliability - mechanical reliability - repairable systems

    International Nuclear Information System (INIS)

    Akersten, P.A.

    1985-01-01

    The present thesis consists of four papers, three of which are of a expositary nature and one more theoretical. The first two papers have a natural coupling to the man-machine interface. The first paper is devoted to the concept of maintainability and the role of man as maintenance technician. The second paper discusses aspects of human reliability, mainly studying man as operator. However, maintenance tasks can be studied in the same manner. The third paper concerns reliability prediction for mechanical components. This is an area of vital importance for the reliability practitioner, who needs realistic and easy-to-use mathematical models for different failure modes. The fourth paper discusses mathematical models for repairable systems, especially the problem of testing whether a constant event intensity model is adequate or not. (author)

  7. Repair process and a repaired component

    Energy Technology Data Exchange (ETDEWEB)

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

    2018-02-20

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

  8. 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

  9. Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

    International Nuclear Information System (INIS)

    Conde, João; Silva, Susana N; Azevedo, Ana P; Teixeira, Valdemar; Pina, Julieta Esperança; Rueff, José; Gaspar, Jorge F

    2009-01-01

    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. 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). 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. 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

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

    Science.gov (United States)

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

    2015-11-03

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

  11. The role of the HCR system in the repair of lethal lesions of Bacillus subtilis phages and their transfecting DNA damaged by radiation and alkylating agents

    International Nuclear Information System (INIS)

    Vizdalova, M.; Janovska, E.; Zhestyanikov, V.D.

    1980-01-01

    The role of the HCR system in the repair of prelethal lesions induced by UV light, γ radiation and alkylating agents was studied in the Bacillus subtilis SPP1 phage, its heat sensitive mutants (N3, N73 nad ts 1 ) and corresponding infectious DNA. The survival of phages and their transfecting DNA after treatment with UV light is substantially higher in hcr + cells than in hcr cells, the differences being more striking in intact phages than in their transfecting DNA's. Repair inhibitors reduce survival in hcr + cells: caffeine lowers the survival of UV-irradiated phage SPP1 in exponentially growing hcr + cells but has no effect on its survival in competent hcr + cells; acriflavin and ethidium bromide decrease the survival of the UV-irradiated SPP1 phage in both exponentially growing and competent hcr + cells to the level of survival observed in hcr cells; moreover, ethidium bromide lowers the number of infective centres in hcr + cells of the UV-irradiated DNA of the SPP1 phage. Repair inhibitors do not lower the survival of the UV-irradiated phages or their DNA in hcr cells. The repair mechanism under study also effectively repairs lesions induced by polyfunctional alkylating agents in the transfecting DNA's of B. subtilis phages but is not functional with lesions induced by these agents in free phages and lesions caused in the phages and their DNA by ethyl methanesulphonate or γ radiation. (author)

  12. The role of the DNA repair system in increasing the viability of E.coli cells under the action of small UV doses

    International Nuclear Information System (INIS)

    Kuzin, A.M.; Vilenchik, M.M.; Isakov, B.K.; AN Kazakhskoj SSR, Alma-Ata. Inst. Botaniki)

    1976-01-01

    The authors studied the action of the ultraviolet light (UV) on the colony-forming ability of E.coli K12-HCR + cultured in a meat infusion broth in the presence of glucose. An unusual shape of the curve indicates that the number of viable cells increases under the action of low UV doses. The experiment was repeated seven times, and each time the phenomenon was fully asserted (p 0.01). So it was suggested that low UV doses (about 140 erg/mm 2 ) activate the system of dark DNA repair (induction of the synthesis of repair enzymes) which repairs 'spontaneous' DNA defects and increases the number of colony-forming cells. (orig.) [de

  13. Role of the DNA repair system in increasing the viability of E. coli cells under the action of small UV doses

    Energy Technology Data Exchange (ETDEWEB)

    Kuzin, A M; Vilenchik, M M; Isakov, B K [AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki; AN Kazakhskoj SSR, Alma-Ata. Inst. Botaniki)

    1976-12-01

    The authors studied the action of the ultraviolet light (UV) on the colony-forming ability of E.coli K12-HCR/sup +/ cultured in a meat infusion broth in the presence of glucose. An unusual shape of the curve indicates that the number of viable cells increases under the action of low UV doses. The experiment was repeated seven times, and each time the phenomenon was fully asserted (p 0.01). So it was suggested that low UV doses (about 140 erg/mm/sup 2/) activate the system of dark DNA repair (induction of the synthesis of repair enzymes) which repairs 'spontaneous' DNA defects and increases the number of colony-forming cells.

  14. Development of an auto-welding system for CRD nozzle repair welds using a 3D laser vision sensor

    International Nuclear Information System (INIS)

    Park, K.; Kim, Y.; Byeon, J.; Sung, K.; Yeom, C.; Rhee, S.

    2007-01-01

    A control rod device (CRD) nozzle attaches to the hemispherical surface of a reactor head with J-groove welding. Primary water stress corrosion cracking (PWSCC) causes degradation in these welds, which requires that these defect areas be repaired. To perform this repair welding automatically on a complicated weld groove shape, an auto-welding system was developed incorporating a laser vision sensor that measures the 3-dimensional (3D) shape of the groove and a weld-path creation program that calculates the weld-path parameters. Welding trials with a J-groove workpiece were performed to establish a basis for developing this auto-welding system. Because the reactor head is placed on a lay down support, the outer-most region of the CRD nozzle has restricted access. Due to this tight space, several parameters of the design, such as size, weight and movement of the auto-welding system, had to be carefully considered. The cross section of the J-groove weld is basically an oval shape where the included angle of the J-groove ranges from 0 to 57 degrees. To measure the complex shape, we used double lasers coupled to a single charge coupled device (CCD) camera. We then developed a program to generate the weld-path parameters using the measured 3D shape as a basis. The program has the ability to determine the first and final welding positions and to calculate all weld-path parameters. An optimized image-processing algorithm was applied to resolve noise interference and diffused reflection of the joint surfaces. The auto-welding system is composed of a 4-axis manipulator, gas tungsten arc welding (GTAW) power supply, an optimized designed and manufactured GTAW torch and a 3D laser vision sensor. Through welding trials with 0 and 38-degree included-angle workpieces with both J-groove and U-groove weld, the performance of this auto-welding system was qualified for field application

  15. The INNOVATION Trial: four-year safety and effectiveness of the INCRAFT® AAA Stent-Graft System for endovascular repair.

    Science.gov (United States)

    Pratesi, Giovanni; Pratesi, Carlo; Chiesa, Roberto; Coppi, Gioacchino; Scheinert, Dierk; Brunkwall, Jan S; van der Meulen, Stefaan; Torsello, Giovanni

    2017-10-01

    This paper reports the 4-year safety and effectiveness of the INCRAFT® AAA Stent-Graft System (Cordis Corp., Milpitas, CA, USA), an ultra-low-profile device for the treatment of abdominal aortic aneurysms. The INNOVATION Trial is the prospective, first-in-human, multicenter trial to evaluate the safety and effectiveness of the INCRAFT® System. Patients underwent annual clinical and computed tomography angiography examination as part of the study protocol. The INCRAFT® AAA Stent-Graft System is a customizable tri-modular design, with an ultra-low profile (14-Fr) delivery system. Patient were treated under approved protocol, the prescribed clinical and imaging follow-up at annually through 5 years. Results analyzed and adjudicated by a clinical events committee, independent core laboratory, and a data safety and monitoring board. This manuscript reports results through 4 years of follow-up. A total of 60 patients were enrolled in the trial, all of whom were successfully treated. Follow-up rates at 1 and 4 years were 93% (56/60) and 85% (51/60), respectively. All-cause mortality at 4 years was 17.6% and no death was AAA-, device-, or procedure-related. The secondary reintervention rate at 1 year was 4.6%, primarily the result of stent thrombosis. In total, 10 patients required 13 post-procedure interventions within 4-years of follow-up (2 to repair a type I endoleak, 4 to repair a type II endoleak, 1 for stent thrombosis, 1 for renal stenosis, 1 for aneurysm enlargement, 2 for limb migration and 2 for prosthesis stenosis or occlusion). There were 4 cases (10%) of aneurysm enlargement reported at the 4 year follow-up. At 4 years, 38 out of 39 patients were free from type I and III endoleaks. There were no proximal type I or type III endoleaks at 4-year follow-up. Core laboratory evaluation of the postoperative imaging studies indicated absence of endograft migration while a single fracture was demonstrated without any clinical sequelae. The INCRAFT® AAA Stent

  16. Mitek Anchor System: a new technique for tenodesis and ligamentous repair of the foot and ankle.

    Science.gov (United States)

    Pederson, B; Tesoro, D; Wertheimer, S J; Coraci, M

    1991-01-01

    The authors present an alternative method for securing tendon and ligaments to bone, utilizing the Mitek Anchor System. The description of the Mitek system and technique of application is presented. Technical simplicity and ease of adaptability within the foot and ankle are distinct advantages of this System.

  17. On Birnbaum importance assessment for aging multi-state system under minimal repair by using the Lz-transform method

    International Nuclear Information System (INIS)

    Lisnianski, Anatoly; Frenkel, Ilia; Khvatskin, Lev

    2015-01-01

    This paper considers a reliability importance evaluation for components in an aging multi-state system. In practical reliability engineering a “curse of dimensionality” (the large number of states that should be analyzed for a multi-state system model) is a main obstacle for importance assessment. In order to challenge the problem, this paper proposes a new method that is based on an L Z -transform of the discrete-state continuous-time Markov process and on Ushakov's Universal Generating Operator. The paper shows that the proposed method can drastically reduce a computational burden. In order to illustrate the method, a solution of a real world problem is presented as a numerical example. - Highlights: • Aging multi-state system under minimal repair is studied. • A new method for Birnbaum importance assessment is developed. • The method is based on the L Z -transform. • The proposed method provides a drastic reduction of computation burden. • Numerical example is presented in order to illustrate the method

  18. 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.

  19. A Robotic System for Inspection and Repair of Small Diameter Pipelines

    Directory of Open Access Journals (Sweden)

    S. A. Vorotnikov

    2015-01-01

    Full Text Available This paper deals with the construction and control system of miniature robotic system that is designed to move and make inspection inside small diameter pipelines. It gives an overview of ways to move a microsize robotic system inside the small diameter pipe. The proposed design consists of information module and three traction modules, including modules for fixing, linear moving and angular positioning. This paper describes the design and operation of a robotic system and its different modules. Also are shown the structure of the robot control system, the basic calculations of construct and some simulation results of the individual modules of the robot.

  20. Discrete time analysis of a repairable machine

    OpenAIRE

    Alfa, Attahiru Sule; Castro, I. T.

    2002-01-01

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

  1. Molecular biological mechanisms I. DNA repair

    International Nuclear Information System (INIS)

    Friedl, A.A.

    2000-01-01

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

  2. Meniscal repair devices.

    Science.gov (United States)

    Barber, F A; Herbert, M A

    2000-09-01

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

  3. Quantitative MRI comparison of systemic hemodynamics in Mustard/Senning repaired patients and healthy volunteers at rest

    International Nuclear Information System (INIS)

    Laffon, Eric; Jimenez, Maria; Choussat, Alain; Latrabe, Valerie; Ducassou, Dominique; Marthan, Roger; Laurent, Francois

    2004-01-01

    The purpose of the present study was to non-invasively compare ascending aortic blood flow and cross-sectional area (CSA) variations vs time in Mustard or Senning repaired (MSR) patients against those of healthy volunteers at rest. Velocity-encoded MR imaging was performed in 10 male patients (age range 18-24 years, median age 20.5 years) late after a Mustard or Senning correction, and in 10 male healthy volunteers (age range 21-25 years, median age 22.5 years), at the upper part of the ascending aorta. Both aortic cross-sectional area (CSA) and blood-flow variations were recorded over a complete cardiac cycle, with a 30-ms time of resolution. The body-surface area (BSA), the mean CSA over the systolic phase, and the BSA-normalized systemic ventricle power and work were significantly lower in the patient series compared with those of the volunteer series. The BSA-normalized right ventricle (RV) power and work of MSR patients were equal to 87 and 83% on average of those of the left ventricle (LV) of healthy volunteers. We conclude that, at rest, the mechanical performance of the systemic RV in MSR patients is significantly lower than that of the LV in healthy volunteers. Furthermore, the significantly lower aortic CSA found in MSR patients than in healthy volunteers may reveal an increase in the vasomotor tone. (orig.)

  4. Procedures for maintenance and repairs

    International Nuclear Information System (INIS)

    Pickel, E.

    1981-01-01

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

  5. Inspection, maintenance, and repair of large pumps and piping systems using advanced robotic tools

    International Nuclear Information System (INIS)

    Lewis, R.K.; Radigan, T.M.

    1998-01-01

    Operating and maintaining large pumps and piping systems can be an expensive proposition. Proper inspections and monitoring can reduce costs. This was difficult in the past, since detailed pump inspections could only be performed by disassembly and many portions of piping systems are buried or covered with insulation. Once these components were disassembled, a majority of the cost was already incurred. At that point, expensive part replacement usually took place whether it was needed or not. With the completion of the Pipe Walkertrademark/LIP System and the planned development of the Submersible Walkertrademark, this situation is due to change. The specifications for these inspection and maintenance robots will ensure that. Their ability to traverse both horizontal and vertical, forward and backward, make them unique tools. They will open the door for some innovative approaches to inspection and maintenance of large pumps and piping systems

  6. Genomic Instability Promoted by Overexpression of Mismatch Repair Factors in Yeast: A Model for Understanding Cancer Progression.

    Science.gov (United States)

    Chakraborty, Ujani; Dinh, Timothy A; Alani, Eric

    2018-04-13

    Mismatch repair (MMR) proteins act in spellchecker roles to excise misincorporation errors that occur during DNA replication. Curiously, large-scale analyses of a variety of cancers showed that increased expression of MMR proteins often correlated with tumor aggressiveness, metastasis, and early recurrence. To better understand these observations, we used the TCGA and GENT databases to analyze MMR protein expression in cancers. We found that the MMR genes MSH2 and MSH6 are overexpressed more frequently than MSH3 , and that MSH2 and MSH6 are often co-overexpressed as a result of copy number amplifications of these genes. These observations encouraged us to test the effects of upregulating MMR protein levels in baker's yeast, where we can sensitively monitor genome instability phenotypes associated with cancer initiation and progression. Msh6 overexpression (2 to 4-fold) almost completely disrupted mechanisms that prevent recombination between divergent DNA sequences by interacting with the DNA polymerase processivity clamp PCNA and by sequestering the Sgs1 helicase. Importantly, co-overexpression of Msh2 and Msh6 (∼8-fold) conferred, in a PCNA interaction dependent manner, several genome instability phenotypes including increased mutation rate, increased sensitivity to the DNA replication inhibitor hydroxyurea and the DNA damaging agents methyl methanesulfonate and 4-nitroquinoline N-oxide, and elevated loss of heterozygosity. Msh2 and Msh6 co-overexpression also altered the cell cycle distribution of exponentially growing cells, resulting in an increased fraction of unbudded cells, consistent with a larger percentage of cells in G1. These novel observations suggested that overexpression of MSH factors affected the integrity of the DNA replication fork, causing genome instability phenotypes that could be important for promoting cancer progression. Copyright © 2018, Genetics.

  7. An Analysis of the Reflector Cooling System Repair Status after the Initial Operation of HANARO

    Energy Technology Data Exchange (ETDEWEB)

    Park, Young Chul; Seo, Kyoung Woo; Chi, Dae Young; Yoon, Hyun Gi [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Park, Jung Geun [Safety Evaluation Department, System D and D Co., Daejeon (Korea, Republic of)

    2011-05-15

    HANARO, an open-tank-in-pool type multi-purpose research reactor of 30 MWth power in Korea, has been operating normally since its initial criticality in February, 1995. During the last operation period of HANARO, when a trouble occurred, the trouble was fixed on site. As preventive maintenance can reduce the corrective maintenance, the reasons of the occurred troubles are reviewed to prepare preventive maintenance. About twelve hundred cases of work requests and nonconformance reports (NCRs) have been issued since the initial criticality of HANARO. The cases are analyzed according to the trouble status, the trouble equipment function and the cause of the major trouble for reflector cooling system (RCS, hereinafter) including cover gas system and leakage monitoring and collection system

  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. Comparison between state graphs and fault trees for sequential and repairable systems

    International Nuclear Information System (INIS)

    Soussan, D.; Saignes, P.

    1996-01-01

    In French PSA (Probabilistic Safety Assessment) 1300 for the 1300 Mwe PWR plants carried out by EDF, sequential and reparable systems are modeled with state graphs. This method is particularly convenient for modeling dynamic systems with long-term missions but induces a bad traceability and understandability of models. In the objective of providing elements for rewriting PSA 1300 with only boolean models, EDF has asked CEA to participate to a methodological study. The aim is to carry out a feasibility study of transposition of state graphs models into fault trees on Component Cooling System and Essential Service Water System (CCS/ESWS) and to draw a methodological guide for transposition. The study realized on CCS/ESWS involves two main axes: quantification of cold source loss (as an accident sequence initiating event, called H1); quantification of the CCS/ESWS missions in accident sequences. The subject of this article is to show that this transformation is applicable with minimum distortions of the results and to determine the hypotheses, the conditions and the limits of application of this conversion. (authors). 2 refs

  10. Nuclear power plant steam pipes repairing with TIRANT 3 robot system

    International Nuclear Information System (INIS)

    Soto Tomas, Marcelo; Curiel Nieva, Marceliano; Monzo Blasco, Enrique; Rodriguez, Salvador Pineda; Vaquer Perez, Juan I.

    2011-01-01

    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 postural position (usually kneeling) in small 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. For all these reasons, Grupo Dominguis has developed the TIRANT 3 robot, a worldwide innovative system, for metallization of steam pipes inner surface. TIRANT 3 robot is teleoperated 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 depending on required type and thickness of wire. TIRANT 3 system has successfully worked in 2010 during the stops refueling of the Units I and II of Laguna Verde nuclear power plant in Mexico. (author)

  11. Incorporating Flexibility in the Design of Repairable Systems - Design of Microgrids

    Science.gov (United States)

    2014-01-01

    MICROGRIDS Vijitashwa Pandey1 Annette Skowronska1,2...optimization of complex systems such as a microgrid is however, computationally intensive. The problem is exacerbated if we must incorporate...flexibility in terms of allowing the microgrid architecture and its running protocol to change with time. To reduce the computational effort, this paper

  12. Expert system for assisting the repair operations on the control racks of the control rods assembly in a 900 MW PWR type reactor

    International Nuclear Information System (INIS)

    Monnier, B.; Doutre, J.L.; Franco, A.

    1990-01-01

    The expert system presented was developed for assisting the repair operations on the control equipment of the control rod assembly in a PWR type reactor. The expert system allows the representation of expert knowledge and diagnostic reasoning. The objective of the expert system is to achieve the most precise diagnostic and localizing of the breakdown elements, by processing the data acquired during breakdown. The development steps, the structure and the applications of the expert system are summarized. The expert system operates in an IBM PC equipped with a AMAIA 8 Mo card. A time schedule of 18 months is predicted [fr

  13. 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.

  14. Nuclear Power Plant Steam Pipes repairing with Tirant 3R Robot System

    International Nuclear Information System (INIS)

    Ruiz-Martinez, Jose-Tomas; Soto-Tomas, Marcelo; Curiel-Nieva, Marceliano; Monzo-Blasco, Enrique; Pineda-Rodriguez, Salvador; Vaquer-Perez, Juan-Ignacio

    2012-09-01

    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 flow assisted corrosion (FAC), increasing resistance to abrasion and deteriorations. 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 flow assisted 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 R system, a worldwide innovative system, for metallization of steam pipes inner surface. TIRANT 3 R system 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 R 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

  15. Aircraft Propeller Hub Repair

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-13

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

  16. Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Christopher S Campbell

    2014-05-01

    Full Text Available In Saccharomyces cerevisiae, the essential mismatch repair (MMR endonuclease Mlh1-Pms1 forms foci promoted by Msh2-Msh6 or Msh2-Msh3 in response to mispaired bases. Here we analyzed the Mlh1-Mlh2 complex, whose role in MMR has been unclear. Mlh1-Mlh2 formed foci that often colocalized with and had a longer lifetime than Mlh1-Pms1 foci. Mlh1-Mlh2 foci were similar to Mlh1-Pms1 foci: they required mispair recognition by Msh2-Msh6, increased in response to increased mispairs or downstream defects in MMR, and formed after induction of DNA damage by phleomycin but not double-stranded breaks by I-SceI. Mlh1-Mlh2 could be recruited to mispair-containing DNA in vitro by either Msh2-Msh6 or Msh2-Msh3. Deletion of MLH2 caused a synergistic increase in mutation rate in combination with deletion of MSH6 or reduced expression of Pms1. Phylogenetic analysis demonstrated that the S. cerevisiae Mlh2 protein and the mammalian PMS1 protein are homologs. These results support a hypothesis that Mlh1-Mlh2 is a non-essential accessory factor that acts to enhance the activity of Mlh1-Pms1.

  17. DNA mismatch repair gene MLH1 induces apoptosis in prostate cancer cells.

    Science.gov (United States)

    Fukuhara, Shinichiro; Chang, Inik; Mitsui, Yozo; Chiyomaru, Takeshi; Yamamura, Soichiro; Majid, Shahana; Saini, Sharanjot; Hirata, Hiroshi; Deng, Guoren; Gill, Ankurpreet; Wong, Darryn K; Shiina, Hiroaki; Nonomura, Norio; Dahiya, Rajvir; Tanaka, Yuichiro

    2014-11-30

    Mismatch repair (MMR) enzymes have been shown to be deficient in prostate cancer (PCa). MMR can influence the regulation of tumor development in various cancers but their role on PCa has not been investigated. The aim of the present study was to determine the functional effects of the mutL-homolog 1 (MLH1) gene on growth of PCa cells. The DU145 cell line has been established as MLH1-deficient and thus, this cell line was utilized to determine effects of MLH1 by gene expression. Lack of MLH1 protein expression was confirmed by Western blotting in DU145 cells whereas levels were high in normal PWR-1E and RWPE-1 prostatic cells. MLH1-expressing stable transfectant DU145 cells were then created to characterize the effects this MMR gene has on various growth properties. Expression of MLH1 resulted in decreased cell proliferation, migration and invasion properties. Lack of cell growth in vivo also indicated a tumor suppressive effect by MLH1. Interestingly, MLH1 caused an increase in apoptosis along with phosphorylated c-Abl, and treatment with MLH1 siRNAs countered this effect. Furthermore, inhibition of c-Abl with STI571 also abrogated the effect on apoptosis caused by MLH1. These results demonstrate MLH1 protects against PCa development by inducing c-Abl-mediated apoptosis.

  18. Failure analysis of a repairable system: The case study of a cam-driven reciprocating pump

    Science.gov (United States)

    Dudenhoeffer, Donald D.

    1994-09-01

    This thesis supplies a statistical and economic tool for analysis of the failure characteristics of one typical piece of equipment under evaluation: a cam-driven reciprocating pump used in the submarine's distillation system. Comprehensive statistical techniques and parametric modeling are employed to identify and quantify pump failure characteristics. Specific areas of attention include: the derivation of an optimal maximum replacement interval based on costs, an evaluation of the mission reliability for the pump as a function of pump age, and a calculation of the expected times between failures. The purpose of this analysis is to evaluate current maintenance practices of time-based replacement and examine the consequences of different replacement intervals in terms of costs and mission reliability. Tradeoffs exist between cost savings and system reliability that must be fully understood prior to making any policy decisions.

  19. Ligament Augmentation and Reconstruction System Failures in Repair of Grade V Acromioclavicular Joint Dislocation

    Directory of Open Access Journals (Sweden)

    Martin K.-H. Li

    2017-01-01

    Full Text Available The Ligament Augmentation and Reconstruction System® (LARS® represents a popular synthetic anatomical reduction method for acromioclavicular joint dislocation by means of coracoclavicular ligament reconstruction. To our knowledge, no early failure has been documented in the literature. We present two unusual cases of LARS failure, one at four months after implant and the other at three weeks, without obvious causes, requiring re-do reconstruction, and discuss potential contributory factors.

  20. Pelvic organ prolapse repair using the Uphold (TM) Vaginal Support System

    OpenAIRE

    Altman, Daniel; Mikkola, Tomi S.; Bek, Karl Moller; Rahkola-Soisalo, Paivi; Gunnarsson, Jonas; Engh, Marie Ellstrom; Falconer, Christian; Nordic TVM Grp

    2016-01-01

    The objective was to assess safety and clinical outcomes in women operated on using the Uphold (TM) Lite Vaginal Support System. We carried out a 1-year, multicenter, prospective, single cohort study of 207 women with symptomatic Pelvic Organ Prolapse Quantification (POP-Q) stage aeyen2 apical pelvic organ prolapse, with or without concomitant anterior vaginal wall prolapse. Safety data were collected using a standardized questionnaire. Anatomical outcome was assessed by the POP-Q and subject...

  1. 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)

  2. Availability allocation to repairable systems with genetic algorithms: a multi-objective formulation

    International Nuclear Information System (INIS)

    Elegbede, Charles; Adjallah, Kondo

    2003-01-01

    This paper describes a methodology based on genetic algorithms (GA) and experiments plan to optimize the availability and the cost of reparable parallel-series systems. It is a NP-hard problem of multi-objective combinatorial optimization, modeled with continuous and discrete variables. By using the weighting technique, the problem is transformed into a single-objective optimization problem whose constraints are then relaxed by the exterior penalty technique. We then propose a search of solution through GA, whose parameters are adjusted using experiments plan technique. A numerical example is used to assess the method

  3. 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

    2013-01-01

    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. PMID:24064601

  4. Drug-Loadable Calcium Alginate Hydrogel System for Use in Oral Bone Tissue Repair.

    Science.gov (United States)

    Chen, Luyuan; Shen, Renze; Komasa, Satoshi; Xue, Yanxiang; Jin, Bingyu; Hou, Yepo; Okazaki, Joji; Gao, Jie

    2017-05-06

    This study developed a drug-loadable hydrogel system with high plasticity and favorable biological properties to enhance oral bone tissue regeneration. Hydrogels of different calcium alginate concentrations were prepared. Their swelling ratio, degradation time, and bovine serum albumin (BSA) release rate were measured. Human periodontal ligament cells (hPDLCs) and bone marrow stromal cells (BMSCs) were cultured with both calcium alginate hydrogels and polylactic acid (PLA), and then we examined the proliferation of cells. Inflammatory-related factor gene expressions of hPDLCs and osteogenesis-related gene expressions of BMSCs were observed. Materials were implanted into the subcutaneous tissue of rabbits to determine the biosecurity properties of the materials. The materials were also implanted in mandibular bone defects and then scanned using micro-CT. The calcium alginate hydrogels caused less inflammation than the PLA. The number of mineralized nodules and the expression of osteoblast-related genes were significantly higher in the hydrogel group compared with the control group. When the materials were implanted in subcutaneous tissue, materials showed favorable biocompatibility. The calcium alginate hydrogels had superior osteoinductive bone ability to the PLA. The drug-loadable calcium alginate hydrogel system is a potential bone defect reparation material for clinical dental application.

  5. 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 ...

  6. Loss of Cdx2 expression in primary tumors and lymph node metastases is specific for mismatch repair-deficiency in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Heather eDawson

    2013-10-01

    Full Text Available Background: Approximately 20% of all colorectal cancers are hypothesized to arise from the serrated pathway characterized by mutation in BRAF, high-level CpG Island Methylator Phenotype (CIMP and microsatellite instability/mismatch repair (MMR-deficiency. MMR-deficient cancers show frequent losses of Cdx2, a homeodomain transcription factor. Here, we determine the predictive value of Cdx2 expression for MMR-deficiency and investigate changes in expression between primary cancers and matched lymph node metastases. Methods: Immunohistochemistry for Cdx2, Mlh1, Msh2, Msh6, and Pms2 was performed on whole tissue sections from 201 patients with primary colorectal cancer and 59 cases of matched lymph node metastases. Receiver operating characteristic (ROC curve analysis and Area under the Curve (AUC were investigated; association of Cdx2 with clinicopathological features and patient survival was carried out.Results Loss of Cdx2 expression was associated with higher tumor grade (p=0.0002, advanced pT (p=0.0166, and perineural invasion (p=0.0228. Cdx2 loss was an unfavorable prognostic factor in univariate (p=0.0145 and multivariate (p=0.0427; HR (95%CI: 0.58 (0.34-0.98 analysis. The accuracy (AUC for discriminating MMR-proficient and –deficient cancers was 87% (OR (95%CI:0.96 (0.95-0.98; p<0.0001. Specificity and negative predictive value for MMR-deficiency was 99.1% and 96.3%. 174 patients had MMR-proficient cancers, of which 60 (34.5% showed Cdx2 loss. Cdx2 loss in metastases was related to MMR-deficiency (p<0.0001. There was no difference in expression between primary tumors and matched metastases.Conclusion: Loss of Cdx2 is a sensitive and specific predictor of MMR-deficiency, but is not limited to these tumors, suggesting that events upstream of the development of MSI may impact Cdx2 expression.

  7. Repairing Canada’s Mining-Tax System to Be Less Distorting and Complex

    Directory of Open Access Journals (Sweden)

    Duanjie Chen

    2013-05-01

    Full Text Available The province of Ontario ended its most recent fiscal year with a $12 billion deficit and the Fraser Institute has calculated that the province is in worse financial shape than even the fiscally appalling state of California. One would think that a province so financially debilitated would want to avoid giving unnecessary and wasteful tax breaks to resource companies. Yet, a review of the mining-tax regimes across the country finds that Ontario’s system — specifically its provincial resource allowance, which duplicates the allowances provided by Ottawa that shield miners from risk — is redundant, expensive and wasteful. Ontario is not the only province requiring a modernization of its mining-tax regime. In every province except Nova Scotia and New Brunswick, mining firms enjoy a lower marginal rate for taxes and royalties than for non-resource companies. The inevitable result has been a distortion of investment toward mining projects that might otherwise be economically inefficient. That means that in major oil-producing provinces, such as Alberta, Saskatchewan and Newfoundland, mining investment benefits from larger tax incentives than oil and gas investment. The reasons for favouring the mining of metal over oil are at least unclear and certainly economically unjustifiable. The federal government has already begun making several changes to its tax policies to scale back preferential and irrational inducements for mining investment, including, most recently, reducing accelerated depreciation allowances for certain mining assets and phasing out the corporate Mineral Exploration Tax Credit and the Atlantic Investment Tax Credit for resources. But Ottawa’s efforts to modernize Canada’s mining-tax structure can only go so far, when provinces continue to rely on what are often overly complex tax systems that have a distortionary effect on economic decisions being made by investors. The next step in modernizing Canada’s mining-tax system

  8. Comparative analysis of the machine repair Problem with imperfect coverage and service pressure condition

    Science.gov (United States)

    Wang, Kuo-Hsiung; Liou, Cheng-Dar; Lin, Yu-Hsueh

    2013-02-01

    We analyze the warm-standby M/M/R machine repair problem with multiple imperfect coverage which involving the service pressure condition. When an operating machine (or warm standby) fails, it may be immediately detected, located, and replaced with a coverage probability c by a standby if one is available. A recursive method is used to develop the steady-state analytic solutions. The total expected profit function per unit time is derived to determine the joint optimal values at the maximum profit. We utilize the direct search method to measure the various characteristics of the profit function followed by Quasi-Newton method to search the optimal solutions.

  9. 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

  10. Risk of metachronous colon cancer following surgery for rectal cancer in mismatch repair gene mutation carriers.

    Science.gov (United States)

    Win, Aung Ko; Parry, Susan; Parry, Bryan; Kalady, Matthew F; Macrae, Finlay A; Ahnen, Dennis J; Young, Graeme P; Lipton, Lara; Winship, Ingrid; Boussioutas, Alex; Young, Joanne P; Buchanan, Daniel D; Arnold, Julie; Le Marchand, Loïc; Newcomb, Polly A; Haile, Robert W; Lindor, Noralane M; Gallinger, Steven; Hopper, John L; Jenkins, Mark A

    2013-06-01

    Despite regular surveillance colonoscopy, the metachronous colorectal cancer risk for mismatch repair (MMR) gene mutation carriers after segmental resection for colon cancer is high and total or subtotal colectomy is the preferred option. However, if the index cancer is in the rectum, management decisions are complicated by considerations of impaired bowel function. We aimed to estimate the risk of metachronous colon cancer for MMR gene mutation carriers who underwent a proctectomy for index rectal cancer. This retrospective cohort study comprised 79 carriers of germline mutation in a MMR gene (18 MLH1, 55 MSH2, 4 MSH6, and 2 PMS2) from the Colon Cancer Family Registry who had had a proctectomy for index rectal cancer. Cumulative risks of metachronous colon cancer were calculated using the Kaplan-Meier method. During median 9 years (range 1-32 years) of observation since the first diagnosis of rectal cancer, 21 carriers (27 %) were diagnosed with metachronous colon cancer (incidence 24.25, 95 % confidence interval [CI] 15.81-37.19 per 1,000 person-years). Cumulative risk of metachronous colon cancer was 19 % (95 % CI 9-31 %) at 10 years, 47 (95 % CI 31-68 %) at 20 years, and 69 % (95 % CI 45-89 %) at 30 years after surgical resection. The frequency of surveillance colonoscopy was 1 colonoscopy per 1.16 years (95 % CI 1.01-1.31 years). The AJCC stages of the metachronous cancers, where available, were 72 % stage I, 22 % stage II, and 6 % stage III. Given the high metachronous colon cancer risk for MMR gene mutation carriers diagnosed with an index rectal cancer, proctocolectomy may need to be considered.

  11. 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.

  12. Pelvic organ prolapse repair using the Uphold™ Vaginal Support System: a 1-year multicenter study.

    Science.gov (United States)

    Altman, Daniel; Mikkola, Tomi S; Bek, Karl Möller; Rahkola-Soisalo, Päivi; Gunnarsson, Jonas; Engh, Marie Ellström; Falconer, Christian

    2016-09-01

    The objective was to assess safety and clinical outcomes in women operated on using the Uphold™ Lite Vaginal Support System. We carried out a 1-year, multicenter, prospective, single cohort study of 207 women with symptomatic Pelvic Organ Prolapse Quantification (POP-Q) stage ≥2 apical pelvic organ prolapse, with or without concomitant anterior vaginal wall prolapse. Safety data were collected using a standardized questionnaire. Anatomical outcome was assessed by the POP-Q and subjective outcomes by the Pelvic Floor Distress Inventory after 2 months and 1 year using a one-way repeated measures analysis of variance. Pain was evaluated using a visual analog scale. The overall rate of serious complications was 4.3 % (9 out of 207 patients), including 3 patients with bladder perforations, 1 with bleeding >1,000 ml, 2 who had undergone re-operations with complete mesh removal because of pain, and 3 surgical interventions during follow-up because of mesh exposure. POP-Q stage ≤1 after 1 year was 94 % and subjective symptom relief was reported by 91 % of patients (p transvaginal mesh kits.

  13. Both hMutSα and hMutSß DNA mismatch repair complexes participate in 5-fluorouracil cytotoxicity.

    Directory of Open Access Journals (Sweden)

    Akihiro Tajima

    Full Text Available 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.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.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.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.

  14. Extracellular Matrix (ECM) Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair

    Science.gov (United States)

    Park, Sang-Hyug; Kim, Moon Suk; Kim, Young Jick; Choi, Byung Hyune; Lee, Chun Tek; Park, So Ra; Min, Byoung-Hyun

    2016-01-01

    Recombinant human transforming growth factor beta-3 (rhTGF-β3) is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM) membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS) are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs) using western blot and circular dichroism (CD) analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+) rhTGF-β3 EMLDS) in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair. PMID:27258120

  15. Extracellular Matrix (ECM Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair.

    Directory of Open Access Journals (Sweden)

    Soon Sim Yang

    Full Text Available Recombinant human transforming growth factor beta-3 (rhTGF-β3 is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs using western blot and circular dichroism (CD analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+ rhTGF-β3 EMLDS in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair.

  16. Pms2 and uracil-DNA glycosylases act jointly in the mismatch repair pathway to generate Ig gene mutations at A-T base pairs.

    Science.gov (United States)

    Girelli Zubani, Giulia; Zivojnovic, Marija; De Smet, Annie; Albagli-Curiel, Olivier; Huetz, François; Weill, Jean-Claude; Reynaud, Claude-Agnès; Storck, Sébastien

    2017-04-03

    During somatic hypermutation (SHM) of immunoglobulin genes, uracils introduced by activation-induced cytidine deaminase are processed by uracil-DNA glycosylase (UNG) and mismatch repair (MMR) pathways to generate mutations at G-C and A-T base pairs, respectively. Paradoxically, the MMR-nicking complex Pms2/Mlh1 is apparently dispensable for A-T mutagenesis. Thus, how detection of U:G mismatches is translated into the single-strand nick required for error-prone synthesis is an open question. One model proposed that UNG could cooperate with MMR by excising a second uracil in the vicinity of the U:G mismatch, but it failed to explain the low impact of UNG inactivation on A-T mutagenesis. In this study, we show that uracils generated in the G1 phase in B cells can generate equal proportions of A-T and G-C mutations, which suggests that UNG and MMR can operate within the same time frame during SHM. Furthermore, we show that Ung -/- Pms2 -/- mice display a 50% reduction in mutations at A-T base pairs and that most remaining mutations at A-T bases depend on two additional uracil glycosylases, thymine-DNA glycosylase and SMUG1. These results demonstrate that Pms2/Mlh1 and multiple uracil glycosylases act jointly, each one with a distinct strand bias, to enlarge the immunoglobulin gene mutation spectrum from G-C to A-T bases. © 2017 Girelli Zubani et al.

  17. 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.

  18. DNA repair , cell repair and radiosensitivity

    International Nuclear Information System (INIS)

    Zhestyanikov, V.D.

    1983-01-01

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

  19. Efficacy and safety of Elevate® system on apical and anterior compartment prolapse repair with personal technique modification

    Directory of Open Access Journals (Sweden)

    Daniele Castellani

    Full Text Available ABSTRACT Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

  20. Design and preliminary validation of a mobile application-based expert system to facilitate repair of medical equipment in resource-limited health settings

    Directory of Open Access Journals (Sweden)

    Wong AL

    2018-05-01

    Full Text Available Alison L Wong,1,2 Kelly M Lacob,1 Madeline G Wilson,1 Stacie M Zwolski,1 Soumyadipta Acharya1 1Center for Bioengineering, Innovation and Design, Johns Hopkins University, Baltimore, MD, USA; 2Division of Plastic Surgery, Dalhousie University, Halifax, NS, Canada Background: One of the greatest barriers to safe surgery is the availability of functional biomedical equipment. Biomedical technicians play a major role in ensuring that equipment is functional. Following in-field observations and an online survey, a mobile application was developed to aid technicians in troubleshooting biomedical equipment. It was hypothesized that this application could be used to aid technicians in equipment repair, as modeled by repair of a pulse oximeter.Methods: To identify specific barriers to equipment repair and maintenance for biomedical technicians, an online survey was conducted to determine current practices and challenges. These findings were used to guide the development of a mobile application system that guides technicians through maintenance and repair tasks. A convenience sample of technicians in Ethiopia tested the application using a broken pulse oximeter task and following this completed usability and content validity surveys.Results: Fifty-three technicians from 13 countries responded to the initial survey. The results of the survey showed that technicians find equipment manuals most useful, but these are not easily accessible. Many do not know how to or are uncomfortable reaching out to human resources. Thirty-three technicians completed the broken pulse oximeter task using the application. All were able to appropriately identify and repair the equipment, and post-task surveys of usability and content validity demonstrated highly positive scores (Agree to Strongly Agree on both scales.Discussion: This research demonstrates the need for improved access to resources for technicians and shows that a mobile application can be used to address a gap in

  1. 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.

  2. Repair of potentially lethal damage following irradiation with x rays or cyclotron neutrons: response of the EMT-6/UW tumor system treated under various growth conditions in vitro and in vivo

    International Nuclear Information System (INIS)

    Rasey, J.S.; Nelson, N.J.

    1981-01-01

    Postirradiation potentially lethal damage (PLD) repair was examined in the EMT-6/UW tumor system under a variety of in vitro and in vivo growth conditions. Following x irradiation, surviving fraction increased in fed and unfed plateau cultures if subculture and plating were delayed; in exponentially growing cultures if they were covered with depleted medium for the first 6 h postirradiation; and in tumors in vivo if excision for preparation of a cell suspension was delayed. Following irradiation with 21.5 meV (d + → Be) neutrons, PLD repair was measurable only in unfed plateau cultures when subculture was delayed and in exponentially growing cells exposed to depleted culture medium immediately after irradiation. In x-irradiated EMT-6/UW cells, the greatest repair capacity and the highest surviving fraction ratios were measured in unfed plateau cultures; the least repair was observed in exponentially growing cells exposed to depleted medium. Thus post-neutron repair was not limited to situations where the amount of repair of photon PLD is large. The demonstration of PLD repair in tumors irradiated in vivo with X rays and the absence of such repair after neutrons could have important implications in radiotherapy if this is a general phenomenon

  3. 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.

  4. Protective Effect of Diphlorethohydroxycarmalol against Ultraviolet B Radiation-Induced DNA Damage by Inducing the Nucleotide Excision Repair System in HaCaT Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    Mei Jing Piao

    2015-09-01

    Full Text Available We investigated the protective properties of diphlorethohydroxycarmalol (DPHC, a phlorotannin, against ultraviolet B (UVB radiation-induced cyclobutane pyrimidine dimers (CPDs in HaCaT human keratinocytes. The nucleotide excision repair (NER system is the pathway by which cells identify and repair bulky, helix-distorting DNA lesions such as ultraviolet (UV radiation-induced CPDs and 6-4 photoproducts. CPDs levels were elevated in UVB-exposed cells; however, this increase was reduced by DPHC. Expression levels of xeroderma pigmentosum complementation group C (XPC and excision repair cross-complementing 1 (ERCC1, which are essential components of the NER pathway, were induced in DPHC-treated cells. Expression of XPC and ERCC1 were reduced following UVB exposure, whereas DPHC treatment partially restored the levels of both proteins. DPHC also increased expression of transcription factor specificity protein 1 (SP1 and sirtuin 1, an up-regulator of XPC, in UVB-exposed cells. DPHC restored binding of the SP1 to the XPC promoter, which is reduced in UVB-exposed cells. These results indicate that DPHC can protect cells against UVB-induced DNA damage by inducing the NER system.

  5. DNA repair in Mycobacterium tuberculosis revisited.

    Science.gov (United States)

    Dos Vultos, Tiago; Mestre, Olga; Tonjum, Tone; Gicquel, Brigitte

    2009-05-01

    Our understanding of Mycobacterium tuberculosis DNA repair mechanisms is still poor compared with that of other bacterial organisms. However, the publication of the first complete M. tuberculosis genome sequence 10 years ago boosted the study of DNA repair systems in this organism. A first step in the elucidation of M. tuberculosis DNA repair mechanisms was taken by Mizrahi and Andersen, who identified homologs of genes involved in the reversal or repair of DNA damage in Escherichia coli and related organisms. Genes required for nucleotide excision repair, base excision repair, recombination, and SOS repair and mutagenesis were identified. Notably, no homologs of genes involved in mismatch repair were identified. Novel characteristics of the M. tuberculosis DNA repair machinery have been found over the last decade, such as nonhomologous end joining, the presence of Mpg, ERCC3 and Hlr - proteins previously presumed to be produced exclusively in mammalian cells - and the recently discovered bifunctional dCTP deaminase:dUTPase. The study of these systems is important to develop therapeutic agents that can counteract M. tuberculosis evolutionary changes and to prevent adaptive events resulting in antibiotic resistance. This review summarizes our current understanding of the M. tuberculosis DNA repair system.

  6. High levels of BRC4 induced by a Tet-On 3G system suppress DNA repair and impair cell proliferation in vertebrate cells.

    Science.gov (United States)

    Abe, Takuya; Branzei, Dana

    2014-10-01

    Transient induction or suppression of target genes is useful to study the function of toxic or essential genes in cells. Here we apply a Tet-On 3G system to DT40 lymphoma B cell lines, validating it for three different genes. Using this tool, we then show that overexpression of the chicken BRC4 repeat of the tumor suppressor BRCA2 impairs cell proliferation and induces chromosomal breaks. Mechanistically, high levels of BRC4 suppress double strand break-induced homologous recombination, inhibit the formation of RAD51 recombination repair foci, reduce cellular resistance to DNA damaging agents and induce a G2 damage checkpoint-mediated cell-cycle arrest. The above phenotypes are mediated by BRC4 capability to bind and inhibit RAD51. The toxicity associated with BRC4 overexpression is exacerbated by chemotherapeutic agents and reversed by RAD51 overexpression, but it is neither aggravated nor suppressed by a deficit in the non-homologous end-joining pathway of double strand break repair. We further find that the endogenous BRCA2 mediates the cytotoxicity associated with BRC4 induction, thus underscoring the possibility that BRC4 or other domains of BRCA2 cooperate with ectopic BRC4 in regulating repair activities or mitotic cell division. In all, the results demonstrate the utility of the Tet-On 3G system in DT40 research and underpin a model in which BRC4 role on cell proliferation and chromosome repair arises primarily from its suppressive role on RAD51 functions. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Development of diagnosis and repair system for steelmaking refractories; Seikoyo taikabutsu no shindan hoshu gijutsu no kakuritsu

    Energy Technology Data Exchange (ETDEWEB)

    Aso, S.; Harada, S.; Tsutsui, Y. [Nippon Steel Corp., Tokyo (Japan)

    1996-06-01

    The latest measurement equipment and repair method were introduced into the work area of all refractories in the process of torpedo cars, hot metal preliminary treatment, hot metal pans, secondary refining, and cast pans so as to improve the cost of the newest advanced steelmaking refractories. As a result, the refractory cost could be reduced by 10%. This paper introduces the improvement in RH refractories and refractories for hot metal preliminary treatment. As for basic items, in addition to the visual observation, the thickness of refractories was quantified using equipment (laser profile meter, thermotracer, and NS sensor) for the furnace stop in the minimum remaining length. An ITV was also installed in the facilities where the visual check is difficult to carry out. Repair is mainly done by spraying. A thermal spraying repair method with high durability was used for the repair. A method that relieves a thermal shock was used for preheating. Moreover, measures that make the temperature gradient in the thickness direction uniform by using newly developed microwave drying equipment were taken for drying of unburned refractories. 4 refs., 13 figs., 2 tabs.

  8. 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.

  9. The effectiveness of measles-mumps-rubella (MMR) vaccination in the prevention of pediatric hospitalizations for targeted and untargeted infections: A retrospective cohort study.

    Science.gov (United States)

    La Torre, Giuseppe; Saulle, Rosella; Unim, Brigid; Meggiolaro, Angela; Barbato, Angelo; Mannocci, Alice; Spadea, Antonietta

    2017-08-03

    To evaluate the effectiveness of the measles-mumps-rubella (MMR) vaccine in reducing hospitalizations for infectious disease, targeted and not targeted, as well as from respiratory diseases in children in Rome. The cohort was recomposed through record linkage of 2 archives (vaccination register and hospital discharge records. The analysis included 11,004 children. 20.9% did not receive the MMR vaccination, 49% and 30.1% received one and 2 doses. There were no hospitalizations for rubella, 2 for mumps, and 12 for measles. The vaccine was highly protective against measles and mumps hospitalizations (HR = 0.10; 95% CI: 0.03.0.34). Regarding all infectious diseases there were 414 hospitalizations, and the vaccine was protective (HR = 0.29; 95% CI: 0.25 to 0.34). Concerning respiratory diseases, there were 809 admissions (7.4%), and the vaccine was highly protective (HR: 0.18; 95% CI: 0.07 to 0.48). MMR vaccination is effective for the primary prevention of target and not targeted infectious diseases and may also limit hospitalizations for respiratory diseases.

  10. Application of nonhomogeneous Poisson process to reliability analysis of repairable systems of a nuclear power plant with rates of occurrence of failures time-dependent

    International Nuclear Information System (INIS)

    Saldanha, Pedro L.C.; Simone, Elaine A. de; Melo, Paulo Fernando F.F. e

    1996-01-01

    Aging is used to mean the continuous process which physical characteristics of a system, a structure or an equipment changes with time or use. Their effects are increases in failure probabilities of a system, a structure or an equipment, and their are calculated using time-dependent failure rate models. The purpose of this paper is to present an application of the nonhomogeneous Poisson process as a model to study rates of occurrence of failures when they are time-dependent. To this application, an analysis of reliability of service water pumps of a typical nuclear power plant is made, as long as the pumps are effectively repaired components. (author)

  11. The experience from operation of electronic personal dosimetry system at Dukovany, Temelin and Mochovce NPPs after repair of Siemens dosemeters eliminating false doses

    International Nuclear Information System (INIS)

    Malysak, J.; Kocvara, S.; Jurochova, B.; Zelenka, Z.; Schacherl, M.; Zrubec, M.; Kaiser, H.

    2003-01-01

    This presentation summarizes the operational experience of the Electronic Personal Dosimetry Systems installed at Dukovany, Temelin and Mochovce NPPs. The system consists of three basic parts: Electronic personal dosemeters (EPD); Physical layer (HW); Logical layer (SW). Number of false doses before and after correction is presented. This presentation has demonstrated the possibilities of SEOD system and the possibility of easy dose comparison between the individual NPPs after introducing this electronic dosimetry system. Basically, the results of film and electronic dosimetry systems are according to our findings nearly identical. Electronic dosemeter sensitivity to interfering electromagnetic fields is a problem which is easily re-movable. In addition, if we know this problem, these false doses in the SEOD system can be easily revealed (e.g. by investigation of histograms) and repaired

  12. Underwater coating repair cuts nuclear maintenance costs

    International Nuclear Information System (INIS)

    Stuart, C.O.

    1993-01-01

    This article discusses the cleaning and recoating/repair of condensate tanks or other vessels in a nuclear power plant. The topics of the article include the safety and regulatory need for this system of repair, a description of the work done on the Brown's Ferry MK-1 suppression chamber, coating failure mechanisms, qualitative inspection, quantitative inspection, quantitative inspection results, spot repairs, and economic considerations

  13. Rapid road repair vehicle

    Science.gov (United States)

    Mara, Leo M.

    1998-01-01

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

  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. 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. PMID:26251592

  16. Simple detection of germline microsatellite instability for diagnosis of constitutional mismatch repair cancer syndrome.

    Science.gov (United States)

    Ingham, Danielle; Diggle, Christine P; Berry, Ian; Bristow, Claire A; Hayward, Bruce E; Rahman, Nazneen; Markham, Alexander F; Sheridan, Eamonn G; Bonthron, David T; Carr, Ian M

    2013-06-01

    Heterozygous mutations in DNA mismatch repair (MMR) genes result in predisposition to colorectal cancer (hereditary nonpolyposis colorectal cancer or Lynch syndrome). Patients with biallelic mutations in these genes, however, present earlier, with constitutional mismatch repair deficiency cancer syndrome (CMMRD), which is characterized by a spectrum of rare childhood malignancies and café-au-lait skin patches. The hallmark of MMR deficiency, microsatellite instability (MSI), is readily detectable in tumor DNA in Lynch syndrome, but is also present in constitutional DNA of CMMRD patients. However, detection of constitutional or germline MSI (gMSI) has hitherto relied on technically difficult assays that are not routinely applicable for clinical diagnosis. Consequently, we have developed a simple high-throughput screening methodology to detect gMSI in CMMRD patients based on the presence of stutter peaks flanking a dinucleotide repeat allele when amplified from patient blood DNA samples. Using the three different microsatellite markers, the gMSI ratio was determined in a cohort of normal individuals and 10 CMMRD patients, with biallelic germline mutations in PMS2 (seven patients), MSH2 (one patient), or MSH6 (two patients). Subjects with either PMS2 or MSH2 mutations were easily identified; however, this measure was not altered in patients with CMMRD due to MSH6 mutation. © 2013 Wiley Periodicals, Inc.

  17. DNA mismatch repair deficiency accelerates lung neoplasm development in K-rasLA1/+ mice: a brief report

    International Nuclear Information System (INIS)

    Downey, Charlene M; Jirik, Frank R

    2015-01-01

    Inherited as well as acquired deficiencies in specific DNA mismatch repair (MMR) components are associated with the development of a wide range of benign and malignant neoplasms. Loss of key members such as MSH2 and MLH1 severely cripples the ability of the cell to recognize and correct such lesions as base:base mismatches and replicative DNA polymerase errors such as slippages at repetitive sequences. Genomic instability resulting from MMR deficiency not only predisposes cells to malignant transformation but may also promote tumor progression. To test the latter, we interbred Msh2 −/− mice with the K-ras LA1/+ transgenic line that spontaneously develops a range of premalignant and malignant lung lesions. Compared to K-ras LA1/+ mice, K-ras LA1/+ ; Msh2 −/− mice developed lung adenomas and adenocarcinomas at an increased frequency and also demonstrated evidence of accelerated adenocarcinoma growth. Since MMR defects have been identified in some human lung cancers, the mutant mice may not only be of preclinical utility but they will also be useful in identifying gene alterations able to act in concert with Kras mutants to promote tumor progression

  18. Repair of DNA damage induced by anthanthrene, a polycyclic aromatic hydrocarbon (PAH) without bay or fjord regions

    DEFF Research Database (Denmark)

    Madsen, Claus Desler; Johannessen, Christian; Rasmussen, Lene Juel

    2009-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants, formed during incomplete burning of coal, oil and gas. Several PAHs have carcinogenic and mutagenic potencies, but these compounds must be activated in order to exert their mutagenic effects. One of the principal pathways...... proposed for metabolic activation of PAHs involves the cytochrome P450 enzymes. The DNA damaging potential of cytochrome P450-activated PAHs is generally associated with their bay and fjord regions, and the DNA repair response of PAHs containing such regions has been thoroughly studied. However, little...... in response to DNA damage induced by cytochrome P450-activated anthanthrene. In cell extracts, functional nucleotide excision repair (NER) and mismatch repair (MMR) activities were necessary to trigger a response to anthanthrene metabolite-induced DNA damage. In cell cultures, NER was responsible...

  19. 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. 1371.118 Section 1371.118 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE DEPARTMENT SUPPLEMENTAL REGULATIONS ACQUISITIONS INVOLVING SHIP CONSTRUCTION AND SHIP REPAIR Provisions and Clauses 1371.118 Changes—ship repair. Insert clause...

  20. Nucleotide excision repair II: From yeast to mammals

    NARCIS (Netherlands)

    J.H.J. Hoeijmakers (Jan)

    1993-01-01

    textabstractAn intricate network of repair systems safeguards the integrity of genetic material, by eliminating DNA lesions induced by numerous environmental and endogenous genotoxic agents. Nucleotide excision repair (NER) is one of the most versatile DNA repair systems. Deficiencies in this