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Sample records for rbds contained mutations

  1. Structure of RDE-4 dsRBDs and mutational studies provide insights into dsRNA recognition in the Caenorhabditis elegans RNAi pathway.

    Science.gov (United States)

    Chiliveri, Sai Chaitanya; Deshmukh, Mandar V

    2014-02-15

    The association of RDE-4 (RNAi defective 4), a protein containing two dsRBDs (dsRNA-binding domains), with long dsRNA and Dcr-1 (Dicer1 homologue) initiates the siRNA pathway in Caenorhabditis elegans. Unlike its homologues in higher eukaryotes, RDE-4 dsRBDs possess weak (micromolar) affinity for short dsRNA. With increasing length of dsRNA, RDE-4 exhibits enhanced affinity due to co-operativity. The linker and dsRBD2 are indispensable for RDE-4's simultaneous interaction with dsRNA and Dcr-1. In the present study, we have determined the solution structures of RDE-4 constructs that contain both dsRBDs and the linker region. In addition to the canonical dsRBD fold, both dsRBDs of RDE-4 show modified structural features such as truncation in the β1-β2 loop that rationalize RDE-4's relatively weak dsRNA affinity. Structure and binding studies demonstrate that dsRBD2 plays a decisive role in the RDE-4-dsRNA interaction; however, in contrast with previous findings, we found ephemeral interaction of RDE-4 dsRBD1 with dsRNA. More importantly, mutations in two tandem lysine residues (Lys217 and Lys218) in dsRBD2 impair RDE-4's dsRNA-binding ability and could obliterate RNAi initiation in C. elegans. Additionally, we postulate a structural basis for the minimal requirement of linker and dsRBD2 for RDE-4's association with dsRNA and Dcr-1.

  2. Defective Proteasome Delivery of Polyubiquitinated Proteins by Ubiquilin-2 Proteins Containing ALS Mutations.

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    Lydia Chang

    Full Text Available Ubiquilin proteins facilitate delivery of ubiquitinated proteins to the proteasome for degradation. Interest in the proteins has been heightened by the discovery that gene mutations in UBQLN2 cause dominant inheritance of amyotrophic lateral sclerosis (ALS. However, the mechanisms by which the mutations cause ALS are not known. Here we report on the underlying defect of ubiquilin-2 proteins containing ALS-linked mutations in affecting proteasome-mediated degradation. We found that overexpression of ubiquilin-2 proteins containing any one of five different ALS mutations slow degradation of Myc, a prototypic proteasome substrate. Examination of coprecipitating proteins indicated that the mutant proteins are generally capable of binding polyubiquitinated proteins, but defective in binding the proteasome. GST-pulldown studies revealed that many of the mutants bind weaker to the S5a subunit of the proteasome, compared with wild type (WT ubiquilin-2 protein. The results suggest the mutant proteins are unable to deliver their captured cargo to the proteasome for degradation, which presumably leads to toxicity. Quantification of cell death is consistent with this idea. Measurement of protein turnover further indicated the mutant proteins have longer half-lives than WT ubiquilin-2. Our studies provide novel insight into the mechanism by which ALS-linked mutations in UBQLN2 interfere with protein degradation.

  3. Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.D.; Sun, F.; Wallace, D.C. [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1997-02-01

    Leber hereditary optic neuropathy (LHON) is a type of blindness caused by mtDNA mutations. Three LHON mtDNA mutations at nucleotide positions 3460, 11778, and 14484 are specific for LHON and account for 90% of worldwide cases and are thus designated as {open_quotes}primary{close_quotes} LHON mutations. Fifteen other {open_quotes}secondary{close_quotes} LHON mtDNA mutations have been identified, but their pathogenicity is unclear. mtDNA haplotype and phylogenetic analysis of the primary LHON mutations in North American Caucasian patients and controls has shown that, unlike the 3460 and 11778 mutations, which are distributed throughout the European-derived (Caucasian) mtDNA phylogeny, patients containing the 14484 mutation tended to be associated with European mtDNA haplotype J. To investigate this apparent clustering, we performed {chi}{sup 2}-based statistical analyses to compare the distribution of LHON patients on the Caucasian phylogenetic tree. Our results indicate that, unlike the 3460 and 11778 mutations, the 14484 mutation was not distributed on the phylogeny in proportion to the frequencies of the major Caucasian mtDNA haplogroups found in North America. The 14484 mutation was next shown to occur on the haplogroup J background more frequently that expected, consistent with the observation that {approximately}75% of worldwide 14484-positive LHON patients occur in association with haplogroup J. The 11778 mutation also exhibited a moderate clustering on haplogroup J. These observations were supported by statistical analysis using all available mutation frequencies reported in the literature. This paper thus illustrates the potential importance of genetic background in certain mtDNA-based diseases, speculates on a pathogenic role for a subset of LHON secondary mutations and their interaction with primary mutations, and provides support for a polygenic model for LHON expression in some cases. 18 refs., 3 tabs.

  4. CD40-mediated apoptosis in murine B-lymphoma lines containing mutated p53

    DEFF Research Database (Denmark)

    Hollmann, Annette C; Gong, Qiaoke; Owens, Trevor

    2002-01-01

    Crosslinking CD40 induces normal B-cells to proliferate and differentiate but causes many tumor cell lines to undergo apoptosis. As p53 is required for many apoptotic pathways, we analyzed the effects of CD40 ligation and their correlation with p53 function in four murine B-lymphoma lines. A20...... of detectable p21 mRNA in A20 and M12 cells. P21 mRNA was increased to detectable levels in M12 cells upon CD40 ligation; however, blocking this effect with the p53 inhibitor pifithrin had no effect on CD40-mediated apoptosis. Sequencing showed that p53 in A20 and M12 cells contained point mutations leading...... to amino acid substitutions in DNA binding regions, but was unmutated in WEHI231 and WEHI 279. These results suggest that CD40-mediated apoptosis can occur in the absence of functional p53....

  5. Radiation-induced germ-line mutations detected by a direct comparison of parents and children DNA sequences containing SNPs

    International Nuclear Information System (INIS)

    Morimyo, M.; Hongo, E.; Higashi, T.; Wu, J.; Matsumoto, I.; Okamoto, M.; Kawano, A.; Tsuji, S.

    2003-01-01

    Full text: Germ-line mutation is detected in mice but not in humans. To estimate genetic risk of humans, a new approach to extrapolate from animal data to humans or to directly detect radiation-induced mutations in man is expected. We have developed a new method to detect germ-line mutations by directly comparing DNA sequences of parents and children. The nucleotide sequences among mouse strains are almost identical except SNP markers that are detected at 1/1000 frequency. When gamma-irradiated male mice are mated with female mice, heterogeneous nucleotide sequences induced in children DNA are a candidate of mutation, whose assignment can be done by SNP analysis. This system can easily detect all types of mutations such as transition, transversion, frameshift and deletion induced by radiation and can be applied to humans having genetically heterogeneous nucleotide sequences and many SNP markers. C3H male mice of 8 weeks of gestation were irradiated with gamma rays of 3 and 1 Gy and after 3 weeks, they were mated with the same aged C57BL female mice. After 3 weeks breeding, DNA was extracted from parents and children mice. The nucleotide sequences of 150 STS markers containing 300-900 bp and SNPs of parents and children DNA were determined by a direct sequencing; amplification of STS markers by Taq DNA polymerase, purification of PCR products, and DNA sequencing with a dye-terminator method. At each radiation dose, a total amount of 5 Mb DNA sequences were examined to detect radiation-induced mutations. We could find 6 deletions in 3 Gy irradiated mice but not in 1 Gy and control mice. The mutation frequency was about 4.0 x 10 -7 /bp/ Gy or 1.6 x 10 -4 /locus/Gy, and suggested the non-linear increase of mutation rate with dose

  6. Mutation mechanisms that underlie turnover of a human telomere-adjacent segmental duplication containing an unstable minisatellite.

    Science.gov (United States)

    Hills, Mark; Jeyapalan, Jennie N; Foxon, Jennifer L; Royle, Nicola J

    2007-04-01

    Subterminal regions, juxtaposed to telomeres on human chromosomes, contain a high density of segmental duplications, but relatively little is known about the evolutionary processes that underlie sequence turnover in these regions. We have characterized a segmental duplication adjacent to the Xp/Yp telomere, each copy containing a hypervariable array of the DXYS14 minisatellite. Both DXYS14 repeat arrays mutate at a high rate (0.3 and 0.2% per gamete) but linkage disequilibrium analysis across 27 SNPs and a direct crossover assay show that recombination during meiosis is suppressed. Therefore instability at DXYS14a and b is dominated by intra-allelic processes or possibly conversion limited to the repeat arrays. Furthermore some chromosomes (14%) carry only one copy of the duplicon, including one DXYS14 repeat array that is also highly mutable (1.2% per gamete). To explain these and other observations, we propose there is another low-rate mutation process that causes copy number change in part or all of the duplicon.

  7. Somatic mosaicism containing double mutations in PTCH1 revealed by generation of induced pluripotent stem cells from nevoid basal cell carcinoma syndrome.

    Science.gov (United States)

    Ikemoto, Yu; Takayama, Yoshinaga; Fujii, Katsunori; Masuda, Mokuri; Kato, Chise; Hatsuse, Hiromi; Fujitani, Kazuko; Nagao, Kazuaki; Kameyama, Kohzoh; Ikehara, Hajime; Toyoda, Masashi; Umezawa, Akihiro; Miyashita, Toshiyuki

    2017-08-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterised by developmental defects and tumorigenesis, such as medulloblastomas and basal cell carcinomas, caused by mutations of the patched-1 ( PTCH1 ) gene. In this article, we seek to demonstrate a mosaicism containing double mutations in PTCH1 in an individual with NBCCS. A de novo germline mutation of PTCH1 (c.272delG) was detected in a 31-year-old woman with NBCCS. Gene analysis of two out of four induced pluripotent stem cell (iPSC) clones established from the patient unexpectedly revealed an additional mutation, c.274delT. Deep sequencing confirmed a low-prevalence somatic mutation (5.5%-15.6% depending on the tissue) identical to the one found in iPSC clones. This is the first case of mosaicism unequivocally demonstrated in NBCCS. Furthermore, the mosaicism is unique in that the patient carries one normal and two mutant alleles. Because these mutations are located in close proximity, reversion error is likely to be involved in this event rather than a spontaneous mutation. In addition, this study indicates that gene analysis of iPSC clones can contribute to the detection of mosaicism containing a minor population carrying a second mutation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Discovery of potential drugs for human-infecting H7N9 virus containing R294K mutation

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    He JY

    2014-12-01

    Full Text Available Jiao-Yu He,1,* Cheng Li,2,* Guo Wu3 1College of Life Sciences and Key Laboratory for Bio-resources of Ministry of Education, Sichuan University, 2College of Agronomy, Sichuan Agricultural University, 3College of Life Sciences, Sichuan Normal University, Chengdu, People’s Republic of China *These authors contributed equally to this work Background: After the first epidemic wave from February through May 2013, the influenza A (H7N9 virus emerged and has followed a second epidemic wave since June 2013. As of June 27, 2014, the outbreak of H7N9 had caused 450 confirmed cases of human infection, with 165 deaths included. The case-fatality rate of all confirmed cases is about 36%, making the H7N9 virus a significant threat to people’s health. At present, neuraminidase inhibitors are the only licensed antiviral medications available to treat H7N9 infections in humans. Oseltamivir is the most commonly used inhibitor, and it is also a front-line drug for the threatening H7N9. Unfortunately, it has been reported that patients treated with oseltamivir can induce R294K (Arg294Lys substitution in the H7N9 virus, which is a rare mutation and can reduce the antiviral efficacy of inhibitors. Even worse, deaths caused by such mutation after oseltamivir treatment have already been reported, indicating that the need to find substitutive neuraminidase inhibitors for currently available drugs to treat drug-resistant H7N9 is really pressing.Materials and methods: First, the structure of H7N9 containing the R294K substitution was downloaded from the Protein Data Bank, and structural information of approved drugs was downloaded from the ZINC (ZINC Is Not Commercial database. Taking oseltamivir carboxylate as a reference drug, we then filtered these molecules through virtual screening to find out potential inhibitors targeting the mutated H7N9 virus. For further evaluation, we carried out a 14 ns molecular dynamic simulation for each H7N9–drug complex and

  9. Containment

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    The primary mission of the Containment Group is to ensure that underground nuclear tests are satisfactorily contained. The main goal is the development of sound technical bases for containment-related methodology. Major areas of activity include siting, geologic description, emplacement hole stemming, and phenomenological predictions. Performance results of sanded gypsum concrete plugs on the Jefferson, Panamint, Cornucopia, Labquark, and Bodie events are given. Activities are also described in the following areas: computational capabilities site description, predictive modeling, and cavity-pressure measurement. Containment publications are listed. 8 references

  10. Proton nuclear magnetic resonance studies on bulge-containing DNA oligonucleotides from a mutational hot-spot sequence

    International Nuclear Information System (INIS)

    Woodson, S.A.; Crothers, D.M.

    1987-01-01

    A series of bulge-containing and normal double-helical synthetic oligodeoxyribonucleotides, of sequence corresponding to a frame-shift mutational hot spot in the λ C/sub I/ gene, are compared by proton magnetic resonance spectroscopy at 500 MHz. The imino proton resonances are assigned by one-dimensional nuclear Overhauser effect spectroscopy. Nonselective T 1 inversion-recovery experiments are used to determine exchangeable proton lifetimes and to compare helix stability and dynamics of the three duplexes. An extra adenosine flanking the internal G-C base pairs has a strongly localized effect on helix stability, but the destabilizing effect of an extra cytidine in a C tract is delocalized over the entire G-C run. These data lead to the conclusion that the position of the bulge migrates along the run in the fast-exchange limit on the NMR time scale. Rapid migration of the bulge defect in homopolymeric sequences may help rationalize both frame-shift mutagenesis and translational frame shifting. The authors estimate that the unfavorable free energy of a localized bulge defect is 2.9-3.2 kcal/mol, in good agreement with earlier estimates for RNA helices

  11. A Point Mutation in an F-Box Domain-Containing Protein Is Responsible for Brown Hull Phenotype in Rice

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    Xu Xia

    2016-01-01

    Full Text Available The accumulation of pigments affects the color of rice hulls while only limited information is known about its underlying mechanisms. In the present study, a rice brown hull 6 (bh6 mutant was isolated from an ethane methyl sulfonate (EMS-induced IR64 mutant bank. Brown pigments started to accumulate in bh6 rice hulls after heading and reached a higher level in mature seeds. Some major agronomic traits including panicle length and 1000-grain weight in bh6 were significantly lower than those in its corresponding wild type IR64, while other agronomic traits such as plant height, growth duration and seed-setting rate were largely similar between the two genotypes. The analysis of pigment content showed that the contents of total flavonoids and anthocyanin in bh6 hulls were significantly higher than those in IR64 hulls. Our results showed that the brown hull phenotype in bh6 was controlled by a single recessive gene which locates on the long arm of chromosome 9. Sequencing analysis detected a single base substitution (G/A at position 1013 of the candidate gene (LOC_Os09g12150 encoding an F-box domain-containing protein (FBX310. Functional complementation experiment using the wild type allele can rescue the phenotype in bh6. Thus, we named this mutated gene as OsFBX310bh6, an allele of OsFBX310 functioning as an inhibitor of brown hull. The isolation of OsFBX310bh6 and its wild type allele can provide useful experimental materials and will facilitate the studies on revealing the mechanisms of flavonoid metabolism in monocot plants.

  12. Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

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    Soo-Yon Rhee

    2017-04-01

    Full Text Available Tenofovir disoproxil fumarate (TDF genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs, we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 – A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F – were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.

  13. The C-terminal extension of human RTEL1, mutated in Hoyeraal-Hreidarsson syndrome, contains harmonin-N-like domains.

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    Faure, Guilhem; Revy, Patrick; Schertzer, Michael; Londono-Vallejo, Arturo; Callebaut, Isabelle

    2014-06-01

    Several studies have recently shown that germline mutations in RTEL1, an essential DNA helicase involved in telomere regulation and DNA repair, cause Hoyeraal-Hreidarsson syndrome (HHS), a severe form of dyskeratosis congenita. Using original new softwares, facilitating the delineation of the different domains of the protein and the identification of remote relationships for orphan domains, we outline here that the C-terminal extension of RTEL1, downstream of its catalytic domain and including several HHS-associated mutations, contains a yet unidentified tandem of harmonin-N-like domains, which may serve as a hub for partner interaction. This finding highlights the potential critical role of this region for the function of RTEL1 and gives insights into the impact that the identified mutations would have on the structure and function of these domains. © 2013 Wiley Periodicals, Inc.

  14. One adenosine deaminase allele in a patient with severe combined immunodeficiency contains a point mutation abolishing enzyme activity.

    OpenAIRE

    Valerio, D; Dekker, B M; Duyvesteyn, M G; van der Voorn, L; Berkvens, T M; van Ormondt, H; van der Eb, A J

    1986-01-01

    We have cloned and sequenced an adenosine deaminase (ADA) gene from a patient with severe combined immunodeficiency (SCID) caused by inherited ADA deficiency. Two point mutations were found, resulting in amino acid substitutions at positions 80 (Lys to Arg) and 304 (Leu to Arg) of the protein. Hybridization experiments with synthetic oligonucleotide probes showed that the determined mutations are present in both DNA and RNA from the ADA-SCID patient. In addition, wild-type sequences could be ...

  15. Mutations in valosin-containing protein (VCP) decrease ADP/ATP translocation across the mitochondrial membrane and impair energy metabolism in human neurons.

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    Ludtmann, Marthe H R; Arber, Charles; Bartolome, Fernando; de Vicente, Macarena; Preza, Elisavet; Carro, Eva; Houlden, Henry; Gandhi, Sonia; Wray, Selina; Abramov, Andrey Y

    2017-05-26

    Mutations in the gene encoding valosin-containing protein (VCP) lead to multisystem proteinopathies including frontotemporal dementia. We have previously shown that patient-derived VCP mutant fibroblasts exhibit lower mitochondrial membrane potential, uncoupled respiration, and reduced ATP levels. This study addresses the underlying basis for mitochondrial uncoupling using VCP knockdown neuroblastoma cell lines, induced pluripotent stem cells (iPSCs), and iPSC-derived cortical neurons from patients with pathogenic mutations in VCP Using fluorescent live cell imaging and respiration analysis we demonstrate a VCP mutation/knockdown-induced dysregulation in the adenine nucleotide translocase, which results in a slower rate of ADP or ATP translocation across the mitochondrial membranes. This deregulation can explain the mitochondrial uncoupling and lower ATP levels in VCP mutation-bearing neurons via reduced ADP availability for ATP synthesis. This study provides evidence for a role of adenine nucleotide translocase in the mechanism underlying altered mitochondrial function in VCP-related degeneration, and this new insight may inform efforts to better understand and manage neurodegenerative disease and other proteinopathies. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Recombinant Marburg viruses containing mutations in the IID region of VP35 prevent inhibition of Host immune responses.

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    Albariño, César G; Wiggleton Guerrero, Lisa; Spengler, Jessica R; Uebelhoer, Luke S; Chakrabarti, Ayan K; Nichol, Stuart T; Towner, Jonathan S

    2015-02-01

    Previous in vitro studies have demonstrated that Ebola and Marburg virus (EBOV and MARV) VP35 antagonize the host cell immune response. Moreover, specific mutations in the IFN inhibitory domain (IID) of EBOV and MARV VP35 that abrogate their interaction with virus-derived dsRNA, lack the ability to inhibit the host immune response. To investigate the role of MARV VP35 in the context of infectious virus, we used our reverse genetics system to generate two recombinant MARVs carrying specific mutations in the IID region of VP35. Our data show that wild-type and mutant viruses grow to similar titers in interferon deficient cells, but exhibit attenuated growth in interferon-competent cells. Furthermore, in contrast to wild-type virus, both MARV mutants were unable to inhibit expression of various antiviral genes. The MARV VP35 mutants exhibit similar phenotypes to those previously described for EBOV, suggesting the existence of a shared immune-modulatory strategy between filoviruses. Published by Elsevier Inc.

  17. Increased PRPP synthetase activity in cultured rat hepatoma cells containing mutations in the hypoxanthine-guanine phosphoribosyltransferase gene.

    Science.gov (United States)

    Graf, L H; McRoberts, J A; Harrison, T M; Martin, D W

    1976-07-01

    Nine independently derived clones of mutagenized rat hepatoma cells selected for resistance to 6-mercaptopurine (6-MP) or 6-thioguanine (6-ThioG) have been isolated. Each has severely reduced catalytic activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and seven of them possess significantly increased activities of phosphoribosylpyrophosphate (PRPP) synthetase. The degrees of elevations of PRPP synthetase activities do not correlate with the degrees of deficiencies of HPRT activities. The cells from one of these clones, 1020/12, posses 40% of the normal HPRT catalytic activity and overproduce purines. We have extensively examined the cells from this clone. Immunotration studies of 1020/12 cells indicate that there is a mutation in the structural gene for HPRT. Although they possess increased specific catalytic activities of the enzyme. PRPP synthetase, the catalytic parameters, heat stability, and isoelectric pH of PRPP synthetase from 1020/12 cells are indistinguishable from those of the enzyme from wild-type cells. The cause of purine overproduction by 1020/12 cells appears to be the elevated PRPP synthetase activity, rather than a PRPP "sparing" effect stemming from reduced HPRT activity. Support for this idea is provided by the observation that the complete loss of HPRT activity in a clone derived from 1020/12 cells does not further enhance the levels of PRPP synthetase or purine overproduction. We propose that the elevated levels of PRPP synthetase activity in these HPRT deficient cells result from a mutational event in the structural gene for HPRT, and that this causes the disruption of a previously undescribed regulatory function of this gene on the expression of the PRPP synthetase gene.

  18. Prion protein with Y145STOP mutation induces mitochondria-mediated apoptosis and PrP-containing deposits in vitro

    International Nuclear Information System (INIS)

    Hachiya, Naomi S.; Watanabe, Kota; Kawabata, Makiko Y.; Jozuka, Akiko; Kozuka, Yoshimichi; Sakasegawa, Yuji; Kaneko, Kiyotoshi

    2005-01-01

    A pathogenic truncation of an amber mutation at codon 145 (Y145STOP) in Gerstmann-Straussler-Scheinker disease (GSS) was investigated through the real-time imaging in living cells, by utilizing GFP-PrP constructs. GFP-PrP(1-144) exhibited an aberrant localization to mitochondria in mouse neuroblastoma neuro2a (N2a) and HpL3-4 cells, a hippocampal cell line established from prnp gene-ablated mice, whereas full-length GFP-PrP did not. The aberrant mitochondrial localization was also confirmed by Western blot analysis. Since GFP-PrP(1-121), as previously reported, and full-length GFP-PrP do not exhibit such mitochondrial localization, the mitochondrial localization of GFP-PrP(1-144) requires not only PrP residues 121-144 (in human sequence) but also COOH-terminal truncation in the current experimental condition. Subsequently, the GFP-PrP(1-144) induced a change in the mitochondrial innermembrane potential (ΔΨ m ), release of cytochrome c from the intermembrane space into the cytosol, and DNA fragmentation in these cells. Non-fluorescent PrP(1-144) also induced the DNA fragmentation in N2a and HpL3-4 cells after the proteasomal inhibition. These data may provide clues as to the molecular mechanism of the neurotoxic property of Y145STOP mutation. Furthermore, immunoelectron microscopy revealed numerous electron-dense deposits in mitochondria clusters of GFP-PrP(1-144)-transfected N2a cells, whereas no deposit was detected in the cells transfected with full-length GFP-PrP. Co-localization of GFP/PrP-immunogold particles with porin-immunogold particles as a mitochondrial marker was observed in such electron-dense vesicular foci, resembling those found in autophagic vacuoles forming secondary lysosomes. Whether such electron-dense deposits may serve as a seed for the growth of amyloid plaques, a characteristic feature of GSS with Y145STOP, awaits further investigations

  19. Molecular analysis of congenital goitres with hypothyroidism caused by defective thyroglobulin synthesis. Identification of a novel c.7006C>T [p.R2317X] mutation and expression of minigenes containing nonsense mutations in exon 7.

    Science.gov (United States)

    Machiavelli, Gloria A; Caputo, Mariela; Rivolta, Carina M; Olcese, María C; Gruñeiro-Papendieck, Laura; Chiesa, Ana; González-Sarmiento, Rogelio; Targovnik, Héctor M

    2010-01-01

    Thyroglobulin (TG) deficiency is an autosomal-recessive disorder that results in thyroid dyshormonogenesis. A number of distinct mutations have been identified as causing human hypothyroid goitre. The purpose of this study was to identify and characterize new mutations in the TG gene in an attempt to increase the understanding of the genetic mechanism responsible for this disorder. A total of six patients from four nonconsanguineous families with marked impairment of TG synthesis were studied. Single-strand conformation polymorphism (SSCP) analysis, sequencing of DNA, genotyping, expression of chimeric minigenes and bioinformatic analysis were performed. Four different inactivating TG mutations were identified: one novel mutation (c.7006C>T [p.R2317X]) and three previously reported (c.886C>T [p.R277X], c.6701C>A [p.A2215D] and c.6725G>A [p.R2223H]). Consequently, one patient carried a compound heterozygous for p.R2223H/p.R2317X mutations; two brothers showed a homozygous p.A2215D substitution and the remaining three patients, from two families with typical phenotype, had a single p.R277X mutated allele. We also showed functional evidences that premature stop codons inserted at different positions in exon 7, which disrupt exonic splicing enhancer (ESE) sequences, do not interfere with exon definition and processing. In this study, we have identified a novel nonsense mutation p.R2317X in the acetylcholinesterase homology domain of TG. We have also observed that nonsense mutations do not interfere with the pre-mRNA splicing of exon 7. The results are in accordance with previous observations confirming the genetic heterogeneity of TG defects.

  20. Identification of Immunogenic Cytotoxic T Lymphocyte Epitopes Containing Drug Resistance Mutations in Antiretroviral Treatment-Naïve HIV-Infected Individuals.

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    Juan Blanco-Heredia

    Full Text Available Therapeutic HIV vaccines may prove helpful to intensify antiretroviral treatment (ART efficacy and may be an integral part of future cure strategies.We examined IFN-gamma ELISpot responses to a panel of 218 HIV clade B consensus-based HIV protease-reverse transcriptase peptides, designed to mimic previously described and predicted cytotoxic T lymphocyte epitopes overlapping drug resistance (DR positions, that either included the consensus sequence or the DR variant sequence, in 49 ART-naïve HIV-infected individuals. Next generation sequencing was used to assess the presence of minority DR variants in circulating viral populations.Although a wide spectrum of differential magnitudes of response to DR vs. WT peptide pairs was observed, responses to DR peptides were frequent and strong in the study cohort. No difference between the median magnitudes of response to DR vs. WT peptides was observed. Interestingly, of the 22 peptides that were recognized by >15% of the participants, two-thirds (64% corresponded to DR peptides. When analysing responses per peptide pair per individual, responses to only WT (median 4 pairs/individual or DR (median 6 pairs/individual were more common than responses to both WT and DR (median 2 pairs/individual; p<0.001. While the presence of ELISpot responses to WT peptides was frequently associated with the presence of the corresponding peptide sequence in the patient's virus (mean 68% of cases, responses to DR peptides were generally not associated with the presence of DR mutations in the viral population, even at low frequencies (mean 1.4% of cases; p = 0.0002.Our data suggests that DR peptides are frequently immunogenic and raises the potential benefit of broadening the antigens included in a therapeutic vaccine approach to immunogenic epitopes containing common DR sequences. Further studies are needed to assess the quality of responses elicited by DR peptides.

  1. Mutation breeding newsletter. No. 45

    International Nuclear Information System (INIS)

    2001-07-01

    This issue of the Mutation Breeding newsletter contains 39 articles dealing with radiation induced mutations and chemical mutagenesis techniques in plant breeding programs with the aims of improving crop productivity and disease resistance as well as exploring genetic variabilities

  2. Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1 vaccine candidates containing stabilized mutations in the P/C and L genes

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    Skiadopoulos Mario H

    2007-07-01

    Full Text Available Abstract Background Two recombinant, live attenuated human parainfluenza virus type 1 (rHPIV1 mutant viruses have been developed, using a reverse genetics system, for evaluation as potential intranasal vaccine candidates. These rHPIV1 vaccine candidates have two non-temperature sensitive (non-ts attenuating (att mutations primarily in the P/C gene, namely CR84GHNT553A (two point mutations used together as a set and CΔ170 (a short deletion mutation, and two ts att mutations in the L gene, namely LY942A (a point mutation, and LΔ1710–11 (a short deletion, the last of which has not been previously described. The latter three mutations were specifically designed for increased genetic and phenotypic stability. These mutations were evaluated on the HPIV1 backbone, both individually and in combination, for attenuation, immunogenicity, and protective efficacy in African green monkeys (AGMs. Results The rHPIV1 mutant bearing the novel LΔ1710–11 mutation was highly ts and attenuated in AGMs and was immunogenic and efficacious against HPIV1 wt challenge. The rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 vaccine candidates were highly ts, with shut-off temperatures of 38°C and 35°C, respectively, and were highly attenuated in AGMs. Immunization with rHPIV1-CR84G/Δ170HNT553ALY942A protected against HPIV1 wt challenge in both the upper and lower respiratory tracts. In contrast, rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 was not protective in AGMs due to over-attenuation, but it is expected to replicate more efficiently and be more immunogenic in the natural human host. Conclusion The rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 vaccine candidates are clearly highly attenuated in AGMs and clinical trials are planned to address safety and immunogenicity in humans.

  3. Mutations in type 3 reovirus that determine binding to sialic acid are contained in the fibrous tail domain of viral attachment protein sigma1.

    Science.gov (United States)

    Chappell, J D; Gunn, V L; Wetzel, J D; Baer, G S; Dermody, T S

    1997-03-01

    The reovirus attachment protein, sigma1, determines numerous aspects of reovirus-induced disease, including viral virulence, pathways of spread, and tropism for certain types of cells in the central nervous system. The sigma1 protein projects from the virion surface and consists of two distinct morphologic domains, a virion-distal globular domain known as the head and an elongated fibrous domain, termed the tail, which is anchored into the virion capsid. To better understand structure-function relationships of sigma1 protein, we conducted experiments to identify sequences in sigma1 important for viral binding to sialic acid, a component of the receptor for type 3 reovirus. Three serotype 3 reovirus strains incapable of binding sialylated receptors were adapted to growth in murine erythroleukemia (MEL) cells, in which sialic acid is essential for reovirus infectivity. MEL-adapted (MA) mutant viruses isolated by serial passage in MEL cells acquired the capacity to bind sialic acid-containing receptors and demonstrated a dependence on sialic acid for infection of MEL cells. Analysis of reassortant viruses isolated from crosses of an MA mutant virus and a reovirus strain that does not bind sialic acid indicated that the sigma1 protein is solely responsible for efficient growth of MA mutant viruses in MEL cells. The deduced sigma1 amino acid sequences of the MA mutant viruses revealed that each strain contains a substitution within a short region of sequence in the sigma1 tail predicted to form beta-sheet. These studies identify specific sequences that determine the capacity of reovirus to bind sialylated receptors and suggest a location for a sialic acid-binding domain. Furthermore, the results support a model in which type 3 sigma1 protein contains discrete receptor binding domains, one in the head and another in the tail that binds sialic acid.

  4. Mutation Breeding Newsletter. No. 37

    International Nuclear Information System (INIS)

    1991-01-01

    This newsletter contains a brief account of FAO/IAEA meetings held in 1990 on plant breeding involving the use of induced mutations. It also features a list of commercially available plant cultivars produced by such techniques. Refs and tabs

  5. Mutation Breeding Newsletter. No. 39

    International Nuclear Information System (INIS)

    1992-01-01

    This newsletter contains brief articles on the use of radiation to induce mutations in plants; radiation-induced mutants in Chrysanthemum; disrupting the association between oil and protein content in soybean seeds; mutation studies on bougainvillea; a new pepper cultivar; and the use of mutation induction to improve the quality of yam beans. A short review of the seminar on the use of mutation and related biotechnology for crop improvement in the Middle East and Mediterranean regions, and a description of a Co-ordinated Research Programme on the application of DNA-based marker mutations for the improvement of cereals and other sexually reproduced crop species are also included. Two tables are given: these are based on the ''FAO/IAEA Mutant Varieties Database'' and show the number of mutated varieties and the number of officially released mutant varieties in particular crops/species. Refs and tabs

  6. In Vitro Resistance Studies with Bacteria That Exhibit Low Mutation Frequencies: Prediction of “Antimutant” Linezolid Concentrations Using a Mixed Inoculum Containing both Susceptible and Resistant Staphylococcus aureus

    Science.gov (United States)

    Golikova, Maria V.; Strukova, Elena N.; Portnoy, Yury A.; Romanov, Andrey V.; Edelstein, Mikhail V.; Zinner, Stephen H.

    2014-01-01

    Bacterial resistance studies using in vitro dynamic models are highly dependent on the starting inoculum that might or might not contain spontaneously resistant mutants (RMs). To delineate concentration-resistance relationships with linezolid-exposed Staphylococcus aureus, a mixed inoculum containing both susceptible cells and RMs was used. An RM selected after the 9th passage of the parent strain (MIC, 2 μg/ml) on antibiotic-containing media (RM9; MIC, 8 μg/ml) was chosen for the pharmacodynamic studies, because the mutant prevention concentration (MPC) of linezolid against the parent strain in the presence of RM9 at 102 (but not at 104) CFU/ml did not differ from the MPC value determined in the absence of the RMs. Five-day treatments with twice-daily linezolid doses were simulated at concentrations either between the MIC and MPC or above the MPC. S. aureus RMs (resistant to 2× and 4× MIC but not 8× and 16× MIC) were enriched at ratios of the 24-h area under the concentration-time curve (AUC24) to the MIC that provide linezolid concentrations between the MIC and MPC for 100% (AUC24/MIC, 60 h) and 86% (AUC24/MIC, 120 h) of the dosing interval. No such enrichment occurred when linezolid concentrations were above the MIC and below the MPC for a shorter time (37% of the dosing interval; AUC24/MIC, 240 h) or when concentrations were consistently above the MPC (AUC24/MIC, 480 h). These findings obtained using linezolid-susceptible staphylococci supplemented with RMs support the mutant selection window hypothesis. This method provides an option to delineate antibiotic concentration-resistance relationships with bacteria that exhibit low mutation frequencies. PMID:25451050

  7. Mutational analysis of the RNA-binding domain of the Prunus necrotic ringspot virus (PNRSV) movement protein reveals its requirement for cell-to-cell movement.

    Science.gov (United States)

    Carmen Herranz, Ma; Sanchez-Navarro, Jesús-Angel; Saurí, Ana; Mingarro, Ismael; Pallás, Vicente

    2005-08-15

    The movement protein (MP) of Prunus necrotic ringspot virus (PNRSV) is required for cell-to-cell movement. MP subcellular localization studies using a GFP fusion protein revealed highly punctate structures between neighboring cells, believed to represent plasmodesmata. Deletion of the RNA-binding domain (RBD) of PNRSV MP abolishes the cell-to-cell movement. A mutational analysis on this RBD was performed in order to identify in vivo the features that govern viral transport. Loss of positive charges prevented the cell-to-cell movement even though all mutants showed a similar accumulation level in protoplasts to those observed with the wild-type (wt) MP. Synthetic peptides representing the mutants and wild-type RBDs were used to study RNA-binding affinities by EMSA assays being approximately 20-fold lower in the mutants. Circular dichroism analyses revealed that the secondary structure of the peptides was not significantly affected by mutations. The involvement of the affinity changes between the viral RNA and the MP in the viral cell-to-cell movement is discussed.

  8. Mutational analysis of the RNA-binding domain of the Prunus necrotic ringspot virus (PNRSV) movement protein reveals its requirement for cell-to-cell movement

    International Nuclear Information System (INIS)

    Carmen Herranz, Ma; Sanchez-Navarro, Jesus-Angel; Sauri, Ana; Mingarro, Ismael; Pallas, Vicente

    2005-01-01

    The movement protein (MP) of Prunus necrotic ringspot virus (PNRSV) is required for cell-to-cell movement. MP subcellular localization studies using a GFP fusion protein revealed highly punctate structures between neighboring cells, believed to represent plasmodesmata. Deletion of the RNA-binding domain (RBD) of PNRSV MP abolishes the cell-to-cell movement. A mutational analysis on this RBD was performed in order to identify in vivo the features that govern viral transport. Loss of positive charges prevented the cell-to-cell movement even though all mutants showed a similar accumulation level in protoplasts to those observed with the wild-type (wt) MP. Synthetic peptides representing the mutants and wild-type RBDs were used to study RNA-binding affinities by EMSA assays being approximately 20-fold lower in the mutants. Circular dichroism analyses revealed that the secondary structure of the peptides was not significantly affected by mutations. The involvement of the affinity changes between the viral RNA and the MP in the viral cell-to-cell movement is discussed

  9. Mutations induced by ultraviolet light

    International Nuclear Information System (INIS)

    Pfeifer, Gerd P.; You, Young-Hyun; Besaratinia, Ahmad

    2005-01-01

    The different ultraviolet (UV) wavelength components, UVA (320-400 nm), UVB (280-320 nm), and UVC (200-280 nm), have distinct mutagenic properties. A hallmark of UVC and UVB mutagenesis is the high frequency of transition mutations at dipyrimidine sequences containing cytosine. In human skin cancers, about 35% of all mutations in the p53 gene are transitions at dipyrimidines within the sequence 5'-TCG and 5'-CCG, and these are localized at several mutational hotspots. Since 5'-CG sequences are methylated along the p53 coding sequence in human cells, these mutations may be derived from sunlight-induced pyrimidine dimers forming at sequences that contain 5-methylcytosine. Cyclobutane pyrimidine dimers (CPDs) form preferentially at dipyrimidines containing 5-methylcytosine when cells are irradiated with UVB or sunlight. In order to define the contribution of 5-methylcytosine to sunlight-induced mutations, the lacI and cII transgenes in mouse fibroblasts were used as mutational targets. After 254 nm UVC irradiation, only 6-9% of the base substitutions were at dipyrimidines containing 5-methylcytosine. However, 24-32% of the solar light-induced mutations were at dipyrimidines that contain 5-methylcytosine and most of these mutations were transitions. Thus, CPDs forming preferentially at dipyrimidines with 5-methylcytosine are responsible for a considerable fraction of the mutations induced by sunlight in mammalian cells. Using mouse cell lines harboring photoproduct-specific photolyases and mutational reporter genes, we showed that CPDs (rather than 6-4 photoproducts or other lesions) are responsible for the great majority of UVB-induced mutations. An important component of UVB mutagenesis is the deamination of cytosine and 5-methylcytosine within CPDs. The mutational specificity of long-wave UVA (340-400 nm) is distinct from that of the shorter wavelength UV and is characterized mainly by G to T transversions presumably arising through mechanisms involving oxidized DNA

  10. Manual on mutation breeding. 2. ed.

    International Nuclear Information System (INIS)

    1977-01-01

    The manual is a compilation of work done on the use of induced mutations in plant breeding, and presents general methods and techniques in this field. The use of chemical mutagens and ionizing radiations (X-rays, gamma rays, α- and β-particles, protons, neutrons) are described as well as the effects of these mutagens. The different types of mutations achieved can be divided into genome mutations, chromosome mutations and extra nuclear mutations. Separate chapters deal with mutation techniques in breeding seed-propagated species and asexually propagated plants (examples of development of cultivars given). Plant characters which can be improved by mutation breeding include yield, ripening time, growth habit, disease resistance and tolerance to environmental factors (temperature, salinity etc.). The use of mutagens for some specific plant breeding problems is discussed and attention is also paid to somatic cell genetics in connection with induced mutations. The manual contains a comprehensive bibliography (60 p. references) and a subject index

  11. New mutations in APOB100 involved in familial hypobetalipoproteinemia

    DEFF Research Database (Denmark)

    Brusgaard, Klaus; Kjaersgaard, Lars; Hansen, Anne-Birthe Bo

    2011-01-01

    Familial hypolipoproteinemia (FHBL) is characterized by an inherited low plasma level of apolipoprotein B containing lipoproteins. FHBL may be caused by mutations of APOB. Individuals with FHBL typically have intestinal malabsorption and frequently suffer from a deficiency of fat-soluble vitamins....... Most mutations that cause FHBL are APOB truncating mutations. Here we describe a patient with FHBL caused by a novel truncating mutation together with a novel missense mutation....

  12. Volatility of Mutator Phenotypes at Single Cell Resolution.

    Directory of Open Access Journals (Sweden)

    Scott R Kennedy

    2015-04-01

    Full Text Available Mutator phenotypes accelerate the evolutionary process of neoplastic transformation. Historically, the measurement of mutation rates has relied on scoring the occurrence of rare mutations in target genes in large populations of cells. Averaging mutation rates over large cell populations assumes that new mutations arise at a constant rate during each cell division. If the mutation rate is not constant, an expanding mutator population may contain subclones with widely divergent rates of evolution. Here, we report mutation rate measurements of individual cell divisions of mutator yeast deficient in DNA polymerase ε proofreading and base-base mismatch repair. Our data are best fit by a model in which cells can assume one of two distinct mutator states, with mutation rates that differ by an order of magnitude. In error-prone cell divisions, mutations occurred on the same chromosome more frequently than expected by chance, often in DNA with similar predicted replication timing, consistent with a spatiotemporal dimension to the hypermutator state. Mapping of mutations onto predicted replicons revealed that mutations were enriched in the first half of the replicon as well as near termination zones. Taken together, our findings show that individual genome replication events exhibit an unexpected volatility that may deepen our understanding of the evolution of mutator-driven malignancies.

  13. Mutation in cultured mammalian cells

    International Nuclear Information System (INIS)

    Nakamura, N.; Okada, S.

    1982-01-01

    Mammalian cell cultures were exposed to gamma-rays at various dose rates. Dose-rate effects were observed in cultured somatic cells of the mouse for cell killing and mutations resistant to 6-thioguanine (TGsup(r)) and to methotrexate (MTXsup(r)). Linear quadratic model may be applied to cell killing and TGsup(r) mutations in some cases but can not explain the whole data. Results at low doses with far low dose-rate were not predictable from data at high doses with acute or chronic irradiation. Radioprotective effects of dimethyl sulfoxide were seen only after acute exposure but not after chronic one, suggesting that damages by indirect action of radiations may be potentially reparable by cells. TGsup(r) mutations seem to contain gross structural changes whereas MTXsup(r) ones may have smaller alterations. (Namekawa, K.)

  14. The CDC Hemophilia B mutation project mutation list: a new online resource.

    Science.gov (United States)

    Li, Tengguo; Miller, Connie H; Payne, Amanda B; Craig Hooper, W

    2013-11-01

    Hemophilia B (HB) is caused by mutations in the human gene F9. The mutation type plays a pivotal role in genetic counseling and prediction of inhibitor development. To help the HB community understand the molecular etiology of HB, we have developed a listing of all F9 mutations that are reported to cause HB based on the literature and existing databases. The Centers for Disease Control and Prevention (CDC) Hemophilia B Mutation Project (CHBMP) mutation list is compiled in an easily accessible format of Microsoft Excel and contains 1083 unique mutations that are reported to cause HB. Each mutation is identified using Human Genome Variation Society (HGVS) nomenclature standards. The mutation types and the predicted changes in amino acids, if applicable, are also provided. Related information including the location of mutation, severity of HB, the presence of inhibitor, and original publication reference are listed as well. Therefore, our mutation list provides an easily accessible resource for genetic counselors and HB researchers to predict inhibitors. The CHBMP mutation list is freely accessible at http://www.cdc.gov/hemophiliamutations.

  15. Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings

    DEFF Research Database (Denmark)

    Cozzi-Lepri, Alessandro; Phillips, Andrew N; Martinez-Picado, Javier

    2009-01-01

    BACKGROUND: Because changes in antiretroviral therapy in resource-limited settings (RLSs) are delayed until patients experience immunological or clinical failure, it is important to be able to estimate the consequences in terms of accumulation of thymidine analogue (TA) mutations (TAMs). METHODS...... until the second GRT. RESULTS: At the time of the first GRT in a pair (t0), 1 year after virological failure, a median of 3 TAMs were detected, mutations 41L and 215Y in 65% of pairs and 67N in 52%. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (PYFUs) (1/4.3 years; 95......% confidence interval, 3.7-5.0 years). Greater predicted activity of the TA at t0, TAM profile 2 (TAM2; vs TAM profile 1 [TAM1]) profiles at t0, use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) at t0 (vs combined NNRTI and protease inhibitor), and acquisition of HIV infection through heterosexual...

  16. Mutational robustness of gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Aalt D J van Dijk

    Full Text Available Mutational robustness of gene regulatory networks refers to their ability to generate constant biological output upon mutations that change network structure. Such networks contain regulatory interactions (transcription factor-target gene interactions but often also protein-protein interactions between transcription factors. Using computational modeling, we study factors that influence robustness and we infer several network properties governing it. These include the type of mutation, i.e. whether a regulatory interaction or a protein-protein interaction is mutated, and in the case of mutation of a regulatory interaction, the sign of the interaction (activating vs. repressive. In addition, we analyze the effect of combinations of mutations and we compare networks containing monomeric with those containing dimeric transcription factors. Our results are consistent with available data on biological networks, for example based on evolutionary conservation of network features. As a novel and remarkable property, we predict that networks are more robust against mutations in monomer than in dimer transcription factors, a prediction for which analysis of conservation of DNA binding residues in monomeric vs. dimeric transcription factors provides indirect evidence.

  17. Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+

    DEFF Research Database (Denmark)

    Venco, Paola; Bonora, Massimo; Giorgi, Carlotta

    2015-01-01

    19orf12 protein was not exclusively present in mitochondria, but also in the Endoplasmic Reticulum (ER) and MAM (Mitochondria Associated Membrane), while mutant C19orf12 variants presented a different localization. Moreover, after induction of oxidative stress, a GFP-tagged C19orf12 wild-type protein...... was able to relocate to the cytosol. On the contrary, mutant isoforms were not able to respond to oxidative stress. High mitochondrial calcium concentration and increased H2O2 induced apoptosis were found in fibroblasts derived from one patient as compared to controls. C19orf12 protein is a 17 k...... to rearrange in a structural domain, which is homologs to the N-terminal regulatory domain of the magnesium transporter MgtE, suggesting that C19orf12 may act as a regulatory protein for human MgtE transporters. The mutations here described affect respectively one glycine residue of the glycine zipper motifs...

  18. Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+.

    Directory of Open Access Journals (Sweden)

    Paola eVenco

    2015-05-01

    Full Text Available Mutations in C19orf12 have been identified in patients affected by Neurodegeneration with Brain Iron Accumulation (NBIA, a clinical entity characterized by iron accumulation in the basal ganglia. By using western blot analysis with specific antibody and confocal studies, we showed that wild-type C19orf12 protein was not exclusively present in mitochondria, but also in the Endoplasmic Reticulum (ER and MAM (Mitochondria Associated Membrane, while mutant C19orf12 variants presented a different localization. Moreover, after induction of oxidative stress, a GFP-tagged C19orf12 wild-type protein was able to relocate to the cytosol. On the contrary, mutant isoforms were not able to respond to oxidative stress. High mitochondrial calcium concentration and increased H2O2 induced apoptosis were found in fibroblasts derived from one patient as compared to controls.C19orf12 protein is a 17kDa mitochondrial membrane-associated protein whose function is still unknown. Our in silico investigation suggests that, the glycine zipper motifs of C19orf12 form helical regions spanning the membrane. The N- and C-terminal regions with respect to the transmembrane portion, on the contrary, are predicted to rearrange in a structural domain, which is homologues to the N-terminal regulatory domain of the magnesium transporter MgtE, suggesting that C19orf12 may act as a regulatory protein for human MgtE transporters. The mutations here described affect respectively one glycine residue of the glycine zipper motifs, which are involved in dimerization of transmembrane helices and predicted to impair the correct localization of the protein into the membranes, and one residue present in the regulatory domain, which is important for protein-protein interaction.

  19. Mutation update for the PORCN gene

    DEFF Research Database (Denmark)

    Lombardi, Maria Paola; Bulk, Saskia; Celli, Jacopo

    2011-01-01

    Mutations in the PORCN gene were first identified in Goltz-Gorlin syndrome patients in 2007. Since then, several reports have been published describing a large variety of genetic defects resulting in the Goltz-Gorlin syndrome, and mutations or deletions were also reported in angioma serpiginosum......, the pentalogy of Cantrell and Limb-Body Wall Complex. Here we present a review of the published mutations in the PORCN gene to date and report on seven new mutations together with the corresponding clinical data. Based on the review we have created a Web-based locus-specific database that lists all identified...... variants and allows the inclusion of future reports. The database is based on the Leiden Open (source) Variation Database (LOVD) software, and is accessible online at http://www.lovd.nl/porcn. At present, the database contains 106 variants, representing 68 different mutations, scattered along the whole...

  20. Mutation breeding newsletter. No. 41

    International Nuclear Information System (INIS)

    1994-07-01

    This newsletter contains short descriptions of research methods for the use of radiation to induce mutations and facilitate plant breeding. This method is used to develop species of plants that can survive in harsh climates and thus provide a food supply for humans and animals. Some of the mutants discussed include a salt tolerant barley, a disease resistant shrub, a cold tolerant chickpea, a highly productive Canavalia virosa and productive tomato. Refs, figs and tabs

  1. Molecular methods for the detection of mutations.

    Science.gov (United States)

    Monteiro, C; Marcelino, L A; Conde, A R; Saraiva, C; Giphart-Gassler, M; De Nooij-van Dalen, A G; Van Buuren-van Seggelen, V; Van der Keur, M; May, C A; Cole, J; Lehmann, A R; Steinsgrimsdottir, H; Beare, D; Capulas, E; Armour, J A

    2000-01-01

    We report the results of a collaborative study aimed at developing reliable, direct assays for mutation in human cells. The project used common lymphoblastoid cell lines, both with and without mutagen treatment, as a shared resource to validate the development of new molecular methods for the detection of low-level mutations in the presence of a large excess of normal alleles. As the "gold standard, " hprt mutation frequencies were also measured on the same samples. The methods under development included i) the restriction site mutation (RSM) assay, in which mutations lead to the destruction of a restriction site; ii) minisatellite length-change mutation, in which mutations lead to alleles containing new numbers of tandem repeat units; iii) loss of heterozygosity for HLA epitopes, in which antibodies can be used to direct selection for mutant cells; iv) multiple fluorescence-based long linker arm nucleotides assay (mf-LLA) technology, for the detection of substitutional mutations; v) detection of alterations in the TP53 locus using a (CA) array as the target for the screening; and vi) PCR analysis of lymphocytes for the presence of the BCL2 t(14:18) translocation. The relative merits of these molecular methods are discussed, and a comparison made with more "traditional" methods.

  2. Shielding container

    International Nuclear Information System (INIS)

    Darling, K.A.M.

    1981-01-01

    A shielding container incorporates a dense shield, for example of depleted uranium, cast around a tubular member of curvilinear configuration for accommodating a radiation source capsule. A lining for the tubular member, in the form of a close-coiled flexible guide, provides easy replaceability to counter wear while the container is in service. Container life is extended, and maintenance costs are reduced. (author)

  3. Reactor container

    International Nuclear Information System (INIS)

    Ichiki, Tadaharu; Saba, Kazuhisa.

    1979-01-01

    Purpose: To improve the earthquake resistance as well as reduce the size of a container for a nuclear reactor with no adverse effects on the decrease of impact shock to the container and shortening of construction step. Constitution: Reinforcing profile steel materials are welded longitudinally and transversely to the inner surface of a container, and inner steel plates are secured to the above profile steel materials while keeping a gap between the materials and the container. Reactor shielding wall planted to the base concrete of the container is mounted to the pressure vessel, and main steam pipeways secured by the transverse beams and led to the outside of container is connected. This can improve the rigidity earthquake strength and the safetiness against the increase in the inside pressure upon failures of the container. (Yoshino, Y.)

  4. Deletion mutations of bacteriophage

    International Nuclear Information System (INIS)

    Ryo, Yeikou

    1975-01-01

    Resolution of mutation mechanism with structural changes of DNA was discussed through the studies using bacteriophage lambda. One of deletion mutations inductions of phage lambda is the irradiation of ultraviolet ray. It is not clear if the inductions are caused by errors in reparation of ultraviolet-induced damage or by the activation of int gene. Because the effective site of int gene lies within the regions unnecessary for existing, it is considered that int gene is connected to deletion mutations induction. A certain system using prophage complementarity enables to detect deletion mutations at essential hereditary sites and to solve the relations of deletion mutations with other recombination system, DNA reproduction and repairment system. Duplication and multiplication of hereditary elements were discussed. If lambda deletion mutations of the system, which can control recombination, reproduction and repairment of added DNA, are constructed, mutations mechanism with great changes of DNA structure can be solved by phage lambda. (Ichikawa, K.)

  5. Mutational specificity of γ-rays

    International Nuclear Information System (INIS)

    Hoebee, Barbara.

    1990-01-01

    The aim of the study described in this thesis was to get more information on the mutagenic properties of radiation-induced DNA modifications and the possible mechanisms involved in radiation-induced mutagenesis, principally by investigating the kinds of mutations by DNA sequence analysis. The mutations were analyzed after γ-irradiation of recombinant bacteriophage M13 and plasmide pUC DNA in diluted aqueous solutions, followed by transfection or transformation to E. coli cells, in which the damaged DNA molecules are repaired and replicated. Error-prone repair, misrepair or bypass of lesions during replication may lead to the introduction of mutations. Both the M13 and the plasmid DNA used in our mutation studies contain a mutation target sequence, which makes an easy selection and sequence analysis of mutant DNA molecules possible. Under the radiation conditions used, e.g. irradiation of diluted aqueous DNA solutions, only DNA damage occurs introduced by the water derived OH* and H* radicals and the hydrated electrons. By using different gas conditions during irradiation the relative yields of these reaction species can be manipulated, which opens up the opportunity to determine their effects separately. The mutation spectrum obtained in double-stranded (ds) M13DNA after irradiation under oxic conditions and the mutation spectrum obtained under the same conditions and in the same mutation target but cloned in plasmid DNA, are described. The mutation specificity under anoxic conditions in ds M13DNA is given. Results obtained after irradiation of ds M13DNA under N 2 conditions are discussed together with experiments with single-stranded DNA. Similarities and differences between radiation-induced mutation spectra obtained by other groups and those presented in this thesis are discussed. (author). 155 refs.; 134 figs.; 16 tabs

  6. Reactor container

    International Nuclear Information System (INIS)

    Naruse, Yoshihiro.

    1990-01-01

    The thickness of steel shell plates in a reactor container embedded in sand cussions is monitored to recognize the corrosion of the steel shell plates. That is, the reactor pressure vessel is contained in a reactor container shell and the sand cussions are disposed on the lower outside of the reactor container shell to elastically support the shell. A pit is disposed at a position opposing to the sand cussions for measuring the thickness of the reactor container shell plates. The pit is usually closed by a closing member. In the reactor container thus constituted, the closing member can be removed upon periodical inspection to measure the thickness of the shell plates. Accordingly, the corrosion of the steel shell plates can be recognized by the change of the plate thickness. (I.S.)

  7. A container

    DEFF Research Database (Denmark)

    2012-01-01

    A container assembly for the containment of fluids or solids under a pressure different from the ambient pressure comprising a container (2) comprising an opening and an annular sealing, a lid (3) comprising a central portion (5) and engagement means (7) for engaging the annular flange, and sealing...... means (10) wherein the engagement means (7) is adapted, via the sealing means, to seal the opening when the pressure of the container assembly differs from the ambient pressure in such a way that the central portion (5) flexes in the axial direction which leads to a radial tightening of the engagement...... means (7) to the container, wherein the container further comprises locking means (12) that can be positioned so that the central portion is hindered from flexing in at least one direction....

  8. Shielded container

    International Nuclear Information System (INIS)

    Fries, B.A.

    1978-01-01

    A shielded container for transportation of radioactive materials is disclosed in which leakage from the container is minimized due to constructional features including, inter alia, forming the container of a series of telescoping members having sliding fits between adjacent side walls and having at least two of the members including machine sealed lids and at least two of the elements including hand-tightenable caps

  9. DNA mutation motifs in the genes associated with inherited diseases.

    Directory of Open Access Journals (Sweden)

    Michal Růžička

    Full Text Available Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate. These sites are termed hotspots and exhibit a higher mutation frequency than expected by chance. In contrast, DNA sequences with lower mutation frequencies than expected by chance are termed coldspots. Mutation hotspots are usually derived from a mutation spectrum, which reflects particular population where an effect of a common ancestor plays a role. To detect coldspots/hotspots unaffected by population bias, we analysed the presence of germline mutations obtained from HGMD database in the 5-nucleotide segments repeatedly occurring in genes associated with common inherited disorders, in particular, the PAH, LDLR, CFTR, F8, and F9 genes. Statistically significant sequences (mutational motifs rarely associated with mutations (coldspots and frequently associated with mutations (hotspots exhibited characteristic sequence patterns, e.g. coldspots contained purine tract while hotspots showed alternating purine-pyrimidine bases, often with the presence of CpG dinucleotide. Using molecular dynamics simulations and free energy calculations, we analysed the global bending properties of two selected coldspots and two hotspots with a G/T mismatch. We observed that the coldspots were inherently more flexible than the hotspots. We assume that this property might be critical for effective mismatch repair as DNA with a mutation recognized by MutSα protein is noticeably bent.

  10. The SHOX region and its mutations.

    Science.gov (United States)

    Capone, L; Iughetti, L; Sabatini, S; Bacciaglia, A; Forabosco, A

    2010-06-01

    The short stature homeobox-containing (SHOX) gene lies in the pseudoautosomal region 1 (PAR1) that comprises 2.6 Mb of the short-arm tips of both the X and Y chromosomes. It is known that its heterozygous mutations cause Leri-Weill dyschondrosteosis (LWD) (OMIM #127300), while its homozygous mutations cause a severe form of dwarfism known as Langer mesomelic dysplasia (LMD) (OMIM #249700). The analysis of 238 LWD patients between 1998 and 2007 by multiple authors shows a prevalence of deletions (46.4%) compared to point mutations (21.2%). On the whole, deletions and point mutations account for about 67% of LWD patients. SHOX is located within a 1000 kb desert region without genes. The comparative genomic analysis of this region between genomes of different vertebrates has led to the identification of evolutionarily conserved non-coding DNA elements (CNE). Further functional studies have shown that one of these CNE downstream of the SHOX gene is necessary for the expression of SHOX; this is considered to be typical "enhancer" activity. Including the enhancer, the overall mutation of the SHOX region in LWD patients does not hold in 100% of cases. Various authors have demonstrated the existence of other CNE both downstream and upstream of SHOX regions. The resulting conclusion is that it is necessary to reanalyze all LWD/LMD patients without SHOX mutations for the presence of mutations in the 5'- and 3'-flanking SHOX regions.

  11. Reactor container

    International Nuclear Information System (INIS)

    Fukazawa, Masanori.

    1991-01-01

    A system for controlling combustible gases, it has been constituted at present such that the combustible gases are controlled by exhausting them to the wet well of a reactor container. In this system, however, there has been a problem, in a reactor container having plenums in addition to the wet well and the dry well, that the combustible gases in such plenums can not be controlled. In view of the above, in the present invention, suction ports or exhaust ports of the combustible gas control system are disposed to the wet well, the dry well and the plenums to control the combustible gases in the reactor container. Since this can control the combustible gases in the entire reactor container, the integrity of the reactor container can be ensured. (T.M.)

  12. A new general model for predicting melting thermodynamics of complementary and mismatched B-form duplexes containing locked nucleic acids: application to probe design for digital PCR detection of somatic mutations.

    Science.gov (United States)

    Hughesman, Curtis; Fakhfakh, Kareem; Bidshahri, Roza; Lund, H Louise; Haynes, Charles

    2015-02-17

    Advances in real-time polymerase chain reaction (PCR), as well as the emergence of digital PCR (dPCR) and useful modified nucleotide chemistries, including locked nucleic acids (LNAs), have created the potential to improve and expand clinical applications of PCR through their ability to better quantify and differentiate amplification products, but fully realizing this potential will require robust methods for designing dual-labeled hydrolysis probes and predicting their hybridization thermodynamics as a function of their sequence, chemistry, and template complementarity. We present here a nearest-neighbor thermodynamic model that accurately predicts the melting thermodynamics of a short oligonucleotide duplexed either to its perfect complement or to a template containing mismatched base pairs. The model may be applied to pure-DNA duplexes or to duplexes for which one strand contains any number and pattern of LNA substitutions. Perturbations to duplex stability arising from mismatched DNA:DNA or LNA:DNA base pairs are treated at the Gibbs energy level to maintain statistical significance in the regressed model parameters. This approach, when combined with the model's accounting of the temperature dependencies of the melting enthalpy and entropy, permits accurate prediction of T(m) values for pure-DNA homoduplexes or LNA-substituted heteroduplexes containing one or two independent mismatched base pairs. Terms accounting for changes in solution conditions and terminal addition of fluorescent dyes and quenchers are then introduced so that the model may be used to accurately predict and thereby tailor the T(m) of a pure-DNA or LNA-substituted hydrolysis probe when duplexed either to its perfect-match template or to a template harboring a noncomplementary base. The model, which builds on classic nearest-neighbor thermodynamics, should therefore be of use to clinicians and biologists who require probes that distinguish and quantify two closely related alleles in either a

  13. Tumor‐associated DNA mutation detection in individuals undergoing colonoscopy

    OpenAIRE

    Fleshner, Phillip; Braunstein, Glenn D.; Ovsepyan, Gayane; Tonozzi, Theresa R.; Kammesheidt, Anja

    2017-01-01

    Abstract The majority of colorectal cancers (CRC) harbor somatic mutations and epigenetic modifications in the tumor tissue, and some of these mutations can be detected in plasma as circulating tumor DNA (ctDNA). Precancerous colorectal lesions also contain many of these same mutations. This study examined plasma for ctDNA from patients undergoing a screening or diagnostic colonoscopy to determine the sensitivity and specificity of the ctDNA panel for detecting CRC and precancerous lesions. T...

  14. Reactor containment

    International Nuclear Information System (INIS)

    Kawabe, Ryuhei; Yamaki, Rika.

    1990-01-01

    A water vessel is disposed and the gas phase portion of the water vessel is connected to a reactor container by a pipeline having a valve disposed at the midway thereof. A pipe in communication with external air is extended upwardly from the liquid phase portion to a considerable height so as to resist against the back pressure by a waterhead in the pipeline. Accordingly, when the pressure in the container is reduced to a negative level, air passes through the pipeline and uprises through the liquid phase portion in the water vessel in the form of bubbles and then flows into the reactor container. When the pressure inside of the reactor goes higher, since the liquid surface in the water vessel is forced down, water is pushed up into the pipeline. Since the waterhead pressure of a column of water in the pipeline and the pressure of the reactor container are well-balanced, gases in the reactor container are not leaked to the outside. Further, in a case if a great positive pressure is formed in the reactor container, the inner pressure overcomes the waterhead of the column of water, so that the gases containing radioactive aerosol uprise in the pipeline. Since water and the gases flow being in contact with each other, this can provide the effect of removing aerosol. (T.M.)

  15. Better plants through mutations

    International Nuclear Information System (INIS)

    1988-01-01

    This is a public relations film describing problems associated with the genetic improvement of crop plants through induced mutations. Mutations are the ultimate source of genetic variation in plants. Mutation induction is now established as a practical tool in plant breeding. The Joint FAO/IAEA Division and the IAEA's laboratory at Seibersdorf have supported research and practical implementation of mutation breeding of both seed propagated and vegetatively propagated plants. Plant biotechnology based on in vitro culture and recombinant DNA technology will make a further significant contribution to plant breeding

  16. Sharps container

    Science.gov (United States)

    Lee, Angelene M. (Inventor)

    1992-01-01

    This invention relates to a system for use in disposing of potentially hazardous items and more particularly a Sharps receptacle for used hypodermic needles and the like. A Sharps container is constructed from lightweight alodined nonmagnetic metal material with a cup member having an elongated tapered shape and length greater than its transverse dimensions. A magnet in the cup member provides for metal retention in the container. A nonmagnetic lid member has an opening and spring biased closure flap member. The flap member is constructed from stainless steel. A Velcro patch on the container permits selective attachment at desired locations.

  17. Reactor container

    International Nuclear Information System (INIS)

    Kojima, Yoshihiro; Hosomi, Kenji; Otonari, Jun-ichiro.

    1997-01-01

    In the present invention, a catalyst for oxidizing hydrogen to be disposed in a reactor container upon rupture of pipelines of a reactor primary coolant system is prevented from deposition of water droplets formed from a reactor container spray to suppress elevation of hydrogen concentration in the reactor container. Namely, a catalytic combustion gas concentration control system comprises a catalyst for oxidizing hydrogen and a support thereof. In addition, there is also disposed a water droplet deposition-preventing means for preventing deposition of water droplets in a reactor pressure vessel on the catalyst. Then, the effect of the catalyst upon catalytic oxidation reaction of hydrogen can be kept high. The local elevation of hydrogen concentration can be prevented even upon occurrence of such a phenomenon that various kinds of mobile forces in the container such as dry well cooling system are lost. (I.S.)

  18. Variable mutation rates as an adaptive strategy in replicator populations.

    Directory of Open Access Journals (Sweden)

    Michael Stich

    2010-06-01

    Full Text Available For evolving populations of replicators, there is much evidence that the effect of mutations on fitness depends on the degree of adaptation to the selective pressures at play. In optimized populations, most mutations have deleterious effects, such that low mutation rates are favoured. In contrast to this, in populations thriving in changing environments a larger fraction of mutations have beneficial effects, providing the diversity necessary to adapt to new conditions. What is more, non-adapted populations occasionally benefit from an increase in the mutation rate. Therefore, there is no optimal universal value of the mutation rate and species attempt to adjust it to their momentary adaptive needs. In this work we have used stationary populations of RNA molecules evolving in silico to investigate the relationship between the degree of adaptation of an optimized population and the value of the mutation rate promoting maximal adaptation in a short time to a new selective pressure. Our results show that this value can significantly differ from the optimal value at mutation-selection equilibrium, being strongly influenced by the structure of the population when the adaptive process begins. In the short-term, highly optimized populations containing little variability respond better to environmental changes upon an increase of the mutation rate, whereas populations with a lower degree of optimization but higher variability benefit from reducing the mutation rate to adapt rapidly. These findings show a good agreement with the behaviour exhibited by actual organisms that replicate their genomes under broadly different mutation rates.

  19. Frequency and distribution of Notch mutations in tumor cell lines

    International Nuclear Information System (INIS)

    Mutvei, Anders Peter; Fredlund, Erik; Lendahl, Urban

    2015-01-01

    Deregulated Notch signaling is linked to a variety of tumors and it is therefore important to learn more about the frequency and distribution of Notch mutations in a tumor context. In this report, we use data from the recently developed Cancer Cell Line Encyclopedia to assess the frequency and distribution of Notch mutations in a large panel of cancer cell lines in silico. Our results show that the mutation frequency of Notch receptor and ligand genes is at par with that for established oncogenes and higher than for a set of house-keeping genes. Mutations were found across all four Notch receptor genes, but with notable differences between protein domains, mutations were for example more prevalent in the regions encoding the LNR and PEST domains in the Notch intracellular domain. Furthermore, an in silico estimation of functional impact showed that deleterious mutations cluster to the ligand-binding and the intracellular domains of NOTCH1. For most cell line groups, the mutation frequency of Notch genes is higher than in associated primary tumors. Our results shed new light on the spectrum of Notch mutations after in vitro culturing of tumor cells. The higher mutation frequency in tumor cell lines indicates that Notch mutations are associated with a growth advantage in vitro, and thus may be considered to be driver mutations in a tumor cell line context. The online version of this article (doi:10.1186/s12885-015-1278-x) contains supplementary material, which is available to authorized users

  20. Germline cytotoxic lymphocytes defective mutations in Chinese patients with lymphoma.

    Science.gov (United States)

    Chen, Xue; Zhang, Yang; Wang, Fang; Wang, Mangju; Teng, Wen; Lin, Yuehui; Han, Xiangping; Jin, Fangyuan; Xu, Yuanli; Cao, Panxiang; Fang, Jiancheng; Zhu, Ping; Tong, Chunrong; Liu, Hongxing

    2017-11-01

    Certain patients with lymphoma may harbor mutations in perforin 1 (PRF1), unc-13 homolog D (UNC13D), syntaxin 11 (STX11), STXBP2 (syntaxin binding protein 2) or SH2 domain containing 1A (SH2D1A), which causes functional defects of cytotoxic lymphocytes. Data regarding the association between genetic defects and the development of lymphoma in Chinese patients are limited to date. In the present study, 90 patients with lymphoma were analyzed for UNC13D, PRF1, STXBP2, STX11, SH2D1A and X-linked inhibitor of apoptosis. Mutations were observed in 24 (26.67%) patients; 16 patients exhibited mutations in UNC13D, 7 exhibited PRF1 mutations, and 1 exhibited monoallelic mutation in STX11. UNC13D c.2588G>A/p.G863D mutation was detected in 9 patients (10.00%) and in 4/210 controls (1.90%). This mutation was predicted to be pathogenic and it predominantly existed in the Chinese population. These findings suggest that impaired cytotoxic machinery may represent a predisposing factor for the development of lymphoma. Furthermore, these data describe a distinct mutation spectrum in Chinese patients with lymphoma, whereby UNC13D is the most frequently mutated gene. In addition, these findings suggest UNC13D c.2588G>A mutation is a founder mutation in Chinese patients.

  1. Mutation Breeding for Crop Improvement

    International Nuclear Information System (INIS)

    Rajbir, S. Sangwan

    2017-01-01

    Chromosomes contain genes responsible of different traits of any organism. Induced mutation using chemical mutagens and radiation to modify molecular structure of plants played a major role in the development of high genetic variability and help develop new superior crop varieties. The Mutation Breeding is applicable to all plants and has generated lot of agronomically interesting mutants, both in vegetatively and seed propagated plants. The technique is easy but long and challenging to detect, isolate and characterize the mutant and gene. A specific dose of irradiation has to be used to obtain desired mutants. However, with modern molecular technique, the gene responsible for mutation can be identified. The CRISPR-Cas9 allows the removal of a specific gene which is responsible of unwanted trait and replacing it with a gene which induces a desired trait. There have been more than 2700 officially released mutant varieties from 170 different plant species in more than 60 countries throughout the world and A more participatory approach, involving all stakeholders in plant breeding, is needed to ensure that it is demand/farmers driven.

  2. Mutation and premating isolation

    Science.gov (United States)

    Woodruff, R. C.; Thompson, J. N. Jr

    2002-01-01

    While premating isolation might be traceable to different genetic mechanisms in different species, evidence supports the idea that as few as one or two genes may often be sufficient to initiate isolation. Thus, new mutation can theoretically play a key role in the process. But it has long been thought that a new isolation mutation would fail, because there would be no other individuals for the isolation-mutation-carrier to mate with. We now realize that premeiotic mutations are very common and will yield a cluster of progeny carrying the same new mutant allele. In this paper, we discuss the evidence for genetically simple premating isolation barriers and the role that clusters of an isolation mutation may play in initiating allopatric, and even sympatric, species divisions.

  3. Acromelic frontonasal dysostosis and ZSWIM6 mutation

    DEFF Research Database (Denmark)

    Twigg, Stephen R F; Ousager, Lilian Bomme; Miller, Kerry A

    2016-01-01

    Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this...... sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling....

  4. Reactor container

    International Nuclear Information System (INIS)

    Furukawa, Hideyasu; Oyamada, Osamu; Uozumi, Hiroto.

    1976-01-01

    Purpose: To provide a container for a reactor provided with a pressure suppressing chamber pool which can prevent bubble vibrating load, particularly negative pressure generated at the time of starting to release exhaust from a main steam escape-safety valve from being transmitted to a lower liner plate of the container. Constitution: This arrangement is characterized in that a safety valve exhaust pool for main steam escape, in which a pressure suppressing chamber pool is separated and intercepted from pool water in the pressure suppressing chamber pool, a safety valve exhaust pipe is open into said safety valve exhaust pool, and an isolator member, which isolates the bottom liner plate in the pressure suppressing chamber pool from the pool water, is disposed on the bottom of the safety valve exhaust pool. (Nakamura, S.)

  5. CONTAIN calculations

    International Nuclear Information System (INIS)

    Scholtyssek, W.

    1995-01-01

    In the first phase of a benchmark comparison, the CONTAIN code was used to calculate an assumed EPR accident 'medium-sized leak in the cold leg', especially for the first two days after initiation of the accident. The results for global characteristics compare well with those of FIPLOC, MELCOR and WAVCO calculations, if the same materials data are used as input. However, significant differences show up for local quantities such as flows through leakages. (orig.)

  6. Reactor container

    International Nuclear Information System (INIS)

    Kato, Masami; Nishio, Masahide.

    1987-01-01

    Purpose: To prevent the rupture of the dry well even when the melted reactor core drops into a reactor pedestal cavity. Constitution: In a reactor container in which a dry well disposed above the reactor pedestal cavity for containing the reactor pressure vessel and a torus type suppression chamber for containing pressure suppression water are connected with each other, the pedestal cavity and the suppression chamber are disposed such that the flow level of the pedestal cavity is lower than the level of the pressure suppression water. Further, a pressure suppression water introduction pipeway for introducing the pressure suppression water into the reactor pedestal cavity is disposed by way of an ON-OFF valve. In case if the melted reactor core should fall into the pedestal cavity, the ON-OFF valve for the pressure suppression water introduction pipeway is opened to introduce the pressure suppression water in the suppression chamber into the pedestal cavity to cool the melted reactor core. (Ikeda, J.)

  7. Plasma container

    International Nuclear Information System (INIS)

    Ebisawa, Katsuyuki.

    1985-01-01

    Purpose: To enable to easily detect that the thickness of material to be abraded is reduced to an allowable limit from the outerside of the plasma container even during usual operation in a plasma vessel for a thermonuclear device. Constitution: A labelled material is disposed to the inside or rear face of constituent members of a plasma container undergoing the irradiation of plasma particles. A limiter plate to be abraded in the plasma container is composed of an armour member and heat removing plate, in which the armour member is made of graphite and heat-removing plate is made of copper. If the armour member is continuously abraded under the effect of sputtering due to plasma particles, silicon nitride embedded so far in the graphite at last appears on the surface of the limiter plate to undergo the impact shocks of the plasma particles. Accordingly, abrasion of the limiter material can be detected by a detector comprising gas chromatography and it can easily be detected from the outside of the plasma content even during normal operation. (Horiuchi, T.)

  8. Reactor container

    International Nuclear Information System (INIS)

    Shibata, Satoru; Kawashima, Hiroaki

    1984-01-01

    Purpose: To optimize the temperature distribution of the reactor container so as to moderate the thermal stress distribution on the reactor wall of LMFBR type reactor. Constitution: A good heat conductor (made of Al or Cu) is appended on the outer side of the reactor container wall from below the liquid level to the lower face of a deck plate. Further, heat insulators are disposed to the outside of the good heat conductor. Furthermore, a gas-cooling duct is circumferentially disposed at the contact portion between the good heat conductor and the deck plate around the reactor container. This enables to flow the cold heat from the liquid metal rapidly through the good heat conductor to the cooling duct and allows to maintain the temperature distribution on the reactor wall substantially linear even with the abrupt temperature change in the liquid metal. Further, by appending the good heat conductor covered with inactive metals not only on the outer side but also on the inside of the reactor wall to introduce the heat near the liquid level to the upper portion and escape the same to the cooling layer below the roof slab, the effect can be improved further. (Ikeda, J.)

  9. Rapid detection of single nucleotide mutation in p53 gene based on ...

    Indian Academy of Sciences (India)

    mutation.27 Nevertheless, more than 50% of all human tumors contain p53 mutation; ... gene mutation detection in various fields of biology and medicine persuaded us to find ..... Yola M L, Eren T and Atar N 2014 Electrochim. Acta. 125 38. 26.

  10. Genetic Mutations in Cancer

    Science.gov (United States)

    Many different types of genetic mutations are found in cancer cells. This infographic outlines certain types of alterations that are present in cancer, such as missense, nonsense, frameshift, and chromosome rearrangements.

  11. AIP mutations and gigantism.

    Science.gov (United States)

    Rostomyan, Liliya; Potorac, Iulia; Beckers, Pablo; Daly, Adrian F; Beckers, Albert

    2017-06-01

    AIP mutations are rare in sporadic acromegaly but they are seen at a higher frequency among certain specific populations of pituitary adenoma patients (pituitary gigantism cases, familial isolated pituitary adenoma (FIPA) kindreds, and patients with macroadenomas who are diagnosed ≤30 years). AIP mutations are most prevalent in patients with pituitary gigantism (29% of this group were found to have mutations in AIP gene). These data support targeted genetic screening for AIP mutations/deletions in these groups of pituitary adenoma patients. Earlier diagnosis of AIP-related acromegaly-gigantism cases enables timely clinical evaluation and treatment, thereby improving outcomes in terms of excessive linear growth and acromegaly comorbidities. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Mutation breeding in peas

    Energy Technology Data Exchange (ETDEWEB)

    Jaranowski, J [Institute of Genetics and Plant Breeding, Academy of Agriculture, Poznan (Poland); Micke, A [Joint FAO/IAEA Division of Isotope and Radiation Applications of Atomic Energy for Food and Agricultural Development, International Atomic Energy Agency, Vienna (Austria)

    1985-02-01

    The pea as an ancient crop plant still today has wide uses and is an import source of food protein. It is also an important object for genetic studies and as such has been widely used in mutation induction experiments. However, in comparison with cereals this ancient crop plant (like several other grain legumes) has gained relatively little from advances in breeding. The review focuses on the prospects of genetic improvement of pea by induced mutations, discusses principles and gives methodological information. (author)

  13. Mutation breeding in peas

    International Nuclear Information System (INIS)

    Jaranowski, J.; Micke, A.

    1985-01-01

    The pea as an ancient crop plant still today has wide uses and is an import source of food protein. It is also an important object for genetic studies and as such has been widely used in mutation induction experiments. However, in comparison with cereals this ancient crop plant (like several other grain legumes) has gained relatively little from advances in breeding. The review focuses on the prospects of genetic improvement of pea by induced mutations, discusses principles and gives methodological information. (author)

  14. CONTAIN calculations; CONTAIN-Rechnungen

    Energy Technology Data Exchange (ETDEWEB)

    Scholtyssek, W.

    1995-08-01

    In the first phase of a benchmark comparison, the CONTAIN code was used to calculate an assumed EPR accident `medium-sized leak in the cold leg`, especially for the first two days after initiation of the accident. The results for global characteristics compare well with those of FIPLOC, MELCOR and WAVCO calculations, if the same materials data are used as input. However, significant differences show up for local quantities such as flows through leakages. (orig.)

  15. Reactor container

    International Nuclear Information System (INIS)

    Hidaka, Masataka; Hatamiya, Shigeo; Kawasaki, Terufumi; Fukui, Toru; Suzuki, Hiroaki; Kataoka, Yoshiyuki; Kawabe, Ryuhei; Murase, Michio; Naito, Masanori.

    1990-01-01

    In order to suppress the pressure elevation in a reactor container due to high temperature and high pressure steams jetted out upon pipeway rupture accidents in the reactor container, the steams are introduced to a pressure suppression chamber for condensating them in stored coolants. However, the ability for suppressing the pressure elevation and steam coagulation are deteriorated due to the presence of inactive incondensible gases. Then, there are disposed a vent channel for introducing the steams in a dry well to a pressure suppression chamber in the reactor pressure vessel, a closed space disposed at the position lower than a usual liquid level, a first channel having an inlet in the pressure suppression chamber and an exit in the closed space and a second means connected by way of a backflow checking means for preventing the flow directing to the closed space. The first paths are present by plurality, a portion of which constitutes a syphon. The incondensible gases and the steams are discharged to the dry well at high pressure by using the difference of the water head for a long cooling time after the pipeway rupture accident. Then, safety can be improved without using dynamic equipments as driving source. (N.H.)

  16. Frequency of common CFTR gene mutations in Venezuelan patients with cystic fibrosis

    OpenAIRE

    Sánchez, Karen; Arcia, Orlando; Matute, Xiorama; Mindiola, Luz; Chaustre, Ismenia; Takiff, Howard

    2014-01-01

    Mutations in the CFTR gene in Cystic Fibrosis (CF) patients have geographic differences and there is scant data on their prevalence in Venezuelan patients. This study determined the frequency of common CFTR gene mutations in these patients. We amplified and sequenced exons 7, 10, 11, 19, 20 and 21, which contain the most common CFTR mutations, from 105 Venezuelan patients in the National CF Program. Eleven different mutations were identified, four with frequencies greater than 1%: p.Phe508del...

  17. Reactor container

    International Nuclear Information System (INIS)

    Oyamada, Osamu; Furukawa, Hideyasu; Uozumi, Hiroto.

    1979-01-01

    Purpose: To lower the position of an intermediate slab within a reactor container and fitting a heat insulating material to the inner wall of said intermediate slab, whereby a space for a control rod exchanging device and thermal stresses of the inner peripheral wall are lowered. Constitution: In the pedestal at the lower part of a reactor pressure vessel there is formed an intermediate slab at a position lower than diaphragm floor slab of the outer periphery of the pedestal thereby to secure a space for providing automatic exchanging device of a control rod driving device. Futhermore, a heat insulating material is fitted to the inner peripheral wall at the upper side of the intermediate slab part, and the temperature gradient in the wall thickness direction at the time of a piping rupture trouble is made gentle, and thermal stresses at the inner peripheral wall are lowered. (Sekiya, K.)

  18. Containment vessel

    International Nuclear Information System (INIS)

    Zbirohowski-Koscia, K.F.; Roberts, A.C.

    1980-01-01

    A concrete containment vessel for nuclear reactors is disclosed that is spherical and that has prestressing tendons disposed in first, second and third sets, the tendons of each set being all substantially concentric and centred around a respective one of the three orthogonal axes of the sphere; the tendons of the first set being anchored at each end at a first anchor rib running around a circumference of the vessel, the tendons of the second set being anchored at each end at a second anchor rib running around a circumference of the sphere and disposed at 90 0 to the first rib, and the tendons of the third set being anchored some to the first rib and the remainder to the second rib. (author)

  19. Performance of mitochondrial DNA mutations detecting early stage cancer

    International Nuclear Information System (INIS)

    Jakupciak, John P; Srivastava, Sudhir; Sidransky, David; O'Connell, Catherine D; Maragh, Samantha; Markowitz, Maura E; Greenberg, Alissa K; Hoque, Mohammad O; Maitra, Anirban; Barker, Peter E; Wagner, Paul D; Rom, William N

    2008-01-01

    Mutations in the mitochondrial genome (mtgenome) have been associated with cancer and many other disorders. These mutations can be point mutations or deletions, or admixtures (heteroplasmy). The detection of mtDNA mutations in body fluids using resequencing microarrays, which are more sensitive than other sequencing methods, could provide a strategy to measure mutation loads in remote anatomical sites. We determined the mtDNA mutation load in the entire mitochondrial genome of 26 individuals with different early stage cancers (lung, bladder, kidney) and 12 heavy smokers without cancer. MtDNA was sequenced from three matched specimens (blood, tumor and body fluid) from each cancer patient and two matched specimens (blood and sputum) from smokers without cancer. The inherited wildtype sequence in the blood was compared to the sequences present in the tumor and body fluid, detected using the Affymetrix Genechip ® Human Mitochondrial Resequencing Array 1.0 and supplemented by capillary sequencing for noncoding region. Using this high-throughput method, 75% of the tumors were found to contain mtDNA mutations, higher than in our previous studies, and 36% of the body fluids from these cancer patients contained mtDNA mutations. Most of the mutations detected were heteroplasmic. A statistically significantly higher heteroplasmy rate occurred in tumor specimens when compared to both body fluid of cancer patients and sputum of controls, and in patient blood compared to blood of controls. Only 2 of the 12 sputum specimens from heavy smokers without cancer (17%) contained mtDNA mutations. Although patient mutations were spread throughout the mtDNA genome in the lung, bladder and kidney series, a statistically significant elevation of tRNA and ND complex mutations was detected in tumors. Our findings indicate comprehensive mtDNA resequencing can be a high-throughput tool for detecting mutations in clinical samples with potential applications for cancer detection, but it is

  20. Mutator activity in Schizophyllum commune

    Energy Technology Data Exchange (ETDEWEB)

    Shneyour, Y.; Koltin, Y. (Tel Aviv Univ. (Israel). Dept. of Microbiology)

    1983-01-01

    A strain with an elevated level of spontaneous mutations and an especially high rate of reversion at a specific locus (pab/sup -/) was identified. The mutator trait is recessive. UV sensitivity and the absence of a UV-specific endonucleolytic activity were associated with the enhancement of the mutation rate in mutator strains. The endonuclease associated with the regulation of the mutation rate also acted on single-stranded DNA. The molecular weight of this enzyme is about 38,000 daltons.

  1. IDH Mutations: Genotype-Phenotype Correlation and Prognostic Impact

    Directory of Open Access Journals (Sweden)

    Xiao-Wei Wang

    2014-01-01

    Full Text Available IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1R132H, IDH1nonR132H, and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1nonR132H in astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q and IDH mutation to define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated—which contains mostly TP53 mutated tumors, and none of these alterations. We confirmed that IDH mutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge on IDH mutation prognostic impact and genotype-phenotype associations.

  2. Rice breeding with induced mutations

    Energy Technology Data Exchange (ETDEWEB)

    1968-06-01

    The Joint FAO/IAEA Division of Atomic Energy in Food and Agriculture decided in 1964 to organize a co-ordinated research programme on the use of induced mutations in rice breeding. The programme was organized within the framework of activities of the International Rice Commission. This is a report of the Third Co-ordination Meeting of the participants, which was held in Taipei, 5-9 June 1967. As the projects, which together make up the co-ordinated programme, are at different stages of progress, the report contains a variety of papers including completed studies, field and progress reports, and highlights of the discussions with some additional recommendations prepared by the participants. Refs, figs and tabs.

  3. Are There Mutator Polymerases?

    Directory of Open Access Journals (Sweden)

    Miguel Garcia-Diaz

    2003-01-01

    Full Text Available DNA polymerases are involved in different cellular events, including genome replication and DNA repair. In the last few years, a large number of novel DNA polymerases have been discovered, and the biochemical analysis of their properties has revealed a long list of intriguing features. Some of these polymerases have a very low fidelity and have been suggested to play mutator roles in different processes, like translesion synthesis or somatic hypermutation. The current view of these processes is reviewed, and the current understanding of DNA polymerases and their role as mutator enzymes is discussed.

  4. MUTATIONS IN CALMODULIN GENES

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder. The ...... the binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  5. Mutation, somatic mutation and diseases of man

    International Nuclear Information System (INIS)

    Burnet, F.M.

    1976-01-01

    The relevance of the intrinsic mutagenesis for the evolution process, genetic diseases and the process of aging is exemplified. The fundamental reaction is the function of the DNA and the DNA-enzymes like the DNA-polymerases in replication, repair, and transcription. These defects are responsible for the mutation frequency and the genetic drift in the evolution process. They cause genetic diseases like Xeroderma pigmentosum which is described here in detail. The accumulation of structural and functional mistakes leads to diseases of old age, for example to autoimmune diseases and immune suppression. There is a proportionality between the duration of life and the frequency of mistakes in the enzymatic repair system. No possibility of prophylaxis or therapy is seen. Methods for prognosis could be developed. (AJ) [de

  6. Mutations and chromosomal aberrations

    International Nuclear Information System (INIS)

    Kihlman, B.A.

    1977-01-01

    The genetic changes of mutations and chromosomal aberrations are discussed. The consequences of both depend not only on the type of genetic change produced but also on the type of cell that is affected and on the development stage of the organism. (C.F.)

  7. Mutations in GABRB3

    DEFF Research Database (Denmark)

    Møller, Rikke S; Wuttke, Thomas V; Helbig, Ingo

    2017-01-01

    OBJECTIVE: To examine the role of mutations in GABRB3 encoding the β3 subunit of the GABAA receptor in individual patients with epilepsy with regard to causality, the spectrum of genetic variants, their pathophysiology, and associated phenotypes. METHODS: We performed massive parallel sequencing ...

  8. Kin Selection - Mutation Balance

    DEFF Research Database (Denmark)

    Dyken, J. David Van; Linksvayer, Timothy Arnold; Wade, Michael J.

    2011-01-01

    selection-mutation balance, which provides an evolutionary null hypothesis for the statics and dynamics of cheating. When social interactions have linear fitness effects and Hamilton´s rule is satisfied, selection is never strong enough to eliminate recurrent cheater mutants from a population, but cheater...

  9. Secondary Containers and Service Containers for Pesticides

    Science.gov (United States)

    Secondary containers and service containers are used by pesticide applicators in the process of applying a pesticide. EPA does not require secondary containers or service containers to be labeled or to meet particular construction standards. Learn more.

  10. Mutations in galactosemia

    Energy Technology Data Exchange (ETDEWEB)

    Reichardt, J.K.V. [Univ. of Southern California School of Medicine, Los Angeles, CA (United States)

    1995-10-01

    This Letter raises four issues concerning two papers on galactosemia published in the March 1995 of the Journal. First, table 2 in the paper by Elsas et al. incorrectly attributes seven galactose-l-phosphate uridyl transferase (GALT) mutations (S135L, L195P, K285N, N314D, R333W, R333G, and K334R). The table also fails to mention that others have reported the same two findings attributed to {open_quotes}Leslie et al.; Elsas et al. and in press{close_quotes} and {open_quotes}Leslie et al.; Elsas et al.{close_quotes} The first finding on the prevalence of the Q188R galactosemia mutation in the G/G Caucasian population has also been described by Ng et al., and the second finding on the correlation of the N314D GALT mutation with the Duarte variant was reported by Lin et al. Second, Elsas et al. suggest that the E203K and N314D mutations may {open_quotes}produce intra-allelic complementation when in cis{close_quotes}. This speculation is supported by the activity data of individual III-2 but is inconsistent with the activities of three other individuals I-1, II-1, and III-1 of the same pedigree. The GALT activity measured in these three individuals suggests a dominant negative effect of E203K in E203K-N314D chromosomes, since they all have less than normal activity. Thus, the preponderance of the data in this paper is at odds with the authors speculation. It is worth recalling that Lin et al. also identified four N314D GALT mutations on 95 galactosemic chromosomes examined. A similar situation also appears to be the case in proband III-1 (with genotype E203K-N314D/IVSC) in the Elsas et al. paper. 9 refs.

  11. Mutation breeding newsletter. No. 33

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1989-01-01

    This issue of the newsletter reports a number of research news and research abstracts on application of radiation induced mutation techniques to increase mutagenesis and mutation frequency in plant breeding projects.

  12. Mutation breeding newsletter. No. 33

    International Nuclear Information System (INIS)

    1989-01-01

    This issue of the newsletter reports a number of research news and research abstracts on application of radiation induced mutation techniques to increase mutagenesis and mutation frequency in plant breeding projects

  13. Plant mutation breeding for crop improvement. V.2

    International Nuclear Information System (INIS)

    1991-01-01

    This volume contains the proceedings of the final two sessions of the FAO/IAEA Symposium on Plant Mutation Breeding for Crop Improvement, focussing on mutation breeding with particular objectives and the methodology of mutation breeding. The individual contributions are indexed separately. Although a wide variety of topics is included, the emphasis is on the use of (mainly gamma) radiation to induce economically useful mutants in cereals and legumes. The results of many conventional plant breeding programs are also presented. Refs, figs and tabs

  14. Plant mutation breeding for crop improvement. V.1

    International Nuclear Information System (INIS)

    1991-01-01

    This volume contains the proceedings of the first two sessions of the FAO/IAEA Symposium on Plant Mutation Breeding for Crop Improvement, focussing on mutation breeding in particular countries and crop-specific mutation breeding. The individual contributions are indexed separately. Although a wide variety of topics is included, the emphasis is on the use of (mainly gamma) radiation to induce economically useful mutants in cereals and legumes. The results of many conventional plant breeding programs are also presented. Refs, figs and tabs

  15. Prevalence, Mutation Patterns, and Effects on Protease Inhibitor Susceptibility of the L76V Mutation in HIV-1 Protease▿ †

    Science.gov (United States)

    Young, Thomas P.; Parkin, Neil T.; Stawiski, Eric; Pilot-Matias, Tami; Trinh, Roger; Kempf, Dale J.; Norton, Michael

    2010-01-01

    Patterns of HIV-1 protease inhibitor (PI) resistance-associated mutations (RAMs) and effects on PI susceptibility associated with the L76V mutation were studied in a large database. Of 20,501 sequences with ≥1 PI RAM, 3.2% contained L76V; L76V was alone in 0.04%. Common partner mutations included M46I, I54V, V82A, I84V, and L90M. L76V was associated with a 2- to 6-fold decrease in susceptibility to lopinavir, darunavir, amprenavir, and indinavir and a 7- to 8-fold increase in susceptibility to atazanavir and saquinavir. PMID:20805393

  16. Mutation breeding in pepper

    Energy Technology Data Exchange (ETDEWEB)

    Daskalov, S [Plant Breeding Unit, Joint FAO/IAEA Division of Isotope and Radiation Applications of Atomic Energy for Food and Agricultural Development, Seibersdorf Laboratory, International Atomic Energy Agency, Vienna (Austria)

    1986-03-01

    Pepper (Capsicum sp.) is an important vegetable and spice crop widely grown in tropical as well as in temperate regions. Until recently the improvement programmes were based mainly on using natural sources of germ plasma, crossbreeding and exploiting the heterosis of F{sub 1} hybrids. However, interest in using induced mutations is growing. A great number of agronomically useful mutants as well as mutants valuable for genetic, cytological and physiological studies have been induced and described. In this review information is presented about suitable mutagen treatment procedures with radiation as well as chemicals, M{sub 1} effects, handling the treated material in M{sub 1}, M{sub 2} and subsequent generations, and mutant screening procedures. This is supplemented by a description of reported useful mutants and released cultivars. Finally, general advice is given on when and how to incorporate mutation induction in Capsicum improvement programmes. (author)

  17. Mutation breeding in pepper

    International Nuclear Information System (INIS)

    Daskalov, S.

    1986-01-01

    Pepper (Capsicum sp.) is an important vegetable and spice crop widely grown in tropical as well as in temperate regions. Until recently the improvement programmes were based mainly on using natural sources of germ plasma, crossbreeding and exploiting the heterosis of F 1 hybrids. However, interest in using induced mutations is growing. A great number of agronomically useful mutants as well as mutants valuable for genetic, cytological and physiological studies have been induced and described. In this review information is presented about suitable mutagen treatment procedures with radiation as well as chemicals, M 1 effects, handling the treated material in M 1 , M 2 and subsequent generations, and mutant screening procedures. This is supplemented by a description of reported useful mutants and released cultivars. Finally, general advice is given on when and how to incorporate mutation induction in Capsicum improvement programmes. (author)

  18. Mutated hilltop inflation revisited

    Science.gov (United States)

    Pal, Barun Kumar

    2018-05-01

    In this work we re-investigate pros and cons of mutated hilltop inflation. Applying Hamilton-Jacobi formalism we solve inflationary dynamics and find that inflation goes on along the {W}_{-1} branch of the Lambert function. Depending on the model parameter mutated hilltop model renders two types of inflationary solutions: one corresponds to small inflaton excursion during observable inflation and the other describes large field inflation. The inflationary observables from curvature perturbation are in tune with the current data for a wide range of the model parameter. The small field branch predicts negligible amount of tensor to scalar ratio r˜ O(10^{-4}), while the large field sector is capable of generating high amplitude for tensor perturbations, r˜ O(10^{-1}). Also, the spectral index is almost independent of the model parameter along with a very small negative amount of scalar running. Finally we find that the mutated hilltop inflation closely resembles the α -attractor class of inflationary models in the limit of α φ ≫ 1.

  19. Mutation breeding in jute

    International Nuclear Information System (INIS)

    Joshua, D.C.

    1980-01-01

    Mutagenic studies in jute in general dealt with the morphological abnormalities of the M 1 generation in great detail. Of late, induction of a wide spectrum of viable mutations have been reported in different varieties of both the species. Mutations affecting several traits of agronomic importance such as, plant height, time of flowering, fibre yield and quality, resistance to pests and diseases are also available. Cytological analysis of a large collection of induced mutants resulted in the isolation of seven trisomics in an olitorius variety. Several anatomical parameters which are the components of fibre yield, have also received attention. Some mutants with completely altered morphology were used for interpreting the evolution of leaf shape in Tiliaceas and related families. A capsularis variety developed using mutation breeding technique has been released for cultivation. Several others, including derivatives of inter-mutant hybridization have been found to perform well at different locations in the All India Coordinated Trials. Presently, chemical mutagenesis and induction of mutants of physiological significance are receiving considerable attention. The induced variability is being used in genetic and linkage studies. (author)

  20. Advantages of a single-cycle production assay to study cell culture-adaptive mutations of hepatitis C virus

    DEFF Research Database (Denmark)

    Russell, Rodney S; Meunier, Jean-Christophe; Takikawa, Shingo

    2008-01-01

    mutations that were selected during serial passage in Huh-7.5 cells were studied. Recombinant genomes containing all five mutations produced 3-4 logs more infectious virions than did wild type. Neither a coding mutation in NS5A nor a silent mutation in E2 was adaptive, whereas coding mutations in E2, p7......The JFH1 strain of hepatitis C virus (HCV) is unique among HCV isolates, in that the wild-type virus can traverse the entire replication cycle in cultured cells. However, without adaptive mutations, only low levels of infectious virus are produced. In the present study, the effects of five...

  1. Calreticulin Mutations in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Noa Lavi

    2014-10-01

    Full Text Available With the discovery of the JAK2V617F mutation in patients with Philadelphia chromosome-negative (Ph− myeloproliferative neoplasms (MPNs in 2005, major advances have been made in the diagnosis of MPNs, in understanding of their pathogenesis involving the JAK/STAT pathway, and finally in the development of novel therapies targeting this pathway. Nevertheless, it remains unknown which mutations exist in approximately one-third of patients with non-mutated JAK2 or MPL essential thrombocythemia (ET and primary myelofibrosis (PMF. At the end of 2013, two studies identified recurrent mutations in the gene encoding calreticulin (CALR using whole-exome sequencing. These mutations were revealed in the majority of ET and PMF patients with non-mutated JAK2 or MPL but not in polycythemia vera patients. Somatic 52-bp deletions (type 1 mutations and recurrent 5-bp insertions (type 2 mutations in exon 9 of the CALR gene (the last exon encoding the C-terminal amino acids of the protein calreticulin were detected and found always to generate frameshift mutations. All detected mutant calreticulin proteins shared a novel amino acid sequence at the C-terminal. Mutations in CALR are acquired early in the clonal history of the disease, and they cause activation of JAK/STAT signaling. The CALR mutations are the second most frequent mutations in Ph− MPN patients after the JAK2V617F mutation, and their detection has significantly improved the diagnostic approach for ET and PMF. The characteristics of the CALR mutations as well as their diagnostic, clinical, and pathogenesis implications are discussed in this review.

  2. Mitochondrial mutations in subjects with psychiatric disorders.

    Directory of Open Access Journals (Sweden)

    Adolfo Sequeira

    Full Text Available A considerable body of evidence supports the role of mitochondrial dysfunction in psychiatric disorders and mitochondrial DNA (mtDNA mutations are known to alter brain energy metabolism, neurotransmission, and cause neurodegenerative disorders. Genetic studies focusing on common nuclear genome variants associated with these disorders have produced genome wide significant results but those studies have not directly studied mtDNA variants. The purpose of this study is to investigate, using next generation sequencing, the involvement of mtDNA variation in bipolar disorder, schizophrenia, major depressive disorder, and methamphetamine use. MtDNA extracted from multiple brain regions and blood were sequenced (121 mtDNA samples with an average of 8,800x coverage and compared to an electronic database containing 26,850 mtDNA genomes. We confirmed novel and rare variants, and confirmed next generation sequencing error hotspots by traditional sequencing and genotyping methods. We observed a significant increase of non-synonymous mutations found in individuals with schizophrenia. Novel and rare non-synonymous mutations were found in psychiatric cases in mtDNA genes: ND6, ATP6, CYTB, and ND2. We also observed mtDNA heteroplasmy in brain at a locus previously associated with schizophrenia (T16519C. Large differences in heteroplasmy levels across brain regions within subjects suggest that somatic mutations accumulate differentially in brain regions. Finally, multiplasmy, a heteroplasmic measure of repeat length, was observed in brain from selective cases at a higher frequency than controls. These results offer support for increased rates of mtDNA substitutions in schizophrenia shown in our prior results. The variable levels of heteroplasmic/multiplasmic somatic mutations that occur in brain may be indicators of genetic instability in mtDNA.

  3. Mutation breeding in chickpea

    International Nuclear Information System (INIS)

    2009-01-01

    Chickpea is an important food legume in Turkey. Turkey is one of the most important gene centers in the world for legumes. The most widely known characteristic of chickpea is that it is an important vegetable protein source used in human and animal nutrition. However, the dry grains of chickpea, has 2-3 times more protein than our traditional food of wheat. In addition, cheakpea is also energy source because of its high carbohydrate content. It is very rich in some vitamin and mineral basis. In the plant breeding, mutation induction has become an effective way of supplementing existing germplasm and improving cultivars. Many successful examples of mutation induction have proved that mutation breeding is an effective and important approach to food legume improvement. The induced mutation technique in chickpea has proved successful and good results have been attained. Realizing the potential of induced mutations, a mutation breeding programme was initiated at the Nuclear Agriculture Section of the Saraykoey Nuclear Research and Training Center in 1994. The purpose of the study was to obtain high yielding chickpea mutants with large seeds, good cooking quality and high protein content. Beside this some characters such as higher adaptation ability, tolerant to cold and drought, increased machinery harvest type, higher yield, resistant to diseases especially to antracnose and pest were investigated too. Parents varieties were ILC-482, AK-7114 and AKCIN-91 (9 % seed moisture content and germination percentage 98 %) in these experiments. The irradiation doses were 0 (control), 50, 100, 150, 200, 250, 300, 350, 400, 500 ve 600 Gy for greenhouse experiments and 0 (control), 50, 100, 150, 200, 250, 300, 350 ve 400 Gy for field experiments, respectively. One thousand seeds for per treatment were sown in the field for the M 1 . At maturity, 3500 single plants were harvested and 20 seeds were taken from each M 1 plant and planted in the following season. During plant growth

  4. Presence of a consensus DNA motif at nearby DNA sequence of the mutation susceptible CG nucleotides.

    Science.gov (United States)

    Chowdhury, Kaushik; Kumar, Suresh; Sharma, Tanu; Sharma, Ankit; Bhagat, Meenakshi; Kamai, Asangla; Ford, Bridget M; Asthana, Shailendra; Mandal, Chandi C

    2018-01-10

    Complexity in tissues affected by cancer arises from somatic mutations and epigenetic modifications in the genome. The mutation susceptible hotspots present within the genome indicate a non-random nature and/or a position specific selection of mutation. An association exists between the occurrence of mutations and epigenetic DNA methylation. This study is primarily aimed at determining mutation status, and identifying a signature for predicting mutation prone zones of tumor suppressor (TS) genes. Nearby sequences from the top five positions having a higher mutation frequency in each gene of 42 TS genes were selected from a cosmic database and were considered as mutation prone zones. The conserved motifs present in the mutation prone DNA fragments were identified. Molecular docking studies were done to determine putative interactions between the identified conserved motifs and enzyme methyltransferase DNMT1. Collective analysis of 42 TS genes found GC as the most commonly replaced and AT as the most commonly formed residues after mutation. Analysis of the top 5 mutated positions of each gene (210 DNA segments for 42 TS genes) identified that CG nucleotides of the amino acid codons (e.g., Arginine) are most susceptible to mutation, and found a consensus DNA "T/AGC/GAGGA/TG" sequence present in these mutation prone DNA segments. Similar to TS genes, analysis of 54 oncogenes not only found CG nucleotides of the amino acid Arg as the most susceptible to mutation, but also identified the presence of similar consensus DNA motifs in the mutation prone DNA fragments (270 DNA segments for 54 oncogenes) of oncogenes. Docking studies depicted that, upon binding of DNMT1 methylates to this consensus DNA motif (C residues of CpG islands), mutation was likely to occur. Thus, this study proposes that DNMT1 mediated methylation in chromosomal DNA may decrease if a foreign DNA segment containing this consensus sequence along with CG nucleotides is exogenously introduced to dividing

  5. Age-related cancer mutations associated with clonal hematopoietic expansion

    Science.gov (United States)

    Xie, Mingchao; Lu, Charles; Wang, Jiayin; McLellan, Michael D.; Johnson, Kimberly J.; Wendl, Michael C.; McMichael, Joshua F.; Schmidt, Heather K.; Yellapantula, Venkata; Miller, Christopher A.; Ozenberger, Bradley A.; Welch, John S.; Link, Daniel C.; Walter, Matthew J.; Mardis, Elaine R.; Dipersio, John F.; Chen, Feng; Wilson, Richard K.; Ley, Timothy J.; Ding, Li

    2015-01-01

    Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. We analyzed blood-derived sequence data from 2,728 individuals within The Cancer Genome Atlas, and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age. Remarkably, 83% of these mutations were from 19 leukemia/lymphoma-associated genes, and nine were recurrently mutated (DNMT3A, TET2, JAK2, ASXL1, TP53, GNAS, PPM1D, BCORL1 and SF3B1). We identified 14 additional mutations in a very small fraction of blood cells, possibly representing the earliest stages of clonal expansion in hematopoietic stem cells. Comparison of these findings to mutations in hematological malignancies identified several recurrently mutated genes that may be disease initiators. Our analyses show that the blood cells of more than 2% of individuals (5–6% of people older than 70 years) contain mutations that may represent premalignant, initiating events that cause clonal hematopoietic expansion. PMID:25326804

  6. Use of γ-ray-induced mutations in the genome era in rice

    International Nuclear Information System (INIS)

    Kusaba, Makoto

    2007-01-01

    Ionizing radiation has been used for inducing mutations and improving crops since the discovery by STADLER (1928) that X-rays could induce mutations in barley. At the end of 2004, the whole genome sequence of rice was determined (INTERNATIONAL RICE GENOME SEQUENCING PROJECT, 2005). What can γ-ray-induced mutations contribute now that this has been achieved? One answer could be the elucidation of the functions of the numerous genes revealed by the complete sequence of the rice genome. This includes identification of mutants through reverse genetics and the isolation of genes containing mutations through forward genetics using molecular markers and sequence information. Another answer could be mutation breeding using reverse genetics. But first we must know what kind of DNA lesions are caused by γ-rays. In this article, I describe the production of DNA lesions, and then discuss how γ-ray-induced mutations can contribute to the elucidation of gene function and to mutation breeding. (author)

  7. Induced mutations in citrus

    International Nuclear Information System (INIS)

    Spiegel-Roy, P.; Vardi, Aliza

    1990-01-01

    Full text: Parthenocarpic tendency is an important prerequisite for successful induction of seedlessness in breeding and especially in mutation breeding. A gene for asynapsis and accompanying seedless fruit has been found by us in inbred progeny of cv. 'Wilking'. Using budwood irradiation by gamma rays, seedless mutants of 'Eureka' and 'Villafranca' lemon (original clone of the latter has 25 seeds) and 'Minneola' tangelo have been obtained. Ovule sterility of the three mutants is nearly complete, with some pollen fertility still remaining. A semi-compact mutant of Shamouti orange has been obtained by irradiation. A programme for inducing seedlessness in easy peeling citrus varieties and selections has been initiated. (author)

  8. Induced skeletal mutations

    International Nuclear Information System (INIS)

    Selby, P.B.

    1979-01-01

    This paper describes a large-scale experiment that, by means of breeding tests, confirmed that many dominant skeletal mutations are induced by large-dose radiation exposure. The author also discusses: (1) the major advantages and disadvantages of the skeletal method in improving estimates of genetic hazard to man; (2) future uses of the skeletal method; (3) direct estimation of risk beyond the first generation using the skeletal method; and (4) the possibility of using the skeletal method as a quick and easy screen for chemical mutagens

  9. [FANCA gene mutation analysis in Fanconi anemia patients].

    Science.gov (United States)

    Chen, Fei; Peng, Guang-Jie; Zhang, Kejian; Hu, Qun; Zhang, Liu-Qing; Liu, Ai-Guo

    2005-10-01

    To screen the FANCA gene mutation and explore the FANCA protein function in Fanconi anemia (FA) patients. FANCA protein expression and its interaction with FANCF were analyzed using Western blot and immunoprecipitation in 3 cases of FA-A. Genomic DNA was used for MLPA analysis followed by sequencing. FANCA protein was undetectable and FANCA and FANCF protein interaction was impaired in these 3 cases of FA-A. Each case of FA-A contained biallelic pathogenic mutations in FANCA gene. No functional FANCA protein was found in these 3 cases of FA-A, and intragenic deletion, frame shift and splice site mutation were the major pathogenic mutations found in FANCA gene.

  10. Mutations induced in plant breeding

    International Nuclear Information System (INIS)

    Barriga B, P.

    1984-01-01

    The most significant aspects of the use of ionizing radiations in plant breeding are reviewed. Aspects such as basic principles of mutation, expression and selection in obtention of mutants, methods for using induced mutations and sucess achieved with this methodology in plant breeding are reviewed. Results obtained in a program of induced mutation on wheat for high content of protein and lysine at the Universidad Austral de Chile are presented. (Author)

  11. Mutations induced in plant breeding

    Energy Technology Data Exchange (ETDEWEB)

    Barriga B, P. (Universidad Austral de Chile, Valdivia. Inst. de Produccion y Sanidad Vegetal)

    1984-10-01

    The most significant aspects of the use of ionizing radiations in plant breeding are reviewed. Aspects such as basic principles of mutation, expression and selection in obtention of mutants, methods for using induced mutations and sucess achieved with this methodology in plant breeding are reviewed. Results obtained in a program of induced mutation on wheat for high content of protein and lysine at the Universidad Austral de Chile are presented.

  12. Novel mutations and mutation combinations of ryanodine receptor in a chlorantraniliprole resistant population of Plutella xylostella (L.)

    Science.gov (United States)

    Guo, Lei; Liang, Pei; Zhou, Xuguo; Gao, Xiwu

    2014-01-01

    A previous study documented a glycine to glutamic acid mutation (G4946E) in ryanodine receptor (RyR) was highly correlated to diamide insecticide resistance in field populations of Plutella xylostella (Lepidoptera: Plutellidae). In this study, a field population collected in Yunnan province, China, exhibited a 2128-fold resistance to chlorantraniliprole. Sequence comparison between resistant and susceptible P. xylostella revealed three novel mutations including a glutamic acid to valine substitution (E1338D), a glutamine to leucine substitution (Q4594L) and an isoleucine to methionine substitution (I4790M) in highly conserved regions of RyR. Frequency analysis of all four mutations in this field population showed that the three new mutations showed a high frequency of 100%, while the G4946E had a frequency of 20%. Furthermore, the florescent ligand binding assay revealed that the RyR containing multiple mutations displayed a significantly lower affinity to the chlorantraniliprole. The combined results suggested that the co-existence of different combinations of the four mutations was involved in the chlorantraniliprole resistance. An allele-specific PCR based method was developed for the diagnosis of the four mutations in the field populations of P. xylostella. PMID:25377064

  13. Mutation breeding newsletter. No. 43

    International Nuclear Information System (INIS)

    1997-10-01

    This issue of the Newsletter includes articles dealing with radiation induced mutation based plant breeding research findings aimed at improving productivity, disease resistance and tolerance of stress conditions

  14. Mutation breeding in mangosteen

    International Nuclear Information System (INIS)

    Mohd Khalid Mohd Zain

    2002-01-01

    Mangosteen the queen of the tropical fruits is apomitic and only a cultivar is reported and it reproduces asexually. Conventional breeding is not possible and the other methods to create variabilities are through genetic engineering and mutation breeding. The former technique is still in the infantry stage in mangosteen research while the latter has been an established tool in breeding to improve cultivars. In this mutation breeding seeds of mangosteen were irradiated using gamma rays and the LD 50 for mangosteen was determined and noted to be very low at 10 Gy. After sowing in the seedbed, the seedlings were transplanted in polybags and observed in the nursery bed for about one year before planted in the field under old oil palm trees in Station MARDI, Kluang. After evaluation and screening, about 120 mutant mangosteen plants were selected and planted in Kluang. The plants were observed and some growth data taken. There were some mutant plants that have good growth vigour and more vigorous that the control plants. The trial are now in the fourth year and the plants are still in the juvenile stage. (Author)

  15. Mutation breeding in chickpea

    International Nuclear Information System (INIS)

    Sagel, Z.; Tutluer, M. I.; Peskircioglu, H.; Kantoglu, Y.; Kunter, B.

    2009-01-01

    Chickpea is an important food legume in Turkey. Turkey is one of the most important gene centers in the world for legumes. Realizing the potential of induced mutations, a mutation breeding programme was initiated at the Nuclear Agriculture Section of the Saraykoy Nuclear Research and Training Center in 1994. The purpose of the study was to obtain high yielding chickpea mutants with large seeds, good cooking quality and high protein content. Beside this some characters such as higher adaptation ability, tolerant to cold and drought, increased machinery harvest type, higher yield, resistant to diseases especially to antracnose and pest were investigated too. Parent varieties were ILC-482, AK-7114 and AKCIN-91 had been used in these experiments. The irradiation doses were 0 (control), 50, 100, 150, 200, 250, 300, 350 and 400 Gy for field experiments, respectively. As a result of these experiments, two promising mutant lines were chosen and given to the Seed Registration and Certification Center for official registration These two promising mutants were tested at five different locations of Turkey, in 2004 and 2005 years. After 2 years of registration experiments one of outstanding mutants was officially released as mutant chickpea variety under the name TAEK-SAGEL, in 2006. Some basic characteristics of this mutant are; earliness (95-100 day), high yield capacity (180-220 kg/da), high seed protein (22-25 %), first pot height (20-25 cm), 100 seeds weight (42-48 g), cooking time (35-40 min) and resistance to Ascochyta blight.

  16. Characterization of carbon ion-induced mutations in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Shikazono, N.; Suzuki, C.; Kitamura, S.; Watanabe, H.; Tano, S.; Tanaka, A.

    2003-01-01

    Full text: Irradiation of Arabidopsis thaliana by carbon ions was carried out to investigate the mutational effect of ion particles in higher plants. The averaged mutation rate of carbon ions was 2.0 X 10 -6 / Gy, which was 18-fold higher than that of electrons. PCR analysis of the carbon ion-induced mutants showed that, out of 28 mutant alleles, 14 had point-like mutations within the gene, while 14 contained large structural alterations. In the case of 12 electron-induced mutants, 9 had point-like mutations within the gene, while 3 contained large structural alterations. These results suggest that carbon ions are more likely to induce large structural alterations compared with electrons. Further sequence analysis revealed that most of the point-like mutations induced by carbon ions were short deletions. In the case of rearrangements, DNA strand breaks were found to be rejoined using, if present, short homologous sequences for both types of radiation. After carbon ion-irradiation, small deletions were frequently observed around the breakpoints, whereas duplications of terminal sequence were found after electron-irradiation. These results suggest that non-homologous end joining (NHEJ) pathway operates after plant cells are exposed to both ion particles and electrons but that different mode of rejoining deals with the broken ends produced by each radiation. From the present results, it seems reasonable to assume that carbon ions could predominantly induce null mutations in Arabidopsis. The fact that the molecular nature of carbon ion-induced mutation was different from that of electrons and that the molecular mechanisms of cells to induce mutations appeared to be also different implicates that ion particle is not only valuable as a new mutagen but also useful as a new tool to study repair mechanisms of certain types of DNA damage

  17. Energy parasites trigger oncogene mutation.

    Science.gov (United States)

    Pokorný, Jiří; Pokorný, Jan; Jandová, Anna; Kobilková, Jitka; Vrba, Jan; Vrba, Jan

    2016-10-01

    Cancer initialization can be explained as a result of parasitic virus energy consumption leading to randomized genome chemical bonding. Analysis of experimental data on cell-mediated immunity (CMI) containing about 12,000 cases of healthy humans, cancer patients and patients with precancerous cervical lesions disclosed that the specific cancer and the non-specific lactate dehydrogenase-elevating (LDH) virus antigen elicit similar responses. The specific antigen is effective only in cancer type of its origin but the non-specific antigen in all examined cancers. CMI results of CIN patients display both healthy and cancer state. The ribonucleic acid (RNA) of the LDH virus parasitizing on energy reduces the ratio of coherent/random oscillations. Decreased effect of coherent cellular electromagnetic field on bonding electrons in biological macromolecules leads to elevating probability of random genome reactions. Overlapping of wave functions in biological macromolecules depends on energy of the cellular electromagnetic field which supplies energy to bonding electrons for selective chemical bonds. CMI responses of cancer and LDH virus antigens in all examined healthy, precancerous and cancer cases point to energy mechanism in cancer initiation. Dependence of the rate of biochemical reactions on biological electromagnetic field explains yet unknown mechanism of genome mutation.

  18. Waste container and method for containing waste

    International Nuclear Information System (INIS)

    Ono, Akira; Matsushita, Mitsuhiro; Doi, Makoto; Nakatani, Seiichi.

    1990-01-01

    In a waste container, water-proof membranes and rare earth element layers are formed on the inner surface of a steel plate concrete container in which steel plates are embedded. Further, rear earth element detectors are disposed each from the inner side of the steel plate concrete container by way of a pressure pipe to the outer side of the container. As a method for actually containing wastes, when a plurality of vessels in which wastes are fixed are collectively enhoused to the waste container, cussioning materials are attached to the inner surface of the container and wastes fixing containers are stacked successively in a plurality of rows in a bag made of elastic materials. Subsequently, fixing materials are filled and tightly sealed in the waste container. When the waste container thus constituted is buried underground, even if it should be deformed to cause intrusion of rain water to the inside of the container, the rare earth elements in the container dissolved in the rain water can be detected by the detectors, the containers are exchanged before the rain water intruding to the inner side is leached to the surrounding ground, to previously prevent the leakage of radioactive nuclides. (K.M.)

  19. Studies on mutation techniques in rice breeding

    International Nuclear Information System (INIS)

    Wang Cailian; Chen Qiufang; Jin Wei

    2001-01-01

    Synthetical techniques for improving rice mutation breeding efficiency were studied. The techniques consist of corresponding relationship between radiosensitivity and mutation frequency, choosing appropriate materials, combination of physical and chemical mutagens, mutagenic effects of the new mutagenic agents as proton, ions, synchronous irradiation and space mutation. These techniques and methods for inducing mutations are very valuable to increase inducing mutation efficiency and breeding level

  20. Phenylalanine hydroxylase gene mutations in the United States: Report from the maternal PKU collaborative study

    Energy Technology Data Exchange (ETDEWEB)

    Guldberg, P.; Henriksen, K.F.; Guettler, F. [John F. Kennedy Inst., Glostrup (Denmark)] [and others

    1996-07-01

    The major cause of hyperphenylalaninemia is mutations in the gene encoding phenylalanine hydroxylase (PAH). The known mutations have been identified primarily in European patients. The purpose of this study was to determine the spectrum of mutations responsible for PAH deficiency in the United States. One hundred forty-nine patients enrolled in the Maternal PKU Collaborative Study were subjects for clinical and molecular investigations. PAH gene mutations associated with phenylketonuria (PKU) or mild hyperphenylalaninemia (MHP) were identified on 279 of 294 independent mutant chromosomes, a diagnostic efficiency of 95%. The spectrum is composed of 71 different mutations, including 47 missense mutations, 11 splice mutations, 5 nonsense mutations, and 8 microdeletions. Sixteen previously unreported mutations were identified. Among the novel mutations, five were found in patients with MHP, and the remainder were found in patients with PKU. The most common mutations were R408W, IVS12nt1g{r_arrow}a, and Y414C, accounting for 18.7%, 7.8% and 5.4% of the mutant chromosomes, respectively. Thirteen mutations had relative frequencies of 1%-5%, and 55 mutations each had frequencies {le}1%. The mutational spectrum corresponded to that observed for the European ancestry of the U.S. population. To evaluate the extent of allelic variation at the PAH locus within the United States in comparison with other populations, we used allele frequencies to calculate the homozygosity for 11 populations where >90% ascertainment has been obtained. The United States was shown to contain one of the most heterogeneous populations, with homozygosity values similar to Sicily and ethnically mixed sample populations in Europe. The extent of allelic heterogeneity must be a major determining factor in the choice of mutation-detection methodology for molecular diagnosis in PAH deficiency. 47 refs., 1 fig., 5 tabs.

  1. Distribution of the PKU mutation 165T in Spain and Latin America

    Energy Technology Data Exchange (ETDEWEB)

    Perez, B.; deLucca, M.; Desviat, L.R. [UAM-CSIC, Madrid (Spain)] [and others

    1994-09-01

    The 165T mutation is the second most common mutation in the Spanish PKU patients. In order to provide some additional data about the origin of this mutation, we have analyzed 452 PKU alleles from all regions of Spain. The mutation was found in 9% of alleles. We have found a South-North gradient with a highest frequency in the South and the lowest in the North. In the North-West regions (which has the greatest Celtic influence in Spain) the frequency was 7%. The chromosomes bearing this mutation contained the 8 repeat VNTR allele, as has been described in other populations. In view of these results, we suggest an origin other than Celtic for this mutation. On the other hand, we have analyzed 406 PKU alleles from five Latin American countries, 158 from Brazil, 170 from Chile, 56 from Argentina, 14 from Mexico and 8 from Venezuela. Unlike the results of the IVS10 mutation, 165T is present in Latin America with a low frequency. The results show that this mutation is rare in Chile (1%) and is absent in the chromosomes analyzed from Argentina, Mexico and Venezuela. Only in Brazil has this mutation been found in 5% of the alleles. Up to now, Spain is the only Mediterranean country where this mutation is present with a relatively high frequency. This mutation has been detected in the Portuguese patients and would also have migrated to Brazil.

  2. Sigma virus and mutation in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Paquin, S.L.A.

    1977-01-01

    - The objectives of these experiments have been (1) to verify and evidence more fully the action of sigma in causing recessive lethal mutation on the X chromosome of Drosophila, both in the male and the female germ line; (2) to extend the study of sigma-induced recessive lethal mutation to the Drosophila autosomes; (3) to explore the possibility that this mutagenesis is site-directed; (4) to study the effects of sigma virus in conjunction with radiation in increasing non-disjunction and dominant lethality. The virus increases the rate of radiation-induced nondisjunction by altering meiotic chromosomal behavior. Percentage of non-disjunction with 500 rads of x-rays in the virus-free flies was 0.176, while in sigma-containing lines it was 0.333. With high doses of either x or neutron radiation, the presence of the virus enhances the frequency of dominant lethality. The difference is especially significant with the fast neutrons. The results indicate that sigma, and presumably other viruses, are indeed environmental mutagens and are, therefore, factors in the rate of background or spontaneous mutation

  3. Mutation breeding in soybean

    International Nuclear Information System (INIS)

    Baradjanegara, A.A.

    1983-01-01

    In Indonesia, soybean is one of the important crop after rice. It is generally cultivated in the lowlands and rarely in the highlands. Seeds of soybean variety ORBA were treated with various doses of fast neutrons, gamma rays, EMS and NaN 3 with the aims of studying the mutagen effects in M-1 and M-2 generations and also to select mutants adapted to highland conditions. D-50 doses for gamma rays, fast neutrons and EMS were around 23 krad, 2,300 rad, 0.3%, respectively. Much higher chlorophyll mutation frequency was observed in EMS treatment of 0.3%. Seven mutants were shorter and four early mutants matured from 4 to 20 days earlier than the control plants. Two early mutants were quite adaptable in both the low and highlands and produced better yields than the parental material. (author)

  4. Founder Mutations in Xeroderma Pigmentosum

    Science.gov (United States)

    Tamura, Deborah; DiGiovanna, John J.; Kraemer, Kenneth H.

    2012-01-01

    In this issue, Soufir et al. report a founder mutation in the XPC DNA repair gene in 74% of families with xeroderma pigmentosum (XP) in the Maghreb region (Algeria, Morocco, and Tunisia) of northern Africa. These patients have a high frequency of skin cancer. The presence of this founder mutation provides an opportunity for genetic counseling and early diagnosis of XP. PMID:20463673

  5. Mutations causative of familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Benn, Marianne; Watts, Gerald F; Tybjærg-Hansen, Anne

    2016-01-01

    causing mutations in 98 098 participants from the general population, the Copenhagen General Population Study. METHODS AND RESULTS: We genotyped for LDLR[W23X;W66G;W556S] and APOB[R3500Q] accounting for 38.7% of pathogenic FH mutations in Copenhagen. Clinical FH assessment excluded mutation information......-cholesterol concentration to discriminate between mutation carriers and non-carriers was 4.4 mmol/L. CONCLUSION: Familial hypercholesterolaemia-causing mutations are estimated to occur in 1:217 in the general population and are best identified by a definite or probable phenotypic diagnosis of FH based on the DLCN criteria....... The prevalence of the four FH mutations was 0.18% (1:565), suggesting a total prevalence of FH mutations of 0.46% (1:217). Using the Dutch Lipid Clinic Network (DLCN) criteria, odds ratios for an FH mutation were 439 (95% CI: 170-1 138) for definite FH, 90 (53-152) for probable FH, and 18 (13-25) for possible FH...

  6. Container crane for sea freight containers

    NARCIS (Netherlands)

    Luttekes, E.; Rijsenbrij, J.C.

    2001-01-01

    The invention relates to a container crane for loading and unloading seaborne containers. The container crane comprises a bridge girder (7), a jib (8), at least two crabs (11, 12) which can travel along the said bridge girder and/or jib and are provided with hoist means for lifting and lowering the

  7. MPL mutations in myeloproliferative disorders

    DEFF Research Database (Denmark)

    Beer, Philip A.; Campbell, Peter J.; Scott, Linda M.

    2008-01-01

    Activating mutations of MPL exon 10 have been described in a minority of patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET), but their prevalence and clinical significance are unclear. Here we demonstrate that MPL mutations outside exon 10 are uncommon in platelet c......DNA and identify 4 different exon 10 mutations in granulocyte DNA from a retrospective cohort of 200 patients with ET or IMF. Allele-specific polymerase chain reaction was then used to genotype 776 samples from patients with ET entered into the PT-1 studies. MPL mutations were identified in 8.5% of JAK2 V617F......(-) patients and a single V617F(+) patient. Patients carrying the W515K allele had a significantly higher allele burden than did those with the W515L allele, suggesting a functional difference between the 2 variants. Compared with V617F(+) ET patients, those with MPL mutations displayed lower hemoglobin...

  8. Mutation induction by heavy ions

    Science.gov (United States)

    Kiefer, J.; Stoll, U.; Schneider, E.

    1994-10-01

    Mutation induction by heavy ions is compared in yeast and mammalian cells. Since mutants can only be recovered in survivors the influence of inactivation cross sections has to be taken into account. It is shown that both the size of the sensitive cellular site as well as track structure play an important role. Another parameter which influences the probability of mutation induction is repair: Contrary to naive assumptions primary radiation damage does not directly lead to mutations but requires modification to reconstitute the genetic machinery so that mutants can survive. The molecular structure of mutations was analyzed after exposure to deuterons by amplification with the aid of polymerase chain reaction. The results-although preliminary-demonstrate that even with densely ionizing particles a large fraction does not carry big deletions which suggests that point mutations may also be induced by heavy ions.

  9. Mutation breeding in ornamental plants

    International Nuclear Information System (INIS)

    Datta, S.K.

    1990-01-01

    Full text: Mutation induction produced a large number of new promising varieties in ornamental species. 37 new mutants of Chrysanthemum and 14 of rose have been developed by mutations and released for commercialisation. The mutations in flower colour/shape were detected as chimeras in M 1 V 1 , M 1 V 2 , M 1 V 3 generations. The mutation frequency varied with the cultivar and exposure to gamma rays. Comparative analysis of original cultivars and their respective induced mutants on cytomorphological, anatomical and biochemical characters are being carried out for better understanding of the mechanism involved in the origin and evolution of somatic flower colour/shape mutations. Cytological analysis with reference to chromosomal aberrations, chromosome number, ICV, INV and DNA content gave no differences between the original and mutant cultivars. Analysis of florets/petal pigments by TLC and spectrophotometric methods indicated both qualitative and quantitative changes. (author)

  10. Screening for functional sequence variations and mutations in ABCA1

    NARCIS (Netherlands)

    Probst, Mario C. O.; Thumann, Harald; Aslanidis, Charalampos; Langmann, Thomas; Buechler, Christa; Patsch, Wolfgang; Baralle, Francisco E.; Dallinga-Thie, Geesje M.; Geisel, Jürgen; Keller, Christiane; Menys, Valentine C.; Schmitz, Gerd

    2004-01-01

    Mutations in the ATP-binding cassette 1 transporter gene (ABCA1) are responsible for the genetic HDL-deficiency syndromes, which are characterized by severely diminished plasma HDL-C levels and a predisposition to cardiovascular disease and splenomegaly. The ABCA1 gene contains 50 exons and codes

  11. Mutational and Evolutionary Analyses of Bovine Reprimo Gene ...

    African Journals Online (AJOL)

    It can therefore be concluded that bovine RPRM gene contained 4 transition mutations and 5 indels that can be used in marker assisted selection. Evolutionary findings also demonstrated the existence of a divergent evolution between bovine RPRM gene and RPRM gene of fishes and frog. Keywords: Identity, phylogeny ...

  12. Continuous containment monitoring with containment pressure fluctuation

    International Nuclear Information System (INIS)

    Dick, J.E.

    1996-01-01

    The monitoring of the integrity of containments particularly but not exclusively for nuclear plants is dealt with in this invention. While this application is primarily concerned with containment monitoring in the context of the single unit design, it is expected that the concepts presented will be universally applicable to any containment design, including containments for non-nuclear applications such as biological laboratories. The nuclear industry has long been interested in a means of monitoring containment integrity on a continuous basis, that is, while the reactor is operating normally. 12 refs., 2 figs

  13. Mutational meltdown in laboratory yeast populations

    NARCIS (Netherlands)

    Zeyl, C.; Mizesko, M.; Visser, de J.A.G.M.

    2001-01-01

    In small or repeatedly bottlenecked populations, mutations are expected to accumulate by genetic drift, causing fitness declines. In mutational meltdown models, such fitness declines further reduce population size, thus accelerating additional mutation accumulation and leading to extinction. Because

  14. Structural Implications of Mutations Conferring Rifampin Resistance in Mycobacterium leprae.

    Science.gov (United States)

    Vedithi, Sundeep Chaitanya; Malhotra, Sony; Das, Madhusmita; Daniel, Sheela; Kishore, Nanda; George, Anuja; Arumugam, Shantha; Rajan, Lakshmi; Ebenezer, Mannam; Ascher, David B; Arnold, Eddy; Blundell, Tom L

    2018-03-22

    The rpoB gene encodes the β subunit of RNA polymerase holoenzyme in Mycobacterium leprae (M. leprae). Missense mutations in the rpoB gene were identified as etiological factors for rifampin resistance in leprosy. In the present study, we identified mutations corresponding to rifampin resistance in relapsed leprosy cases from three hospitals in southern India which treat leprosy patients. DNA was extracted from skin biopsies of 35 relapse/multidrug therapy non-respondent leprosy cases, and PCR was performed to amplify the 276 bp rifampin resistance-determining region of the rpoB gene. PCR products were sequenced, and mutations were identified in four out of the 35 cases at codon positions D441Y, D441V, S437L and H476R. The structural and functional effects of these mutations were assessed in the context of three-dimensional comparative models of wild-type and mutant M. leprae RNA polymerase holoenzyme (RNAP), based on the recently solved crystal structures of RNAP of Mycobacterium tuberculosis, containing a synthetic nucleic acid scaffold and rifampin. The resistance mutations were observed to alter the hydrogen-bonding and hydrophobic interactions of rifampin and the 5' ribonucleotide of the growing RNA transcript. This study demonstrates that rifampin-resistant strains of M. leprae among leprosy patients in southern India are likely to arise from mutations that affect the drug-binding site and stability of RNAP.

  15. Role of Mitochondrial DNA Mutations in Cellular Vulnerability to Mitochondria-Specific Environmental Toxins

    National Research Council Canada - National Science Library

    Hirsch, Etienne C

    2005-01-01

    .... To test such a hypothesis in Parkinson's disease we proposed to: 1) develop an animal model with accumulated mtDNA mutations in catecholaminergic neurons by creating a transgenic mouse containing a tyrosine hydroxylase (TH...

  16. Minisequencing mitochondrial DNA pathogenic mutations

    Directory of Open Access Journals (Sweden)

    Carracedo Ángel

    2008-04-01

    Full Text Available Abstract Background There are a number of well-known mutations responsible of common mitochondrial DNA (mtDNA diseases. In order to overcome technical problems related to the analysis of complete mtDNA genomes, a variety of different techniques have been proposed that allow the screening of coding region pathogenic mutations. Methods We here propose a minisequencing assay for the analysis of mtDNA mutations. In a single reaction, we interrogate a total of 25 pathogenic mutations distributed all around the whole mtDNA genome in a sample of patients suspected for mtDNA disease. Results We have detected 11 causal homoplasmic mutations in patients suspected for Leber disease, which were further confirmed by standard automatic sequencing. Mutations m.11778G>A and m.14484T>C occur at higher frequency than expected by change in the Galician (northwest Spain patients carrying haplogroup J lineages (Fisher's Exact test, P-value Conclusion We here developed a minisequencing genotyping method for the screening of the most common pathogenic mtDNA mutations which is simple, fast, and low-cost. The technique is robust and reproducible and can easily be implemented in standard clinical laboratories.

  17. Mutation breeding in malting barley

    Energy Technology Data Exchange (ETDEWEB)

    Hiraki, Makoto; Sanada, Matsuyoshi

    1984-03-01

    The released varieties of malting barley through mutation breeding is more than ten in number, including foreign varieties. In Japan four varieties has been released so far. We started mutation breeding in 1956 together with cross breeding that we employed before. Until now, Gamma 4, Amagi Nijo 1 and Fuji Nijo 2 have been produced from the direct use of induced mutations and Nirasaki Nijo 8 from the indirect use of them. Mutation breeding has been used mainly in the partial improvement of agronomic characteristics since the selection for malting quality was very complicated. As the variety bred by induced mutation is usually equivalent to the original variety in malting quality, both this new variety and the original one could be cultivated in the same area without any problem on later malt production. Particularly when one farmer cultivates barley in an extensive acreage, he can harvest at the best time according to the different maturing time of each variety. From these points of view, mutation breeding is an efficient tool in malting barley breeding. Mutagens we have used so far are X-rays, ..gamma..-rays, neutron and chemicals such as dES. From our experience in selection, the low dose of radiation and chemical mutagens are more effective in selection of point mutation than the high dose of radiation which tends to produce many abnormal but few practical mutants. (author).

  18. Identification of Constrained Cancer Driver Genes Based on Mutation Timing

    Science.gov (United States)

    Sakoparnig, Thomas; Fried, Patrick; Beerenwinkel, Niko

    2015-01-01

    Cancer drivers are genomic alterations that provide cells containing them with a selective advantage over their local competitors, whereas neutral passengers do not change the somatic fitness of cells. Cancer-driving mutations are usually discriminated from passenger mutations by their higher degree of recurrence in tumor samples. However, there is increasing evidence that many additional driver mutations may exist that occur at very low frequencies among tumors. This observation has prompted alternative methods for driver detection, including finding groups of mutually exclusive mutations and incorporating prior biological knowledge about gene function or network structure. Dependencies among drivers due to epistatic interactions can also result in low mutation frequencies, but this effect has been ignored in driver detection so far. Here, we present a new computational approach for identifying genomic alterations that occur at low frequencies because they depend on other events. Unlike passengers, these constrained mutations display punctuated patterns of occurrence in time. We test this driver–passenger discrimination approach based on mutation timing in extensive simulation studies, and we apply it to cross-sectional copy number alteration (CNA) data from ovarian cancer, CNA and single-nucleotide variant (SNV) data from breast tumors and SNV data from colorectal cancer. Among the top ranked predicted drivers, we find low-frequency genes that have already been shown to be involved in carcinogenesis, as well as many new candidate drivers. The mutation timing approach is orthogonal and complementary to existing driver prediction methods. It will help identifying from cancer genome data the alterations that drive tumor progression. PMID:25569148

  19. HNPCC: Six new pathogenic mutations

    Directory of Open Access Journals (Sweden)

    Epplen Joerg T

    2004-06-01

    Full Text Available Abstract Background Hereditary non-polyposis colorectal cancer (HNPCC is an autosomal dominant disease with a high risk for colorectal and endometrial cancer caused by germline mutations in DNA mismatch-repair genes (MMR. HNPCC accounts for approximately 2 to 5% of all colorectal cancers. Here we present 6 novel mutations in the DNA mismatch-repair genes MLH1, MSH2 and MSH6. Methods Patients with clinical diagnosis of HNPCC were counselled. Tumor specimen were analysed for microsatellite instability and immunohistochemistry for MLH1, MSH2 and MSH6 protein was performed. If one of these proteins was not detectable in the tumor mutation analysis of the corresponding gene was carried out. Results We identified 6 frameshift mutations (2 in MLH1, 3 in MSH2, 1 in MSH6 resulting in a premature stop: two mutations in MLH1 (c.2198_2199insAACA [p.N733fsX745], c.2076_2077delTG [p.G693fsX702], three mutations in MSH2 (c.810_811delGT [p.C271fsX282], c.763_766delAGTGinsTT [p.F255fsX282], c.873_876delGACT [p.L292fsX298] and one mutation in MSH6 (c.1421_1422dupTG [p.C475fsX480]. All six tumors tested for microsatellite instability showed high levels of microsatellite instability (MSI-H. Conclusions HNPCC in families with MSH6 germline mutations may show an age of onset that is comparable to this of patients with MLH1 and MSH2 mutations.

  20. APR1400 Containment Simulation with CONTAIN code

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Moon Kyu; Chung, Bub Dong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2010-05-15

    The more realistic containment pressure variation predicted by the CONTAIN code through the coupled analysis during a large break loss of coolant accident in the nuclear power plant is expected to provide more accurate prediction for the plant behavior than a standalone MARS-KS calculation. The input deck has been generated based on the already available ARP- 1400 input for CONTEMPT code. Similarly to the CONTEMPT input deck, a simple two-cell model was adopted to model the containment behavior, one cell for the containment inner volume and another cell for the environment condition. The developed input for the CONTAIN code is to be eventually applied for the coupled code calculation of MARS-KS/CONTAIN

  1. APR1400 Containment Simulation with CONTAIN code

    International Nuclear Information System (INIS)

    Hwang, Moon Kyu; Chung, Bub Dong

    2010-01-01

    The more realistic containment pressure variation predicted by the CONTAIN code through the coupled analysis during a large break loss of coolant accident in the nuclear power plant is expected to provide more accurate prediction for the plant behavior than a standalone MARS-KS calculation. The input deck has been generated based on the already available ARP- 1400 input for CONTEMPT code. Similarly to the CONTEMPT input deck, a simple two-cell model was adopted to model the containment behavior, one cell for the containment inner volume and another cell for the environment condition. The developed input for the CONTAIN code is to be eventually applied for the coupled code calculation of MARS-KS/CONTAIN

  2. Effectiveness of containment sprays in containment management

    International Nuclear Information System (INIS)

    Nourbakhsh, H.P.; Perez, S.E.; Lehner, J.R.

    1993-05-01

    A limited study has been performed assessing the effectiveness of containment sprays-to mitigate particular challenges which may occur during a severe accident. Certain aspects of three specific topics related to using sprays under severe accident conditions were investigated. The first was the effectiveness of sprays connected to an alternate water supple and pumping source because the actual containment spray pumps are inoperable. This situation could occur during a station blackout. The second topic concerned the adverse as well as beneficial effects of using containment sprays during severe accident scenario where the containment atmosphere contains substantial quantities of hydrogen along with steam. The third topic was the feasibility of using containment sprays to moderate the consequences of DCH

  3. Factor V Leiden Mutation and PT 20210 Mutation Test

    Science.gov (United States)

    ... Disorders Fibromyalgia Food and Waterborne Illness Fungal Infections Gout Graves Disease Guillain-Barré Syndrome Hashimoto Thyroiditis Heart ... Tested? To determine whether you have an inherited gene mutation that increases your risk of developing a ...

  4. Radiation mutation breeding

    International Nuclear Information System (INIS)

    Song, Hi Sup; Kim, Jae Sung; Kim, Jin Kyu; Shin, In Chul; Lim, Young Taek

    1998-04-01

    In order to develop an advanced technical knowledge for the selection of better mutants, some of the crops were irradiated and the mutation rate, the survival rate and the method for selction of a mutant were studied. Furthermore, this study aimed to obtain basic data applicable to the development of genetic resources by evaluation and analysis the specific character for selection of the superior mutant and its plant breeding. 1. selection of the mutant with a superior resistance against environment in the principal crops 1) New varieties of mutant rices such as Wonpyeongbyeo, Wongwangbyeo, Winmibyeo, and heogseon chalbeyeo (sticky forma) were registered in the national variety list and made an application to crop variety protection right. They are under review now. 2) We also keep on studying on the number of a grain of 8 lines of excellent mutant rice for the purpose of improvement of breeding . 3) We selected 3 lines which have a resistance to pod and stem blight in large soybean, 31 lines with small grain size and higher yield, 112 lines of soybean of cooking, 7 lines of low lipoxygenase content, and 12 lines with decreased phytic acid content by 20 % compared to the previous level. 2. Selection of advanced Mugunwha (Rose of Sharon) mutant 1) Bagseul, a new variety of mutant, was developed and 30 plantlets of it are being proliferated. 2) Fifty-three lines of a mutant having a various morphologies were selected

  5. Radiation mutation breeding

    Energy Technology Data Exchange (ETDEWEB)

    Song, Hi Sup; Kim, Jae Sung; Kim, Jin Kyu; Shin, In Chul; Lim, Young Taek

    1998-04-01

    In order to develop an advanced technical knowledge for the selection of better mutants, some of the crops were irradiated and the mutation rate, the survival rate and the method for selction of a mutant were studied. Furthermore, this study aimed to obtain basic data applicable to the development of genetic resources by evaluation and analysis the specific character for selection of the superior mutant and its plant breeding. 1. selection of the mutant with a superior resistance against environment in the principal crops 1) New varieties of mutant rices such as Wonpyeongbyeo, Wongwangbyeo, Winmibyeo, and heogseon chalbeyeo (sticky forma) were registered in the national variety list and made an application to crop variety protection right. They are under review now. 2) We also keep on studying on the number of a grain of 8 lines of excellent mutant rice for the purpose of improvement of breeding . 3) We selected 3 lines which have a resistance to pod and stem blight in large soybean, 31 lines with small grain size and higher yield, 112 lines of soybean of cooking, 7 lines of low lipoxygenase content, and 12 lines with decreased phytic acid content by 20 % compared to the previous level. 2. Selection of advanced Mugunwha (Rose of Sharon) mutant 1) Bagseul, a new variety of mutant, was developed and 30 plantlets of it are being proliferated. 2) Fifty-three lines of a mutant having a various morphologies were selected.

  6. Mutation breeding in wheat

    International Nuclear Information System (INIS)

    Amer, I.M.

    2002-01-01

    The study aims to improve the productivity of wheat by using gamma ray (100 - 600 Gy) in mutation breading. Five local varieties were used and the program continued for the Sakha 69 for seven generations. Seeds irradiated with 600 Gy were not germinated in the field, while low doses (100-150 Gy) stimulated the root growth and spike length. The higher doses caused gradual decrease of growth with differences in varieties response. in the second generation, a genetic differences were noticed in most varieties using doses of 100-300 Gy, and the dispike was disappeared when 250 Gy was used. 79 plants from irradiated Sakha 69 were selected according to spike length and the number of grains and planted with the control to test the third generation. differences between the varieties were noticed and 8 mutants with high productivity were selected and evaluated in the fourth and fifth generations with the local variety. The mutants improve the productivity and in particular the mutants Nos.. (19-1), (14-3), and (30-2). The experiment showed the relation between the planting sites and the mutants in the sixth and seven generations

  7. Induced mutations in castor

    International Nuclear Information System (INIS)

    Ganesan, K.; Javad Hussain, H.S.; Vindhiyavarman, P.

    2001-01-01

    Castor (Ricinus communis L.) is an important oilseed crop in India. To create variability mutations were induced in two cultivars 'TMV5' (maturing in 130-140 days) and 'CO1' (perennial type). Gamma rays and diethyl sulphate and ethidium bromide were used for seed treatment. Ten doses, from 100 to 1000 Gy were employed. For chemical mutagenesis five concentrations of mutagenes from 10 to 50 mM were tried. No economic mutants could be isolated after treatment with the chemical mutagens. The following economic mutants were identified in the dose 300 Gy of gamma rays. Annual types from perennial CO 1 castor CO 1 is a perennial variety (8-10 years) with bold seeds (100 seed weight 90 g) and high oil content (57%). Twenty-one lines were isolated with annual types (160-180 days) with high yield potential as well as bold seeds and high oil content. These mutants, identified in M 3 generation were bred true in subsequent generations up to M 8 generation. Critical evaluation of the mutants in yield evaluation trials is in progress

  8. The (1+λ) evolutionary algorithm with self-adjusting mutation rate

    DEFF Research Database (Denmark)

    Doerr, Benjamin; Witt, Carsten; Gießen, Christian

    2017-01-01

    We propose a new way to self-adjust the mutation rate in population-based evolutionary algorithms. Roughly speaking, it consists of creating half the offspring with a mutation rate that is twice the current mutation rate and the other half with half the current rate. The mutation rate is then upd......We propose a new way to self-adjust the mutation rate in population-based evolutionary algorithms. Roughly speaking, it consists of creating half the offspring with a mutation rate that is twice the current mutation rate and the other half with half the current rate. The mutation rate...... is then updated to the rate used in that subpopulation which contains the best offspring. We analyze how the (1 + A) evolutionary algorithm with this self-adjusting mutation rate optimizes the OneMax test function. We prove that this dynamic version of the (1 + A) EA finds the optimum in an expected optimization...... time (number of fitness evaluations) of O(nA/log A + n log n). This time is asymptotically smaller than the optimization time of the classic (1 + A) EA. Previous work shows that this performance is best-possible among all A-parallel mutation-based unbiased black-box algorithms. This result shows...

  9. Empty Container Logistics

    Directory of Open Access Journals (Sweden)

    Jakov Karmelić

    2012-05-01

    Full Text Available Within the whole world container traffic, the largest share of containers is in the status of repositioning. Container repositioning results from the need for harmonization between the point of empty container accumulation and the point of demand, and waiting time for the availability of the first next transport of cargo. This status of containers on the container market is the consequence of imbalances in the worldwide trade distribution on most important shipping routes. The need for fast and effective reallocation of empty containers causes high costs and often represents an obstacle affecting the efficiency of port container terminals and inland carriers.In accordance with the above issue, this paper is mainly focused on the analysis of the data concerning global container capacities and the roots of container equipment imbalances, with the aim of determining the importance of empty container management and the need for empty container micro-logistic planning at the spread port area.

  10. Mutation of miRNA target sequences during human evolution

    DEFF Research Database (Denmark)

    Gardner, Paul P; Vinther, Jeppe

    2008-01-01

    It has long-been hypothesized that changes in non-protein-coding genes and the regulatory sequences controlling expression could undergo positive selection. Here we identify 402 putative microRNA (miRNA) target sequences that have been mutated specifically in the human lineage and show that genes...... containing such deletions are more highly expressed than their mouse orthologs. Our findings indicate that some miRNA target mutations are fixed by positive selection and might have been involved in the evolution of human-specific traits....

  11. Empty Container Logistics

    OpenAIRE

    Jakov Karmelić; Čedomir Dundović; Ines Kolanović

    2012-01-01

    Within the whole world container traffic, the largest share of containers is in the status of repositioning. Container repositioning results from the need for harmonization between the point of empty container accumulation and the point of demand, and waiting time for the availability of the first next transport of cargo. This status of containers on the container market is the consequence of imbalances in the worldwide trade distribution on most important shipping routes. The need for fast a...

  12. FAUST/CONTAIN; FAUST/CONTAIN

    Energy Technology Data Exchange (ETDEWEB)

    Cherdron, W.; Minges, J.; Sauter, H.; Schuetz, W.

    1995-08-01

    The FAUNA facility has been restructured after completion of the sodium fire experiments. It is now serving LWR research, cf. report II on program no. 32.21.02 concerning steam explosions. The CONTAIN code system for computing the thermodynamic, aerosol and radiological phenomena in a containment under severe accident conditions is being developed with a new to fission product release and transport. (orig.)

  13. Mutation breeding newsletter. No. 22

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1983-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  14. Mutation breeding newsletter. No. 34

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1989-07-01

    This issue of the Newsletter presents abstracts and short communications of research results on radiation and chemical induced mutation breeding projects. Positive traits such as disease resistance and increased productivity are highlighted.

  15. Mutation breeding newsletter. No. 29

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1987-02-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  16. Mutation breeding newsletter. No. 15

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1980-02-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  17. Mutation breeding newsletter. No. 5

    International Nuclear Information System (INIS)

    1975-02-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  18. Mutation breeding newsletter. No. 15

    International Nuclear Information System (INIS)

    1980-02-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  19. Mutation breeding newsletter. No. 14

    International Nuclear Information System (INIS)

    1979-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  20. Mutation breeding newsletter. No. 16

    International Nuclear Information System (INIS)

    1980-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  1. Mutation breeding newsletter. No. 12

    International Nuclear Information System (INIS)

    1978-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  2. Mutation breeding newsletter. No. 28

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1986-09-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  3. Mutation breeding newsletter. No. 29

    International Nuclear Information System (INIS)

    1987-02-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  4. Mutation breeding newsletter. No. 9

    International Nuclear Information System (INIS)

    1977-01-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  5. Mutation breeding newsletter. No. 7

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1976-01-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  6. Mutation breeding newsletter. No. 4

    International Nuclear Information System (INIS)

    1974-08-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  7. Mutation breeding newsletter. No. 18

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1981-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  8. Mutation breeding newsletter. No. 9

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1977-01-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  9. Mutation breeding newsletter. No. 34

    International Nuclear Information System (INIS)

    1989-07-01

    This issue of the Newsletter presents abstracts and short communications of research results on radiation and chemical induced mutation breeding projects. Positive traits such as disease resistance and increased productivity are highlighted

  10. Mutation breeding newsletter. No. 24

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1984-07-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  11. Mutation breeding newsletter. No. 32

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1988-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  12. Mutation breeding newsletter. No. 36

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1990-07-01

    This issue of the Newsletter presents abstracts and short communications of research results on radiation and chemical induced mutation breeding projects. Positive traits such as disease resistance and increased productivity are highlighted.

  13. Mutation breeding newsletter. No. 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1974-01-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  14. Mutation breeding newsletter. No. 3

    International Nuclear Information System (INIS)

    1974-01-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  15. Mutation breeding newsletter. No. 11

    International Nuclear Information System (INIS)

    1978-02-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  16. Mutation breeding newsletter. No. 6

    International Nuclear Information System (INIS)

    1975-08-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  17. Mutation breeding newsletter. No. 1

    International Nuclear Information System (INIS)

    1972-05-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  18. Mutation breeding newsletter. No. 31

    International Nuclear Information System (INIS)

    1988-03-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  19. Mutation breeding newsletter. No. 44

    International Nuclear Information System (INIS)

    1999-04-01

    This issue of the Newsletter presents research reports on the role of radiation induced mutation and chemical mutagens in improving productivity, disease resistance; cold and salinity tolerance of various crops and ornamental plants

  20. Mutation breeding newsletter. No. 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1972-05-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  1. Mutation breeding newsletter. No. 25

    International Nuclear Information System (INIS)

    1985-01-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  2. Mutation breeding newsletter. No. 32

    International Nuclear Information System (INIS)

    1988-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  3. Mutation breeding newsletter. No. 5

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1975-02-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  4. Mutation breeding newsletter. No. 20

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1982-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  5. Mutation breeding newsletter. No. 28

    International Nuclear Information System (INIS)

    1986-09-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  6. Mutation breeding newsletter. No. 17

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1981-03-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  7. Mutation breeding newsletter. No. 16

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1980-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  8. Mutation breeding newsletter. No. 8

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1976-09-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  9. Mutation breeding newsletter. No. 4

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1974-08-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  10. Mutation breeding newsletter. No. 12

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1978-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  11. Mutation breeding newsletter. No. 6

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1975-08-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  12. Mutation breeding newsletter. No. 10

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1977-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  13. Mutation breeding newsletter. No. 14

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1979-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  14. Mutation breeding newsletter. No. 36

    International Nuclear Information System (INIS)

    1990-07-01

    This issue of the Newsletter presents abstracts and short communications of research results on radiation and chemical induced mutation breeding projects. Positive traits such as disease resistance and increased productivity are highlighted

  15. CHRNE Mutation and Congenital Myasthenia

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-01-01

    Full Text Available The CHRNE e1293insG mutation was identified in 14 (60% of 23 North African families with an early onset form of congenital myasthenic syndrome studied at centers in France, Tunisia, Algeria, and UK.

  16. Mutation breeding newsletter. No. 19

    International Nuclear Information System (INIS)

    1982-01-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  17. Mutation breeding newsletter. No. 7

    International Nuclear Information System (INIS)

    1976-01-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  18. Mutation breeding newsletter. No. 24

    International Nuclear Information System (INIS)

    1984-07-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  19. Mutation breeding newsletter. No. 20

    International Nuclear Information System (INIS)

    1982-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  20. Mutation breeding newsletter. No. 18

    International Nuclear Information System (INIS)

    1981-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  1. Mutation breeding newsletter. No. 31

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1988-03-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  2. Mutation breeding newsletter. No. 27

    International Nuclear Information System (INIS)

    1986-02-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  3. Mutation breeding newsletter. No. 26

    International Nuclear Information System (INIS)

    1985-10-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  4. Mutation breeding newsletter. No. 17

    International Nuclear Information System (INIS)

    1981-03-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  5. Mutation breeding newsletter. No. 30

    International Nuclear Information System (INIS)

    1987-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  6. Mutation breeding newsletter. No. 13

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1979-02-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  7. Mutation breeding newsletter. No. 30

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1987-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  8. Mutation breeding newsletter. No. 19

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1982-01-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  9. Mutation breeding newsletter. No. 26

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1985-10-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  10. Mutation breeding newsletter. No. 25

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1985-01-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  11. Mutation breeding newsletter. No. 23

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1983-01-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  12. Mutation breeding newsletter. No. 27

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1986-02-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  13. Mutation breeding newsletter. No. 2

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1973-02-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  14. Mutation breeding newsletter. No. 11

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1978-02-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants.

  15. Mutation breeding newsletter. No. 23

    International Nuclear Information System (INIS)

    1983-01-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  16. Mutation breeding newsletter. No. 2

    International Nuclear Information System (INIS)

    1973-02-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  17. Mutation breeding newsletter. No. 10

    International Nuclear Information System (INIS)

    1977-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  18. Mutation breeding newsletter. No. 8

    International Nuclear Information System (INIS)

    1976-09-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  19. Mutation breeding newsletter. No. 13

    International Nuclear Information System (INIS)

    1979-02-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  20. BRAF mutations in conjunctival melanoma

    DEFF Research Database (Denmark)

    Larsen, Ann-Cathrine; Dahl, Christina; Dahmcke, Christina M.

    2016-01-01

    with atypia. BRAF mutations were identified in 39 of 111 (35%) cases. The rate ratio of BRAF-mutated versus BRAF-wild-type melanoma did not change over time. BRAF mutations were associated with T1 stage (p = 0.007), young age (p = 0.001), male gender (p = 0.02), sun-exposed location (p = 0.01), mixed....../non-pigmented tumour colour (p = 0.02) and nevus origin (p = 0.005), but did not associate with prognosis. BRAF status in conjunctival melanoma and paired premalignant lesions corresponded in 19 of 20 cases. Immunohistochemistry detected BRAF V600E mutations with a sensitivity of 0.94 and a specificity of 1...

  1. Mutation breeding newsletter. No. 22

    International Nuclear Information System (INIS)

    1983-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  2. Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility.

    Science.gov (United States)

    Melikian, George L; Rhee, Soo-Yon; Taylor, Jonathan; Fessel, W Jeffrey; Kaufman, David; Towner, William; Troia-Cancio, Paolo V; Zolopa, Andrew; Robbins, Gregory K; Kagan, Ron; Israelski, Dennis; Shafer, Robert W

    2012-05-01

    Determining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.

  3. Mutation breeding in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Neto, A T; Menten, J O.M. [Centro de Energia Nuclear na Agricultura, Piracicaba (Brazil); Ando, A

    1980-03-01

    How mutation induction is used for plant breeding in Brazil is reported. For upland rice, the combined treatment with gamma-ray and mutagens (ethylene imine or ethylmethane sulfonate) has been used on the variety, Dourado Precoce, and some mutants with shortculm length and/or earliness without altering the productivity have been obtained. A project on the quantitative and qualitative protein improvement in upland rice was also started in 1979. In corn, the effect of gamma-irradiation on heterosis has been analyzed, and it was found that the single hybrids from two parental lines derived from irradiated seeds had increased ear productivity. For beans (Phaseolus yulgaris), gamma-irradiation and chemical mutagens have been used to induce the mutants with different seed color, disease resistance to golden mosaic virus and Xanthomonas phaseoli, earliness, high productivity and high protein content. Some mutants with partly improved characters have been obtained in these experiments. Two varieties of wheat tolerant to aluminum toxicity have been obtained, but the one showed high lodging due to its unfavorable plant height, and the other was highly susceptible to culm rust. Therefore, irradiation experiments have been started to improve these characters. The projects involving the use of gamma-irradiation have been tested to obtain the mutant lines insensitive to photoperiod and resistant to bud-blight in soybean, the mutant lines resistant to mosaic virus in papaya, the photoperiod-insensitive mutants in sorghum, the mosaic virus resistant and non-flowering mutants in sugar cane, and the Fusarium and nematode-resistant mutants in black pepper.

  4. Nuclear reactor container

    International Nuclear Information System (INIS)

    Ishiyama, Takenori.

    1989-01-01

    This invention concerns a nuclear reactor container in which heat is removed from a container by external water injection. Heat is removed from the container by immersing the lower portion of the container into water and scattering spary water from above. Thus, the container can be cooled by the spray water falling down along the outer wall of the container to condensate and cool vapors filled in the container upon occurrence of accidents. Further, since the inside of the container can be cooled also during usual operation, it can also serve as a dry well cooler. Accordingly, heat is removed from the reactor container upon occurrence of accidents by the automatic operation of a spray device corresponding to the change of the internal temperature and the pressure in the reactor container. Further, since all of these devices are disposed out of container, maintenance is also facilitated. (I.S.)

  5. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine.

    Science.gov (United States)

    Stenson, Peter D; Mort, Matthew; Ball, Edward V; Shaw, Katy; Phillips, Andrew; Cooper, David N

    2014-01-01

    The Human Gene Mutation Database (HGMD®) is a comprehensive collection of germline mutations in nuclear genes that underlie, or are associated with, human inherited disease. By June 2013, the database contained over 141,000 different lesions detected in over 5,700 different genes, with new mutation entries currently accumulating at a rate exceeding 10,000 per annum. HGMD was originally established in 1996 for the scientific study of mutational mechanisms in human genes. However, it has since acquired a much broader utility as a central unified disease-oriented mutation repository utilized by human molecular geneticists, genome scientists, molecular biologists, clinicians and genetic counsellors as well as by those specializing in biopharmaceuticals, bioinformatics and personalized genomics. The public version of HGMD (http://www.hgmd.org) is freely available to registered users from academic institutions/non-profit organizations whilst the subscription version (HGMD Professional) is available to academic, clinical and commercial users under license via BIOBASE GmbH.

  6. High resolution melting for mutation scanning of TP53 exons 5–8

    International Nuclear Information System (INIS)

    Krypuy, Michael; Dobrovic, Alexander; Ahmed, Ahmed Ashour; Etemadmoghadam, Dariush; Hyland, Sarah J; Australian Ovarian Cancer Study Group; Fazio, Anna de; Fox, Stephen B; Brenton, James D; Bowtell, David D

    2007-01-01

    p53 is commonly inactivated by mutations in the DNA-binding domain in a wide range of cancers. As mutant p53 often influences response to therapy, effective and rapid methods to scan for mutations in TP53 are likely to be of clinical value. We therefore evaluated the use of high resolution melting (HRM) as a rapid mutation scanning tool for TP53 in tumour samples. We designed PCR amplicons for HRM mutation scanning of TP53 exons 5 to 8 and tested them with DNA from cell lines hemizygous or homozygous for known mutations. We assessed the sensitivity of each PCR amplicon using dilutions of cell line DNA in normal wild-type DNA. We then performed a blinded assessment on ovarian tumour DNA samples that had been previously sequenced for mutations in TP53 to assess the sensitivity and positive predictive value of the HRM technique. We also performed HRM analysis on breast tumour DNA samples with unknown TP53 mutation status. One cell line mutation was not readily observed when exon 5 was amplified. As exon 5 contained multiple melting domains, we divided the exon into two amplicons for further screening. Sequence changes were also introduced into some of the primers to improve the melting characteristics of the amplicon. Aberrant HRM curves indicative of TP53 mutations were observed for each of the samples in the ovarian tumour DNA panel. Comparison of the HRM results with the sequencing results revealed that each mutation was detected by HRM in the correct exon. For the breast tumour panel, we detected seven aberrant melt profiles by HRM and subsequent sequencing confirmed the presence of these and no other mutations in the predicted exons. HRM is an effective technique for simple and rapid scanning of TP53 mutations that can markedly reduce the amount of sequencing required in mutational studies of TP53

  7. Screening of three Mediterranean phenylketonuria mutations in ...

    Indian Academy of Sciences (India)

    as the most frequent mutation (Dahri et al. 2010). The. E280K mutation was also reported in Mediterranean popu- lations (Guldberg et al. 1993). Since Tunisia is a Mediter- ranean country, patients with PKU are presumed to have these mutations. The aim of this study was to assess prevalence of the three above mutations ...

  8. Signatures of mutational processes in human cancer

    NARCIS (Netherlands)

    Alexandrov, L.B.; Nik-Zainal, S.; Wedge, D.C.; Aparicio, S.A.; Behjati, S.; Biankin, A.V.; Bignell, G.R.; Bolli, N.; Borg, A.; Borresen-Dale, A.L.; Boyault, S.; Burkhardt, B.; Butler, A.P.; Caldas, C.; Davies, H.R.; Desmedt, C.; Eils, R.; Eyfjord, J.E.; Foekens, J.A.; Greaves, M.; Hosoda, F.; Hutter, B.; Ilicic, T.; Imbeaud, S.; Imielinsk, M.; Jager, N.; Jones, D.T.; Knappskog, S.; Kool, M.; Lakhani, S.R.; Lopez-Otin, C.; Martin, S.; Munshi, N.C.; Nakamura, H.; Northcott, P.A.; Pajic, M.; Papaemmanuil, E.; Paradiso, A.; Pearson, J.V.; Puente, X.S.; Raine, K.; Ramakrishna, M.; Richardson, A.L.; Richter, J.; Rosenstiel, P.; Schlesner, M.; Schumacher, T.N.; Span, P.N.; Teague, J.W.; Totoki, Y.; Tutt, A.N.; Valdes-Mas, R.; Buuren, M.M. van; Veer, L. van 't; Vincent-Salomon, A.; Waddell, N.; Yates, L.R.; Zucman-Rossi, J.; Futreal, P.A.; McDermott, U.; Lichter, P.; Meyerson, M.; Grimmond, S.M.; Siebert, R.; Campo, E.; Shibata, T.; Pfister, S.M.; Campbell, P.J.; Stratton, M.R.; Schlooz-Vries, M.S.; Tol, J.J. van; Laarhoven, H.W. van; Sweep, F.C.; Bult, P.; et al.,

    2013-01-01

    All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362

  9. A common Greenlandic Inuit BRCA1 RING domain founder mutation

    DEFF Research Database (Denmark)

    Hansen, T.v.O.; Ejlertsen, B.; Albrechtsen, Anders

    2009-01-01

    of the families had members with ovarian cancer, suggesting that the RING domain may be an ovarian cancer hotspot. By SNP array analysis, we find that all 13 families share a 4.5 Mb genomic fragment containing the BRCA1 gene, showing that the mutation originates from a founder. Finally, analysis of 1152 Inuit......, representing almost ~2% of the total Greenlandic Inuit population, showed that the frequency of the mutation was 1.0%. We conclude that the BRCA1 nucleotide 234 T > G is a common Greenlandic Inuit founder mutation. The relative high frequency in the general population, together with the ease of screening...... and possibility to reduce mortality in gene carriers, may warrant screening of the Greenlandic Inuit population. Provided screening is efficient, about 5% of breast- and 13% of ovarian cancers, respectively, may be prevented Udgivelsesdato: 2009/5...

  10. Containment performance improvement program

    International Nuclear Information System (INIS)

    Beckner, W.; Mitchell, J.; Soffer, L.; Chow, E.; Lane, J.; Ridgely, J.

    1990-01-01

    The Containment Performance Improvement (CPI) program has been one of the main elements in the US Nuclear Regulatory Commission's (NRC's) integrated approach to closure of severe accident issues for US nuclear power plants. During the course of the program, results from various probabilistic risk assessment (PRA) studies and from severe accident research programs for the five US containment types have been examined to identify significant containment challenges and to evaluate potential improvements. The five containment types considered are: the boiling water reactor (BMR) Mark I containment, the BWR Mark II containment, the BWR Mark III containment, the pressurized water reactor (PWR) ice condenser containment, and the PWR dry containments (including both subatmospheric and large subtypes). The focus of the CPI program has been containment performance and accident mitigation, however, insights are also being obtained in the areas of accident prevention and accident management

  11. Initiating a watch list for Ebola virus antibody escape mutations

    Directory of Open Access Journals (Sweden)

    Craig R. Miller

    2016-02-01

    Full Text Available The 2014 Ebola virus (EBOV outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.

  12. Initiating a watch list for Ebola virus antibody escape mutations.

    Science.gov (United States)

    Miller, Craig R; Johnson, Erin L; Burke, Aran Z; Martin, Kyle P; Miura, Tanya A; Wichman, Holly A; Brown, Celeste J; Ytreberg, F Marty

    2016-01-01

    The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP) of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans) at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.

  13. Sucrose and IQ induced mutations in rat colon by independent

    DEFF Research Database (Denmark)

    Hansen, Max; Hald, M. T.; Autrup, H.

    2004-01-01

    Sucrose-rich diets have repeatedly been observed to have co-carcinogenic actions in colon and liver of rats and to increase the number of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) induced aberrant crypt foci in rat colon. To investigate a possible interaction between sucrose and IQ...... on the genotoxicity in rat liver and colon, we gave Big Blue rats(TM) a diet containing sucrose (0%, 3.45% or 13.4% w/w) and/or IQ (70 ppm) for a period of 3 weeks. Sucrose and IQ increased the mutation frequency in the colon. The effect of combined treatments with IQ and sucrose on the mutation frequencies...... was additive indicating that sucrose and IQ act independently. This was supported by the mutation spectra where sucrose expands the background mutations in the colon, whereas IQ, in other studies, more specifically has induced G:C --> T:A transversions. In the liver IQ increased the mutation frequency, whereas...

  14. Common Β- Thalassaemia Mutations in

    Directory of Open Access Journals (Sweden)

    P Azarfam

    2005-01-01

    Full Text Available Introduction: β –Thalassaemia was first explained by Thomas Cooly as Cooly’s anaemia in 1925. The β- thalassaemias are hereditary autosomal disorders with decreased or absent β-globin chain synthesis. The most common genetic defects in β-thalassaemias are caused by point mutations, micro deletions or insertions within the β-globin gene. Material and Methods: In this research , 142 blood samples (64 from childrens hospital of Tabriz , 15 samples from Shahid Gazi hospital of Tabriz , 18 from Urumia and 45 samples from Aliasghar hospital of Ardebil were taken from thalassaemic patients (who were previously diagnosed .Then 117 non-familial samples were selected . The DNA of the lymphocytes of blood samples was extracted by boiling and Proteinase K- SDS procedure, and mutations were detected by ARMS-PCR methods. Results: From the results obtained, eleven most common mutations,most of which were Mediterranean mutations were detected as follows; IVS-I-110(G-A, IVS-I-1(G-A ،IVS-I-5(G-C ,Frameshift Codon 44 (-C,( codon5(-CT,IVS-1-6(T-C, IVS-I-25(-25bp del ,Frameshift 8.9 (+G ,IVS-II-1(G-A ,Codon 39(C-T, Codon 30(G-C the mutations of the samples were defined. The results showed that Frameshift 8.9 (+G, IVS-I-110 (G-A ,IVS-II-I(G-A, IVS-I-5(G-C, IVS-I-1(G-A , Frameshift Codon 44(-C , codon5(-CT , IVS-1-6(T-C , IVS-I-25(-25bp del with a frequency of 29.9%, 25.47%,17.83%, 7.00%, 6.36% , 6.63% , 3.8% , 2.5% , 0.63% represented the most common mutations in North - west Iran. No mutations in Codon 39(C-T and Codon 30(G-C were detected. Cunclusion: The frequency of the same mutations in patients from North - West of Iran seems to be different as compared to other regions like Turkey, Pakistan, Lebanon and Fars province of Iran. The pattern of mutations in this region is more or less the same as in the Mediterranean region, but different from South west Asia and East Asia.

  15. Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype

    Directory of Open Access Journals (Sweden)

    Matei Irina

    2001-08-01

    Full Text Available Abstract Background Genomic instability has been reported at microsatellite tracts in few coding sequences. We have shown that the Bloom syndrome BLM gene may be a target of microsatelliteinstability (MSI in a short poly-adenine repeat located in its coding region. To further characterize the involvement of BLM in tumorigenesis, we have investigated mutations in nine genes containing coding microsatellites in microsatellite mutator phenotype (MMP positive and negative gastric carcinomas (GCs. Methods We analyzed 50 gastric carcinomas (GCs for mutations in the BLM poly(A tract aswell as in the coding microsatellites of the TGFβ1-RII, IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes. Results BLM mutations were found in 27% of MMP+ GCs (4/15 cases but not in any of the MMP negative GCs (0/35 cases. The frequency of mutations in the other eight coding regions microsatellite was the following: TGFβ1-RII (60 %, BAX (27%, hMSH6 (20%,hMSH3 (13%, CBL (13%, IGFIIR (7%, RECQL (0% and WRN (0%. Mutations in BLM appear to be more frequently associated with frameshifts in BAX and in hMSH6and/or hMSH3. Tumors with BLM alterations present a higher frequency of unstable mono- and trinucleotide repeats located in coding regions as compared with mutator phenotype tumors without BLM frameshifts. Conclusions BLM frameshifts are frequent alterations in GCs specifically associated with MMP+tumors. We suggest that BLM loss of function by MSI may increase the genetic instability of a pre-existent unstable genotype in gastric tumors.

  16. Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype

    Science.gov (United States)

    Calin, George; Ranzani, Guglielmina N; Amadori, Dino; Herlea, Vlad; Matei, Irina; Barbanti-Brodano, Giuseppe; Negrini, Massimo

    2001-01-01

    Background Genomic instability has been reported at microsatellite tracts in few coding sequences. We have shown that the Bloom syndrome BLM gene may be a target of microsatelliteinstability (MSI) in a short poly-adenine repeat located in its coding region. To further characterize the involvement of BLM in tumorigenesis, we have investigated mutations in nine genes containing coding microsatellites in microsatellite mutator phenotype (MMP) positive and negative gastric carcinomas (GCs). Methods We analyzed 50 gastric carcinomas (GCs) for mutations in the BLM poly(A) tract aswell as in the coding microsatellites of the TGFβ1-RII, IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes. Results BLM mutations were found in 27% of MMP+ GCs (4/15 cases) but not in any of the MMP negative GCs (0/35 cases). The frequency of mutations in the other eight coding regions microsatellite was the following: TGFβ1-RII (60 %), BAX (27%), hMSH6 (20%),hMSH3 (13%), CBL (13%), IGFIIR (7%), RECQL (0%) and WRN (0%). Mutations in BLM appear to be more frequently associated with frameshifts in BAX and in hMSH6and/or hMSH3. Tumors with BLM alterations present a higher frequency of unstable mono- and trinucleotide repeats located in coding regions as compared with mutator phenotype tumors without BLM frameshifts. Conclusions BLM frameshifts are frequent alterations in GCs specifically associated with MMP+tumors. We suggest that BLM loss of function by MSI may increase the genetic instability of a pre-existent unstable genotype in gastric tumors. PMID:11532193

  17. SQSTM1 Mutations and Glaucoma.

    Directory of Open Access Journals (Sweden)

    Todd E Scheetz

    Full Text Available Glaucoma is the most common cause of irreversible blindness worldwide. One subset of glaucoma, normal tension glaucoma (NTG occurs in the absence of high intraocular pressure. Mutations in two genes, optineurin (OPTN and TANK binding kinase 1 (TBK1, cause familial NTG and have known roles in the catabolic cellular process autophagy. TKB1 encodes a kinase that phosphorylates OPTN, an autophagy receptor, which ultimately activates autophagy. The sequestosome (SQSTM1 gene also encodes an autophagy receptor and also is a target of TBK1 phosphorylation. Consequently, we hypothesized that mutations in SQSTM1 may also cause NTG. We tested this hypothesis by searching for glaucoma-causing mutations in a cohort of NTG patients (n = 308 and matched controls (n = 157 using Sanger sequencing. An additional 1098 population control samples were also analyzed using whole exome sequencing. A total of 17 non-synonymous mutations were detected which were not significantly skewed between cases and controls when analyzed separately, or as a group (p > 0.05. These data suggest that SQSTM1 mutations are not a common cause of NTG.

  18. Mutation breeding in Philippine fruits

    International Nuclear Information System (INIS)

    Espino, R.R.C.

    1987-09-01

    Studies were made to establish standard conditions for mutation induction by gamma-irradiation to be performed in combination with in-vitro culture for banana and citrus spp. Besides this, radio-sensitivity of seeds and/or plantlets of mango, sugar apple, soursop, lanzones and Jack fruit was investigated and primary observation on the occurrence of mutation was made. For the mutagenesis of banana shoot tip cultures, radio-sensitivity of plantlets derived from the culture as well as fresh-cultured shoots was examined and phenotypes indicative of mutation, such as chlorophyl streaking, slow growth, pigmentation and varied bunch orientation were recorded. Isozyme analysis for mutated protein structure was not conclusive. In the in-vitro culture of Citrus spp., seeds placed on fresh media as well as germinating seeds and two-leaf stage seedlings in test tubes were examined for their radio-sensitivity. Irradiated materials were propagated for further observation. In these two crops, basic methodology for mutation induction with combined use of in-vitro culture and gamma-irradiation was established. In mango, sugar apple, soursop, lanzones and Jack fruit, basic data on radiosensitivity were obtained. In mango, leaf abnormalities were observed after the treatment of scions

  19. A simple algebraic cancer equation: calculating how cancers may arise with normal mutation rates

    Directory of Open Access Journals (Sweden)

    Shibata Darryl

    2010-01-01

    Full Text Available Abstract Background The purpose of this article is to present a relatively easy to understand cancer model where transformation occurs when the first cell, among many at risk within a colon, accumulates a set of driver mutations. The analysis of this model yields a simple algebraic equation, which takes as inputs the number of stem cells, mutation and division rates, and the number of driver mutations, and makes predictions about cancer epidemiology. Methods The equation [p = 1 - (1 - (1 - (1 - udkNm ] calculates the probability of cancer (p and contains five parameters: the number of divisions (d, the number of stem cells (N × m, the number of critical rate-limiting pathway driver mutations (k, and the mutation rate (u. In this model progression to cancer "starts" at conception and mutations accumulate with cell division. Transformation occurs when a critical number of rate-limiting pathway mutations first accumulates within a single stem cell. Results When applied to several colorectal cancer data sets, parameter values consistent with crypt stem cell biology and normal mutation rates were able to match the increase in cancer with aging, and the mutation frequencies found in cancer genomes. The equation can help explain how cancer risks may vary with age, height, germline mutations, and aspirin use. APC mutations may shorten pathways to cancer by effectively increasing the numbers of stem cells at risk. Conclusions The equation illustrates that age-related increases in cancer frequencies may result from relatively normal division and mutation rates. Although this equation does not encompass all of the known complexity of cancer, it may be useful, especially in a teaching setting, to help illustrate relationships between small and large cancer features.

  20. Accident resistant transport container

    Science.gov (United States)

    Anderson, J.A.; Cole, K.K.

    The invention relates to a container for the safe air transport of plutonium having several intermediate wood layers and a load spreader intermediate an inner container and an outer shell for mitigation of shock during a hypothetical accident.

  1. Nuclear reactor containment device

    International Nuclear Information System (INIS)

    Ichiki, Tadaharu.

    1980-01-01

    Purpose: To reduce the volume of a containment shell and decrease the size of a containment equipment for BWR type reactors by connecting the containment shell and a suppression pool with slanted vent tubes to thereby shorten the vent tubes. Constitution: A pressure vessel containing a reactor core is installed at the center of a building and a containment vessel for the nuclear reactor that contains the pressure vessel forms a cabin. To a building situated below the containment shell, is provided a suppression chamber in which cooling water is charged to form a suppression pool. The suppression pool is communicated with vent tubes that pass through the partition wall of the containment vessel. The vent tubes are slanted and their lower openings are immersed in coolants. Therefore, if accident is resulted and fluid at high temperature and high pressure is jetted from the pressure vessel, the jetting fluid is injected and condensated in the cooling water. (Moriyama, K.)

  2. Accident resistant transport container

    International Nuclear Information System (INIS)

    Andersen, J.A.; Cole, J.K.

    1980-01-01

    The invention relates to a container for the safe air transport of plutonium having several intermediate wood layers and a load spreader intermediate an inner container and an outer shell for mitigation of shock during a hypothetical accident

  3. Mutation induction in grasspea (Lathyrus sativus L.)

    International Nuclear Information System (INIS)

    Ali, M.S.; Shaikh, M.A.Q.; Islam, M.S.; Saha, C.S.

    1989-01-01

    Full text: Grasspea is a widely grown food legume in Bangladesh, suited particularly for marginal conditions. Its yields are low, its main drawback, however, is that the seeds contain a neurotoxin BOAA, which requires heat degradation before consumption. The genetic base of local varieties is rather narrow. Introduced varieties are even lower yielding than the local ones or fail to flower and produce seeds. Thus, mutation induction of local cultivars should be regarded as a means for creating useful genetic variation. Seeds of the grasspea cultivar 'BINA Acc. No.1' collected from Jessore were treated with 2-5 mM solutions of sodium azide. A wide range of genetic variation was obtained regarding plant height, number of pods per plant, days to maturity. (author)

  4. Partiality and Container Monads

    DEFF Research Database (Denmark)

    Uustalu, Tarmo; Veltri, Niccolò

    2017-01-01

    the relationship between containers and lifting monads. We show that the lifting monads usually employed in type theory can be specified in terms of containers. Moreover, we give a precise characterization of containers whose interpretations carry a lifting monad structure. We show that these conditions...

  5. Thalassemia mutations in Gaziantep, Turkey

    African Journals Online (AJOL)

    STORAGESEVER

    2010-02-22

    Feb 22, 2010 ... Table 3. Frequency of β-thalassemia mutations in the Eastern Mediterranean. Mutation. This study Turkey Cyprus Greece Syria Palestine Bulgaria Azerbaijan Iran Iraq. IVS 1.110 (G>A). 29.1. 39.3. 79.7. 42.1. 24.1. 17.6. 24.2. 20.2. 4.8 1.9. IVS 2.1 (G>A). 12.3. 4.7. -. 3.3. 4.2. 2.9. -. -. 33.9 18.3. IVS 1.1 (G>A).

  6. Stowing the Right Containers on Container Vessels

    DEFF Research Database (Denmark)

    Jensen, Rune Møller

    2014-01-01

    ’s largest container vessels using standard mathematical programming techniques and off-the-shelf solvers. The presentation will provide basic insight into the domain, with pointers to further information that enable you to join in this promising new path of operations research and business....

  7. Passive containment system

    International Nuclear Information System (INIS)

    Kleimola, F.W.

    1977-01-01

    Disclosed is a containment system that provides complete protection entirely by passive means for the loss of coolant accident in a nuclear power plant and wherein all stored energy released in the coolant blowdown is contained and absorbed while the nuclear fuel is prevented from over-heating by a high containment back-pressure and a reactor vessel refill system. The primary containment vessel is restored to a high sub-atmospheric pressure within a few minutes after accident initiation and the decay heat is safely transferred to the environment while radiolytic hydrogen is contained by passive means. 20 claims, 14 figures

  8. Characterization of six mutations in Exon 37 of neurofibromatosis type 1 gene

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyaya, M.; Osborn, M.; Maynard, J.; Harper, P. [Institute of Medical Genetics, Cardiff, Wales (United Kingdom)

    1996-07-26

    Neurofibromatosis type 1 (NF1) is one of the most common inherited disorders, with an incidence of 1 in 3,000. We screened a total of 320 unrelated NF1 patients for mutations in exon 37 of the NF1 gene. Six independent mutations were identified, of which three are novel, and these include a recurrent nonsense mutation identified in 2 unrelated patients at codon 2281 (G2281X), a 1-bp insertion (6791 ins A) resulting in a change of TAG (tyrosine) to a TAA (stop codon), and a 3-bp deletion (6839 del TAC) which generated a frameshift. Another recurrent nonsense mutation, Y2264X, which was detected in 2 unrelated patients in this study, was also previously reported in 2 NF1 individuals. All the mutations were identified within a contiguous 49-bp sequence. Further studies are warranted to support the notion that this region of the gene contains highly mutable sequences. 17 refs., 2 figs., 1 tab.

  9. Group 4. Containment

    International Nuclear Information System (INIS)

    McCauley, V.S.; Keiser, J.R.

    1992-01-01

    This paper summarizes the findings of the Containment Working Group which met at the Workshop on Radioactive, Hazardous, and/or Mixed Waste Sludge Management. The Containment Working Group (CWG) examined the problems associated with providing adequate containment of waste forms from both short- and long-term storage. By its nature, containment encompasses a wide variety of waste forms, storage conditions, container types, containment schemes, and handling activities. A containment system can be anything from a 55-gal drum to a 100-ft-long underground vault. Because of the diverse nature of containment systems, the CWG chose to focus its limited time on broad issues that are applicable to the design of any containment system, rather than attempting to address problems specific to a particular containment system or waste-form type. Four major issues were identified by the CWG. They relate to: (1) service conditions and required system performance; (2) ultimate disposition; (3) cost and schedule; and (4) acceptance criteria, including quality assurance/quality control (QA/QC) concerns. All of the issues raised by the group are similar in that they all help to define containment system requirements

  10. Fibre-concrete container

    International Nuclear Information System (INIS)

    2000-01-01

    In this leaflet the fibre-concrete container for radioactive wastes is described. The fibre container is made of fibre-concrete that contains cement, aggregate, sand, filter, flame-silica, super-plastificator, water and scattered metal fibres. The fibre-concrete container has a dice shape with outer dimension 1.7 x 1.7 x 1.7 m. It is mounted of a container body, a container cover and two caps. Total weight of container is 4,240 kg, maximum weight of loaded container do not must exceed 15,000 kg. The physical and mechanical properties of the fibre-concrete container are described in detail. The fibre-concrete container manufactured for storing of low and intermediate radioactive wastes. A fibre-concrete container utilization to store of radioactive wastes solves these problems: increase of stability of stored packages of radioactive waste; watertightness within 300 years at least; static stability of bearing space; better utilization of bearing spaces; insulation of radioactive waste in a case of seismic and geological event; increase of fire resistance; and transport of radioactive waste

  11. A Biologically Based Approach to the Mutation of Code

    Science.gov (United States)

    1999-09-01

    instructions called a genome. This genome contains the master blueprint for all cellular structures and functions within the organism for the duration of...structures known as chromosomes, which are found in the nucleus of all non-somatic cells. Many procaryotic organisms have single-stranded DNA. An...coding sequence of a gene, or by an aberrant cellular recombination process. One way to reduce the chances of a harmful mutation occuring is to

  12. Energy parasites trigger oncogene mutation

    Czech Academy of Sciences Publication Activity Database

    Pokorný, Jiří; Pokorný, Jan; Jandová, Anna; Kobilková, J.; Vrba, J.; Vrba, J. jr.

    2016-01-01

    Roč. 92, č. 10 (2016), s. 577-582 ISSN 0955-3002 R&D Projects: GA ČR GA16-12757S Institutional support: RVO:68378271 ; RVO:67985882 Keywords : cancer initiation * cell-mediated immunity * coherent electromagnetic states * genome somatic mutation * LDH virus * parasitic energy consumption Subject RIV: BO - Biophysics Impact factor: 1.992, year: 2016

  13. Induced mutation of Dendrobium orchid

    International Nuclear Information System (INIS)

    Sakinah Ariffin; Mohd Nazir Basiran

    2000-01-01

    Dendrobiiim orchids serve as the main orchid cut flower export of Malaysia. The wide range of colour and forms presently available in the market are obtained through hybridisation. Induced mutation breeding program was initiated on a commercial variety Dendrobium 'Sonia Kai' to explore the possibilities of obtaining new colour and forms. Matured seeds from self pollination were cultured and irradiated at 35 Gy at the protocorm-like bodies (PLBS) stage. Selection of induced mutations was done after the first flowering of the plants regenerated from the irradiated protocorms. Results showed changes in flower colour, shape and size. Most of these chances are expressed in different combinations in the petals, sepals and lip of the flowers. Thus, resulting. in a very wide spectrum of mutations. Some of these chances are not stable. To date, mutants that showed stable characteristics changes are grouped into 11 categories based on flower colour and form. These results show that the combination of its vitro technique and induced mutation can be applied in orchid breeding to produce new interesting and attractive variety for the market

  14. Mutational specificity of SOS mutagenesis

    International Nuclear Information System (INIS)

    Kato, Takeshi

    1986-01-01

    In an approach to the isolation of mutants of E. coli unable to produce mutations by ultraviolet light, the author has found new umuC-mutants. Their properties could be explained by ''SOS hypothesis of Radman and Witkin'', which has now been justified by many investigators. Analysis of the umuC region of E. coli chromosome cloned in pSK 100 has led to the conclusion that two genes, umuD and umuC, having the capacity of mutation induction express in the same mechanism as that of SOS genes, which is known to be inhibited by LexA protein bonding to ''SOS box'' found at promotor region. Suppressor analysis for mutational specificity has revealed: (i) umuDC-independent mutagens, such as EMS and (oh) 4 Cy, induce selected base substitution alone; and (ii) umuDC-dependent mutagens, such as X-rays and gamma-rays, induce various types of base substitution simultaneously, although they have mutational specificity. In the umuDC-dependent processes of basechange mutagenesis, the spectra of base substitution were a mixture of base substitution reflecting the specific base damages induced by individual mutagens and nonspecific base substitution. In conclusion, base substitution plays the most important role in umuDC-dependent mutagenesis, although mutagenesis of umuDC proteins remains uncertain. (Namekawa, K.)

  15. Contribution of silent mutations to thermal adaptation of RNA bacteriophage Qβ.

    Science.gov (United States)

    Kashiwagi, Akiko; Sugawara, Ryu; Sano Tsushima, Fumie; Kumagai, Tomofumi; Yomo, Tetsuya

    2014-10-01

    Changes in protein function and other biological properties, such as RNA structure, are crucial for adaptation of organisms to novel or inhibitory environments. To investigate how mutations that do not alter amino acid sequence may be positively selected, we performed a thermal adaptation experiment using the single-stranded RNA bacteriophage Qβ in which the culture temperature was increased from 37.2°C to 41.2°C and finally to an inhibitory temperature of 43.6°C in a stepwise manner in three independent lines. Whole-genome analysis revealed 31 mutations, including 14 mutations that did not result in amino acid sequence alterations, in this thermal adaptation. Eight of the 31 mutations were observed in all three lines. Reconstruction and fitness analyses of Qβ strains containing only mutations observed in all three lines indicated that five mutations that did not result in amino acid sequence changes but increased the amplification ratio appeared in the course of adaptation to growth at 41.2°C. Moreover, these mutations provided a suitable genetic background for subsequent mutations, altering the fitness contribution from deleterious to beneficial. These results clearly showed that mutations that do not alter the amino acid sequence play important roles in adaptation of this single-stranded RNA virus to elevated temperature. Recent studies using whole-genome analysis technology suggested the importance of mutations that do not alter the amino acid sequence for adaptation of organisms to novel environmental conditions. It is necessary to investigate how these mutations may be positively selected and to determine to what degree such mutations that do not alter amino acid sequences contribute to adaptive evolution. Here, we report the roles of these silent mutations in thermal adaptation of RNA bacteriophage Qβ based on experimental evolution during which Qβ showed adaptation to growth at an inhibitory temperature. Intriguingly, four synonymous mutations and

  16. Mutated genes as research tool

    International Nuclear Information System (INIS)

    1981-01-01

    Green plants are the ultimate source of all resources required for man's life, his food, his clothes, and almost all his energy requirements. Primitive prehistoric man could live from the abundance of nature surrounding him. Man today, dominating nature in terms of numbers and exploiting its limited resources, cannot exist without employing his intelligence to direct natural evolution. Plant sciences, therefore, are not a matter of curiosity but an essential requirement. From such considerations, the IAEA and FAO jointly organized a symposium to assess the value of mutation research for various kinds of plant science, which directly or indirectly might contribute to sustaining and improving crop production. The benefit through developing better cultivars that plant breeders can derive from using the additional genetic resources resulting from mutation induction has been assessed before at other FAO/IAEA meetings (Rome 1964, Pullman 1969, Ban 1974, Ibadan 1978) and is also monitored in the Mutation Breeding Newsletter, published by IAEA twice a year. Several hundred plant cultivars which carry economically important characters because their genes have been altered by ionizing radiation or other mutagens, are grown by farmers and horticulturists in many parts of the world. But the benefit derived from such mutant varieties is without any doubt surpassed by the contribution which mutation research has made towards the advancement of genetics. For this reason, a major part of the papers and discussions at the symposium dealt with the role induced-mutation research played in providing insight into gene action and gene interaction, the organization of genes in plant chromosomes in view of homology and homoeology, the evolutionary role of gene duplication and polyploidy, the relevance of gene blocks, the possibilities for chromosome engineering, the functioning of cytroplasmic inheritance and the genetic dynamics of populations. In discussing the evolutionary role of

  17. Radiation-induced mutation at minisatellite loci

    International Nuclear Information System (INIS)

    Dubrova, Y.E.; Nesterov, V.N.; Krouchinsky, N.G.

    1997-01-01

    We are studying the radiation-induced increase of mutation rate in minisatellite loci in mice and humans. Minisatellite mutations were scored by multilocus DNA fingerprint analysis in the progeny of γ-irradiated and non-irradiated mice. The frequency of mutation in offspring of irradiated males was 1.7 higher that in the control group. Germline mutation at human minisatellite loci was studied among children born in heavily polluted areas of the Mogilev district of Belarus after the Chernobyl accident and in a control population. The frequency of mutation assayed both by DNA fingerprinting and by eight single locus probes was found to be two times higher in the exposed families than in the control group. Furthermore, mutation rate was correlated with the parental radiation dose for chronic exposure 137 Cs, consistent with radiation-induction of germline mutation. The potential use of minisatellites in monitoring germline mutation in humans will be discussed

  18. Recurrent LDL-receptor mutation causes familial ...

    African Journals Online (AJOL)

    1995-05-05

    May 5, 1995 ... 3. eaudet . New. Recurrent LDL-receptor mutation causes familial hypercholesterolaemia in ... amplification refractory mutation system (ARMS)" and single- strand conformation .... Location. Afrikaner. Mixed race. ApaLl.

  19. Aerosol in the containment

    International Nuclear Information System (INIS)

    Lanza, S.; Mariotti, P.

    1986-01-01

    The US program LACE (LWR Aerosol Containment Experiments), in which Italy participates together with several European countries, Canada and Japan, aims at evaluating by means of a large scale experimental activity at HEDL the retention in the pipings and primary container of the radioactive aerosol released following severe accidents in light water reactors. At the same time these experiences will make available data through which the codes used to analyse the behaviour of the aerosol in the containment and to verify whether by means of the codes of thermohydraulic computation it is possible to evaluate with sufficient accuracy variable influencing the aerosol behaviour, can be validated. This report shows and compares the results obtained by the participants in the LACE program with the aerosol containment codes NAVA 5 and CONTAIN for the pre-test computations of the test LA 1, in which an accident called containment by pass is simulated

  20. Sulfur-Containing Agrochemicals.

    Science.gov (United States)

    Devendar, Ponnam; Yang, Guang-Fu

    2017-10-09

    Modern agricultural chemistry has to support farmers by providing innovative agrochemicals. In this context, the introduction of sulfur atoms into an active ingredient is still an important tool in modulating the properties of new crop-protection compounds. More than 30% of today's agrochemicals contain at least one sulfur atom, mainly in fungicides, herbicides and insecticides. A number of recently developed sulfur-containing agrochemical candidates represent a novel class of chemical compounds with new modes of action, so we intend to highlight the emerging interest in commercially active sulfur-containing compounds. This chapter gives a comprehensive overview of selected leading sulfur-containing pesticidal chemical families namely: sulfonylureas, sulfonamides, sulfur-containing heterocyclics, thioureas, sulfides, sulfones, sulfoxides and sulfoximines. Also, the most suitable large-scale synthetic methods of the recently launched or provisionally approved sulfur-containing agrochemicals from respective chemical families have been highlighted.

  1. Reactor container structure

    International Nuclear Information System (INIS)

    Sato, Yoshimi; Fukuda, Yoshio.

    1993-01-01

    A main container of an FBR type reactor using liquid sodium as coolants is attached to a roof slug. The main container contains, as coolants, lower temperature sodium, and high temperature sodium above a reactor core and a partitioning plate. The main container has a structure comprising only longitudinal welded joints in parallel with axial direction in the vicinity of the liquid surface of high temperature sodium where a temperature gradient is steep and great thermal stresses are caused without disposing lateral welded joints in perpendicular to axial direction. Only the longitudinal welded joints having a great fatigue strength are thus disposed in the vicinity of the liquid surface of the high temperature sodium where axial thermal stresses are caused. This can improve reliability of strength at the welded portions of the main container against repeating thermal stresses caused in vicinity of the liquid surface of the main container from a view point of welding method. (I.N.)

  2. High security container

    International Nuclear Information System (INIS)

    Moreau, P.J.-M.; Monsterleet, G.A.

    1979-01-01

    This invention concerns containments, vessels or tanks for containing and protecting products or installations of various kinds, to be called by the general denomination 'containers'. Such products can be, inter alia, liquids such as natural gas, ammonia, vinyle chloride and hydrocarbons. Far from just forming simple means of storage, the containers used for this must now be capable of withstanding fire, sabotage for instance rocket fire, even impacts from aircraft, earthquakes and other aggressions of the same kind. The particular object of this invention is to create a container withstanding all these various agressions. It must also be considered that this container can not only be used for storing products or materials but also for enclosing particularly dangerous or delicate installations, such as nuclear or chemical reactors [fr

  3. Definition of containment failure

    International Nuclear Information System (INIS)

    Cybulskis, P.

    1982-01-01

    Core meltdown accidents of the types considered in probabilistic risk assessments (PRA's) have been predicted to lead to pressures that will challenge the integrity of containment structures. Review of a number of PRA's indicates considerable variation in the predicted probability of containment failure as a function of pressure. Since the results of PRA's are sensitive to the prediction of the occurrence and the timing of containment failure, better understanding of realistic containment capabilities and a more consistent approach to the definition of containment failure pressures are required. Additionally, since the size and location of the failure can also significantly influence the prediction of reactor accident risk, further understanding of likely failure modes is required. The thresholds and modes of containment failure may not be independent

  4. Frequency of Somatic TP53 Mutations in Combination with Known Pathogenic Mutations in Colon Adenocarcinoma, Non–Small Cell Lung Carcinoma, and Gliomas as Identified by Next-Generation Sequencing

    Directory of Open Access Journals (Sweden)

    Zahra Shajani-Yi

    2018-03-01

    Full Text Available The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective. In this study, we identified the frequency of individual TP53 mutations in patients with colon adenocarcinoma (48%, non–small cell lung carcinoma (NSCLC (36%, and glioma/glioblastoma (28% at our institution using next-generation sequencing. We also identified the occurrence of somatic mutations in numerous actionable genes including BRAF, EGFR, KRAS, IDH1, and PIK3CA that occurred concurrently with these TP53 mutations. Of the 480 tumors examined that contained one or more mutations in the TP53 gene, 219 were colon adenocarcinomas, 215 were NSCLCs, and 46 were gliomas/glioblastomas. Among the patients positive for TP53 mutations diagnosed with colon adenocarcinoma, 50% also showed at least one mutation in pathogenic genes of which 14% were BRAF, 33% were KRAS, and 3% were NRAS. Forty-seven percent of NSCLC patients harboring TP53 mutations also had a mutation in at least one actionable pathogenic variant with the following frequencies: BRAF: 4%, EGFR: 10%, KRAS: 28%, and PIK3CA: 4%. Fifty-two percent of patients diagnosed with glioma/glioblastoma with a positive TP53 mutation had at least one concurrent mutation in a known pathogenic gene of which 9% were CDKN2A, 41% were IDH1, and 11% were PIK3CA.

  5. Adaptive mutation: has the unicorn landed?

    Science.gov (United States)

    Foster, P L

    1998-01-01

    Reversion of an episomal Lac- allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not "adaptive" in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution. PMID:9560365

  6. Adaptive mutation: has the unicorn landed?

    Science.gov (United States)

    Foster, P L

    1998-04-01

    Reversion of an episomal Lac- allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not "adaptive" in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution.

  7. Urinary Tract Effects of HPSE2 Mutations

    OpenAIRE

    Stuart, H; Roberts, N; Hilton, E; McKenzie, E; Daly, S; Hadfield, K; Rahal, J; Gardiner, N; Tanley, S; Lewis, M; Sites, E; Angle, B; Alves, C; Lourenço, T; Rodrigues, M

    2015-01-01

    Urofacial syndrome (UFS) is an autosomal recessive congenital disease featuring grimacing and incomplete bladder emptying. Mutations of HPSE2, encoding heparanase 2, a heparanase 1 inhibitor, occur in UFS, but knowledge about the HPSE2 mutation spectrum is limited. Here, seven UFS kindreds with HPSE2 mutations are presented, including one with deleted asparagine 254, suggesting a role for this amino acid, which is conserved in vertebrate orthologs. HPSE2 mutations were absent in 23 non-neurog...

  8. Molecular analysis of carbon ion-induced mutations in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Shikazono, Naoya; Tanaka, Atsushi; Watanabe, Hiroshi; Tano, Shigemitsu; Yokota, Yukihiko

    1998-01-01

    In order to elucidate the characteristics of the mutations induced by ion particles at the molecular level in plants, mutated loci in carbon ion-induced mutants of Arabidopsis were investigated by PCR and Southern blot analyses. In the present study, two lines of gl1 mutant and two lines of tt4 mutant were isolated after carbon ion-irradiation. Out of four mutants, one had a deletion, other two contained rearrangements, and one had a point-like mutation. From the present result, it was suggested that ion particles induced different kinds of alterations of the DNA and therefore they could produce various types of mutant alleles in plants. (author)

  9. Bibliography. Examples of literature related to the use of induced mutations in cross-breeding

    International Nuclear Information System (INIS)

    Micke, A.

    1976-01-01

    The bibliography contains about 400 references arranged alphabetically under the following 20 headings: Genetic analysis of mutants; Mutant gene combination and interaction; Pleiotropy versus linkage; Genetic background; Heterosis and overdominance; Mutations in heterozygous plants such as vegetatively propagated plants; Mutations in hybrids of self-pollinators; Distant hybridization; Increasing recombination; Alteration in the reproductive system; Alteration of photoperiodic response; Self and cross-incompatibility; Male or female sterility; Adaptability of mutants and mutant hybrids; Mutation induction in cross pollinators; Dwarfing mutant genes in cross-breeding; Protein mutants in cross-breeding; Disease resistant mutants in cross-breeding; Practical cross-breeding programmes using mutants; Spontaneous versus induced genetic diversity

  10. A Color Mutation Hadronic Soft Interaction Model -- Eikonal Formalism and Branching Evolution

    OpenAIRE

    Cao, Zhen

    1998-01-01

    ECOMB is established as a hadronic multiparticle production generator by soft interaction. It incorporates the eikonal formalism, parton model, color mutation, branching, resonance production and decay. A partonic cluster, being color-neutral initially, splits into smaller color-neutral clusters successively due to the color mutation of the quarks. The process stops at hadronic resonance, $q\\bar q$ pair, formation. The model contains self-similar dynamics and exhibits scaling behavior in the ...

  11. The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts

    International Nuclear Information System (INIS)

    Kang, Min-Gu; Kim, Hye-Ran; Seo, Bo-Young; Lee, Jun Hyung; Choi, Seok-Yong; Kim, Soo-Hyun; Shin, Jong-Hee; Suh, Soon-Pal; Ahn, Jae-Sook; Shin, Myung-Geun

    2015-01-01

    Mutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated. The effects of these mutations on clinical outcomes have been diverse and contrasting. We examined a cohort of 129 de novo MDS patients, who did not harbor RS, for mutations affecting three spliceosomal genes (SF3B1, U2AF1, and SRSF2). The mutation rates of SF3B1, U2AF1, and SRSF2 were 7.0 %, 7.8 %, and 10.1 %, respectively. Compared with previously reported results, these rates were relatively infrequent. The SRSF2 mutation strongly correlated with old age (P < 0.001), while the mutation status of SF3B1 did not affect overall survival (OS), progression-free survival (PFS), or acute myeloid leukemia (AML) transformation. In contrast, MDS patients with mutations in U2AF1 or SRSF2 exhibited inferior PFS. The U2AF1 mutation was associated with inferior OS in low-risk MDS patients (P = 0.035). The SRSF2 mutation was somewhat associated with AML transformation (P = 0.083). Our findings suggest that the frequencies of the SF3B1, U2AF1, and SRSF2 splicing gene mutations in MDS without RS were relatively low. We also demonstrated that the U2AF1 and SRSF2 mutations were associated with an unfavorable prognostic impact in MDS patients without RS. The online version of this article (doi:10.1186/s12885-015-1493-5) contains supplementary material, which is available to authorized users

  12. Identification of novel mutations in X-linked retinitis pigmentosa families and implications for diagnostic testing

    Science.gov (United States)

    Glaus, Esther; Lorenz, Birgit; Netzer, Christian; Li, Yün; Schambeck, Maria; Wittmer, Mariana; Feil, Silke; Kirschner-Schwabe, Renate; Rosenberg, Thomas; Cremers, Frans P.M.; Bergen, Arthur A.B.; Barthelmes, Daniel; Baraki, Husnia; Schmid, Fabian; Tanner, Gaby; Fleischhauer, Johannes; Orth, Ulrike; Becker, Christian; Wegscheider, Erika; Nürnberg, Gudrun; Nürnberg, Peter; Bolz, Hanno Jörn; Gal, Andreas; Berger, Wolfgang

    2008-01-01

    Purpose The goal of this study was to identify mutations in X-chromosomal genes associated with retinitis pigmentosa (RP) in patients from Germany, The Netherlands, Denmark, and Switzerland. Methods In addition to all coding exons of RP2, exons 1 through 15, 9a, ORF15, 15a and 15b of RPGR were screened for mutations. PCR products were amplified from genomic DNA extracted from blood samples and analyzed by direct sequencing. In one family with apparently dominant inheritance of RP, linkage analysis identified an interval on the X chromosome containing RPGR, and mutation screening revealed a pathogenic variant in this gene. Patients of this family were examined clinically and by X-inactivation studies. Results This study included 141 RP families with possible X-chromosomal inheritance. In total, we identified 46 families with pathogenic sequence alterations in RPGR and RP2, of which 17 mutations have not been described previously. Two of the novel mutations represent the most 3’-terminal pathogenic sequence variants in RPGR and RP2 reported to date. In exon ORF15 of RPGR, we found eight novel and 14 known mutations. All lead to a disruption of open reading frame. Of the families with suggested X-chromosomal inheritance, 35% showed mutations in ORF15. In addition, we found five novel mutations in other exons of RPGR and four in RP2. Deletions in ORF15 of RPGR were identified in three families in which female carriers showed variable manifestation of the phenotype. Furthermore, an ORF15 mutation was found in an RP patient who additionally carries a 6.4 kbp deletion downstream of the coding region of exon ORF15. We did not identify mutations in 39 sporadic male cases from Switzerland. Conclusions RPGR mutations were confirmed to be the most frequent cause of RP in families with an X-chromosomal inheritance pattern. We propose a screening strategy to provide molecular diagnostics in these families. PMID:18552978

  13. Radiological containment handbook

    International Nuclear Information System (INIS)

    1982-10-01

    The purpose of this NUREG is to be used as a reference text. It is meant to be used by the working personnel as a guide for using temporary radiological containments. The installing group and health physics group may vary among organizations but responsibilities and duties will not change. It covers installation and inspection containments; working and operating guidelines; operating requirement; emergency procedures; and removal of containments

  14. Pituitary tumors containing cholecystokinin

    DEFF Research Database (Denmark)

    Rehfeld, J F; Lindholm, J; Andersen, B N

    1987-01-01

    We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained......'s disease and 7 acromegaly with adenomas containing ACTH. The cholecystokinin peptides from the tumors were smaller and less sulfated than cholecystokinin from normal pituitary glands. We conclude that ACTH-producing pituitary cells may also produce an altered form of cholecystokinin....

  15. Containment safety margins

    International Nuclear Information System (INIS)

    Von Riesemann, W.A.

    1980-01-01

    Objective of the Containment Safety Margins program is the development and verification of methodologies which are capable of reliably predicting the ultimate load-carrying capability of light water reactor containment structures under accident and severe environments. The program was initiated in June 1980 at Sandia and this paper addresses the first phase of the program which is essentially a planning effort. Brief comments are made about the second phase, which will involve testing of containment models

  16. Multicusp plasma containment apparatus

    International Nuclear Information System (INIS)

    Limpaecher, R.

    1980-01-01

    It has been discovered that plasma containment by a chamber having multi-pole magnetic cusp reflecting walls in combination with electronic injection for electrostatic containment provides the means for generating magnetic field free quiescent plasmas for practical application in ion-pumps, electronic switches, and the like. 1250 ''alnico v'' magnets 1/2 '' X 1/2 '' X 1 1/2 '' provide containment in one embodiment. Electromagnets embodying toroidal funneling extend the principle to fusion apparatus

  17. Establishment of novel monoclonal antibodies KMab-1 and MMab-1 specific for IDH2 mutations

    International Nuclear Information System (INIS)

    Kaneko, Mika Kato; Morita, Shunpei; Tsujimoto, Yuta; Yanagiya, Ryo; Nasu, Kana; Sasaki, Hiroko; Hozumi, Yasukazu; Goto, Kaoru; Natsume, Atsushi; Watanabe, Mika; Kumabe, Toshihiro; Takano, Shingo; Kato, Yukinari

    2013-01-01

    Highlights: ► IDH1/2 mutations are early and frequent genetic alterations in gliomas. ► We established anti-mutated IDH2-specific mAbs KMab-1 and MMab-1. ► KMab-1 or MMab-1 specifically reacted with mutated IDH2 in ELISA. ► MMab-1 specifically stained IDH2-R172M-expressing CHO cells in ICC. ► MMab-1 specifically stained IDH2-R172M-expressing gliomas in IHC. - Abstract: Isocitrate dehydrogenase 1/2 (IDH1/2) mutations have been detected in gliomas, cartilaginous tumors, and leukemias. IDH1/2 mutations are early and frequent genetic alterations, are specific to a single codon in the conserved and functionally important Arginine 132 (R132) in IDH1 and Arginine 172 (R172) in IDH2. We previously established several monoclonal antibodies (mAbs), which are specific for IDH1 mutations: clones IMab-1 or HMab-1 against IDH1-R132H or clone SMab-1 against IDH1-R132S. However, specific mAbs against IDH2 mutations have not been reported. To establish IDH2-mutation-specific mAbs, we immunized mice or rats with each mutation-containing IDH2 peptides including IDH2-R172K and IDH2-R172M. After cell fusion, IDH2 mutation-specific mAbs were screened in Enzyme-Linked Immunosorbent Assay (ELISA). Established mAbs KMab-1 and MMab-1 reacted with the IDH2-R172K and IDH2-R172M peptides, respectively, but not with IDH2-wild type (WT) in ELISA. Western-blot analysis also showed that KMab-1 and MMab-1 reacted with the IDH2-R172K and IDH2-R172M recombinant proteins, respectively, not with IDH2-WT or other IDH2 mutants, indicating that KMab-1 and MMab-1 are IDH2-mutation-specific. Furthermore, MMab-1 specifically stained the IDH2-R172M-expressing cells in immunocytochemistry, but did not stain IDH2-WT and other IDH2-mutation-containing cells. In immunohistochemical analysis, MMab-1 specifically stained IDH2-R172M-expressing glioma. This is the first report to establish anti-IDH2-mutation-specific mAbs, which could be useful in diagnosis of mutation-bearing tumors

  18. Establishment of novel monoclonal antibodies KMab-1 and MMab-1 specific for IDH2 mutations

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Mika Kato [Regional Innovation Strategy Support Program, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Molecular Tumor Marker Research Team, Global COE Program, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585 (Japan); Morita, Shunpei; Tsujimoto, Yuta; Yanagiya, Ryo; Nasu, Kana; Sasaki, Hiroko [Molecular Tumor Marker Research Team, Global COE Program, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585 (Japan); Hozumi, Yasukazu; Goto, Kaoru [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585 (Japan); Natsume, Atsushi [Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Watanabe, Mika [Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Kumabe, Toshihiro [Department of Neurosurgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574 (Japan); Takano, Shingo [Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575 (Japan); Kato, Yukinari, E-mail: yukinari-k@bea.hi-ho.ne.jp [Regional Innovation Strategy Support Program, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Molecular Tumor Marker Research Team, Global COE Program, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585 (Japan)

    2013-03-01

    Highlights: ► IDH1/2 mutations are early and frequent genetic alterations in gliomas. ► We established anti-mutated IDH2-specific mAbs KMab-1 and MMab-1. ► KMab-1 or MMab-1 specifically reacted with mutated IDH2 in ELISA. ► MMab-1 specifically stained IDH2-R172M-expressing CHO cells in ICC. ► MMab-1 specifically stained IDH2-R172M-expressing gliomas in IHC. - Abstract: Isocitrate dehydrogenase 1/2 (IDH1/2) mutations have been detected in gliomas, cartilaginous tumors, and leukemias. IDH1/2 mutations are early and frequent genetic alterations, are specific to a single codon in the conserved and functionally important Arginine 132 (R132) in IDH1 and Arginine 172 (R172) in IDH2. We previously established several monoclonal antibodies (mAbs), which are specific for IDH1 mutations: clones IMab-1 or HMab-1 against IDH1-R132H or clone SMab-1 against IDH1-R132S. However, specific mAbs against IDH2 mutations have not been reported. To establish IDH2-mutation-specific mAbs, we immunized mice or rats with each mutation-containing IDH2 peptides including IDH2-R172K and IDH2-R172M. After cell fusion, IDH2 mutation-specific mAbs were screened in Enzyme-Linked Immunosorbent Assay (ELISA). Established mAbs KMab-1 and MMab-1 reacted with the IDH2-R172K and IDH2-R172M peptides, respectively, but not with IDH2-wild type (WT) in ELISA. Western-blot analysis also showed that KMab-1 and MMab-1 reacted with the IDH2-R172K and IDH2-R172M recombinant proteins, respectively, not with IDH2-WT or other IDH2 mutants, indicating that KMab-1 and MMab-1 are IDH2-mutation-specific. Furthermore, MMab-1 specifically stained the IDH2-R172M-expressing cells in immunocytochemistry, but did not stain IDH2-WT and other IDH2-mutation-containing cells. In immunohistochemical analysis, MMab-1 specifically stained IDH2-R172M-expressing glioma. This is the first report to establish anti-IDH2-mutation-specific mAbs, which could be useful in diagnosis of mutation-bearing tumors.

  19. Radioactive material transporting container

    International Nuclear Information System (INIS)

    Watabe, Yukio.

    1990-01-01

    As a supporting member of a sealing container for containing spent fuels, etc., a straight pipe or a cylinder has been used. However, upon dropping test, the supporting member is buckled toward the central axis of a transporting container and a shock absorber is crushed in the axial direction to prevent its pushing force to the outer side, which may possibly hinder normal shock moderating function. Then, at least more than one-half of the supporting member is protruded radially to the outer side of the sealing container beyond the fixed portion with the sealed container, so that the member has a portion extended in the radial outside of the transporting container with an angle greater than the angle formed between a line connecting the outer circumference at the bottom of an outer cylinder with the gravitational center of the transporting container and the central axis of the transporting container. As a result, buckling of the supporting member toward the central axis of the transporting container upon dropping test can be prevented and the deformation of the shock absorber is neither not prevented to exhibit normal shock absorbing effect. This can improve the reliability and reduce the amount of shock absorbers. (N.H.)

  20. CONTAIN independent peer review

    International Nuclear Information System (INIS)

    Boyack, B.E.; Corradini, M.L.; Khatib-Rahbar, M.; Loyalka, S.K.; Smith, P.N.

    1995-01-01

    The CONTAIN code was developed by Sandia National Laboratories under the sponsorship of the US Nuclear Regulatory Commission (NRC) to provide integrated analyses of containment phenomena. It is used to predict nuclear reactor containment loads, radiological source terms, and associated physical phenomena for a range of accident conditions encompassing both design-basis and severe accidents. The code's targeted applications include support for containment-related experimental programs, light water and advanced light water reactor plant analysis, and analytical support for resolution of specific technical issues such as direct containment heating. The NRC decided that a broad technical review of the code should be performed by technical experts to determine its overall technical adequacy. For this purpose, a six-member CONTAIN Peer Review Committee was organized and a peer review as conducted. While the review was in progress, the NRC issued a draft ''Revised Severe Accident Code Strategy'' that incorporated revised design objectives and targeted applications for the CONTAIN code. The committee continued its effort to develop findings relative to the original NRC statement of design objectives and targeted applications. However, the revised CONTAIN design objectives and targeted applications. However, the revised CONTAIN design objectives and targeted applications were considered by the Committee in assigning priorities to the Committee's recommendations. The Committee determined some improvements are warranted and provided recommendations in five code-related areas: (1) documentation, (2) user guidance, (3) modeling capability, (4) code assessment, and (5) technical assessment

  1. CONTAIN independent peer review

    Energy Technology Data Exchange (ETDEWEB)

    Boyack, B.E. [Los Alamos National Lab., NM (United States); Corradini, M.L. [Univ. of Wisconsin, Madison, WI (United States). Nuclear Engineering Dept.; Denning, R.S. [Battelle Memorial Inst., Columbus, OH (United States); Khatib-Rahbar, M. [Energy Research Inc., Rockville, MD (United States); Loyalka, S.K. [Univ. of Missouri, Columbia, MO (United States); Smith, P.N. [AEA Technology, Dorchester (United Kingdom). Winfrith Technology Center

    1995-01-01

    The CONTAIN code was developed by Sandia National Laboratories under the sponsorship of the US Nuclear Regulatory Commission (NRC) to provide integrated analyses of containment phenomena. It is used to predict nuclear reactor containment loads, radiological source terms, and associated physical phenomena for a range of accident conditions encompassing both design-basis and severe accidents. The code`s targeted applications include support for containment-related experimental programs, light water and advanced light water reactor plant analysis, and analytical support for resolution of specific technical issues such as direct containment heating. The NRC decided that a broad technical review of the code should be performed by technical experts to determine its overall technical adequacy. For this purpose, a six-member CONTAIN Peer Review Committee was organized and a peer review as conducted. While the review was in progress, the NRC issued a draft ``Revised Severe Accident Code Strategy`` that incorporated revised design objectives and targeted applications for the CONTAIN code. The committee continued its effort to develop findings relative to the original NRC statement of design objectives and targeted applications. However, the revised CONTAIN design objectives and targeted applications. However, the revised CONTAIN design objectives and targeted applications were considered by the Committee in assigning priorities to the Committee`s recommendations. The Committee determined some improvements are warranted and provided recommendations in five code-related areas: (1) documentation, (2) user guidance, (3) modeling capability, (4) code assessment, and (5) technical assessment.

  2. Reactor container cooling device

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Koji; Kinoshita, Shoichiro

    1995-11-10

    The device of the present invention efficiently lowers pressure and temperature in a reactor container upon occurrence of a severe accident in a BWR-type reactor and can cool the inside of the container for a long period of time. That is, (1) pipelines on the side of an exhaustion tower of a filter portion in a filter bent device of the reactor container are in communication with pipelines on the side of a steam inlet of a static container cooling device by way of horizontal pipelines, (2) a back flow check valve is disposed to horizontal pipelines, (3) a steam discharge valve for a pressure vessel is disposed closer to the reactor container than the joint portion between the pipelines on the side of the steam inlet and the horizontal pipelines. Upon occurrence of a severe accident, when the pressure vessel should be ruptured and steams containing aerosol in the reactor core should be filled in the reactor container, the inlet valve of the static container cooling device is closed. Steams are flown into the filter bent device of the reactor container, where the aerosols can be removed. (I.S.).

  3. Age-related mutations associated with clonal hematopoietic expansion and malignancies.

    Science.gov (United States)

    Xie, Mingchao; Lu, Charles; Wang, Jiayin; McLellan, Michael D; Johnson, Kimberly J; Wendl, Michael C; McMichael, Joshua F; Schmidt, Heather K; Yellapantula, Venkata; Miller, Christopher A; Ozenberger, Bradley A; Welch, John S; Link, Daniel C; Walter, Matthew J; Mardis, Elaine R; Dipersio, John F; Chen, Feng; Wilson, Richard K; Ley, Timothy J; Ding, Li

    2014-12-01

    Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. The Cancer Genome Atlas (TCGA) provides a unique resource for comprehensive discovery of mutations and genes in blood that may contribute to the clonal expansion of hematopoietic stem/progenitor cells. Here, we analyzed blood-derived sequence data from 2,728 individuals from TCGA and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age. Remarkably, 83% of these mutations were from 19 leukemia and/or lymphoma-associated genes, and nine were recurrently mutated (DNMT3A, TET2, JAK2, ASXL1, TP53, GNAS, PPM1D, BCORL1 and SF3B1). We identified 14 additional mutations in a very small fraction of blood cells, possibly representing the earliest stages of clonal expansion in hematopoietic stem cells. Comparison of these findings to mutations in hematological malignancies identified several recurrently mutated genes that may be disease initiators. Our analyses show that the blood cells of more than 2% of individuals (5-6% of people older than 70 years) contain mutations that may represent premalignant events that cause clonal hematopoietic expansion.

  4. Haploid rice plants in mutation studies

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, S [Institute of Radiation Breeding, Ministry of Agriculture and Forestry, Ohmiya, Ibaraki-ken (Japan)

    1970-03-01

    Studies were made on chlorophyll-deficient sectors and diploid-like sectors in haploid rice plants exposed to chronic gamma irradiation, and on germinal mutations in diploid strains derived from the haploid plants. The induction and elimination of somatic mutations in haploid plants and the occurrence of drastic germinal mutations in diploid strains from haploid plants are discussed. (author)

  5. Studies of human mutation rates: Progress report

    International Nuclear Information System (INIS)

    Neel, J.V.

    1988-01-01

    Progress was recorded between January 1 and July 1, 1987 on a project entitled ''Studies of Human Mutation Rates''. Studies underway include methodology for studying mutation at the DNA level, algorithms for automated analyses of two-dimensional polyacrylamide DNA gels, theoretical and applied population genetics, and studies of mutation frequency in A-bomb survivors

  6. Mitochondrial mutations drive prostate cancer aggression

    DEFF Research Database (Denmark)

    Hopkins, Julia F.; Sabelnykova, Veronica Y.; Weischenfeldt, Joachim

    2017-01-01

    Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer...... in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer....

  7. Highly prevalent LIPH founder mutations causing autosomal recessive woolly hair/hypotrichosis in Japan and the genotype/phenotype correlations.

    Directory of Open Access Journals (Sweden)

    Kana Tanahashi

    Full Text Available Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH, and the 2 missense mutations c.736T>A (p.Cys246Ser and c.742C>A (p.His248Asn are considered prevalent founder mutations for ARWH in the Japanese population. To reveal genotype/phenotype correlations in ARWH cases in Japan and the haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13 patients had woolly hair, and 1 patient had complete baldness since birth. An LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3 of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of mild hypotrichosis with woolly hair was restricted to the patients with the homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the alleles containing the LIPH c.736T>A mutation had a haplotype identical to that reported previously, although 4 alleles out of 5 chromosomes containing the LIPH c.742C>A mutation had a different haplotype from the previously reported founder allele. These alleles with c.742C>A are thought to be the third founder LIPH mutation causing ARWH. To accurately determine the prevalence of the founder mutations, we investigated allele frequencies of those mutations in 819 Japanese controls. Heterozygous c.736T>A mutations were found in 13 controls (allele frequency: 0.0079; carrier rate: 0.016, and heterozygous c.742C>A mutations were found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024. In conclusion, this study confirms the more accurate allele frequencies of the pathogenic founder mutations of LIPH and shows that there is a third founder mutation in Japan. In addition, the present findings suggest that the mutation patterns of LIPH might be associated with hypotrichosis severity in ARWH.

  8. FAUST/CONTAIN

    International Nuclear Information System (INIS)

    Cherdron, W.; Minges, J.; Sauter, H.; Schuetz, W.

    1995-01-01

    The FAUNA facility has been restructured after completion of the sodium fire experiments. It is now serving LWR research, cf. report II on program no. 32.21.02 concerning steam explosions. The CONTAIN code system for computing the thermodynamic, aerosol and radiological phenomena in a containment under severe accident conditions is being developed with a new to fission product release and transport. (orig.)

  9. Explosive composition containing water

    Energy Technology Data Exchange (ETDEWEB)

    Cattermole, G.R.; Lyerly, W.M.; Cummings, A.M.

    1971-11-26

    This addition to Fr. 1,583,223, issued 31 May 1968, describes an explosive composition containing a water in oil emulsion. The composition contains an oxidizing mineral salt, a nitrate base salt as sensitizer, water, an organic fuel, a lipophilic emulsifier, and incorporates gas bubbles. The composition has a performance which is improved over and above the original patent.

  10. Tougher containment design goals

    International Nuclear Information System (INIS)

    O'Farrelly, C.

    1978-01-01

    Present day LWR containment design goals are reviewed, together with their potential failure modes. Rasmussen's estimates of failure probabilities are discussed and the concept of ''delayed failure'' is seen to be a valuable safety goal for hypothetical accidents. The paper investigates the inherent coremelt resistance capability of various containment designs and suggests improvements, with special emphasis on increasing the failure delay times. (author)

  11. CONTAINER TERMINALS IN EUROPE

    Directory of Open Access Journals (Sweden)

    Bart W. WIEGMANS

    2001-01-01

    Full Text Available This paper aims to address the linkage between logistics (in particular, the management of marketing channel flows and transport markets, while also the interaction between these two markets and intermodal container terminals is analysed. The marketing channel theory is used to describe all relevant actors and flows that run through marketing channels, starting with customer needs and ending with customer satisfaction. Porter's theory of competitive advantages is used to review competitive forces in both markets. Finally, a competitor analysis is performed for the logistics and transport market. These theories are applied so as to be able to determine the competitive position of intermodal container terminals with a view to the management of marketing channel flows and the physical transport of freight flows. Hence, the central question of this paper is: Which markets are served by intermodal container terminals and with whom are they competing? At present, neither the maritime container terminals nor the continental container terminals appear to have a significant influence in the logistics service market; they concentrate mainly on the physical movement of containers (transshipment. Furthermore, maritime container terminals and continental container terminals are not dominant players in the transport service market. Our conclusion is that continental terminals are predominantly competing with unimodal road transport, with neighbouring continental terminals and with barge transport companies.

  12. CONTAINER FOR USED TEXTILES

    CERN Multimedia

    Relation with the Host States

    2001-01-01

    We should like to remind you that a special container for textiles for the Association 'Réalise/Rapid Service' of Geneva is located in the car park outside the Meyrin site. The Association has informed us that 3 306 kg of textiles were deposited in the container in 2000 and wishes to convey its warm gratitude to all donors.

  13. Containment and surveillance devices

    International Nuclear Information System (INIS)

    Campbell, J.W.; Johnson, C.S.; Stieff, L.R.

    The growing acceptance of containment and surveillance as a means to increase safeguards effectiveness has provided impetus to the development of improved surveillance and containment devices. Five recently developed devices are described. The devices include one photographic and two television surveillance systems and two high security seals that can be verified while installed

  14. Nuclear reactor container

    International Nuclear Information System (INIS)

    Yamaki, Rika; Kawabe, Ryuhei.

    1989-01-01

    A venturi scrubber is connected to a nuclear reactor container. Gases containing radioactive aerosols in the container are introduced into the venturi scrubber in the form of a high speed stream under the pressure of the container. The radioactive aerosols are captured by inertia collision due to the velocity difference between the high speed gas stream and water droplets. In the case of the present invention, since the high pressure of the reactor container generated upon accident is utilized, compressor, etc. is no more required, thereby enabling to reduce the size of the aerosol removing device. Further, since no external power is used, the radioactive aerosols can be removed with no starting failure upon accidents. (T.M.)

  15. Containment vessel drain system

    Science.gov (United States)

    Harris, Scott G.

    2018-01-30

    A system for draining a containment vessel may include a drain inlet located in a lower portion of the containment vessel. The containment vessel may be at least partially filled with a liquid, and the drain inlet may be located below a surface of the liquid. The system may further comprise an inlet located in an upper portion of the containment vessel. The inlet may be configured to insert pressurized gas into the containment vessel to form a pressurized region above the surface of the liquid, and the pressurized region may operate to apply a surface pressure that forces the liquid into the drain inlet. Additionally, a fluid separation device may be operatively connected to the drain inlet. The fluid separation device may be configured to separate the liquid from the pressurized gas that enters the drain inlet after the surface of the liquid falls below the drain inlet.

  16. Radiation induced chlorophyll mutations in rice

    International Nuclear Information System (INIS)

    Bari, G.; Mustafa, G.; Soomro, A.M.; Baloch, A.W.

    1985-01-01

    Air dried grains of four local varieties of rice were treated with gamma-rays and fast neutrons for determining their mutagenic effectiveness through the occurence of chlorophyll mutations. Fast neutrons were more effective in inducing chlorophyll mutations and the rice variety Basmati 370 produced maximum number of mutations followed by varieties Sonahri Sugdasi, Jajai 77 and Sada Gulab. The highest frequency of chlorophyll mutations was that of albina types followed by striata types. The xantha, viridis and tigrina types of mutations were less frequent. (authors)

  17. Mutation Clusters from Cancer Exome.

    Science.gov (United States)

    Kakushadze, Zura; Yu, Willie

    2017-08-15

    We apply our statistically deterministic machine learning/clustering algorithm *K-means (recently developed in https://ssrn.com/abstract=2908286) to 10,656 published exome samples for 32 cancer types. A majority of cancer types exhibit a mutation clustering structure. Our results are in-sample stable. They are also out-of-sample stable when applied to 1389 published genome samples across 14 cancer types. In contrast, we find in- and out-of-sample instabilities in cancer signatures extracted from exome samples via nonnegative matrix factorization (NMF), a computationally-costly and non-deterministic method. Extracting stable mutation structures from exome data could have important implications for speed and cost, which are critical for early-stage cancer diagnostics, such as novel blood-test methods currently in development.

  18. Gene mutations in hepatocellular adenomas

    DEFF Research Database (Denmark)

    Raft, Marie B; Jørgensen, Ernö N; Vainer, Ben

    2015-01-01

    is associated with bi-allelic mutations in the TCF1 gene and morphologically has marked steatosis. β-catenin activating HCA has increased activity of the Wnt/β-catenin pathway and is associated with possible malignant transformation. Inflammatory HCA is characterized by an oncogene-induced inflammation due...... to alterations in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. In the diagnostic setting, sub classification of HCA is based primarily on immunohistochemical analyzes, and has had an increasing impact on choice of treatment and individual prognostic assessment....... This review offers an overview of the reported gene mutations associated with hepatocellular adenomas together with a discussion of the diagnostic and prognostic value....

  19. The condensed mutation in sunflower

    International Nuclear Information System (INIS)

    Leclercq, P.

    1978-01-01

    Three inbred lines of sunflower were treated with gamma rays. In the progeny of one of these lines, the desired dwarf mutation appeared with a high frequency (23%). The dwarfing was accompanied by various undesirable characteristics (lateness, poor seed production, etc.), for which correction through genetic diversification and selection is in progress. The ratio capitulum diameter/stem height has increased from 1/8 up to 1/3 [fr

  20. Rare beneficial mutations can halt Muller's ratchet

    Science.gov (United States)

    Balick, Daniel; Goyal, Sidhartha; Jerison, Elizabeth; Neher, Richard; Shraiman, Boris; Desai, Michael

    2012-02-01

    In viral, bacterial, and other asexual populations, the vast majority of non-neutral mutations are deleterious. This motivates the application of models without beneficial mutations. Here we show that the presence of surprisingly few compensatory mutations halts fitness decay in these models. Production of deleterious mutations is balanced by purifying selection, stabilizing the fitness distribution. However, stochastic vanishing of fitness classes can lead to slow fitness decay (i.e. Muller's ratchet). For weakly deleterious mutations, production overwhelms purification, rapidly decreasing population fitness. We show that when beneficial mutations are introduced, a stable steady state emerges in the form of a dynamic mutation-selection balance. We argue this state is generic for all mutation rates and population sizes, and is reached as an end state as genomes become saturated by either beneficial or deleterious mutations. Assuming all mutations have the same magnitude selective effect, we calculate the fraction of beneficial mutations necessary to maintain the dynamic balance. This may explain the unexpected maintenance of asexual genomes, as in mitochondria, in the presence of selection. This will affect in the statistics of genetic diversity in these populations.

  1. Rare and unexpected beta thalassemic mutations in Qazvin ...

    African Journals Online (AJOL)

    About 13 beta-globin mutations encompass 70 - 90% of mutation spectrum in Iran. These mutations are called common beta-globin mutations. The rest are rare or unknown mutations. The objective of this study was to identify and describe rare or unknown beta-globin mutations in Qazvin province. EDTAcontaining venous ...

  2. Rare and unexpected beta thalassemic mutations in Qazvin ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-01-04

    Jan 4, 2010 ... About 13 beta-globin mutations encompass 70 - 90% of mutation spectrum in Iran. These mutations are called common beta-globin mutations. The rest are rare or unknown mutations. The objective of this study was to identify and describe rare or unknown beta-globin mutations in Qazvin province. EDTA-.

  3. Mutation breeding in vegetable crops

    International Nuclear Information System (INIS)

    Yamaguchi, Takashi

    1984-01-01

    Vegetables breed by seeds and vegetative organs. In main vegetables, the differentiation of clopping types, the adoption of monoculture and year-round production and shipment are carried out, adapting to various socio-economic and cultivation conditions. Protected agriculture has advanced mainly for fruit vegetables, and the seeds for sale have become almost hybrid varieties. Reflecting the situation like this, the demand for breeding is diversified and characteristic, and the case of applying mutation breeding seems to be many. The present status of the mutation breeding of vegetables is not yet well under way, but about 40 raised varieties have been published in the world. The characters introduced by induced mutation and irradiation were compact form, harvesting aptitude, the forms and properties of stems and leaves, anti-lodging property, the size, form and uniformity of fruits, male sterility and so on. The radiation sources used were mostly gamma ray or X-ray, but sometimes, combined irradiation was used. As the results obtained in Japan, burdocks as an example of gamma ray irradiation to seeds, tomatoes as an example of inducing the compound resistance against disease injury and lettuces as an example of internal beta irradiation are reported. (Kako, I.)

  4. Induced mutations in sesame breeding

    International Nuclear Information System (INIS)

    Ashri, A.

    2001-01-01

    The scope of induced mutations in sesame (Sesamum indicum L.) breeding is reviewed. So far in Egypt, India, Iraq, Rep. of Korea, and Sri Lanka, 14 officially released varieties have been developed through induced mutations: 12 directly and 2 through cross breeding (one using the 'dt45' induced mutant from Israel). For another variety released in China there are no details. The induced mutations approach was adopted primarily in order to obtain genetic variability that was not available in the germplasm collection. The mutagens commonly applied have been gamma rays, EMS and sodium azide. Sesame seeds can withstand high mutagen doses, and there are genotypic differences in sensitivity between varieties. The mutants induced in the above named countries and others include better yield, improved seed retention, determinate habit, modified plant architecture and size, more uniform and shorter maturation period, earliness, resistance to diseases, genic male sterility, seed coat color, higher oil content and modified fatty acids composition. Some of the induced mutants have already given rise to improved varieties, the breeding value of other mutants is now being assessed and still others can serve as useful markers in genetic studies and breeding programmes. (author)

  5. Germline APC mutations in hepatoblastoma.

    Science.gov (United States)

    Yang, Adeline; Sisson, Rebecca; Gupta, Anita; Tiao, Greg; Geller, James I

    2018-04-01

    Conflicting reports on the frequency of germline adenomatous polyposis coli (APC) gene mutations in patients with hepatoblastoma (HB) have called into question the clinical value of APC mutation testing on apparently sporadic HB. An Institutional Review Board approved retrospective review of clinical data collected from patients with HB who received APC testing at our institution was conducted. All HB patients seen at Cincinnati Children's Hospital Medical Center were eligible for testing. Potential genotype/phenotype correlations were assessed. As of July 2015, 29 patients with HB had received constitutional APC testing. Four (14%) were found to have APC pathogenic truncations of the APC protein and in addition two (7%) had APC missense variants of unknown clinical significance. Two patients (7%) had family histories indicative of familial adenomatous polyposis (FAP). Response to chemotherapy tracked differently in APC pathogenic cases, with a slower imaging response despite an equivalent or slightly faster α-fetoprotein (AFP) response. The prevalence of pathogenic APC variants in apparently sporadic HB may be higher than previously detected. Differences in time to imaging response, despite similar AFP response, may impact surgical planning. All patients with HB warrant germline APC mutation testing for underlying FAP. © 2017 Wiley Periodicals, Inc.

  6. Mutation induction by ion beams in plants

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Atsushi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2001-03-01

    The effect of ion beams such as C, He, and Ne ions was investigated on the mutation induction in plants with the expectation that ion beams of high linear energy transfer (LET) can frequently produce large DNA alternation such as inversion, translocation and large deletion rather than point mutation. Mutation frequency was investigated using Arabidopsis visible phenotype loci and was 8 to 33 fold higher for 220 MeV carbon ions than for electrons. Mutation spectrum was investigated on the flower color of chrysanthemum cv to find that flower mutants induced by ion beams show complex and stripe types rather than single color. Polymerase chain reaction analysis was performed to investigate DNA alteration of mutations. In conclusion, the characteristics of ion beams for the mutation induction are 1) high frequency, 2) broad mutation spectrum, and 3) novel mutants. (S. Ohno)

  7. Mutation induction by ion beams in plants

    International Nuclear Information System (INIS)

    Tanaka, Atsushi

    2001-01-01

    The effect of ion beams such as C, He, and Ne ions was investigated on the mutation induction in plants with the expectation that ion beams of high linear energy transfer (LET) can frequently produce large DNA alternation such as inversion, translocation and large deletion rather than point mutation. Mutation frequency was investigated using Arabidopsis visible phenotype loci and was 8 to 33 fold higher for 220 MeV carbon ions than for electrons. Mutation spectrum was investigated on the flower color of chrysanthemum cv to find that flower mutants induced by ion beams show complex and stripe types rather than single color. Polymerase chain reaction analysis was performed to investigate DNA alteration of mutations. In conclusion, the characteristics of ion beams for the mutation induction are 1) high frequency, 2) broad mutation spectrum, and 3) novel mutants. (S. Ohno)

  8. Identification of five novel FBN1 mutations by non-radioactive single-strand conformation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, W.; Qian, C.; Comeau, K.; Francke, U. [Stanford Univ. Medical Center, Stanford, CA (United States)

    1994-09-01

    Marfan syndrome (MFS), one of the most common genetic disorders of connective tissue, is characterized by variable manifestations in skeletal, cardiovascular and ocular systems. Mutations in the fibrillin gene on chromosome 15 (FBN1) have been shown to cause MFS. To examine the relationship between FBN1 gene mutations, fibrillin protein function and MFS phenotypes, we screened for alternations in the fibrillin coding sequence in fibroblast derived cDNA from MFS patients. To date, abnormally migrating bands in more than 20 unrelated MFS patients have been identified by using non-radioactive single-strand conformation analysis and silver staining. Five altered bands have been directly sequenced. Two missense mutations and three splice site mutations have been identified. Both missense mutations substitute another amino acid for a cysteine residue (C1402W and C1672R) in EGF-like motifs of the fibrillin polypeptide chain. The two splice site mutations are at nucleotide positions 6994+1 (G{yields}A), and 7205-2 (A{yields}G) and result in in-frame skipping of exon 56 and 58, respectively. Skipping of exon 56 occurs in 50% of mutant transcripts. Use of a cryptic splice site 51 bp upstream of the normal donor site results in half of the mutant transcripts containing part of exon 56. Both products contain in-frame deletions. Another splice site mutation, identified by exon screening from patient genomic DNA using intron primers, is at nucleotide position 2293+2 (T{yields}A), but the predicted exon skipping has not been detected at the RT-PCR level. This may be due to instability of the mutant transcript. Including the mutations reported here, a total of 8 out of 36 published FBN1 gene mutations involve exon skipping. It may be inferred that FBN1 exon skipping plays an important pathogenic role in MFS.

  9. Container for hydrogen isotopes

    Energy Technology Data Exchange (ETDEWEB)

    1976-01-12

    A container is described for storage, shipping and and dispensing of hydrogen isotopes such as hydrogen, deuterium, tritium, or mixtures of the same. The container is compact, safe against fracture or accident, and is reusable. It consists of an outer housing with suitable inlet and outlet openings and electrical feed elements, the housing containing an activated sorber material in the form, for example of titanium sponge or an activated zirconium aluminate cartridge. The gas to be stored is introduced into the chamber under conditions of heat and vacuum and is retained in the sorber material. Subsequently, it may be released by heating the unit to drive off the stored gas at desired rates.

  10. Improvements in containers

    International Nuclear Information System (INIS)

    Guy, R.

    1977-01-01

    An improved container is described for transporting radioactive materials, such as irradiated Magnox fuel elements. It has a lid fixed to the container body and at the corners of the lid has shock absorbers that project from the corners and have part-spheroidal shape. The centre of curvature of the surface of the spheroid is positioned within the lid, so that impact loads on a shock absorber tend to hold it to the container rather than dislodge it. The shock absorbers may be Al-Si alloy castings. (U.K.)

  11. The Container Stowage Problem

    DEFF Research Database (Denmark)

    Janstrup, Kira; Rose, Trine Høyer; Andersen, Kent Høj

    The main purpose of this project is to use integer programming to create a model that minimizes the costs for container transportation by ship. To make the model as realistic as possible it will be based on information from a large shipping company about the vessel layout and container types....... In addition to our project two other projects are made where an optimal solution to the container stowage problem also is tried to be found, but by using constraint programming and local search instead respectively. We will therefore in the end compare these three methods and the achieved results on fastness...

  12. The Container Stowage Problem

    DEFF Research Database (Denmark)

    Janstrup, Kira

    2010-01-01

    The main purpose of this project is to use integer programming to create a model that minimizes the costs for container transportation by ship. To make the model as realistic as possible it will be based on information from a large shipping company about the vessel layout and container types....... In addition to our project two other projects are made where an optimal solution to the container stowage problem also is tried to be found, but by using constraint programming and local search instead respectively. We will therefore in the end compare these three methods and the achieved results on fastness...

  13. Container for hydrogen isotopes

    International Nuclear Information System (INIS)

    1976-01-01

    A container is described for storage, shipping and and dispensing of hydrogen isotopes such as hydrogen, deuterium, tritium, or mixtures of the same. The container is compact, safe against fracture or accident, and is reusable. It consists of an outer housing with suitable inlet and outlet openings and electrical feed elements, the housing containing an activated sorber material in the form, for example of titanium sponge or an activated zirconium aluminate cartridge. The gas to be stored is introduced into the chamber under conditions of heat and vacuum and is retained in the sorber material. Subsequently, it may be released by heating the unit to drive off the stored gas at desired rates

  14. Oncogene mutational profile in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang ZC

    2014-03-01

    Full Text Available Zi-Chen Zhang,1,* Sha Fu,1,* Fang Wang,1 Hai-Yun Wang,1 Yi-Xin Zeng,2 Jian-Yong Shao11Department of Molecular Diagnostics, 2Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Nasopharyngeal carcinoma (NPC is a common tumor in Southern China, but the oncogene mutational status of NPC patients has not been clarified. Using time-of-flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined in 123 NPC patients. The relationships between mutational status and clinical data were assessed with a χ2 or Fisher's exact test. Survival analysis was performed using the Kaplan–Meier method with the log-rank test. In 123 patients, 21 (17.1% NPC tumors were positive for mutations in eight oncogenes: six patients had PIK3CA mutations (4.9%, five NRAS mutations (4.1%, four KIT mutations (3.3%, two PDGFRA mutations (1.6%, two ABL mutations (1.6%, and one with simultaneous mutations in HRAS, EGFR, and BRAF (1%. Patients with mutations were more likely to relapse or develop metastasis than those with wild-type alleles (P=0.019. No differences or correlations were found in other clinical characteristics or in patient survival. No mutations were detected in oncogenes AKT1, AKT2, CDK, ERBB2, FGFR1, FGFR3, FLT3, JAK2, KRAS, MET, and RET. These results demonstrate an association between NPC and mutations in NRAS, KIT, PIK3CA, PDGFRA, and ABL, which are associated with patient relapse and metastasis. Keywords: NPC, oncogene, mutation

  15. FREIGHT CONTAINER LIFTING STANDARD

    Energy Technology Data Exchange (ETDEWEB)

    POWERS DJ; SCOTT MA; MACKEY TC

    2010-01-13

    This standard details the correct methods of lifting and handling Series 1 freight containers following ISO-3874 and ISO-1496. The changes within RPP-40736 will allow better reading comprehension, as well as correcting editorial errors.

  16. Helical type vacuum container

    International Nuclear Information System (INIS)

    Owada, Kimio.

    1989-01-01

    Helical type vacuum containers in the prior art lack in considerations for thermal expansion stresses to helical coils, and there is a possibility of coil ruptures. The object of the present invention is to avoid the rupture of helical coils wound around the outer surface of a vacuum container against heat expansion if any. That is, bellows or heat expansion absorbing means are disposed to a cross section of a helical type vacuum container. With such a constitution, thermal expansion of helical coils per se due to temperature elevation of the coils during electric supply can be absorbed by expansion of the bellows or absorption of the heat expansion absorbing means. Further, this can be attained by arranging shear pins in the direction perpendicular to the bellows axis so that the bellows are not distorted when the helical coils are wound around the helical type vacuum container. (I.S.)

  17. Regular expression containment

    DEFF Research Database (Denmark)

    Henglein, Fritz; Nielsen, Lasse

    2011-01-01

    We present a new sound and complete axiomatization of regular expression containment. It consists of the conventional axiomatiza- tion of concatenation, alternation, empty set and (the singleton set containing) the empty string as an idempotent semiring, the fixed- point rule E* = 1 + E × E......* for Kleene-star, and a general coin- duction rule as the only additional rule. Our axiomatization gives rise to a natural computational inter- pretation of regular expressions as simple types that represent parse trees, and of containment proofs as coercions. This gives the axiom- atization a Curry......-Howard-style constructive interpretation: Con- tainment proofs do not only certify a language-theoretic contain- ment, but, under our computational interpretation, constructively transform a membership proof of a string in one regular expres- sion into a membership proof of the same string in another regular expression. We...

  18. Radioactive Material Containment Bags

    National Research Council Canada - National Science Library

    2000-01-01

    The audit was requested by Senator Joseph I. Lieberman based on allegations made by a contractor, Defense Apparel Services, about the Navy's actions on three contracts for radioactive material containment bags...

  19. Containment structure optimization

    International Nuclear Information System (INIS)

    Putman, S.; Walser, A.

    1979-01-01

    The major design features investigated are: dome shape, the prestress level provided to counteract accident pressure, the effect of diameter variation, and the design pressure used to size the containment. The optimum dome shape and optimum prestress level are used to investigate the effect of variations in diameter and design pressure on containment cost. The containment internal diameter is fixed at 150 feet for investigation of dome shape, prestress level and design prestress. A hemispherical dome containment with a prestress level of 1.25 P/sub a/ is recommended regardless of design pressure selected. A design pressure of 60 psi is recommended. No significant cost penalty is associated with diameter variation in the range of 145 to 155 feet

  20. Radioactive waste sealing container

    International Nuclear Information System (INIS)

    Tozawa, S.; Kitamura, T.; Sugimoto, S.

    1984-01-01

    A low- to medium-level radioactive waste sealing container is constructed by depositing a foundation coating consisting essentially of zinc, cadmium or a zinc-aluminum alloy over a steel base, then coating an organic synthetic resin paint containing a metal phosphate over the foundation coating, and thereafter coating an acryl resin, epoxy resin, and/or polyurethane paint. The sealing container can consist of a main container body, a lid placed over the main body, and fixing members for clamping and fixing the lid to the main body. Each fixing member may consist of a material obtained by depositing a coating consisting essentially of cadmium or a zinc-aluminum alloy over a steel base

  1. Lightweight flywheel containment

    Science.gov (United States)

    Smith, James R.

    2004-06-29

    A lightweight flywheel containment composed of a combination of layers of various material which absorb the energy of a flywheel structural failure. The various layers of material act as a vacuum barrier, momentum spreader, energy absorber, and reaction plate. The flywheel containment structure has been experimentally demonstrated to contain carbon fiber fragments with a velocity of 1,000 m/s and has an aerial density of less than 6.5 g/square centimeters. The flywheel containment, may for example, be composed of an inner high toughness structural layer, and energy absorbing layer, and an outer support layer. Optionally, a layer of impedance matching material may be utilized intermediate the flywheel rotor and the inner high toughness layer.

  2. Novel mutations in the USH1C gene in Usher syndrome patients.

    Science.gov (United States)

    Aparisi, María José; García-García, Gema; Jaijo, Teresa; Rodrigo, Regina; Graziano, Claudio; Seri, Marco; Simsek, Tulay; Simsek, Enver; Bernal, Sara; Baiget, Montserrat; Pérez-Garrigues, Herminio; Aller, Elena; Millán, José María

    2010-12-31

    Usher syndrome type I (USH1) is an autosomal recessive disorder characterized by severe-profound sensorineural hearing loss, retinitis pigmentosa, and vestibular areflexia. To date, five USH1 genes have been identified. One of these genes is Usher syndrome 1C (USH1C), which encodes a protein, harmonin, containing PDZ domains. The aim of the present work was the mutation screening of the USH1C gene in a cohort of 33 Usher syndrome patients, to identify the genetic cause of the disease and to determine the relative involvement of this gene in USH1 pathogenesis in the Spanish population. Thirty-three patients were screened for mutations in the USH1C gene by direct sequencing. Some had already been screened for mutations in the other known USH1 genes (myosin VIIA [MYO7A], cadherin-related 23 [CDH23], protocadherin-related 15 [PCDH15], and Usher syndrome 1G [USH1G]), but no mutation was found. Two novel mutations were found in the USH1C gene: a non-sense mutation (p.C224X) and a frame-shift mutation (p.D124TfsX7). These mutations were found in a homozygous state in two unrelated USH1 patients. In the present study, we detected two novel pathogenic mutations in the USH1C gene. Our results suggest that mutations in USH1C are responsible for 1.5% of USH1 disease in patients of Spanish origin (considering the total cohort of 65 Spanish USH1 patients since 2005), indicating that USH1C is a rare form of USH in this population.

  3. Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

    Science.gov (United States)

    Li, Junyan; Jing, Ruilin; Wei, Hongyi; Wang, Minghao; Qi, Xiaowei; Liu, Haoxi; Liu, Jian; Ou, Jianghua; Jiang, Weihua; Tian, Fuguo; Sheng, Yuan; Li, Hengyu; Xu, Hong; Zhang, Ruishan; Guan, Aihua; Liu, Ke; Jiang, Hongchuan; Ren, Yu; He, Jianjun; Huang, Weiwei; Liao, Ning; Cai, Xiangjun; Ming, Jia; Ling, Rui; Xu, Yan; Hu, Chunyan; Zhang, Jianguo; Guo, Baoliang; Ouyang, Lizhi; Shuai, Ping; Liu, Zhenzhen; Zhong, Ling; Zeng, Zhen; Zhang, Ting; Xuan, Zhaoling; Tan, Xuanni; Liang, Junbin; Pan, Qinwen; Chen, Li; Zhang, Fan; Fan, Linjun; Zhang, Yi; Yang, Xinhua; Li, Jingbo; Chen, Chongjian; Jiang, Jun

    2018-05-12

    Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n=937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n=18), PALB2 (n=11), CHEK2 (n=6), ATM (n=6), and BARD1 (n=5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes. This article is protected by copyright. All rights reserved. © 2018 UICC.

  4. CONTAINER FOR USED TEXTILES

    CERN Multimedia

    Relations avec les Pays hôtes

    2000-01-01

    We should like to remind you that a special container for textiles for the Association 'Réalise/Rapid Service' of Geneva is located in the car park outside the Meyrin site.The Association has informed us that 2 530 kg of textiles were deposited in the container in 1998 and wishes to convey its warm gratitude to all donors.Relations with the Host StatesTel. 75152

  5. Fusion impulse containment

    International Nuclear Information System (INIS)

    Bohachevsky, I.O.

    1979-01-01

    The characteristics of impact fusion energy releases are not known sufficiently well to examine in detail specific containment vessel concepts or designs. Therefore it appears appropriate to formulate the impulse containment problem in general and to derive results in the form of explicit expressions from which magnitude estimates and parametric dependencies (trends) can be inferred conveniently and rapidly. In the following presentation we carry out this task using assumptions and approximations that are required to perform the analysis

  6. Associations between mutations and a VNTR in the human phenylalanine hydroxylase gene

    Energy Technology Data Exchange (ETDEWEB)

    Goltsov, A.A.; Eisensmith, R.C.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (United States)); Konecki, D.S.; Lichter-Konecki, U.

    1992-09-01

    The HindIII RFLP in the human phenylalanine hydroxylase (PAH) gene is caused by the presence of an AT-rich (70%) minisatellite region. This region contains various multiples of 30-bp tandem repeats and is located 3 kb downstream of the final exon of the gene. PCR-mediated amplification of this region from haplotyped PAH chromosomes indicates that the previously reported 4.0-kb HindIII allele contains three of these repeats, while the 4.4-kb HindIII allele contains 12 of these repeats. The 4.2-kb HindIII fragment can contain six, seven, eight, or nine copies of this repeat. These variations permit more detailed analysis of mutant haplotypes 1, 5, 6, and, possibly, others. Kindred analysis in phenylketonuria families demonstrates Mendelian segregation of these VNTR alleles, as well as associations between theses alleles and certain PAH mutations. The R261Q mutation, associated with haplotype 1, is associated almost exclusively with an allele containing eight repeats; the R408W mutation, when occurring on a haplotype 1 background, may also be associated with the eight-repeat VNTR allele. Other PAH mutations associated with haplotype 1, R252W and P281L, do not appear to segregate with specific VNTR alleles. The IVS-10 mutation, when associated with haplotype 6, is associated exclusively with an allele containing seven repeats. The combined use of this VNTR system and the existing RFLP haplotype system will increase the performance of prenatal diagnostic tests based on haplotype analysis. In addition, this VNTR may prove useful in studies concerning the origins and distributions of PAH mutations in different human populations. 32 refs., 3 figs., 3 tabs.

  7. Containment vessel stability analysis

    International Nuclear Information System (INIS)

    Harstead, G.A.; Morris, N.F.; Unsal, A.I.

    1983-01-01

    The stability analysis for a steel containment shell is presented herein. The containment is a freestanding shell consisting of a vertical cylinder with a hemispherical dome. It is stiffened by large ring stiffeners and relatively small longitudinal stiffeners. The containment vessel is subjected to both static and dynamic loads which can cause buckling. These loads must be combined prior to their use in a stability analysis. The buckling loads were computed with the aid of the ASME Code case N-284 used in conjunction with general purpose computer codes and in-house programs. The equations contained in the Code case were used to compute the knockdown factors due to shell imperfections. After these knockdown factors were applied to the critical stress states determined by freezing the maximum dynamic stresses and combining them with other static stresses, a linear bifurcation analysis was carried out with the aid of the BOSOR4 program. Since the containment shell contained large penetrations, the Code case had to be supplemented by a local buckling analysis of the shell area surrounding the largest penetration. This analysis was carried out with the aid of the NASTRAN program. Although the factor of safety against buckling obtained in this analysis was satisfactory, it is claimed that the use of the Code case knockdown factors are unduly conservative when applied to the analysis of buckling around penetrations. (orig.)

  8. Engineered mutations in fibrillin-1 leading to Marfan syndrome act at the protein, cellular and organismal levels.

    Science.gov (United States)

    Zeyer, Karina A; Reinhardt, Dieter P

    2015-01-01

    Fibrillins are the major components of microfibrils in the extracellular matrix of elastic and non-elastic tissues. They are multi-domain proteins, containing primarily calcium binding epidermal growth factor-like (cbEGF) domains and 8-cysteine/transforming growth factor-beta binding protein-like (TB) domains. Mutations in the fibrillin-1 gene give rise to Marfan syndrome, a connective tissue disorder with clinical complications in the cardiovascular, skeletal, ocular and other organ systems. Here, we review the consequences of engineered Marfan syndrome mutations in fibrillin-1 at the protein, cellular and organismal levels. Representative point mutations associated with Marfan syndrome in affected individuals have been introduced and analyzed in recombinant fibrillin-1 fragments. Those mutations affect fibrillin-1 on a structural and functional level. Mutations which impair folding of cbEGF domains can affect protein trafficking. Protein folding disrupted by some mutations can lead to defective secretion in mutant fibrillin-1 fragments, whereas fragments with other Marfan mutations are secreted normally. Many Marfan mutations render fibrillin-1 more susceptible to proteolysis. There is also evidence that some mutations affect heparin binding. Few mutations have been further analyzed in mouse models. An extensively studied mouse model of Marfan syndrome expresses mouse fibrillin-1 with a missense mutation (p.C1039G). The mice display similar characteristics to human patients with Marfan syndrome. Overall, the analyses of engineered mutations leading to Marfan syndrome provide important insights into the pathogenic molecular mechanisms exerted by mutated fibrillin-1. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. VarWalker: personalized mutation network analysis of putative cancer genes from next-generation sequencing data.

    Science.gov (United States)

    Jia, Peilin; Zhao, Zhongming

    2014-02-01

    A major challenge in interpreting the large volume of mutation data identified by next-generation sequencing (NGS) is to distinguish driver mutations from neutral passenger mutations to facilitate the identification of targetable genes and new drugs. Current approaches are primarily based on mutation frequencies of single-genes, which lack the power to detect infrequently mutated driver genes and ignore functional interconnection and regulation among cancer genes. We propose a novel mutation network method, VarWalker, to prioritize driver genes in large scale cancer mutation data. VarWalker fits generalized additive models for each sample based on sample-specific mutation profiles and builds on the joint frequency of both mutation genes and their close interactors. These interactors are selected and optimized using the Random Walk with Restart algorithm in a protein-protein interaction network. We applied the method in >300 tumor genomes in two large-scale NGS benchmark datasets: 183 lung adenocarcinoma samples and 121 melanoma samples. In each cancer, we derived a consensus mutation subnetwork containing significantly enriched consensus cancer genes and cancer-related functional pathways. These cancer-specific mutation networks were then validated using independent datasets for each cancer. Importantly, VarWalker prioritizes well-known, infrequently mutated genes, which are shown to interact with highly recurrently mutated genes yet have been ignored by conventional single-gene-based approaches. Utilizing VarWalker, we demonstrated that network-assisted approaches can be effectively adapted to facilitate the detection of cancer driver genes in NGS data.

  10. Characterization of a mutation commonly associated with persistent stuttering: evidence for a founder mutation

    Science.gov (United States)

    Fedyna, Alison; Drayna, Dennis; Kang, Changsoo

    2010-01-01

    Stuttering is a disorder which affects the fluency of speech. It has been shown to have high heritability, and has recently been linked to mutations in the GNPTAB gene. One such mutation, Glu1200Lys, has been repeatedly observed in unrelated families and individual cases. Eight unrelated individuals carrying this mutation were analyzed in an effort to distinguish whether these arise from repeated mutation at the same site, or whether they represent a founder mutation with a single origin. Results show that all 12 chromosomes carrying this mutation share a common haplotype in this region, indicating it is a founder mutation. Further analysis estimated the age of this allele to be ~572 generations. Construction of a cladogram tracing the mutation through our study sample also supports the founder mutation hypothesis. PMID:20944643

  11. MET amplification, expression, and exon 14 mutations in colorectal adenocarcinoma.

    Science.gov (United States)

    Zhang, Meng; Li, Guichao; Sun, Xiangjie; Ni, Shujuan; Tan, Cong; Xu, Midie; Huang, Dan; Ren, Fei; Li, Dawei; Wei, Ping; Du, Xiang

    2018-04-08

    MET amplification, expression, and splice mutations at exon 14 result in dysregulation of the MET signaling pathway. The aim of this study was to identify the relationship between MET amplification, protein or mRNA expression, and mutations in colorectal cancer (CRC). MET immunohistochemistry (IHC) was used for MET protein expression analysis and fluorescence in situ hybridization (FISH) was used for MET amplification detection. Both analyses were performed in tissue microarrays (TMA) containing 294 of colorectal adenocarcinoma tissue samples and 131 samples of adjacent normal epithelial tissue. MET mRNA expression was examined by real-time quantitative polymerase chain reaction (qRT-PCR) in 72 fresh colorectal adenocarcinoma tissue samples and adjacent normal colon tissue. PCR sequencing was performed to screen for MET exon 14 splice mutations in 59 fresh CRC tissue samples. Our results showed that MET protein expression was higher in colorectal tumor tissue than in adjacent normal intestinal epithelium. Positive MET protein expression was associated with significantly poorer overall survival (OS) and disease-free survival (DFS). Multivariate analysis revealed that positive MET protein expression was an independent risk factor for DFS, but not for OS. MET mRNA expression was upregulated in tumor tissues compared with the adjacent normal tissues. The incidence of MET amplification was 4.4%. None of the patients was positive for MET mutation. Collectively, MET was overexpressed in colorectal adenocarcinoma, and its positive protein expression predicted a poorer outcome in CRC patients. Furthermore, according to our results, MET amplification and 14 exon mutation are extremely rare events in colorectal adenocarcinoma. Copyright © 2018. Published by Elsevier Inc.

  12. Predictable Phenotypes of Antibiotic Resistance Mutations.

    Science.gov (United States)

    Knopp, M; Andersson, D I

    2018-05-15

    Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions between different resistance mutations are often predictable from the characteristics of the individual mutations. IMPORTANCE The spread of antibiotic-resistant bacteria imposes an urgent threat to public health. The ability to forecast the evolutionary success of resistant mutants would help to combat dissemination of antibiotic resistance. Previous studies have shown that the phenotypic effects (fitness and resistance level) of resistance mutations can vary substantially depending on the genetic context in which they occur. We conducted a broad screen using many different resistance mutations and host strains to identify potential epistatic interactions between various types of resistance mutations and to determine the effect of strain

  13. Suppression of different classes of somatic mutations in Arabidopsis by vir gene-expressing Agrobacterium strains.

    Science.gov (United States)

    Shah, Jasmine M; Ramakrishnan, Anantha Maharasi; Singh, Amit Kumar; Ramachandran, Subalakshmi; Unniyampurath, Unnikrishnan; Jayshankar, Ajitha; Balasundaram, Nithya; Dhanapal, Shanmuhapreya; Hyde, Geoff; Baskar, Ramamurthy

    2015-08-26

    Agrobacterium infection, which is widely used to generate transgenic plants, is often accompanied by T-DNA-linked mutations and transpositions in flowering plants. It is not known if Agrobacterium infection also affects the rates of point mutations, somatic homologous recombinations (SHR) and frame-shift mutations (FSM). We examined the effects of Agrobacterium infection on five types of somatic mutations using a set of mutation detector lines of Arabidopsis thaliana. To verify the effect of secreted factors, we exposed the plants to different Agrobacterium strains, including wild type (Ach5), its derivatives lacking vir genes, oncogenes or T-DNA, and the heat-killed form for 48 h post-infection; also, for a smaller set of strains, we examined the rates of three types of mutations at multiple time-points. The mutation detector lines carried a non-functional β-glucuronidase gene (GUS) and a reversion of mutated GUS to its functional form resulted in blue spots. Based on the number of blue spots visible in plants grown for a further two weeks, we estimated the mutation frequencies. For plants co-cultivated for 48 h with Agrobacterium, if the strain contained vir genes, then the rates of transversions, SHRs and FSMs (measured 2 weeks later) were lower than those of uninfected controls. In contrast, co-cultivation for 48 h with any of the Agrobacterium strains raised the transposition rates above control levels. The multiple time-point study showed that in seedlings co-cultivated with wild type Ach5, the reduced rates of transversions and SHRs after 48 h co-cultivation represent an apparent suppression of an earlier short-lived increase in mutation rates (peaking for plants co-cultivated for 3 h). An increase after 3 h co-cultivation was also seen for rates of transversions (but not SHR) in seedlings exposed to the strain lacking vir genes, oncogenes and T-DNA. However, the mutation rates in plants co-cultivated for longer times with this strain subsequently

  14. MutHTP: Mutations in Human Transmembrane Proteins.

    Science.gov (United States)

    A, Kulandaisamy; S, Binny Priya; R, Sakthivel; Tarnovskaya, Svetlana; Bizin, Ilya; Hönigschmid, Peter; Frishman, Dmitrij; Gromiha, M Michael

    2018-02-01

    We have developed a novel database, MutHTP, which contains information on 183395 disease-associated and 17827 neutral mutations in human transmembrane proteins. For each mutation site MutHTP provides a description of its location with respect to the membrane protein topology, structural environment (if available) and functional features. Comprehensive visualization, search, display and download options are available. The database is publicly available at http://www.iitm.ac.in/bioinfo/MutHTP/. The website is implemented using HTML, PHP and javascript and supports recent versions of all major browsers, such as Firefox, Chrome and Opera. gromiha@iitm.ac.in. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  15. MPL mutation profile in JAK2 mutation-negative patients with myeloproliferative disorders.

    Science.gov (United States)

    Ma, Wanlong; Zhang, Xi; Wang, Xiuqiang; Zhang, Zhong; Yeh, Chen-Hsiung; Uyeji, Jennifer; Albitar, Maher

    2011-03-01

    Mutations in the thrombopoietin receptor gene (myeloproliferative leukemia, MPL) have been reported in patients with JAK2 V617F-negative chronic myeloproliferative disorders (MPDs). We evaluated the prevalence of MPL mutations relative to JAK2 mutations in patients with suspected MPDs. A total of 2790 patient samples submitted for JAK2 mutation analysis were tested using real-time polymerase chain reaction and bidirectional sequencing of plasma RNA. JAK2 V617F-negative samples were tested for JAK2 exons 12 to 14 mutations, and those with negative results were then tested for mutations in MPL exons 10 and 11. Of the 2790 patients, 529 (18.96%) had V617F, 12 (0.43%) had small insertions or deletions in exon 12, and 7 (0.25%) had other JAK2 mutations in exons 12 to 14. Of the 2242 JAK2 mutation-negative patients, 68 (3.03%) had MPL mutations. W515L was the predominant MPL mutation (n=46; 68%), and 10 (15%) patients had other W515 variants. The remaining MPL mutations (n=12, 17%) were detected at other locations in exons 10 and 11 and included 3 insertion/deletion mutations. The S505N mutation, associated with familial MPD, was detected in 3 patients. Overall, for every 100 V617F mutations in patients with suspected MPDs, there were 12.9 MPL mutations, 2.3 JAK2 exon 12 mutations, and 1.3 JAK2 exons 13 to 14 mutations. These findings suggest that MPL mutation screening should be performed before JAK2 exons 12 to 14 testing in JAK2 V617F-negative patients with suspected MPDs.

  16. Calreticulin Mutations in Bulgarian MPN Patients.

    Science.gov (United States)

    Pavlov, Ivan; Hadjiev, Evgueniy; Alaikov, Tzvetan; Spassova, Sylva; Stoimenov, Angel; Naumova, Elissaveta; Shivarov, Velizar; Ivanova, Milena

    2018-01-01

    Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the cases with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). We applied four molecular genetic methods for identification of CALR exon 9 mutations, including high resolution melt (HRM) analysis, Sanger sequencing, semiconductor target genes sequencing and whole exome sequencing. A total of 78 patients with myeloid malignancies were included in the study. We identified 14 CALR exon 9 mutated cases out of 78 studied patients with myeloid malignancies. All mutated patients were diagnosed with MPN being either PMF (n = 7) or ET (n = 7). Nine cases had type 1 mutations and 5 cases had type 2 mutations. CALR exon 9, MPL exon 10 and JAK2 p. V617F were mutually exclusive. There were no statistically significant differences in the hematological parameters between the cases with CALR and JAK2 or MPL mutations. Notably, all four techniques were fully concordant in the detection of CALR mutations. This is one of the few reports on the CALR mutations frequency in South-eastern populations. Our study shows that the frequency and patterns of these mutations is identical to those in the patients' cohorts from Western countries. Besides we demonstrated the utility of four different methods for their detection.

  17. The IARC TP53 mutation database: a resource for studying the significance of TP53 mutations in human cancers

    Directory of Open Access Journals (Sweden)

    Magali Olivier

    2007-02-01

    Full Text Available

    The tumor suppressor gene TP53 is frequently inactivated by gene mutations in many types of human sporadic cancers, and inherited TP53 mutations predispose to a wide spectrum of early-onset tumors (Li-Fraumeni et Li-Fraumenilike Syndromes. All TP53 gene variations (somatic and germline mutations, as well as polymorphisms that are reported in the scientific literature or in SNP databases are compiled in the IARC TP53 Database. This database provides structured data and analysis tools to study mutation patterns in human cancers and cell-lines and to investigate the clinical impact of mutations. It contains annotations related to the clinical and pathological characteristics of tumors, as well as the demographics and carcinogen exposure of patients. The IARC TP53 web site (http://www-p53.iarc.fr/ provides a search interface for the core database and includes a comprehensive user guide, a slideshow on TP53 mutations in human cancer, protocols and references for sequencing TP53 gene, and links to relevant publications and bioinformatics databases. The database interface allows download of entire data sets and propose various tools for the selection, analysis and downloads of specific sets of data according to user's query.

    Recently, new annotations on the functional properties of mutant p53 proteins have been integrated in this database. Indeed, the most frequent TP53 alterations observed in cancers (75% are missense mutations that result in the production of a mutant protein that differ from the wildtype by one single amino-acid. The characterization of the biological activities of these mutant proteins is thus very important. Over the last ten years, a great amount of systematic data has been generated from experimental assays performed in

  18. Mutational Context and Diverse Clonal Development in Early and Late Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Iver Nordentoft

    2014-06-01

    Full Text Available Bladder cancer (or urothelial cell carcinoma [UCC] is characterized by field disease (malignant alterations in surrounding mucosa and frequent recurrences. Whole-genome, exome, and transcriptome sequencing of 38 tumors, including four metachronous tumor pairs and 20 superficial tumors, identified an APOBEC mutational signature in one-third. This was biased toward the sense strand, correlated with mean expression level, and clustered near breakpoints. A > G mutations were up to eight times more frequent on the sense strand (p < 0.002 in [ACG]AT contexts. The patient-specific APOBEC signature was negatively correlated to repair-gene expression and was not related to clinicopathological parameters. Mutations in gene families and single genes were related to tumor stage, and expression of chromatin modifiers correlated with survival. Evolutionary and subclonal analyses of early/late tumor pairs showed a unitary origin, and discrete tumor clones contained mutated cancer genes. The ancestral clones contained Pik3ca/Kdm6a mutations and may reflect the field-disease mutations shared among later tumors.

  19. Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter.

    Science.gov (United States)

    Tonacchera, M; Agretti, P; Chiovato, L; Rosellini, V; Ceccarini, G; Perri, A; Viacava, P; Naccarato, A G; Miccoli, P; Pinchera, A; Vitti, P

    2000-06-01

    Toxic multinodular goiter, a heterogeneous disease producing hyperthyroidism, is frequently found in iodine-deficient areas. The pathogenesis of this common clinical entity is still unclear. The aim of the present study was to search for activating TSH receptor (TSHr) or Gs alpha mutations in areas of toxic or functionally autonomous multinodular goiters that appeared hyperfunctioning at thyroid scintiscan but did not clearly correspond to definite nodules at physical or ultrasonographic examination. Surgical tissue specimens from nine patients were carefully dissected, matching thyroid scintiscan and thyroid ultrasonography, to isolate hyperfunctioning and nonfunctioning areas even if they did not correspond to well-defined nodules. TSHr and Gs alpha mutations were searched for by direct sequencing after PCR amplification of genomic DNA. Only 2 adenomas were identified at microscopic examination, whereas the remaining 18 hyperfunctioning areas corresponded to hyperplastic nodules containing multiple aggregates of micromacrofollicules not surrounded by a capsule. Activating TSHr mutations were detected in 14 of these 20 hyperfunctioning areas, whereas no mutation was identified in nonfunctioning nodules or areas contained in the same gland. No Gs alpha mutation was found. In conclusion, activating TSHr mutations are present in the majority of nonadenomatous hyperfunctioning nodules scattered throughout the gland in patients with toxic or functionally autonomous multinodular goiter.

  20. Photoreactivation of conversion and de novo suppressor mutation in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Bockrath, R C; Plamer, J E [Indiana Univ., Indianapolis (USA). Dept. of Microbiology

    1977-04-01

    Studies of mutagenesis and photoreactivation in various E.coli strains have shown that conversion mutation of a mutant containing an amber suppressor to one containing an ochre suppressor is sensitive to photoreactivation. Direct photoreactivation by photoreactivating light (PRL) after uv mutagenesis reduced mutation frequencies by a factor of about 2 for each minute of exposure during the first 5 to 8 min of exposure for cells with normal repair capacity. Conversion and potential de novo suppressor mutations were about equally sensitive. For conversion, the sensitivities to PRL were identical in the repair-normal and excisions-repair-deficient strains. For de novo suppressor mutation, the rate of mutation frequency reduction by PRL in the repair-deficient strain was about one-half that in the other strains. The results suggest that ultraviolet radiation produces both de novo suppressor mutation and conversion at the sup(E,B) locus by photoreversible pyrimidine dimers in the DNA. The causative dimers could be Thy()Cyt dimers in the transcribed strand or the non-transcribed strand, respectively.

  1. Roselle improvement through conventional and mutation breeding

    International Nuclear Information System (INIS)

    Mohamad Omar; Mohd Nazir Basiran; Azhar Mohamad; Shuhaimi Shamsuddin

    2002-01-01

    Roselle (Hibiscus sabdariffa L.) from Malvaceae family is relatively a new crop in Malaysia. The origin is not fully known but believed to be from West Africa, although the plant is found native from India to Malaysia. The calyxes, stems and leaves are acid and closely resemble the cranberry (Vaccinium spp.) in flavour. Anthocyanins, which are now receiving a growing importance as natural food colorant, are responsible for the red to purple color of the calyx and other parts of the plant. The calyxes from the flowers are processed to produce juice for drink containing very high vitamin C (ascorbic acid), and also into jam, jelly and dried products. Interestingly, many other parts of the plant are also claimed to have various medicinal values. Presently, roselle is planted in Terengganu (175 ha in 2002) on bris soils, but its planting has spread to some parts of Kelantan, Pahang, Johor and also Sarawak. The number of roselle varieties available for planting is very limited; however, the effort carried out for roselle improvement thus far is equally very limited. There has been very little serious conventional breeding attempted, although varietal evaluation has had been carried out, particularly in form of agronomic trials. Since 1999, several studies on induced mutations have been attempted at UKM. A preliminary polyploidization study was conducted to determine the effects of colchicine concentrations of 0%, 0.04%, 0.08%, 0.12% and 0.16% and soaking times of 2 and 4 hours at room temperature (30 degree C) on 2-day old germinated seeds on morpho-agronomic traits (e.g. number of branches, internode length, leaf length, leaf width, number of flowers and days to flowering), ploidy level and pollen grain size in treated and also derived generations. Flow cytometric analyses of nuclear DNA AT content of leaf samples using LB01 lysis buffer and DNA specific fluorochrome DAPI (4',6-diamidino-2-phenylindole) staining were carried out using a flow cytometer at MINT, Bangi

  2. Component nuclear containment structure

    International Nuclear Information System (INIS)

    Harstead, G.A.

    1979-01-01

    The invention described is intended for use primarily as a nuclear containment structure. Such structures are required to surround the nuclear steam supply system and to contain the effects of breaks in the nuclear steam supply system, or i.e. loss of coolant accidents. Nuclear containment structures are required to withstand internal pressure and temperatures which result from loss of coolant accidents, and to provide for radiation shielding during operation and during the loss of coolant accident, as well as to resist all other applied loads, such as earthquakes. The nuclear containment structure described herein is a composite nuclear containment structure, and is one which structurally combines two previous systems; namely, a steel vessel, and a lined concrete structure. The steel vessel provides strength to resist internal pressure and accommodate temperature increases, the lined concrete structure provides resistance to internal pressure by having a liner which will prevent leakage, and which is in contact with the concrete structure which provides the strength to resist the pressure

  3. Nuclear reactor containing facility

    International Nuclear Information System (INIS)

    Hidaka, Masataka; Murase, Michio.

    1994-01-01

    In a reactor containing facility, a condensation means is disposed above the water level of a cooling water pool to condensate steams of the cooling water pool, and return the condensated water to the cooling water pool. Upon occurrence of a pipeline rupture accident, steams generated by after-heat of a reactor core are caused to flow into a bent tube, blown from the exit of the bent tube into a suppression pool and condensated in a suppression pool water, thereby suppressing the pressure in the reactor container. Cooling water in the cooling water pool is boiled by heat conduction due to the condensation of steams, then the steams are exhausted to the outside of the reactor container to remove the heat of the reactor container to the outside of the reactor. In addition, since cooling water is supplied to the cooling water pool quasi-permanently by gravity as a natural force, the reactor container can be cooled by the cooling water pool for a long period of time. Since the condensation means is constituted with a closed loop and interrupted from the outside, radioactive materials are never released to the outside. (N.H.)

  4. Passive cooling containment study

    International Nuclear Information System (INIS)

    Shin, J.J.; Iotti, R.C.; Wright, R.F.

    1993-01-01

    Pressure and temperature transients of nuclear reactor containment following postulated loss of coolant accident with a coincident station blackout due to total loss of all alternating current power are studied analytically and experimentally for the full scale NPR (New Production Reactor). All the reactor and containment cooling under this condition would rely on the passive cooling system which removes reactor decay heat and provides emergency core and containment cooling. Containment passive cooling for this study takes place in the annulus between containment steel shell and concrete shield building by natural convection air flow and thermal radiation. Various heat transfer coefficients inside annular air space were investigated by running the modified CONTEMPT code CONTEMPT-NPR. In order to verify proper heat transfer coefficient, temperature, heat flux, and velocity profiles were measured inside annular air space of the test facility which is a 24 foot (7.3m) high, steam heated inner cylinder of three foot (.91m) diameter and five and half foot (1.7m) diameter outer cylinder. Comparison of CONTEMPT-NPR and WGOTHIC was done for reduced scale NPR

  5. Novel SOX2 mutations and genotype-phenotype correlation in anophthalmia and microphthalmia.

    Science.gov (United States)

    Schneider, Adele; Bardakjian, Tanya; Reis, Linda M; Tyler, Rebecca C; Semina, Elena V

    2009-12-01

    SOX2 represents a High Mobility Group domain containing transcription factor that is essential for normal development in vertebrates. Mutations in SOX2 are known to result in a spectrum of severe ocular phenotypes in humans, also typically associated with other systemic defects. Ocular phenotypes include anophthalmia/microphthalmia (A/M), optic nerve hypoplasia, ocular coloboma and other eye anomalies. We screened 51 unrelated individuals with A/M and identified SOX2 mutations in the coding region of the gene in 10 individuals. Seven of the identified mutations are novel alterations, while the remaining three individuals carry the previously reported recurrent 20-nucleotide deletion in SOX2, c.70del20. Among the SOX2-positive cases, seven patients had bilateral A/M and mutations resulting in premature termination of the normal protein sequence (7/38; 18% of all bilateral cases), one patient had bilateral A/M associated with a single amino acid insertion (1/38; 3% of bilateral cases), and the final two patients demonstrated unilateral A/M associated with missense mutations (2/13; 15% of all unilateral cases). These findings and review of previously reported cases suggest a potential genotype/phenotype correlation for SOX2 mutations with missense changes generally leading to less severe ocular defects. In addition, we report a new familial case of affected siblings with maternal mosaicism for the identified SOX2 mutation, which further underscores the importance of parental testing to provide accurate genetic counseling to families.

  6. A functional alternative splicing mutation in AIRE gene causes autoimmune polyendocrine syndrome type 1.

    Directory of Open Access Journals (Sweden)

    Junyu Zhang

    Full Text Available Autoimmune polyendocrine syndrome type 1 (APS-1 is a rare autosomal recessive disease defined by the presence of two of the three conditions: mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Loss-of-function mutations of the autoimmune regulator (AIRE gene have been linked to APS-1. Here we report mutational analysis and functional characterization of an AIRE mutation in a consanguineous Chinese family with APS-1. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. We identified a homozygous missense AIRE mutation c.463G>A (p.Gly155Ser in two siblings with different clinical features of APS-1. In silico splice-site prediction and minigene analysis were carried out to study the potential pathological consequence. Minigene splicing analysis and subsequent cDNA sequencing revealed that the AIRE mutation potentially compromised the recognition of the splice donor of intron 3, causing alternative pre-mRNA splicing by intron 3 retention. Furthermore, the aberrant AIRE transcript was identified in a heterozygous carrier of the c.463G>A mutation. The aberrant intron 3-retaining transcript generated a truncated protein (p.G155fsX203 containing the first 154 AIRE amino acids and followed by 48 aberrant amino acids. Therefore, our study represents the first functional characterization of the alternatively spliced AIRE mutation that may explain the pathogenetic role in APS-1.

  7. Predicting Effects of Tropomyosin Mutations on Cardiac Muscle Contraction through Myofilament Modeling

    Directory of Open Access Journals (Sweden)

    Lorenzo Rakesh Sewanan

    2016-10-01

    Full Text Available Point mutations to the human gene TPM1 have been implicated in the development of both hypertrophic and dilated cardiomyopathies. Such observations have led to studies investigating the link between single residue changes and the biophysical behavior of the tropomyosin molecule. However, the degree to which these molecular perturbations explain the performance of intact sarcomeres containing mutant tropomyosin remains uncertain. Here, we present a modeling approach that integrates various aspects of tropomyosin’s molecular properties into a cohesive paradigm representing their impact on muscle function. In particular, we considered the effects of tropomyosin mutations on (1 persistence length, (2 equilibrium between thin filament blocked and closed regulatory states, and (3 the crossbridge duty cycle. After demonstrating the ability of the new model to capture Ca-dependent myofilament responses during both dynamic and steady-state activation, we used it to capture the effects of hypertrophic cardiomyopathy (HCM related E180G and D175N mutations on skinned myofiber mechanics. Our analysis indicates that the fiber-level effects of the two mutations can be accurately described by a combination of changes to the three tropomyosin properties represented in the model. Subsequently, we used the model to predict mutation effects on muscle twitch. Both mutations led to increased twitch contractility as a consequence of diminished cooperative inhibition between thin filament regulatory units. Overall, simulations suggest that a common twitch phenotype for HCM-linked tropomyosin mutations includes both increased contractility and elevated diastolic tension.

  8. KMeyeDB: a graphical database of mutations in genes that cause eye diseases.

    Science.gov (United States)

    Kawamura, Takashi; Ohtsubo, Masafumi; Mitsuyama, Susumu; Ohno-Nakamura, Saho; Shimizu, Nobuyoshi; Minoshima, Shinsei

    2010-06-01

    KMeyeDB (http://mutview.dmb.med.keio.ac.jp/) is a database of human gene mutations that cause eye diseases. We have substantially enriched the amount of data in the database, which now contains information about the mutations of 167 human genes causing eye-related diseases including retinitis pigmentosa, cone-rod dystrophy, night blindness, Oguchi disease, Stargardt disease, macular degeneration, Leber congenital amaurosis, corneal dystrophy, cataract, glaucoma, retinoblastoma, Bardet-Biedl syndrome, and Usher syndrome. KMeyeDB is operated using the database software MutationView, which deals with various characters of mutations, gene structure, protein functional domains, and polymerase chain reaction (PCR) primers, as well as clinical data for each case. Users can access the database using an ordinary Internet browser with smooth user-interface, without user registration. The results are displayed on the graphical windows together with statistical calculations. All mutations and associated data have been collected from published articles. Careful data analysis with KMeyeDB revealed many interesting features regarding the mutations in 167 genes that cause 326 different types of eye diseases. Some genes are involved in multiple types of eye diseases, whereas several eye diseases are caused by different mutations in one gene.

  9. Mutation Spectrum and Phenotypic Features in Noonan Syndrome with PTPN11 Mutations: Definition of Two Novel Mutations.

    Science.gov (United States)

    Atik, Tahir; Aykut, Ayca; Hazan, Filiz; Onay, Huseyin; Goksen, Damla; Darcan, Sukran; Tukun, Ajlan; Ozkinay, Ferda

    2016-06-01

    To evaluate the spectrum of PTPN11 gene mutations in Noonan syndrome patients and to study the genotype-phenotype associations. In this study, twenty Noonan syndrome patients with PTPN11 mutations were included. The patients underwent a detailed clinical and physical evaluation. To identify inherited cases, parents of all mutation positive patients were analyzed. Thirteen different PTPN11 mutations, two of them being novel, were detected in the study group. These mutations included eleven missense mutations: p.G60A, p.D61N, p.Y62D, p.Y63C, p.E69Q, p.Q79R, p.Y279C,p.N308D, p.N308S, p.M504V, p.Q510R and two novel missense mutations: p.I56V and p.I282M. The frequency of cardiac abnormalities and short stature were found to be 80 % and 80 %, respectively. Mental retardation was not observed in patients having exon 8 mutations. No significant correlations were detected between other phenotypic features and genotypes. By identifying genotype-phenotype correlations, this study provides information on phenotypes observed in NS patients with different PTPN11 mutations.

  10. Induced Mutations in Thai Rice

    International Nuclear Information System (INIS)

    Klakhaeng, Kanchana

    2014-01-01

    Rice is the primary source of food for more than half of the world's population. It benefits greatly from technological inputs in the area of breeding such as induced mutation. Induced mutation can produce mutants with significant improvement in plant type, maturity, yields and protein ratio when compared to the parent. These improved traits enable the mutants to fit into farming systems with either shorter or longer growing seasons. Three induced mutant rice varieties, including RD6, RD10 and RD15, are well accepted by farmers and consumers in Thailand. RD6 and RD15 were aromatic, photosensitive varieties which were derived from KDML105 by acute irradiation of 20 and 15 kilorad gamma ray, respectively. After induced mutation, pedigree selection was applied. RD6 showed drought tolerance and also good grain quality including softness and good aroma with a higher average yield than the famous glutinous variety, San-Pah-Tong. Additionally, it was resistant to blast and brown spot diseases with an average yield of 4.19 tons/ha. RD15 showed drought tolerance and resistance to brown spot disease with the highest yield of 3.5 tons/ha. These two mutant varieties are currently the most famous aromatic rice varieties in Thailand. On the other hand, RD10 is a glutinous, photoperiod insensitive rice variety which was derived from RD1 by irradiation of 1 kilorad fast neutrons. RD10 showed good grain quality such as softness and stickiness with the yield of 4.25 tons/ha. As an on-going project, recommended rice varieties were irradiated with electron beam for anaerobic germination ability, submergence tolerance, stagnant-flood tolerance and also internode elongation.

  11. Spectrum of CFTR gene mutations in Ecuadorian cystic fibrosis patients: the second report of the p.H609R mutation.

    Science.gov (United States)

    Ortiz, Sofía C; Aguirre, Santiago J; Flores, Sofía; Maldonado, Claudio; Mejía, Juan; Salinas, Lilian

    2017-11-01

    High heterogeneity in the CFTR gene mutations disturbs the molecular diagnosis of cystic fibrosis (CF). In order to improve the diagnosis of CF in our country, the present study aims to define a panel of common CFTR gene mutations by sequencing 27 exons of the gene in Ecuadorian Cystic Fibrosis patients. Forty-eight Ecuadorian individuals with suspected/confirmed CF diagnosis were included. Twenty-seven exons of CFTR gene were sequenced to find sequence variations. Prevalence of pathogenic variations were determined and compared with other countries' data. We found 70 sequence variations. Eight of these are CF-causing mutations: p.F508del, p.G85E, p.G330E, p.A455E, p.G970S, W1098X, R1162X, and N1303K. Also this study is the second report of p.H609R in Ecuadorian population. Mutation prevalence differences between Ecuadorian population and other Latin America countries were found. The panel of mutations suggested as an initial screening for the Ecuadorian population with cystic fibrosis should contain the mutations: p.F508del, p.G85E, p.G330E, p.A455E, p.G970S, W1098X, R1162X, and N1303K. © 2017 NETLAB Laboratorios Especializados. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

  12. Non-syndromic hearing loss caused by the dominant cis mutation R75Q with the recessive mutation V37I of the GJB2 (Connexin 26) gene.

    Science.gov (United States)

    Kim, Juwon; Jung, Jinsei; Lee, Min Goo; Choi, Jae Young; Lee, Kyung-A

    2015-06-19

    GJB2 alleles containing two cis mutations have been rarely found in non-syndromic hearing loss. Herein, we present a Korean patient with non-syndromic hearing loss caused by the R75Q cis mutation with V37I, which arose de novo in the father and was inherited by the patient. Biochemical coupling and hemichannel permeability assays were performed after molecular cloning and transfection of HEK293T cells. Student's t-tests or analysis of variance followed by Tukey's multiple comparison test was used as statistical analysis. Biochemical coupling was significantly reduced in connexin 26 (Cx26)-R75Q- and Cx26-V37I-transfected cells, with greater extent in Cx26-R75Q and Cx26-R75Q+V37I cells. Interestingly, our patient and his father with the mutations had more residual hearing compared with patients with the dominant mutation alone. Although the difference in hemichannel activity between R75Q alone and R75Q in combination with V37I failed to reach significance, it is of note that there is a possibility that V37I located upstream of R75Q might have the ability to ameliorate R75Q expression. Our study emphasizes the importance of cis mutations with R75Q, as the gene effect of R75Q can be modulated depending on the type of additional mutation.

  13. Induced mutations for crop improvement

    International Nuclear Information System (INIS)

    Micke, A.; Donini, B.; Maluszynski, M.

    1990-01-01

    Mutation induction has become an established tool in plant breeding to supplement existing germ plasma and to improve cultivars in certain specific traits. Hundreds of improved varieties have been released to farmers for many different crop species, demonstrating the economic value of the technology. Limitations arise mainly from the large mutagenized populations to be screened and from the unsatisfactory selection methods. Both limitations may be eased to some extent by advances in techniques of plant in-vitro culture. (author). Refs, 1 fig., 7 tabs

  14. Container for radioactive materials

    International Nuclear Information System (INIS)

    Housholder, W.R.; Greer, N.L.

    1976-01-01

    The improvement of the construction of containers for the transport of nuclear fuels is proposed where above all, the insulating mass suggested is important as it acts as a safeguard in case of an accident. The container consists of a metal casing in which there is a pressure boiler and a gamma-shielding device, spacers between the metal casing and the shielding device as well as an insulation filling the space between them. The insulating material is a water-in-resin emulsion which is hardened or cross-linked by peroxide and which can furthermore contain up to 50 wt.% solid silicious material such as vermuculite or chopped glass fibre. The construction and variations of the insulating mass composition are described in great detail. (HR) [de

  15. Container for liquefied gas

    Energy Technology Data Exchange (ETDEWEB)

    Short, A J

    1967-05-18

    Containers for liquefied gases are of double-wall construction with a vacuum between the 2 walls; the upper end of the neck contains a vapor chamber and is equipped with means for withdrawing gas from the container. According to this invention, the vapor chamber is connected to a damping chamber by means of a choke line which has an internal diameter of at least 1.6 mm and a length equal to at least 52 times the diameter. The damping chamber has a volume of at least 5 cu cm and is larger than the outer part of the chamber. The interior length of the damping chamber is at least twice the diameter of the choke line. (5 claims)

  16. Subatmospheric double containment system

    International Nuclear Information System (INIS)

    Gans, D. Jr.; Noble, J.H.

    1978-01-01

    A reinforced concrete double wall nuclear containment structure with each wall including an essentially impervious membrane or liner and porous concrete filling the annulus between the two walls is described. The interior of the structure is maintained at subatmospheric pressure, and the annulus between the two walls is maintained at a subatmospheric pressure intermediate between that of the interior and the surrounding atmospheric pressure, during normal operation. In the event of an accident within the containment structure the interior pressure may exceed atmospheric pressure, but leakage from the interior to the annulus between the double walls will not result in the pressure of the annulus exceeding atmospheric pressure so that there is no net outleakage from the containment structure

  17. Advanced Containment System

    Science.gov (United States)

    Kostelnik, Kevin M.; Kawamura, Hideki; Richardson, John G.; Noda, Masaru

    2004-10-12

    An advanced containment system for containing buried waste and associated leachate. A trench is dug on either side of the zone of interest containing the buried waste so as to accommodate a micro tunnel boring machine. A series of small diameter tunnels are serially excavated underneath the buried waste. The tunnels are excavated by the micro tunnel boring machine at a consistent depth and are substantially parallel to each other. As tunneling progresses, steel casing sections are connected end to end in the excavated portion of the tunnel so that a steel tube is formed. Each casing section has complementary interlocking structure running its length that interlocks with complementary interlocking structure on the adjacent casing section. Thus, once the first tube is emplaced, placement of subsequent tubes is facilitated by the complementary interlocking structure on the adjacent, previously placed, casing sections.

  18. Radioactive liquid containing vessel

    International Nuclear Information System (INIS)

    Sakurada, Tetsuo; Kawamura, Hironobu.

    1993-01-01

    Cooling jackets are coiled around the outer circumference of a container vessel, and the outer circumference thereof is covered with a surrounding plate. A liquid of good conductivity (for example, water) is filled between the cooling jackets and the surrounding plate. A radioactive liquid is supplied to the container vessel passing through a supply pipe and discharged passing through a discharge pipe. Cooling water at high pressure is passed through the cooling water jackets in order to remove the heat generated from the radioactive liquid. Since cooling water at high pressure is thus passed through the coiled pipes, the wall thickness of the container vessel and the cooling water jackets can be reduced, thereby enabling to reduce the cost. Further, even if the radioactive liquid is leaked, there is no worry of contaminating cooling water, to prevent contamination. (I.N.)

  19. Container for hydrogen isotopes

    International Nuclear Information System (INIS)

    Solomon, D.E.

    1977-01-01

    A container for the storage, shipping and dispensing of hydrogen isotopes such as hydrogen, deuterium, tritium, or mixtures of the same which has compactness, which is safe against fracture or accident, and which is reusable is described. The container consists of an outer housing with suitable inlet and outlet openings and electrical feed elements, the housing containing an activated sorber material in the form, for example, of titanium sponge or an activated zirconium aluminate cartridge. The gas to be stored is introduced into the chamber under conditions of heat and vacuum and will be retained in the sorber material. Subsequently, it may be released by heating the unit to drive off the stored gas at desired rates

  20. Steel containment buckling

    International Nuclear Information System (INIS)

    Butler, T.A.; Baker, W.E.

    1987-01-01

    Two aspects of buckling of a free-standing nuclear containment building were investigated in a combined experimental and analytical program. In the first part of the study, the response of a scale model of a containment building to dynamic base excitation is investigated. A simple harmonic signal was used for preliminary studies followed by experiments with scaled earthquake signals as the excitation source. The experiments and accompanying analyses indicate that the scale model response to earthquake-type excitations is very complex and that current analytical methods may require that a dynamic capacity reduction factor be incorporated. The second part of the study quantified the effects of framing at large penetrations on the static buckling capacity of scale model containments. Results show little effect from the framing for the scale models constructed from the polycarbonate, Lexan. However, additional studies with a model constructed of the prototypic steel material are recommended. (orig.)

  1. Steel containment buckling

    International Nuclear Information System (INIS)

    Butler, T.A.; Baker, W.E.

    1986-01-01

    Two aspects of buckling of a free-standing nuclear steel containment building were investigated in a combined experimental and analytical program. In the first part of the study, the response of a scale model of a containment building to dynamic base excitation is investigated. A simple harmonic signal was used for preliminary studies followed by experiments with scaled earthquake signals as the excitation source. The experiments and accompanying analyses indicate that the scale model response to earthquake-type excitations is very complex and that current analytical methods may require a dynamic capacity reduction factor to be incorporated. The second part of the study quantified the effects of framing at large penetrations on the static buckling capacity of scale model containments. Results show little effect from the framing for the scale models constructed from the polycarbonate, Lexan. However, additional studies with a model constructed of the prototypic steel material are suggested

  2. EGFR mutation frequency and effectiveness of erlotinib

    DEFF Research Database (Denmark)

    Weber, Britta; Hager, Henrik; Sorensen, Boe S

    2014-01-01

    mutation (S768I), and two complex mutations. Seven percent of the patients were never smokers. The differences in median progression-free survival and overall survival between the mutated group and the wild-type group were 8.0 vs. 2.5 months, p...-1 vs. 2-3) and line of treatment (1st vs. 2nd and 3rd) had no influence on outcome in EGFR-mutated patients. CONCLUSION: We found a higher frequency of EGFR mutations than expected in a cohort with less than 10% never smokers. The outcome after treatment with erlotinib was much better in patients......OBJECTIVES: In 2008, we initiated a prospective study to explore the frequency and predictive value of epidermal growth factor receptor (EGFR) mutations in an unselected population of Danish patients with non-small cell lung cancer offered treatment with erlotinib, mainly in second-line. MATERIALS...

  3. Mutation, Witten index, and quiver invariant

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Heeyeon [Perimeter Institute for Theoretical Physics,31 Caroline Street North, Waterloo, N2L 2Y5, Ontario (Canada); Lee, Seung-Joo [Department of Physics, Robeson Hall, Virginia Tech,Blacksburg, VA 24061 (United States); Yi, Piljin [School of Physics, Korea Institute for Advanced Study,Seoul 130-722 (Korea, Republic of)

    2015-07-20

    We explore Seiberg-like dualities, or mutations, for N=4 quiver quantum mechanics in the context of wall-crossing. In contrast to higher dimensions, the 1d Seiberg-duality must be performed with much care. With fixed Fayet-Iliopoulos constants, at most two nodes can be mutated, one left and the other right, mapping a chamber of a quiver into a chamber of a mutated quiver. We delineate this complex pattern for triangle quivers and show how the Witten indices are preserved under such finely chosen mutations. On the other hand, the quiver invariants, or wall-crossing-safe part of supersymmetric spectra, mutate more straightforwardly, whereby a quiver is mapped to a quiver. The mutation rule that preserves the quiver invariant is different from the usual one, however, which we explore and confirm numerically.

  4. Mutation, Witten index, and quiver invariant

    International Nuclear Information System (INIS)

    Kim, Heeyeon; Lee, Seung-Joo; Yi, Piljin

    2015-01-01

    We explore Seiberg-like dualities, or mutations, for N=4 quiver quantum mechanics in the context of wall-crossing. In contrast to higher dimensions, the 1d Seiberg-duality must be performed with much care. With fixed Fayet-Iliopoulos constants, at most two nodes can be mutated, one left and the other right, mapping a chamber of a quiver into a chamber of a mutated quiver. We delineate this complex pattern for triangle quivers and show how the Witten indices are preserved under such finely chosen mutations. On the other hand, the quiver invariants, or wall-crossing-safe part of supersymmetric spectra, mutate more straightforwardly, whereby a quiver is mapped to a quiver. The mutation rule that preserves the quiver invariant is different from the usual one, however, which we explore and confirm numerically.

  5. A NEW MUTATION OPERATOR IN GENETIC PROGRAMMING

    Directory of Open Access Journals (Sweden)

    Anuradha Purohit

    2013-01-01

    Full Text Available This paper proposes a new type of mutation operator, FEDS (Fitness, Elitism, Depth, and Size mutation in genetic programming. The concept behind the new mutation operator is inspired from already introduced FEDS crossover operator to handle the problem of code bloating. FEDS mutation operates by using local elitism replacement in combination with depth limit and size of the trees to reduce bloat with a subsequent improvement in the performance of trees (program structures. We have designed a multiclass classifier for some benchmark datasets to test the performance of proposed mutation. The results show that when the initial run uses FEDS crossover and the concluding run uses FEDS mutation, then not only is the final result significantly improved but there is reduction in bloat also.

  6. Westinghouse radiological containment guide

    International Nuclear Information System (INIS)

    Aitken, S.B.; Brown, R.L.; Cantrell, J.R.; Wilcox, D.P.

    1994-03-01

    This document provides uniform guidance for Westinghouse contractors on the implementation of radiological containments. This document reflects standard industry practices and is provided as a guide. The guidance presented herein is consistent with the requirements of the DOE Radiological Control Manual (DOE N 5480.6). This guidance should further serve to enable and encourage the use of containments for contamination control and to accomplish the following: Minimize personnel contamination; Prevent the spread of contamination; Minimize the required use of protective clothing and personal protective equipment; Minimize the generation of waste

  7. Bellefonte primary containment structure

    International Nuclear Information System (INIS)

    Olyniec, J.H.

    1981-01-01

    Construction of the reactor building primary containment structure at the Bellefonte Nuclear Plant involved several specialized construction techniques. This two unit plant is one of the nine nuclear units at six different sites now under construction by the Tennessee Valley Authority (TVA). The post-Tensioned, cast-in-place interior steel lined containment structure is unique within TVA. Problems during construction were identified at weekly planning meetings, and options were discussed. Close coordination between craft supervisors and on-site engineering personnel drew together ''hands-on''experience and technical background. Details of the construction techniques, problems, and solutions are presented

  8. Livet er en container

    DEFF Research Database (Denmark)

    Moestrup, Steffen Damkjær

    2008-01-01

    Med Container går Lukas Moodysson for alvor filmeksperimentets vej. Filmen har en række indholdsmæssige træk til fælles med Moodyssons tidligere værker, men den formmæssige tilgang skal især findes i den amerikanske avantgardefilm.......Med Container går Lukas Moodysson for alvor filmeksperimentets vej. Filmen har en række indholdsmæssige træk til fælles med Moodyssons tidligere værker, men den formmæssige tilgang skal især findes i den amerikanske avantgardefilm....

  9. Orimulsion containment and recovery

    International Nuclear Information System (INIS)

    Sommerville, M.

    1999-01-01

    This paper focuses on the need for examination of Orimulsion fuel and its spill behaviour in the light of the anticipated increase in consumption of this fuel which comprises bitumen dispersed in water with addition of a small amount of surfactant. The behaviour and fate of Orimulsion at sea, and observations from experimental and sea trials are examined. The identification of spill control techniques, spill detection, the predictive modeling of the spill and response, sub-surface plume measurement, and containment and deflection are considered. Recovery of the bitumen produced from an Orimulsion spill, combined containment and recovery, dispersed Orimulsion, and beach cleaning are addressed. The properties of Orimulsion are tabulated. (UK)

  10. Westinghouse radiological containment guide

    Energy Technology Data Exchange (ETDEWEB)

    Aitken, S.B. [Idaho National Engineering Lab., Idaho Falls, ID (United States); Brown, R.L. [Westinghouse Hanford Co., Richland, WA (United States); Cantrell, J.R. [Westinghouse Savannah River Co., Aiken, SC (United States); Wilcox, D.P. [West Valley Nuclear Services Co., Inc., West Valley, NY (United States)

    1994-03-01

    This document provides uniform guidance for Westinghouse contractors on the implementation of radiological containments. This document reflects standard industry practices and is provided as a guide. The guidance presented herein is consistent with the requirements of the DOE Radiological Control Manual (DOE N 5480.6). This guidance should further serve to enable and encourage the use of containments for contamination control and to accomplish the following: Minimize personnel contamination; Prevent the spread of contamination; Minimize the required use of protective clothing and personal protective equipment; Minimize the generation of waste.

  11. Radioactive waste processing container

    International Nuclear Information System (INIS)

    Ishizaki, Kanjiro; Koyanagi, Naoaki; Sakamoto, Hiroyuki; Uchida, Ikuo.

    1992-01-01

    A radioactive waste processing container used for processing radioactive wastes into solidification products suitable to disposal such as underground burying or ocean discarding is constituted by using cements. As the cements, calcium sulfoaluminate clinker mainly comprising calcium sulfoaluminate compound; 3CaO 3Al 2 O 3 CaSO 4 , Portland cement and aqueous blast furnace slug is used for instance. Calciumhydroxide formed from the Portland cement is consumed for hydration of the calcium sulfoaluminate clinker. According, calcium hydroxide is substantially eliminated in the cement constituent layer of the container. With such a constitution, damages such as crackings and peelings are less caused, to improve durability and safety. (I.N.)

  12. Material containment enclosure

    International Nuclear Information System (INIS)

    Carlson, D.O.

    1993-01-01

    An isolation enclosure and a group of isolation enclosures are described which are useful when a relatively large containment area is required. The enclosure is in the form of a ring having a section removed so that a technician may enter the center area of the ring. In a preferred embodiment, an access zone is located in the transparent wall of the enclosure and extends around the inner perimeter of the ring so that a technician can insert his hands into the enclosure to reach any point within. The inventive enclosures provide more containment area per unit area of floor space than conventional material isolation enclosures. 3 figures

  13. The Mutational Robustness of Influenza A Virus.

    Directory of Open Access Journals (Sweden)

    Elisa Visher

    2016-08-01

    Full Text Available A virus' mutational robustness is described in terms of the strength and distribution of the mutational fitness effects, or MFE. The distribution of MFE is central to many questions in evolutionary theory and is a key parameter in models of molecular evolution. Here we define the mutational fitness effects in influenza A virus by generating 128 viruses, each with a single nucleotide mutation. In contrast to mutational scanning approaches, this strategy allowed us to unambiguously assign fitness values to individual mutations. The presence of each desired mutation and the absence of additional mutations were verified by next generation sequencing of each stock. A mutation was considered lethal only after we failed to rescue virus in three independent transfections. We measured the fitness of each viable mutant relative to the wild type by quantitative RT-PCR following direct competition on A549 cells. We found that 31.6% of the mutations in the genome-wide dataset were lethal and that the lethal fraction did not differ appreciably between the HA- and NA-encoding segments and the rest of the genome. Of the viable mutants, the fitness mean and standard deviation were 0.80 and 0.22 in the genome-wide dataset and best modeled as a beta distribution. The fitness impact of mutation was marginally lower in the segments coding for HA and NA (0.88 ± 0.16 than in the other 6 segments (0.78 ± 0.24, and their respective beta distributions had slightly different shape parameters. The results for influenza A virus are remarkably similar to our own analysis of CirSeq-derived fitness values from poliovirus and previously published data from other small, single stranded DNA and RNA viruses. These data suggest that genome size, and not nucleic acid type or mode of replication, is the main determinant of viral mutational fitness effects.

  14. POLE somatic mutations in advanced colorectal cancer.

    Science.gov (United States)

    Guerra, Joana; Pinto, Carla; Pinto, Diana; Pinheiro, Manuela; Silva, Romina; Peixoto, Ana; Rocha, Patrícia; Veiga, Isabel; Santos, Catarina; Santos, Rui; Cabreira, Verónica; Lopes, Paula; Henrique, Rui; Teixeira, Manuel R

    2017-12-01

    Despite all the knowledge already gathered, the picture of somatic genetic changes in colorectal tumorigenesis is far from complete. Recently, germline and somatic mutations in the exonuclease domain of polymerase epsilon, catalytic subunit (POLE) gene have been reported in a small subset of microsatellite-stable and hypermutated colorectal carcinomas (CRCs), affecting the proofreading activity of the enzyme and leading to misincorporation of bases during DNA replication. To evaluate the role of POLE mutations in colorectal carcinogenesis, namely in advanced CRC, we searched for somatic mutations by Sanger sequencing in tumor DNA samples from 307 cases. Microsatellite instability and mutation analyses of a panel of oncogenes were performed in the tumors harboring POLE mutations. Three heterozygous mutations were found in two tumors, the c.857C>G, p.Pro286Arg, the c.901G>A, p.Asp301Asn, and the c.1376C>T, p.Ser459Phe. Of the POLE-mutated CRCs, one tumor was microsatellite-stable and the other had low microsatellite instability, whereas KRAS and PIK3CA mutations were found in one tumor each. We conclude that POLE somatic mutations exist but are rare in advanced CRC, with further larger studies being necessary to evaluate its biological and clinical implications. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  15. Mutation direction by irradiation in rice

    International Nuclear Information System (INIS)

    Wang Cailian; Chen Qiufang; Jin Wei; Lu Yimei

    2001-01-01

    The mutation directions of rice were studied. The results indicated that the mutation directions of rice induced by 14 C were invert correlation to their genetic backgrounds of tested rice varieties, i.e. early mature and short stem varieties produced later mature and higher stem mutation; late mature and high stem varieties produced earlier mature and shorter stem mutation; the varieties of middle maturity and height produced both direction mutations of earlier and later maturity or shorter and higher stem. The mutation directions induced by 14 C were also related to treated doses and stages. Frequency of earlier maturity mutation by protons treatment were higher than those induced by other mutagens. Frequency of later maturity by γ-rays were higher than those induced by other mutagens. Frequency of short stem mutation by synchronous irradiation (soft X-rays) were higher than those induced by other mutagens. Frequency of beneficial mutation induced by proton treatment were higher than those induced by γ-rays

  16. Epilepsy caused by CDKL5 mutations.

    Science.gov (United States)

    Castrén, Maija; Gaily, Eija; Tengström, Carola; Lähdetie, Jaana; Archer, Hayley; Ala-Mello, Sirpa

    2011-01-01

    Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) have been identified in female patients with early onset epileptic encephalopathy and severe mental retardation with a Rett-like phenotype. Subsequently CDKL5 mutations were shown to be associated with more diverse phenotypes including mild epilepsy and autism without epilepsy. Furthermore, CDKL5 mutations were found in patients with Angelman-like phenotype. The severity of epilepsy associated with CDKL5 mutations was recently shown to correlate with the type of CDKL5 mutations and epilepsy was identified to involve three distinct sequential stages. Here, we describe the phenotype of a severe form of neurodevelopmental disease in a female patient with a de novo nonsense mutation of the CDKL5 gene c.175C > T (p.R59X) affecting the catalytic domain of CDKL5 protein. Mutations in the CDKL5 gene are less common in males and can be associated with a genomic deletion as found in our male patient with a deletion of 0.3 Mb at Xp22.13 including the CDKL5 gene. We review phenotypes associated with CDKL5 mutations and examine putative relationships between the clinical epilepsy phenotype and the type of the mutation in the CDKL5 gene. © 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  17. Mutation studies on garden roses: a review

    International Nuclear Information System (INIS)

    Datta, S.K.

    1997-01-01

    Most of the modern roses are the result of hybridization, selection and spontaneous mutation. For floriculture trade, there is always demand and necessity for new varieties due to change in taste and fashion. Mutation breeding is an established method for crop improvement. Induced somatic mutation breeding holds promise for effective improvement and have high potential for bringing about genetic improvement and it has led to a great burst of flower colour, form, pattern and other variations in rose by using ionizing radiations. The details of prospects and utilization of induced mutation breeding technique for developing new rose varieties have been compiled. (author)

  18. Repair-resistant mutation in Neurospora

    International Nuclear Information System (INIS)

    Stadler, D.; Macleod, H.; Loo, M.

    1987-01-01

    Chronic UV treatment produces severalfold fewer mutations in Neurospora conidia than does the same total dose of acute UV. Experiments were designed to determine the conditions required for chronic UV mutagenesis. Measurement of the coincidence frequency for two independent mutations revealed the existence of a subset of cells which are mutable by chronic UV. Analysis of forward mutation at the mtr locus showed that the genetic alterations produced by chronic UV were virtually all point mutants, even though the assay system could detect alterations or deletions extending into neighboring genes. A significant fraction of the mutants produced by acute UV were multigenic deletions. The size of the dose-rate effect (acute UV mutation frequency divided by chronic UV mutation frequency) was compared for several different mutation assay systems. Forward mutations (recessive lethals and mtr) gave values ranging from four to nine. For events which were restricted to specific molecular sites (specific reversions and nonsense suppressor mutations), there was a wider range of dose-rate ratios. This suggests that chronic UV mutation may be restricted to certain molecular sequences or configurations

  19. Mutation breedings in ornamental plants

    International Nuclear Information System (INIS)

    Matsubara, Hisao

    1984-01-01

    Several methods of obtaining somatic mutant plants by γ-ray irradiation on pieces of tissues as in vitro adventitious bud technique or small cutting methods with repeated pruning are described. 1) The irradiation to the adventitious buds in the small pieces of organ cultured in vitro and to the small cuttings are employed. Culture beds of agar or of Japanese Kanuma soil were used in vitro culture. In these experiments, Japanese Kanuma soil bed in in vitro culture worked well for root development and transplant of the induced mutants. 2) Combination with in vitro culture and repeated pruning technique were used for isolation and fixation of solid somatic mutant from small sectorial mutation induced by irradiation. This method was successful for begonia, chrysanthemum, aberia and winter daphne. 3) These data indicates that most of the induced mutant plants were non-chimeric, while a few others were chimeric. Among the new varieties, ''Gin-Sei'', ''Ryoku-Ha'', ''Big-Cross'', ''Kaede-Iron'', ''Mei-Fu-Hana-Tsukubane-Utsugi'' and ''Daphne-γ-3'' are non-chimeric, and ''Mini-Mini-Iron'' and ''Orange-Iron'' are chimeric. Moreover, these new varieties have remarkably differed in size and in color pattern from original variety. From the experimental results of somatic mutation, it is indicated that plant tissue culture have enormous potential in radiation breeding and in rapid propagation of the somatic mutant. (author)

  20. Mutation breeding in vegetable crops

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Takashi

    1984-03-01

    Vegetables breed by seeds and vegetative organs. In main vegetables, the differentiation of clopping types, the adoption of monoculture and year-round production and shipment are carried out, adapting to various socio-economic and cultivation conditions. Protected agriculture has advanced mainly for fruit vegetables, and the seeds for sale have become almost hybrid varieties. Reflecting this situation, the demand for breeding is diversified and characteristic. The present status of mutation breeding of vegetables is not yet well under way, but reports of about 40 raised varieties have been published in the world. The characters introduced by induced mutation and irradiation are compact form, harvesting aptitude, the forms and properties of stems and leaves, anti-lodging property, the size, form and uniformity of fruits, male sterility and so on. The radiation sources used were mostly gamma ray or X-ray, but sometimes, combined irradiation was used. Results obtained in Japan include: burdocks as an example to gamma ray irradiation of seeds; tomatoes as an example of inducing compound resistance against disease injury; and lettuce as an example of internal beta irradiation. (Kako, I.).

  1. Containment heat removal system

    International Nuclear Information System (INIS)

    Wade, G.E.; Barbanti, G.; Gou, P.F.; Rao, A.S.; Hsu, L.C.

    1992-01-01

    This patent describes a nuclear system of a type including a containment having a nuclear reactor therein, the nuclear reactor including a pressure vessel and a core in the pressure vessel, the system. It comprises a gravity pool of coolant disposed at an elevation sufficient to permit a flow of coolant into the nuclear reactor pressure vessel against a predetermined pressure within the nuclear reactor pressure vessel; means for reducing a pressure of steam in the nuclear reactor pressure vessel to a value less than the predetermined pressure in the event of a nuclear accident, the means including a depressurization valve connected to the pressure vessel, the means further including steam heat dissipating means such dissipating means including a suppression pool; a supply of water in the suppression pool, there being a headspace in the suppression pool above the water supply; a substantial amount of air in the head space; means for feeding pressurized steam from the nuclear reactor pressure vessel to a location under a surface of the supply of water, the supply of water being effective to absorb heat sufficient to reduce steam pressure below the predetermined pressure; and a check valve for communicating the headspace with the containment, the check valve being oriented to vent air in the headspace to the containment when a pressure in the headspace exceeds a pressure in the containment by a predetermined pressure differential

  2. WASTE CONTAINMENT OVERVIEW

    Science.gov (United States)

    BSE waste is derived from diseased animals such as BSE (bovine spongiform encepilopothy, also known as Mad Cow) in cattle and CWD (chronic wasting disease) in deer and elk. Landfilling is examined as a disposal option and this presentation introduces waste containment technology...

  3. Confinement contains condensates

    DEFF Research Database (Denmark)

    Brodsky, S. J.; Roberts, C. D.; Shrock, R.

    2012-01-01

    been viewed as constant empirical mass scales that fill all space-time, are instead wholly contained within hadrons; i.e., they are a property of hadrons themselves and expressed, e.g., in their Bethe-Salpeter or light-front wave functions. We explain that this paradigm is consistent with empirical...

  4. Containers, facilitators, innovators?

    DEFF Research Database (Denmark)

    Makkonen, Teemu; Merisalo, Maria; Inkinen, Tommi

    2018-01-01

    : are they containers, facilitators or innovators? This is investigated here through empirical material derived from 27 interviews with top departmental management in three Finnish cities (Helsinki, Espoo and Vantaa). The results show that local city governments (LCGs) consider cities as facilitators of innovation...

  5. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  6. Containing contraceptive costs

    African Journals Online (AJOL)

    April 2015, Vol. 105, No. 4. Containing contraceptive costs. There are about 7 billion people living on our planet. In many countries resources are strained and we seek to slow down the rate of population growth. There are obviously many factors that lead to rapid population growth. Contraceptive methods are an important.

  7. CONCRETE REACTOR CONTAINMENT

    Energy Technology Data Exchange (ETDEWEB)

    Lumb, Ralph F.; Hall, William F.; Fruchtbaum, Jacob

    1963-06-15

    The results of various leak-rate tests demonstrate the practicality of concrete as primary containment for the maximum credible accident for a research reactor employing plate-type fuel and having a power in excess of one megawatt. Leak-test time was shortened substantially by measuring the relaxation time for overpressure decay, which is a function of leak rate. (auth)

  8. Reactor containing facility

    International Nuclear Information System (INIS)

    Akagawa, Katsuhiko.

    1992-01-01

    A cooling space having a predetermined capacity is formed between a reactor container and concrete walls. A circulation loop disposed to the outside of the concrete walls is connected to the top and the bottom of the cooling space. The circulation loop has a circulation pump and a heat exchanger, and a cooling water supply pipe is connected to the upstream of the circulation pump for introducing cooling water from the outside. Upon occurrence of loss of coolant accident, cooling water is introduced from the cooling water supply pipe to the cooling space between the reactor container and the concrete walls after shut-down of the reactor operation. Then, cooling water is circulated while being cooled by the heat exchanger, to cool the reactor container by cooling water flown in the cooling space. This can cool the reactor container in a short period of time upon occurrence of the loss of coolant accident. Accordingly, a repairing operation for a ruptured portion can be conducted rapidly. (I.N.)

  9. Microarray-based mutation detection and phenotypic characterization in Korean patients with retinitis pigmentosa

    Science.gov (United States)

    Kim, Cinoo; Kim, Kwang Joong; Bok, Jeong; Lee, Eun-Ju; Kim, Dong-Joon; Oh, Ji Hee; Park, Sung Pyo; Shin, Joo Young; Lee, Jong-Young

    2012-01-01

    Purpose To evaluate microarray-based genotyping technology for the detection of mutations responsible for retinitis pigmentosa (RP) and to perform phenotypic characterization of patients with pathogenic mutations. Methods DNA from 336 patients with RP and 360 controls was analyzed using the GoldenGate assay with microbeads containing 95 previously reported disease-associated mutations from 28 RP genes. Mutations identified by microarray-based genotyping were confirmed by direct sequencing. Segregation analysis and phenotypic characterization were performed in patients with mutations. The disease severity was assessed by visual acuity, electroretinography, optical coherence tomography, and kinetic perimetry. Results Ten RP-related mutations of five RP genes (PRP3 pre-mRNA processing factor 3 homolog [PRPF3], rhodopsin [RHO], phosphodiesterase 6B [PDE6B], peripherin 2 [PRPH2], and retinitis pigmentosa 1 [RP1]) were identified in 26 of the 336 patients (7.7%) and in six of the 360 controls (1.7%). The p.H557Y mutation in PDE6B, which was homozygous in four patients and heterozygous in nine patients, was the most frequent mutation (2.5%). Mutation segregation was assessed in four families. Among the patients with missense mutations, the most severe phenotype occurred in patients with p.D984G in RP1; less severe phenotypes occurred in patients with p.R135W in RHO; a relatively moderate phenotype occurred in patients with p.T494M in PRPF3, p.H557Y in PDE6B, or p.W316G in PRPH2; and a mild phenotype was seen in a patient with p.D190N in RHO. Conclusions The results reveal that the GoldenGate assay may not be an efficient method for molecular diagnosis in RP patients with rare mutations, although it has proven to be reliable and efficient for high-throughput genotyping of single-nucleotide polymorphisms. The clinical features varied according to the mutations. Continuous effort to identify novel RP genes and mutations in a population is needed to improve the efficiency and

  10. Induced mutation for disease resistance in legumes

    International Nuclear Information System (INIS)

    Bravo, A.

    1984-01-01

    Mutation breeding has been used for developing genotypes that may contain resistance to: a) A necrotic strain of common mosaic virus, in common bean (Phaseolus vulgaris L.); b) Soil fungi causing root rots in chickpea (Cicer arietinum L.); c) The fungus Uromyces fabae that causes rust in lentil plants (Lens culinaria). Seeds of these three species were treated with gamma rays in doses of 1,000, 3,000, 6,000, and 9,000 rads. Treated materials and controls were grown during 1979. Chickpea M2 plants were grown in a naturally infested soil with soil-borne fungi. Lentil plants were sprayed with a suspension of spores of the rust fungus. Common bean M2 plants were sprayed with a solution containing virus particles. Ninety-three symptomless chickpea plants were identified in the M2 population. For lentil there were 47 symptomless plants and for common bean, 244 M2 plants with minor virus damage. Eight M3 progenies of chickpea, originated from symptomless M2 plants, had a high rate of survival and showed none or very little damage by root rots. In addition, some morphological changes were detected in other M3 chickpea progenies. Two progenies had larger leaflets, as compared to the control plants and those of other progenies. One progeny showed a more erect growth habit. These new traits have been attributed to genetic changes induced by the radiation treatments. By contrast to these promising results with chickpea no progress has been detected in the plant populations of common bean and lentil. (author)

  11. Diversity and frequency of kdr mutations within Anopheles sinensis populations from Guangxi, China.

    Science.gov (United States)

    Yang, Chan; Feng, Xiangyang; Huang, Zushi; Li, Mei; Qiu, Xinghui

    2016-08-15

    Anopheles sinensis is a major vector of malaria in China and its control is under great threat as the development of insecticide resistance. Voltage-gated sodium channel (VGSC) is the target of several classes of insecticides. Genetic mutations of VGSC have been documented to confer knockdown resistance (kdr) to dichlorodiphenyltrichloroethane (DDT) and pyrethroids in mosquitoes. To control this vector efficiently, it is important to know the resistance-associated genetic mutations, their distribution frequencies and genealogical relations. Three hundreds and thirteen (313) adults of An. sinensis collected from nine locations across Guangxi Zhuang Autonomous Region were used. The partial sequence of the An. sinensis voltage gated sodium channel gene (AS-VGSC) containing codon 1014 was sequenced. PHASE2.1 was used to construct the haplotypes of each individual, and the accuracy of haplotypes was further confirmed by clone sequencing. The genealogical relations of kdr mutations in AS-VGSC was analysed using TCS 2.1 and Network 5.0. Sixteen AS-VGSC haplotypes including seven haplotypes carrying non-synonymous mutations at codon 1014, and fifty-five AS-VGSC genotypes were identified from 313 mosquitoes collected from nine geographical locations across Guangxi. The number of haplotypes in each of the nine populations ranged from 5 to 13. The frequency of haplotypes carrying kdr mutations ranged from 2.7 to 80.0 % within the nine populations, of which 1014C was unexpectedly high in the northeast of Guangxi. Genealogical analysis suggested multiple origins of kdr mutations in An. sinensis. Diverse haplotypes of AS-VGSC are distributed in Guangxi. The presence of haplotypes carrying mutations at codon 1014 indicates a risk of pyrethroid and DDT resistance. The kdr mutations show differential distribution geographically, with high frequencies occurred in the northeast of Guangxi. Genealogical analysis suggests multiple origins of kdr mutations in An. sinensis populations

  12. Guanine holes are prominent targets for mutation in cancer and inherited disease.

    Directory of Open Access Journals (Sweden)

    Albino Bacolla

    Full Text Available Single base substitutions constitute the most frequent type of human gene mutation and are a leading cause of cancer and inherited disease. These alterations occur non-randomly in DNA, being strongly influenced by the local nucleotide sequence context. However, the molecular mechanisms underlying such sequence context-dependent mutagenesis are not fully understood. Using bioinformatics, computational and molecular modeling analyses, we have determined the frequencies of mutation at G • C bp in the context of all 64 5'-NGNN-3' motifs that contain the mutation at the second position. Twenty-four datasets were employed, comprising >530,000 somatic single base substitutions from 21 cancer genomes, >77,000 germline single-base substitutions causing or associated with human inherited disease and 16.7 million benign germline single-nucleotide variants. In several cancer types, the number of mutated motifs correlated both with the free energies of base stacking and the energies required for abstracting an electron from the target guanines (ionization potentials. Similar correlations were also evident for the pathological missense and nonsense germline mutations, but only when the target guanines were located on the non-transcribed DNA strand. Likewise, pathogenic splicing mutations predominantly affected positions in which a purine was located on the non-transcribed DNA strand. Novel candidate driver mutations and tissue-specific mutational patterns were also identified in the cancer datasets. We conclude that electron transfer reactions within the DNA molecule contribute to sequence context-dependent mutagenesis, involving both somatic driver and passenger mutations in cancer, as well as germline alterations causing or associated with inherited disease.

  13. Polycythemia and paraganglioma with a novel somatic HIF2A mutation in a male.

    Science.gov (United States)

    Toyoda, Hidemi; Hirayama, Jyunya; Sugimoto, Yuka; Uchida, Keiichi; Ohishi, Kohshi; Hirayama, Masahiro; Komada, Yoshihiro

    2014-06-01

    Recently, a new syndrome of paraganglioma, somatostatinoma, and polycythemia has been discovered (known as Pacak-Zhuang syndrome). This new syndrome, with somatic HIF2A gain-of-function mutations, has never been reported in male patients. We describe a male patient with Pacak-Zhuang syndrome who carries a newly discovered HIF2A mutation. Congenital polycythemias have diverse etiologies, including germline mutations in the oxygen-sensing pathway. These include von Hippel-Lindau (Chuvash polycythemia), prolyl hydroxylase domain-containing protein-2, and hypoxia-inducible factor-2α (HIF-2α). Somatic gain-of-function mutations in the gene encoding HIF-2α were reported in patients with paraganglioma and polycythemia and have been found exclusively in female patients. Through sequencing of the HIF2A using DNA from paraganglioma in 15-year-old male patient, we identified a novel mutation of HIF2A: a heterozygous C to A substitution at base 1589 in exon 12 of HIF2A. The mutation was not found in germline DNA from leukocytes. The C1589A mutations resulted in substitution of alanine 530 in the HIF-2α protein with glutamic acid. This mutation is undoubtedly associated with increased HIF-2α activity and increased protein half-life, because it affects the vicinity of the prolyl hydroxylase target residue, proline 531. To our knowledge, this is the first report describing Pacak-Zhuang syndrome with somatic gain-of-function mutation in HIF2A in a male patient. Congenital polycythemia of unknown origin should raise suspicion for the novel disorder Pacak-Zhuang syndrome, even in male patients. Copyright © 2014 by the American Academy of Pediatrics.

  14. Novel Secondary Somatic Mutations in Ewing's Sarcoma and Desmoplastic Small Round Cell Tumors

    Science.gov (United States)

    Janku, Filip; Ludwig, Joseph A.; Naing, Aung; Benjamin, Robert S.; Brown, Robert E.; Anderson, Pete; Kurzrock, Razelle

    2014-01-01

    Background Ewing's sarcoma (ES) and desmoplastic small round cell tumors (DSRCT) are small round blue cell tumors driven by an N-terminal containing EWS translocation. Very few somatic mutations have been reported in ES, and none have been identified in DSRCT. The aim of this study is to explore potential actionable mutations in ES and DSRCT. Methodology Twenty eight patients with ES or DSRCT had tumor tissue available that could be analyzed by one of the following methods: 1) Next-generation exome sequencing platform; 2) Multiplex PCR/Mass Spectroscopy; 3) Polymerase chain reaction (PCR)-based single- gene mutation screening; 4) Sanger sequencing; 5) Morphoproteomics. Principal Findings Novel somatic mutations were identified in four out of 18 patients with advanced ES and two of 10 patients with advanced DSRCT (six out of 28 (21.4%));KRAS (n = 1), PTPRD (n = 1), GRB10 (n = 2), MET (n = 2) and PIK3CA (n = 1). One patient with both PTPRD and GRB10 mutations and one with a GRB10 mutation achieved a complete remission (CR) on an Insulin like growth factor 1 receptor (IGF1R) inhibitor based treatment. One patient, who achieved a partial remission (PR) with IGF1R inhibitor treatment, but later developed resistance, demonstrated a KRAS mutation in the post-treatment resistant tumor, but not in the pre-treatment tumor suggesting that the RAF/RAS/MEK pathway was activated with progression. Conclusions We have reported several different mutations in advanced ES and DSRCT that have direct implications for molecularly-directed targeted therapy. Our technology agnostic approach provides an initial mutational roadmap used in the path towards individualized combination therapy. PMID:25119929

  15. Mutation Analysis in Classical Phenylketonuria Patients Followed by Detecting Haplotypes Linked to Some PAH Mutations.

    Science.gov (United States)

    Dehghanian, Fatemeh; Silawi, Mohammad; Tabei, Seyed M B

    2017-02-01

    Deficiency of phenylalanine hydroxylase (PAH) enzyme and elevation of phenylalanine in body fluids cause phenylketonuria (PKU). The gold standard for confirming PKU and PAH deficiency is detecting causal mutations by direct sequencing of the coding exons and splicing involved sequences of the PAH gene. Furthermore, haplotype analysis could be considered as an auxiliary approach for detecting PKU causative mutations before direct sequencing of the PAH gene by making comparisons between prior detected mutation linked-haplotypes and new PKU case haplotypes with undetermined mutations. In this study, 13 unrelated classical PKU patients took part in the study detecting causative mutations. Mutations were identified by polymerase chain reaction (PCR) and direct sequencing in all patients. After that, haplotype analysis was performed by studying VNTR and PAHSTR markers (linked genetic markers of the PAH gene) through application of PCR and capillary electrophoresis (CE). Mutation analysis was performed successfully and the detected mutations were as follows: c.782G>A, c.754C>T, c.842C>G, c.113-115delTCT, c.688G>A, and c.696A>G. Additionally, PAHSTR/VNTR haplotypes were detected to discover haplotypes linked to each mutation. Mutation detection is the best approach for confirming PAH enzyme deficiency in PKU patients. Due to the relatively large size of the PAH gene and high cost of the direct sequencing in developing countries, haplotype analysis could be used before DNA sequencing and mutation detection for a faster and cheaper way via identifying probable mutated exons.

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

    International Nuclear Information System (INIS)

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

    1976-01-01

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

  17. Germline cytotoxic lymphocytes defective mutations in Chinese patients with lymphoma

    OpenAIRE

    Chen, Xue; Zhang, Yang; Wang, Fang; Wang, Mangju; Teng, Wen; Lin, Yuehui; Han, Xiangping; Jin, Fangyuan; Xu, Yuanli; Cao, Panxiang; Fang, Jiancheng; Zhu, Ping; Tong, Chunrong; Liu, Hongxing

    2017-01-01

    Certain patients with lymphoma may harbor mutations in perforin 1 (PRF1), unc-13 homolog D (UNC13D), syntaxin 11 (STX11), STXBP2 (syntaxin binding protein 2) or SH2 domain containing 1A (SH2D1A), which causes functional defects of cytotoxic lymphocytes. Data regarding the association between genetic defects and the development of lymphoma in Chinese patients are limited to date. In the present study, 90 patients with lymphoma were analyzed for UNC13D, PRF1, STXBP2, STX11, SH2D1A and X-linked ...

  18. Reactor container facility

    International Nuclear Information System (INIS)

    Saito, Takashi; Nagasaka, Hideo.

    1990-01-01

    A dry-well pool for spontaneously circulating stored pool water and a suppression pool for flooding a pressure vessel by feeding water, when required, to a flooding gap by means of spontaneous falling upto the flooding position, thereby flooding the pressure vessel are contained at the inside of a reactor container. Thus, when loss of coolant accidents such as caused by main pipe rupture accidents should happen, pool water in the suppression pool is supplied to the flooding gap by spontaneously falling. Further, if the flooding water uprises exceeding a predetermined level, the flooding gap is in communication with the dry-well pool at the upper and the lower portions respectively. Accordingly, flooding water at high temperature heated by the after-heat of the reactor core is returned again into the flooding gap to cool the reactor core repeatedly. (T.M.)

  19. Nuclear reactor container

    International Nuclear Information System (INIS)

    Fujimoto, Kiyoshi; Kataoka, Yoshiyuki; Murase, Michio; Fujii, Tadashi; Susuki, Akira.

    1994-01-01

    A wet well space above a pressure suppression pool is divided into a first wet well on the side in contact with the pressure suppression pool and a second wet well on the side not in contact with the pool. Cooling water is contained in the second wet well and it is in communication with the first wet well by pipelines. Since steams flown into the second well are condensed in the cooling water, they continuously transfer from the first wet well to the second wet well, thereby capable of eliminating the effects of incondensible gases in the first wet well. With such procedures, the effect of the incondensible gases can be eliminated even without cooling from the outside of the reactor. Heat accumulation can be increased in a container of any material, so that thermal load on cooling circuits for removing after-heat can be mitigated. (T.M.)

  20. Nuclear steam system containment

    International Nuclear Information System (INIS)

    Jabsen, F.

    1980-01-01

    An improved containment used for radiation shielding and pressure suppression comprising a dry well includes a pressure vessel, a plurality of concentric wall means, said plurality of concentric wall means defining at least three annular regions about said dry well. A first annular region provides the containment used for radiation shielding, a second annular region is substantially dry, a third annular region provides a wet well for relieving fluid pressure released from the pressure vessel into the dry well. Pipe connection means extend in the wet well from the dry well, a pool of liquid is disposed to partially fill said third annular region, the upper end portion of the second and third annular regions having an enclosure, and a plurality of baffle plates extending vertically downward from said enclosure in said third annular region into said pool of liquid so as to circumferentially divide the upper portion of said third annular region into a plurality of circumferential upper portions

  1. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogeno...... of the solutions used in the study nor was it present as a residual material in blank HPLC runs. CONCLUSIONS: Morphine is present in human gliomas, suggesting that it may exert an action that effects tumour physiology/pathology.......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  2. Steel containment buckling

    International Nuclear Information System (INIS)

    Bennett, J.G.; Fly, G.W.; Baker, W.E.

    1984-01-01

    The Steel Containment Buckling program is in its fourth phase of work directed at the evaluation of the effects of the structural failure mode of steel containments when the membrane stresses are compressive. The structural failure mode for this state of stress is instability or buckling. The program to date has investigated: (1) the effect on overall buckling capacity of the ASME area replacement method for reinforcing around circular penetrations; (2) a set of benchmark experiments on ring-stiffened shells having reinforced and framed penetrations; (3) large and small scale experiments on knuckle region buckling from internal pressure and post-buckling behavior to failure for vessel heads having torispherical geometries; and (4) buckling under time-dependent loadings (dynamic buckling). The first two investigations are complete, the knuckle buckling experimental efforts are complete with data analysis and reporting in progress, and the dynamic buckling experimental and analytical work is in progress

  3. BWR steel containment corrosion

    Energy Technology Data Exchange (ETDEWEB)

    Tan, C.P.; Bagchi, G.

    1996-04-01

    The report describes regulatory actions taken after corrosion was discovered in the drywell at the Oyster Creek Plant and in the torus at the Nine Mile Point 1 Plant. The report describes the causes of corrosion, requirements for monitoring corrosion, and measures to mitigate the corrosive environment for the two plants. The report describes the issuances of generic letters and information notices either to collect information to determine whether the problem is generic or to alert the licensees of similar plants about the existence of such a problem. Implementation of measures to enhance the containment performance under severe accident conditions is discussed. A study by Brookhaven National Laboratory (BNL) of the performance of a degraded containment under severe accident conditions is summarized. The details of the BNL study are in the appendix to the report.

  4. Container for centrifuging blood

    International Nuclear Information System (INIS)

    Narra, R.K.

    1982-01-01

    A container is described for use in drawing patient's blood, centrifuging the blood and then labelling the separated red cells with sup(99m)Tc. It consists of a tube with a central chamber and a lower portion provided with an aperture in which a weir is supported and extends into the central chamber. The weir has a central channel. A resilient plug seals the aperture. (author)

  5. Hydrogen storage container

    Science.gov (United States)

    Wang, Jy-An John; Feng, Zhili; Zhang, Wei

    2017-02-07

    An apparatus and system is described for storing high-pressure fluids such as hydrogen. An inner tank and pre-stressed concrete pressure vessel share the structural and/or pressure load on the inner tank. The system and apparatus provide a high performance and low cost container while mitigating hydrogen embrittlement of the metal tank. System is useful for distributing hydrogen to a power grid or to a vehicle refueling station.

  6. Nuclear reactor container

    International Nuclear Information System (INIS)

    Hosaka, Seiichi.

    1988-01-01

    Cables coverd with non-halogen covering material are used as electric wire cables wired for supplying electric power to a reactor recycling pump. Silicone rubber having specified molecular formula is used for the non-halogen covering material. As a result, formation of chlorine in a nuclear reactor container can be eliminated and increase in the deposited salts to SUS pipeways, etc. can be prevented, to avoid the occurrence of stress corrosion cracks. (H.T.)

  7. Materials designed for containments

    International Nuclear Information System (INIS)

    Piehl, K.H.

    1976-01-01

    The present article points out that high-tensile fine-grained steels have been used successfully in the construction of reactor containments, spherical gasometers, and pressure vessels. It has been confirmed that their use requires safety measures concerning lay out and production. Viscosity properties of high-tensile, fine-grained steels can be improved significantly by means of electroslag remelting. The extent to which this improvement influences the heat-affected zone is being examined. (orig./RW) [de

  8. Mutations in LRRC50 predispose zebrafish and humans to seminomas.

    Directory of Open Access Journals (Sweden)

    Sander G Basten

    2013-04-01

    Full Text Available Seminoma is a subclass of human testicular germ cell tumors (TGCT, the most frequently observed cancer in young men with a rising incidence. Here we describe the identification of a novel gene predisposing specifically to seminoma formation in a vertebrate model organism. Zebrafish carrying a heterozygous nonsense mutation in Leucine-Rich Repeat Containing protein 50 (lrrc50 also called dnaaf1, associated previously with ciliary function, are found to be highly susceptible to the formation of seminomas. Genotyping of these zebrafish tumors shows loss of heterozygosity (LOH of the wild-type lrrc50 allele in 44.4% of tumor samples, correlating with tumor progression. In humans we identified heterozygous germline LRRC50 mutations in two different pedigrees with a family history of seminomas, resulting in a nonsense Arg488* change and a missense Thr590Met change, which show reduced expression of the wild-type allele in seminomas. Zebrafish in vivo complementation studies indicate the Thr590Met to be a loss-of-function mutation. Moreover, we show that a pathogenic Gln307Glu change is significantly enriched in individuals with seminoma tumors (13% of our cohort. Together, our study introduces an animal model for seminoma and suggests LRRC50 to be a novel tumor suppressor implicated in human seminoma pathogenesis.

  9. Familial neurohypophyseal diabetes insipidus associated with a signal peptide mutation

    Energy Technology Data Exchange (ETDEWEB)

    McLeod, J.F.; Gaskill, M.B.; Bradley, G.S.; Robertson, G.L. (Northwestern Univ. Medical School, Chicago, IL (United States)); Kovacs, L. (Comenius Univ. Medical School, Bratislava (Slovakia)); Rittig, S. (Univ. of Aarhus, Aarhus (Denmark))

    1993-09-01

    The authors studied the pathophysiology, natural history, and genetic basis of familial neurohypophyseal diabetes insipidus (FNDI) in a caucasian kindred. Twelve members had polyuria and a deficiency of plasma vasopressin (AVP), which progressed in severity over time. Another had normal urine volumes and plasma AVP when first tested at age 3 yr, but developed severe FNDI a year later. For unknown reasons, one man had a normal urine volume despite severe AVP deficiency and a history of polyuria in the past. When the AVP-neurophysin-II gene was amplified and sequenced, exon 2/3 was normal, but 7 of 12 clones of exon 1 contained a base substitution (G[yields]A) predicting a substitution of threonine for alanine at the -1 position of the signal peptide. Restriction analysis found the mutation in all 14 affected members, but in none of the 41 controls of 19 adult members with normal urine volumes and plasma or urinary AVP (lod score = 5.7). The mutation was also found in 2 infants in whom AVP was normal when tested at 6 and 9 months of age. We hypothesize that a mutation in exon 1 of the AVP-neurophysin-II gene caused FNDI in this kindred by making an abnormally processed precursor that gradually destroys vasopressinergic neurons. 46 refs., 6 figs.

  10. Containment structure tendon investigation

    International Nuclear Information System (INIS)

    Fulton, J.F.; Murray, K.H.

    1983-01-01

    The paper describes an investigation into the possible causes of lower-than-predicted tendon forces which were measured during past tendon surveillances for a concrete containment. The containment is post tensioned by vertical tendons which are anchored into a rock foundation. The tendons were originally stressed in 1969, and lift-off tests were performed on six occasions subsequent to this date over a period of 11 years. The tendon forces measured in these tests were generally lower than predicted, and by 1979 the prestress level in the containment was only marginally above the design requirement. The tendons were retensioned in 1980, and by this time an investigation into the possible causes was underway. Potential causes investigated include the rock anchors and surrounding rock, elastomeric pad creep, wire stresses, thermal effects, stressing equipment and lift-off procedures, and wire stress relaxation. The investigation activities included stress relaxation testing of wires pulled from actual tendons. The stress relaxation test program included wire specimens at several different temperature and initial stress levels and the effect of a varying temperature history on the stress relaxation property of the wires. For purpose of future force predictions of the retensioned tendons, the test program included tests to determine the effect on stress relaxation due to restressing the wires after they had relaxed for 1000 hours and 10,000 hours. (orig./GL)

  11. Nuclear reactor container

    International Nuclear Information System (INIS)

    Fukui, Tooru; Murase, Michio; Kataoka, Yoshiyuki; Hidaka, Masataka; Sumita, Isao; Tominaga, Kenji.

    1992-01-01

    In a nuclear reactor container, a chamber in communication with a wet well of a pressure suppression chamber is disposed and situated to such a position that the temperature is lower than a chamber containing pool water upon occurrence of loss of coolant accident. In addition, the inner surface of the pressure suppression chamber is constituted with steel walls in contact with pool water, and an outer circumferential pool is disposed at the outer circumferential surface thereof. Further, a circulation channel is disposed, and a water intake port is disposed at a position higher than an exit to the pool water, and a water discharge port is opened in the pool water at a position lower than the exit to the pool water. With such a constitution, the allowable temperature of the pressure suppression pool water can be elevated to a saturated steam temperature corresponding to the resistant pressure of the container, so that the temperature difference between the pressure suppression pool and the outer side thereof is increased by so much, to improve thermal radiation performance. Accordingly, it can be utilized as a pressure suppression means for a plant of greater power. Further, thermal conduction efficiency from the pool water region of the pressure suppression chamber to the outer circumferential pool water is improved, or thermal radiation area is enlarged due to the circulation channel, to improve the heat radiation performance. (N.H.)

  12. Container for liquid metal

    International Nuclear Information System (INIS)

    Abe, Yoshihito; Imazu, Takayuki; Ueda, Sabuo; Ueya, Katsumi.

    1980-01-01

    Purpose: To arrange a vapor trapping member of a specific structure at the inlet part of a cylindrical gap formed by the inner peripheral surface of the circular opening of a container and the outer peripheral surface of a rotary plug thereby to prevent ingress of vapor in the upper part of the cylindrical gap for a long period of time. Constitution: A sealing material receiving tray is fitted to the container side of the inlet part of a cylindrical gap, and a partition plate is fitted to the rotary plug side. The tray is filled with a sealing material consisting of a large number of steel balls, mesh wire gages and the like, and the partition plate is placed in the tray thereby to carry out sealing of the container. Liquid metal vapor evaporating from the liquid level of the liquid metal adheres to the sealing material to fill the gap, and therefore ingress of vapor to the upper part of the cylindrical gap is prevented, and there is no possibility of causing seal cutting due to the use for a long period. (Sekiya, K.)

  13. Genome Analysis of a Transmissible Lineage of Pseudomonas aeruginosa Reveals Pathoadaptive Mutations and Distinct Evolutionary Paths of Hypermutators

    DEFF Research Database (Denmark)

    Marvig, Rasmus Lykke; Johansen, Helle Krogh; Molin, Søren

    2013-01-01

    Genome sequencing of bacterial pathogens has advanced our understanding of their evolution, epidemiology, and response to antibiotic therapy. However, we still have only a limited knowledge of the molecular changes in in vivo evolving bacterial populations in relation to long-term, chronic...... targeted by mutations to optimize pathogen fitness (pathoadaptive mutations). These genes were related to antibiotic resistance, the cell envelope, or regulatory functions, and we find that the prevalence of pathoadaptive mutations correlates with evolutionary success of co-evolving sub-lineages. The long...... likelihood to acquire mutations and identify two homopolymer-containing genes preferentially mutated in hypermutators. This homopolymer facilitated differential mutagenesis provides a novel genome-wide perspective on the different evolutionary trajectories of hypermutators, which may help explain...

  14. Containment Code Validation Matrix

    International Nuclear Information System (INIS)

    Chin, Yu-Shan; Mathew, P.M.; Glowa, Glenn; Dickson, Ray; Liang, Zhe; Leitch, Brian; Barber, Duncan; Vasic, Aleks; Bentaib, Ahmed; Journeau, Christophe; Malet, Jeanne; Studer, Etienne; Meynet, Nicolas; Piluso, Pascal; Gelain, Thomas; Michielsen, Nathalie; Peillon, Samuel; Porcheron, Emmanuel; Albiol, Thierry; Clement, Bernard; Sonnenkalb, Martin; Klein-Hessling, Walter; Arndt, Siegfried; Weber, Gunter; Yanez, Jorge; Kotchourko, Alexei; Kuznetsov, Mike; Sangiorgi, Marco; Fontanet, Joan; Herranz, Luis; Garcia De La Rua, Carmen; Santiago, Aleza Enciso; Andreani, Michele; Paladino, Domenico; Dreier, Joerg; Lee, Richard; Amri, Abdallah

    2014-01-01

    The Committee on the Safety of Nuclear Installations (CSNI) formed the CCVM (Containment Code Validation Matrix) task group in 2002. The objective of this group was to define a basic set of available experiments for code validation, covering the range of containment (ex-vessel) phenomena expected in the course of light and heavy water reactor design basis accidents and beyond design basis accidents/severe accidents. It was to consider phenomena relevant to pressurised heavy water reactor (PHWR), pressurised water reactor (PWR) and boiling water reactor (BWR) designs of Western origin as well as of Eastern European VVER types. This work would complement the two existing CSNI validation matrices for thermal hydraulic code validation (NEA/CSNI/R(1993)14) and In-vessel core degradation (NEA/CSNI/R(2001)21). The report initially provides a brief overview of the main features of a PWR, BWR, CANDU and VVER reactors. It also provides an overview of the ex-vessel corium retention (core catcher). It then provides a general overview of the accident progression for light water and heavy water reactors. The main focus is to capture most of the phenomena and safety systems employed in these reactor types and to highlight the differences. This CCVM contains a description of 127 phenomena, broken down into 6 categories: - Containment Thermal-hydraulics Phenomena; - Hydrogen Behaviour (Combustion, Mitigation and Generation) Phenomena; - Aerosol and Fission Product Behaviour Phenomena; - Iodine Chemistry Phenomena; - Core Melt Distribution and Behaviour in Containment Phenomena; - Systems Phenomena. A synopsis is provided for each phenomenon, including a description, references for further information, significance for DBA and SA/BDBA and a list of experiments that may be used for code validation. The report identified 213 experiments, broken down into the same six categories (as done for the phenomena). An experiment synopsis is provided for each test. Along with a test description

  15. Mutation update for the PORCN gene

    NARCIS (Netherlands)

    Lombardi, Maria Paola; Bulk, Saskia; Celli, Jacopo; Lampe, Anne; Gabbett, Michael T.; Ousager, Lillian Bomme; van der Smagt, Jasper J.; Soller, Maria; Stattin, Eva-Lena; Mannens, Marcel A. M. M.; Smigiel, Robert; Hennekam, Raoul C.

    2011-01-01

    Mutations in the PORCN gene were first identified in Goltz-Gorlin syndrome patients in 2007. Since then, several reports have been published describing a large variety of genetic defects resulting in the Goltz-Gorlin syndrome, and mutations or deletions were also reported in angioma serpiginosum,

  16. Gene mutations in children with chronic pancreatitis.

    Science.gov (United States)

    Witt, H

    2001-01-01

    In the last few years, several genes have been identified as being associated with hereditary and idiopathic chronic pancreatitis (CP), i.e. PRSS1, CFTR and SPINK1. In this study, we investigated 164 unrelated children and adolescents with CP for mutations in disease-associated genes by direct DNA sequencing, SSCP, RFLP and melting curve analysis. In 15 patients, we detected a PRSS1 mutation (8 with A16V, 5 with R122H, 2 with N29I), and in 34 patients, a SPINK1 mutation (30 with N34S, 4 with others). SPINK1 mutations were predominantly found in patients without a family history (29/121). Ten patients were homozygous for N34S, SPINK1 mutations were most common in 'idiopathic' CP, whereas patients with 'hereditary' CP predominantly showed a PRSS1 mutation (R122H, N29I). In patients without a family history, the most common PRSS1 mutation was A16V (7/121). In conclusion, our data suggest that CP may be inherited in a dominant, recessive or multigenetic manner as a result of mutations in the above-mentioned or as yet unidentified genes. This challenges the concept of idiopathic CP as a nongenetic disorder and the differentiation between hereditary and idiopathic CP. Therefore, we propose to classify CP as either 'primary CP' (with or without a family history) or 'secondary CP' caused by toxic, metabolic or other factors.

  17. 'A' by Aspergillus terreus through mutation

    African Journals Online (AJOL)

    The highest drug yielding isolate FCBP-58 was subjected to both physical and chemical mutation to increase the biosynthetic capabilities of Cyclosporin 'A'. In this study, mutation was carried out by ultraviolet radiation (254 nm) and alkylating agent ethylmethane sulphonate (EMS). UV 5 min time treatment was proved to be ...

  18. TFAP2B mutation and dental anomalies.

    Science.gov (United States)

    Tanasubsinn, Natchaya; Sittiwangkul, Rekwan; Pongprot, Yupada; Kawasaki, Katsushige; Ohazama, Atsushi; Sastraruji, Thanapat; Kaewgahya, Massupa; Kantaputra, Piranit Nik

    2017-08-01

    Mutations inTFAP2B has been reported in patients with isolated patent ductus arteriosus (PDA) and Char syndrome. We performed mutation analysis of TFAP2B in 43 patients with isolated PDA, 7 patients with PDA with other congenital heart defects and 286 patients with isolated tooth agenesis with or without other dental anomalies. The heterozygous c.1006G>A mutation was identified in 20 individuals. Those mutation carriers consisted of 1 patient with term PDA (1/43), 16 patients with isolated tooth agenesis with or without other dental anomalies (16/286; 5.6%), 1 patient with PDA and severe valvular aortic stenosis and tooth agenesis (1/4) and 2 normal controls (2/100; 1%). The mutation is predicted to cause an amino-acid substitution p.Val336Ile in the TFAP2B protein. Tfap2b expression during early mouse tooth development supports the association of TFAP2B mutation and dental anomalies. It is hypothesized that this incidence might have been the result of founder effect. Here we report for the first time that TFAP2B mutation is associated with tooth agenesis, microdontia, supernumerary tooth and root maldevelopment. In addition, we also found that TFAP2B mutations, the common causes of PDA in Caucasian, are not the common cause of PDA in Thai population.

  19. Expanding CEP290 mutational spectrum in ciliopathies

    NARCIS (Netherlands)

    Travaglini, Lorena; Brancati, Francesco; Attie-Bitach, Tania; Audollent, Sophie; Bertini, Enrico; Kaplan, Josseline; Perrault, Isabelle; Iannicelli, Miriam; Mancuso, Brunella; Rigoli, Luciana; Rozet, Jean-Michel; Swistun, Dominika; Tolentino, Jerlyn; Dallapiccola, Bruno; Gleeson, Joseph G.; Valente, Enza Maria; Zankl, A.; Leventer, R.; Grattan-Smith, P.; Janecke, A.; D'Hooghe, M.; Sznajer, Y.; van Coster, R.; Demerleir, L.; Dias, K.; Moco, C.; Moreira, A.; Kim, C. Ae; Maegawa, G.; Petkovic, D.; Abdel-Salam, G. M. H.; Abdel-Aleem, A.; Zaki, M. S.; Marti, I.; Quijano-Roy, S.; Sigaudy, S.; de Lonlay, P.; Romano, S.; Touraine, R.; Koenig, M.; Lagier-Tourenne, C.; Messer, J.; Collignon, P.; Wolf, N.; Philippi, H.; Kitsiou Tzeli, S.; Halldorsson, S.; Johannsdottir, J.; Ludvigsson, P.; Phadke, S. R.; Udani, V.; Stuart, B.; Magee, A.; Lev, D.; Michelson, M.; Ben-Zeev, B.; Fischetto, R.; Benedicenti, F.; Stanzial, F.; Borgatti, R.; Accorsi, P.; Battaglia, S.; Fazzi, E.; Giordano, L.; Pinelli, L.; Boccone, L.; Bigoni, S.; Ferlini, A.; Donati, M. A.; Caridi, G.; Divizia, M. T.; Faravelli, F.; Ghiggeri, G.; Pessagno, A.; Briguglio, M.; Briuglia, S.; Salpietro, C. D.; Tortorella, G.; Adami, A.; Castorina, P.; Lalatta, F.; Marra, G.; Riva, D.; Scelsa, B.; Spaccini, L.; Uziel, G.; del Giudice, E.; Laverda, A. M.; Ludwig, K.; Permunian, A.; Suppiej, A.; Signorini, S.; Uggetti, C.; Battini, R.; Di Giacomo, M.; Cilio, M. R.; Di Sabato, M. L.; Leuzzi, V.; Parisi, P.; Pollazzon, M.; Silengo, M.; de Vescovi, R.; Greco, D.; Romano, C.; Cazzagon, M.; Simonati, A.; Al-Tawari, A. A.; Bastaki, L.; Mégarbané, A.; Sabolic Avramovska, V.; de Jong, M. M.; Stromme, P.; Koul, R.; Rajab, A.; Azam, M.; Barbot, C.; Martorell Sampol, L.; Rodriguez, B.; Pascual-Castroviejo, I.; Teber, S.; Anlar, B.; Comu, S.; Karaca, E.; Kayserili, H.; Yüksel, A.; Akcakus, M.; Al Gazali, L.; Sztriha, L.; Nicholl, D.; Woods, C. G.; Bennett, C.; Hurst, J.; Sheridan, E.; Barnicoat, A.; Hennekam, R.; Lees, M.; Blair, E.; Bernes, S.; Sanchez, H.; Clark, A. E.; DeMarco, E.; Donahue, C.; Sherr, E.; Hahn, J.; Sanger, T. D.; Gallager, T. E.; Dobyns, W. B.; Daugherty, C.; Krishnamoorthy, K. S.; Sarco, D.; Walsh, C. A.; McKanna, T.; Milisa, J.; Chung, W. K.; de Vivo, D. C.; Raynes, H.; Schubert, R.; Seward, A.; Brooks, D. G.; Goldstein, A.; Caldwell, J.; Finsecke, E.; Maria, B. L.; Holden, K.; Cruse, R. P.; Swoboda, K. J.; Viskochil, D.

    2009-01-01

    Ciliopathies are an expanding group of rare conditions characterized by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears an intriguing allelic spectrum, being commonly mutated in Joubert

  20. p53 mutations promote proteasomal activity.

    Science.gov (United States)

    Oren, Moshe; Kotler, Eran

    2016-07-27

    p53 mutations occur very frequently in human cancer. Besides abrogating the tumour suppressive functions of wild-type p53, many of those mutations also acquire oncogenic gain-of-function activities. Augmentation of proteasome activity is now reported as a common gain-of-function mechanism shared by different p53 mutants, which promotes cancer resistance to proteasome inhibitors.

  1. MT-CYB mutations in hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Hagen, Christian M; Aidt, Frederik H; Havndrup, Ole

    2013-01-01

    Mitochondrial dysfunction is a characteristic of heart failure. Mutations in mitochondrial DNA, particularly in MT-CYB coding for cytochrome B in complex III (CIII), have been associated with isolated hypertrophic cardiomyopathy (HCM). We hypothesized that MT-CYB mutations might play an important...... and m.15482T>C; p.S246P were identified. Modeling showed that the p.C93Y mutation leads to disruption of the tertiary structure of Cytb by helix displacement, interfering with protein-heme interaction. The p.S246P mutation induces a diproline structure, which alters local secondary structure and induces...... of HCM patients. We propose that further patients with HCM should be examined for mutations in MT-CYB in order to clarify the role of these variants....

  2. Survival of mutations arising during invasions.

    Science.gov (United States)

    Miller, Judith R

    2010-03-01

    When a neutral mutation arises in an invading population, it quickly either dies out or 'surfs', i.e. it comes to occupy almost all the habitat available at its time of origin. Beneficial mutations can also surf, as can deleterious mutations over finite time spans. We develop descriptive statistical models that quantify the relationship between the probability that a mutation will surf and demographic parameters for a cellular automaton model of surfing. We also provide a simple analytic model that performs well at predicting the probability of surfing for neutral and beneficial mutations in one dimension. The results suggest that factors - possibly including even abiotic factors - that promote invasion success may also increase the probability of surfing and associated adaptive genetic change, conditioned on such success.

  3. Genaesthics : Breast Surgery in BRCA1/2 Gene Mutation Carriers

    NARCIS (Netherlands)

    V.M.T. van Verschuer (Victorien)

    2017-01-01

    markdownabstractThe present thesis focuses on breast surgery in BRCA1/2 gene mutation carriers. The topics that are studied vary broadly, representing the multiple disciplines that are involved in the diagnostic work-up and treatment of BRCA1/2-associated breast cancer. The first part contains

  4. FBXW7 mutations in patients with advanced cancers: clinical and molecular characteristics and outcomes with mTOR inhibitors.

    Directory of Open Access Journals (Sweden)

    Denis L Jardim

    Full Text Available FBXW7 is a tumor suppressor gene responsible for the degradation of several proto-oncogenes. Preclinical data suggest that FBXW7 mutations sensitize cells to mTOR inhibitors. Clinicopathologic characteristics of cancer patients with FBXW7 mutations and their responses to mTOR inhibitors remain unknown.Using multiplex gene panels we evaluated how the FBXW7 mutation affected the cancer phenotype of patients referred to a phase I clinic starting January 2012. Whenever possible patients positive for FBXW7 mutation were treated with regimens containing an mTOR inhibitors and their outcomes were reviewed.FBXW7 mutations were detected in 17 of 418 patients (4.0%. Among tumor types with more than 10 patients tested, FBXW7 mutations occurred in colorectal cancer (7/49; 14.3%, squamous cell cancer of head and neck (2/18; 11.1%, liver (1/13; 7.7%, and ovarian cancers (1/40; 2.5%. No one clinical, pathological or demographic feature was characteristic of the FBXW7-mutated patient population. The mutation occurred in isolation in only 2/17 (12% patients, and KRAS was frequently found as a concomitant mutation, especially in patients with colorectal cancer (6/7; 86%. Ten patients were treated on a protocol containing an mTOR inhibitor, with a median time to treatment failure of 2.8 months (range, 1.3-6.8. One patient with liver cancer (fibrolamellar subtype continues to have a prolonged stable disease for 6.8+ months.In patients with advanced cancers, somatic mutations in FBXW7 usually occur with other simultaneous molecular aberrations, which can contribute to limited therapeutic efficacy of mTOR inhibitors.

  5. Containment condensing heat transfer

    International Nuclear Information System (INIS)

    Gido, R.G.; Koestel, A.

    1983-01-01

    This report presents a mechanistic heat-transfer model that is valid for large scale containment heat sinks. The model development is based on the determination that the condensation is controlled by mass diffusion through the vapor-air boundary layer, and the application of the classic Reynolds' analogy to formulate expressions for the transfer of heat and mass based on hydrodynamic measurements of the momentum transfer. As a result, the analysis depends on the quantification of the shear stress (momentum transfer) at the interface between the condensate film and the vapor-air boundary layer. In addition, the currently used Tagami and Uchida test observations and their range of applicability are explained

  6. Identification of a novel BRCA1 nucleotide 4803delCC/c.4684delCC mutation and a nucleotide 249T>A/c.130T>A (p.Cys44Ser) mutation in two Greenlandic Inuit families

    DEFF Research Database (Denmark)

    Hansen, Thomas van Overeem; Jønson, Lars; Albrechtsen, Anders

    2010-01-01

    Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We have recently identified a Greenlandic Inuit BRCA1 nucleotide 234T>G/c.115T>G (p.Cys39Gly) founder mutation, which at that time was the only disease-causing BRCA1/BRCA2 mutation...... identified in this population. Here, we describe the identification of a novel disease-causing BRCA1 nucleotide 4803delCC/c.4684delCC mutation in a Greenlandic Inuit with ovarian cancer. The mutation introduces a frameshift and a premature stop at codon 1572. We have also identified a BRCA1 nucleotide 249T......>A/c.130T>A (p.Cys44Ser) mutation in another Greenlandic individual with ovarian cancer. This patient share a 1-2 Mb genomic fragment, containing the BRCA1 gene, with four Danish families harbouring the same mutation, suggesting that the 249T>A/c.130T>A (p.Cys44Ser) mutation originates from a Danish...

  7. Tyr120Asp mutation alters domain flexibility and dynamics of MeCP2 DNA binding domain leading to impaired DNA interaction: Atomistic characterization of a Rett syndrome causing mutation.

    Science.gov (United States)

    D'Annessa, Ilda; Gandaglia, Anna; Brivio, Elena; Stefanelli, Gilda; Frasca, Angelisa; Landsberger, Nicoletta; Di Marino, Daniele

    2018-05-01

    Mutations in the X-linked MECP2 gene represent the main origin of Rett syndrome, causing a profound intellectual disability in females. MeCP2 is an epigenetic transcriptional regulator containing two main functional domains: a methyl-CpG binding domain (MBD) and a transcription repression domain (TRD). Over 600 pathogenic mutations were reported to affect the whole protein; almost half of missense mutations affect the MBD. Understanding the impact of these mutations on the MBD structure and interaction with DNA will foster the comprehension of their pathogenicity and possibly genotype/phenotype correlation studies. Herein, we use molecular dynamics simulations to obtain a detailed view of the dynamics of WT and mutated MBD in the presence and absence of DNA. The pathogenic mutation Y120D is used as paradigm for our studies. Further, since the Y120 residue was previously found to be a phosphorylation site, we characterize the dynamic profile of the MBD also in the presence of Y120 phosphorylation (pY120). We found that addition of a phosphate group to Y120 or mutation in aspartic acid affect domain mobility that samples an alternative conformational space with respect to the WT, leading to impaired ability to interact with DNA. Experimental assays showing a significant reduction in the binding affinity between the mutated MBD and the DNA confirmed our predictions. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Spectrum of mutations in homozygous familial hypercholesterolemia in India, with four novel mutations.

    Science.gov (United States)

    Setia, Nitika; Saxena, Renu; Arora, Anjali; Verma, Ishwar C

    2016-12-01

    Homozygous familial hypercholesterolemia (FH) is a rare but serious, inherited disorder of lipid metabolism characterized by very high total and LDL cholesterol levels from birth. It presents as cutaneous and tendon xanthomas since childhood, with or without cardiac involvement. FH is commonly caused by mutations in three genes, i.e. LDL receptor (LDLR), apolipoprotein B (ApoB) and PCSK9. We aimed to determine the spectrum of mutations in cases of homozygous FH in Asian Indians and evaluate if there was any similarity to the mutations observed in Caucasians. Sixteen homozygous FH subjects from eleven families were analyzed for mutations by Sanger sequencing. Large rearrangements in LDLR gene were evaluated by multiplex ligation probe dependent amplification (MLPA) technique. Ten mutations were observed in LDLR gene, of which four mutations were novel. No mutation was detected in ApoB gene and common PCSK9 mutation (p.D374Y). Fourteen cases had homozygous mutations; one had compound heterozygous mutation, while no mutation was detected in one clinically homozygous case. We report an interesting "Triple hit" case with features of homozygous FH. The spectrum of mutations in the Asian Indian population is quite heterogeneous. Of the mutations identified, 40% were novel. No mutation was observed in exons 3, 9 and 14 of LDLR gene, which are considered to be hot spots in studies done on Asian Indians in South Africa. Early detection followed by aggressive therapy, and cascade screening of extended families has been initiated to reduce the morbidity and mortality in these patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome

    Directory of Open Access Journals (Sweden)

    Sehgal S

    2008-01-01

    Full Text Available In north India the number of paediatric cases with acquired immunodeficiency syndrome (AIDS is on the rise. Most drug combinations used for treatment of AIDS incorporate nevirapine, resistance to which develops very fast if given singly or because of unplanned interruptions. This paper investigates presence of mutations at codon 103 and codon 215 of the HIV pol gene causing resistance to nevirapine and zidovudine (AZT respectively in 25 children with AIDS. Mutations T215Y and K103N were detected by a nested cum amplification refractory mutation system polymerase chain reaction (ARMS PCR and the results were confirmed by direct sequencing in five randomly selected cases. Nineteen patients had received nevirapine containing regimen and six were drug naive. Mutation K103N was observed in 56% (14/25 of the children while mutation T215Y was found in none. Two of the six drug naοve children also showed K103N mutation. Thus, Indian children drug naοve or treated with nevirapine containing regimens show a high rate of mutation conferring resistance to nevirapine which calls for a judicious use of nevirapine both in antenatal and postnatal setting.

  10. Pyrosequencing, a method approved to detect the two major EGFR mutations for anti EGFR therapy in NSCLC

    Directory of Open Access Journals (Sweden)

    Richard Marie-Jeanne

    2011-05-01

    Full Text Available Abstract Background Epidermal Growth Factor Receptor (EGFR mutations, especially in-frame deletions in exon 19 (ΔLRE and a point mutation in exon 21 (L858R predict gefitinib sensitivity in patients with non-small cell lung cancer. Several methods are currently described for their detection but the gold standard for tissue samples remains direct DNA sequencing, which requires samples containing at least 50% of tumor cells. Methods We designed a pyrosequencing assay based on nested PCR for the characterization of theses mutations on formalin-fixed and paraffin-embedded tumor tissue. Results This method is highly specific and permits precise characterization of all the exon 19 deletions. Its sensitivity is higher than that of "BigDye terminator" sequencing and enabled detection of 3 additional mutations in the 58 NSCLC tested. The concordance between the two methods was very good (97.4%. In the prospective analysis of 213 samples, 7 (3.3% samples were not analyzed and EGFR mutations were detected in 18 (8.7% patients. However, we observed a deficit of mutation detection when the samples were very poor in tumor cells. Conclusions pyrosequencing is then a highly accurate method for detecting ΔLRE and L858R EGFR mutations in patients with NSCLC when the samples contain at least 20% of tumor cells.

  11. NMD Microarray Analysis for Rapid Genome-Wide Screen of Mutated Genes in Cancer

    Directory of Open Access Journals (Sweden)

    Maija Wolf

    2005-01-01

    Full Text Available Gene mutations play a critical role in cancer development and progression, and their identification offers possibilities for accurate diagnostics and therapeutic targeting. Finding genes undergoing mutations is challenging and slow, even in the post-genomic era. A new approach was recently developed by Noensie and Dietz to prioritize and focus the search, making use of nonsense-mediated mRNA decay (NMD inhibition and microarray analysis (NMD microarrays in the identification of transcripts containing nonsense mutations. We combined NMD microarrays with array-based CGH (comparative genomic hybridization in order to identify inactivation of tumor suppressor genes in cancer. Such a “mutatomics” screening of prostate cancer cell lines led to the identification of inactivating mutations in the EPHB2 gene. Up to 8% of metastatic uncultured prostate cancers also showed mutations of this gene whose loss of function may confer loss of tissue architecture. NMD microarray analysis could turn out to be a powerful research method to identify novel mutated genes in cancer cell lines, providing targets that could then be further investigated for their clinical relevance and therapeutic potential.

  12. New mutations and an updated database for the patched-1 (PTCH1) gene.

    Science.gov (United States)

    Reinders, Marie G; van Hout, Antonius F; Cosgun, Betûl; Paulussen, Aimée D; Leter, Edward M; Steijlen, Peter M; Mosterd, Klara; van Geel, Michel; Gille, Johan J

    2018-05-01

    Basal cell nevus syndrome (BCNS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), maxillary keratocysts, and cerebral calcifications. BCNS most commonly is caused by a germline mutation in the patched-1 (PTCH1) gene. PTCH1 mutations are also described in patients with holoprosencephaly. We have established a locus-specific database for the PTCH1 gene using the Leiden Open Variation Database (LOVD). We included 117 new PTCH1 variations, in addition to 331 previously published unique PTCH1 mutations. These new mutations were found in 141 patients who had a positive PTCH1 mutation analysis in either the VU University Medical Centre (VUMC) or Maastricht University Medical Centre (MUMC) between 1995 and 2015. The database contains 331 previously published unique PTCH1 mutations and 117 new PTCH1 variations. We have established a locus-specific database for the PTCH1 gene using the Leiden Open Variation Database (LOVD). The database provides an open collection for both clinicians and researchers and is accessible online at http://www.lovd.nl/PTCH1. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

  13. Loss-of-function CARD8 mutation causes NLRP3 inflammasome activation and Crohn's disease.

    Science.gov (United States)

    Mao, Liming; Kitani, Atsushi; Similuk, Morgan; Oler, Andrew J; Albenberg, Lindsey; Kelsen, Judith; Aktay, Atiye; Quezado, Martha; Yao, Michael; Montgomery-Recht, Kim; Fuss, Ivan J; Strober, Warren

    2018-05-01

    In these studies, we evaluated the contribution of the NLRP3 inflammasome to Crohn's disease (CD) in a kindred containing individuals having a missense mutation in CARD8, a protein known to inhibit this inflammasome. Whole exome sequencing and PCR studies identified the affected individuals as having a V44I mutation in a single allele of the T60 isoform of CARD8. The serum levels of IL-1β in the affected individuals were increased compared with those in healthy controls, and their peripheral monocytes produced increased amounts of IL-1β when stimulated by NLRP3 activators. Immunoblot studies probing the basis of these findings showed that mutated T60 CARD8 failed to downregulate the NLRP3 inflammasome because it did not bind to NLRP3 and inhibit its oligomerization. In addition, these studies showed that mutated T60 CARD8 exerted a dominant-negative effect by its capacity to bind to and form oligomers with unmutated T60 or T48 CARD8 that impeded their binding to NLRP3. Finally, inflammasome activation studies revealed that intact but not mutated CARD8 prevented NLRP3 deubiquitination and serine dephosphorylation. CD due to a CARD8 mutation was not effectively treated by anti-TNF-α, but did respond to IL-1β inhibitors. Thus, patients with anti-TNF-α-resistant CD may respond to this treatment option.

  14. Glutaric acidemia type II: gene structure and mutations of the electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) gene.

    Science.gov (United States)

    Goodman, Stephen I; Binard, Robert J; Woontner, Michael R; Frerman, Frank E

    2002-01-01

    Glutaric acidemia type II is a human inborn error of metabolism which can be due to defects in either subunit of electron transfer flavoprotein (ETF) or in ETF:ubiquinone oxidoreductase (ETF:QO), but few disease-causing mutations have been described. The ETF:QO gene is located on 4q33, and contains 13 exons. Primers to amplify these exons are presented, together with mutations identified by molecular analysis of 20 ETF:QO-deficient patients. Twenty-one different disease-causing mutations were identified on 36 of the 40 chromosomes.

  15. Mutations in nif genes that cause Klebsiella pneumoniae to be derepressed for nitrogenase synthesis in the presence of ammonium.

    OpenAIRE

    MacNeil, D; Brill, W J

    1980-01-01

    Four Nif+ revertants from strains with polar insertions in nifL, were insensitive to ammonium and amino acid repression of nitrogenase synthesis. These strains have mutations located in or near the nifL region. The derepressed phenotype was dominant in a merodiploid containing a nif+ plasmid. These nif regulatory mutations also suppressed the Nif- phenotype of Gln- strains. Thus, regulation by fixed nitrogen (possible via glutamine synthetase) occurs on the nifLA operon but not on the other s...

  16. Nuclear reactor container

    International Nuclear Information System (INIS)

    Moriyama, Takeo; Ochiai, Kanehiro; Niino, Tsuyoshi; Kodama, Toyokazu; Hirako, Shizuka.

    1988-01-01

    Purpose: To obtain structures suitable to a container structures for nuclear power plants used in those districts where earthquakes occur frequently, in which no local stresses are caused to the fundamental base portions and the workability for the fundamental structures is improved. Constitution: Basic stabilizers are attached to a nuclear reactor container (PCV) and a basic concrete recess for receiving a basic stabilizer is disposed in basic concretes. A top stabilizer is joined and fixed to a top stabilizer receiving plate at the inside of an outer shielding wall. On the other hand, a PCV top recess for conducting the load of PCV to the top stabilizer is attached to the top of the PCV. By disposing stabilizer structures allowing miner displacements at the two points, that is, the top and the lowermost portion of the PCV, no local stress concentrations can be generated to the extension on the axial direction of components due to the inner pressure of the PCV and to the horizontal load applied to the upper portion of the PCV upon earthquakes. (Yoshino, Y.)

  17. Definition of containment issues

    International Nuclear Information System (INIS)

    Walker, D.H.

    1982-01-01

    Public Law 96-567 Nuclear Safety Research, Development and Demonstration Act of 1980, directed the US Department of Energy (DOE) to provide an accelerated and coordinated program for developing practical generic improvements that would enhance the capability for safe, reliable and economical operation of Light Water Nuclear Reactor Power Stations. The DOE approach to defining such a program will consist of two phases, (1) definition of program requirements and (2) implementation of the program plan. This paper summarizes the results of the program definition phase for the containment integrity function. The definition phase effort was carried out by two groups of knowledgeable technical experts from the nuclear industry, one of which addressed containment integrity. Tabulated in the paper are the issues identified by the working groups and their associated priorities. Also tabulated are those high priority issues for which ongoing programs do not appear to provide sufficient information to resolve the issue. The results of this review show that existing programs to a great extent address existing issues in a manner such that the issues should be resolved by the programs

  18. In vitro mutation breeding of bananas and plantains. Final reports of an FAO/IAEA co-ordinated research programme from 1988 to 1993

    International Nuclear Information System (INIS)

    1995-06-01

    This document contains 9 final reports of the participants at the FAO/IAEA co-ordinated research programme on 'In vitro mutation breeding of bananas and plantains'. A separate abstract was prepared for each report. Refs, figs and tabs

  19. In vitro mutation breeding of bananas and plantains. Final reports of an FAO/IAEA co-ordinated research programme from 1988 to 1993

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-06-01

    This document contains 9 final reports of the participants at the FAO/IAEA co-ordinated research programme on `In vitro mutation breeding of bananas and plantains`. A separate abstract was prepared for each report. Refs, figs and tabs.

  20. Development of Trombay pulse crop varieties mutation through induced mutation

    International Nuclear Information System (INIS)

    Dhole, V.J.; Reddy, K.S.

    2016-01-01

    The food prices including pulses were beginning to increase from 2008, something that was not expected to happen before 2020. It was due to climate change, a scarcity of good arable land, water and nutrients. With these obstacles, we must produce almost double than what we are producing now to achieve food security by 2050. It can be achieved through crop improvement. Crop improvement is the art and science of changing the genetic make of crop plant in desire direction through various method of plant breeding. Mutation breeding is one of the techniques which utilize the physical and chemical mutagens to create genetic variability. Till date more than 3200 mutant varieties have been developed worldwide in which two physical mutagens i.e. X-rays and gamma rays have major contributions. Bhabha Atomic Research Centre is one of the leading institutes in India where nuclear energy is used for crop improvement, which resulted in to development of 43 improved high yielding varieties in different crops including 19 varieties of pulse crops. These varieties are contributing significantly to production of pulses and ultimately to national food security. (author)

  1. Biallelic germline and somatic mutations in malignant mesothelioma: multiple mutations in transcription regulators including mSWI/SNF genes.

    Science.gov (United States)

    Yoshikawa, Yoshie; Sato, Ayuko; Tsujimura, Tohru; Otsuki, Taiichiro; Fukuoka, Kazuya; Hasegawa, Seiki; Nakano, Takashi; Hashimoto-Tamaoki, Tomoko

    2015-02-01

    We detected low levels of acetylation for histone H3 tail lysines in malignant mesothelioma (MM) cell lines resistant to histone deacetylase inhibitors. To identify the possible genetic causes related to the low histone acetylation levels, whole-exome sequencing was conducted with MM cell lines established from eight patients. A mono-allelic variant of BRD1 was common to two MM cell lines with very low acetylation levels. We identified 318 homozygous protein-damaging variants/mutations (18-78 variants/mutations per patient); annotation analysis showed enrichment of the molecules associated with mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complexes and co-activators that facilitate initiation of transcription. In seven of the patients, we detected a combination of variants in histone modifiers or transcription factors/co-factors, in addition to variants in mSWI/SNF. Direct sequencing showed that homozygous mutations in SMARCA4, PBRM1 and ARID2 were somatic. In one patient, homozygous germline variants were observed for SMARCC1 and SETD2 in chr3p22.1-3p14.2. These exhibited extended germline homozygosity and were in regions containing somatic mutations, leading to a loss of BAP1 and PBRM1 expression in MM cell line. Most protein-damaging variants were heterozygous in normal tissues. Heterozygous germline variants were often converted into hemizygous variants by mono-allelic deletion, and were rarely homozygous because of acquired uniparental disomy. Our findings imply that MM might develop through the somatic inactivation of mSWI/SNF complex subunits and/or histone modifiers, including BAP1, in subjects that have rare germline variants of these transcription regulators and/or transcription factors/co-factors, and in regions prone to mono-allelic deletion during oncogenesis. © 2014 UICC.

  2. Consumer Products Containing Radioactive Materials

    Science.gov (United States)

    Fact Sheet Adopted: February 2010 Health Physics Society Specialists in Radiation Safety Consumer Products Containing Radioactive Materials Everything we encounter in our daily lives contains some radioactive material, ...

  3. Benchmarking infrastructure for mutation text mining.

    Science.gov (United States)

    Klein, Artjom; Riazanov, Alexandre; Hindle, Matthew M; Baker, Christopher Jo

    2014-02-25

    Experimental research on the automatic extraction of information about mutations from texts is greatly hindered by the lack of consensus evaluation infrastructure for the testing and benchmarking of mutation text mining systems. We propose a community-oriented annotation and benchmarking infrastructure to support development, testing, benchmarking, and comparison of mutation text mining systems. The design is based on semantic standards, where RDF is used to represent annotations, an OWL ontology provides an extensible schema for the data and SPARQL is used to compute various performance metrics, so that in many cases no programming is needed to analyze results from a text mining system. While large benchmark corpora for biological entity and relation extraction are focused mostly on genes, proteins, diseases, and species, our benchmarking infrastructure fills the gap for mutation information. The core infrastructure comprises (1) an ontology for modelling annotations, (2) SPARQL queries for computing performance metrics, and (3) a sizeable collection of manually curated documents, that can support mutation grounding and mutation impact extraction experiments. We have developed the principal infrastructure for the benchmarking of mutation text mining tasks. The use of RDF and OWL as the representation for corpora ensures extensibility. The infrastructure is suitable for out-of-the-box use in several important scenarios and is ready, in its current state, for initial community adoption.

  4. Sequential acquisition of mutations in myelodysplastic syndromes.

    Science.gov (United States)

    Makishima, Hideki

    2017-01-01

    Recent progress in next-generation sequencing technologies allows us to discover frequent mutations throughout the coding regions of myelodysplastic syndromes (MDS), potentially providing us with virtually a complete spectrum of driver mutations in this disease. As shown by many study groups these days, such driver mutations are acquired in a gene-specific fashion. For instance, DDX41 mutations are observed in germline cells long before MDS presentation. In blood samples from healthy elderly individuals, somatic DNMT3A and TET2 mutations are detected as age-related clonal hematopoiesis and are believed to be a risk factor for hematological neoplasms. In MDS, mutations of genes such as NRAS and FLT3, designated as Type-1 genes, may be significantly associated with leukemic evolution. Another type (Type-2) of genes, including RUNX1 and GATA2, are related to progression from low-risk to high-risk MDS. Overall, various driver mutations are sequentially acquired in MDS, at a specific time, in either germline cells, normal hematopoietic cells, or clonal MDS cells.

  5. Benchmarking infrastructure for mutation text mining

    Science.gov (United States)

    2014-01-01

    Background Experimental research on the automatic extraction of information about mutations from texts is greatly hindered by the lack of consensus evaluation infrastructure for the testing and benchmarking of mutation text mining systems. Results We propose a community-oriented annotation and benchmarking infrastructure to support development, testing, benchmarking, and comparison of mutation text mining systems. The design is based on semantic standards, where RDF is used to represent annotations, an OWL ontology provides an extensible schema for the data and SPARQL is used to compute various performance metrics, so that in many cases no programming is needed to analyze results from a text mining system. While large benchmark corpora for biological entity and relation extraction are focused mostly on genes, proteins, diseases, and species, our benchmarking infrastructure fills the gap for mutation information. The core infrastructure comprises (1) an ontology for modelling annotations, (2) SPARQL queries for computing performance metrics, and (3) a sizeable collection of manually curated documents, that can support mutation grounding and mutation impact extraction experiments. Conclusion We have developed the principal infrastructure for the benchmarking of mutation text mining tasks. The use of RDF and OWL as the representation for corpora ensures extensibility. The infrastructure is suitable for out-of-the-box use in several important scenarios and is ready, in its current state, for initial community adoption. PMID:24568600

  6. New mutations affecting induced mutagenesis in yeast.

    Science.gov (United States)

    Lawrence, C W; Krauss, B R; Christensen, R B

    1985-01-01

    Previously isolated mutations in baker's yeast, Saccharomyces cerevisiae, that impair induced mutagenesis were all identified with the aid of tests that either exclusively or predominantly detect base-pair substitutions. To avoid this bias, we have screened 11 366 potentially mutant clones for UV-induced reversion of the frameshift allele, his4-38, and have identified 10 mutants that give much reduced yields of revertants. Complementation and recombination tests show that 6 of these carry mutations at the previously known REV1, REV1 and REV3 loci, while the remaining 4 define 3 new genes, REV4 (2 mutations), REV5 and REV6. The rev4 mutations are readily suppressed in many genetic backgrounds and, like the rev5 mutation, impart only a limited deficiency for induced mutagenesis: it is likely, therefore that the REV4+ and REV5+ gene functions are only remotely concerned with this process. The rev6 mutants have a more general deficiency, however, as well as marked sensitivity to UV and an increased spontaneous mutation rate, properties that suggest the REV6 gene is directly involved in mutation induction. The REV5 gene is located about 1 cM proximal to CYC1 on chromosome X.

  7. Fidelity and mutational spectrum of Pfu DNA polymerase on a human mitochondrial DNA sequence.

    Science.gov (United States)

    André, P; Kim, A; Khrapko, K; Thilly, W G

    1997-08-01

    The study of rare genetic changes in human tissues requires specialized techniques. Point mutations at fractions at or below 10(-6) must be observed to discover even the most prominent features of the point mutational spectrum. PCR permits the increase in number of mutant copies but does so at the expense of creating many additional mutations or "PCR noise". Thus, each DNA sequence studied must be characterized with regard to the DNA polymerase and conditions used to avoid interpreting a PCR-generated mutation as one arising in human tissue. The thermostable DNA polymerase derived from Pyrococcus furiosus designated Pfu has the highest fidelity of any DNA thermostable polymerase studied to date, and this property recommends it for analyses of tissue mutational spectra. Here, we apply constant denaturant capillary electrophoresis (CDCE) to separate and isolate the products of DNA amplification. This new strategy permitted direct enumeration and identification of point mutations created by Pfu DNA polymerase in a 96-bp low melting domain of a human mitochondrial sequence despite the very low mutant fractions generated in the PCR process. This sequence, containing part of the tRNA glycine and NADH dehydrogenase subunit 3 genes, is the target of our studies of mitochondrial mutagenesis in human cells and tissues. Incorrectly synthesized sequences were separated from the wild type as mutant/wild-type heteroduplexes by sequential enrichment on CDCE. An artificially constructed mutant was used as an internal standard to permit calculation of the mutant fraction. Our study found that the average error rate (mutations per base pair duplication) of Pfu was 6.5 x 10(-7), and five of its more frequent mutations (hot spots) consisted of three transversions (GC-->TA, AT-->TA, and AT-->CG), one transition (AT-->GC), and one 1-bp deletion (in an AAAAAA sequence). To achieve an even higher sensitivity, the amount of Pfu-induced mutants must be reduced.

  8. Coordinated Changes in Mutation and Growth Rates Induced by Genome Reduction

    Directory of Open Access Journals (Sweden)

    Issei Nishimura

    2017-07-01

    Full Text Available Genome size is determined during evolution, but it can also be altered by genetic engineering in laboratories. The systematic characterization of reduced genomes provides valuable insights into the cellular properties that are quantitatively described by the global parameters related to the dynamics of growth and mutation. In the present study, we analyzed a small collection of W3110 Escherichia coli derivatives containing either the wild-type genome or reduced genomes of various lengths to examine whether the mutation rate, a global parameter representing genomic plasticity, was affected by genome reduction. We found that the mutation rates of these cells increased with genome reduction. The correlation between genome length and mutation rate, which has been reported for the evolution of bacteria, was also identified, intriguingly, for genome reduction. Gene function enrichment analysis indicated that the deletion of many of the genes encoding membrane and transport proteins play a role in the mutation rate changes mediated by genome reduction. Furthermore, the increase in the mutation rate with genome reduction was highly associated with a decrease in the growth rate in a nutrition-dependent manner; thus, poorer media showed a larger change that was of higher significance. This negative correlation was strongly supported by experimental evidence that the serial transfer of the reduced genome improved the growth rate and reduced the mutation rate to a large extent. Taken together, the global parameters corresponding to the genome, growth, and mutation showed a coordinated relationship, which might be an essential working principle for balancing the cellular dynamics appropriate to the environment.

  9. The impact of KRAS mutations on VEGF-A production and tumour vascular network

    International Nuclear Information System (INIS)

    Figueras, Agnès; Arbos, Maria Antonia; Quiles, Maria Teresa; Viñals, Francesc; Germà, Josep Ramón; Capellà, Gabriel

    2013-01-01

    The malignant potential of tumour cells may be influenced by the molecular nature of KRAS mutations being codon 13 mutations less aggressive than codon 12 ones. Their metabolic profile is also different, with an increased anaerobic glycolytic metabolism in cells harbouring codon 12 KRAS mutations compared with cells containing codon 13 mutations. We hypothesized that this distinct metabolic behaviour could be associated with different HIF-1α expression and a distinct angiogenic profile. Codon13 KRAS mutation (ASP13) or codon12 KRAS mutation (CYS12) NIH3T3 transfectants were analyzed in vitro and in vivo. Expression of HIF-1α, and VEGF-A was studied at RNA and protein levels. Regulation of VEGF-A promoter activity was assessed by means of luciferase assays using different plasmid constructs. Vascular network was assessed in tumors growing after subcutaneous inoculation. Non parametric statistics were used for analysis of results. Our results show that in normoxic conditions ASP13 transfectants exhibited less HIF-1α protein levels and activity than CYS12. In contrast, codon 13 transfectants exhibited higher VEGF-A mRNA and protein levels and enhanced VEGF-A promoter activity. These differences were due to a differential activation of Sp1/AP2 transcription elements of the VEGF-A promoter associated with increased ERKs signalling in ASP13 transfectants. Subcutaneous CYS12 tumours expressed less VEGF-A and showed a higher microvessel density (MVD) than ASP13 tumours. In contrast, prominent vessels were only observed in the latter. Subtle changes in the molecular nature of KRAS oncogene activating mutations occurring in tumour cells have a major impact on the vascular strategy devised providing with new insights on the role of KRAS mutations on angiogenesis

  10. Mutations in the Norrie disease gene.

    Science.gov (United States)

    Schuback, D E; Chen, Z Y; Craig, I W; Breakefield, X O; Sims, K B

    1995-01-01

    We report our experience to date in mutation identification in the Norrie disease (ND) gene. We carried out mutational analysis in 26 kindreds in an attempt to identify regions presumed critical to protein function and potentially correlated with generation of the disease phenotype. All coding exons, as well as noncoding regions of exons 1 and 2, 636 nucleotides in the noncoding region of exon 3, and 197 nucleotides of 5' flanking sequence, were analyzed for single-strand conformation polymorphisms (SSCP) by polymerase chain reaction (PCR) amplification of genomic DNA. DNA fragments that showed altered SSCP band mobilities were sequenced to locate the specific mutations. In addition to three previously described submicroscopic deletions encompassing the entire ND gene, we have now identified 6 intragenic deletions, 8 missense (seven point mutations, one 9-bp deletion), 6 nonsense (three point mutations, three single bp deletions/frameshift) and one 10-bp insertion, creating an expanded repeat in the 5' noncoding region of exon 1. Thus, mutations have been identified in a total of 24 of 26 (92%) of the kindreds we have studied to date. With the exception of two different mutations, each found in two apparently unrelated kindreds, these mutations are unique and expand the genotype database. Localization of the majority of point mutations at or near cysteine residues, potentially critical in protein tertiary structure, supports a previous protein model for norrin as member of a cystine knot growth factor family (Meitinger et al., 1993). Genotype-phenotype correlations were not evident with the limited clinical data available, except in the cases of larger submicroscopic deletions associated with a more severe neurologic syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. JAK and MPL mutations in myeloid malignancies.

    Science.gov (United States)

    Tefferi, Ayalew

    2008-03-01

    The Janus family of non-receptor tyrosine kinases (JAK1, JAK2, JAK3 and tyrosine kinase 2) transduces signals downstream of type I and II cytokine receptors via signal transducers and activators of transcription (STATs). JAK3 is important in lymphoid and JAK2 in myeloid cell proliferation and differentiation. The thrombopoietin receptor MPL is one of several JAK2 cognate receptors and is essential for myelopoiesis in general and megakaryopoiesis in particular. Germline loss-of-function (LOF) JAK3 and MPL mutations cause severe combined immunodeficiency and congenital amegakaryocytic thrombocytopenia, respectively. Germline gain-of-function (GOF) MPL mutation (MPLS505N) causes familial thrombocytosis. Somatic JAK3 (e.g. JAK3A572V, JAK3V722I, JAK3P132T) and fusion JAK2 (e.g. ETV6-JAK2, PCM1-JAK2, BCR-JAK2) mutations have respectively been described in acute megakaryocytic leukemia and acute leukemia/chronic myeloid malignancies. However, current attention is focused on JAK2 (e.g. JAK2V617F, JAK2 exon 12 mutations) and MPL (e.g. MPLW515L/K/S, MPLS505N) mutations associated with myeloproliferative neoplasms (MPNs). A JAK2 mutation, primarily JAK2V617F, is invariably associated with polycythemia vera (PV). The latter mutation also occurs in the majority of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). MPL mutational frequency in MPNs is substantially less (<10%). In general, despite a certain degree of genotype - phenotype correlations, the prognostic relevance of harbouring one of these mutations, or their allele burden when present, remains dubious. Regardless, based on the logical assumption that amplified JAK-STAT signalling is central to the pathogenesis of PV, ET and PMF, several anti-JAK2 tyrosine kinase inhibitors have been developed and are currently being tested in humans with these disorders.

  12. Nuclear reactor container

    International Nuclear Information System (INIS)

    Kawabe, Ryuhei; Yamaki, Rika.

    1989-01-01

    Aerosol filters considered so far for nuclear reactor containers in conventional BWR type nuclear power plants make the facility larger and involve a risk of clogging. In view of the above, in the present invention, the diameter of a flow channel of gases entering from a bent pipe to a suppression pool is made smaller thereby decreasing the diameter of gas bubbles in the supperssional pool. Since this reduces the force of surface tension, the diameter of resulted gas bubbles is made remarkably smaller as compared with the case where the gases are released from the lower end of the bent pipe. Since the absorption velocity of bubble-entrained aerosols into water is in proportion to the square of the bubble diameter, the absorption efficiency can be increased remarkably by reducing the diameter of the gas bubbles. Accordingly, it is possible to improve the efficiency of eliminating radioactivity of released gases. (K.M.)

  13. AKAVI containment data report

    Energy Technology Data Exchange (ETDEWEB)

    Stubbs, T.; Heinle, R.

    1995-08-01

    The AKAVI event was detonated in hole U2es of the Nevada Test Site as indicated. The device had a depth-of-burial (DOB) of 494 m in the Paintbrush Tuff of area 2, about 90 m above the standing water level and 300 m above the Paleozoic formation. Stemming of the 2.44 m diameter emplacement hole followed the plan. A log of the stemming operations was maintained by Holmes & Narver. Detonation time was 07:00 PST on December 3, 1981 and 103 minutes later a surface collapse occurred leaving a crater with mean radius of 90.5 m and maximum depth of 19.5 m. No radiation arrivals were detected above ground and the AKAVI containment was considered successful.

  14. AKAVI containment data report

    International Nuclear Information System (INIS)

    Stubbs, T.; Heinle, R.

    1995-08-01

    The AKAVI event was detonated in hole U2es of the Nevada Test Site as indicated. The device had a depth-of-burial (DOB) of 494 m in the Paintbrush Tuff of area 2, about 90 m above the standing water level and 300 m above the Paleozoic formation. Stemming of the 2.44 m diameter emplacement hole followed the plan. A log of the stemming operations was maintained by Holmes ampersand Narver. Detonation time was 07:00 PST on December 3, 1981 and 103 minutes later a surface collapse occurred leaving a crater with mean radius of 90.5 m and maximum depth of 19.5 m. No radiation arrivals were detected above ground and the AKAVI containment was considered successful

  15. Plutonium waste container identification

    International Nuclear Information System (INIS)

    Schmierer, T.J.

    1979-01-01

    The purpose of this paper is to define the parameters of a method for identifying plutonium waste containers. This information will form the basis for a permanent committee to develop a complete identification program for use throughout the world. Although a large portion of the information will be on handwritten notebooks and may not be as extensive as is desired, it will all be helpful. The final information will be programmed into computer language and be available to all interested parties as well as a central control committee which will have the expertise to provide each government with advice on the packaging, storage, and measurement of the waste for which it is responsible. As time progresses, this central control committee should develop permanent storage sites and establish a system of records which will last for hundreds of years

  16. Reactor containment vessel

    International Nuclear Information System (INIS)

    Ochiai, Kanehiro; Hayagumo, Sunao; Morikawa, Matsuo.

    1981-01-01

    Purpose: To safety and simplify the structure in a reactor containment vessel. Constitution: Steam flow channels with steam jetting ports communicating to coolants are provided between a communication channel and coolants in a pressure suppression chamber. Upon loss of coolant accidents, pressure in a dry well will increase, then force downwards water in an annulus portion and further flow out the water through steam jetting ports into a suppression pool. Thus, the steam flow channel is filled with steams or airs present in the dry well, which are released through the steam jetting ports into the pressure suppression chamber. Even though water is violently vibrated owing to the upward movement of air bubbles and condensation of steam bubbles, the annular portion and the steam jetting ports are filled with steams or the like, direct dynamic loads onto the structures such as communication channels can be avoided. (J.P.N.)

  17. Container for irradiated fuel

    International Nuclear Information System (INIS)

    Guy, R.

    1978-01-01

    The transport container for irradiated or used nuclear fuel is provided with an identical heat shield against fires on the top and bottom sides. Each heat shield consists of two inner nickel plates, whose contact surfaces are polished to a mirror finish and an outer plate of stainless steel. The nickel plate on the box is spot welded to it while the second nickel plate is spot welded to the steel plate. Both together are in turn welded so as to be leaktight to the edges of the box. For extreme heat effects and based on the different (bimetal) coefficients of expansion, the steel plate with the nickel plate attached to it bulges away from the box. The second nickel plate remains at the box, so that a subpressure space is formed with the mirror nickel surfaces. The heat radiation and heat conduction to the box are greatly reduced by this. (DG) [de

  18. Phosphate glasses, containing nitrogen

    International Nuclear Information System (INIS)

    Lisitsyna, E.A.; Khalilev, V.D.; Koryavin, A.A.; Goncharova, L.N.

    1987-01-01

    Possibilities of nitrogen-containing glass synthesis by the introduction into the charge of ammonium salts, as well as aluminium nitride, are studied. Zinc alumoyttrium phosphate glass (mol. %) Zn(PO 3 ) 2 - 4O, Al(PO 3 ) 3 - 3O, Y(PO 3 ) 3 -3O is suggested as a matrix. It is shown that the effect of amide and imide groups on the properties of the glass is less noticeable than the effect of nitride groups. Direct introduction of nitride constituent was realized using AlN, but aluminium introduction was taken into account so that the oxide was subtracted. The attempt to introduce more than 2.5 mass % of nitrogen into initial matrix by aluminium nitride has failed due to repeated restoration of glass with amorphous phosphorus isolation

  19. ITER containment structures

    International Nuclear Information System (INIS)

    Sadakov, S.; Fauser, F.; Nelson, B.

    1991-01-01

    This document describes the results and recommendations of the Containment Structures Design Unit (CSDU) on the containment structures for ITER, made in the context of the Conceptual Design Phase. The document describes the following subsystems: (1) the primary vacuum vessel (VV), (2) the attaching locks (AL) of the invessel components, (3) the plasma passive and active stabilizers, (4) the cryostat vessel, and (5) the machine gravity supports. Although for most components reference designs were selected, for some of these alternative design options were described, because unresolved problems necessitate further research and development. Conclusions and future needs are summarized for each of the above subsystems: (1) a reference VV design was selected, while most critical VV future needs are the feasibility studies of manufacturing, assembly, and the repair/disassembly/reassembly by remote handling. Alternative, thin-wall options appear attractive and should be studied further during the Engineering Design Activities; (2) no reference design solution was selected for the AL system, as AL design requirements are extremely difficult and internally contradictory, while there is no existing tokamak precedent, but instead, five different approaches will be further researched early in the Engineering Design Phase; (3) significant progress is reported on passive loops, for which the ''twin-loops'' concept is ready to be advanced into the Engineering Design Phase, and on active coils, where a new coil positioning prevents interference with the blanket removal paths, and the current joints are located in a secondary vacuum or in the atmosphere of the reactor hall, repairable by remote handling; (4) a full metallic welded cryostat design with increased toroidal resistance was chosen, but with a design based on concrete with a thin inner metallic liner as a back-up in case detailed nuclear shielding requirements would force the cryostat to act as biological shield; (5) out

  20. Mutations in the satellite cell gene MEGF10 cause a recessive congenital myopathy with minicores.

    Science.gov (United States)

    Boyden, Steven E; Mahoney, Lane J; Kawahara, Genri; Myers, Jennifer A; Mitsuhashi, Satomi; Estrella, Elicia A; Duncan, Anna R; Dey, Friederike; DeChene, Elizabeth T; Blasko-Goehringer, Jessica M; Bönnemann, Carsten G; Darras, Basil T; Mendell, Jerry R; Lidov, Hart G W; Nishino, Ichizo; Beggs, Alan H; Kunkel, Louis M; Kang, Peter B

    2012-05-01

    We ascertained a nuclear family in which three of four siblings were affected with an unclassified autosomal recessive myopathy characterized by severe weakness, respiratory impairment, scoliosis, joint contractures, and an unusual combination of dystrophic and myopathic features on muscle biopsy. Whole genome sequence from one affected subject was filtered using linkage data and variant databases. A single gene, MEGF10, contained nonsynonymous mutations that co-segregated with the phenotype. Affected subjects were compound heterozygous for missense mutations c.976T > C (p.C326R) and c.2320T > C (p.C774R). Screening the MEGF10 open reading frame in 190 patients with genetically unexplained myopathies revealed a heterozygous mutation, c.211C > T (p.R71W), in one additional subject with a similar clinical and histological presentation as the discovery family. All three mutations were absent from at least 645 genotyped unaffected control subjects. MEGF10 contains 17 atypical epidermal growth factor-like domains, each of which contains eight cysteine residues that likely form disulfide bonds. Both the p.C326R and p.C774R mutations alter one of these residues, which are completely conserved in vertebrates. Previous work showed that murine Megf10 is required for preserving the undifferentiated, proliferative potential of satellite cells, myogenic precursors that regenerate skeletal muscle in response to injury or disease. Here, knockdown of megf10 in zebrafish by four different morpholinos resulted in abnormal phenotypes including unhatched eggs, curved tails, impaired motility, and disorganized muscle tissue, corroborating the pathogenicity of the human mutations. Our data establish the importance of MEGF10 in human skeletal muscle and suggest satellite cell dysfunction as a novel myopathic mechanism.

  1. Petroleum pollution and mutation in mangroves

    International Nuclear Information System (INIS)

    Klekowski, E.J. Jr.; Corredor, J.E.; Morell, J.M.; Del Castillo, C.A.

    1994-01-01

    Chlorophyll-deficiency has often been used as a sensitive genetic end-point in plant mutation research. The frequency of trees heterozygous for nuclear chlorophyll-deficient mutations was determined for mangrove populations growing along the southwest coast of Puerto Rico. The frequency of heterozygotes was strongly correlated with the concentration of polycyclic aromatic hydrocarbons in the underlying sediment and with both acute and chronic petroleum pollution. Although epidemiological studies can seldom prove causation, a strong correlation is certainly compatible with a cause-effect relationship. Our results suggest that the biota of oil-polluted habitats may be experiencing increased mutation. (Author)

  2. Molecular mechanisms of induced-mutations

    International Nuclear Information System (INIS)

    Kato, Takeshi

    1985-01-01

    The outcome of recent studies on mechanisms of induced-mutations is outlined with particular emphasis on the dependence of recA gene function in Escherichia coli. Genes involved in spontaneous mutation and x-ray- and chemical-induced mutation and genes involved in adaptive response are presented. As for SOS mutagenesis, SOS-induced regulation mechanisms and mutagenic routes are described. Furthermore, specificity of mutagens themselves are discussed in relation to mechanisms of base substitution, frameshift, and deletion mutagenesis. (Namekawa, K.)

  3. Prevalent mutations in fatty acid oxidation disorders

    DEFF Research Database (Denmark)

    Gregersen, N; Andresen, B S; Bross, P

    2000-01-01

    UNLABELLED: The mutational spectrum in a given disease-associated gene is often comprised of a large number of different mutations, of which a single or a few are present in a large proportion of diseased individuals. Such prevalent mutations are known in four genes of the fatty acid oxidation...... of the disease in question and determination of the carrier frequency in the general population may help in elucidating the penetrance of the genotype. This is exemplified in disorders of mitochondrial fatty acid oxidation....

  4. Mutation breeding newsletter. No. 40

    International Nuclear Information System (INIS)

    1993-01-01

    This newsletter contains an obituary to Iosif Abramovitch Rapoport and an outline of three new co-ordinated research programmes as well as a number of short contributed articles concerning the development and testing of mutant plant lines. These contributed articles have been indexed separately

  5. Identification of novel splice site mutation IVS9 + 1(G > A) and novel complex allele G355R/R359X in Type 1 Gaucher patients heterozygous for mutation N370S.

    Science.gov (United States)

    Hoitsema, Kourtnee; Amato, Dominick; Khan, Aneal; Sirrs, Sandra; Choy, Francis Y M

    2016-09-01

    Gaucher disease is an autosomal recessive lysosomal storage disorder resulting from deficient glucocerebrosidase activity. More than 350 mutations that cause Gaucher disease have been described to date. Novel mutations can potentially provide insight into the glucocerebrosidase structure-function relationship and biochemical basis of the disease. Here, we report the identification of two novel mutations in two unrelated patients with type I (non-neuronopathic) Gaucher disease: 1) a splice site mutation IVS9 + 1G > A; and (2) a complex allele (cis) G355R/R359X. Both patients have a common N370S mutation in the other allele. The splice site mutation results from an intronic base substitution (G to A, c.1328 + 1, g.5005) at the donor splice site of exon and intron 9. The complex allele results from two point mutations in exon 8 of glucocerebrosidase (G to C at c.1180, g.4396, and T to C at c. 1192, g.4408) substituting glycine by arginine (G355R) and arginine by a premature termination (R359X), respectively. In order to demonstrate that G355R/R359X are in cis arrangement, PCR-amplified glucocerebrosidase exon 8 genomic DNA from the patient was cloned into the vector pJET1.2 in Escherichia coli TOP10® strain. Out of the 15 clones that were sequence analyzed, 10 contained the normal allele sequence and 5 contained the complex allele G355R/R359X sequence showing both mutations in cis arrangement. Restriction fragment length polymorphism analysis using Hph1 restriction endonuclease digest was established for the IVS9 + 1G > A mutation for confirmation and efficient identification of this mutation in future patients. Past literature suggests that mutations affecting splicing patterns of the glucocerebrosidase transcript as well as mutations in Gaucher complex alleles are detrimental to enzyme activity. However, compound heterozygosity with N370S, a mild mutation, will lead to a mild phenotype. The cases reported here support these past findings.

  6. TP53 mutations in clinically normal mucosa adjacent to oral carcinomas

    DEFF Research Database (Denmark)

    Thode, Christenze; Bilde, Anders; von Buchwald, Christian

    2010-01-01

    BACKGROUND: The tumour-suppressor protein p53 often accumulates in histologically normal epithelium adjacent to oral squamous cell carcinomas (OSCC). We investigated whether this was associated with mutations in TP53, the gene for p53, and might implicate impending malignancy. METHODS: Specimens...... products were separated by denatured gradient gel electrophoresis. Fragments with a deviant DGEE pattern were sequenced. RESULTS: TP53 mutations were found in six of 18 tumours. Fourteen specimens contained histologically normal mucosa adjacent to the tumour; 13 of these showed small clusters of p53...

  7. Exome sequencing reveals VCP mutations as a cause of familial ALS

    OpenAIRE

    Johnson, Janel O.; Mandrioli, Jessica; Benatar, Michael; Abramzon, Yevgeniya; Van Deerlin, Vivianna M.; Trojanowski, John Q.; Gibbs, J Raphael; Brunetti, Maura; Gronka, Susan; Wuu, Joanne; Ding, Jinhui; McCluskey, Leo; Martinez-Lage, Maria; Falcone, Dana; Hernandez, Dena G.

    2010-01-01

    Using exome sequencing, we identified a p.R191Q amino acid change in the valosin-containing protein (VCP) gene in an Italian family with autosomal dominantly inherited amyotrophic lateral sclerosis (ALS). Mutations in VCP have previously been identified in families with Inclusion Body Myopathy, Paget’s disease and Frontotemporal Dementia (IBMPFD). Screening of VCP in a cohort of 210 familial ALS cases and 78 autopsy-proven ALS cases identified four additional mutations including a p.R155H mut...

  8. Mutation accumulation and fitness effects in hybridogenetic populations: a comparison to sexual and asexual systems

    Directory of Open Access Journals (Sweden)

    Bagheri Homayoun C

    2007-05-01

    Full Text Available Abstract Background Female only unisexual vertebrates that reproduce by hybridogenesis show an unusual genetic composition. They are of hybrid origin but show no recombination between the genomes of their parental species. Instead, the paternal genome is discarded from the germline prior to meiosis, and gametes (eggs only contain solely unrecombined maternal genomes. Hence hybridogens only transmit maternally inherited mutations. Hybridity is restored each generation by backcrossing with males of the sexual parental species whose genome was eliminated. In contrast, recombining sexual species propagate an intermixed pool of mutations derived from the maternal and paternal parts of the genome. If mutation rates are lower in female gametes than males, it raises the possibility for lower mutation accumulation in a hybridogenetic population, and consequently, higher population fitness than its sexual counterpart. Results We show through Monte-Carlo simulations that at higher male to female mutation ratios, and sufficiently large population sizes, hybridogenetic populations can carry a lower mutation load than sexual species. This effect is more pronounced with synergistic forms of epistasis. Mutations accumulate faster on the sexual part of the genome, and with the purifying effects of epistasis, it makes it more difficult for mutations to be transmitted on the clonal part of the genome. In smaller populations, the same mechanism reduces the speed of Muller's Ratchet and the number of fixed mutations compared to similar asexual species. Conclusion Since mutation accumulation can be less pronounced in hybridogenetic populations, the question arises why hybridogenetic organisms are so scarce compared to sexual species. In considering this, it is likely that comparison of population fitnesses is not sufficient. Despite competition with the sexual parental species, hybrid populations are dependent on the maintenance of – and contact with – their

  9. From containment to ... syzygy

    Energy Technology Data Exchange (ETDEWEB)

    Carr, H.M.

    1995-04-18

    The U S. is at an historic crossroads following the end of the Cold War. The old twin themes of containment and deterrence must now give way to a newer vision of the U.S. role as we approach the 21st century. This paper follows a visioning process requiring development of alternatives based on signposts, values and frameworks. Signposts are current domestic and global environments revealing a U.S. in economic trouble with budget and trade defidts, a falling dollar and multiplying peace operations at a time when Europe and Japan are becoming economic superpowers. Although U.S. values must be protected, economic competition requires increased emphasis on realpolitik. A balanced framework of internationalism and reduced multilateralism will suit the current environment and U.S. purposes. Recognizing that the U.S. must retain leadership to protect national interests, the vision unfolds as an alignment of major powers-a syzygy of purpose-with Europe, Japan, and the U.S. in a concert of power, sharing economic, political and military burdens to ensure world stability. Thus, the new U.S. role could be primus inter pares of a Pax Consortis with common interests and goals, allowing the U.S. time to restore its economic vitality.

  10. Do pyrotechnics contain radium?

    Energy Technology Data Exchange (ETDEWEB)

    Steinhauser, Georg; Musilek, Andreas, E-mail: georg.steinhauser@ati.ac.a [Vienna University of Technology, Atominstitut der Oesterreichischen Universitaeten, Stadionallee 2, A-1020 Wien (Austria)

    2009-07-15

    Many pyrotechnic devices contain barium nitrate which is used as an oxidizer and colouring agent primarily for green-coloured fireworks. Similarly, strontium nitrate is used for red-coloured pyrotechnic effects. Due to their chemical similarities to radium, barium and strontium ores can accumulate radium, causing a remarkable activity in these minerals. Radium in such contaminated raw materials can be processed together with the barium or strontium, unless extensive purification of the ores was undertaken. For example, the utilization of 'radiobarite' for the production of pyrotechnic ingredients can therefore cause atmospheric pollution with radium aerosols when the firework is displayed, resulting in negative health effects upon inhalation of these aerosols. In this study, we investigated the occurrence of gamma-photon-emitting radionuclides in several pyrotechnic devices. The highest specific activities were due to K-40 (up to 20 Bq g{sup -1}, average value 14 Bq g{sup -1}). Radium-226 activities were in the range of 16-260 mBq g{sup -1} (average value 81 mBq g{sup -1}). Since no uranium was found in any of the samples, indeed, a slight enrichment of Ra-226 in coloured pyrotechnics can be observed. Radioactive impurities stemming from the Th-232 decay chain were found in many samples as well. In the course of novel developments aiming at the 'greening' of pyrotechnics, the potential radioactive hazard should be considered as well.

  11. Containment and release management

    International Nuclear Information System (INIS)

    Lehner, J.R.; Pratt, W.T.

    1988-01-01

    Reducing the risk from potentially severe accidents by appropriate accident management strategies is receiving increased attention from the international reactor safety community. Considerable uncertainty still surrounds some of the physical phenomena likely to occur during a severe accident. The USNRC, in developing its research plan for accident management, wants to ensure that both the developers and implementers of accident management strategies are aware of the uncertainty associated with the plant operators' ability to correctly diagnose an accident, as well as the uncertainties associated with various preventive and mitigative strategies. The use of a particular accident management strategy can have both positive and negative effects on the status of a plant and these effects must be carefully weighed before a particular course of action is chosen and implemented. By using examples of severe accident scenarios, initial insights are presented here regarding the indications plant operators may have to alert them to particular accident states. Insights are also offered on the various management actions operators and plant technical staff might pursue for particular accident situations and the pros and cons associated with such actions. The examples given are taken for the most part from the containment and release phase of accident management, since this is the current focus of the effort in the accident management area at Brookhaven National Laboratory. 2 refs

  12. Fission reactor container

    International Nuclear Information System (INIS)

    Akagawa, Katsuhiko.

    1991-01-01

    Cooling water is sent without using dynamic equipments upon loss of coolants accident in a pressure vessel by improving an arrangement of a nuclear reactor pressure vessel. That is, a containing space is formed at the center of a suppression chamber for storing cooling water while being partitioned with each other, in which the pressure vessel is placed. Further, a water reservoir is formed above the pressure vessel. Then a water discharge pipe is connected to the reservoir for submerging the stored water over the pressure vessel upon occurrence of loss of coolants accident. Further, a water injection pipe is disposed between the pressure suppression chamber and the pressure vessel for injecting the cooling water in the pressure suppression chamber to the reactor core of the pressure vessel by the difference of a water head upon loss of coolants accident. With such a constitution, the pressure vessel has high earthquake proofness. Further, upon loss of coolants accident of the pressure vessel, the cooling water in the reservoir is discharged to submerge and cool the pressure vessel efficiently. Further, the reactor core of the pressure vessel can certainly be cooled by the cooling water of the pressure suppression chamber without relying on dynamic equipments. (I.S.)

  13. Nuclear reactor container

    International Nuclear Information System (INIS)

    Shioiri, Akio.

    1992-01-01

    In a nuclear reactor container, a vent tube communication port is disposed to a pressure suppression pool at a position higher than the pool water therein for communication with an upper dry well, and the upper end opening of a dry well communication pipe is disposed at a position higher than the communication port. When condensate return pipeline is ruptured in the upper dry well, water in a water source pool is injected to the pressure vessel and partially discharged out of the ruptured port and a depressurization valve connected to the pressure vessel to the inside of the upper dry well. The discharged water stays in the upper dry well and, when the water level reaches the height of the vent tube communication port, it flows into the pressure suppression pool. Even in a state that the entire amount of water in the water source pool is supplied, since water does not reach the upper opening port of the dry well communication pipe, water does not flow into a lower dry well. Accordingly, the motor of a control rod drives disposed in the lower dry well can be prevented from submerging. The reactor core can be cooled more reliably, to improve the reliability of the pressure suppression function. (N.H.)

  14. Reactor container spray device

    International Nuclear Information System (INIS)

    Yanai, Ryoichi.

    1980-01-01

    Purpose: To enable decrease in the heat and the concentration of radioactive iodine released from the reactor vessel into the reactor container in the spray device of BWR type reactors. Constitution: A plurality of water receiving trays are disposed below the spray nozzle in the dry well and communicated to a pressure suppression chamber by way of drain pipeways passing through a diaphragm floor. When the recycling system is ruptured and coolants in the reactor vessel and radioactive iodine in the reactor core are released into the dry well, spray water is discharged from the spray nozzle to eliminate the heat and the radioactive iodine in the dry well. In this case, the receiving trays collect the portions of spray water whose absorption power for the heat and radioactive iodine is nearly saturated and falls them into the pool water of the pressure suppression chamber. Consequently, other portions of the spray water that still possess absorption power can be jetted with no hindrance, to increase the efficiency for the removal of the heat and iodine of the spray droplets. (Horiuchi, T.)

  15. MCR Container Tools

    Energy Technology Data Exchange (ETDEWEB)

    2018-01-01

    MathWorks' MATLAB is widely used in academia and industry for prototyping, data analysis, data processing, etc. Many users compile their programs using the MATLAB Compiler to run on workstations/computing clusters via the free MATLAB Compiler Runtime (MCR). The MCR facilitates the execution of code calling Application Programming Interfaces (API) functions from both base MATLAB and MATLAB toolboxes. In a Linux environment, a sizable number of third-party runtime dependencies (i.e. shared libraries) are necessary. Unfortunately, to the MTLAB community's knowledge, these dependencies are not documented, leaving system administrators and/or end-users to find/install the necessary libraries either as runtime errors resulting from them missing or by inspecting the header information of Executable and Linkable Format (ELF) libraries of the MCR to determine which ones are missing from the system. To address various shortcomings, Docker Images based on Community Enterprise Operating System (CentOS) 7, a derivative of Redhat Enterprise Linux (RHEL) 7, containing recent (2015-2017) MCR releases and their dependencies were created. These images, along with a provided sample Docker Compose YAML Script, can be used to create a simulated computing cluster where MATLAB Compiler created binaries can be executed using a sample Slurm Workload Manager script.

  16. Do pyrotechnics contain radium?

    International Nuclear Information System (INIS)

    Steinhauser, Georg; Musilek, Andreas

    2009-01-01

    Many pyrotechnic devices contain barium nitrate which is used as an oxidizer and colouring agent primarily for green-coloured fireworks. Similarly, strontium nitrate is used for red-coloured pyrotechnic effects. Due to their chemical similarities to radium, barium and strontium ores can accumulate radium, causing a remarkable activity in these minerals. Radium in such contaminated raw materials can be processed together with the barium or strontium, unless extensive purification of the ores was undertaken. For example, the utilization of 'radiobarite' for the production of pyrotechnic ingredients can therefore cause atmospheric pollution with radium aerosols when the firework is displayed, resulting in negative health effects upon inhalation of these aerosols. In this study, we investigated the occurrence of gamma-photon-emitting radionuclides in several pyrotechnic devices. The highest specific activities were due to K-40 (up to 20 Bq g -1 , average value 14 Bq g -1 ). Radium-226 activities were in the range of 16-260 mBq g -1 (average value 81 mBq g -1 ). Since no uranium was found in any of the samples, indeed, a slight enrichment of Ra-226 in coloured pyrotechnics can be observed. Radioactive impurities stemming from the Th-232 decay chain were found in many samples as well. In the course of novel developments aiming at the 'greening' of pyrotechnics, the potential radioactive hazard should be considered as well.

  17. MUTATION BREEDING AS MALNUTRITION IN NIGE TATION ...

    African Journals Online (AJOL)

    userpc

    span, early maturing, high nutritional composition and yields with l is study ... Mutation (a change in genetic material of organism) ... 2001), modified plant architecture, closed capsules ... found in the mutants of wheat inbred lines originated ...

  18. Progress of mutation breeding in Thailand

    Energy Technology Data Exchange (ETDEWEB)

    Purivirojkul, Watchara; Vithayatherarat, Pradab [Pathumthani Rice Research Center (Thailand)

    2001-03-01

    The objectives in rice improvement in Thailand are to improve not only for high yielding and good grain quality but also for resistance to diseases and insects and tolerance to biotic stresses. Brief history of research and progress in rice mutation breeding in Thailand is presented. It includes the varieties of method such as using gamma rays, fast neutron and chemical mutagens, for example EMS (ethylmethane sulfonate) and EI (ethylene imine) for mutation works. Among all, improvements of Pathumthani 60 for short-statured plant type, RD23 for blast resistance, Basmati 370 for short-statured plant type, and Pra Doo Daeng for short-statured plant type and awnless grain are reported. To conclude, it is important to find the adequate doses of mutagen treatments that give maximum mutation frequencies, to know the optimal treatments or proper selection methods and to have well-defined objectives to create the success of mutation breeding. (S. Ohno)

  19. Radiation-induced mutations in mammals

    International Nuclear Information System (INIS)

    Ehling, U.H.

    1993-01-01

    The aims of the proposed project are to provide a better basis for extrapolation of animal data to man. Genetic endpoint, strain and species comparisons are made, which will provide critical experimental data regarding strategies in extrapolating laboratory animal data to man. Experiments were conducted to systematically compare the spontaneous and radiation-induced mutation rates for recessive specific-locus, dominant cataract and enzyme activity alleles in the mouse as well as a comparison of the mutation rate in the mouse and hamster for dominant cataract and enzyme activity alleles. The comparison of the radiation-dose response for recessive specific-locus and dominant cataract mutations are extended. Selected mutations are characterized at the genetic, biochemical and molecular levels. (R.P.) 5 refs., 3 tabs

  20. Progress of mutation breeding in Thailand

    International Nuclear Information System (INIS)

    Purivirojkul, Watchara; Vithayatherarat, Pradab

    2001-01-01

    The objectives in rice improvement in Thailand are to improve not only for high yielding and good grain quality but also for resistance to diseases and insects and tolerance to biotic stresses. Brief history of research and progress in rice mutation breeding in Thailand is presented. It includes the varieties of method such as using gamma rays, fast neutron and chemical mutagens, for example EMS (ethylmethane sulfonate) and EI (ethylene imine) for mutation works. Among all, improvements of Pathumthani 60 for short-statured plant type, RD23 for blast resistance, Basmati 370 for short-statured plant type, and Pra Doo Daeng for short-statured plant type and awnless grain are reported. To conclude, it is important to find the adequate doses of mutagen treatments that give maximum mutation frequencies, to know the optimal treatments or proper selection methods and to have well-defined objectives to create the success of mutation breeding. (S. Ohno)

  1. IFITM5 mutations and osteogenesis imperfecta.

    Science.gov (United States)

    Hanagata, Nobutaka

    2016-03-01

    Interferon-induced transmembrane protein 5 (IFITM5) is an osteoblast-specific membrane protein that has been shown to be a positive regulatory factor for mineralization in vitro. However, Ifitm5 knockout mice do not exhibit serious bone abnormalities, and thus the function of IFITM5 in vivo remains unclear. Recently, a single point mutation (c.-14C>T) in the 5' untranslated region of IFITM5 was identified in patients with osteogenesis imperfecta type V (OI-V). Furthermore, a single point mutation (c.119C>T) in the coding region of IFITM5 was identified in OI patients with more severe symptoms than patients with OI-V. Although IFITM5 is not directly involved in the formation of bone in vivo, the reason why IFITM5 mutations cause OI remains a major mystery. In this review, the current state of knowledge of OI pathological mechanisms due to IFITM5 mutations will be reviewed.

  2. Modification of mutation frequency in Saccharomyces Cerevisiae

    International Nuclear Information System (INIS)

    Vashishat, R.K.; Kakar, S.N.

    1976-01-01

    In a reverse mutation system, using haploid, histidine-requirinq strain of Saccharomyces cerevisiae, the frequency of uv-induced prototrophs increased if the post-irradiation minimal medium was supplemented with limited amounts of histidine. Addition of natural amino acids or RNA bases in the post-irradiation minimal medium, with or without histidine, also increased the uv-induced mutation frequency. Thus, post-irradiation conditions favouring protein and RNA synthesis, are effective in increasing uv-induced mutations in yeast. As compared to uv light, nitrous acid was more effective in inducing reversions in this strain and the frequency increased if the treated cells were plated on minimal medium supplemented with limited amounts of histidine. However, the addition of amino acids or RNA bases decreased the number of revertants. An additional inclusion of histidine reversed the suppressive effect of these metabolites. The mutation induction processes are thus different or differently modifiable in uv and nitrous acid. (author)

  3. Cross-resistance patterns to acetolactate synthase (ALS)-inhibiting herbicides of flixweed (Descurainia sophia L.) conferred by different combinations of ALS isozymes with a Pro-197-Thr mutation or a novel Trp-574-Leu mutation.

    Science.gov (United States)

    Deng, Wei; Yang, Qian; Zhang, Yongzhi; Jiao, Hongtao; Mei, Yu; Li, Xuefeng; Zheng, Mingqi

    2017-03-01

    Acetolactate synthase (ALS) is the common target of ALS-inhibiting herbicides, and target-site ALS mutations are the main mechanism of resistance to ALS-inhibiting herbicides. In this study, ALS1 and ALS2 genes with full lengths of 2004bp and 1998bp respectively were cloned in individual plants of susceptible (S) or resistant (R) flixweed (Descurainia sophia L.) populations. Two ALS mutations of Pro-197-Thr and/or Trp-574-Leu were identified in plants of three R biotypes (HB24, HB30 and HB42). In order to investigate the function of ALS isozymes in ALS-inhibiting herbicide resistance, pHB24 (a Pro-197-Thr mutation in ALS1 and a wild type ALS2), pHB42 (a Trp-574-Leu mutation in ALS1 and a wild type ALS2) and pHB30 (a Trp-574-Leu mutation in ALS1 and a Pro-197-Thr mutation in ALS2) subpopulations individually homozygous for different ALS mutations were generated. Individuals of pHB30 had mutations in each isozyme of ALS and had higher resistance than pHB24 and pHB42 populations containing mutations in only one ALS isozyme. Moreover, the pHB24 had resistance to SU, TP and SCT herbicides, whereas pHB24 and pHB42 had resistance to these classes of herbicides as well as IMI and PTB herbicides. The sensitivity of isolated ALS enzyme to inhibition by herbicides in these populations correlated with whole plant resistance levels. Therefore, reduced ALS sensitivity resulting from the mutations in ALS was responsible for resistance to ALS-inhibiting herbicides in flixweed. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Induced mutations - a tool in plant research

    International Nuclear Information System (INIS)

    1981-01-01

    These proceedings include 34 papers and 18 brief descriptions of poster presentations in the following areas as they are affected by induced mutations: advancement of genetics, plant evolution, plant physiology, plant parasites, plant symbioses, in vitro culture, gene ecology and plant breeding. Only a relatively small number of papers are of direct nuclear interest essentially in view of the mutations being induced by ionizing radiations. The papers of nuclear interest have been entered as separate and individual items of input

  5. Learning resistance mutation pathways of HIV

    OpenAIRE

    Ramon, Jan; Dubrovskaya, Snezhana; Blockeel, Hendrik

    2007-01-01

    We propose a novel machine learning algorithm for learning mutation pathways of viruses from a population of viral DNA strands. More specifically, given a number of sequences, the algorithm constructs a phylogenetic tree that expresses the ancestry of the sequences, and at the same time builds a model describing dependencies between mutations that is consistent with the data as well as the phylogenetic tree. Our approach extends existing approaches for phylogenetic tree construction by not as...

  6. Mitochondrial DNA mutations in human tumor cells

    OpenAIRE

    LI, HUI; HONG, ZE-HUI

    2012-01-01

    Mitochondria play significant roles in cellular energy metabolism, free radical generation and apoptosis. The dysfunction of mitochondria is correlated with the origin and progression of tumors; thus, mutations in the mitochondrial genome that affect mitochondrial function may be one of the causal factors of tumorigenesis. Although the role of mitochondrial DNA (mtDNA) mutations in carcinogenesis has been investigated extensively by various approaches, the conclusions remain controversial to ...

  7. Identifying driver mutations in sequenced cancer genomes

    DEFF Research Database (Denmark)

    Raphael, Benjamin J; Dobson, Jason R; Oesper, Layla

    2014-01-01

    High-throughput DNA sequencing is revolutionizing the study of cancer and enabling the measurement of the somatic mutations that drive cancer development. However, the resulting sequencing datasets are large and complex, obscuring the clinically important mutations in a background of errors, nois...... patterns of mutual exclusivity. These techniques, coupled with advances in high-throughput DNA sequencing, are enabling precision medicine approaches to the diagnosis and treatment of cancer....

  8. Mutation Rates of STR Systems in Danes

    DEFF Research Database (Denmark)

    Andersen, Kim Emil; Bøttcher, Susanne Gammelgaard; Christensen, Susanne

    Danish paternity cases in the period 1999 to 2005 were investigated regarding mutation rates in STR loci. STR-typing was performed by the Applied Biosystems AmplfStr Profiler Plus kit in the period 1999 to early 2005, hereafter named the PP9, and by Applied Biosystems AmplfStr Identifier kit for ...... and kits. Sex and STR locus specific mutation rates were estimated with 95% confidence limits by the method of Clopper and Pearson (1934)....

  9. Factor V Leiden mutation in pregnancy.

    Science.gov (United States)

    Cohen, Susan Murphy

    2004-01-01

    Normal maternal adaptation to pregnancy significantly increases the risk for thrombus formation. Inherited thrombophilias further increase risk for deep venous thrombosis and adverse outcome in pregnancy. Factor V Leiden mutation is the most common inherited thrombophilia, occurring in approximately 5% of the White and 1% of the Black populations. Nurses should be knowledgeable about screening for and diagnosis of factor V Leiden mutation, risk reduction counseling, recommended care of the affected patient, and implications of anticoagulant therapy during the perinatal period.

  10. Mutation induction in plants by ionizing radiation

    International Nuclear Information System (INIS)

    1985-01-01

    This training film deals with the use of x-rays, gamma rays and fast neutrons for mutation induction in plants. Specific features of different types of ionizing radiation and of biological materials are outlined and methods demonstrated which control modifying factors and warrant an efficient physical mutagenesis. The first step of mutation breeding aims at an enhanced level of genetic variation which forms the basis for mutant selection and use in plant breeding

  11. Use of induced mutations in soybean breeding

    International Nuclear Information System (INIS)

    Zakri, A.H.; Jalani, B.S.; Ng, K.F.

    1981-01-01

    Artificial induction of mutation in plants is carried out using #betta#-irradiation and ethyl metanesulphonate (EMS) to expand the genetic variability of locally-grown soybean. This aspect of mutation breeding complements of conventional breeding approach undertaken by the Joint Malaysia Soybean Breeding Project group. Recovery of agronomically-important mutants such as earliness, lateness, bigger seed size and improved plant architecture were recorded. The significance of these findings is discussed. (author)

  12. Latex allergy and filaggrin null mutations

    DEFF Research Database (Denmark)

    Carlsen, Berit C; Meldgaard, Michael; Hamann, Dathan

    2011-01-01

    to aeroallergens and it is possible that filaggrin null mutations also increase the risk of latex allergy. The aim of this paper was to examine the association between filaggrin null mutations and type I latex allergy. Methods Twenty latex allergic and 24 non-latex allergic dentists and dental assistants...... in the cases in this study may not have occurred through direct skin contact but through the respiratory organs via latex proteins that are absorbed in glove powder and aerosolized...

  13. Mutation breeding of autotetraploid Achimenes cultivars

    International Nuclear Information System (INIS)

    Broertjes, C.

    1976-01-01

    Colchicine-induced autotetraploids of three Achimenes cultivars were irradiated with X-rays or fast neutrons. The results were compared, in one cultivar, with those of the irradiated diploid form. The mutation frequency after irradiation of the autotetraploid was a 20-40 fold higher as compared to the corresponding diploid. These results may open new possibilities for mutation breeding, though they are hard to explain. Several promising mutants were selected. (author)

  14. Exploring the common molecular basis for the universal DNA mutation bias: Revival of Loewdin mutation model

    International Nuclear Information System (INIS)

    Fu, Liang-Yu; Wang, Guang-Zhong; Ma, Bin-Guang; Zhang, Hong-Yu

    2011-01-01

    Highlights: → There exists a universal G:C → A:T mutation bias in three domains of life. → This universal mutation bias has not been sufficiently explained. → A DNA mutation model proposed by Loewdin 40 years ago offers a common explanation. -- Abstract: Recently, numerous genome analyses revealed the existence of a universal G:C → A:T mutation bias in bacteria, fungi, plants and animals. To explore the molecular basis for this mutation bias, we examined the three well-known DNA mutation models, i.e., oxidative damage model, UV-radiation damage model and CpG hypermutation model. It was revealed that these models cannot provide a sufficient explanation to the universal mutation bias. Therefore, we resorted to a DNA mutation model proposed by Loewdin 40 years ago, which was based on inter-base double proton transfers (DPT). Since DPT is a fundamental and spontaneous chemical process and occurs much more frequently within GC pairs than AT pairs, Loewdin model offers a common explanation for the observed universal mutation bias and thus has broad biological implications.

  15. The Oenothera plastome mutator: effect of UV irradiation and nitroso-methyl urea on mutation frequencies

    International Nuclear Information System (INIS)

    Sears, B.B.; Sokalski, M.B.

    1991-01-01

    Oenothera plants homozygous for a recessive plastome mutator allele (pm) showed spontaneous mutation frequencies for plastome genes that are 200-fold higher than spontaneous levels. Mutations occurred at high frequencies in plants grown in the field, in a glasshouse, or as leaf tip cultures under fluorescent light, indicating that the plastome mutator activity is UV-independent. However, the chlorotic sectors became visible at an earlier stage of development when seedlings were irradiated, compared to seedlings that were not exposed to UV. These results imply that the rate of sorting-out was increased by the irradiation treatment, possibly due to a decrease in the effective number of multiplication-competent plastids, or a reduction in the extent of cytoplasmic mixing. Nitroso-methyl urea treatment of seeds had a dramatic effect on mutation frequency in both wild-type and plastome mutator samples. When the background mutation rates were low, the combination of the plastome mutator nucleus and the chemical mutagenesis treatment resulted in a synergistic effect, suggesting that the plastome mutator may involve a cpDNA repair pathway. (author)

  16. Diploid yeast cells yield homozygous spontaneous mutations

    Science.gov (United States)

    Esposito, M. S.; Bruschi, C. V.; Brushi, C. V. (Principal Investigator)

    1993-01-01

    A leucine-requiring hybrid of Saccharomyces cerevisiae, homoallelic at the LEU1 locus (leu1-12/leu1-12) and heterozygous for three chromosome-VII genetic markers distal to the LEU1 locus, was employed to inquire: (1) whether spontaneous gene mutation and mitotic segregation of heterozygous markers occur in positive nonrandom association and (2) whether homozygous LEU1/LEU1 mutant diploids are generated. The results demonstrate that gene mutation of leu1-12 to LEU1 and mitotic segregation of heterozygous chromosome-VII markers occur in strong positive nonrandom association, suggesting that the stimulatory DNA lesion is both mutagenic and recombinogenic. In addition, genetic analysis of diploid Leu+ revertants revealed that approximately 3% of mutations of leu1-12 to LEU1 result in LEU1/LEU1 homozygotes. Red-white sectored Leu+ colonies exhibit genotypes that implicate post-replicational chromatid breakage and exchange near the site of leu1-12 reversion, chromosome loss, and subsequent restitution of diploidy, in the sequence of events leading to mutational homozygosis. By analogy, diploid cell populations can yield variants homozygous for novel recessive gene mutations at biologically significant rates. Mutational homozygosis may be relevant to both carcinogenesis and the evolution of asexual diploid organisms.

  17. The Mutations Associated with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ruti Parvari

    2012-01-01

    Full Text Available Cardiomyopathy is an important cause of heart failure and a major indication for heart transplantation in children and adults. This paper describes the state of the genetic knowledge of dilated cardiomyopathy (DCM. The identification of the causing mutation is important since presymptomatic interventions of DCM have proven value in preventing morbidity and mortality. Additionally, as in general in genetic studies, the identification of the mutated genes has a direct clinical impact for the families and population involved. Identifying causative mutations immediately amplifies the possibilities for disease prevention through carrier screening and prenatal testing. This often lifts a burden of social isolation from affected families, since healthy family members can be assured of having healthy children. Identification of the mutated genes holds the potential to lead to the understanding of disease etiology, pathophysiology, and therefore potential therapy. This paper presents the genetic variations, or disease-causing mutations, contributing to the pathogenesis of hereditary DCM, and tries to relate these to the functions of the mutated genes.

  18. Apparent directional selection by biased pleiotropic mutation.

    Science.gov (United States)

    Tanaka, Yoshinari

    2010-07-01

    Pleiotropic effects of deleterious mutations are considered to be among the factors responsible for genetic constraints on evolution by long-term directional selection acting on a quantitative trait. If pleiotropic phenotypic effects are biased in a particular direction, mutations generate apparent directional selection, which refers to the covariance between fitness and the trait owing to a linear association between the number of mutations possessed by individuals and the genotypic values of the trait. The present analysis has shown how the equilibrium mean value of the trait is determined by a balance between directional selection and biased pleiotropic mutations. Assuming that genes act additively both on the trait and on fitness, the total variance-standardized directional selection gradient was decomposed into apparent and true components. Experimental data on mutation bias from the bristle traits of Drosophila and life history traits of Daphnia suggest that apparent selection explains a small but significant fraction of directional selection pressure that is observed in nature; the data suggest that changes induced in a trait by biased pleiotropic mutation (i.e., by apparent directional selection) are easily compensated for by (true) directional selection.

  19. Study on space mutation breeding of rice

    International Nuclear Information System (INIS)

    Xu Jianlong; Lin Yizi; Xi Yongan; Jiang Xingcun; Li Jinguo

    1997-01-01

    Air-dried seeds of rice variety ZR9 were carried by high altitude balloon (HAB) and recoverable satellite (RS) for space mutation. Mutagentic effects of high altitude environment (HAE) of 30∼38 km and outer space environment (OSE) of 218∼326 km above sea level on rice plant were studied. The results indicated that the germination percentage (GP) of seeds was obviously lower than that of the controls. the mutation in plant height (PH) and growth period duration (GPD) of SP 1 carried by HAB were induced. However, the GP of seeds and characters of SP 1 carried by RS had no evident change. More stronger segregation of major characters such as PH, GPD and length of panicle, appeared in the two SP 2 generations resulting from HAB and RS. And their mutation frequency were 4.31% and 4.10% respectively. Mutation lines selected from the two mutation progenies improved significantly in PH, GPD, disease resistance and yield. Therefore, space mutation could be considered as a new breeding method

  20. TOX3 mutations in breast cancer.

    Directory of Open Access Journals (Sweden)

    James Owain Jones

    Full Text Available TOX3 maps to 16q12, a region commonly lost in breast cancers and recently implicated in the risk of developing breast cancer. However, not much is known of the role of TOX3 itself in breast cancer biology. This is the first study to determine the importance of TOX3 mutations in breast cancers. We screened TOX3 for mutations in 133 breast tumours and identified four mutations (three missense, one in-frame deletion of 30 base pairs in six primary tumours, corresponding to an overall mutation frequency of 4.5%. One potentially deleterious missense mutation in exon 3 (Leu129Phe was identified in one tumour (genomic DNA and cDNA. Whilst copy number changes of 16q12 are common in breast cancer, our data show that mutations of TOX3 are present at low frequency in tumours. Our results support that TOX3 should be further investigated to elucidate its role in breast cancer biology.