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Sample records for 0-50 rad range

  1. 28 CFR 0.50 - General functions.

    2010-07-01

    ..., enforcement, and investigatory activities under section 102 of the Immigration Reform and Control Act of 1986, as amended. Editorial Note: For Federal Register citations affecting § 0.50, see the List of CFR..., abortion, sterilization, credit, and constitutional and civil rights of Indians arising under 25...

  2. ERRATA SHEET for Post-Closure Inspection Report for Corrective Action Unit 407: Roller Coaster RadSafe Area Tonopah Test Range, Nevada, Calendar year 2001; TOPICAL

    The fifth sentence of the first paragraph on Page 1 of the Post Closure Inspection Report for Corrective Action Unit 407: Roller Coaster RadSafe Area, Tonopah Test Range, Nevada erroneously states that Revision 1 of the CR was issued in December of 2001 and was approved by NDEP on January 7, 2002. The sentence should state that Revision 1 of the CR was issued in December of 2001 and was approved by NDEP on February 22, 2002

  3. Unusual isotope effects for diffusion in VH 0.50 and VT 0.50

    Nonclassical diffusion processes for hydrogen isotopes in metals and other solids remain interesting and unresolved challenges. Although numerous diffusion measurements have been performed on dilute solutions of hydrogen, deuterium, and tritium in metals, relatively few results are available for diffusion of hydrogen isotopes in the hydride phases formed at higher concentrations. Since diffusion coefficients are generally dependent upon concentration, this disparity is partially due to the difficulty in preparing samples with identical contents. The vanadium hydride phases are promising candidates to study isotopic diffusion. Recent nuclear magnetic resonance (NMR) studies of proton spin-lattice relaxation times T1 for b.c.t. βphase VH /SUB x/ (0.4< x<0.9) have shown anomalous hydrogen diffusion behavior. Furthermore, the remark ably large differences between the VH /SUB x/ and VD /SUB x/ phase diagrams suggest that significant isotope effects may also occur in the diffusion processes. In fact, several unusual isotope effects in diffusion behavior for VH 0.50 and VT 0.50 are indicated from the present NMR relaxation times. Tritium atoms in β-VT 0.5 diffuse more rapidly and with a smaller activation energy than hydrogen atoms in β-VH 0.5. These inverse isotope effects are related to an enhanced T-atom mobility i β-VT 0.50 that arises from atomic exchange processes between T-atoms on inequivalent interstitial sites

  4. Directional frustration of magnetic moments in (U0.50Dy0.50)Ni2B2C

    Polycrystalline (U0.50Dy0.50)Ni2B2C solid solution was prepared and found by X-ray diffraction to crystallize in BCT LuNi2B2C-type structure (space group I4/mmm) of the end compounds UNi2B2C and DyNi2B2C. AC susceptibility and magnetization show paramagnetic behavior down to 6.5 K, with the values θ=-5(5) K and μeff=7.7(1) μB, compatible with those of the end compounds, and indicate possible cooperative phenomena at lower temperatures. The observed paramagnetism, at variance with antiferromagnetic ordering in (Pr0.50Dy0.50)Ni2B2C, is attributed to a directional frustration of the magnetic moments on the (U,Dy) site

  5. RadLex

    U.S. Department of Health & Human Services — RadLex is a controlled terminology for radiology and serves as a single unified source of radiology terms for radiology practice, education, and research. RadLex is...

  6. Thickness dependent structural, magnetic and magneto-transport properties of epitaxial Nd0.50Sr0.50MnO3 thin films

    Kumar, Pawan; Singh, Hari Krishna

    2016-05-01

    We report the thickness-dependent structural, magnetic and magneto-transport properties in epitaxial Nd0.50Sr0.50MnO3 thin films (10 to 300nm) prepared by DC magnetron sputtering technique on single crystalline (001) oriented substrate LaAlO3. X-ray diffraction pattern reveals the epitaxial growth of all the films and the out-of-plane lattice parameter of films were found to increase with thickness. As thickness of the film increases the paramagnetic insulator (PMI) to ferromagnetic metal (FMM) transition temperature (TC), charge ordered transition temperature (TCO) and magnetic moment were found to increase with a strong bifurcation in ZFC-FC magnetization. The asymmetry in the coercivity seen in field dependent magnetization loops (M-H loops) suggests the presence of exchange bias (EB) effect. While temperature dependent resistivity of films show the semiconducting nature for thickness 10-200nm in temperature range from 5-300K, the film of thickness 300nm shows the insulator to metal transition with transition temperature (TIM) at 175K. Temperature dependent low field magnetoresistance (LFMR) measured at 4kOe found to decrease with thickness and for high field magnetoresistance (HFMR) at 40kOe and 60kOe also show similar dependence and a crossover at intermediate temperature range in the magnitude of MR between 10nm and 200nm films at constant field. Colossal increase in magnetoresistance observed for 10nm film at low temperature.

  7. RadWorks Project

    National Aeronautics and Space Administration — For the first two years of the project (FY12-13), the RadWorks project has consisted of two top-level elements. The first element involved the prototype and...

  8. Reach Address Database (RAD)

    U.S. Environmental Protection Agency — The Reach Address Database (RAD) stores the reach address of each Water Program feature that has been linked to the underlying surface water features (streams,...

  9. Interactions of checkpoint-genes RAD9, RAD17, RAD24 and RAD53 determining radioresistance of Yeast Saccharomyces Cerevisiae

    The mechanisms of genetic control of progress through the division cell cycle (checkpoint-control) in yeast Saccharomyces cerevisiae have been studied intensively. To investigate the role of checkpoint-genes RAD9, RAD17, RAD24, RAD53 in cell radioresistance we have investigated cell sensitivity of double mutants to γ-ray. Double mutants involving various combinations with rad9Δ show epistatic interactions, i.e. the sensitivity of the double mutants to γ-ray was no greater than that of more sensitive of the two single mutants. This suggests that all these genes govern the same pathway. This group of genes was named RAD9-epistasis group. It is interesting to note that the genes RAD9 and RAD53 have positive effect but RAD17 and RAD24 have negative effect on radiosensitivity of yeast cells. Interactions between mutations may differ depending on the agent γ-ray or UV-light, for example mutations rad9Δ and rad24Δ show additive effect for γ-ray and epistatic effect for UV-light

  10. RadGenomics project

    Human health is determined by a complex interplay of factors, predominantly between genetic susceptibility, environmental conditions and aging. The ultimate aim of the RadGenomics (Radiation Genomics) project is to understand the implications of heterogeneity in responses to ionizing radiation arising from genetic variation between individuals in the human population. The rapid progression of the human genome sequencing and the recent development of new technologies in molecular genetics are providing us with new opportunities to understand the genetic basis of individual differences in susceptibility to natural and/or artificial environmental factors, including radiation exposure. The RadGenomics project will inevitably lead to improved protocols for personalized radiotherapy and reductions in the potential side effects of such treatment. The project will contribute to future research into the molecular mechanisms of radiation sensitivity in humans and will stimulate the development of new high-throughput technologies for a broader application of biological and medical sciences. The staff members are specialists in a variety of fields, including genome science, radiation biology, medical science, molecular biology, and informatics, and have joined the RadGenomics project from various universities, companies, and research institutes. The project started in April 2001. (author)

  11. Role of Pr cations and the low temperature transition in Pr{sub 0.50}Sr{sub 0.50}CoO{sub 3}: A comparison to Pr{sub 0.50}Ca{sub 0.50}CoO{sub 3}

    Padilla-Pantoja, J., E-mail: jpadilla@icmab.es [Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Campus univ. de Bellaterra, E-08193 Bellaterra (Spain); Barón-González, A.J. [Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Campus univ. de Bellaterra, E-08193 Bellaterra (Spain); Grupo Física de Materiales, Universidad Pedagógica y Tecnológica de Colombia, Tunja (Colombia); Bozzo, B. [Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Campus univ. de Bellaterra, E-08193 Bellaterra (Spain); Blasco, J. [Instituto de Ciencia de Materiales de Aragón, CSIC-Univ. de Zaragoza, 50009 Zaragoza (Spain); Ritter, C. [Institute Laue Langevin, BP 156, 38042 Grenoble Cedex 9 (France); Herrero-Martín, J. [ALBA Synchrotron Light Source, 08290 Cerdanyola del Vallès, Barcelona (Spain); García-Muñoz, J.L. [Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Campus univ. de Bellaterra, E-08193 Bellaterra (Spain)

    2014-12-15

    The low temperature properties of Pr{sub 0.50}Sr{sub 0.50}CoO{sub 3} are studied in comparison to Pr{sub 0.50}Ca{sub 0.50}CoO{sub 3}, which is known to exhibit a Pr{sup 3+}/Pr{sup 4+} valence shift below T{sub MI}∼80 K. The evolution of the Pr–O network strongly differs in the Sr and Ca compounds, but both have in common a prominent and sudden contraction of some Pr–O bonds. The structural phase transition that accompanies the so-called magnetocrystalline anisotropy transition at T{sub S}∼120 K in Pr{sub 0.50}Sr{sub 0.50}CoO{sub 3} brings about a notable contraction of some Pr–O{sub 2} bonds. The observations give support to the active participation of Pr-4f electrons at the intriguing magnetostructural transition (T{sub S}) in Pr{sub 0.50}Sr{sub 0.50}CoO{sub 3}. In addition, we have confirmed that (in absence of praseodymium) the magnetostructural transition is suppressed in (Nd{sub 2/3}La{sub 1/3}){sub 0.50}Sr{sub 0.50}CoO{sub 3}, a perovskite with the same average cationic size at the A-site than Pr{sub 0.50}Sr{sub 0.50}CoO{sub 3}.

  12. From first-order magneto-elastic to magneto-structural transition in (Mn,Fe)1.95P0.50Si0.50 compounds

    Dung, N.H.; Zhang, L; Ou, Z.Q.; Brück, E

    2012-01-01

    We report on structural, magnetic, and magnetocaloric properties of MnxFe1.95−xP0.50Si0.50 (x ≥ 1.10) compounds. With increasing the Mn:Fe ratio, a first-order magneto-elastic transition gradually changes into a first-order magneto-structural transition via a second-order magnetic transition. The study also shows that thermal hysteresis can be tuned by varying the Mn:Fe ratio. Small thermal hysteresis (less than 1 K) can be obtained while maintaining a giant magnetocaloric effect. This achiev...

  13. Complex formation in yeast double-strand break repair: participation of Rad51, Rad52, Rad55, and Rad57 proteins.

    Hays, S L; Firmenich, A A; Berg, P

    1995-01-01

    The repair of DNA double-strand breaks in Saccharomyces cerevisiae requires genes of the RAD52 epistasis group, of which RAD55 and RAD57 are members. Here, we show that the x-ray sensitivity of rad55 and rad57 mutant strains is suppressible by overexpression of RAD51 or RAD52. Virtually complete suppression is provided by the simultaneous overexpression of RAD51 and RAD52. This suppression occurs at 23 degrees C, where these mutants are more sensitive to x-rays, as well as at 30 degrees C and...

  14. Electrical conduction mechanism and improved multiferroic properties of NFO/ (Pb0.50Sr0.50) TiO3 bilayer nanostructure composite thin film

    Bala, Kanchan; Ram, Mast; Sharma, Hakikat; Negi, N. S.

    2016-05-01

    Multiferroic 2-2 type layered NFO/ (Pb0.50Sr0.50) TiO3 composite thin film on Pt/TiO2/Si substrate was prepared by novel metallo-Organic process using spin coating technique. The structural and surface morphology were confirmed by X-Ray diffraction (XRD) atomic force microscope (AFM). Significantly improved ferroelectric properties (Ps ˜ 8.69, Pr ˜ 3.19 µC/cm2 and Ec ˜ 419kV/cm) and magnetic properties (Ms), (Mr) and (Hc) is (104emu/cc, 0.8emu/cc and 25Oe.) were observed at room temperature. Our observation provides an effective way to manipulate the conduction behavior to understand the leakage current density of multiferroic composites film at the interface. Poole-Frankel tunneling conduction mechanism dominates the leakage current of films in the relatively high electric filed.

  15. Identification of cloned genes that complement the rad50-1, rad51-1, rad54-3 and rad55-3 mutations in yeast

    Plasmids that complement the rad50-1, rad51-1, rad54-3 and rad55-3 mutations in yeast, have been isolated. They were obtained by transforming strains, carrying the leu2-112 leu2-3 alleles and the particular rad mutation, with YEp13 plasmids containing near random yeast DNA inserts. Rad+ clones were identified among the Leu+ transformants. Integration by targeting into the RAD55 locus showed that the rad55-3 complementing plasmid contained the actual RAD55 gene. BamHI fragments from each of the plasmids that complement rad50-1, rad51-1 and rad54-3, all of which lacked Rad+ activity, were subcloned into the integrating plasmid YIp5 and the hybrid plasmids were used to transform a Rad+ Ura- strain to Ura+. By genetic mapping, the rad51 and rad54 subclones were shown to integrate at their respective loci. However, the rad50 subclones integrated at a site unlinked to the RAD50 locus. This suggests that no homology exists between this BamHI fragment and the RAD50 gene. Integration at the RAD54 locus of the rad54 subclone made the host cell Ura+ but Rad-; excision of the plasmid was shown to be x-ray inducible and to restore the Ura- Rad+ phenotype. These results indicate that the BamHI fragment of the RAD54 plasmid is internal to the RAD54 gene. We can conclude also that the RAD54 gene is not essential as cells bearing a disrupted copy of this gene are able to survive. Additionally, a plasmid carrying an amber suppressor has been isolated and characterized

  16. Synthesis, structure, and physicochemical investigations of the new α Cu0.50TiO(PO4) oxyphosphate

    The room-temperature crystal structure of a new Cu(II) oxyphosphate-α Cu0.50IITiO(PO4)-was determined from X-ray single crystals diffraction data, in the monoclinic system, space group P21/c. The refinement from 5561 independent reflections lead to the following parameters: a=7.5612(4)A, b=7.0919(4)A, c=7.4874(4)A, β=122.25(1)o, Z=4, with the final R=0.0198, wR=0.0510. The structure of α Cu0.50IITiO(PO4) can be described as a TiOPO4 framework constituted by chains of tilted corner-sharing [TiO6] octahedra running parallel to the c-axis and cross linked by phosphate [PO4] tetrahedra, where one-half of octahedral cavities created are occupied by Cu atoms. Ti atoms are displaced from the center of octahedra units in alternating long (2.308 A) and short (1.722 A) Ti-O(1) bonds along chains. Such O(1) atoms not linked to P atoms justify the oxyphosphate formulation α Cu0.50TiO(PO4). The divalent cations Cu2+ occupy a Jahn-Teller distorted octahedron sharing two faces with two [TiO6] octahedra. EPR and optical measurements are in good agreement with structural data. The X-ray diffraction results are supported by Raman and infrared spectroscopy studies that confirmed the existence of the infinite chains -Ti-O-Ti-O-Ti-. α Cu0.50TiO(PO4) shows a Curie-Weiss paramagnetic behavior in the temperature range 4-80 K. - Graphical abstract: Projection of the structure of α Cu0.50TiO(PO4) along the a-axis

  17. Extreme Temperature, Rad-Hard Power Management ASIC Project

    National Aeronautics and Space Administration — Ridgetop Group will design a rad-hard Application Specific Integrated Circuit (ASIC) for spacecraft power management that is functional over a temperature range of...

  18. Rad Pole Cam Development

    The RadPoleCam was developed to provide Department Of Energy (DOE) first responders the capability to assess the radiological and visual condition of remote or inaccessible locations. Real time gamma isotopic identification is provided to the first responder in the form of audio feedback (i.e. spoken through head phones) from a gamma detector mounted on a collapsible pole that can extend from 1 to 9 meters (6 to 29 feet). Simultaneously, selectable direct and side looking visual images are provided from the 5cm (2in) diameter, waterproof probe tip. The lightweight, self contained, ruggedized, system will provide a rapidly deployable field system for visual and radiological search and assessment of confined spaces and extended reach locations

  19. Rad52 and Rad59 exhibit both overlapping and distinct functions

    Feng, Qi; Düring, Louis; Antúnez de Mayolo, Adriana;

    2007-01-01

    annealing of complementary single-stranded DNA in vitro, but only Rad52 interacts with replication protein A and the Rad51 recombinase. We have studied the functional overlap between Rad52 and Rad59 in living cells using chimeras of the two proteins and site-directed mutagenesis. We find that Rad52 and Rad...

  20. Ionizing radiation-induced foci formation of mammalian Rad51 and Rad54 depends on the Rad51 paralogs, but not on Rad52

    Homologous recombination is of major importance for the prevention of genomic instability during chromosome duplication and repair of DNA damage, especially double-strand breaks. Biochemical experiments have revealed that during the process of homologous recombination the RAD52 group proteins, including Rad51, Rad52 and Rad54, are involved in an essential step: formation of a joint molecule between the broken DNA and the intact repair template. Accessory proteins for this reaction include the Rad51 paralogs and BRCA2. The significance of homologous recombination for the cell is underscored by the evolutionary conservation of the Rad51, Rad52 and Rad54 proteins from yeast to humans. Upon treatment of cells with ionizing radiation, the RAD52 group proteins accumulate at the sites of DNA damage into so-called foci. For the yeast Saccharomyces cerevisiae, foci formation of Rad51 and Rad54 is abrogated in the absence of Rad52, while Rad51 foci formation does occur in the absence of the Rad51 paralog Rad55. By contrast, we show here that in mammalian cells, Rad52 is not required for foci formation of Rad51 and Rad54. Furthermore, radiation-induced foci formation of Rad51 and Rad54 is impaired in all Rad51 paralog and BRCA2 mutant cell lines tested, while Rad52 foci formation is not influenced by a mutation in any of these recombination proteins. Despite their evolutionary conservation and biochemical similarities, S. cerevisiae and mammalian Rad52 appear to differentially contribute to the DNA-damage response

  1. Investigations of the regulation of cerebral circulation by means of functional changes observed on unanaesthetized rabbits during hypoxia, paradoxical sleep and after whole-body γ-exposure (850-150 rad dose range)

    Both the general effects and the effects on cerebral circulation of whole-body exposure were studied at doses of 850, 650, 450, 250 and 150 rads. Early functional changes following exposure demonstrated two juxtaposed mechanisms, a central one and a peripheral one. The central process, slightly sensitive to the dose-effect, occurred earlier and should be at the origin of hyperthermia, hyperventilation, tachycardia, skin vasoconstruction and a slight increase of arterial pressure. The peripheral mechanisms, occurring slightly later should be more sensitive to the dose-effect and might be at the origin of hypothermic effects and cardiovascular depression. The increase of cerebral blood flow occurring at the 450 rad dose should be best explained by the presence of vasotropic substances. A twofold component of cerebral vasotonicity should be assumed that would depend on the autonomous nervous system and myogenous autoregulation

  2. Laser-Assisted Synthesis of Mn0.50Zn0.50Fe2O4 Nanomaterial: Characterization and In Vitro Inhibition Activity towards Bacillus subtilis Biofilm

    Shaukat Ali Shahid

    2015-01-01

    Full Text Available There is growing interest in the development of novel nanomaterials with potential antimicrobial activity and lesser toxicity. In the current research work, Mn0.5Zn0.5Fe2O4 nanoparticles were synthesized via a novel coprecipitation cum laser ablation technique yielding fine spinal structured material. The synthesized nanomaterial was structurally characterized by X-ray diffraction technique which confirmed the formation and the crystalline nature of Mn0.50Zn0.50Fe2O4 nanomaterial. The crystallite size determined by Debye-Scherrer’s formula was found to be ~12 nm. The formation of nanoparticles was evidenced by scanning electron microscopy. Energy dispersive X-ray analysis (EDXA was performed for elemental analysis. The synthesized nanomaterial was interestingly found to be an effective antimicrobial agent and inhibited the growth of Bacillus subtilis biofilm formation. The 5 µg of Mn0.5Zn0.5Fe2O4 nanomaterial dissolved in 1 mL of DMSO showed excellent biofilm inhibitory activity 91.23% ± 1.87 against Bacillus subtilis.

  3. RadFlexPro Project

    National Aeronautics and Space Administration — Our proposed multilayered, flexible, graded Z radiation shielding, RadFlexPro, provides radiation protection for astronauts in EVA for NASA's future space missions....

  4. Wallac automatic alarm dosimeter type RAD21

    The Automatic Alarm Dosimeter type RAD 21 is a batterypowered personal dosemeter and exposure rate alarm monitor, designed to be worn on the body, covering an exposure range from 0.1 to 999.9 mR and has an audible alarm which can be pre-set over the range 1 mR h-1 to 250 mR h-1. The instrument is designed to measure x- and γ radiation over the energy range 50 keV to 3 MeV. The facilities and controls, the radiation, electrical, environmental and mechanical characteristics, and the manual, have been evaluated. (U.K.)

  5. Long Term RadNet Quality Data

    U.S. Environmental Protection Agency — This RadNet Quality Data Asset includes all data since initiation and when ERAMS was expanded to become RadNet, name changed to reflect new mission. This includes...

  6. Preferential binding of yeast Rad4-Rad23 complex to damaged DNA

    The yeast Rad4 and Rad23 proteins form a complex that is involved in nucleotide excision repair (NER). Their function in this process is not known yet, but genetic data suggest that they act in an early step in NER. We have purified an epitope-tagged Rad4.Rad23 (tRad4. Rad23) complex from yeast cells, using a clone overproducing Rad4 with a hemagglutinin-tag at its C terminus. tRad4.Rad23 complex purified by both conventional and immuno-affinity chromatography complements the in vitro repair defect of rad4 and rad23 mutant extracts, demonstrating that these proteins are functional in NER. Using electrophoretic mobility shift assays, we show preferential binding of the tRad4.Rad23 complex to damaged DNA in vitro. UV-irradiated, as well as N-acetoxy-2-(acetylamino)fluorene-treated DNA, is efficiently bound by the protein complex. These data suggest that Rad4.Rad23 interacts with DNA damage during NER and may play a role in recognition of the damage

  7. Rare adipose disorders (RADs) masquerading as obesity

    Karen L HERBST

    2012-01-01

    Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL),lipedema and Dercum's disease (DD) may be misdiagnosed as obesity.Lifestyle changes,such as reduced caloric intake and increased physical activity are standard care for obesity.Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs,these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs.RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL,or by primary vascular and lymphatic dysfunction in lipedema and DD.People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone.In order to improve recognition of RADs apart from obesity,the diagnostic criteria,histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies,acquired partial lipodystrophies and obesity with which they may be confused.Treatment recommendations focus on evidencebased data and include lymphatic decongestive therapy,medications and supplements that support loss of RAD SAT.Associated RAD conditions including depression,anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs.Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations.

  8. Mapping the interaction domains between Rad51B and Rad51C; predictions and experiment

    Rad51B and Rad51C are proteins important in the repair of DNA double strand breaks through homologous recombination. These proteins have been confirmed to form a complex both in vitro and in yeast cells. Homology modeling was used to predict the 3D structures of Rad51B and Rad51C. Similar to Rad51, these proteins appear to have two distinct domains-an N-terminal putative DNA binding domain and a C-terminal domain that contains the Walker A and Walker B motifs that are important for the ATPase activity of these proteins. Deletion mutants were created, based on our models, to determine how the Rad51B/C complex is formed. We have shown that preserving the integrity of an internal beta sheet, predicted in both proteins, is vital to observing complex formation between Rad51B and Rad51C. Our predictions, that the N terminus of Rad51B binds the C terminus of Rad51C, have been verified by yeast two hybrid analysis and co-immunoprecipitation of these protein fragments from baculoviral infected insect cells. By iterative modeling and experiment, we have determined that a 15 amino acid length fragment on Rad51B is critical for binding Rad51C. Point mutations in this fragment are being used to determine the points of contact between Rad51B and Rad51C

  9. Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination

    Taylor, Martin R.G.; Špírek, Mário; Chaurasiya, Kathy R.; Ward, Jordan D.; Carzaniga, Raffaella; Yu, Xiong; Egelman, Edward H.; Collinson, Lucy M.; Rueda, David; Krejci, Lumir; Boulton, Simon J.

    2015-01-01

    Summary Repair of DNA double strand breaks by homologous recombination (HR) is initiated by Rad51 filament nucleation on single-stranded DNA (ssDNA), which catalyzes strand exchange with homologous duplex DNA. BRCA2 and the Rad51 paralogs are tumor suppressors and critical mediators of Rad51. To gain insight into Rad51 paralog function, we investigated a heterodimeric Rad51 paralog complex, RFS-1/RIP-1, and uncovered the molecular basis by which Rad51 paralogs promote HR. Unlike BRCA2, which ...

  10. Complex formation by the human Rad51B and Rad51C DNA repair proteins and their activities in vitro

    Lio, Yi-Ching; Mazin, Alexander V.; Kowalczykowski, Stephen C.; Chen, David J.

    2003-01-01

    The human Rad51 protein is essential for DNA repair by homologous recombination. In addition to Rad51 protein, five paralogs have been identified: Rad51B/Rad51L1, Rad51C/Rad51L2, Rad51D/Rad51L3, XRCC2, and XRCC3. To further characterize a subset of these proteins, recombinant Rad51, Rad51B-(His)(6), and Rad51C proteins were individually expressed employing the baculovirus system, and each was purified from Sf9 insect cells. Evidence from nickel-nitrilotriacetic acid pull-down experiments demonstrates a highly stable Rad51B.Rad51C heterodimer, which interacts weakly with Rad51. Rad51B and Rad51C proteins were found to bind single- and double-stranded DNA and to preferentially bind 3'-end-tailed double-stranded DNA. The ability to bind DNA was elevated with mixed Rad51 and Rad51C, as well as with mixed Rad51B and Rad51C, compared with that of the individual protein. In addition, both Rad51B and Rad51C exhibit DNA-stimulated ATPase activity. Rad51C displays an ATP-independent apparent DNA strand exchange activity, whereas Rad51B shows no such activity; this apparent strand exchange ability results actually from a duplex DNA destabilization capability of Rad51C. By analogy to the yeast Rad55 and Rad57, our results suggest that Rad51B and Rad51C function through interactions with the human Rad51 recombinase and play a crucial role in the homologous recombinational repair pathway.

  11. Contributions of the RAD51 N-terminal domain to BRCA2-RAD51 interaction.

    Subramanyam, Shyamal; Jones, William T; Spies, Maria; Spies, M Ashley

    2013-10-01

    RAD51 DNA strand exchange protein catalyzes the central step in homologous recombination, a cellular process fundamentally important for accurate repair of damaged chromosomes, preservation of the genetic integrity, restart of collapsed replication forks and telomere maintenance. BRCA2 protein, a product of the breast cancer susceptibility gene, is a key recombination mediator that interacts with RAD51 and facilitates RAD51 nucleoprotein filament formation on single-stranded DNA generated at the sites of DNA damage. An accurate atomistic level description of this interaction, however, is limited to a partial crystal structure of the RAD51 core fused to BRC4 peptide. Here, by integrating homology modeling and molecular dynamics, we generated a structure of the full-length RAD51 in complex with BRC4 peptide. Our model predicted previously unknown hydrogen bonding patterns involving the N-terminal domain (NTD) of RAD51. These interactions guide positioning of the BRC4 peptide within a cavity between the core and the NTDs; the peptide binding separates the two domains and restricts internal dynamics of RAD51 protomers. The model's depiction of the RAD51-BRC4 complex was validated by free energy calculations and in vitro functional analysis of rationally designed mutants. All generated mutants, RAD51(E42A), RAD51(E59A), RAD51(E237A), RAD51(E59A/E237A) and RAD51(E42A/E59A/E237A) maintained basic biochemical activities of the wild-type RAD51, but displayed reduced affinities for the BRC4 peptide. Strong correlation between the calculated and experimental binding energies confirmed the predicted structure of the RAD51-BRC4 complex and highlighted the importance of RAD51 NTD in RAD51-BRCA2 interaction. PMID:23935068

  12. Preparation structure and dielectric behaviour of the system Sr1-LaTi1-FeO3( ≤ 0.50)

    Om Parkash; Devendra Kumar; C C Christopher

    2003-10-01

    Formation of solid solution has been explored in the valence compensated perovskite oxide system Sr1-LaTi1-FeO3 ( ≤ 0.50). XRD studies indicate the formation of solid solution for the whole range investigated. All the compositions synthesised have cubic structure similar to undoped SrTiO3. Study of dielectric behaviour of these materials show that orientational polarisation and space charge polarisation contribute significantly to it.

  13. Regulation of Rad51-Mediated Homologous Recombination by BRCA2, DSS1 and RAD52

    Rants, Louise Olthaver Juhl

    involved with the proteasome. In U. maydis, the Rad52 orthologue seems relegated to a less prominent role than in Saccharomyces cerevisiae, similar to what is found in human cells. We find that Rad52 functionally overlaps with Brh2-ΔNBD, and Rad52 colocalizes with both Brh2 and Rfa1 (subunit of RPA) in...

  14. Mutations in yeast Rad51 that partially bypass the requirement for Rad55 and Rad57 in DNA repair by increasing the stability of Rad51–DNA complexes

    Fortin, Gary S.; Symington, Lorraine S.

    2004-01-01

    Yeast Rad51 promotes homologous pairing and strand exchange in vitro, but this activity is inefficient in the absence of the accessory proteins, RPA, Rad52, Rad54 and the Rad55–Rad57 heterodimer. A class of rad51 alleles was isolated that suppresses the requirement for RAD55 and RAD57 in DNA repair, but not the other accessory factors. Five of the six mutations isolated map to the region of Rad51 that by modeling with RecA corresponds to one of the DNA-binding sites. The other mutation is in ...

  15. Physical mapping and cloning of RAD56

    Mathiasen, David P; Gallina, Irene; Germann, Susanne Manuela;

    2013-01-01

    Here we report the physical mapping of the rad56-1 mutation to the NAT3 gene, which encodes the catalytic subunit of the NatB N-terminal acetyltransferase in Saccharomyces cerevisiae. Mutation of RAD56 causes sensitivity to X-rays, methyl methanesulfonate, zeocin, camptothecin and hydroxyurea, bu...

  16. RAD51AP2, a novel vertebrate- and meiotic-specific protein, sharesa conserved RAD51-interacting C-terminal domain with RAD51AP1/PIR51

    Kovalenko, Oleg V.; Wiese, Claudia; Schild, David

    2006-07-25

    Many interacting proteins regulate and/or assist the activities of RAD51, a recombinase which plays a critical role in both DNA repair and meiotic recombination. Yeast two-hybrid screening of a human testis cDNA library revealed a new protein, RAD51AP2 (RAD51 Associated Protein 2), that interacts strongly with RAD51. A full-length cDNA clone predicts a novel vertebrate specific protein of 1159 residues, and the RAD51AP2 transcript was observed only in meiotic tissue (i.e. adult testis and fetal ovary), suggesting a meiotic-specific function for RAD51AP2. In HEK293 cells the interaction of RAD51 with an ectopically-expressed recombinant large fragment of RAD51AP2 requires the C-terminal 57 residues of RAD51AP2. This RAD51-binding region shows 81% homology to the C-terminus of RAD51AP1/PIR51, an otherwise totally unrelated RAD51-binding partner that is ubiquitously expressed. Analyses using truncations and point mutations in both RAD51AP1 and RAD51AP2 demonstrate that these proteins use the same structural motif for RAD51 binding. RAD54 shares some homology with this RAD51-binding motif, but this homologous region plays only an accessory role to the adjacent main RAD51-interacting region, which has been narrowed here to 40 amino acids. A novel protein, RAD51AP2, has been discovered that interacts with RAD51 through a C-terminal motif also present in RAD51AP1.

  17. RAD51B in Familial Breast Cancer

    Pelttari, Liisa M.

    2016-01-01

    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possi...

  18. Synergistic interactions between RAD5, RAD16, and RAD54, three partially homologous yeast DNA repair genes each in a different repair pathway

    Considerable homology has recently been noted between the proteins encoded by the RAD5, RAD16 and RAD54 genes of Saccharomyces cerevisiae. These genes are members of the RAD6, RAD3 and RAD50 epistasis groups, respectively, which correspond to the three major DNA repair pathways in yeast. These proteins also share homology with other eucaryotic proteins, including those encoded by SNF2 and MO1 of yeast, brahma and lodestar of Drosophila and the human ERCC6 gene. The homology shares features with known helicases, suggesting a newly identified helicase subfamily. We have constructed a series of congenic single-, double- and triple-deletion mutants involving RAD5, RAD16 and RAD54 to examine the interactions between these genes. Each deletion mutation alone has only a moderate effect on survival after exposure to UV radiation. Each pairwise-double mutant exhibits marked synergism. The triple-deletion mutant displays further synergism. These results confirm the assignment of the RAD54 gene to the RAD50 epistasis group and suggest that the RAD16 gene plays a larger role in DNA repair after exposure to UV radiation than has been suggested previously. Additionally, the proteins encoded by RAD5, RAD16, and RAD54 may compete for the same substrate after damage induced by UV radiation, possibly at an early step in their respective pathways. 49 refs., 6 figs., 2 tabs

  19. RadNet Air Quality (Deployable) Data

    U.S. Environmental Protection Agency — RadNet Deployable Monitoring is designed to collect radiological and meteorological information and data asset needed to establish the impact of radiation levels on...

  20. Evidence of phase separation in Nd1-xSrxMnO3 (x=0.50,0.51,0.52,0.53,0.54,0.55)

    鲁毅; 李庆安; 邸乃力; 李润伟; 马骁; 寇志起; 成昭华

    2003-01-01

    The temperature dependence of Mn ion magnetization and the conductivity difference versus temperature provide phase separation evidence in Nd1-xSrxMnOs (x=0.50, 0.51, 0.52, 0.53, 0.54, 0.55). This is different from other reports and may suggest that a fully charge-ordered state exists in quite a narrow range; the sample preparation procedure affects the charge ordering. The polaron effect also plays an important role in explaining the conductivity.

  1. Pediatric meuroblastoma: postoperative radiation therapy using less than 2000 rad

    There is considerable controversy regarding the role of radiaiton therapy in the treatment of neuroblastoma. Postoperative irradiation in the range of 2500-4000 rad is commonly used in the treatment of Evans Stage II or III disease, but there are no data in the literature to suggest the optimum dose of radiation that is necessary. Because much lower doses have been used at the University of Florida, a retrospective study was undertaken in an attempt to determine the optimum dose necessary in conjunction with surgery. From March 1964 through July 1979, 21 children with Stage II or III neuroblastoma were seen at the University of Florida. One patient died postoperatively. The remainder received postoperative irradiation with doses ranging from 900 to 4500 rad. The lower dose of radiation used did not adversely influence survival, particularly for patients less than two years of age diagnosis. In this group, no patient had a local recurrence or died of disease, even though nine of 15 available patients received doses of 900-1500 rad

  2. Pediatric meuroblastoma: postoperative radiation therapy using less than 2000 rad

    Jacobson, H.M.; Marcus, R.B. Jr; Thar, T.L.; Million, R.R.; Graham-Pole, J.R.; Talbert, J.L.

    1983-04-01

    There is considerable controversy regarding the role of radiaiton therapy in the treatment of neuroblastoma. Postoperative irradiation in the range of 2500-4000 rad is commonly used in the treatment of Evans Stage II or III disease, but there are no data in the literature to suggest the optimum dose of radiation that is necessary. Because much lower doses have been used at the University of Florida, a retrospective study was undertaken in an attempt to determine the optimum dose necessary in conjunction with surgery. From March 1964 through July 1979, 21 children with Stage II or III neuroblastoma were seen at the University of Florida. One patient died postoperatively. The remainder received postoperative irradiation with doses ranging from 900 to 4500 rad. The lower dose of radiation used did not adversely influence survival, particularly for patients less than two years of age diagnosis. In this group, no patient had a local recurrence or died of disease, even though nine of 15 available patients received doses of 900-1500 rad.

  3. RadConEd: A Graphical Data Editor for the Radiological Consequences Model, RadCon

    This document describes the application, RadConEd, which has been designed and implemented to enable users of the RadCon system to update these parameter files. The RadCon system is written in the Java programming language, and as such provides portability across computer platforms. The software described in this report was developed in line with the portability requirements of RadCon, thus providing a uniform user interface across computer platforms and bypassing the need of using system editors. In addition a number of data integrity measures were implemented

  4. RadCon: A Radiological Consequences Model

    RadCon estimates the dose received by user selected groups in the population from an accidental release of radionuclides to the environment. The exposure pathways considered are external exposure from the cloud and ground and internal exposure from inhalation and ingestion of contaminated food. Atmospheric dispersion modelling is carried out externally to RadCon.Given a two dimensional time varying air and ground concentration of radioactive elements, RadCon allows the user to: view the air and ground concentration over the affected area, select optional parameters and calculate the dose to people,display the results to the user, and change the parameter values. RadCon offers two user interfaces: 1) the standard graphical user interface which is started using Java DoseApp at the command line, or by setting up a shortcut to this command (particularly when RadCon is installed on a PC) and 2) the text based interface used to generate information for the model inter-comparison exercise . This is initiated using Java BIOMASS at the command line, or an equivalent shortcut. The text based interface was developed for research purposes and is not generally available. Appendices A, B and C provide a summary of instructions on setting up RadCon. This will generally be carried out by the computer support personnel

  5. Analysis list: Rad23b [Chip-atlas[Archive

    Full Text Available Rad23b Pluripotent stem cell + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Rad2...3b.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Rad23b.5.tsv http://dbarchive.biosc...iencedbc.jp/kyushu-u/mm9/target/Rad23b.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Rad23b.Plu

  6. ezRAD: a simplified method for genomic genotyping in non-model organisms

    Robert J. Toonen

    2013-11-01

    Full Text Available Here, we introduce ezRAD, a novel strategy for restriction site–associated DNA (RAD that requires little technical expertise or investment in laboratory equipment, and demonstrate its utility for ten non-model organisms across a wide taxonomic range. ezRAD differs from other RAD methods primarily through its use of standard Illumina TruSeq library preparation kits, which makes it possible for any laboratory to send out to a commercial genomic core facility for library preparation and next-generation sequencing with virtually no additional investment beyond the cost of the service itself. This simplification opens RADseq to any lab with the ability to extract DNA and perform a restriction digest. ezRAD also differs from others in its flexibility to use any restriction enzyme (or combination of enzymes that cuts frequently enough to generate fragments of the desired size range, without requiring the purchase of separate adapters for each enzyme or a sonication step, which can further decrease the cost involved in choosing optimal enzymes for particular species and research questions. We apply this method across a wide taxonomic diversity of non-model organisms to demonstrate the utility and flexibility of our approach. The simplicity of ezRAD makes it particularly useful for the discovery of single nucleotide polymorphisms and targeted amplicon sequencing in natural populations of non-model organisms that have been historically understudied because of lack of genomic information.

  7. Determination of radon concentration in water using RAD7 with RAD H2O accessories

    In the last decade, the radon issue has become one of the major problems of radiation protection. Radon exposure occurs when using water for showering, washing dishes, cooking and drinking water. RAD7 and Rad H20 accessories were used in order to measure radon concentration in water sample. In this study, four types of water were concerns which are reverse osmosis (drinking water), mineral water, tap water and well water. Reverse osmosis (drinking water) and mineral water were bought from the nearest supermarket while tap water and well water were taken from selected areas of Pulau Pinang and Kedah. Total 20 samples were taken with 5 samples for each type of water. The measured radon concentration ranged from 2.9±2.9 to 79.5±17 pCi/L, 2.9±2.9 to 67.8±16 pCi/L, 15.97±7 to 144.25±24 pCi/L and 374.89±37 to 6409.03±130 pCi/L in reverse osmosis (drinking water), mineral water, tap water and well water. Well water has the highest radon compared to others. It was due to their geological element such as granite. Results for all types of water are presented and compared with maximum contamination limit (MCL) recommended by United State Environmental Protection Agency (USEPA) which is 300pCi/L. Reverse osmosis water, mineral water and tap water were fall below MCL. However, well water was exceeded maximum level that was recommended. Thus, these findings were suggested that an action should be taken to reduce radon concentration level in well water as well as reduce a health risk towards the public

  8. MSL-RAD radiation environment measurements.

    Guo, Jingnan; Zeitlin, Cary; Wimmer-Schweingruber, Robert F; Hassler, Donald M; Ehresmann, Bent; Köhler, Jan; Böhm, Eckart; Böttcher, Stephan; Brinza, David; Burmeister, Sönke; Cucinotta, Francis; Martin, Cesar; Posner, Arik; Rafkin, Scot; Reitz, Guenther

    2015-09-01

    In this study, results are presented from the on-board radiation assessment detector (RAD) of Mars Science Laboratory (MSL). RAD is designed to measure the energetic particle radiation environment, which consists of galactic cosmic rays (GCRs) and solar energetic particles (SEPs) as well as secondary particles created by nuclear interactions of primary particles in the shielding (during cruise) or Martian soil and atmosphere (surface measurements). During the cruise, RAD collected data on space radiation from inside the craft, thus allowing for a reasonable estimation of what a human crew travelling to/from Mars might be exposed to. On the surface of Mars, RAD is shielded by the atmosphere (from above) and the planet itself (from below). RAD measures the first detailed radiation data from the surface of another planet, and they are highly relevant for planning future crewed missions. The results for radiation dose and dose equivalent (a quantity most directly related to human health risk) are presented during the cruise phase, as well as on the Martian surface. Dose and dose equivalent are dominated by the continuous GCR radiation, but several SEP events were also detected and are discussed here. PMID:25969529

  9. Radiological information management system (RadIMS)

    Westinghouse Idaho Nuclear Company, Inc. (WINCO) is developing and implementing an information management system, known as RadIMS, to track and record personnel exposure to ionizing radiation. RadIMS has been designed to fulfill all the requirements of US Department of Energy (USDOE) Order 5480.11, ''Radiation Protection for Occupational Workers.'' This Order requires the contractor to maintain detailed radiation exposure records on all individuals who work at the facility. These records must be retrievable for the entire working life of the individual and be available to other USDOE contractors on request. To meet these general needs, RadIMS provides for retrieval of detailed, comprehensive individual exposure histories as well as the usual online interactions to accomplish day-today radiation protection operations. These two extremes of functionality require different approaches in the WINCO computing environment. The exposure histories include database text, paper, microfilm, and electronic bitmaps

  10. Evaluation of COTS Rad Detection Apps

    Wagner, Eric [National Security Technologies, LLC. (NSTec), Mercury, NV (United States)

    2014-02-01

    Mobile applications are currently under distribution to smart phones utilizing the built-in charge coupled-device (CCD) camera as a radiation detector. The CCD detector has a very low but measurable gamma interaction cross section so the mechanism is feasible, especially for higher dose rate environments. Given that in a large release of radioactive material these ‘crowd sourced’ measurements will be put forth for consideration, a testing and evaluation of the accuracy and uncertainty of the Apps is a critical endeavor. Not only is the accuracy of the reported measurement of concern to the immediate user’s safety, a quantitative uncertainty is required for a government response such as the Federal Radiological Monitoring and Assessment Center (FRMAC) to accept the values for consideration in the determination of regions exceeding protective action guidelines. Already, prompted by the Fukushima nuclear material releases, several repositories of this crowd-sourced data have been created (http://japan.failedrobot.com, http://www.stubbytour.com/nuc/index_en.asp, and http://www.rdtn.org) although the question remains as to the reliability of measurements incorporated into these repositories. In cases of conflict between the real-time published crowd-sourced data and governmental protective actions prepared literature should be on-hand documenting why the difference, if any, exists. Four applications for iOS devices were obtained along with hardware to benchmark their performance. Gamma/X-Ray Detector by Stephan Hotto, Geiger Camera by Senscare, and RadioactivityCounter App by Hotray LTD are all the applications available for distribution within the US that utilize the CCD camera sensor for detection of radiation levels. The CellRad app under development by Idaho National Laboratory for the Android platform was evaluated. In addition, iRad Geiger with the associated hardware accessory was also benchmarked. Radiation fields were generated in a Cs-137 JL Shepherd

  11. Evaluation of COTS Rad Detection Apps

    Mobile applications are currently under distribution to smart phones utilizing the built-in charge coupled-device (CCD) camera as a radiation detector. The CCD detector has a very low but measurable gamma interaction cross section so the mechanism is feasible, especially for higher dose rate environments. Given that in a large release of radioactive material these 'crowd sourced' measurements will be put forth for consideration, a testing and evaluation of the accuracy and uncertainty of the Apps is a critical endeavor. Not only is the accuracy of the reported measurement of concern to the immediate user's safety, a quantitative uncertainty is required for a government response such as the Federal Radiological Monitoring and Assessment Center (FRMAC) to accept the values for consideration in the determination of regions exceeding protective action guidelines. Already, prompted by the Fukushima nuclear material releases, several repositories of this crowd-sourced data have been created (http://japan.failedrobot.com, http://www.stubbytour.com/nuc/index_en.asp, and http://www.rdtn.org) although the question remains as to the reliability of measurements incorporated into these repositories. In cases of conflict between the real-time published crowd-sourced data and governmental protective actions prepared literature should be on-hand documenting why the difference, if any, exists. Four applications for iOS devices were obtained along with hardware to benchmark their performance. Gamma/X-Ray Detector by Stephan Hotto, Geiger Camera by Senscare, and RadioactivityCounter App by Hotray LTD are all the applications available for distribution within the US that utilize the CCD camera sensor for detection of radiation levels. The CellRad app under development by Idaho National Laboratory for the Android platform was evaluated. In addition, iRad Geiger with the associated hardware accessory was also benchmarked. Radiation fields were generated in a Cs-137 JL

  12. Fission yeast Rad52 phosphorylation restrains error prone recombination pathways.

    Bellini, Angela; Girard, Pierre-Marie; Tessier, Ludovic; Sage, Evelyne; Francesconi, Stefania

    2014-01-01

    Rad52 is a key protein in homologous recombination (HR), a DNA repair pathway dedicated to double strand breaks and recovery of blocked or collapsed replication forks. Rad52 allows Rad51 loading on single strand DNA, an event required for strand invasion and D-loop formation. In addition, Rad52 functions also in Rad51 independent pathways because of its ability to promote single strand annealing (SSA) that leads to loss of genetic material and to promote D-loops formation that are cleaved by Mus81 endonuclease. We have previously reported that fission yeast Rad52 is phosphorylated in a Sty1 dependent manner upon oxidative stress and in cells where the early step of HR is impaired because of lack of Rad51. Here we show that Rad52 is also constitutively phosphorylated in mus81 null cells and that Sty1 partially impinges on such phosphorylation. As upon oxidative stress, the Rad52 phosphorylation in rad51 and mus81 null cells appears to be independent of Tel1, Rad3 and Cdc2. Most importantly, we show that mutating serine 365 to glycine (S365G) in Rad52 leads to loss of the constitutive Rad52 phosphorylation observed in cells lacking Rad51 and to partial loss of Rad52 phosphorylation in cells lacking Mus81. Contrariwise, phosphorylation of Rad52-S365G protein is not affected upon oxidative stress. These results indicate that different Rad52 residues are phosphorylated in a Sty1 dependent manner in response to these distinct situations. Analysis of spontaneous HR at direct repeats shows that mutating serine 365 leads to an increase in spontaneous deletion-type recombinants issued from mitotic recombination that are Mus81 dependent. In addition, the recombination rate in the rad52-S365G mutant is further increased by hydroxyurea, a drug to which mutant cells are sensitive. PMID:24748152

  13. Environmental Radiation Studies Utilizing RadNet

    Jackson, Steven

    2010-03-01

    RadNet is an Environmental Protection Agency (EPA) managed environmental radiation and air quality monitoring station that has been recently installed on the Angelo State University campus. RadNet cycles air through a filter which collects particulate matter for an examination of alpha and beta activities of contained material. This project includes defining dominant alpha and beta emitters in the local environment, conducting a correlation study involving the effect of weather and wind direction on filter activity, physical interpretation of air quality index (AQI), and the use of X-ray fluorescence to verify radon decay progeny in the local environment.

  14. Rietveld refinements of the solid solution Li(1-2x)Ni xTiO(PO4) (0 ≤ x ≤ 0.50)

    Li(1-2x)Ni xTiO(PO4) oxyphosphates with 0 ≤ x ≤ 0.10 crystallize in the orthorhombic system with the space group Pnma, those with 0.10 1/c and compositions with 0.25 0.50Ni0.25TiO(PO4) and Ni0.50TiO(PO4). The structure of the compositions 0 ≤ x ≤ 0.25 is based on a three-dimensional anionic framework constructed of chains of alternating TiO6 octahedra and PO4 tetrahedra, with the lithium and nickel atoms in the cavities in the framework. The dominant structural units in the compositions are chains of tilted corner-sharing TiO6 octahedra running parallel to one of the axis. The oxygen atoms of the shared corners, not implied in (PO4) tetrahedra, justify the oxyphosphate designation. Titanium atoms are displaced from the geometrical center of the octahedra resulting in alternating long (∼2.25 A) and short (∼1.71 A) Ti-O(1) bonds. The four remaining Ti-O bond distances have intermediate values ranging from 1.91 to 2.06 A

  15. Nanoscale Ferroelectric Switchable Polarization and Leakage Current Behavior in (Ba0.50Sr0.50(Ti0.80Sn0.20O3 Thin Films Prepared Using Chemical Solution Deposition

    Venkata Sreenivas Puli

    2015-01-01

    Full Text Available Nanoscale switchable ferroelectric (Ba0.50Sr0.50(Ti0.80Sn0.20O3-BSTS polycrystalline thin films with a perovskite structure were prepared on Pt/TiOx/SiO2/Si substrate by chemical solution deposition. X-ray diffraction (XRD spectra indicate that a cubic perovskite crystalline structure and Raman spectra revealed that a tetragonal perovskite crystalline structure is present in the thin films. Sr2+ and Sn4+ cosubstituted film exhibited the lowest leakage current density. Piezoresponse Force Microscopy (PFM technique has been employed to acquire out-of-plane (OPP piezoresponse images and local piezoelectric hysteresis loop in polycrystalline BSTS films. PFM phase and amplitude images reveal nanoscale ferroelectric switching behavior at room temperature. Square patterns with dark and bright contrasts were written by local poling and reversible nature of the piezoresponse behavior was established. Local piezoelectric butterfly amplitude and phase hysteresis loops display ferroelectric nature at nanoscale level. The significance of this paper is to present ferroelectric/piezoelectric nature in present BSTS films at nanoscale level and corroborating ferroelectric behavior by utilizing Raman spectroscopy. Thus, further optimizing physical and electrical properties, BSTS films might be useful for practical applications which include nonvolatile ferroelectric memories, data-storage media, piezoelectric actuators, and electric energy storage capacitors.

  16. μSR studies on the response of spin dynamics to applying or removing magnetic field—Typical Ising spin glass Fe0.50Mn0.50TiO3

    Torikai, Eiko; Ito, Atsuko; Watanabe, Isao; Nagamine, Kanetada

    2006-03-01

    One of the distinguishing properties of spin glass (SG) systems is a long-time relaxation of magnetization below the SG transition temperature. Motivated by the interests on how the microscopic spin dynamics is related to the macroscopic behavior of spin system in the SG state, we have performed the μSR measurement for a typical Ising SG system Fe 0.50Mn 0.50TiO 3 under various experimental conditions. We also pay attention to how the spin dynamics responds to a sudden change of magnetic fields. Thus, we have discussed the spin dynamics of SG system which had not been detected before our μSR measurement. For example, we have shown that the switching-off of a magnetic field at the field-cooled state makes the spin fluctuations faster. Moreover, such spin fluctuations have shown to remain faster at least up to the order of 2 h, although the thermoremanent magnetization decays dramatically within 2 h.

  17. Synthesis, structure refinement and characterisation of a new oxyphosphate Mg0.50TiO(PO4)

    A new titanium oxyphosphate Mg0.50TiO(PO4) has been synthesized and characterized by several physical techniques: X-ray diffraction, 31P MAS-NMR, Raman diffusion, infrared absorption and diffuse reflectance spectroscopy. It crystallizes in the monoclinic system with unit cell parameters: a = 7.367(9), b = 7.385(8), c = 7.373(9) A, β = 120.23(1), with the space group P21/c (no. 14), Z = 4. The crystal structure has been refined by the Rietveld method using X-ray powder diffraction. The conventional R indices obtained are R wp = 0.138, R p = 0.096 and R B = 0.0459. The structure of Mg0.50TiO(PO4) consists of infinite chains of corner-shared [TiO6] octahedra parallel to the c-axis, crosslinked by corner-shared [PO4] tetrahedra. These infinite chains have alternating short (1.74 A) and long (2.26 A) Ti-O bonds and are similar to those found in titanium oxyphosphate MII0.50TiO(PO4) (M2+ = Fe2+, Co2+, Ni2+, Cu2+, Zn2+). The magnesium atom is located in an antiprism between two [TiO6] octahedra. 31P MAS NMR showed only a single 31P resonance line, in a good agreement with the crystal structure. Raman and IR spectra show strong bands respectively at 765 and 815 cm-1, attributed to the vibration of -Ti-O-Ti-O- bonds in the infinite chains. The gap due to the Oxygen-Titanium(IV) charge transfer is 3.37 eV

  18. NMR study of phase transitions in VT/sub 0.50/ and VT/sub 0.75/

    The work describes the preparation of polycrystalline VT/sub 0.50/ and VT/sub 0.75/ and observations of phase transitions using pulse nuclear magnetic resonance measurements of triton relaxation times. The critical temperatures (T/sub c/) for the phase transitions in the VT/sub x/ samples follow the mass-dependent trends found for VH/sub x/ and VD/sub x/ and qualitatively obey the isotopic dependence predicted by the theoretical models of Entin et al. 23 refs

  19. Xe-bearing hydrocarbon ions: Observation of Xe.acetylene+rad and Xe.benzene+rad radical cations and calculations of their ground state structures

    Cui, Zhong-hua; Attah, Isaac K.; Platt, Sean P.; Aziz, Saadullah G.; Kertesz, Miklos; El-Shall, M. S.

    2016-04-01

    This work reports evidence for novel types of Xe-bearing hydrocarbon radical cations. The Xe.acetylene+rad radical cation adduct is observed at nearly room temperature using the mass-selected drift cell technique. The irreversible addition of the Xe atom and the lack of back dissociation to HCCH+rad + Xe is consistent with the calculated binding energy of 0.85 eV to be contrasted with the metastable nature of the neutral Xe.acetylene adduct. The observed Xe.benzene+rad radical cation appears to be a weakly bound complex stabilized mainly by ion-induced dipole interaction consistent with a calculated binding energy in the range of 0.14-0.17 eV.

  20. HiRadMat: materials under scrutiny

    Anaïs Schaeffer

    2011-01-01

    CERN's new facility, HiRadMat (High Radiation to Materials), which is designed to test materials for the world's future particle accelerators, should be operational and welcoming its first experiments by the end of the year.   The HiRadMat facility, located in the TNC tunnel. The materials used in the LHC and its experiments are exposed to very high-energy particles. The LHC machine experts obviously didn't wait for the first collisions in the world's most powerful accelerator to put the materials through their paces - the equipment was validated following a series of stringent tests. And these tests will get even tougher now, with the arrival of HiRadMat. The tunnel that formerly housed the West Area Neutrino Facility (WANF) has been completely revamped to make way for CERN's latest facility, HiRadMat. Supported by the Radioprotection service, a team from the Engineering (EN) Department handled the dismantling operations from October 2009 to December 2010. "We could only work on disman...

  1. RadNet Air Quality (Fixed Station) Data

    U.S. Environmental Protection Agency — RadNet is a national network of monitoring stations that regularly collect air for analysis of radioactivity. The RadNet network, which has stations in each State,...

  2. Promotion of Homologous Recombination and Genomic Stability byRAD51AP1 via RAD51 Recombinase Enhancement

    Wiese, Claudia; Dray, Eloise; Groesser, Torsten; San Filippo,Joseph; Shi, Idina; Collins, David W.; Tsai, Miaw-Sheue; Williams,Gareth; Rydberg, Bjorn; Sung, Patrick; Schild, David

    2007-04-11

    Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand pairing step in HR. RAD51AP1 (RAD51 Associated Protein 1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA damaging treatment. Purified RAD51AP1 binds dsDNA and RAD51, and it greatly stimulates the RAD51-mediated D-loop reaction. Biochemical and cytological results show that RAD51AP1 functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide the first evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.

  3. Karyotype rearrangements in a wine yeast strain by rad52-dependent and rad52-independent mechanisms

    Carro, David; Bartra, Enric; Piña, Benjamín

    2003-01-01

    Yeast strains isolated from the wild may undergo karyotype changes during vegetative growth, a characteristic that compromises their utility in genetic improvement projects for industrial purposes. Karyotype instability is a dominant trait, segregating among meiotic derivatives as if it depended upon only a few genetic elements. We show that disrupting the RAD52 gene in a hypervariable strain partially stabilizes its karyotype. Specifically, RAD52 disruption eliminated recombination at telome...

  4. Co-expression with RadA and the characterization of stRad55B, a RadA paralog from the hyperthermophilic crenarchaea Sulfolobus tokodaii

    2008-01-01

    ST0838 (designed stRad55B) is one of the four RadA paralogs (or Rad55 homologues) in the genome of the hyperthermophilic crenarchaeon Sulfolobus tokodaii. The gene is induced by UV irradiation, sug-gesting that it is involved in DNA recombinational repair in this organism. However, this protein could not be expressed normally in vitro. In this study, thermostable and soluble stRad55B was obtained by co-expression with S. tokodaii RadA (stRadA) in E. coli, and the enzymatic properties were examined. It was found that stRad55B bound ssDNA preferentially and had a very weak ATPase activity that was not stimulated by DNA. The recombinant protein inhibited the strand exchange activity promoted by stRadA, indicating that stRad55B might be an inhibitor to the homologous recombination in this ar-chaeon. The results will be helpful for further functional and interaction analysis of RadA paralogs and for the understanding of the mechanism of recombinational repair in archaea.

  5. Co-expression with RadA and the characterization of stRad55B, a RadA paralog from the hyperthermophilic crenarchaea Sulfolobus tokodaii

    2008-01-01

    ST0838 (designed stRad55B) is one of the four RadA paralogs (or Rad55 homologues) in the genome of the hyperthermophilic crenarchaeon Sulfolobus tokodaii. The gene is induced by UV irradiation, suggesting that it is involved in DNA recombinational repair in this organism. However, this protein could not be expressed normally in vitro. In this study, thermostable and soluble stRad55B was obtained by co-expression with S. tokodaii RadA (stRadA) in E. coli, and the enzymatic properties were examined. It was found that stRad55B bound ssDNA preferentially and had a very weak ATPase activity that was not stimulated by DNA. The recombinant protein inhibited the strand exchange activity promoted by stRadA, indicating that stRad55B might be an inhibitor to the homologous recombination in this archaeon. The results will be helpful for further functional and interaction analysis of RadA paralogs and for the understanding of the mechanism of recombinational repair in archaea.

  6. Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population

    Song, Honglin; Dicks, Ed; Ramus, Susan J; Tyrer, Jonathan P; Intermaggio, Maria P; Hayward, Jane; Edlund, Christopher K; Conti, David; Harrington, Patricia; Fraser, Lindsay; Philpott, Susan; Anderson, Christopher; Rosenthal, Adam; Gentry-Maharaj, Aleksandra; Bowtell, David D; Alsop, Kathryn; Cicek, Mine S; Cunningham, Julie M; Fridley, Brooke L; Alsop, Jennifer; Jimenez-Linan, Mercedes; Høgdall, Estrid; Høgdall, Claus K; Jensen, Allan; Kjaer, Susanne Krüger; Lubiński, Jan; Huzarski, Tomasz; Jakubowska, Anna; Gronwald, Jacek; Poblete, Samantha; Lele, Shashi; Sucheston-Campbell, Lara; Moysich, Kirsten B; Odunsi, Kunle; Goode, Ellen L; Menon, Usha; Jacobs, Ian J; Gayther, Simon A; Pharoah, Paul D P

    2015-01-01

    PURPOSE: The aim of this study was to estimate the contribution of deleterious mutations in the RAD51B, RAD51C, and RAD51D genes to invasive epithelial ovarian cancer (EOC) in the population and in a screening trial of individuals at high risk of ovarian cancer. PATIENTS AND METHODS: The coding...... sequence and splice site boundaries of the three RAD51 genes were sequenced and analyzed in germline DNA from a case-control study of 3,429 patients with invasive EOC and 2,772 controls as well as in 2,000 unaffected women who were BRCA1/BRCA2 negative from the United Kingdom Familial Ovarian Cancer...... (RAD51C, n = 7; RAD51D, n = 5; and RAD51B, n = 1), which was a significantly greater rate than in controls (P < .001); furthermore, RAD51 mutation carriers were more likely than noncarriers to have a family history of ovarian cancer (P < .001). CONCLUSION: These results confirm that RAD51C and RAD51D...

  7. Inter-subunit interactions that coordinate Rad51's activities

    A.A. Grigorescu (Arabela); J.H.A. Vissers (Joseph); D. Ristic (Dejan); Y.Z. Pigli (Ying); T.W. Lynch (Thomas); C. Wyman (Claire); P.A. Rice (Phoebe)

    2009-01-01

    textabstractRad51 is the central catalyst of homologous recombination in eukaryotes and is thus critical for maintaining genomic integrity. Recent crystal structures of filaments formed by Rad51 and the closely related archeal RadA and eubacterial RecA proteins place the ATPase site at the protomeri

  8. RAD51B in Familial Breast Cancer

    Pelttari, Liisa M.; Khan, Sofia; Vuorela, Mikko; Kiiski, Johanna I.; Vilske, Sara; Nevanlinna, Viivi; Ranta, Salla; Schleutker, Johanna; Winqvist, Robert; Kallioniemi, Anne; Dörk, Thilo; Bogdanova, Natalia V.; Figueroa, Jonine; Pharoah, Paul D. P.; Schmidt, Marjanka K.; Dunning, Alison M.; García-Closas, Montserrat; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Hopper, John L.; Southey, Melissa C.; Rosenberg, Efraim H.; Fasching, Peter A.; Beckmann, Matthias W.; Peto, Julian; dos-Santos-Silva, Isabel; Sawyer, Elinor J.; Tomlinson, Ian; Burwinkel, Barbara; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Nordestgaard, Børge G.; Benitez, Javier; González-Neira, Anna; Neuhausen, Susan L.; Anton-Culver, Hoda; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Brüning, Thomas; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Van Dyck, Laurien; Janssen, Hilde; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Peterlongo, Paolo; Hallberg, Emily; Olson, Janet E.; Giles, Graham G.; Milne, Roger L.; Haiman, Christopher A.; Schumacher, Fredrick; Simard, Jacques; Dumont, Martine; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Grip, Mervi; Andrulis, Irene L.; Glendon, Gord; Devilee, Peter; Seynaeve, Caroline; Hooning, Maartje J.; Collée, Margriet; Cox, Angela; Cross, Simon S.; Shah, Mitul; Luben, Robert N.; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Couch, Fergus J.; Yannoukakos, Drakoulis; Orr, Nick; Swerdlow, Anthony; Darabi, Hatef; Li, Jingmei; Czene, Kamila; Hall, Per; Easton, Douglas F.; Mattson, Johanna; Blomqvist, Carl; Aittomäki, Kristiina; Nevanlinna, Heli

    2016-01-01

    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk. PMID:27149063

  9. RAD51B in Familial Breast Cancer.

    Liisa M Pelttari

    Full Text Available Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC that were genotyped on a custom chip (iCOGS. We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259 and population controls (n = 3586 from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR: 1.15, 95% confidence interval (CI: 1.11-1.19, P = 8.88 x 10-16 and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11, compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

  10. Dose Calibration of the ISS-RAD Fast Neutron Detector

    Zeitlin, C.

    2015-01-01

    The ISS-RAD instrument has been fabricated by Southwest Research Institute and delivered to NASA for flight to the ISS in late 2015 or early 2016. ISS-RAD is essentially two instruments that share a common interface to ISS. The two instruments are the Charged Particle Detector (CPD), which is very similar to the MSL-RAD detector on Mars, and the Fast Neutron Detector (FND), which is a boron-loaded plastic scintillator with readout optimized for the 0.5 to 10 MeV energy range. As the FND is completely new, it has been necessary to develop methodology to allow it to be used to measure the neutron dose and dose equivalent. This talk will focus on the methods developed and their implementation using calibration data obtained in quasi-monoenergetic (QMN) neutron fields at the PTB facility in Braunschweig, Germany. The QMN data allow us to determine an approximate response function, from which we estimate dose and dose equivalent contributions per detected neutron as a function of the pulse height. We refer to these as the "pSv per count" curves for dose equivalent and the "pGy per count" curves for dose. The FND is required to provide a dose equivalent measurement with an accuracy of ?10% of the known value in a calibrated AmBe field. Four variants of the analysis method were developed, corresponding to two different approximations of the pSv per count curve, and two different implementations, one for real-time analysis onboard ISS and one for ground analysis. We will show that the preferred method, when applied in either real-time or ground analysis, yields good accuracy for the AmBe field. We find that the real-time algorithm is more susceptible to chance-coincidence background than is the algorithm used in ground analysis, so that the best estimates will come from the latter.

  11. A Statistical Analysis of Laser Ablated Ba(Sub 0.50)Sr(Sub 0.50)TiO(Sub 3)/LaAlO(Sub 3) Films for Microwave Applications

    Romanofsky, R. R.; Varaljay, N. C.; Alterovitz, S. A.; Miranda, F. A.; Mueller, C. M.; VanKeuls, F. W.; Kim, J.; Harshavardhan, K. S.

    2002-01-01

    The NASA Glenn Research Center is constructing a 616 element scanning phased array antenna using thin film Ba(sub x)Sr(sub 1-x)TiO(sub 3) based phase shifters. A critical milestone is the production of 616 identical phase shifters at 19 GHz with [asymptotically equal to]4 dB insertion loss and at least 337.5 deg phase shift with 3 percent bandwidth. It is well known that there is a direct relationship between dielectric tuning and loss due to the Kramers-Kronig relationship and that film crystallinity and strain, affected by the substrate template, play an important role. Ba(sub 0.50)Sr(sub 0.50)TiO (sub 3) films, nominally 400 nm thick, were deposited on 48 0.25 mm thick, 5 cm diameter LaAlO(sub 3) wafers. Although previous results suggested that Mn-doped films on MgO were intrinsically superior in terms of phase shift per unit loss, for this application phase shift per unit length was more important. The composition was selected as a compromise between tuning and loss for room temperature operation (e.g. crystallinity progressively degrades for Ba concentrations in excess of 30 percent). As a prelude to fabricating the array, it was necessary to process, screen, and inventory a large number of samples. Variable angle ellipsometry was used to characterize refractive index and film thickness across each wafer. Microstructural properties of the thin films were characterized using high resolution X-ray diffractometry. Finally, prototype phase shifters and resonators were patterned on each wafer and RE probed to measure tuning as a function of dc bias voltage as well as peak (0 field) permittivity and unloaded Q. The relationship among film quality and uniformity and performance is analyzed. This work presents the first statistically relevant study of film quality and microwave performance and represents a milestone towards commercialization of thin ferroelectric films for microwave applications.

  12. CRED Subsurface Temperature Recorder (STR); NWHI, MID; Long: -177.32334, Lat: 28.24437 (WGS84); Sensor Depth: 0.50m; Data Range: 20030729-20041001.

    National Oceanic and Atmospheric Administration, Department of Commerce — Data from Coral Reef Ecosystem Division (CRED), NOAA Pacific Islands Fisheries Science Center (PIFSC) Subsurface Temperature Recorders (STR) provide a time series...

  13. Analysis list: RAD21 [Chip-atlas[Archive

    Full Text Available ncedbc.jp/kyushu-u/hg19/target/RAD21.1.tsv http://dbarchive.biosciencedbc.jp/kyushu...-u/hg19/target/RAD21.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/RAD21.10.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/RAD21.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/RAD21.Breast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/RAD21.Dige...stive_tract.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/RAD21.Liver.tsv,http://dbarchive.bioscience

  14. Monte Carlo calculation of the energy response characteristics of a RadFET radiation detector

    The Metal -Oxide Semiconductor Field-Effect-Transistor (MOSFET, RadFET) is frequently used as a sensor of ionizing radiation in nuclear-medicine, diagnostic-radiology, radiotherapy quality-assurance and in the nuclear and space industries. We focused our investigations on calculating the energy response of a p-type RadFET to low-energy photons in range from 12 keV to 2 MeV and on understanding the influence of uncertainties in the composition and geometry of the device in calculating the energy response function. All results were normalized to unit air kerma incident on the RadFET for incident photon energy of 1.1 MeV. The calculations of the energy response characteristics of a RadFET radiation detector were performed via Monte Carlo simulations using the MCNPX code and for a limited number of incident photon energies the FOTELP code was also used for the sake of comparison. The geometry of the RadFET was modeled as a simple stack of appropriate materials. Our goal was to obtain results with statistical uncertainties better than 1% (fulfilled in MCNPX calculations for all incident energies which resulted in simulations with 1 - 2x109 histories.

  15. Sturgeon conservation genomics: SNP discovery and validation using RAD sequencing.

    Ogden, R; Gharbi, K; Mugue, N; Martinsohn, J; Senn, H; Davey, J W; Pourkazemi, M; McEwing, R; Eland, C; Vidotto, M; Sergeev, A; Congiu, L

    2013-06-01

    Caviar-producing sturgeons belonging to the genus Acipenser are considered to be one of the most endangered species groups in the world. Continued overfishing in spite of increasing legislation, zero catch quotas and extensive aquaculture production have led to the collapse of wild stocks across Europe and Asia. The evolutionary relationships among Adriatic, Russian, Persian and Siberian sturgeons are complex because of past introgression events and remain poorly understood. Conservation management, traceability and enforcement suffer a lack of appropriate DNA markers for the genetic identification of sturgeon at the species, population and individual level. This study employed RAD sequencing to discover and characterize single nucleotide polymorphism (SNP) DNA markers for use in sturgeon conservation in these four tetraploid species over three biological levels, using a single sequencing lane. Four population meta-samples and eight individual samples from one family were barcoded separately before sequencing. Analysis of 14.4 Gb of paired-end RAD data focused on the identification of SNPs in the paired-end contig, with subsequent in silico and empirical validation of candidate markers. Thousands of putatively informative markers were identified including, for the first time, SNPs that show population-wide differentiation between Russian and Persian sturgeons, representing an important advance in our ability to manage these cryptic species. The results highlight the challenges of genotyping-by-sequencing in polyploid taxa, while establishing the potential genetic resources for developing a new range of caviar traceability and enforcement tools. PMID:23473098

  16. Two isoforms of plant RAD23 complement a UV-sensitive rad23 mutant in yeast

    DNA repair by nucleotide excision (NER) has been demonstrated in plant cells at the biochemical level but until now none of the molecular components of the plant NER complex has been identified. In this paper, the cloning and characterization of two isoforms of RAD23 from carrot (Daucus carota L.) are reported. It has been suggested that RAD23 in yeast is an assembly factor of the NER complex required for transcription-coupled repair as well as efficient overall genome repair. A functional assay demonstrated that both plant homologues complement the UV-sensitive phenotype of a rad23 deletion mutant of yeast. This result suggests that homologous polypeptides may catalyse NER in plants and yeast and, possibly, by a similar mechanism

  17. Inter-observer variability within BI-RADS and RANZCR mammographic density assessment schemes

    Damases, Christine N.; Mello-Thoms, Claudia; McEntee, Mark F.

    2016-03-01

    This study compares variability associated with two visual mammographic density (MD) assessment methods using two separate samples of radiologists. The image test-set comprised of images obtained from 20 women (age 42-89 years). The images were assessed for their MD by twenty American Board of Radiology (ABR) examiners and twenty-six radiologists registered with the Royal Australian and New Zealand College of Radiologists (RANZCR). Images were assessed using the same technology and conditions, however the ABR radiologists used the BI-RADS and the RANZCR radiologists used the RANZCR breast density synoptic. Both scales use a 4-point assessment. The images were then grouped as low- and high-density; low including BIRADS 1 and 2 or RANZCR 1 and 2 and high including BI-RADS 3 and 4 or RANZCR 3 and 4. Four-point BI-RADS and RANZCR showed no or negligible correlation (ρ=-0.029 p<0.859). The average inter-observer agreement on the BI-RADS scale had a Kappa of 0.565; [95% CI = 0.519 - 0.610], and ranged between 0.328-0.669 while the inter-observer agreement using the RANZCR scale had a Kappa of 0.360; [95% CI = 0.308 - 0.412] and a range of 0.078-0.499. Our findings show a wider range of inter-observer variability among RANZCR registered radiologists than the ABR examiners.

  18. Nuclear localization of Rad51B is independent of BRCA2

    Miller, K A; Hinz, J M; Yamada, A; Thompson, L H; Albala, J S

    2005-06-28

    Human Rad51 is critical for the maintenance of genome stability through its role in the repair of DNA double-strand breaks. Rad51B (Rad51L1/hRec2) is one of the five known paralogs of human Rad51 found in a multi-protein complex with three other Rad51 paralogs, Rad51C, Rad51D and Xrcc2. Examination of EGFP-Rad51B fusion protein in HeLa S3 cells and immunofluorescence in several human cell lines confirms the nuclear localization of Rad51B. This is the first report to detail putative interactions of a Rad51 paralog protein with BRCA2. Utilization of a BRCA2 mutant cell line, CAPAN-1 suggests that Rad51B localizes to the nucleus independent of BRCA2. Although both Rad51B and BRCA2 are clearly involved in the homologous recombinational repair pathway, Rad51B and BRCA2 do not appear to associate directly. Furthermore, mutations in the KKLK motif of Rad51B, amino acid residues 4-7, mislocalizes Rad51B to the cytoplasm suggesting that this is the nuclear localization signal for the Rad51B protein. Examination of wild-type EGFP-Rad51B fusion protein in mammalian cells deficient in Rad51C showed that Rad51B localizes to the nucleus independent of Rad51C; further suggesting that Rad51B, like Rad51C, contains its own nuclear localization signal.

  19. Correlation of RAD51 and radiosensitization of methotrexate

    Objective: To evaluate the correlation between homologous recombination repair protein RAD51 and methotrexate-enhanced radiosensitivity. Methods: Western blot and RT-PCR assays were used to detect RAD51 expression in HOS osteosarcoma cells exposed to γ-ray irradiation alone and in combination with methotrexate. Colony formation assay was used to test the survival fraction of HOS cells exposed to γ-rays and methotrexate. Results: Methotrexate inhibited both protein and RNA expressions of RAD51, and the combination of radiation and methotrexate enhanced the inhibition of RAD51 expression. Moreover, transfection of cells with RAD51 gene decreased cellular sensitivity to methotrexate and γ-rays. The sensitizer enhancement ratios after irradiation in combination with methotrexate were 1.51 and 0.99, respectively. Methotrexate was a preferred radiosensitizer to HOS cell. Conclusions: RAD51 might be involved in the methotrexate-enhanced radiosensitivity. (authors)

  20. Analysis list: Rad51 [Chip-atlas[Archive

    Full Text Available Rad51 Blood,Gonad + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Rad51.1.tsv http://dba...rchive.biosciencedbc.jp/kyushu-u/mm9/target/Rad51.5.tsv http://dbarchive.biosciencedbc.jp/k...yushu-u/mm9/target/Rad51.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Rad51.Blood.tsv,http://dba...rchive.biosciencedbc.jp/kyushu-u/mm9/colo/Rad51.Gonad.tsv http://dbarchive.bios...ciencedbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gonad.gml ...

  1. Type I interferon-dependent activation of NK cells by rAd28 or rAd35, but not rAd5, leads to loss of vector-insert expression.

    Johnson, Matthew J; Björkström, Niklas K; Petrovas, Constantinos; Liang, Frank; Gall, Jason G D; Loré, Karin; Koup, Richard A

    2014-02-01

    Vaccines constructed from rare-serotype recombinant adenovirus vectors (rAd) such as rAd serotype 28 (rAd28) and rAd35 are currently being explored as alternatives to rAd5-based vaccines because they circumvent the problems with pre-existing immunity that complicate the effectiveness of rAd5 vaccines. However, previous work has demonstrated that the immunogenicity of rAd28 and rAd35 is substantially lower than rAd5. Here we show that rAd28 and rAd35 increase apoptosis of antigen presenting cells (APCs), such as monocytes, relative to rAd5 and mock infected controls. APCs undergoing apoptosis showed an increased loss of vector-insert expression. Loss of vector-insert expression correlated with activation of NK cells, which resulted in apoptosis of co-cultured monocytes. Finally, we show that activation of NK cells is dependent on IFNα which is produced by exposure to rAd28 or rAd35, but not to rAd5. Taken together, these data demonstrate that IFNα-induced activation of NK cells leads to increased monocyte apoptosis and subsequent vector-insert loss. This may be a possible mechanism that results in reduced immunogenicity of rAd28 and rAd35-based vectors. PMID:24325826

  2. Sample preparation for 2b-RAD genotyping

    sprotocols

    2015-01-01

    Authors: Shi Wang, Eli Meyer, John McKay & Mikhail Matz ### Abstract High-throughput sequencing of restriction site-associated genomic DNA (RAD) is now a widely used approach for simultaneously discovering and profiling genetic polymorphisms. We describe an alternative approach for RAD genotyping with several useful features, called 2b-RAD for the use of type IIB restriction endonucleases (AlfI, BsaXI). The fragments excised by type IIB enzymes are uniform in length, streamlining ...

  3. Effects of phosphorylation on function of the Rad GTPase.

    Moyers, J S; Zhu, J; Kahn, C R

    1998-08-01

    Rad, Gem and Kir possess unique structural features in comparison with other Ras-like GTPases, including a C-terminal 31-residue extension that lacks typical prenylation motifs. We have recently shown that Rad and Gem bind calmodulin in a Ca2+-dependent manner via this C-terminal extension, involving residues 278-297 in human Rad. This domain also contains several consensus sites for serine phosphorylation, and Rad is complexed with calmodulin-dependent protein kinase II (CaMKII) in C2C12 cells. Here we show that Rad serves as a substrate for phosphorylation by CaMKII, cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and casein kinase II (CKII) with stoichiometries in vitro of 0.2-1.3 mol of phosphate/mol of Rad. By deletion and point mutation analysis we show that phosphorylation by CaMKII and PKA occurs on a single serine residue at position 273, whereas PKC and CKII phosphorylate multiple C-terminal serine residues, including Ser214, Ser257, Ser273, Ser290 and Ser299. Incubation of Rad with PKA decreases GTP binding by 60-70%, but this effect seems to be independent of phosphorylation, as it is observed with the Ser273-->Ala mutant of Rad containing a mutation at the site of PKA phosphorylation. The remainder of the serine kinases have no effect on Rad GTP binding, intrinsic GTP hydrolysis or GTP hydrolysis stimulated by the putative tumour metastasis suppressor nm23. However, phosphorylation of Rad by PKC and CKII abolishes the interaction of Rad with calmodulin. These findings suggest that the binding of Rad to calmodulin, as well as its ability to bind GTP, might be regulated by the activation of several serine kinases. PMID:9677319

  4. RadCat 2.0 User Guide.

    Osborn, Douglas.; Weiner, Ruth F.; Mills, George Scott; Hamp, Steve C.; O' Donnell, Brandon, M.; Orcutt, David J.; Heames, Terence J.; Hinojosa, Daniel

    2005-01-01

    This document provides a detailed discussion and a guide for the use of the RadCat 2.0 Graphical User Interface input file generator for the RADTRAN 5.5 code. The differences between RadCat 2.0 and RadCat 1.0 can be attributed to the differences between RADTRAN 5 and RADTRAN 5.5 as well as clarification for some of the input parameters. 3

  5. Rad52 SUMOylation affects the efficiency of the DNA repair

    Altmannova, Veronika; Eckert-Boulet, Nadine; Arneric, Milica;

    2010-01-01

    Homologous recombination (HR) plays a vital role in DNA metabolic processes including meiosis, DNA repair, DNA replication and rDNA homeostasis. HR defects can lead to pathological outcomes, including genetic diseases and cancer. Recent studies suggest that the post-translational modification by...... recombination and DNA repair....... recombination mediator protein Rad52. Interestingly, Rad52 SUMOylation is enhanced by single-stranded DNA, and we show that SUMOylation of Rad52 also inhibits its DNA binding and annealing activities. The biochemical effects of SUMO modification in vitro are accompanied by a shorter duration of spontaneous Rad...

  6. Effects of Sr2+ doping on the electrical properties of (Bi0.5Na0.50.94Ba0.06TiO3 ceramics

    Amrita Singh

    2015-03-01

    Full Text Available The influence of SrTiO3 addition on the microstructure and various electrical properties of (Bi0.5Na0.50.94Ba0.06TiO3 (BNTBT6 ceramics, fabricated by a conventional high temperature solid state reaction, was investigated. Analysis of X-ray diffraction patterns revealed the formation of phase pure materials with tetragonal unit cell structure, tetragonality parameter c/a in the interval from 0.9940 to 1.0063 and crystallite sizes ranging from 33–76 nm for addition of 0.2 to 1 wt.% of SrTiO3. SEM studies indicated that Sr2+ doping led to decrease in grain size and non-homogeneity of grain distribution for higher SrTiO3 amount (>0.6 wt.%. Complex impedance, modulus, and conductivity studies indicated the presence of grains and grain boundary contribution, non-Debye type of relaxation and NTCR behaviour of the test ceramic samples. Temperature dependent real part of complex permittivity showed peaks at 475 °C and the dielectric loss tangent showed peaks corresponding to 125 °C and 475 °C for almost all compositions. AC activation energies, computed using Arrhenius relation in the temperature range of 325–500 °C for the BNTBT6 ceramic compositions having SrTiO3 concentration from 0.2 to 1.0 wt.%, were seen to have maximal values at the lowest measurement frequency. Amongst the different chosen doped BNTBT6 ceramic compositions, the composition having 0.6 wt.% of SrTiO3 showed the best ferroelectric and piezoelectric response with maximum value of Pr (8.24 µC/cm2, minimum value of Ec (5.73 kV/mm and maximum d33 value (∼46 pC/N.

  7. Piezoelectric, impedance, electric modulus and AC conductivity studies on (Bi0.5Na0.50.95Ba0.05TiO3 ceramic

    Ansu K. Roy

    2013-06-01

    Full Text Available Lead-free piezoelectric perovskite ceramic (Bi0.5Na0.50.95Ba0.05TiO3 (BNT-BT0.05, prepared by conventional high temperature solid state reaction technique at 1160 °C/3h in air atmosphere, is investigated by impedance and modulus spectroscopy in a temperature range 35–400 °C, over a frequency range 100 Hz–1 MHz. The crystal structure, microstructure, and piezoelectric properties as well as the AC conductivity of the sample were studied. Powder X-ray diffraction pattern derived from the resulting data at the room temperature subjected to Rietveld refinements and Williamson-Hall plot analysis confirmed the formation of phase pure compound with monoclinic unit cells having a crystallite-size ~33.8 nm. Observed SEM micrograph showed a uniform distribution of grains inside the sample having an average grain size ~3 mm. Longitudinal piezoelectric charge coefficient of the sample poled under a DC electric field of ~ 2.5 kV/mm at 80 °C in a silicone oil bath was found to be equal to 95 pC/N. The frequency and temperature dependent electrical data analysed in the framework of AC conductivity, complex impedance as well as electric modulus formalisms showed negative temperature coefficient of resistance (NTCR character of the material and the dielectric relaxation in the material to be of non-Debye type. Double power law for the frequency-dependence of AC conductivity and Jump Relaxation Model (JRM were found to explain successfully the mechanism of charge transport in BNT-BT0.05.

  8. Easy Mode Course for Personal Radiation Detectors Thermo Rad Eye

    The presentation describes the use of the Rad Eye Personal Radiation Detector for monitoring and searching.The search alarm of the Rad Eye is based on 6 sigma and its safety alarm is set at 10000 counts per second and 100 micro Sv/h, which is the IAEA default setting

  9. Reactive airways dysfunction syndrome (RADS): fact or fantasy?

    Bardana, E J

    1999-01-01

    Most evidence suggests that RADS is a distinct syndrome and not simply an exacerbation of pre-existing hyperresponsiveness. There is no doubt that much remains to be explained regarding pathogenesis. On the other hand, I urge caution about the claims of "low-level RADS". Here the data are much more anecdotal and leave much to be desired. PMID:10735647

  10. Study on Performance of Empore~(TM) Technetium Rad Disks

    2011-01-01

    EmporeTM Technetium Rad disks produced by 3M Company contain GD-1 sorbent loaded on particles that are embedded in an inert PTFE matrix. In this study, several experiments have been accomplished to evaluate the performance of EmporeTM Technetium Rad disks.

  11. Anomalous weak ferromagnetism in electron-doped Nd{sub 1-x}Sr{sub x}MnO{sub 3} (0.50 {<=} x {<=} 0.62) thin films

    Kumar, Pawan; Dwivedi, Rakesh Kumar [Jaypee Institute of Information Technology, Uttar Pradesh (India); Prasad, Ravikant; Srivastava, Avanish Kumar; Singh, Hari Krishna [National Physical Laboratory, New Delhi (India); Singh, Mangala Prasad [Brock University, St. Catharines (Canada)

    2011-10-15

    In the present work, we demonstrate that an anomalous weak ferromagnetism occurs in the composition range 0.50 {<=} x {<=} 0.62 in nanostructured thin films of Nd{sub 1-x}Sr{sub x}MnO{sub 3} (NSMO). Nanocrystalline thin films of overdoped manganite Nd{sub 1-x}Sr{sub x}MnO{sub 3} (x {approx} 0.50, 0.55, 0.60, and 0.62) are grown on single-crystal LaAlO{sub 3} (001) substrates by using a nebulized chemical spray pyrolysis technique. These single phase films possess an average crystallite size {approx}15 nm, and the width of the grain boundaries is {approx}1 - 2 nm. In the composition range 0.50 {<=} x {<=} 0.62, the ground state of NSMO is an A-type antiferromagnetic (AFM) metallic state. However, in the present films, a broad paramagnetic (PM)-to-ferromagnetic (FM) transition is observed in all the compositions, at T{sub C} {approx} 226 K for x = 0.50 and at 235 K for rest of the samples. All the films show a well-defined M-H hysteresis loop at 5 K. The coercivity (H{sub C}) of these films is much larger than those having compositions in the range 0.35 < x < 0.45. For x = 0.50 (0.62), the films H{sub C} = -1210 (-1484) Oe and +1162 (+1476) Oe. The asymmetry in the coercivity suggests the presence of a weak exchange bias effect in these films. The FM ground state in these films is observed to have a smaller magnetic moment per Mn atom than the expected full moment from the rigid model; we term this as a weak ferromagnetic (WFM) state arising due to the destabilization of the AFM ordering. We propose a possible scenario based on the combined effect of spin reorganization and enhanced orbital disordering in nanosized manganites to explain the observed anomalous weak ferromagnetism in the A-type AFM spin ordered region.

  12. The Saccharomyces cerevisiae RAD9, RAD17, RAD24 and MEC3 genes are required for tolerating irreparable, ultraviolet-induced DNA damage

    In wild-type Saccharomyces cerevisiae, a checkpoint slows the rate of progression of an ongoing S phase in response to exposure to a DNA-alkylating agent. Mutations that eliminate S phase regulation also confer sensitivity to alkylating agents, leading us to suggest that, by regulating the S phase rate, cells are either better able to repair or better able to replicate damaged DNA. In this study, we determine the effects of mutations that impair S phase regulation on the ability of excision repair-defective cells to replicate irreparably UV-damaged DNA. We assay survival after UV irradiation, as well as the genetic consequences of replicating a damaged template, namely mutation and sister chromatid exchange induction. We find that RAD9, RAD17, RAD24, and MEC3 are required for UV-induced (although not spontaneous) mutagenesis, and that RAD9 and RAD17 (but not REV3, RAD24, and MEC3) are required for maximal induction of replication-dependent sister chromatid exchange. Therefore, checkpoint genes not only control cell cycle progression in response to damage, but also play a role in accommodating DNA damage during replication. (author)

  13. Determination of radon concentration in water using RAD7 with RAD H{sub 2}O accessories

    Malik, M. F. I. [Science and Engineering Research Centre (SERC), Universiti Sains Malaysia, Seri Ampangan Nibong Tebal 14300 Penang (Malaysia); Rabaiee, N. A.; Jaafar, M. S. [School of Physics, Universiti Sains Malaysia, 11800 Penang (Malaysia)

    2015-04-24

    In the last decade, the radon issue has become one of the major problems of radiation protection. Radon exposure occurs when using water for showering, washing dishes, cooking and drinking water. RAD7 and Rad H20 accessories were used in order to measure radon concentration in water sample. In this study, four types of water were concerns which are reverse osmosis (drinking water), mineral water, tap water and well water. Reverse osmosis (drinking water) and mineral water were bought from the nearest supermarket while tap water and well water were taken from selected areas of Pulau Pinang and Kedah. Total 20 samples were taken with 5 samples for each type of water. The measured radon concentration ranged from 2.9±2.9 to 79.5±17 pCi/L, 2.9±2.9 to 67.8±16 pCi/L, 15.97±7 to 144.25±24 pCi/L and 374.89±37 to 6409.03±130 pCi/L in reverse osmosis (drinking water), mineral water, tap water and well water. Well water has the highest radon compared to others. It was due to their geological element such as granite. Results for all types of water are presented and compared with maximum contamination limit (MCL) recommended by United State Environmental Protection Agency (USEPA) which is 300pCi/L. Reverse osmosis water, mineral water and tap water were fall below MCL. However, well water was exceeded maximum level that was recommended. Thus, these findings were suggested that an action should be taken to reduce radon concentration level in well water as well as reduce a health risk towards the public.

  14. Synthesis and characterization particles of Ba0,50Sr0,50Co0,80Fe0,20O3 obtained by the citrate-EDTA technique

    The Ba(1-x)Sr(x)Co(1-y)Fe(y)O(3) (BSCF) has been studied as a cathode material for Intermediate Temperature Solid Oxide Fuel Cell, due to its better ion and electron conduction. This work aims to study the synthesis of the compound obtained from the citrate-EDTA technique. Thermogravimetric analysis indicated the formation of the compound above 800 deg C. The materials calcined at temperatures of 700, 800 and 900 deg C for 5 h showed cubic pseudo-perovskite structure, according to the literature. By analysis of X-ray fluorescence were obtained powders with nominal chemical composition in the temperature range studied. The micrographs obtained by SEM and particle size distribution analysis showed the formation of particle with diameters below 1 micron. (author)

  15. Interrogation of the protein-protein interactions between human BRCA2 BRC repeats and RAD51 reveals atomistic determinants of affinity.

    Cole, Daniel J; Rajendra, Eeson; Roberts-Thomson, Meredith; Hardwick, Bryn; McKenzie, Grahame J; Payne, Mike C; Venkitaraman, Ashok R; Skylaris, Chris-Kriton

    2011-07-01

    The breast cancer suppressor BRCA2 controls the recombinase RAD51 in the reactions that mediate homologous DNA recombination, an essential cellular process required for the error-free repair of DNA double-stranded breaks. The primary mode of interaction between BRCA2 and RAD51 is through the BRC repeats, which are ∼35 residue peptide motifs that interact directly with RAD51 in vitro. Human BRCA2, like its mammalian orthologues, contains 8 BRC repeats whose sequence and spacing are evolutionarily conserved. Despite their sequence conservation, there is evidence that the different human BRC repeats have distinct capacities to bind RAD51. A previously published crystal structure reports the structural basis of the interaction between human BRC4 and the catalytic core domain of RAD51. However, no structural information is available regarding the binding of the remaining seven BRC repeats to RAD51, nor is it known why the BRC repeats show marked variation in binding affinity to RAD51 despite only subtle sequence variation. To address these issues, we have performed fluorescence polarisation assays to indirectly measure relative binding affinity, and applied computational simulations to interrogate the behaviour of the eight human BRC-RAD51 complexes, as well as a suite of BRC cancer-associated mutations. Our computational approaches encompass a range of techniques designed to link sequence variation with binding free energy. They include MM-PBSA and thermodynamic integration, which are based on classical force fields, and a recently developed approach to computing binding free energies from large-scale quantum mechanical first principles calculations with the linear-scaling density functional code onetep. Our findings not only reveal how sequence variation in the BRC repeats directly affects affinity with RAD51 and provide significant new insights into the control of RAD51 by human BRCA2, but also exemplify a palette of computational and experimental tools for the

  16. Interrogation of the protein-protein interactions between human BRCA2 BRC repeats and RAD51 reveals atomistic determinants of affinity.

    Daniel J Cole

    2011-07-01

    Full Text Available The breast cancer suppressor BRCA2 controls the recombinase RAD51 in the reactions that mediate homologous DNA recombination, an essential cellular process required for the error-free repair of DNA double-stranded breaks. The primary mode of interaction between BRCA2 and RAD51 is through the BRC repeats, which are ∼35 residue peptide motifs that interact directly with RAD51 in vitro. Human BRCA2, like its mammalian orthologues, contains 8 BRC repeats whose sequence and spacing are evolutionarily conserved. Despite their sequence conservation, there is evidence that the different human BRC repeats have distinct capacities to bind RAD51. A previously published crystal structure reports the structural basis of the interaction between human BRC4 and the catalytic core domain of RAD51. However, no structural information is available regarding the binding of the remaining seven BRC repeats to RAD51, nor is it known why the BRC repeats show marked variation in binding affinity to RAD51 despite only subtle sequence variation. To address these issues, we have performed fluorescence polarisation assays to indirectly measure relative binding affinity, and applied computational simulations to interrogate the behaviour of the eight human BRC-RAD51 complexes, as well as a suite of BRC cancer-associated mutations. Our computational approaches encompass a range of techniques designed to link sequence variation with binding free energy. They include MM-PBSA and thermodynamic integration, which are based on classical force fields, and a recently developed approach to computing binding free energies from large-scale quantum mechanical first principles calculations with the linear-scaling density functional code onetep. Our findings not only reveal how sequence variation in the BRC repeats directly affects affinity with RAD51 and provide significant new insights into the control of RAD51 by human BRCA2, but also exemplify a palette of computational and

  17. Astaxanthin down-regulates Rad51 expression via inactivation of AKT kinase to enhance mitomycin C-induced cytotoxicity in human non-small cell lung cancer cells.

    Ko, Jen-Chung; Chen, Jyh-Cheng; Wang, Tai-Jing; Zheng, Hao-Yu; Chen, Wen-Ching; Chang, Po-Yuan; Lin, Yun-Wei

    2016-04-01

    Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects, including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination, and studies show that chemo-resistant carcinomas exhibit high levels of Rad51 expression. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Astaxanthin treatment (2.5-20μM) decreased Rad51 expression and phospho-AKT(Ser473) protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector rescued the decreased Rad51 mRNA and protein levels in astaxanthin-treated NSCLC cells. Combined treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors (LY294002 or wortmannin) further decreased the Rad51 expression in astaxanthin-exposed A549 and H1703 cells. Knockdown of Rad51 expression by transfection with si-Rad51 RNA or cotreatment with LY294002 further enhanced the cytotoxicity and cell growth inhibition of astaxanthin. Additionally, mitomycin C (MMC) as an anti-tumor antibiotic is widely used in clinical NSCLC chemotherapy. Combination of MMC and astaxanthin synergistically resulted in cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced phospho-AKT(Ser473) level and Rad51 expression. Overexpression of AKT-CA or Flag-tagged Rad51 reversed the astaxanthin and MMC-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in astaxanthin and MMC co-treated cells. In conclusion, astaxanthin enhances MMC-induced cytotoxicity by decreasing Rad51 expression and AKT activation. These findings may provide rationale to combine astaxanthin with MMC for the treatment of NSCLC. PMID:26921637

  18. The SRS2 suppressor of rad6 mutations of Saccharomyces cerevisiae acts by channeling DNA lesions into the RAD52 DNA repair pathway

    rad6 mutants of Saccharomyces cerevisiae are defective in the repair of damaged DNA, DNA damage induced mutagenesis, and sporulation. In order to identify genes that can substitute for RAD6 function, the authors have isolated genomic suppressors of the UV sensitivity of rad6 deletion (rad6Δ) mutations and show that they also suppress the γ-ray sensitivity but not the UV mutagenesis or sporulation defects of rad6. The suppressors show semidominance for suppression of UV sensitivity and dominance for suppression of γ-ray sensitivity. The six suppressor mutations they isolated are all alleles of the same locus and are also allelic to a previously described suppressor of the rad6-1 nonsense mutation, SRS2. They show that suppression of rad6Δ is dependent on the RAD52 recombinational repair pathway since suppression is not observed in the rad6Δ SRS2 strain containing an additional mutation in either the RAD51, RAD52, RAD54, RAD55 or RAD57 genes. Possible mechanisms by which SRS2 may channel unrepaired DNA lesions into the RAD52 DNA repair pathway are discussed

  19. Aktsiisiseaduse muudatused 2006. aastal : aktsiisimäärad / Urmas Koidu

    Koidu, Urmas

    2006-01-01

    2006. aastal jõustunud alkoholi-, tubaka- ja kütuseaktsiisi seaduse muudatustest. Lisatud tabelid: alkoholi aktsiisimäärad Eestis 2006-2008 ja ELi aktsiisi alammäärad (krooni); tubakatoodete aktsiisimäärad Eestis 2006-2008 ja ELi aktsiisi alammäärad; mootorikütuse aktsiisimäärad Eestis ja ELi alammäärad; kütteainete ja elektrienergia aktsiisimäärad Eestis ja ELi alammäärad

  20. Synthesis and characterization particles of Ba{sub 0,50}Sr{sub 0,50}Co{sub 0,80}Fe{sub 0,20}O{sub 3} obtained by the citrate-EDTA technique; Sintese e caracterizacao de particulados de Ba{sub 0,50}Sr{sub 0,50}Co{sub 0,80}Fe{sub 0,20}O{sub 3} obtidos pela tecnica dos citratos-EDTA

    Bonturim, E.; Vargas, R.A.; Andreoli, M.; Seo, E.S.M., E-mail: ebonturim@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (CCTM/IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Ciencia e Tecnologia de Materiais

    2010-07-01

    The Ba{sub (1-x)}Sr{sub (x)}Co{sub (1-y)}Fe{sub (y)}O{sub (3)} (BSCF) has been studied as a cathode material for Intermediate Temperature Solid Oxide Fuel Cell, due to its better ion and electron conduction. This work aims to study the synthesis of the compound obtained from the citrate-EDTA technique. Thermogravimetric analysis indicated the formation of the compound above 800 deg C. The materials calcined at temperatures of 700, 800 and 900 deg C for 5 h showed cubic pseudo-perovskite structure, according to the literature. By analysis of X-ray fluorescence were obtained powders with nominal chemical composition in the temperature range studied. The micrographs obtained by SEM and particle size distribution analysis showed the formation of particle with diameters below 1 micron. (author)

  1. Molecular characterization of RadLV (radiation leukemia virus)

    Following a course of a fractionated whole-body x-irradiation, a high percentage of C57BL/Ka mice develop thymic lymphomas. Radiation leukemia virus (RadLV) can be consistently isolated from these tumors. RadLV can induce identical lymphomas in unirradiated C57BL/Ka mice, and its role as the etiologic agent of these malignancies has been clearly documented. In order to characterize the viral genome at the molecular level, the unintegrated DNA intermediates of several RadLV isolates were prepared. Several different protocols were developed to optimize the yield and quality of restriction endonucleases, and cloned into a bacteriophage vector using recombinant DNA technology. RadLV is a general term used to describe a number of lymphomagenic viruses isolated from (1) primary radiation-induced lymphomas, (2) virus-induced lymphomas, and (3) established cell lines. The RadLV viruses replicate preferentially in the thymus and cause thymic lymphomas. Non-thymotropic, non-oncogenic, fibrotropic viruses can also be isolated from C57BL/Ka mice. Thus, a spectrum of biological activities can be seen among the C57BL/Ka mouse retroviruses. This dissertation reports the molecular cloning of three of the RadLV viruses. They are: (1) RadLV/VL3 and (2) RadLV/RL10, both lymphomagenic viruses, and (3) RadLV/RL15, a non-oncogenic isolate. The generation of restriction maps from both the cloned DNAs and the unintegrated viral DNA intermediates is described. These maps are compared with those of other C57BL/Ka murine retroviruses, and with published maps of other murine leukemia viruses

  2. RAD/COMM ''Cricket'' Test Report

    Chiaro, P J

    2002-01-01

    A series of tests were performed at Oak Ridge National Laboratory (ORNL) to evaluate and characterize the radiological response of a ''Cricket'' radiation detection system. The ''Cricket'' is manufactured by RAD/COMM Systems Corp., which is located in Ontario, Canada. The system is designed to detect radioactive material that may be contained in scrap metal. The Cricket's detection unit is mounted to the base of a grappler and monitors material, while the grappler's tines hold the material. It can also be used to scan material in an attempt to isolate radioactive material if an alarm occurs. Testing was performed at the Environmental Effects Laboratory located at ORNL and operated by the Engineering Science and Technology Division. Tests performed included the following: (1) Background stability, (2) Energy response using sup 2 sup 4 sup 1 Am, sup 1 sup 3 sup 7 Cs, and sup 6 sup 0 Co, (3) Surface uniformity, (4) Angular dependence, (5) Alarm actuation, (6) Alarm threshold vs. background, (7) Shielding, (8) Re...

  3. The Martian surface radiation environment – a comparison of models and MSL/RAD measurements

    Matthiä Daniel

    2016-01-01

    Full Text Available Context: The Radiation Assessment Detector (RAD on the Mars Science Laboratory (MSL has been measuring the radiation environment on the surface of Mars since August 6th 2012. MSL-RAD is the first instrument to provide detailed information about charged and neutral particle spectra and dose rates on the Martian surface, and one of the primary objectives of the RAD investigation is to help improve and validate current radiation transport models. Aims: Applying different numerical transport models with boundary conditions derived from the MSL-RAD environment the goal of this work was to both provide predictions for the particle spectra and the radiation exposure on the Martian surface complementing the RAD sensitive range and, at the same time, validate the results with the experimental data, where applicable. Such validated models can be used to predict dose rates for future manned missions as well as for performing shield optimization studies. Methods: Several particle transport models (GEANT4, PHITS, HZETRN/OLTARIS were used to predict the particle flux and the corresponding radiation environment caused by galactic cosmic radiation on Mars. From the calculated particle spectra the dose rates on the surface are estimated. Results: Calculations of particle spectra and dose rates induced by galactic cosmic radiation on the Martian surface are presented. Although good agreement is found in many cases for the different transport codes, GEANT4, PHITS, and HZETRN/OLTARIS, some models still show large, sometimes order of magnitude discrepancies in certain particle spectra. We have found that RAD data is helping to make better choices of input parameters and physical models. Elements of these validated models can be applied to more detailed studies on how the radiation environment is influenced by solar modulation, Martian atmosphere and soil, and changes due to the Martian seasonal pressure cycle. By extending the range of the calculated particle

  4. The Martian surface radiation environment - a comparison of models and MSL/RAD measurements

    Matthiä, Daniel; Ehresmann, Bent; Lohf, Henning; Köhler, Jan; Zeitlin, Cary; Appel, Jan; Sato, Tatsuhiko; Slaba, Tony; Martin, Cesar; Berger, Thomas; Boehm, Eckart; Boettcher, Stephan; Brinza, David E.; Burmeister, Soenke; Guo, Jingnan; Hassler, Donald M.; Posner, Arik; Rafkin, Scot C. R.; Reitz, Günther; Wilson, John W.; Wimmer-Schweingruber, Robert F.

    2016-03-01

    Context: The Radiation Assessment Detector (RAD) on the Mars Science Laboratory (MSL) has been measuring the radiation environment on the surface of Mars since August 6th 2012. MSL-RAD is the first instrument to provide detailed information about charged and neutral particle spectra and dose rates on the Martian surface, and one of the primary objectives of the RAD investigation is to help improve and validate current radiation transport models. Aims: Applying different numerical transport models with boundary conditions derived from the MSL-RAD environment the goal of this work was to both provide predictions for the particle spectra and the radiation exposure on the Martian surface complementing the RAD sensitive range and, at the same time, validate the results with the experimental data, where applicable. Such validated models can be used to predict dose rates for future manned missions as well as for performing shield optimization studies. Methods: Several particle transport models (GEANT4, PHITS, HZETRN/OLTARIS) were used to predict the particle flux and the corresponding radiation environment caused by galactic cosmic radiation on Mars. From the calculated particle spectra the dose rates on the surface are estimated. Results: Calculations of particle spectra and dose rates induced by galactic cosmic radiation on the Martian surface are presented. Although good agreement is found in many cases for the different transport codes, GEANT4, PHITS, and HZETRN/OLTARIS, some models still show large, sometimes order of magnitude discrepancies in certain particle spectra. We have found that RAD data is helping to make better choices of input parameters and physical models. Elements of these validated models can be applied to more detailed studies on how the radiation environment is influenced by solar modulation, Martian atmosphere and soil, and changes due to the Martian seasonal pressure cycle. By extending the range of the calculated particle spectra with respect to

  5. Rad-hard embedded computers for nuclear robotics

    For requirements of nuclear industries, it is necessary to use robots with embedded rad hard electronics and high level safety. The computer developed for french research program SYROCO is presented in this paper. (authors). 8 refs., 5 figs

  6. RadNet Real-Time Monitoring Spectrometry Data Inventory

    U.S. Environmental Protection Agency — The RadNet Real-Time Monitoring Spectrometry Data Inventory contains measured data used to identify and measure specific radioactive materials in the atmosphere at...

  7. RadNet (Environmental Radiation Ambient Monitoring System)

    U.S. Environmental Protection Agency — RadNet, formerly Environmental Radiation Ambient Monitoring System (ERAMS), is a national network of monitoring stations that regularly collect air, precipitation,...

  8. RadNet-Air Near Real Time Data

    U.S. Environmental Protection Agency — RadNet-Air is a national network of air monitoring stations that regularly collect air samples for near real time analysis of radioactivity. The data is transmitted...

  9. RADTRAN 6/RadCat 6 user guide.

    Weiner, Ruth F.; Hinojosa, Daniel; Heames, Terence John; Farnum, Cathy Ottinger; Kalinina, Elena Arkadievna

    2013-09-01

    This document provides a detailed discussion and a guide for the use of the RadCat 6.0 Graphical User Interface input file generator for the RADTRAN code, Version 6. RadCat 6.0 integrates the newest analysis capabilities of RADTRAN 6.0, including an economic model, updated loss-of-lead shielding model, a new ingestion dose model, and unit conversion. As of this writing, the RADTRAN version in use is RADTRAN 6.02.

  10. Methods for measuring sub-pm rad vertical emittance at the Swiss Light Source

    Breunlin, J.; Andersson, Å.; Milas, N.; Saá Hernández, Á.; Schlott, V.

    2015-12-01

    We report on methods capable of measuring a rms vertical electron beam size of 3 μm with a rms error of less than 10% at a diagnostic beamline at the Swiss Light Source (SLS). This corresponds to a vertical emittance of 0.6 pm rad with a 20% rms error. We showed this capability by presenting the theoretical basis for, and the data from, a series of measurements on a stable beam at 1.6 pm rad vertical emittance at the SLS. The methods presented utilized either π- or σ-polarized synchrotron radiation (SR) in the visible to ultra violet (vis-UV) spectral range. In addition to the established π-polarization method, we introduced a diffraction method with a potentially high resolution capability. Also an intensity imbalanced diffraction scheme was introduced, but was found to be prone to SR induced carbon contamination on optical elements.

  11. Protein-DNA interactions in high speed AFM: single molecule diffusion analysis of human RAD54.

    Sanchez, Humberto; Suzuki, Yuki; Yokokawa, Masatoshi; Takeyasu, Kunio; Wyman, Claire

    2011-11-01

    High-speed AFM (atomic force microscopy also called scanning force microscopy) provides nanometre spatial resolution and sub-second temporal resolution images of individual molecules. We exploit these features to study diffusion and motor activity of the RAD54 DNA repair factor. Human RAD54 functions at critical steps in recombinational-DNA repair. It is a member of the Swi2/Snf2 family of chromatin remodelers that translocate on DNA using ATP hydrolysis. A detailed single molecular description of DNA-protein interactions shows intermediate states and distribution of variable states, usually hidden by ensemble averaging. We measured the motion of individual proteins using single-particle tracking and observed that random walks were affected by imaging-buffer composition. Non-Brownian diffusion events were characterized in the presence and in the absence of nucleotide cofactors. Double-stranded DNA immobilized on the surface functioned as a trap reducing Brownian motion. Distinct short range slides and hops on DNA were visualized by high-speed AFM. These short-range interactions were usually inaccessible by other methods based on optical resolution. RAD54 monomers displayed a diffusive behavior unrelated to the motor activity. PMID:21986699

  12. Compensatory role for Rad52 during recombinational repair in Ustilago maydis

    Kojic, Milorad; Mao, Ninghui; Zhou, Qingwen;

    2008-01-01

    spontaneous mutator activity, allelic recombination or meiosis. GFP-Rad51 foci were formed in rad52 cells following DNA damage, but were initially less intense than normal suggesting a possible role for Rad52 in formation of the Rad51 nucleoprotein filament. A search for interacting genes that confer a...

  13. Avaliação das propriedades do Ba0,50Sr0,50Co0,80Fe0,20O3-d para células a combustível de óxido sólido de temperatura intermediária obtido pelo método citratos-EDTA Evaluation of the properties of Ba0,50Sr0.50Co0.80Fe0.20O3-d obtained by the citrate-EDTA method for intermediate temperature solid oxide fuel cell

    E. Bonturim

    2013-03-01

    Full Text Available Ba0,50Sr0,50Co0,80Fe0,20O3-d (BSCF apresenta propriedades físicas, químicas e microestruturais adequadas para compor o cátodo de uma célula a combustível de óxido sólido de temperatura intermediária (ITSOFC. Este trabalho tem por objetivo a síntese e a caracterização do BSCF obtido pelo método dos citrados-EDTA. Os resultados obtidos por difração de raios X (DRX indicaram fases secundárias para o material calcinado a 700 e 800 ºC e fase única com estrutura cristalina do tipo perovskita para 900 ºC. As micrografias obtidas por microscopia eletrônica de varredura dos particulados evidenciou a formação de aglomerados de tamanho Ba0.50Sr0.50Co0.80Fe0.20O3-d (BSCF presents physical, chemical and microstructural properties suitable to form the cathode of Intermediate Temperature Solid Oxide Fuel Cell (ITSOFC. This work aims the synthesis and characterization of BSCF, obtained by the citrate-EDTA method. The X-ray diffraction results indicate secondary phases for the material calcined at 700 and 800 °C and single phase with perovskite crystalline structure at 900 °C. The SEM-FEG particles micrographs show the formation of < 20 µm clusters. The dilatometric analysis of pellets indicates the sintering temperature at ~ 1050 °C. XRD results of the sintered samples show perovskite single phase. The SEM micrographs confirmed the formation of higher porosity in the samples sintered at 1000 °C/1 h using powders calcined at 900 °C.

  14. Reactivities of radicals of adenine and guanine towards reactive oxygen species and reactive nitrogen oxide species: OH rad and NO 2rad

    Agnihotri, Neha; Mishra, P. C.

    2011-02-01

    Reactions of radicals of the DNA bases with reactive oxygen species and reactive nitrogen oxide species produce mutagenic products. We have studied reactivities of all the carbon sites of radicals of adenine A(-H) rad and guanine G(-H) rad obtained by removal of H-atoms from their nitrogen sites towards OH rad and NO 2rad . We studied stabilities of A(-H) rad and G(-H) rad and binding energies of their adducts with each of OH rad and NO 2rad using density functional theoretic and MP2 calculations employing the AUG-cc-pVDZ basis set. Solvation in aqueous media was treated using the polarization continuum model. The results obtained explain experimental observations.

  15. Intraobserver interpretation of breast ultrasonography following the BI-RADS classification

    Purpose: To use the BI-RADS ultrasound classification in an intraobserver retrospective study of the interpretation of breast images. Materials and Methods: The study used 40 breast ultrasound images recorded in orthogonal planes, obtained from patients with an indication for surgery. Eight professionals experienced in breast imaging analysis retrospectively reviewed these lesions, in three rounds of image interpretation (with a 3-6 months interval between rounds). Observers had no access to information from medical records or histopathological results, and, without their knowledge, in each new round were assigned the same images previously interpreted by them. Fleiss-modified Kappa measures were the study main concordance index. Besides the BI-RADS, a scale grouping its categories 2-3 and 4-5 was also used. The statistical analysis concerned the intraobserver agreement. Results: Kappa values ranged from 0.37 to 0.75 (original categories) and from 0.73 to 0.87 (grouped categories). Overall, out of the 8 observers, 7 presented moderate to substantial concordance (Kappa values 0.51 to 0.74). Conclusion: The BI-RADS is a reporting tool that provides a standardized terminology for US exams. In this study, moderate to substantial concordance in Kappa values was found, in agreement with other studies of the literature.

  16. Yeast rad7-rad16 complex, specific for the nucleotide excision repair of the nontranscribed DNA strand, is an ATP-dependent DNA damage sensor

    In eukaryotes, nucleotide excision repair of ultraviolet light-damaged DNA is a highly intricate process that requires a large number of evolutionary conserved protein factors. Genetic studies in the yeast Saccharomyces cerevisiae have indicated a specific role of the RAD7 and RAD16 genes in the repair of transcriptionally inactive DNA. Here we show that the RAD7- and RAD16-encoded products exist as a complex of 1:1 stoichiometry, exhibiting an apparent dissociation constant (Kd) of <4 x 10(-10) M. The Rad7-Rad16 complex has been purified to near homogeneity in this study and is shown to bind, in an ATP-dependent manner and with high specificity, to DNA damaged by ultraviolet light. Importantly, inclusion of the Rad7-Rad16 complex in the in vitro nucleotide excision repair system that consists entirely of purified components results in a marked stimulation of damage specific incision. Thus, Rad7-Rad16 complex is the ATP-dependent DNA damage sensor that specifically functions with the ensemble of nucleotide excision repair factor (NEF) 1, NEF2, NEF3, and replication protein A in the repair of transcriptionally inactive DNA. We name this novel complex of Rad7 and Rad16 proteins NEF4. (author)

  17. A novel interation of nucleolin with Rad51

    Nucleolin associates with various DNA repair, recombination, and replication proteins, and possesses DNA helicase, strand annealing, and strand pairing activities. Examination of nuclear protein extracts from human somatic cells revealed that nucleolin and Rad51 co-immunoprecipitate. Furthermore, purified recombinant Rad51 associates with in vitro transcribed and translated nucleolin. Electroporation-mediated introduction of anti-nucleolin antibody resulted in a 10- to 20-fold reduction in intra-plasmid homologous recombination activity in human fibrosarcoma cells. Additionally, introduction of anti-nucleolin antibody sensitized cells to death induced by the topoisomerase II inhibitor, amsacrine. Introduction of anti-Rad51 antibody also reduced intra-plasmid homologous recombination activity and induced hypersensitivity to amsacrine-induced cell death. Co-introduction of anti-nucleolin and anti-Rad51 antibodies did not produce additive effects on homologous recombination or on cellular sensitivity to amsacrine. The association of the two proteins raises the intriguing possibility that nucleolin binding to Rad51 may function to regulate homologous recombinational repair of chromosomal DNA

  18. The C-terminal region of Rad52 is essential for Rad52 nuclear and nucleolar localization, and accumulation at DNA damage sites immediately after irradiation

    Highlights: •Rad52 might play a key role in the repair of DSB immediately after irradiation. •EYFP-Rad52 accumulates rapidly at DSB sites and colocalizes with Ku80. •Accumulation of Rad52 at DSB sites is independent of the core NHEJ factors. •Localization and recruitment of Rad52 to DSB sites are dependent on the Rad52 CTR. •Basic amino acids in Rad52 CTR are highly conserved among vertebrate species. -- Abstract: Rad52 plays essential roles in homologous recombination (HR) and repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae. However, in vertebrates, knockouts of the Rad52 gene show no hypersensitivity to agents that induce DSBs. Rad52 localizes in the nucleus and forms foci at a late stage following irradiation. Ku70 and Ku80, which play an essential role in nonhomologous DNA-end-joining (NHEJ), are essential for the accumulation of other core NHEJ factors, e.g., XRCC4, and a HR-related factor, e.g., BRCA1. Here, we show that the subcellular localization of EYFP-Rad52(1–418) changes dynamically during the cell cycle. In addition, EYFP-Rad52(1–418) accumulates rapidly at microirradiated sites and colocalizes with the DSB sensor protein Ku80. Moreover, the accumulation of EYFP-Rad52(1–418) at DSB sites is independent of the core NHEJ factors, i.e., Ku80 and XRCC4. Furthermore, we observed that EYFP-Rad52(1–418) localizes in nucleoli in CHO-K1 cells and XRCC4-deficient cells, but not in Ku80-deficient cells. We also found that Rad52 nuclear localization, nucleolar localization, and accumulation at DSB sites are dependent on eight amino acids (411–418) at the end of the C-terminal region of Rad52 (Rad52 CTR). Furthermore, basic amino acids on Rad52 CTR are highly conserved among mammalian, avian, and fish homologues, suggesting that Rad52 CTR is important for the regulation and function of Rad52 in vertebrates. These findings also suggest that the mechanism underlying the regulation of subcellular localization of Rad52 is

  19. The C-terminal region of Rad52 is essential for Rad52 nuclear and nucleolar localization, and accumulation at DNA damage sites immediately after irradiation

    Koike, Manabu, E-mail: m_koike@nirs.go.jp [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Yutoku, Yasutomo [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Koike, Aki [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2013-05-31

    Highlights: •Rad52 might play a key role in the repair of DSB immediately after irradiation. •EYFP-Rad52 accumulates rapidly at DSB sites and colocalizes with Ku80. •Accumulation of Rad52 at DSB sites is independent of the core NHEJ factors. •Localization and recruitment of Rad52 to DSB sites are dependent on the Rad52 CTR. •Basic amino acids in Rad52 CTR are highly conserved among vertebrate species. -- Abstract: Rad52 plays essential roles in homologous recombination (HR) and repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae. However, in vertebrates, knockouts of the Rad52 gene show no hypersensitivity to agents that induce DSBs. Rad52 localizes in the nucleus and forms foci at a late stage following irradiation. Ku70 and Ku80, which play an essential role in nonhomologous DNA-end-joining (NHEJ), are essential for the accumulation of other core NHEJ factors, e.g., XRCC4, and a HR-related factor, e.g., BRCA1. Here, we show that the subcellular localization of EYFP-Rad52(1–418) changes dynamically during the cell cycle. In addition, EYFP-Rad52(1–418) accumulates rapidly at microirradiated sites and colocalizes with the DSB sensor protein Ku80. Moreover, the accumulation of EYFP-Rad52(1–418) at DSB sites is independent of the core NHEJ factors, i.e., Ku80 and XRCC4. Furthermore, we observed that EYFP-Rad52(1–418) localizes in nucleoli in CHO-K1 cells and XRCC4-deficient cells, but not in Ku80-deficient cells. We also found that Rad52 nuclear localization, nucleolar localization, and accumulation at DSB sites are dependent on eight amino acids (411–418) at the end of the C-terminal region of Rad52 (Rad52 CTR). Furthermore, basic amino acids on Rad52 CTR are highly conserved among mammalian, avian, and fish homologues, suggesting that Rad52 CTR is important for the regulation and function of Rad52 in vertebrates. These findings also suggest that the mechanism underlying the regulation of subcellular localization of Rad52 is

  20. Magnetic properties of U(Ni1-xCux)2Si2 solid solutions in the vicinity of x = 0.50 studied by neutron diffraction and AC-susceptibility

    The magnetic properties of two U(Ni1-xCux)2Si2 solid in the vicinity of x = 0.50 (denoted I and II) have been studied by neutron diffraction and ac-susceptibility. Both materials have ThCr2Si2-type crystallographic structure. AC-susceptibility shows antiferromagnetic transitions at TN150±5 K in UNiCuSi2(I) and 155±5 K in UNiCuSi2(II), followed by several transitions with ferrimagnetic (F) character at lower temperatures. Apart from the transitions to AF-I structure at TN=150K and 152K none of the F transitions is observed by neutron diffraction. Short-range magnetic order, involving several consecutive ferromagnetic planes or ferrimagnetic groups of planes in the AF-I phase, detected by ac-susceptibility and not by neutron diffraction in both materials and therefore significant to x ∼ 0.50, is proposed to explain the unusual susceptibility. (Author)

  1. RAD18 mediates resistance to ionizing radiation in human glioma cells

    Xie, Chen; Wang, Hongwei; Cheng, Hongbin; Li, Jianhua; Wang, Zhi, E-mail: drzwang@gmail.com; Yue, Wu, E-mail: drwuyue@gmail.com

    2014-02-28

    Highlights: • RAD18 is an important mediator of the IR-induced resistance in glioma cell lines. • RAD18 overexpression confers resistance to IR-mediated apoptosis. • The elevated expression of RAD18 is associated with recurrent GBM who underwent IR therapy. - Abstract: Radioresistance remains a major challenge in the treatment of glioblastoma multiforme (GBM). RAD18 a central regulator of translesion DNA synthesis (TLS), has been shown to play an important role in regulating genomic stability and DNA damage response. In the present study, we investigate the relationship between RAD18 and resistance to ionizing radiation (IR) and examined the expression levels of RAD18 in primary and recurrent GBM specimens. Our results showed that RAD18 is an important mediator of the IR-induced resistance in GBM. The expression level of RAD18 in glioma cells correlates with their resistance to IR. Ectopic expression of RAD18 in RAD18-low A172 glioma cells confers significant resistance to IR treatment. Conversely, depletion of endogenous RAD18 in RAD18-high glioma cells sensitized these cells to IR treatment. Moreover, RAD18 overexpression confers resistance to IR-mediated apoptosis in RAD18-low A172 glioma cells, whereas cells deficient in RAD18 exhibit increased apoptosis induced by IR. Furthermore, knockdown of RAD18 in RAD18-high glioma cells disrupts HR-mediated repair, resulting in increased accumulation of DSB. In addition, clinical data indicated that RAD18 was significantly higher in recurrent GBM samples that were exposed to IR compared with the corresponding primary GBM samples. Collectively, our findings reveal that RAD18 may serve as a key mediator of the IR response and may function as a potential target for circumventing IR resistance in human GBM.

  2. Role of dissolved oxygen reduction in improvement inhibition performance of ascorbic acid during copper corrosion in 0.50 mol/L sulphuric acid

    Mohammed; A.Amin

    2010-01-01

    The kinetics of dissolved O_2 reduction and hydrogen evolution reactions on copper surface was studied in naturally aerated and air and O_2-saturated 0.50 mol/L H_2SO_4 solutions using polarization measurements combined with the rotating disc electrode (RDE).The Koutecky-Levich plot indicated that the dissolved O_2 reduction at the copper electrode was an apparent four-electron process.A correlation between the presence of dissolved O_2 and the formation of Cu_2O,confirmed from XRD,was discussed. Ascorbi...

  3. HiRadMat High Intensity Beam Commissioning

    Blanco Sancho, J; Cornelis, K; Goddard, B; Hessler, C; Jensen, L; Kain, V; Meddahi, M; Theis, C; Vincke, H; Vojtyla, P; Wenninger, J

    2011-01-01

    On Wednesday 14 September and Monday 19 September 2011, high intensity proton beam was sent for the first time down the HiRadMat primary beam line (thereafter TT66), onto the beam dump located in the HiRadMat experimental cavern. This high intensity beam commissioning followed a first period of low intensity beam commissioning which took place in June 2011. During the low intensity beam commissioning, it was checked that all beam line equipment operated as specified. Energy matching and beam steering were performed; optics checks did not reveal any optical errors. Aperture measurements confirmed that there were no bottlenecks. Radiation protection monitoring worked as expected and the measurements were within expectation [1]. With the completion of the HiRadMat ventilation system, the high intensity beam commissioning could successfully continue in September 2011. The main outcome is reported in this note.

  4. RadCat 3.0 user guide.

    Hinojosa, Daniel; Penisten, Janelle J.; Dennis, Matthew L.; Osborn, Douglas M.; Weiner, Ruth F.; Heames, Terence John; Marincel, Michelle K.

    2009-05-01

    RADTRAN is an internationally accepted program and code for calculating the risks of transporting radioactive materials. The first versions of the program, RADTRAN I and II, were developed for NUREG-0170 (USNRC, 1977), the first environmental statement on transportation of radioactive materials. RADTRAN and its associated software have undergone a number of improvements and advances consistent with improvements in both available data and computer technology. The version of RADTRAN currently bundled with RadCat is RADTRAN 6.0. This document provides a detailed discussion and a guide for the use of the RadCat 3.0 Graphical User Interface input file generator for the RADTRAN code. RadCat 3.0 integrates the newest analysis capabilities of RADTRAN 6.0 which includes an economic model, updated loss-of-lead shielding model, and unit conversion. As of this writing, the RADTRAN version in use is RADTRAN 6.0.

  5. Performance of the Harshaw DXT-RAD (TLD-100) dosemeter

    Moor, D.M. [Defence Science and Technology Laboratory, Environmental Sciences Department, Alverstoke, Gosport, Hants PO12 2DL (United Kingdom)], E-mail: dmoor@dstl.gov.uk; Horspool, B.; Stokes, R.P. [Defence Science and Technology Laboratory, Environmental Sciences Department, Alverstoke, Gosport, Hants PO12 2DL (United Kingdom)

    2008-02-15

    The Defence Science and Technology Laboratory (Dstl) has type-tested the Harshaw DXT-RAD dosemeter against the International Standard ISO 12794:2000(E) 'Individual thermoluminescence dosemeters for extremities and eyes' [International Organization for Standardization, 2000. International Standard ISO 12794:2000(E). Nuclear energy-radiation protection-individual thermoluminescence dosemeters for extremities and eyes]. The tests carried out included batch homogeneity, reproducibility, linearity, detection threshold, environmental stability (temperature, humidity and light), self irradiation, isotropy, energy response, dose-rate response and neutron response. The DXT-RAD dosemeter satisfied all the requirements of ISO 12794:2000(E), with the exception of its response at low photon energies and intermediate beta energies. However, it should be noted that other forms of the DXT-RAD dosemeter with a thinner entrance window are available to give an improved response to low-energy radiations.

  6. Molecular Basis for Enhancement of the Meiotic DMCI Recombinase by RAD51AP1

    Dray, Eloise; Dunlop, Myun Hwa; Kauppi, Liisa; San Filippo, Joseph San; Wiese, Claudia; Tsai, Miaw-Sheue; Begovic, Sead; Schild, David; Jasin, Maria; Keeney, Scott; Sung, Patrick

    2010-11-05

    Homologous recombination is needed for meiotic chromosome segregation, genome maintenance, and tumor suppression. RAD51AP1 (RAD51 Associated Protein 1) has been shown to interact with and enhance the recombinase activity of RAD51. Accordingly, genetic ablation of RAD51AP1 leads to enhanced sensitivity to and also chromosome aberrations upon DNA damage, demonstrating a role for RAD51AP1 in mitotic homologous recombination. Here we show physical association of RAD51AP1 with the meiosis-specific recombinase DMC1 and a stimulatory effect of RAD51AP1 on the DMC1-mediated D-loop reaction. Mechanistic studies have revealed that RAD51AP1 enhances the ability of the DMC1 presynaptic filament to capture the duplex DNA partner and to assemble the synaptic complex, in which the recombining DNA strands are homologously aligned. We also provide evidence that functional co-operation is dependent on complex formation between DMC1 and RAD51AP1, and that distinct epitopes in RAD51AP1 mediate interactions with RAD51 and DMC1. Finally, we show that RAD51AP1 is expressed in mouse testes, and that RAD51AP1 foci co-localize with a subset of DMC1 foci in spermatocytes. These results suggest that RAD51AP1 also serves an important role in meiotic homologous recombination.

  7. Structural and functional evidence that Rad4 competes with Rad2 for binding to the Tfb1 subunit of TFIIH in NER

    Lafrance-Vanasse, Julien; Arseneault, Geneviève; Cappadocia, Laurent; Legault, Pascale; Omichinski, James G.

    2013-01-01

    XPC/Rad4 (human/yeast) recruits transcription faction IIH (TFIIH) to the nucleotide excision repair (NER) complex through interactions with its p62/Tfb1 and XPB/Ssl2 subunits. TFIIH then recruits XPG/Rad2 through interactions with similar subunits and the two repair factors appear to be mutually exclusive within the NER complex. Here, we show that Rad4 binds the PH domain of the Tfb1 (Tfb1PH) with high affinity. Structural characterization of a Rad4–Tfb1PH complex demonstrates that the Rad4-b...

  8. Rad54 functions as a Heteroduplex DNA Pump Modulated by Its DNA Substrates and Rad51 during D-loop Formation in Homologous Recombination

    Wright, William Douglass; Heyer, Wolf-Dietrich

    2014-01-01

    The displacement loop (D-loop) is the product of homology search and DNA strand invasion, constituting a central intermediate in homologous recombination (HR). In eukaryotes, Rad51 recombinase is assisted in D-loop formation by the Rad54 motor protein. Curiously, Rad54 also disrupts D-loops. How these opposing activities are coordinated toward productive recombination is unknown. Moreover, a seemingly disparate function Rad54 is removal of Rad51 from heteroduplex DNA (hDNA) to allow HR-associ...

  9. HiRadMat Low Intensity Beam Commissioning

    Blanco Sancho, J; Cornelis, K; Goddard, B; Hessler, C; Jensen, L; Kain, V; Meddahi, M; Theis, C; Vojtyla, P; Wenninger, J

    2011-01-01

    On Wednesday 22 June 2011, proton beam was sent for the first time through the HiRadMat primary beam line, onto the beam dump located in the HiRadMat experimental cavern. The aims of the beam commissioning were to check the beam line geometry and design validity, the correct functioning of all beam line equipment and to verify the beam parameters. At the first trial, the proton beam reached the end of the primary beam line and the preliminary checks allowed confirming that all beam equipment and parameters are within the specification.

  10. Misregulation of Rad50 expression in melanoma cells

    Avaritt, Nathan L.; Owens, Richard; Larson, Signe K.; Reynolds, Matthew; Byrum, Stephanie; Kim M Hiatt; Smoller, Bruce R; Tackett, Alan J.; Cheung, Wang L.

    2012-01-01

    DNA double-strand breaks are increased in human melanoma tissue as detected by histone H2AX phosphorylation1,2,3. We investigated two of the downstream effectors of DNA double-strand breaks, Rad50 and 53BP1 (tumor suppressor p53 binding protein 1), to determine if they are altered in human primary melanoma cells. Melanoma cases demonstrated high Rad50 staining (81.8%; 9/11) significantly more frequently than conventional or atypical melanocytic nevi (0%; 0/18). In contrast, the staining patte...

  11. Effect of bacterial RecA expression on DNA repair in the rad51 and rad52 on DNA mutants of Saccharomyces cerevisiae

    Molecular and functional homology between yeast proteins pRad51 and pRad52 and Escherichia coli p RecA involved in re combinational DNA repair led us to investigate possible effects of reA gene expression on DNA repair in rad51 and rad52 mutants of Saccharomyces cerevisiae. The mutant cells were subjected to one of the following treatments: preincubation with 8-methoxypsoralen and subsequent irradiation with 360-nm ultraviolet (UVA) (8-MOP + UVA), irradiation with 254-nm UV light or treatment with methyl methane sulfonate (MMS). While RecA expression did not repair lethal DNA lesions in mutant rad51, it was able to partially restore resistance to 8-MOP + UVA and MMS in rad52. Expression of recA could not complement the sensitivity of rad51rad52 double mutants, indicating that pRad51 may be essential for the repair-stimulating activity of pRecA in the rad52 mutant. Spontaneous mutagenesis was increased, and 8-MOP-photoinduced mutagenesis in rad51. Thus, pRecA may function in yeast DNA repair either as a member of a protein complex or as an individual protein that binds to mutagen-damaged DNA. (author)

  12. Synthesis, structure and characterisation of Fe0.50Ti2(PO4)3: A new material with Nasicon-like structure

    A new iron titanyl phosphate Fe0.50Ti2(PO4)3 was synthesized by both solid-state reaction and Cu2+-Fe2+ ion exchange method. The material was then characterized by X-ray diffraction, Mossbauer, magnetic susceptibility measurements and optical absorption. The crystal structure of the compound was refined, using X-ray powder diffraction data, by the Rietveld profile method; it crystallizes in the rhombohedral system, space group R3-bar, with a=8.511(1)A and c=20.985(3)A, V=1316.45(3)A3 and Z=6. The structure, which is compared to that of Mn0.50Ti2(PO4)3 is built up from [TiO6] octahedra and [PO4] tetrahedra which are linked by corner sharing along the c-axis. Fe2+ cations are located in half of the antiprism MI sites and are orderly distributed with vacancies within the two possible positions of the MI sites of R3-bar. These results were supported by the Mossbauer studies that showed the presence of one Fe2+ site in the high spin state (t2g4eg2). The Curie-Weiss-type behavior is observed in the magnetic susceptibility. Diffuse reflectance spectrum indicates the presence of octahedrally coordinated Fe2+ ions

  13. Magnetic properties of the alloys system CuAl1-xCrxS2 (x = 0.50, 0.75)

    The synthesis, structural characterization and magnetic properties of alloy system CuAl1-xCrxS2 (x = 0.50, 075) are reported. The samples were synthesized by using the direct fusion technique. The chemical analysis (EDX) confirmed the stoichiometric ratio for the concentrations. The powder diffraction patterns were indexed and the principal phases crystallizes with tetragonal symmetry with unit cell parameters a = 5.312(1) A, c = 10.389(2) A for x = 0.50 and a = 5.314(2) A, c = 10.393(2) A for x = 0.75. These alloys behave as antiferromagnetic, with Neel temperature of 37 K and 39 K, respectively. The EPR linewidth for these alloys shows a paramagnetic behavior between 100 and 610 K. The resonance field and the g factor show a slight variation with temperature. These results are discussed in terms of nearest-neighbor Cr+3 (S=3/2) spin-coupled pairs. (Author)

  14. Hybridization Capture Using RAD Probes (hyRAD, a New Tool for Performing Genomic Analyses on Collection Specimens.

    Tomasz Suchan

    Full Text Available In the recent years, many protocols aimed at reproducibly sequencing reduced-genome subsets in non-model organisms have been published. Among them, RAD-sequencing is one of the most widely used. It relies on digesting DNA with specific restriction enzymes and performing size selection on the resulting fragments. Despite its acknowledged utility, this method is of limited use with degraded DNA samples, such as those isolated from museum specimens, as these samples are less likely to harbor fragments long enough to comprise two restriction sites making possible ligation of the adapter sequences (in the case of double-digest RAD or performing size selection of the resulting fragments (in the case of single-digest RAD. Here, we address these limitations by presenting a novel method called hybridization RAD (hyRAD. In this approach, biotinylated RAD fragments, covering a random fraction of the genome, are used as baits for capturing homologous fragments from genomic shotgun sequencing libraries. This simple and cost-effective approach allows sequencing of orthologous loci even from highly degraded DNA samples, opening new avenues of research in the field of museum genomics. Not relying on the restriction site presence, it improves among-sample loci coverage. In a trial study, hyRAD allowed us to obtain a large set of orthologous loci from fresh and museum samples from a non-model butterfly species, with a high proportion of single nucleotide polymorphisms present in all eight analyzed specimens, including 58-year-old museum samples. The utility of the method was further validated using 49 museum and fresh samples of a Palearctic grasshopper species for which the spatial genetic structure was previously assessed using mtDNA amplicons. The application of the method is eventually discussed in a wider context. As it does not rely on the restriction site presence, it is therefore not sensitive to among-sample loci polymorphisms in the restriction sites

  15. The tumor suppressor homolog in fission yeast, myh1+, displays a strong interaction with the checkpoint gene rad1+

    The DNA glycosylase MutY is strongly conserved in evolution, and homologs are found in most eukaryotes and prokaryotes examined. This protein is implicated in repair of oxidative DNA damage, in particular adenine mispaired opposite 7,8-dihydro-8-oxoguanine. Previous investigations in Escherichia coli, fission yeast, and mammalian cells show an association of mutations in MutY homologs with a mutator phenotype and carcinogenesis. Eukaryotic MutY homologs physically associate with several proteins with a role in replication, DNA repair, and checkpoint signaling, specifically the trimeric 9-1-1 complex. In a genetic investigation of the fission yeast MutY homolog, myh1+, we show that the myh1 mutation confers a moderately increased UV sensitivity alone and in combination with mutations in several DNA repair genes. The myh1 rad1, and to a lesser degree myh1 rad9, double mutants display a synthetic interaction resulting in enhanced sensitivity to DNA damaging agents and hydroxyurea. UV irradiation of myh1 rad1 double mutants results in severe chromosome segregation defects and visible DNA fragmentation, and a failure to activate the checkpoint. Additionally, myh1 rad1 double mutants exhibit morphological defects in the absence of DNA damaging agents. We also found a moderate suppression of the slow growth and UV sensitivity of rhp51 mutants by the myh1 mutation. Our results implicate fission yeast Myh1 in repair of a wider range of DNA damage than previously thought, and functionally link it to the checkpoint pathway

  16. Predicting error in detecting mammographic masses among radiology trainees using statistical models based on BI-RADS features

    Grimm, Lars J., E-mail: Lars.grimm@duke.edu; Ghate, Sujata V.; Yoon, Sora C.; Kim, Connie [Department of Radiology, Duke University Medical Center, Box 3808, Durham, North Carolina 27710 (United States); Kuzmiak, Cherie M. [Department of Radiology, University of North Carolina School of Medicine, 2006 Old Clinic, CB No. 7510, Chapel Hill, North Carolina 27599 (United States); Mazurowski, Maciej A. [Duke University Medical Center, Box 2731 Medical Center, Durham, North Carolina 27710 (United States)

    2014-03-15

    Purpose: The purpose of this study is to explore Breast Imaging-Reporting and Data System (BI-RADS) features as predictors of individual errors made by trainees when detecting masses in mammograms. Methods: Ten radiology trainees and three expert breast imagers reviewed 100 mammograms comprised of bilateral medial lateral oblique and craniocaudal views on a research workstation. The cases consisted of normal and biopsy proven benign and malignant masses. For cases with actionable abnormalities, the experts recorded breast (density and axillary lymph nodes) and mass (shape, margin, and density) features according to the BI-RADS lexicon, as well as the abnormality location (depth and clock face). For each trainee, a user-specific multivariate model was constructed to predict the trainee's likelihood of error based on BI-RADS features. The performance of the models was assessed using area under the receive operating characteristic curves (AUC). Results: Despite the variability in errors between different trainees, the individual models were able to predict the likelihood of error for the trainees with a mean AUC of 0.611 (range: 0.502–0.739, 95% Confidence Interval: 0.543–0.680,p < 0.002). Conclusions: Patterns in detection errors for mammographic masses made by radiology trainees can be modeled using BI-RADS features. These findings may have potential implications for the development of future educational materials that are personalized to individual trainees.

  17. Predicting error in detecting mammographic masses among radiology trainees using statistical models based on BI-RADS features

    Purpose: The purpose of this study is to explore Breast Imaging-Reporting and Data System (BI-RADS) features as predictors of individual errors made by trainees when detecting masses in mammograms. Methods: Ten radiology trainees and three expert breast imagers reviewed 100 mammograms comprised of bilateral medial lateral oblique and craniocaudal views on a research workstation. The cases consisted of normal and biopsy proven benign and malignant masses. For cases with actionable abnormalities, the experts recorded breast (density and axillary lymph nodes) and mass (shape, margin, and density) features according to the BI-RADS lexicon, as well as the abnormality location (depth and clock face). For each trainee, a user-specific multivariate model was constructed to predict the trainee's likelihood of error based on BI-RADS features. The performance of the models was assessed using area under the receive operating characteristic curves (AUC). Results: Despite the variability in errors between different trainees, the individual models were able to predict the likelihood of error for the trainees with a mean AUC of 0.611 (range: 0.502–0.739, 95% Confidence Interval: 0.543–0.680,p < 0.002). Conclusions: Patterns in detection errors for mammographic masses made by radiology trainees can be modeled using BI-RADS features. These findings may have potential implications for the development of future educational materials that are personalized to individual trainees

  18. Rad-hard embedded computers for nuclear robotics

    Nuclear industries require robots with embedded rad hard electronics and high reliability. The SYROCO research program allowed to perform efficient industrial prototypes, build according to MICADO architecture, and to design CADMOS architecture. MICADO architecture uses the auto healing property that have CMOS circuits when being switched off during irradiation. (D.L.). 8 refs., 5 figs

  19. Photoemission studies of As{sub x}Se{sub 100-x} (x: 0, 50, 100) films prepared by pulsed-laser deposition-the effect of annealing

    Siokou, A [Foundation of Research and Technology Hellas-Institute of Chemical Engineering and High Temperature Chemical Processes (FORTH/ICE-HT), PO Box 1414, GR-26504, Rio, Patras (Greece); Kalyva, M [Foundation of Research and Technology Hellas-Institute of Chemical Engineering and High Temperature Chemical Processes (FORTH/ICE-HT), PO Box 1414, GR-26504, Rio, Patras (Greece); Yannopoulos, S N [Foundation of Research and Technology Hellas-Institute of Chemical Engineering and High Temperature Chemical Processes (FORTH/ICE-HT), PO Box 1414, GR-26504, Rio, Patras (Greece); Frumar, M [Department of General and Inorganic Chemistry and Research Center, University of Pardubice, Legions Square 565, Pardubice 53210 (Czech Republic); Nemec, P [Department of General and Inorganic Chemistry and Research Center, University of Pardubice, Legions Square 565, Pardubice 53210 (Czech Republic)

    2006-06-14

    Annealing-induced structural changes in amorphous films As{sub x}Se{sub 100-x} (x: 0, 50, 100) prepared by pulsed laser deposition (PLD) on Si substrates were studied by x-ray and ultraviolet photoelectron spectroscopies (XPS, UPS). For x = 50, the analysis of the XPS As 3d peak revealed three distinct local environments in which the As atoms participate in the as-prepared films. The combination of photoemission and work function measurements showed that annealing close to the glass transition temperature induces atomic rearrangements towards the formation of a more homogenous surface composition as well as to a more energetically favoured film structure, by cleavage of the weaker As-As and Se-Se bonds towards the formation of As-Se ones analogously to As-S system films.

  20. Synthesis, structure, magnetic susceptibility and Mossbauer and Raman spectroscopies of the new oxyphosphate Fe0.50TiO(PO4)

    A new iron titanyl oxyphosphate Fe0.50TiO(PO4) was synthesized by both solid-state reaction and Cu2+-Fe2+ ion exchange method. The material was then characterized by X-ray diffraction, Mossbauer spectroscopy, magnetic susceptibility measurements and Raman spectroscopy. The crystal structure of the compound was refined, using X-ray powder diffraction data, by Rietveld profile method; it crytallizes in the monoclinic system, space group P21/c (No.14), with a=7.4039(3)A, b=7.3838(3)A, c=7.4083(3)A, β=120.36o(1), V=349.44(2)A3 and Z=4. The volume of the title compound is comparable to those of the M0.50IITiO(PO4) series, where MII=Mg, Co, Ni and Zn. The framework is built up from [TiO6] octahedra and [PO4] tetrahedra. [TiO6] octahedra are linked together by corners and form infinite chains along the c-axis. Ti atoms are displaced from the center of octahedral units showing an alternating short distance (1.73A) and a long one (2.22A). These chains are linked together by [PO4] tetrahedra. Fe2+ cations occupy a triangle-based antiprism sharing two faces with two [TiO6] octahedra. Mossbauer and magnetic measurements show the existence of iron only in divalent state, located exclusively in octahedral sites with high spin configuration (t2g4eg2). Raman study confirms the existence of Ti-O-Ti chains

  1. Effects of the rad52 gene on recombination in Saccharomyces cerevisiae

    Effects of the rad52 mutation in Saccharomyces cerevisiae on meiotic, γ-ray-induced, uv-induced, and spontaneous mitotic recombination were studied. The rad52/rad52 diploids undergo premeiotic DNA synthesis; sporulation occurs but inviable spores are produced. Intra- and intergenic recombination during meiosis were examined in cells transferred from sporulation medium to vegetative medium at different time intervals. No intragenic recombination was observed at the hisl-1/hisl-315 and trp5-2/trp5-48 heteroalleles. Gene-centromere recombination was also not observed in rad52/rad52 diploids. No γ-ray-induced intragenic mitotic recombination is seen in rad52/rad52 diploids and uv-induced intragenic recombination is greatly reduced. However, spontaneous mitotic recombination is not similarly affected. The RAD52 gene thus functions in recombination in meiosis and in γ-ray and uv-induced mitotic recombination but not in spontaneous mitotic recombination

  2. Interactions between mutations for sensitivity to psoralen photoaddition (pso) and to radiation (rad) in Saccharomyces cerevisiae.

    Henriques, J A; Moustacchi, E

    1981-01-01

    The mode of interaction in haploid Saccharomyces cerevisiae of two pso mutations with each other and with rad mutations affected in their excision-resynthesis (rad3), error-prone (rad6), and deoxyribonucleic acid double-strand break (rad52) repair pathways was determined for various double mutant combinations. Survival data for 8-methoxypsoralen photoaddition, 254-nm ultraviolet light and gamma rays are presented. For 8-methoxypsoralen photoaddition, which induces both deoxyribonucleic acid i...

  3. Rad Hard Active Media For Calorimeters

    Norbeck, E; Möller, A; Onel, Y

    2006-01-01

    Zero-degree calorimeters have limited space and extreme levels of radiation. A simple, low cost, radiation hard design uses tungstenmetal as the absorber and a suitable liquid as the ˇCerenkov radiator. In other applications a PPAC (Parallel Plate Avalanche Counter) operatingwith a suitable atmosphericpressure gas is an attractive active material for a calorimeter. It can be made radiation hard and has sufficient gain in the gas that no electronic components are needed near the detector. It works well even with the highest concentration of shower particles. For this pressure range, R134A (used in auto air conditioners) has many desirable features.

  4. Enhanced electric property and magneto-capacitance co-efficient co-related with modulated Raman spectroscopy of GaFeO3 in (GaFeO3)0.50(Ni0.40Zn0.40Cu0.20Fe2O4)0.50

    Highlights: • Dielectric property of (GaFeO3)0.50(Ni0.40Zn0.40Cu0.20Fe2O4)0.50 (GFO-NZCF). • Enhanced magneto-electric property of GFO-NZCF. • Raman effect in GFO-NZCF. • Magneto-capacitance co-efficient has been enhanced in GFO-NZCF. • Ferroelectric to paraelectric transition at ∼680 K of GFO-NZCF. - Abstract: Multiferroic (MF) nanoparticles of GaFeO3 (GFO) were prepared by sol–gel method. To modulate the magneto-dielectric property, nanoparticles of GFO are incorporated in Ni0.40Zn0.40Cu0.20Fe2O4 (NZCF). Crystallographic phases of all the samples are confirmed by analyzing the X-ray diffractograms using FULLPROF program. The hysteretic behavior observed in the polarization vs. electric field loops recorded at room temperature (RT) confirmed the ferroelectric ordering of GFO and (GaFeO3)0.50(Ni0.40Zn0.40Cu0.20Fe2O4)0.50 (GFO-NZCF). Temperature dependent dielectric constant of GFO and GFO-NZCF shows the ferroelectric to paraelectric transition at 625 and 680 K, respectively. The dielectric constant measured in presence and absence of magnetic field confirmed that the samples are MFs with positive magneto-capacitance (MC) co-efficient. Interestingly, electric polarization and MC co-efficient of GFO are increased in GFO-NZCF. Room temperature Raman spectra of GFO and NZCF have been compared with that of GFO-NZCF and the observed changes have been co-related with the enhanced polarization of GFO-NZCF

  5. ATP-dependent and independent functions of Rad54 in genome maintenance

    S. Agarwal (Sheba); W.A. van Cappellen (Gert); A. Guénolé (Aude); B. Eppink (Berina); S.E.V. Linsen (Sam); E. Meijering (Erik); A.B. Houtsmuller (Adriaan); R. Kanaar (Roland); J. Essers (Jeroen)

    2011-01-01

    textabstractRad54, a member of the SWI/SNF protein family of DNA-dependent ATPases, repairs DNA double-strand breaks (DSBs) through homologous recombination. Here we demonstrate that Rad54 is required for the timely accumulation of the homologous recombination proteins Rad51 and Brca2 at DSBs. Becau

  6. Effect of bacterial recA expression on DNA repair in the rad51 and rad52 mutants of Saccharomyces cerevisiae

    M.A. Morais Jr.

    1998-03-01

    Full Text Available Molecular and functional homology between yeast proteins pRad51 and pRad52 and Escherichia coli pRecA involved in recombinational DNA repair led us to investigate possible effects of recA gene expression on DNA repair in rad51 and rad52 mutants of Saccharomyces cerevisiae. The mutant cells were subjected to one of the following treatments: preincubation with 8-methoxypsoralen and subsequent irradiation with 360-nm ultraviolet (UVA (8-MOP + UVA, irradiation with 254-nm UV light or treatment with methyl methane sulfonate (MMS. While recA expression did not repair lethal DNA lesions in mutant rad51, it was able to partially restore resistance to 8-MOP + UVA and MMS in rad52. Expression of recA could not complement the sensitivity of rad51rad52 double mutants, indicating that pRad51 may be essential for the repair-stimulating activity of pRecA in the rad52 mutant. Spontaneous mutagenesis was increased, and 8-MOP-photoinduced mutagenesis was decreased by the presence of pRecA in rad52, whereas pRecA decreased UV-induced mutagenesis in rad51. Thus, pRecA may function in yeast DNA repair either as a member of a protein complex or as an individual protein that binds to mutagen-damaged DNA.A homologia tanto a nível molecular como funcional entre as proteínas de leveduras pRad51 e pRad52 envolvidas na reparação de DNA tipo recombinacional e pRecA de E. coli nos levou a analisar os possíveis efeitos da expressão do gene recA sobre a reparação de DNA nos mutantes rad51 e rad52 de S. cerevisiae após tratamento com 8-MOP + UVA, com UV e com MMS. A expressão de recA não foi capaz de restaurar a reparação das lesões induzidas no DNA do mutante rad51 após tratamento com esses agentes, entretanto ela restaurou parcialmente a resistência ao 8-MOP + UVA e ao MMS no mutante rad52. A expressão de recA não complementou a sensibilidade do duplo mutante rad51rad52, indicando que pRad51 pode ser essencial para estimular a atividade de reparação da p

  7. Lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized study comparing 750-rad treatment with 2,000-rad treatment

    Twenty patients with intractable rheumatoid arthritis were treated with 750-rad or 2,000-rad lymphoid irradiation in a randomized double-blind comparative study. Over a 12-month followup period, there was a significant improvement in 4 of 7 and 6 of 7 standard parameters of disease activity following treatment with 750 rads and 2,000 rads, respectively. Transient, short-term toxicity was less frequent with the lower dose. In both groups, there was a sustained peripheral blood lymphopenia, a selective depletion of T helper (Leu-3a+) lymphocytes, and reduced in vitro mitogen responses. These changes did not occur, however, in synovial fluid. These results suggest that 750-rad lymphoid irradiation is as effective as, but less toxic than, that with 2,000 rads in the management of patients with intractable rheumatoid arthritis

  8. Non-mass-like breast lesions at ultrasonography: Feature analysis and BI-RADS assessment

    Highlights: • The positive predictive value of an NML lesion on ultrasound ranges from 10 to 79%. • A sizable number of NML malignant lesions are pure DCIS or ILC. • Biopsy is indicated for histopathological diagnosis when an ultrasound NML lesion is recognized. - Abstract: Objective: To analyze the features of non-mass-like (NML) breast lesions on ultrasound (US) and determine their corresponding malignancy rate and to stratify these lesion patterns according to US BI-RADS categories. Materials and methods: One hundred sixty-four consecutive lesions were retrospectively classified into four types according to the US features, the corresponding positive predictive values (PPVs) were obtained. Clinical, imaging, and histopathological findings were reviewed. Results: Among the 164 lesions, 39 (24%) were classified as type Ia, 14 (8%) as type Ib, 39 (24%) as type IIa, 19 (12%) as type IIb, 19 (12%) as type III, and 34 (21%) as type IV. The PPVs for malignancy were 21% for type Ia, 79% for type Ib, 10% for type IIa, 58% for type IIb, 16% for type III, and 21% for type IV. All NML lesions were classified as BI-RADS category 4a (type IIa), 4b (type Ia, III and IV) and 4c (type Ib and IIb) according to their PPVs. There was a significantly higher frequency of malignancy among lesions of type Ib and type IIb compared with the other types (P < 0.01 for each). Lesions with associated calcifications, presence of abnormal axillary nodes, or a mammographic finding of suspected malignancy had a higher probability of malignancy (P < 0.05 for each). Conclusion: US is useful in clarifying the indication for biopsy of NML lesions. The types of US classifications used in our study establish reliable references for the NML patterns when stratified according to the BI-RADS categories

  9. Non-mass-like breast lesions at ultrasonography: Feature analysis and BI-RADS assessment

    Ko, Kai-Hsiung [Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Hsu, Hsian-He, E-mail: hsianhe@yahoo.com.tw [Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Yu, Jyh-Cherng [Department of Surgery, Division of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Peng, Yi-Jen [Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Tung, Ho-Jui [Department of Healthcare Administration, Asia University, Taichung, Taiwan, ROC (China); Chu, Chi-Ming [Section of Health Informatics, Institute of Public Health, National Defense Medical Center and University, Taipei, Taiwan, ROC (China); Chang, Tsun-Hou; Chang, Wei-Chou; Wu, Yu-Cheng; Lin, Yu-Pang; Hsu, Giu-Cheng [Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China)

    2015-01-15

    Highlights: • The positive predictive value of an NML lesion on ultrasound ranges from 10 to 79%. • A sizable number of NML malignant lesions are pure DCIS or ILC. • Biopsy is indicated for histopathological diagnosis when an ultrasound NML lesion is recognized. - Abstract: Objective: To analyze the features of non-mass-like (NML) breast lesions on ultrasound (US) and determine their corresponding malignancy rate and to stratify these lesion patterns according to US BI-RADS categories. Materials and methods: One hundred sixty-four consecutive lesions were retrospectively classified into four types according to the US features, the corresponding positive predictive values (PPVs) were obtained. Clinical, imaging, and histopathological findings were reviewed. Results: Among the 164 lesions, 39 (24%) were classified as type Ia, 14 (8%) as type Ib, 39 (24%) as type IIa, 19 (12%) as type IIb, 19 (12%) as type III, and 34 (21%) as type IV. The PPVs for malignancy were 21% for type Ia, 79% for type Ib, 10% for type IIa, 58% for type IIb, 16% for type III, and 21% for type IV. All NML lesions were classified as BI-RADS category 4a (type IIa), 4b (type Ia, III and IV) and 4c (type Ib and IIb) according to their PPVs. There was a significantly higher frequency of malignancy among lesions of type Ib and type IIb compared with the other types (P < 0.01 for each). Lesions with associated calcifications, presence of abnormal axillary nodes, or a mammographic finding of suspected malignancy had a higher probability of malignancy (P < 0.05 for each). Conclusion: US is useful in clarifying the indication for biopsy of NML lesions. The types of US classifications used in our study establish reliable references for the NML patterns when stratified according to the BI-RADS categories.

  10. Identification of a chicken RAD52 homologue suggests conservation of the RAD52 recombination pathway throughout the evolution of higher eukaryotes.

    Bezzubova, O Y; Schmidt, H.; Ostermann, K.; Heyer, W D; Buerstedde, J M

    1993-01-01

    Degenerate oligonucleotides encoding conserved regions of the Rad52 protein of S. cerevisiae and its homologue, the Rad22 protein of S. pombe, were used to clone a chicken RAD52 counterpart by the polymerase chain reaction. Sequence comparison of the chicken and yeast proteins reveals a strongly conserved region between positions 40 and 178 of the chicken Rad52 sequence indicating that this part of the protein is under strong evolutionary pressure. The first 39 amino acids and the 3' end of t...

  11. Ejecta model development at pRad (u)

    Buttler, William T [Los Alamos National Laboratory; Oro, David M [Los Alamos National Laboratory; Dimonte, Guy [Los Alamos National Laboratory; Terrones, Guillermo [Los Alamos National Laboratory; Morris, Christopher [Los Alamos National Laboratory; Bainbridge, J R [Los Alamos National Laboratory; Hogan, Gary E. [Los Alamos National Laboratory; Hollander, Brian J. [Los Alamos National Laboratory; Holtkamp, David B. [Los Alamos National Laboratory; Kwiathowski, Kris [Los Alamos National Laboratory; Marr-Lyon, Mark [Los Alamos National Laboratory; Mariam, Fesseha G. [Los Alamos National Laboratory; Merrill, Frank E [Los Alamos National Laboratory; Nedrow, Paul [Los Alamos National Laboratory; Saunders, Alexander [Los Alamos National Laboratory; Schwartz, C L [Los Alamos National Laboratory; Stone, B [Los Alamos National Laboratory; Tupa, Dale [Los Alamos National Laboratory; Vogan-McNeil, Wendy S [Los Alamos National Laboratory

    2010-02-09

    In July 2009 we fielded three explosively (HE) driven Richtmyer-Meshkov instability experiments at the LANSCE Proton Radiography Facility (pRad), and in August of 2009 we fielded one flyer plate experiment on the pRad 40 mm powder gun. One HE experiment was done in vacuum, and the other two within four atmospheres of noble gasses: Xe and Ne. These two gases were chosen to study the viscous effects on ejecta formation. It is unexpected, but the viscosity {eta} of Ne is twice that of Xe, and, due to the atomic mass difference between the two, the kinematic viscosity ({eta}/{rho}) of Ne is about ten times that of Xe. The results showed that ejecta formation is sensitively linked to the gas density, which implies that the Weber number is more important in ejecta formation than the Reynolds number.

  12. Low anterior anastomotic dehiscence following preoperative irradiation with 6000 rads

    Blake, D.P.; Bubrick, M.P.; Kochsiek, G.G.; Feeney, D.A.; Johnston, G.R.; Strom, R.L.; Hitchcock, C.R.

    1984-03-01

    Twenty mongrel dogs received 6000 rads of irradiation to the rectum and colon using the Nominal Standard Dosage Equation. Three weeks after irradiation each dog underwent anterior resection of the rectosigmoid with reconstruction randomized to either an EEA stapled or a two layer handsewn anastomosis. Each dog was studied digitally and by barium enema at the time of surgery, on the seventh postoperative day, and at autopsy. Five clinically significant leaks and three radiographic leaks occurred in the EEA stapled anastomoses. The handsewn anastomoses had five clinically significant leaks and two radiographic leaks. The data indicate that low anterior resection with either an EEA stapled or handsewn anastomosis cannot be done safely after 6000 rad preoperative irradiation.

  13. Low anterior anastomotic dehiscence following preoperative irradiation with 6000 rads

    Twenty mongrel dogs received 6000 rads of irradiation to the rectum and colon using the Nominal Standard Dosage Equation. Three weeks after irradiation each dog underwent anterior resection of the rectosigmoid with reconstruction randomized to either an EEA stapled or a two layer handsewn anastomosis. Each dog was studied digitally and by barium enema at the time of surgery, on the seventh postoperative day, and at autopsy. Five clinically significant leaks and three radiographic leaks occurred in the EEA stapled anastomoses. The handsewn anastomoses had five clinically significant leaks and two radiographic leaks. The data indicate that low anterior resection with either an EEA stapled or handsewn anastomosis cannot be done safely after 6000 rad preoperative irradiation

  14. Accurate Crystal Structure Refinement of La3Ta0.25Zr0.50Ga5.25O14

    An accurate X-ray diffraction study of a La3Ta0.25Zr0.50Ga5.25O14 single crystal (a = 8.2574(4) A, c = 5.1465(4) A, sp. gr. P321, Z = 1, R/Rw = 0.62/0.57% for 4144 unique reflections and 91 parameters) has been performed with a simultaneous neutron diffraction analysis. Tantalum, zirconium, and gallium atoms are found to occupy the mixed octahedral position (symmetry 32). Gallium atoms and a few zirconium atoms are in the position on axis 2 in the tetrahedron. The tetrahedral position on axis 3 is completely occupied by gallium atoms, while the large polyhedron on axis 2 is occupied by lanthanum atoms. The high resolution and averaging of the results obtained in two independent X-ray experiments with the same sample provided accu- rate structural data, in particular, on the anharmonicity of thermal atomic vibrations (atomic displacements). The X-ray and neutron diffraction data on the atomic displacements are compared.

  15. RadNet: Open network protocol for radiation data

    Safeguards instrumentation is increasingly being incorporated into remote monitoring applications. In the past, vendors of radiation monitoring instruments typically provided the tools for uploading the monitoring data to a host. However, the proprietary nature of communication protocols lends itself to increased computer support needs and increased installation expenses. As a result, a working group of suppliers and customers of radiation monitoring instruments defined an open network protocol for transferring packets on a local area network from radiation monitoring equipment to network hosts. The protocol was termed RadNet. While it is now primarily used for health physics instruments, RadNet's flexibility and strength make it ideal for remote monitoring of nuclear materials. The incorporation of standard, open protocols ensures that future work will not render present work obsolete; because RadNet utilizes standard Internet protocols, and is itself a non-proprietary standard. The use of industry standards also simplifies the development and implementation of ancillary services, e.g. E-main generation or even pager systems

  16. RadNet: Open network protocol for radiation data

    Rees, B.; Olson, K. [Los Alamos National Lab., NM (United States); Beckes-Talcott, J.; Kadner, S.; Wenderlich, T.; Hoy, M.; Doyle, W. [Aquila Technologies Group, Inc., Albuquerque, NM (United States); Koskelo, M. [Canberra Industries, Meriden, CT (United States)

    1998-12-31

    Safeguards instrumentation is increasingly being incorporated into remote monitoring applications. In the past, vendors of radiation monitoring instruments typically provided the tools for uploading the monitoring data to a host. However, the proprietary nature of communication protocols lends itself to increased computer support needs and increased installation expenses. As a result, a working group of suppliers and customers of radiation monitoring instruments defined an open network protocol for transferring packets on a local area network from radiation monitoring equipment to network hosts. The protocol was termed RadNet. While it is now primarily used for health physics instruments, RadNet`s flexibility and strength make it ideal for remote monitoring of nuclear materials. The incorporation of standard, open protocols ensures that future work will not render present work obsolete; because RadNet utilizes standard Internet protocols, and is itself a non-proprietary standard. The use of industry standards also simplifies the development and implementation of ancillary services, e.g. E-main generation or even pager systems.

  17. Rapid SNP discovery and genetic mapping using sequenced RAD markers.

    Nathan A Baird

    Full Text Available Single nucleotide polymorphism (SNP discovery and genotyping are essential to genetic mapping. There remains a need for a simple, inexpensive platform that allows high-density SNP discovery and genotyping in large populations. Here we describe the sequencing of restriction-site associated DNA (RAD tags, which identified more than 13,000 SNPs, and mapped three traits in two model organisms, using less than half the capacity of one Illumina sequencing run. We demonstrated that different marker densities can be attained by choice of restriction enzyme. Furthermore, we developed a barcoding system for sample multiplexing and fine mapped the genetic basis of lateral plate armor loss in threespine stickleback by identifying recombinant breakpoints in F(2 individuals. Barcoding also facilitated mapping of a second trait, a reduction of pelvic structure, by in silico re-sorting of individuals. To further demonstrate the ease of the RAD sequencing approach we identified polymorphic markers and mapped an induced mutation in Neurospora crassa. Sequencing of RAD markers is an integrated platform for SNP discovery and genotyping. This approach should be widely applicable to genetic mapping in a variety of organisms.

  18. NARAC Dispersion Model Product Integration With RadResponder

    Aluzzi, Fernando [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-09-30

    Work on enhanced cooperation and interoperability of Nuclear Incident Response Teams (NIRT) is a joint effort between DHS/FEMA, DOE/NNSA and EPA. One such effort was the integration between the RadResponder Network, a resource sponsored by FEMA for the management of radiological data during an emergency, and the National Atmospheric Advisory Center (NARAC), a DOE/NNSA modeling resource whose predictions are used to aid radiological emergency preparedness and response. Working together under a FEMA-sponsored project these two radiological response assets developed a capability to read and display plume model prediction results from the NARAC computer system in the RadResponder software tool. As a result of this effort, RadResponder users have been provided with NARAC modeling predictions of contamination areas, radiological dose levels, and protective action areas (e.g., areas warranting worker protection or sheltering/evacuation) to help guide protective action decisions and field monitoring surveys, and gain key situation awareness following a radiological/nuclear accident or incident (e.g., nuclear power plant accident, radiological dispersal device incident, or improvised nuclear detonation incident). This document describes the details of this integration effort.

  19. Rad51 Protein Expression and Survival in Patients with Glioblastoma Multiforme

    Purpose: Treatment of glioblastoma multiforme (GBM) continues to pose a significant therapeutic challenge, with most tumors recurring within the previously irradiated tumor bed. To improve outcomes, we must be able to identify and treat resistant cell populations. Rad51, an enzyme involved in homologous recombinational repair, leads to increased resistance of tumor cells to cytotoxic treatments such as radiotherapy. We hypothesized that Rad51 might contribute to GBM's apparent radioresistance and consequently influence survival. Methods and Materials: A total of 68 patients with an initial diagnosis of GBM were retrospectively evaluated; for 10 of these patients, recurrent tumor specimens were used to construct a tissue microarray. Rad51 protein expression was then correlated with the actual and predicted survival using recursive partitioning analysis. Results: Rad51 protein was elevated in 53% of the GBM specimens at surgery. The Rad51 levels correlated directly with survival, with a median survival of 15 months for patients with elevated Rad51 compared with 9 months for patients with low or absent levels of Rad51 (p = .05). At disease recurrence, 70% of patients had additional increases in Rad51 protein. Increased Rad51 levels at disease recurrence similarly predicted for improved overall survival, with a mean survival of 16 months from the second craniotomy compared with only 4 months for patients with low Rad51 levels (p = .13). Conclusion: Elevated levels of the double-stranded DNA repair protein Rad51 predicted for an increase survival duration in patients with GBM, at both initial tumor presentation and disease recurrence.

  20. Radon and Thoron Concentration measurement of Ground water in Kufa City by using RAD7 detector

    Radon (222Rn) and Thoron (220Rn) concentration in the groundwater samples and their annual effective dose exposure were measured in the Kufa city - Iraq.It is measured by Durridge RAD-7 radon-in-air monitor, RAD-H2O new technique with closed loop aeration concept.Study was identified on the map at the city of Kufa, by GIS.It is found that Radon and Thoron concentration in 20 groundwater samples of studied area.The range is between (0.267- 5.662), (0-0.7486)Bq L-1 respectively, the EPA's maximum contaminant level (MCL) of 11.1 Bq L-1.Also, obtain this study independent of groundwater physical and chemical properties such as (PH and EC) on the radon concentration.The total annual effective dose resulting from radon in groundwater of studied samples were significantly lower than the UNSCEAR and WHO recommended limit for members of the public of 1 mSv.y-1

  1. The AtRAD21.1 and AtRAD21.3 Arabidopsis cohesins play a synergistic role in somatic DNA double strand break damage repair

    da Costa-Nunes, J.A.; Capitao, C.; Kozák, Jaroslav; Costa-Nunes, P.; Ducasa, G.M.; Pontes, O.; Angelis, Karel

    2014-01-01

    Roč. 14, DEC 16 2014 (2014). ISSN 1471-2229 R&D Projects: GA MŠk(CZ) LD13006; GA ČR GA13-06595S Institutional support: RVO:61389030 Keywords : Arabidopsis * AtRAD21.1 * AtRAD21.3 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.813, year: 2014

  2. Disparate requirements for the Walker A and B ATPase motifs ofhuman RAD51D in homologous recombination

    Wiese, Claudia; Hinz, John M.; Tebbs, Robert S.; Nham, Peter B.; Urbin, Salustra S.; Collins, David W.; Thompson, Larry H.; Schild, David

    2006-04-21

    In vertebrates, homologous recombinational repair (HRR) requires RAD51 and five RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C, and RAD51D) that all contain conserved Walker A and B ATPase motifs. In human RAD51D we examined the requirement for these motifs in interactions with XRCC2 and RAD51C, and for survival of cells in response to DNA interstrand crosslinks. Ectopic expression of wild type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line. Although A-motif mutants complement very efficiently, B-motif mutants do not. Consistent with these results, experiments using the yeast two- and three-hybrid systems show that the interactions between RAD51D and its XRCC2 and RAD51C partners also require a functional RAD51D B motif, but not motif A. Similarly, hamster Xrcc2 is unable to bind to the non-complementing human RAD51D B-motif mutants in co-immunoprecipitation assays. We conclude that a functional Walker B motif, but not A motif, is necessary for RAD51D's interactions with other paralogs and for efficient HRR. We present a model in which ATPase sites are formed in a bipartite manner between RAD51D and other RAD51 paralogs.

  3. Interobserver Reproducibility of the PI-RADS Version 2 Lexicon: A Multicenter Study of Six Experienced Prostate Radiologists.

    Rosenkrantz, Andrew B; Ginocchio, Luke A; Cornfeld, Daniel; Froemming, Adam T; Gupta, Rajan T; Turkbey, Baris; Westphalen, Antonio C; Babb, James S; Margolis, Daniel J

    2016-09-01

    Purpose To determine the interobserver reproducibility of the Prostate Imaging Reporting and Data System (PI-RADS) version 2 lexicon. Materials and Methods This retrospective HIPAA-compliant study was institutional review board-approved. Six radiologists from six separate institutions, all experienced in prostate magnetic resonance (MR) imaging, assessed prostate MR imaging examinations performed at a single center by using the PI-RADS lexicon. Readers were provided screen captures that denoted the location of one specific lesion per case. Analysis entailed two sessions (40 and 80 examinations per session) and an intersession training period for individualized feedback and group discussion. Percent agreement (fraction of pairwise reader combinations with concordant readings) was compared between sessions. κ coefficients were computed. Results No substantial difference in interobserver agreement was observed between sessions, and the sessions were subsequently pooled. Agreement for PI-RADS score of 4 or greater was 0.593 in peripheral zone (PZ) and 0.509 in transition zone (TZ). In PZ, reproducibility was moderate to substantial for features related to diffusion-weighted imaging (κ = 0.535-0.619); fair to moderate for features related to dynamic contrast material-enhanced (DCE) imaging (κ = 0.266-0.439); and fair for definite extraprostatic extension on T2-weighted images (κ = 0.289). In TZ, reproducibility for features related to lesion texture and margins on T2-weighted images ranged from 0.136 (moderately hypointense) to 0.529 (encapsulation). Among 63 lesions that underwent targeted biopsy, classification as PI-RADS score of 4 or greater by a majority of readers yielded tumor with a Gleason score of 3+4 or greater in 45.9% (17 of 37), without missing any tumor with a Gleason score of 3+4 or greater. Conclusion Experienced radiologists achieved moderate reproducibility for PI-RADS version 2, and neither required nor benefitted from a training session

  4. Alterações clínicolaboratoriais em pacientes com malária por Plasmodium vivax e deficiência de glicose-6-fosfato desidrogenase tratados com 0,50mg/kg/dia de primaquina Clinical and laboratorial alterations in Plasmodium vivax malaria patients and glucose-6-phosphate dehydrogenase deficiency treated with primaquine at 0.50mg/kg/day

    Mônica C.M. Silva

    2004-06-01

    Full Text Available O efeito adverso da primaquina na dose de 0,50mg/kg/dia foi investigado em onze pacientes com malária vivax (três com deficiência de glicose-6-fosfato desidrogenase. Alterações clínicas e laboratoriais indicaram hemólise aguda apenas nos enzimopênicos, o que fez com que o tratamento fosse interrompido. Nossos resultados sugerem a necessidade do emprego de um teste de triagem para a deficiência de G6PD em áreas endêmicas de malária vivax a fim de se evitar complicações causadas pelo uso da primaquina.The adverse effects of primaquine (0.50mg/kg/day were investigated in eleven patients with vivax malaria (three patients with glucose-6-phosphate dehydrogenase deficiency. Clinical and laboratorial alterations indicated acute hemolysis in only the enzymopenic patients and treatment was interrupted. Our results suggest that screening for G6PD deficiency should be carried out in patients with vivax malaria infection in order to avoid complications due to primaquine.

  5. Physical and microstructural characterization of La0,60Sr0,40Co0,20Fe0,80O3-δ and Ba0,50Sr0,50Co0,80Fe0,20O3-δ ceramics

    The La0,60Sr0,40Co0,20Fe0,80O3-δ (LSCF) and Ba0,50Sr0,50Co0,80Fe0,20O3-δ (BSCF) oxides are studied as cathodes in Solid Oxide Fuel Cell. The objective of this study is to characterize physically and microstructural these materials. The LSCF was synthesized by citrate technique and BSCF for citrates-EDTA, processed under the same conditions. The characterizations of ceramics were performed by X-ray diffraction, dilatometry, scanning electron microscopy and apparent density for Archimedes principle. According to the diffraction technique, confirmed the presence of single phases for LSCF to 800 deg C and BSCF to 900 deg C, with orthorhombic and cubic structures, respectively. For dilatometry were determined the sintering temperatures, near of 1050 deg C to BSCF and 1100 deg C to LSCF. The sintered micrographs at 1000, 1050 and 1100 deg C for 2 hours showed homogeneity microstructure, containing porosity and, attacked thermally, a homogeneous distribution of grains. Finally by bulk density, was estimated porosity between 20 and 30%. (author)

  6. Modulated magneto-dielectric property and exchange bias effect of BiFeO3 incorporated in (BiFeO3)0.50 (Li0.30Zn0.35 Fe2.35O4)0.50 nanocomposite

    Nanoparticles of BiFeO3 (BFO) are prepared by the sol–gel method. These prepared nanoparticles are incorporated in the nanocomposite of (BiFeO3)0.50 (Li0.30Zn0.35 Fe2.35O4)0.50 (BFO-LZFO). The formation of pure crystallographic phase of each component (BFO and LZFO) in the nanocomposite of BFO-LZFO has been confirmed by Rietveld analysis of the X-ray diffractograms using FULLPROF program. Morphology, average particle size and its distribution, crystallographic phase etc. are determined from the high-resolution transmission electron microscopy of BFO-LZFO. Magnetic property of BFO is drastically enhanced in the nanocomposite. An exchange bias effect is also observed in the field cooled and zero field cooled hysteresis loops, which suggest that antiferromagnetic nanoparticles of BFO are encapsulated by ferrimagnetic nanoparticles of LZFO in BFO-LZFO. Magneto-capacitance (MC) co-efficient has been estimated from the values of dielectric constants, measured in presence and absence of magnetic field. Results of magnetic, dielectric and MC co-efficient indicate a strong modulation of magneto-dielectric property of BFO in BFO-LZFO and this would be quite interesting for applications of BFO, a lead free multiferroic

  7. Magnetic properties of the alloys system CuAl{sub 1-x}Cr{sub x}S{sub 2} (x = 0.50, 0.75); Propiedades magneticas del sistema de aleaciones CuAl{sub 1-x}Cr{sub x}S{sub 2} (x = 0.50, 0.75)

    Villarreal, M. A.; Grima, P.; Quintero, M.; Moreno, E.; Fernandez, J. [Universidad de los Andes, Facultad de Ciencias, Centro de Estudios en Semiconductores, Departamento de Fisica, Apdo. de Correos No. 1, La Hechicera, 5251 Merida, (Venezuela, Bolivarian Republic of); Silva, P.; Villegas, J., E-mail: mavu@ula.ve [Instituto Venezolano de Investigaciones Cientificas, Laboratorio de Fisica de la Materia Condensada, Centro de Fisica, Carretera Panamericana Km. 11, Apdo. 21827, 1020-A Caracas (Venezuela, Bolivarian Republic of)

    2013-10-01

    The synthesis, structural characterization and magnetic properties of alloy system CuAl{sub 1-x}Cr{sub x}S{sub 2} (x = 0.50, 075) are reported. The samples were synthesized by using the direct fusion technique. The chemical analysis (EDX) confirmed the stoichiometric ratio for the concentrations. The powder diffraction patterns were indexed and the principal phases crystallizes with tetragonal symmetry with unit cell parameters a = 5.312(1) A, c = 10.389(2) A for x = 0.50 and a = 5.314(2) A, c = 10.393(2) A for x = 0.75. These alloys behave as antiferromagnetic, with Neel temperature of 37 K and 39 K, respectively. The EPR linewidth for these alloys shows a paramagnetic behavior between 100 and 610 K. The resonance field and the g factor show a slight variation with temperature. These results are discussed in terms of nearest-neighbor Cr{sup +3} (S=3/2) spin-coupled pairs. (Author)

  8. Effects of the rad52 gene on recombination in Saccharomyces cerevisiae

    Effects of the rad 52 mutation in Saccharomyces cerevisiae on meiotic, γ-ray-induced, uv-induced and spontaneous mitotic recombination were studied. The rad52/rad52 diploids undergo premeiotic DNA synthesis; sporulation occurs but inviable spores are produced. Both intra and intergenic recombination during meiosis were examined in cells transferred from sporulation medium to vegetative medium at different time intervals. No intragenic recombination was observed at the his1-1/his1-315 and trp-5-2/trp5-48 heteroalleles. Gene-centromere recombination also was not observed in rad/52/rad52 diploids. No γ-ray- or uv-induced intragenic mitotic recombination is seen in rad52/rad52 diploids. The rate of spontaneous mitotic recombination is lowered five-fold at the his1-1/his1-315 and leu1-c/leu1-12 heteroalleles. Spontaneous reversion rates of both his1-1 and his1-315 were elevated 10 to 20 fold in rad52/rad52 diploids. The RAD52 gene function is required for spontaneous mitotic recombination, uv- and γ-ray-induced mitotic recombination and mitotic recombination

  9. RAD6/sup +/ gene of Saccharomyces cerevisiae codes for two mutationally separable deoxyribonucleic acid repair functions

    The response of two mutant alleles of the RAD6/sup +/ gene of Saccharomyces cerevisiae to the ochre translational suppressor SUQ5 was determined. Both the ultraviolet sensitivity phenotype and the deficiency in ultraviolet-induced mutagenesis phenotype of the rad6-1 allelle were suppressed in a [psi/sup +/] background. For the rad6-3 allelle, only the ultraviolet-sensitivity phenotype was suppressible in a [psi/sup +/] background. An SUQ5 rad6-3 [psi/sup +/] strain that was examined showed the normal rad6-3 deficiency in ultraviolet-induced mutagenesis. The authors propose that the RAD6/sup +/ gene is divided into two cistrons, RAD6A and RAD6B. RAD6A codes for an activity responsible for the error-prone repair of ultraviolet-induced lesions in deoxyribonucleic acid but is not involved in a cell's resistance to the lethal effects of ultraviolet light. RAD6B codes for an activity essential for error-free repair of potentially lethal mutagenic damage

  10. RAD24 (=R1/sup S/) gene product of Saccharomyces cerevisiae participates in two different pathways of DNA repair

    The moderately UV- and X-ray-sensitive mutant of Saccharomyces cerevisiae originally designated r1/sup s/ complements all rad and mms mutants available. Therefore, the new nomination rad24-1 according to the RAD nomenclature is suggested. RAD24 maps on chromosome V, close to RAD3 (1.3 cM). In order to associate the RAD24 gene with one of the three repair pathways, double mutants of rad24 and various representative genes of each pathway were constructed. The UV and X-ray sensitivities of the double mutants compared to the single mutants indicate that RAD24 is involved in excision repair of UV damage (RAD3 epistasis group), as well as in recombination repair of UV and X-ray damage (RAD52 epistasis group). Properties of the mutant are discussed which hint at the control of late steps in the pathways

  11. Comparison of Martian Surface Radiation Predictions to the Measurements of Mars Science Laboratory Radiation Assessment Detector (MSL/RAD)

    Kim, Myung-Hee Y.; Cucinotta, Francis A.; Zeitlin, Cary; Hassler, Donald M.; Ehresmann, Bent; Rafkin, Scot C. R.; Wimmer-Schweingruber, Robert F; Boettcher, Stephan; Boehm, Eckart; Guo, Jingnan; Koehler, Jan; Martin, Cesar; Reitz, Guenther; Posner, Erik

    2014-01-01

    For the analysis of radiation risks to astronauts and planning exploratory space missions, detailed knowledge of particle spectra is an important factor. Detailed measurements of the energetic particle radiation environment on the surface of Mars have been made by the Mars Science Laboratory Radiation Assessment Detector (MSL-RAD) on the Curiosity rover since August 2012, and particle fluxes for a wide range of ion species (up to several hundred MeV/u) and high energy neutrons (8 - 1000 MeV) have been available for the first 200 sols. Although the data obtained on the surface of Mars for 200 sols are limited in the narrow energy spectra, the simulation results using the Badhwar-O'Neill galactic cosmic ray (GCR) environment model and the high-charge and energy transport (HZETRN) code are compared to the data. For the nuclear interactions of primary GCR through Mars atmosphere and Curiosity rover, the quantum multiple scattering theory of nuclear fragmentation (QMSFRG) is used, which includes direct knockout, evaporation and nuclear coalescence. Daily atmospheric pressure measurements at Gale Crater by the MSL Rover Environmental Monitoring Station are implemented into transport calculations for describing the daily column depth of atmosphere. Particles impinging on top of the Martian atmosphere reach the RAD after traversing varying depths of atmosphere that depend on the slant angles, and the model accounts for shielding of the RAD by the rest of the instrument. Calculations of stopping particle spectra are in good agreement with the RAD measurements for the first 200 sols by accounting changing heliospheric conditions and atmospheric pressure. Detailed comparisons between model predictions and spectral data of various particle types provide the validation of radiation transport models, and thus increase the accuracy of the predictions of future radiation environments on Mars. These contributions lend support to the understanding of radiation health risks to

  12. Alterações clínicolaboratoriais em pacientes com malária por Plasmodium vivax e deficiência de glicose-6-fosfato desidrogenase tratados com 0,50mg/kg/dia de primaquina Clinical and laboratorial alterations in Plasmodium vivax malaria patients and glucose-6-phosphate dehydrogenase deficiency treated with primaquine at 0.50mg/kg/day

    Mônica C.M. Silva; Eliane B. Santos; Elenild G. Costa; Manoel G. S. Filho; Guerreiro, João F.; Póvoa, Marinete M.

    2004-01-01

    O efeito adverso da primaquina na dose de 0,50mg/kg/dia foi investigado em onze pacientes com malária vivax (três com deficiência de glicose-6-fosfato desidrogenase). Alterações clínicas e laboratoriais indicaram hemólise aguda apenas nos enzimopênicos, o que fez com que o tratamento fosse interrompido. Nossos resultados sugerem a necessidade do emprego de um teste de triagem para a deficiência de G6PD em áreas endêmicas de malária vivax a fim de se evitar complicações causadas pelo uso da pr...

  13. Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1.

    Callender, Tracy L; Laureau, Raphaelle; Wan, Lihong; Chen, Xiangyu; Sandhu, Rima; Laljee, Saif; Zhou, Sai; Suhandynata, Ray T; Prugar, Evelyn; Gaines, William A; Kwon, YoungHo; Börner, G Valentin; Nicolas, Alain; Neiman, Aaron M; Hollingsworth, Nancy M

    2016-08-01

    During meiosis, programmed double strand breaks (DSBs) are repaired preferentially between homologs to generate crossovers that promote proper chromosome segregation at Meiosis I. In many organisms, there are two strand exchange proteins, Rad51 and the meiosis-specific Dmc1, required for interhomolog (IH) bias. This bias requires the presence, but not the strand exchange activity of Rad51, while Dmc1 is responsible for the bulk of meiotic recombination. How these activities are regulated is less well established. In dmc1Δ mutants, Rad51 is actively inhibited, thereby resulting in prophase arrest due to unrepaired DSBs triggering the meiotic recombination checkpoint. This inhibition is dependent upon the meiosis-specific kinase Mek1 and occurs through two different mechanisms that prevent complex formation with the Rad51 accessory factor Rad54: (i) phosphorylation of Rad54 by Mek1 and (ii) binding of Rad51 by the meiosis-specific protein Hed1. An open question has been why inhibition of Mek1 affects Hed1 repression of Rad51. This work shows that Hed1 is a direct substrate of Mek1. Phosphorylation of Hed1 at threonine 40 helps suppress Rad51 activity in dmc1Δ mutants by promoting Hed1 protein stability. Rad51-mediated recombination occurring in the absence of Hed1 phosphorylation results in a significant increase in non-exchange chromosomes despite wild-type levels of crossovers, confirming previous results indicating a defect in crossover assurance. We propose that Rad51 function in meiosis is regulated in part by the coordinated phosphorylation of Rad54 and Hed1 by Mek1. PMID:27483004

  14. Real-time assembly and disassembly of human RAD51 filaments on individual DNA molecules

    van der Heijden, Thijn; Seidel, Ralf; Modesti, Mauro; Kanaar, Roland; Wyman, Claire; Dekker, Cees

    2007-01-01

    textabstractThe human DNA repair protein RAD51 is the crucial component of helical nucleoprotein filaments that drive homologous recombination. The molecular mechanistic details of how this structure facilitates the requisite DNA strand rearrangements are not known but must involve dynamic interactions between RAD51 and DNA. Here, we report the real-time kinetics of human RAD51 filament assembly and disassembly on individual molecules of both single- and double-stranded DNA, as measured using...

  15. Real-time assembly and disassembly of human RAD51 filaments on individual DNA molecules

    Van der Heijden, T.; Seidel, R.; Modesti, M.; Kanaar, R.; Wyman, C; Dekker, C.

    2007-01-01

    The human DNA repair protein RAD51 is the crucial component of helical nucleoprotein filaments that drive homologous recombination. The molecular mechanistic details of how this structure facilitates the requisite DNA strand rearrangements are not known but must involve dynamic interactions between RAD51 and DNA. Here, we report the real-time kinetics of human RAD51 filament assembly and disassembly on individual molecules of both single- and double-stranded DNA, as measured using magnetic tw...

  16. Evaluation of BICRON NE MCP DXT-RAD passive extremity dosemeter

    Yuen, P S; Frketich, G; Rotunda, J

    1999-01-01

    Passive extremity dosemeters currently used in dosimetry communities worldwide have shortcomings. In general, an extremity dosemeter has too thick a detector element, and the dosemeter response is highly energy dependent for beta rays with energies ranging from 200 keV to 2 MeV. It often does not have dosemeter identification, causing problems in the chain of custody. It is often read manually, rendering reading/packing operations very labour intensive. As a result of collaboration between AECL and BICRON NE, a new extremity dosemeter, incorporating a highly sensitive LiF:Mg,Cu,P TLD and tentatively code named MCP DXT-RAD, was developed. It has been evaluated for radiological performance against an ISO draft standard for extremity dosemeters in twelve categories: homogeneity, detection threshold, beta ray energy response, beta angular response, photon energy response, photon angular response, reproducibility, stability under various climatic conditions, linearity, residue, self irradiation, and effect of ligh...

  17. Upward- directed charged particle flux detection in the MSL/RAD instrument

    Appel, Jan Kristoffer; Zeitlin, Cary; Koehler, Jan; Hassler, Donald M.; Rafkin, Scot; Guo, Jingnan; Ehresmann, Bent; Wimmer-Schweingruber, Robert; Matthiä, Daniel; Lohf, Henning

    2016-07-01

    The Mars Science Laboratory rover Curiosity, operating on the surface of Mars, is exposed to radiation fluxes from above and below. Galactic Cosmic Rays travel through the Martian atmosphere, producing a modified spectrum consisting of both primary and secondary particles at ground level. These particles produce an upward- directed secondary particle spectrum as they interact with the Martian soil.These upward- directed particles then pass through the rover and enter the Radiation Assessment Detector onboard the rover from below. Here, we characterize the upward- and downward- directed spectra measured by the detector through a combination of GEANT4 and Planetocosmics simulations. We develop and demonstrate a method to discriminate between upward- and downward- directed particle fluxes during the MSL cruise phase to Mars and the surface science phase. This method enables us to extend the energy range and directionality of RAD beyond its design limits.

  18. Multiple start codons and phosphorylation result in discrete Rad52 protein species

    de Mayolo, A.A.; Lisby, M.; Erdeniz, N.;

    2006-01-01

    protein species are due to promiscuous choice of start codons as well as post-translational modification. Specifically, Rad52 is phosphorylated both in a cell cycle-independent and in a cell cycle-dependent manner. Furthermore, phosphorylation is dependent on the presence of the Rad52 C terminus, but not...... dependent on its interaction with Rad51. We also show that the Rad52 protein can be translated from the last three start sites and expression from any one of them is sufficient for spontaneous recombination and the repair of gamma-ray-induced double-strand breaks....

  19. Rad9 plays an important role in DNA mismatch repair through physical interaction with MLH1

    He, Wei; Zhao, Yun; Zhang, Chunbo; An, Lili; Hu, Zhishang; Liu, Yuheng; Han, Lu; Bi, Lijun; Xie, Zhensheng; Xue, Peng; Yang, Fuquan; Hang, Haiying

    2008-01-01

    Rad9 is conserved from yeast to humans and plays roles in DNA repair (homologous recombination repair, and base-pair excision repair) and cell cycle checkpoint controls. It has not previously been reported whether Rad9 is involved in DNA mismatch repair (MMR). In this study, we have demonstrated that both human and mouse Rad9 interacts physically with the MMR protein MLH1. Disruption of the interaction by a single-point mutation in Rad9 leads to significantly reduced MMR activity. This disrup...

  20. Germline mutation in the RAD51B gene confers predisposition to breast cancer

    Most currently known breast cancer predisposition genes play a role in DNA repair by homologous recombination. Recent studies conducted on RAD51 paralogs, involved in the same DNA repair pathway, have identified rare germline mutations conferring breast and/or ovarian cancer predisposition in the RAD51C, RAD51D and XRCC2 genes. The present study analysed the five RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) to estimate their contribution to breast and ovarian cancer predisposition. The study was conducted on 142 unrelated patients with breast and/or ovarian cancer either with early onset or with a breast/ovarian cancer family history. Patients were referred to a French family cancer clinic and had been previously tested negative for a BRCA1/2 mutation. Coding sequences of the five genes were analysed by EMMA (Enhanced Mismatch Mutation Analysis). Detected variants were characterized by Sanger sequencing analysis. Three splicing mutations and two likely deleterious missense variants were identified: RAD51B c.452 + 3A > G, RAD51C c.706-2A > G, RAD51C c.1026 + 5-1026 + 7del, RAD51B c.475C > T/p.Arg159Cys and XRCC3 c.448C > T/p.Arg150Cys. No RAD51D and XRCC2 gene mutations were detected. These mutations and variants were detected in families with both breast and ovarian cancers, except for the RAD51B c.475C > T/p.Arg159Cys variant that occurred in a family with 3 breast cancer cases. This study identified the first RAD51B mutation in a breast and ovarian cancer family and is the first report of XRCC3 mutation analysis in breast and ovarian cancer. It confirms that RAD51 paralog mutations confer breast and ovarian cancer predisposition and are rare events. In view of the low frequency of RAD51 paralog mutations, international collaboration of family cancer clinics will be required to more accurately estimate their penetrance and establish clinical guidelines in carrier individuals

  1. The epistatic relationship between BRCA2 and the other RAD51 mediators in homologous recombination.

    Yong Qing

    2011-07-01

    Full Text Available RAD51 recombinase polymerizes at the site of double-strand breaks (DSBs where it performs DSB repair. The loss of RAD51 causes extensive chromosomal breaks, leading to apoptosis. The polymerization of RAD51 is regulated by a number of RAD51 mediators, such as BRCA1, BRCA2, RAD52, SFR1, SWS1, and the five RAD51 paralogs, including XRCC3. We here show that brca2-null mutant cells were able to proliferate, indicating that RAD51 can perform DSB repair in the absence of BRCA2. We disrupted the BRCA1, RAD52, SFR1, SWS1, and XRCC3 genes in the brca2-null cells. All the resulting double-mutant cells displayed a phenotype that was very similar to that of the brca2-null cells. We suggest that BRCA2 might thus serve as a platform to recruit various RAD51 mediators at the appropriate position at the DNA-damage site.

  2. RadCon: A radiological consequences model. Technical guide - Version 2.0

    A Radiological Consequence model (RadCon) is being developed at ANSTO to assess the radiological consequences, after an incident, in any climate, using appropriate meteorological and radiological transfer parameters. The major areas of interest to the developers are tropical and subtropical climates. This is particularly so given that it is anticipated that nuclear energy will become a mainstay for economies in these regions within the foreseeable future. Therefore, data acquisition and use of parameter values have been concentrated primarily on these climate types. Atmospheric dispersion and deposition for Australia can be modelled and supplied by the Regional Specialised Meteorological Centre (RSMC, one of five in the world) which is part of the Bureau of Meteorology Research Centre (BMRC), Puri et al. (1992). RadCon combines these data (i.e. the time dependent air and ground concentration generated by the dispersion model or measured quantities in the case of an actual incident) with specific regional parameter values to determine the dose to people via the major pathways of external and internal irradiation. For the external irradiation calculations, data are needed on lifestyle information such as the time spent indoors/outdoors, the high/low physical activity rates for different groups of people (especially critical groups) and shielding factors for housing types. For the internal irradiation calculations, data are needed on food consumption, effect of food processing, transfer parameters (soil to plant, plant to animal) and interception values appropriate for the region under study. Where the relevant data are not available default temperate data are currently used. The results of a wide ranging literature search has highlighted where specific research will be initiated to determine the information required for tropical and sub-tropical regions. The user is able to initiate sensitivity analyses within RadCon. This allows the parameters to be ranked in

  3. Characterization of the interaction between the cohesin subunits Rad21 and SA1/2.

    Nenggang Zhang

    Full Text Available The cohesin complex is responsible for the fidelity of chromosomal segregation during mitosis. It consists of four core subunits, namely Rad21/Mcd1/Scc1, Smc1, Smc3, and one of the yeast Scc3 orthologs SA1 or SA2. Sister chromatid cohesion is generated during DNA replication and maintained until the onset of anaphase. Among the many proposed models of the cohesin complex, the 'core' cohesin subunits Smc1, Smc3, and Rad21 are almost universally displayed as tripartite ring. However, other than its supportive role in the cohesin ring, little is known about the fourth core subunit SA1/SA2. To gain deeper insight into the function of SA1/SA2 in the cohesin complex, we have mapped the interactive regions of SA2 and Rad21 in vitro and ex vivo. Whereas SA2 interacts with Rad21 through a broad region (301-750 aa, Rad21 binds to SA proteins through two SA-binding motifs on Rad21, namely N-terminal (NT and middle part (MP SA-binding motif, located at 60-81 aa of the N-terminus and 383-392 aa of the MP of Rad21, respectively. The MP SA-binding motif is a 10 amino acid, α-helical motif. Deletion of these 10 amino acids or mutation of three conserved amino acids (L(385, F(389, and T(390 in this α-helical motif significantly hinders Rad21 from physically interacting with SA1/2. Besides the MP SA-binding motif, the NT SA-binding motif is also important for SA1/2 interaction. Although mutations on both SA-binding motifs disrupt Rad21-SA1/2 interaction, they had no apparent effect on the Smc1-Smc3-Rad21 interaction. However, the Rad21-Rad21 dimerization was reduced by the mutations, indicating potential involvement of the two SA-binding motifs in the formation of the two-ring handcuff for chromosomal cohesion. Furthermore, mutant Rad21 proteins failed to significantly rescue precocious chromosome separation caused by depletion of endogenous Rad21 in mitotic cells, further indicating the physiological significance of the two SA-binding motifs of Rad21.

  4. Biochemical characterization of plant Rad52 protein from rice (Oryza sativa).

    Nair, Anuradha; Agarwal, Rachna; Chittela, Rajani Kant

    2016-09-01

    DNA damage in living cells is repaired by two main pathways, homologous recombination (HR) and non-homologous end joining (NHEJ). Of all the genes promoting HR, Rad52 (Radiation sensitive 52) is an important gene which is found to be highly conserved across different species. It was believed that RAD52 is absent in plant systems until lately. However, recent genetic studies have shown the presence of RAD52 homologues in plants. Rad52 homologues in plant systems have not yet been characterized biochemically. In the current study, we bring out the biochemical properties of rice Rad52-2a protein. OsRad52-2a was over-expressed in Escherichia coli BL21 (DE3) cells and the protein was purified. The identity of purified OsRad52-2a protein was confirmed via peptide mass fingerprinting. Gel filtration and native PAGE analysis indicated that the OsRad52-2a protein in its native state probably formed an undecameric structure. Purified OsRad52-2a protein showed binding to single stranded DNA, double stranded DNA. Protein also mediated the renaturation of complementary single strands into duplex DNA in both agarose gel and FRET based assays. Put together, OsRad52-2a forms oligomeric structures and binds to ssDNA/dsDNA for mediating an important function like renaturation during homologous recombination. This study represents the first report on biochemical properties of OsRad52-2a protein from important crop like rice. This information will help in dissecting the recombination and repair machinery in plant systems. PMID:27156135

  5. A Rad53 Independent Function of Rad9 Becomes Crucial for Genome Maintenance in the Absence of the RecQ Helicase Sgs1

    Nielsen, Ida; Bentsen, Iben Bach; Andersen, Anni Hangaard;

    2013-01-01

    The conserved family of RecQ DNA helicases consists of caretaker tumour suppressors, that defend genome integrity by acting on several pathways of DNA repair that maintain genome stability. In budding yeast, Sgs1 is the sole RecQ helicase and it has been implicated in checkpoint responses......, replisome stability and dissolution of double Holliday junctions during homologous recombination. In this study we investigate a possible genetic interaction between SGS1 and RAD9 in the cellular response to methyl methane sulphonate (MMS) induced damage and compare this with the genetic interaction between...... SGS1 and RAD24. The Rad9 protein, an adaptor for effector kinase activation, plays well-characterized roles in the DNA damage checkpoint response, whereas Rad24 is characterized as a sensor protein also in the DNA damage checkpoint response. Here we unveil novel insights into the cellular response to...

  6. Temperature calibration of PICO-RAD detectors for radon measurement

    A simple mathematical equation linking the activity of adsorbed radon in the vials to the time of its exposure has been discussed. The calibration coefficient Ks, defined as a measured activity in cpm after a saturation time, corresponding to a radon air concentration of 1 Bq m-3 has been determined for four temperatures: 284, 291, 294 and 298 K. A linear relationship of ln Ks values versus T-1 has been found. The relatively high difference in Ks values: 2.12 and 1.24 cpm/Bq m3 for the temperatures of 284 and 298 K, respectively, was observed. It indicates that temperature fluctuations during Pico-Rad vial exposure may lead to erroneous results if the constant average temperature of exposure is introduced into a commonly used computer program for calculating Rn concentration. (author). 6 refs, 4 figs

  7. Temperature calibration of Pico-Rad detectors for radon measurement

    A simple mathematical equation linking the activity of adsorbed radon in the vials to the time and temperature of its exposure is discussed. The calibration coefficient - Ks, defined as activity measured in cpm after saturation time, corresponding to radon air concentration of 1 Bq m-3, was determined for four temperatures: 284, 291, 294 and 298 K. A linear relationship of ln Ks values versus T-1 was found. The relatively high difference in Ks values: 2.12 and 1.24 cpm/Bq m-3 for the temperatures of 284 and 298 K, respectively, was observed. It indicates that temperature fluctuations during Pico-Rad vial exposure may lead to erroneous results if the constant average temperature of exposure is introduced into a commonly used computer programme for calculating Rn concentration. (author)

  8. A RAD approach to client/server system development

    The capability, richness, and leverage of inexpensive commercial operating systems, off-the-shelf applications, and powerful developing tools have made building feature-rich client/server systems possible in rapid time and at low cost--ushering in a new level of systems integration not before possible. The authors achieve rapid application development (RAD) by using a flexible and extendible client/service integration framework. The framework provides the means to integrate in-house and third-party software applications with databases and expert-system knowledge bases and, where appropriate, provides communication links among the applications. The authors discuss the integration framework's capabilities, explain its underlying system architecture, and outline the methods and tools used to customize and integrate many diverse applications

  9. Identification of novel functional domains of Rad52 in Saccharomyces cerevisiae

    Plate, Iben

    2006-01-01

    . cerevisiae er desuden nem at manipulere genetisk og der eksisterer sofistikerede in vivo assays som muliggør visualisering af reparationsprocessen ved hjælp af fluorescensmikroskopi. Rad52 er et vigtigt protein til reparation af DNA DSB i S. cerevisiae og rad52Δ celler har en alvorlig fænotype med langsom...

  10. A novel Rad gene polymorphism combined with obesity increases risk for type 2 diabetes mellitus

    王国英; 牛天华; 陈常忠; 李琼芳; 徐希平

    2004-01-01

    @@ The ras-associated diabetes (Rad) was initially identified by subtraction cloning from the skeletal muscle of humans with non-insulin dependent diabetes mellitus (type 2 DM).1 Rad mRNA expression is markedly increased in the skeletal muscle of type 2 DM patients compared with normal controls.

  11. RAD6 gene of Saccharomyces cerevisiae encodes a protein containing a tract of 13 consecutive aspartates

    The RAD6 gene of Saccharomyces cerevisiae is required for postreplication repair of UV-damaged DNA, for induced mutagenesis, and for sporulation. The authors have mapped the transcripts and determined the nucleotide sequence of the cloned RAD6 gene. The RAD6 gene encodes two transcripts of 0.98 and 0.86 kilobases which differ only in their 3' termini. The transcribed region contains an open reading frame of 516 nucleotides. The rad6-1 and rad6-3 mutant alleles, which the authors have cloned and sequenced, introduce amber and ochre nonsense mutations, respectively into the open reading frame, proving that it encodes the RAD6 protein. The RAD6 protein predicted by the nucleotide sequence is 172 amino acids long, has a molecular weight of 19,704, and contains 23.3% acidic and 11.6% basic residues. Its most striking feature is the highly acidic carboxyl terminus: 20 of the 23 terminal amino acids are acidic, including 13 consecutive aspartates. RAD6 protein thus resembles high mobility group proteins HMG-1 and HMG-2, which each contain a carboxyl-proximal tract of acidic amino acids. 48 references, 6 figures

  12. Rad52 forms DMA repair and recombination centers during S phase

    Lisby, M.; Rothstein, R.; Mortensen, Uffe Hasbro

    2001-01-01

    cerevisiae, homologous recombination is the major pathway for repairing DNA double-strand breaks. The key role played by Rad52 in this pathway has been attributed to its ability to seek out and mediate annealing of homologous DNA strands. In this study, we find that S. cerevisiae Rad52 fused to green...

  13. Enhancement of the RAD51 Recombinase Activity by the Tumor Suppressor PALB2

    Dray, Eloise; Etchin, Julia; Wiese, Claudia; Saro, Dorina; Williams, Gareth J.; Hammel, Michal; Yu, Xiong; Galkin, Vitold E.; Liu, Dongqing; Tsai, Miaw-Sheue; Sy, Shirley M-H.; Egelman, Edward; Chen, Junjie; Sung, Patrick; Schild, D.

    2010-08-24

    Homologous recombination mediated by the RAD51 recombinase helps eliminate chromosomal lesions, such as DNA double-stranded breaks induced by radiation or arising from injured DNA replication forks. The tumor suppressors BRCA2 and PALB2 act together to deliver RAD51 to chromosomal lesions to initiate repair. Here we document a new function of PALB2 in the enhancement of RAD51's ability to form the D-loop. We show that PALB2 binds DNA and physically interacts with RAD51. Importantly, while PALB2 alone stimulates D-loop formation, a cooperative effect is seen with RAD51AP1, an enhancer of RAD51. This stimulation stems from PALB2's ability to function with RAD51 and RAD51AP1 to assemble the synaptic complex. Our results help unveil a multi-faceted role of PALB2 in chromosome damage repair. Since PALB2 mutations can cause breast and other tumors or lead to Fanconi anemia, our findings are important for understanding the mechanism of tumor suppression in humans.

  14. FBH1 helicase disrupts RAD51 filaments in vitro and modulates homologous recombination in mammalian cells

    Simandlova, Jitka; Zagelbaum, Jennifer; Payne, Miranda J;

    2013-01-01

    filaments on DNA through its ssDNA translocase function. Consistent with this, a mutant mouse embryonic stem cell line with a deletion in the FBH1 helicase domain fails to limit RAD51 chromatin association and shows hyper-recombination. Our data are consistent with FBH1 restraining RAD51 DNA binding under...

  15. RadSTAR L-Band Imaging Scatterometer: Performance Assessment

    Rincon, Rafael; Hildebrand, Peter; Hilliard, Larry

    2007-01-01

    RadSTAR is an instrument development program aimed at combining a radiometer and a scatterometer system into a highly compact configuration that uses a single, electronically scanned antenna to provide co-located and simultaneous measurements of emission and backscatter for airborne and spaceborne applications [I]. The program was designed to map soil moisture and ocean salinity, both important components of the water cycle, and to map sea ice density and thickness, an important factor in ocean-atmosphere heat exchange in Polar Regions. The accuracy in estimation of these and a number of other Earth science parameters can be greatly enhanced by providing the co-aligned radar/radiometer microwave measurements. For instance, radiometer estimates of soil moisture from soil emission are affected by emission from vegetation, and from the roughness of the surface. Complementary measurements using the scatterometer can be used to evaluate the vegetation and surface roughness effects. Hence, the combined observations can provide an improved estimate. As with soil moisture, the ocean salinity is a function of the microwave emission from the sea surface temperature (SST) and sea roughness. There, the addition of radar backscatter measurements of sea roughness enables the correction of the emissivity and provide more accurate estimates of ocean salinity. Similar arguments can be made for other important Earth science parameters. This paper discusses the RadSTAR program, the radar system design, calibration, and digital beamforming techniques, and presents preliminary analysis of the data collected during the test flights. The data sets obtained during the flights and during the radar calibration in the anechoic chamber are also employed to asses the performance of the radar. The paper also discusses the Digital Beamforming Synthetic Aperture Radar (DBSAR) processor, a real-time processor recently developed for the LIS instrument which enables beam synthesis, fine resolutions

  16. Aflatoxin B1-Associated DNA Adducts Stall S Phase and Stimulate Rad51 foci in Saccharomyces cerevisiae

    Michael Fasullo

    2010-01-01

    Full Text Available AFB1 is a potent recombinagen in budding yeast. AFB1 exposure induces RAD51 expression and triggers Rad53 activation in yeast cells that express human CYP1A2. It was unknown, however, when and if Rad51 foci appear. Herein, we show that Rad53 activation correlates with cell-cycle delay in yeast and the subsequent formation of Rad51 foci. In contrast to cells exposed to X-rays, in which Rad51 foci appear exclusively in G2 cells, Rad51 foci in AFB1-exposed cells can appear as soon as cells enter S phase. Although rad51 and rad4 mutants are mildly sensitive to AFB1, chronic exposure of the NER deficient rad4 cells to AFB1 leads to increased lag times, while rad4 rad51 double mutants exhibit synergistic sensitivity and do not grow when exposed to 50 μM AFB1. We suggest RAD51 functions to facilitate DNA replication after replication fork stalling or collapse in AFB1-exposed cells.

  17. Rad52 multimerization is important for its nuclear localization in Saccharomyces cerevisiae

    Plate, Iben; Albertsen, Line; Lisby, Michael;

    2008-01-01

    Rad52 is essential for all homologous recombination and DNA double strand break repair events in Saccharomyces cerevisiae. This protein is multifunctional and contains several domains that allow it to interact with DNA as well as with different repair proteins. However, it has been unclear how Ra...... on the results we propose a model where the additive effect of multiple NLS(Rad52) sequences in a Rad52 ring-structure ensures efficient nuclear localization of Rad52.......52 enters the nucleus. In the present study, we have used a combination of mutagenesis and sequence analysis to show that Rad52 from S. cerevisiae contains a single functional pat7 type NLS essential for its nuclear localization. The region containing the NLS seems only to be involved in nuclear...

  18. Comparison of Danish dichotomous and BI-RADS classifications of mammographic density

    Hodge, Rebecca; Hellmann, Sophie Sell; von Euler-Chelpin, My; Vejborg, Ilse; Andersen, Zorana Jovanovic

    2014-01-01

    : Of the 120 women, 32 (26.7%) were classified as having fatty and 88 (73.3%) as mixed/dense mammographic density, according to Danish dichotomous classification. According to BI-RADS density classification, 12 (10.0%) women were classified as having predominantly fatty (BI-RADS code 1), 46 (38.3%) as...... having scattered fibroglandular (BI-RADS code 2), 57 (47.5%) as having heterogeneously dense (BI-RADS 3), and five (4.2%) as having extremely dense (BI-RADS code 4) mammographic density. The inter-rater variability assessed by weighted kappa statistic showed a substantial agreement (0.75). CONCLUSION......BACKGROUND: In the Copenhagen mammography screening program from 1991 to 2001, mammographic density was classified either as fatty or mixed/dense. This dichotomous mammographic density classification system is unique internationally, and has not been validated before. PURPOSE: To compare the Danish...

  19. Breast Imaging Reporting and Data System (BI-RADS) breast composition descriptors: Automated measurement development for full field digital mammography

    Fowler, E. E.; Sellers, T. A.; Lu, B. [Department of Cancer Epidemiology, Division of Population Sciences, H. Lee Moffitt Cancer Center, Tampa, Florida 33612 (United States); Heine, J. J. [Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center, Tampa, Florida 33612 (United States)

    2013-11-15

    measures were significantly associated with breast cancer status in the adjusted models: (a) OR = 1.95 (1.24, 3.09) for BR{sub pg}; (b) OR = 1.42 (0.87, 2.32) for BR{sub vc}; and (c) OR = 2.13 (1.22, 3.72) for BR{sub vr}. The radiologist-reported measures from the patient records showed a similar association, OR = 1.49 (0.99, 2.24), although only borderline statistically significant.Conclusions: A general framework was developed and validated for converting calibrated mammograms and continuous measures of breast density to fully automated approximations for the BI-RADS breast composition descriptors. The techniques are general and suitable for a broad range of clinical and research applications.

  20. Real-time measurements of the nucleation, growth and dissociation of single Rad51–DNA nucleoprotein filaments

    Miné, Judith; Disseau, Ludovic; Takahashi, Masayuki; Cappello, Giovanni; Dutreix, Marie; Viovy, Jean-Louis

    2007-01-01

    Human Rad51 (hRad51), the protein central to DNA pairing and strand exchange during homologous recombination, polymerizes on DNA to form nucleoprotein filaments. By making use of magnetic tweezers to manipulate individual DNA molecules, we measured the nucleation and growth of hRad51 nucleoprotein filaments, and their subsequent disassembly in real time. The dependence of the initial polymerization rate upon the concentration of hRad51 suggests that the rate-limiting step is the formation of ...

  1. Lysine residue 185 of Rad1 is a topological but not a functional counterpart of lysine residue 164 of PCNA.

    Niek Wit

    Full Text Available Monoubiquitylation of the homotrimeric DNA sliding clamp PCNA at lysine residue 164 (PCNA(K164 is a highly conserved, DNA damage-inducible process that is mediated by the E2/E3 complex Rad6/Rad18. This ubiquitylation event recruits translesion synthesis (TLS polymerases capable of replicating across damaged DNA templates. Besides PCNA, the Rad6/Rad18 complex was recently shown in yeast to ubiquitylate also 9-1-1, a heterotrimeric DNA sliding clamp composed of Rad9, Rad1, and Hus1 in a DNA damage-inducible manner. Based on the highly similar crystal structures of PCNA and 9-1-1, K185 of Rad1 (Rad1(K185 was identified as the only topological equivalent of PCNA(K164. To investigate a potential role of posttranslational modifications of Rad1(K185 in DNA damage management, we here generated a mouse model with a conditional deletable Rad1(K185R allele. The Rad1(K185 residue was found to be dispensable for Chk1 activation, DNA damage survival, and class switch recombination of immunoglobulin genes as well as recruitment of TLS polymerases during somatic hypermutation of immunoglobulin genes. Our data indicate that Rad1(K185 is not a functional counterpart of PCNA(K164.

  2. The response of mammalian cells to UV-light reveals Rad54-dependent and independent pathways of homologous recombination

    Eppink, Berina; Tafel, Agnieszka A; Hanada, Katsuhiro;

    2011-01-01

    lesions in replicating DNA. The core HR protein in mammalian cells is the strand exchange protein RAD51, which is aided by numerous proteins, including RAD54. We used RAD54 as a cellular marker for HR to study the response of mammalian embryonic stem (ES) cells to UV irradiation. In contrast to yeast, ES...

  3. Erythropoietic defect associated with reduced cell proliferation in mice lacking the 26S proteasome shuttling factor Rad23b

    S. Bergink (Steven); A.F. Theil (Arjan); W. Toussaint (Wendy); I.M. de Cuyper (Iris); D.I. Kulu (Divine); T. Clapes (Thomas); R. van der Linden (Reinier); J.A.A. Demmers (Jeroen); E.P. Mul (Eric); F.P. van Alphen (Floris); J.A. Marteijn (Jurgen); T. van Gent (Teus); A. Maas (Alex); C. Robin (Catherine); J.N.J. Philipsen (Sjaak); W. Vermeulen (Wim); J.R. Mitchell (James); L. Gutiérrez (Laura)

    2013-01-01

    textabstractRad23a and Rad23b proteins are linked to nucleotide excision DNA repair (NER) via association with the DNA damage recognition protein xeroderma pigmentosum group C (XPC) are and known to be implicated in protein turnover by the 26S proteasome. Rad23b-null mice are NER proficient, likely

  4. Erythropoietic Defect Associated with Reduced Cell Proliferation in Mice Lacking the 26S Proteasome Shuttling Factor Rad23b

    Bergink, Steven; Theil, Arjan F.; Toussaint, Wendy; De Cuyper, Iris M.; Kulu, Divine I.; Clapes, Thomas; van der Linden, Reinier; Demmers, Jeroen A.; Mul, Eric P.; van Alphen, Floris P.; Marteijn, Jurgen A.; van Gent, Teus; Maas, Alex; Robin, Catherine; Philipsen, Sjaak; Vermeulen, Wim; Mitchell, James R.; Gutierrez, Laura

    2013-01-01

    Rad23a and Rad23b proteins are linked to nucleotide excision DNA repair (NER) via association with the DNA damage recognition protein xeroderma pigmentosum group C (XPC) are and known to be implicated in protein turnover by the 26S proteasome. Rad23b-null mice are NER proficient, likely due to the r

  5. Rad51C deficiency destabilizes XRCC3, impairs recombination and radiosensitizes S/G2-phase cells

    Lio, Yi-Ching; Schild, David; Brenneman, Mark A.; Redpath, J. Leslie; Chen, David J.

    2004-05-01

    The highly conserved Rad51 protein plays an essential role in repairing DNA damage through homologous recombination. In vertebrates, five Rad51 paralogs (Rad51B, Rad51C, Rad51D, XRCC2, XRCC3) are expressed in mitotically growing cells, and are thought to play mediating roles in homologous recombination, though their precise functions remain unclear. Here we report the use of RNA interference to deplete expression of Rad51C protein in human HT1080 and HeLa cells. In HT1080 cells, depletion of Rad51C by small interfering RNA caused a significant reduction of frequency in homologous recombination. The level of XRCC3 protein was also sharply reduced in Rad51C-depleted HeLa cells, suggesting that XRCC3 is dependent for its stability upon heterodimerization with Rad51C. In addition, Rad51C-depleted HeLa cells showed hypersensitivity to the DNA cross-linking agent mitomycin C, and moderately increased sensitivity to ionizing radiation. Importantly, the radiosensitivity of Rad51C-deficient HeLa cells was evident in S and G{sub 2}/M phases of the cell cycle but not in G{sub 1} phase. Together, these results provide direct cellular evidence for the importance of human Rad51C in homologous recombinational repair.

  6. Structure of a hexameric form of RadA recombinase from Methanococcus voltae

    Hexameric rings of RadA recombinase from M. voltae have been crystallized. Structural comparisons suggest that homologues of RadA tend to form double-ringed assemblies. Archaeal RadA proteins are close homologues of eukaryal Rad51 and DMC1 proteins and are remote homologues of bacterial RecA proteins. For the repair of double-stranded breaks in DNA, these recombinases promote a pivotal strand-exchange reaction between homologous single-stranded and double-stranded DNA substrates. This DNA-repair function also plays a key role in the resistance of cancer cells to chemotherapy and radiotherapy and in the resistance of bacterial cells to antibiotics. A hexameric form of a truncated Methanococcus voltae RadA protein devoid of its small N-terminal domain has been crystallized. The RadA hexamers further assemble into two-ringed assemblies. Similar assemblies can be observed in the crystals of Pyrococcus furiosus RadA and Homo sapiens DMC1. In all of these two-ringed assemblies the DNA-interacting L1 region of each protomer points inward towards the centre, creating a highly positively charged locus. The electrostatic characteristics of the central channels can be utilized in the design of novel recombinase inhibitors

  7. Genetic analysis of Escherichia coli RadA: functional motifs and genetic interactions.

    Cooper, Deani L; Boyle, Daniel C; Lovett, Susan T

    2015-03-01

    The RadA/Sms protein is a RecA-related protein found universally in eubacteria and plants, implicated in processing of recombination intermediates. Here we show that the putative Zn finger, Walker A motif, KNRXG motif and Lon protease homology domain of the Escherichia coli RadA protein are required for DNA damage survival. RadA is unlikely to possess protease activity as the putative active site serine is not required. Mutants in RadA have strong synergistic phenotypes with those in the branch migration protein RecG. Sensitivity of radA recG mutants to azidothymidine (AZT) can be rescued by blocking recombination with recA or recF mutations or by overexpression of RuvAB, suggesting that lethal recombination intermediates accumulate in the absence of RadA and RecG. Synthetic genetic interactions for survival to AZT or ciprofloxacin exposure were observed between RadA and known or putative helicases including DinG, Lhr, PriA, Rep, RuvAB, UvrD, YejH and YoaA. These represent the first affected phenotypes reported for Lhr, YejH and YoaA. The specificity of these effects sheds new light on the role of these proteins in DNA damage avoidance and repair and implicates a role in replication gap processing for DinG and YoaA and a role in double-strand break repair for YejH. PMID:25484163

  8. Multiple regulation of Rad51-mediated homologous recombination by fission yeast Fbh1.

    Tsutsui, Yasuhiro; Kurokawa, Yumiko; Ito, Kentaro; Siddique, Md Shahjahan P; Kawano, Yumiko; Yamao, Fumiaki; Iwasaki, Hiroshi

    2014-08-01

    Fbh1, an F-box helicase related to bacterial UvrD, has been proposed to modulate homologous recombination in fission yeast. We provide several lines of evidence for such modulation. Fbh1, but not the related helicases Srs2 and Rqh1, suppressed the formation of crossover recombinants from single HO-induced DNA double-strand breaks. Purified Fbh1 in complex with Skp1 (Fbh1-Skp1 complex) inhibited Rad51-driven DNA strand exchange by disrupting Rad51 nucleoprotein filaments in an ATP-dependent manner; this disruption was alleviated by the Swi5-Sfr1 complex, an auxiliary activator of Rad51. In addition, the reconstituted SCFFbh1 complex, composed of purified Fbh1-Skp1 and Pcu1-Rbx1, displayed ubiquitin-ligase E3 activity toward Rad51. Furthermore, Fbh1 reduced the protein level of Rad51 in stationary phase in an F-box-dependent, but not in a helicase domain-independent manner. These results suggest that Fbh1 negatively regulates Rad51-mediated homologous recombination via its two putative, unrelated activities, namely DNA unwinding/translocation and ubiquitin ligation. In addition to its anti-recombinase activity, we tentatively suggest that Fbh1 might also have a pro-recombination role in vivo, because the Fbh1-Skp1 complex stimulated Rad51-mediated strand exchange in vitro after strand exchange had been initiated. PMID:25165823

  9. Multiple regulation of Rad51-mediated homologous recombination by fission yeast Fbh1.

    Yasuhiro Tsutsui

    2014-08-01

    Full Text Available Fbh1, an F-box helicase related to bacterial UvrD, has been proposed to modulate homologous recombination in fission yeast. We provide several lines of evidence for such modulation. Fbh1, but not the related helicases Srs2 and Rqh1, suppressed the formation of crossover recombinants from single HO-induced DNA double-strand breaks. Purified Fbh1 in complex with Skp1 (Fbh1-Skp1 complex inhibited Rad51-driven DNA strand exchange by disrupting Rad51 nucleoprotein filaments in an ATP-dependent manner; this disruption was alleviated by the Swi5-Sfr1 complex, an auxiliary activator of Rad51. In addition, the reconstituted SCFFbh1 complex, composed of purified Fbh1-Skp1 and Pcu1-Rbx1, displayed ubiquitin-ligase E3 activity toward Rad51. Furthermore, Fbh1 reduced the protein level of Rad51 in stationary phase in an F-box-dependent, but not in a helicase domain-independent manner. These results suggest that Fbh1 negatively regulates Rad51-mediated homologous recombination via its two putative, unrelated activities, namely DNA unwinding/translocation and ubiquitin ligation. In addition to its anti-recombinase activity, we tentatively suggest that Fbh1 might also have a pro-recombination role in vivo, because the Fbh1-Skp1 complex stimulated Rad51-mediated strand exchange in vitro after strand exchange had been initiated.

  10. Breast cancer CADx based on BI-RADS trade mark sign descriptors from two mammographic views

    In this study we compared the performance of computer aided diagnosis (CADx) algorithms based on Breast Imaging Reporting And Data System (BI-RADS trade mark sign ) descriptors from one or two views. To select cases for the study with different mediolateral (MLO) and craniocaudal (CC) view descriptors, we assessed the agreement in BI-RADS trade mark sign lesion descriptors, BI-RADS trade mark sign assessment, and subtlety ratings for 1626 cases from the Digital Database for Screening Mammogrpahy (DDSM) using kappa statistics. We used 115 mass cases with different descriptors for the two views to design linear discriminant analysis (LDA) based CADx algorithms. The CADx algorithms used BI-RADS trade mark sign descriptors and patient age as features. The algorithms based on BI-RADS trade mark sign descriptors from both the views performed marginally better than algorithms based on BI-RADS trade mark sign descriptors from a single view. A system that averaged the results of two classifiers trained separately on the MLO and CC views displayed the best performance (Az=0.920±0.027). Thus, some improvement in performance of BI-RADS trade mark sign based CADx algorithms may be achieved by combining information from two mammographic views

  11. Protective effect of the LevRad on treat of paracoccidioidomycosis

    Paracoccidioides brasiliensis is the agent of Paracoccidioidomycosis (PCM), the most prevalent deep mycosis of Latin America. The period of treat depend on the chemotherapeutic and the severity of disease and its administration not ensure the complete destruction of the fungus. The search for new alternatives is necessary. The aim of this study was to evaluate the protective effect of yeast cells of P. brasiliensis attenuated by gamma irradiation (LevRad) on therapeutic vaccination of BALB/c. The therapeutic potential of LevRad with or without fluconazole was assessed for the first time, intraperitoneally, in BALB/c, 60 days after intratracheal infection with a highly virulent non-irradiated P.brasiliensis isolate. The animals were divided in five experimental groups: uninfected (C-), infected (C+), infected treated with fluconazole (Inmed), infected treated with LevRad (InRad) and infected treated with fluconazole + LevRad (InRadMed). The organs (lungs, spleen and liver) were collected to analyze CFU (colony forming units) and histology. The sera were used to evaluate the immunization efficacy, and to assess IgG subtypes (IgG1, IgG2a, IgG2b, IgG3) and total IgG levels. There was significant decrease in the CFU counts of the lungs of InMed, InRadMed and InRad. No were visualized histopathological alterations in the organs of these groups, except in InRad there was granulomatous lesions unifocal, little and discrete. The levels of IgG and its subtypes IgG2a, IgG2b increased, probably due to the increase of cytokines that promote switching to these isotypes. These preliminary results can provide new prospect for immunotherapy of PCM, but it will be necessary new studies to evaluate administration dose and period treatment. (author)

  12. Rad21-cohesin haploinsufficiency impedes DNA repair and enhances gastrointestinal radiosensitivity in mice.

    Huiling Xu

    Full Text Available Approximately half of cancer-affected patients receive radiotherapy (RT. The doses delivered have been determined upon empirical experience based upon average radiation responses. Ideally higher curative radiation doses might be employed in patients with genuinely normal radiation responses and importantly radiation hypersensitive patients would be spared the consequences of excessive tissue damage if they were identified before treatment. Rad21 is an integral subunit of the cohesin complex, which regulates chromosome segregation and DNA damage responses in eukaryotes. We show here, by targeted inactivation of this key cohesin component in mice, that Rad21 is a DNA-damage response gene that markedly affects animal and cell survival. Biallelic deletion of Rad21 results in early embryonic death. Rad21 heterozygous mutant cells are defective in homologous recombination (HR-mediated gene targeting and sister chromatid exchanges. Rad21+/- animals exhibited sensitivity considerably greater than control littermates when challenged with whole body irradiation (WBI. Importantly, Rad21+/- animals are significantly more sensitive to WBI than Atm heterozygous mutant mice. Since supralethal WBI of mammals most typically leads to death via damage to the gastrointestinal tract (GIT or the haematopoietic system, we determined the functional status of these organs in the irradiated animals. We found evidence for GIT hypersensitivity of the Rad21 mutants and impaired bone marrow stem cell clonogenic regeneration. These data indicate that Rad21 gene dosage is critical for the ionising radiation (IR response. Rad21 mutant mice thus represent a new mammalian model for understanding the molecular basis of irradiation effects on normal tissues and have important implications in the understanding of acute radiation toxicity in normal tissues.

  13. Investigation of the influence of high humidity and exposure duration on the measurement results of radon concentration by means of PicoRad system in the CLOR calibration chamber

    PicoRad system based on activated charcoal collectors and liquid scintillation counter is one of the most popular passive methods of radon measurements which may be used both indoors and in other environments such as caves, tunnels, mines etc. It is well known that charcoal is also a very good adsorber of water vapor and it can reduce adsorption efficiency for radon. In PicoRad collectors, the charcoal is mixed with a dessicant to lower this effect. A series of expositions of PicoRad detectors was performed in a Central Laboratory for Radiological Protection (CLOR) radon calibration/climatic chamber to study the effect of high relative humidity on the airborne radon concentration measurements and the dependence of the results on the duration of exposure. The results obtained from the PicoRad system were referred to the mean concentrations delivered by an AlphaGUARD monitor, Genitron (GmbH), Germany. The main conclusions are the following: 1) the PicoRad system results are not affected by high relative humidity, including extreme values of 90-96%, for the duration of exposure up to ca. 24 h; 2) in the relative humidity range of 75-96% the correction coefficient linearly depends on the duration of exposure reaching a value of ca. 16 for 96 h exposure; 3) the PicoRad system delivers results corresponding better to the mean value of radon concentration in the last 6 h interval of exposure than that in the whole exposure duration. This finding is particularly important for the calibration of PicoRad collectors in the conditions of decreasing radon concentration due to radon decay. (author)

  14. The role of RAD51 in etoposide (VP16) resistance in small cell lung cancer

    Hansen, Lasse Tengbjerg; Lundin, Cecilia; Spang-Thomsen, Mogens;

    2003-01-01

    investigated DSB repair and cellular VP16 sensitivity of SCLC cells. VP16 sensitivity and RAD51, DNA-PK(cs), topoisomerase IIalpha and P-glycoprotein protein levels were determined in 17 SCLC cell lines. In order to unravel the role of RAD51 in VP16 resistance, we cloned the human RAD51 gene, transfected SCLC......Etoposide (VP16) is a potent inducer of DNA double-strand breaks (DSBs) and is efficiently used in small cell lung cancer (SCLC) therapy. However, acquired VP16 resistance remains an important barrier to effective treatment. To understand the underlying mechanisms for VP16 resistance in SCLC, we...

  15. Conduction electron spin resonance in the α-Yb1−xFexAlB4 (0 ⩽ x ⩽ 0.50) and α-LuAlB4 compounds

    β-YbAlB4 has become one of the most studied heavy fermion systems since its discovery due to its remarkable physical properties. This system is the first reported Yb-based heavy-fermion superconductor (HFS) for which the low-T superconducting state emerges from a non-fermi-liquid (NFL) normal state associated with quantum criticality Nakatsuji et al 2008 Nature 4 603. Additionally, it presents a striking and unprecedented electron spin resonance (ESR) signal which behaves as a conduction electron spin resonance (CESR) at high temperatures and acquires features of the Yb3+ local moment ESR at low temperatures. The latter, also named Kondo quasiparticles spin resonance (KQSR), has been defined as a 4f-ce strongly coupled ESR mode that behaves as a local probe of the Kondo quasiparticles in a quantum critical regime, Holanda et al 2011 Phys. Rev. Lett. 107 026402. Interestingly, β-YbAlB4 possesses a previously known structural variant, namely the α-YbAlB4, phase which is a paramagnetic Fermi liquid (FL) at low temperatures Macaluso et al 2007 Chem. Mater. 19 1918. However, it has been recently suggested that the α-YbAlB4 phase may be tuned to NFL behavior and/or magnetic ordering as the compound is doped with Fe. Here we report ESR studies on the α-Yb1−xFexAlB4 (0 ⩽ x ⩽ 0.50) series as well as on the reference compound α-LuAlB4. For all measured samples, the observed ESR signal behaves as a CESR in the entire temperature range (10 K ≲ T ≲ 300 K) in clear contrast with what has been observed for β-YbAlB4. This striking result indicates that the proximity to a quantum critical point is crucial to the occurrence of a KQSR signal. (paper)

  16. Evidence for linear response for the induction of mutations in human cells by x-ray exposures below 10 rads.

    Grosovsky, A J; Little, J B

    1985-01-01

    The induction of 6-thioguanine resistance (6TGR) was studied in continuous human lymphoblast cultures exposed to daily x-ray doses of 1, 2.5, 5, or 10 rads (1 rad = 0.01 gray) for periods up to 1 month. Samples were taken every 5 days for determinations of induced mutation frequency. Cells receiving daily doses of 1-10 rads showed a mutation frequency of 0.069 X 10(-6) 6TGR cell per rad, virtually identical to the value of 0.062 X 10(-6) 6TGR cell per rad determined for lymphoblasts receiving...

  17. Breast imaging reporting and data system (BI-RADS) lexicon for breast MRI: Interobserver variability in the description and assignment of BI-RADS category

    El Khoury, Mona, E-mail: monelkhoury@gmail.com [Centre Hospitalier Universitaire de Montréal, Breast Centre, Radiology Department, 3840 Rue Saint Urbain, Montréal, QC H2W1T8 (Canada); Lalonde, Lucie; David, Julie; Labelle, Maude [Centre Hospitalier Universitaire de Montréal, Breast Centre, Radiology Department, 3840 Rue Saint Urbain, Montréal, QC H2W1T8 (Canada); Mesurolle, Benoit [Centre Hospitalier Universitaire de McGill, Cedar Breast Centre, Radiology Department, 687 Pine Avenue West, Montreal, QC H3A1A1 (Canada); Trop, Isabelle [Centre Hospitalier Universitaire de Montréal, Breast Centre, Radiology Department, 3840 Rue Saint Urbain, Montréal, QC H2W1T8 (Canada)

    2015-01-15

    Highlights: • The use of BI-RADS lexicon in interpreting breast MRI examinations is beneficial. • Our study shows: (a) moderate to substantial agreement between observers and (b) better agreement in interpreting mass than non-mass enhancement (NME). • Careful analysis of the NME should be done to help detect cancer as early as possible. - Abstract: Purpose: To retrospectively evaluate interobserver variability between breast radiologists when describing abnormal enhancement on breast MR examinations and assigning a BI-RADS category using the Breast Imaging Reporting and Data System (BI-RADS) terminology. Materials and methods: Five breast radiologists blinded to patients’ medical history and pathologic results retrospectively and independently reviewed 257 abnormal areas of enhancement on breast MRI performed in 173 women. Each radiologist described the focal enhancement using BI-RADS terminology and assigned a final BI-RADS category. Krippendorff's α coefficient of agreement was used to asses interobserver variability. Results: All radiologists agreed on the morphology of enhancement in 183/257 (71%) lesions, yielding a substantial agreement (Krippendorff's α = 0.71). Moderate agreement was obtained for mass descriptors – shape, margins and internal enhancement – (α = 0.55, 0.51 and 0.45 respectively) and NME (non-mass enhancement) descriptors – distribution and internal enhancement – (α = 0.54 and 0.43). Overall substantial agreement was obtained for BI-RADS category assignment (α = 0.71). It was however only moderate (α = 0.38) for NME compared to mass (α = 0.80). Conclusion: Our study shows good agreement in describing mass and NME on a breast MR examination but a better agreement in predicting malignancy for mass than NME.

  18. Complementary Roles of Yeast Rad4p and Rad34p in Nucleotide Excision Repair of Active and Inactive rRNA Gene Chromatin▿

    Tremblay, Maxime; Teng, Yumin; Paquette, Michel; Waters, Raymond; Conconi, Antonio

    2008-01-01

    Nucleotide excision repair (NER) removes a plethora of DNA lesions. It is performed by a large multisubunit protein complex that finds and repairs damaged DNA in different chromatin contexts and nuclear domains. The nucleolus is the most transcriptionally active domain, and in yeast, transcription-coupled NER occurs in RNA polymerase I-transcribed genes (rDNA). Here we have analyzed the roles of two members of the xeroderma pigmentosum group C family of proteins, Rad4p and Rad34p, during NER ...

  19. Mammography, pathology and BI-RADS categorization in breast ductal carcinoma in situ

    Objective: To explore the mammographic features and value of breast imaging reporting and data system (BI-RADS) in ductal carcinoma-in-situ (DCIS). Methods: The mammography, positive predictive value of BI-RADS categorization, and pathology of DCIS in 30 patients were retrospectively analyzed. Results: Microcalcification was the dominant feature in DCIS and was sand-like, branching or pleomorphic (14 cases). Other features included mass (3) and architectural distortion (2). Mammography was normal in 11 patients. BI-RADS categories were 0 (8 cases), 2 (2 cases), 3 (2 cases), 4 (9 cases) and 5 (9 cases) with positive predictive value of 60.0%. Conclusion: The dominant mammogram feature of DCIS is microcalcification. The positive predictive value of BI-RADS categorization is low and should be complemented by other investigations. (authors)

  20. Variations of dose rate observed by MSL/RAD in transit to Mars

    Guo, Jingnan; Wimmer-Schweingruber, Robert F; Hassler, Donald M; Posner, Arik; Heber, Bernd; Köhler, Jan; Rafkin, Scot; Ehresmann, Bent; Appel, Jan K; Böhm, Eckart; Böttcher, Stephan; Burmeister, Sönke; Brinza, David E; Lohf, Henning; Martin, Cesar; Reitz, Günther

    2015-01-01

    Aims: To predict the cruise radiation environment related to future human missions to Mars, the correlation between solar modulation potential and the dose rate measured by the Radiation Assessment Detector (RAD) has been analyzed and empirical models have been employed to quantify this correlation. Methods: The instrument RAD, onboard Mars Science Laboratory's (MSL) rover Curiosity, measures a broad spectrum of energetic particles along with the radiation dose rate during the 253-day cruise phase as well as on the surface of Mars. With these first ever measurements inside a spacecraft from Earth to Mars, RAD observed the impulsive enhancement of dose rate during solar particle events as well as a gradual evolution of the galactic cosmic ray (GCR) induced radiation dose rate due to the modulation of the primary GCR flux by the solar magnetic field, which correlates with long-term solar activities and heliospheric rotation. Results: We analyzed the dependence of the dose rate measured by RAD on solar modulatio...

  1. Rad-hard Location and Attitude Module (R-LAM) Project

    National Aeronautics and Space Administration — R-LAM (Rad-hard Location and Attitude Module), promises a new generation of both integrated navigation modules and stand-alone navigation subsystems including...

  2. Wide Temperature Rad-Hard ASIC for Process Control of a Fuel Cell System Project

    National Aeronautics and Space Administration — Ridgetop Group developed a top-level design of a rad-hard application-specific integrated circuit (ASIC) for spacecraft power management that is functional over a...

  3. Sol-Rad Net Flux (L 1.0, 1.5, 2.0)

    National Aeronautics and Space Administration — SolRad-Net (Solar Radiation Network) is an established network of ground-based sensors providing high-frequency solar flux measurements in quasi-realtime to the...

  4. RadNet Map Interface for Near-Real-Time Radiation Monitoring Data

    U.S. Environmental Protection Agency — RadNet is a national network of monitoring stations that regularly collect air, precipitation, drinking water, and milk samples for analysis of radioactivity. The...

  5. The checkpoint Saccharomyces cerevisiae Rad9 protein contains a tandem tudor domain that recognizes DNA.

    Lancelot, Nathalie; Charier, Gaëlle; Couprie, Joël; Duband-Goulet, Isabelle; Alpha-Bazin, Béatrice; Quémeneur, Eric; Ma, Emilie; Marsolier-Kergoat, Marie-Claude; Ropars, Virginie; Charbonnier, Jean-Baptiste; Miron, Simona; Craescu, Constantin,; Callebaut, Isabelle; Gilquin, Bernard; Zinn-Justin, Sophie

    2007-01-01

    DNA damage checkpoints are signal transduction pathways that are activated after genotoxic insults to protect genomic integrity. At the site of DNA damage, 'mediator' proteins are in charge of recruiting 'signal transducers' to molecules 'sensing' the damage. Budding yeast Rad9, fission yeast Crb2 and metazoan 53BP1 are presented as mediators involved in the activation of checkpoint kinases. Here we show that, despite low sequence conservation, Rad9 exhibits a tandem tudor domain structurally...

  6. Sudden Telomere Lengthening Triggers a Rad53-dependent Checkpoint in Saccharomyces cerevisiae

    Viscardi, Valeria; Baroni, Enrico; Romano, Michele; Lucchini, Giovanna; Longhese, Maria Pia

    2003-01-01

    Telomeres are specialized functional complexes that ensure chromosome stability by protecting chromosome ends from fusions and degradation and avoiding chromosomal termini from being sensed as DNA breaks. Budding yeast Tel1 is required both for telomere metabolism and for a Rad53-dependent checkpoint responding to unprocessed double-strand breaks. We show that overexpression of a GAL1-TEL1 fusion causes transient telomere lengthening and activation of a Rad53-dependent...

  7. Multiple Rad5 activities mediate sister chromatid recombination to bypass DNA damage at stalled replication forks

    Minca, Eugen C; Kowalski, David

    2010-01-01

    DNA damage that blocks replication is bypassed in order to complete chromosome duplication and preserve cell viability and genome stability. Rad5, a PCNA polyubiquitin ligase and DNA-dependent ATPase in yeast, is orthologous to putative tumor suppressors and controls error-free damage bypass by an unknown mechanism. To identify the mechanism in vivo, we investigated the roles of Rad5 and analyzed the DNA structures that form during damage bypass at site-specific stalled forks present at repli...

  8. RadBall™ Technology Testing and MCNP Modeling of the Tungsten Collimator

    Farfán, Eduardo B.; Foley, Trevor Q.; Coleman, J. Rusty; Jannik, G. Timothy; Holmes, Christopher J.; Oldham, Mark; Adamovics, John; Stanley, Steven J.

    2010-01-01

    The United Kingdom’s National Nuclear Laboratory (NNL) has developed a remote, non-electrical, radiation-mapping device known as RadBall™, which can locate and quantify radioactive hazards within contaminated areas of the nuclear industry. RadBall™ consists of a colander-like outer shell that houses a radiation-sensitive polymer sphere. The outer shell works to collimate radiation sources and those areas of the polymer sphere that are exposed react, becoming increasingly more opaque, in propo...

  9. RadOnc: An Integrated Clinical Database and Information Retrieval System Implemented by HyperCard

    Michael, Patricia A.; Foxlee, R. Heath

    1989-01-01

    RadOnc is a prototype hypermedia program designed for the resident physician which integrates a radiation oncology clinical database with reference information. Basic and clinical science information relevant to radiation oncology with pertinent literature reviews are linked to patient records which contain a clinical summary of the presentation, treatment and results. RadOnc's features include a dictionary, search capability, navigational aids, information printing and archiving, and graphic...

  10. Chemogenetic profiling identifies RAD17 as synthetically lethal with checkpoint kinase inhibition.

    Shen, John Paul; Srivas, Rohith; Gross, Andrew; Li, Jianfeng; Jaehnig, Eric J; Sun, Su Ming; Bojorquez-Gomez, Ana; Licon, Katherine; Sivaganesh, Vignesh; Xu, Jia L; Klepper, Kristin; Yeerna, Huwate; Pekin, Daniel; Qiu, Chu Ping; van Attikum, Haico; Sobol, Robert W; Ideker, Trey

    2015-11-01

    Chemical inhibitors of the checkpoint kinases have shown promise in the treatment of cancer, yet their clinical utility may be limited by a lack of molecular biomarkers to identify specific patients most likely to respond to therapy. To this end, we screened 112 known tumor suppressor genes for synthetic lethal interactions with inhibitors of the CHEK1 and CHEK2 checkpoint kinases. We identified eight interactions, including the Replication Factor C (RFC)-related protein RAD17. Clonogenic assays in RAD17 knockdown cell lines identified a substantial shift in sensitivity to checkpoint kinase inhibition (3.5-fold) as compared to RAD17 wild-type. Additional evidence for this interaction was found in a large-scale functional shRNA screen of over 100 genotyped cancer cell lines, in which CHEK1/2 mutant cell lines were unexpectedly sensitive to RAD17 knockdown. This interaction was widely conserved, as we found that RAD17 interacts strongly with checkpoint kinases in the budding yeast Saccharomyces cerevisiae. In the setting of RAD17 knockdown, CHEK1/2 inhibition was found to be synergistic with inhibition of WEE1, another pharmacologically relevant checkpoint kinase. Accumulation of the DNA damage marker γH2AX following chemical inhibition or transient knockdown of CHEK1, CHEK2 or WEE1 was magnified by knockdown of RAD17. Taken together, our data suggest that CHEK1 or WEE1 inhibitors are likely to have greater clinical efficacy in tumors with RAD17 loss-of-function. PMID:26437225

  11. Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD in mice

    The aim of the present study was to assess recovery from hematopoietic and gastrointestinal damage by Ex-RAD, also known as ON01210.Na (4-carboxystyryl-4-chlorobenzylsulfone, sodium salt), after total body radiation. In our previous study, we reported that Ex-RAD, a small-molecule radioprotectant, enhances survival of mice exposed to gamma radiation, and prevents radiation-induced apoptosis as measured by the inhibition of radiation-induced protein 53 (p53) expression in cultured cells. We have expanded this study to determine best effective dose, dose-reduction factor (DRF), hematological and gastrointestinal protection, and in vivo inhibition of p53 signaling. A total of 500 mg/kg of Ex-RAD administered at 24 h and 15 min before radiation resulted in a DRF of 1.16. Ex-RAD ameliorated radiation-induced hematopoietic damage as monitored by the accelerated recovery of peripheral blood cells, and protection of granulocyte macrophage colony-forming units (GM-CFU) in bone marrow. Western blot analysis on spleen indicated that Ex-RAD treatment inhibited p53 phosphorylation. Ex-RAD treatment reduces terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay (TUNEL)-positive cells in jejunum compared with vehicle-treated mice after radiation injury. Finally, Ex-RAD preserved intestinal crypt cells compared with the vehicle control at 13 and 14 Gy. The results demonstrated that Ex-RAD ameliorates radiation-induced peripheral blood cell depletion, promotes bone marrow recovery, reduces p53 signaling in spleen and protects intestine from radiation injury. (author)

  12. Contribution à l'étude structurale par PY/CG-SM de la matière organique liée aux particules fines (0-50 µm dans quelques sols sous formations naturelles de longue durée au Burkina Faso

    Pallo, FJP.

    2011-01-01

    Full Text Available Contribution to the study by PY/GC-MS of organic matter linked to fine particles (0-50 µm in some soils under long-term natural formations in Burkina Faso. The study aims to enhance the knowledge on organic matter of Arenosols, Ferralsols, and Cambisols in Burkina Faso. It deals with the distribution of C and N in three particles size fractions and is focused on the structures of organic matter linked to the (0-50 µm fraction. The results showed that total organic matter was lower than 2% in all soil units. More than 70% of total carbon were held by the finest fraction. The main products released by PY/GC-MS technique of the (0-50 µm fraction were lignin derived compounds, non lignin derived aromatic compounds, carbohydrates derived compounds, fatty acids methyl esters and nitrogen derived compounds. The aliphatic compounds ranged from C12 to C18, C16 being the dominant one. The aliphatic compounds were negatively correlated with the aromatic compounds. A positive correlation was observed between the nitrogen derived compounds and the amounts of clay. On the other hand, the carbohydrates derived compounds were negatively correlated with clay particles. Furthermore, the study pointed out some different structures of lignin such as syringyl, guaiacyl, and p.hydrophenyl. Depending on the nature of wood (hard wood, soft wood and grasses, they reflected the composition of vegetation on the studied sites. Therefore, PY/GC-MS technique was efficient for structural characterization of low amounts of soil organic matter.

  13. Breast imaging reporting and data system (BI-RADS) US lexicon and final assessment category for solid breast masses: the rates of inter-and intraobserver agreement

    To evaluate the rates of inter-and intraobserver agreement of the BI-RADS US lexicon. Two radiologists reviewed 60 sonograms of solid breast masses to evaluate interobserver agreement. After four weeks, the radiologists reinterpreted the series to evaluate the intraobserver agreement. The radiologists described shape, orientation, margin, lesion boundary, echo pattern, posterior acoustic features and microcalcifications. Final assessment categories and management plans were suggested for each case. The rates of inter-and intraobserver agreements were measured by the use of kappa statistics. Interobserver agreement ranged from the highest for orientation (κ = 0.65) and shape (κ = 0.61) to the lowest for posterior acoustic features (κ = 0.42). For the final assessment categories (κ = 0.46) and management (κ = 0.49), interobserver agreement were moderate. Intraobserver agreement ranged from the highest for microcalcifications in mass (κ = 0.90, 0.82) and orientation (κ 0.87, 0.83) and the lowest for echo patterns (κ = 0.62, 0.57) and posterior acoustic features (κ = 0.59, 0.65). In the final assessment category and management, intraobserver agreements were substantial or nearly complete (κ = 0.65-0.83). There were variable raged inter-and intraobserver agreements in the description of the BI-RADS US lexicon of solid breast masses. Among them, margin and lesion boundary showed lower agreements. A modification of the BI-RADS US lexicon with more detailed guidelines, followed by continuous education, are suggested

  14. High-throughput polymorphism detection and genotyping in Brassica napus using next-generation RAD sequencing

    Bus Anja

    2012-06-01

    Full Text Available Abstract Background The complex genome of rapeseed (Brassica napus is not well understood despite the economic importance of the species. Good knowledge of sequence variation is needed for genetics approaches and breeding purposes. We used a diversity set of B. napus representing eight different germplasm types to sequence genome-wide distributed restriction-site associated DNA (RAD fragments for polymorphism detection and genotyping. Results More than 113,000 RAD clusters with more than 20,000 single nucleotide polymorphisms (SNPs and 125 insertions/deletions were detected and characterized. About one third of the RAD clusters and polymorphisms mapped to the Brassica rapa reference sequence. An even distribution of RAD clusters and polymorphisms was observed across the B. rapa chromosomes, which suggests that there might be an equal distribution over the Brassica oleracea chromosomes, too. The representation of Gene Ontology (GO terms for unigenes with RAD clusters and polymorphisms revealed no signature of selection with respect to the distribution of polymorphisms within genes belonging to a specific GO category. Conclusions Considering the decreasing costs for next-generation sequencing, the results of our study suggest that RAD sequencing is not only a simple and cost-effective method for high-density polymorphism detection but also an alternative to SNP genotyping from transcriptome sequencing or SNP arrays, even for species with complex genomes such as B. napus.

  15. BI-RADS CATEGORIZATION AND POSITIVE PREDICTIVE VALUE OF MAMMOGRAPHIC FEATURES

    2001-01-01

    Objective: To determine whether the categories defined in the Breast Imaging Reporting and Data System (BI-RADS) are useful predictors of malignancy. Methods: A total of 348 cases with benign and malignant breast diseases were collected. Mammographic and pathologic findings were reviewed. Mammograms of 348 cases were characterized according to BI-RADS descriptors and were categorized by the final assessment categories. Results: Of the all 348 patients, 232 (67%) were carcinomas. Significantly more masses with calcification and speculation were found in breast cancers than in benign breast diseases. BI-RADS final assessment categories were category 2 and 3 in 106 cases, in which 75% (79/106) were benign; category 4 and 5 in 242 cases, in which 85% (205/242) were carcinomas. BI-RADS categories 4 and 5 are useful predictors of relative likelihood of malignancy. The features with higher positive predictive values for carcinomas were irregular shape, indistinct or speculated margins, fine or linear calcification morphology, and regional calcification distribution. Conclusion: BI-RADS lexicon is successful in providing a standardized language for physicians to describe lesion morphology. BI-RADS category is useful for predicting the presence of malignancy.

  16. RadCon: A radiological consequence assessment model for environmental protection

    This paper highlights the development of a radiological consequences model (RadCon) for use in the Australian and South East Asian Region, the acquisition of available data for use with the model, and sensitivity analysis ability to target future research. RadCon is a simple easy to use model that assesses the radiological dose consequences to humans resulting from the short-term release of radionuclides to the environment and in the process provides the concentrations of the chosen radionuclides in the selected plants and animals. This way, environmental protection can be addressed. Internal and external exposures from the passing cloud and from radionuclides deposited on the ground can be assessed in humans, and given the required data also in animals. RadCon does not provide atmospheric dispersion and ground deposition estimates and requires input data from meteorological models or measured data. RadCon was tested in an international model inter-comparison program (BIOMASS) sponsored by the International Atomic Energy Agency and performed well. The model continued to evolve over the period of the exercise and the final estimates generated by RadCon were comparable to the test data. From this BIOMASS experience, a module has been added to RadCon to allow the viewing of concentrations of radionuclides in plant and animal products together with the generation of a 95% confidence interval for the estimates. (author)

  17. Overexpressed of RAD51 suppresses recombination defects: a possible mechanism to reverse genomic instability

    Schild, David; Wiese, Claudia

    2009-10-15

    RAD51, a key protein in the homologous recombinational DNA repair (HRR) pathway, is the major strand-transferase required for mitotic recombination. An important early step in HRR is the formation of single-stranded DNA (ss-DNA) coated by RPA (a ss-DNA binding protein). Displacement of RPA by RAD51 is highly regulated and facilitated by a number of different proteins known as the 'recombination mediators'. To assist these recombination mediators, a second group of proteins also is required and we are defining these proteins here as 'recombination co-mediators'. Defects in either recombination mediators or comediators, including BRCA1 and BRCA2, lead to impaired HRR that can genetically be complemented for (i.e. suppressed) by overexpression of RAD51. Defects in HRR have long been known to contribute to genomic instability leading to tumor development. Since genomic instability also slows cell growth, precancerous cells presumably require genomic restabilization to gain a growth advantage. RAD51 is overexpressed in many tumors, and therefore, we hypothesize that the complementing ability of elevated levels of RAD51 in tumors with initial HRR defects limits genomic instability during carcinogenic progression. Of particular interest, this model may also help explain the high frequency of TP53 mutations in human cancers, since wild-type p53 represses RAD51.

  18. Rad18 is required for functional interactions between FANCD2, BRCA2, and Rad51 to repair DNA topoisomerase 1-poisons induced lesions and promote fork recovery

    Tripathi, Kaushlendra; Mani, Chinnadurai; Clark, David W; Palle, Komaraiah

    2016-01-01

    Camptothecin (CPT) and its analogues are chemotherapeutic agents that covalently and reversibly link DNA Topoisomerase I to its nicked DNA intermediate eliciting the formation of DNA double strand breaks (DSB) during replication. The repair of these DSB involves multiple DNA damage response and repair proteins. Here we demonstrate that CPT-induced DNA damage promotes functional interactions between BRCA2, FANCD2, Rad18, and Rad51 to repair the replication-associated DSB through homologous recombination (HR). Loss of any of these proteins leads to equal disruption of HR repair, causes chromosomal aberrations and sensitizes cells to CPT. Rad18 appears to function upstream in this repair pathway as its downregulation prevents activation of FANCD2, diminishes BRCA2 and Rad51 protein levels, formation of nuclear foci of all three proteins and recovery of stalled or collapsed replication forks in response to CPT. Taken together this work further elucidates the complex interplay of DNA repair proteins in the repair of replication-associated DSB. PMID:26871286

  19. Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

    Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

    2006-03-01

    Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

  20. Extending RAD tag analysis to microbial ecology: a comparison between MultiLocus Sequence Typing and 2b-RAD to investigate Listeria monocytogenes genetic structure.

    Pauletto, Marianna; Carraro, Lisa; Babbucci, Massimiliano; Lucchini, Rosaria; Bargelloni, Luca; Cardazzo, Barbara

    2016-05-01

    The advent of next-generation sequencing (NGS) has dramatically changed bacterial typing technologies, increasing our ability to differentiate bacterial isolates. Despite it is now possible to sequence a bacterial genome in a few days and at reasonable costs, most genetic analyses do not require whole-genome sequencing, which also remains impractical for large population samples due to the cost of individual library preparation and bioinformatics. More traditional sequencing approaches, however, such as MultiLocus Sequence Typing (mlst) are quite laborious and time-consuming, especially for large-scale analyses. In this study, a genotyping approach based on restriction site-associated (RAD) tag sequencing, 2b-RAD, was applied to characterize Listeria monocytogenes strains. To verify the feasibility of the method, an in silico analysis was performed on 30 available complete genomes. For the same set of strains, in silico mlst analysis was conducted as well. Subsequently, 2b-RAD and mlst analyses were experimentally carried out on 58 isolates collected from food samples or food-processing sites. The obtained results demonstrate that 2b-RAD predicts mlst types and often provides more detailed information on population structure than mlst. Moreover, the majority of variants differentiating identical sequence type isolates mapped against accessory fragments, thus providing additional information to characterize strains. Although mlst still represents a reliable typing method, large-scale studies on molecular epidemiology and public health, as well as bacterial phylogenetics, population genetics and biosafety could benefit of a low cost and fast turnaround time approach such as the 2b-RAD analysis proposed here. PMID:26613186

  1. Neocarzinostatin-induced Rad51 nuclear focus formation is cell cycle regulated and aberrant in AT cells

    DNA double-stranded breaks are the most detrimental form of DNA damage and, if not repaired properly, may lead to an accumulation of chromosomal aberrations and eventually tumorigenesis. Proteins of the Rad51/Rad52 epitasis group are crucial for the recombinational repair of DNA double-stranded breaks, whereas the Rad50/NBS1/Mre11 nuclease complex is involved in both the recombinational and the end-joining repair of DNA double-stranded breaks. Herein, we demonstrate that the chemotherapeutic enediyne antibiotic neocarzinostatin induced Rad51, but not NBS1, nuclear focus formation in a cell- cycle-dependent manner. Furthermore, neocarzinostatin-induced Rad51 foci formation revealed a slower kinetic change in AT cells, but not in wild-type or NBS cells. In summary, our results suggest that neocarzinostatin induces Rad51 focus formation through an ATM- and cell-cycle-dependent, but NBS1-independent, pathway

  2. Yeast Rad5 Protein Required for Postreplication Repair Has a DNA Helicase Activity Specific for Replication Fork Regression

    Blastyák, András; Pintér, Lajos; Unk, Ildiko; Prakash, Louise; Prakash, Satya; Haracska, Lajos

    2007-01-01

    Summary Lesions in the template DNA strand block the progression of the replication fork. In the yeast Saccharomyces cerevisiae, replication through DNA lesions is mediated by different Rad6-Rad18-dependent means, which include translesion synthesis and a Rad5-dependent postreplicational repair pathway that repairs the discontinuities that form in the DNA synthesized from damaged templates. Although translesion synthesis is well characterized, little is known about the mechanisms that modulat...

  3. Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

    Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; Park, Beomseok; Shim, Yoonjung; Kim, Youngchang; Liu, Lili; van Houten, Bennett; He, Chuan; Ansari, Anjum; Min, Jung-Hyun

    2015-01-01

    The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivity arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.

  4. Metabolic suppressors of trimethoprim and ultraviolet light sensitivities of Saccharomyces cerevisiae rad6 mutants

    Dominant mutations at two newly identified loci, designated SRS1 and SRS2, that metabolically suppress the trimethoprim sensitivity of rad6 and rad18 strains, have been isolated from trimethorprim-resistant mutants arising spontaneously in rad6-1 rad18-2 strains of the yeast Saccharomyces cerevisiae. The SRS2 mutations also efficiently suppress the ultraviolet light sensitivity of the parent strains. They do not, however, suppress their sensitivity to ionizing radiation or their deficiency with respect to induced mutagenesis and sporulation. Such observations support the hypothesis that RAD6-dependent activities can be separated into two functionally distinct groups: a group of error-free repair activities that are responsible for a large amount of the radiation resistance of wild-type strains and also for their resistance to trimethoprim, and a group of error-prone activities that are responsible for induced mutagenesis and are also important in sporulation, but which account at best for only a very small amount of wild-type recovery

  5. Performance comparison of quantitative semantic features and lung-RADS in the National Lung Screening Trial

    Li, Qian; Balagurunathan, Yoganand; Liu, Ying; Schabath, Matthew; Gillies, Robert J.

    2016-03-01

    Background: Lung-RADS is the new oncology classification guideline proposed by American College of Radiology (ACR), which provides recommendation for further follow up in lung cancer screening. However, only two features (solidity and size) are included in this system. We hypothesize that additional sematic features can be used to better characterize lung nodules and diagnose cancer. Objective: We propose to develop and characterize a systematic methodology based on semantic image traits to more accurately predict occurrence of cancerous nodules. Methods: 24 radiological image traits were systematically scored on a point scale (up to 5) by a trained radiologist, and lung-RADS was independently scored. A linear discriminant model was used on the semantic features to access their performance in predicting cancer status. The semantic predictors were then compared to lung-RADS classification in 199 patients (60 cancers, 139 normal controls) obtained from the National Lung Screening Trial. Result: There were different combinations of semantic features that were strong predictors of cancer status. Of these, contour, border definition, size, solidity, focal emphysema, focal fibrosis and location emerged as top candidates. The performance of two semantic features (short axial diameter and contour) had an AUC of 0.945, and was comparable to that of lung-RADS (AUC: 0.871). Conclusion: We propose that a semantics-based discrimination approach may act as a complement to the lung-RADS to predict cancer status.

  6. Multiple Rad5 activities mediate sister chromatid recombination to bypass DNA damage at stalled replication forks.

    Minca, Eugen C; Kowalski, David

    2010-06-11

    DNA damage that blocks replication is bypassed in order to complete chromosome duplication and preserve cell viability and genome stability. Rad5, a PCNA polyubiquitin ligase and DNA-dependent ATPase in yeast, is orthologous to putative tumor suppressors and controls error-free damage bypass by an unknown mechanism. To identify the mechanism in vivo, we investigated the roles of Rad5 and analyzed the DNA structures that form during damage bypass at site-specific stalled forks present at replication origins. Rad5 mediated the formation of recombination-dependent, X-shaped DNA structures containing Holliday junctions between sister chromatids. Mutants lacking these damage-induced chromatid junctions were defective in resolving stalled forks, restarting replication, and completing chromosome duplication. Rad5 polyubiquitin ligase and ATPase domains both contributed to replication fork recombination. Our results indicate that multiple activities of Rad5 function coordinately with homologous recombination factors to enable replication template switch events that join sister chromatids at stalled forks and bypass DNA damage. PMID:20541998

  7. RadNotes: a novel software development tool for radiology education.

    Baxter, A B; Klein, J S; Oesterle, E V

    1997-01-01

    RadNotes is a novel software development tool that enables physicians to develop teaching materials incorporating text and images in an intelligent, highly usable format. Projects undertaken in the RadNotes environment require neither programming expertise nor the assistance of a software engineer. The first of these projects, Thoracic Imaging, integrates image teaching files, concise disease and topic summaries, references, and flash card quizzes into a single program designed to provide an overview of chest radiology. RadNotes is intended to support the academic goals of teaching radiologists by enabling authors to create, edit, and electronically distribute image-oriented presentations. RadNotes also supports the educational goals of physicians who wish to quickly review selected imaging topics, as well as to develop a visual vocabulary of corresponding radiologic anatomy and pathologic conditions. Although Thoracic Imaging was developed with the aim of introducing chest radiology to residents, RadNotes can be used to develop tutorials and image-based tests for all levels; create corresponding World Wide Web sites; and organize notes, images, and references for individual use. PMID:9153710

  8. Resolving RAD51C function in late stages of homologous recombination

    Kuznetsov Sergey G

    2007-06-01

    Full Text Available Abstract DNA double strand breaks are efficiently repaired by homologous recombination. One of the last steps of this process is resolution of Holliday junctions that are formed at the sites of genetic exchange between homologous DNA. Although various resolvases with Holliday junctions processing activity have been identified in bacteriophages, bacteria and archaebacteria, eukaryotic resolvases have been elusive. Recent biochemical evidence has revealed that RAD51C and XRCC3, members of the RAD51-like protein family, are involved in Holliday junction resolution in mammalian cells. However, purified recombinant RAD51C and XRCC3 proteins have not shown any Holliday junction resolution activity. In addition, these proteins did not reveal the presence of a nuclease domain, which raises doubts about their ability to function as a resolvase. Furthermore, oocytes from infertile Rad51C mutant mice exhibit precocious separation of sister chromatids at metaphase II, a phenotype that reflects a defect in sister chromatid cohesion, not a lack of Holliday junction resolution. Here we discuss a model to explain how a Holliday junction resolution defect can lead to sister chromatid separation in mouse oocytes. We also describe other recent in vitro and in vivo evidence supporting a late role for RAD51C in homologous recombination in mammalian cells, which is likely to be resolution of the Holliday junction.

  9. RadBall Technology Testing and MCNP Modeling of the Tungsten Collimator.

    Farfán, Eduardo B; Foley, Trevor Q; Coleman, J Rusty; Jannik, G Timothy; Holmes, Christopher J; Oldham, Mark; Adamovics, John; Stanley, Steven J

    2010-01-01

    The United Kingdom's National Nuclear Laboratory (NNL) has developed a remote, non-electrical, radiation-mapping device known as RadBall(™), which can locate and quantify radioactive hazards within contaminated areas of the nuclear industry. RadBall(™) consists of a colander-like outer shell that houses a radiation-sensitive polymer sphere. The outer shell works to collimate radiation sources and those areas of the polymer sphere that are exposed react, becoming increasingly more opaque, in proportion to the absorbed dose. The polymer sphere is imaged in an optical-CT scanner, which produces a high resolution 3D map of optical attenuation coefficients. Subsequent analysis of the optical attenuation matrix provides information on the spatial distribution of sources in a given area forming a 3D characterization of the area of interest. RadBall(™) has no power requirements and can be positioned in tight or hard-to reach locations. The RadBall(™) technology has been deployed in a number of technology trials in nuclear waste reprocessing plants at Sellafield in the United Kingdom and facilities of the Savannah River National Laboratory (SRNL). This study focuses on the RadBall(™) testing and modeling accomplished at SRNL. PMID:21617740

  10. RadBallTM Technology Testing and MCNP Modeling of the Tungsten Collimator

    Farfán, Eduardo B.; Foley, Trevor Q.; Rusty Coleman, J.; Jannik, G. Timothy; Holmes, Christopher J.; Oldham, Mark; Adamovics, John; Stanley, Steven J.

    2010-11-01

    The UK's National Nuclear Laboratory (NNL) has developed a remote, non-electrical, radiation-mapping device known as RadBallTM, which can locate and quantify radioactive hazards within contaminated areas of the nuclear industry. RadBallTM consists of a colander-like outer shell that houses a radiation-sensitive polymer sphere. The outer shell works to collimate radiation sources and those areas of the polymer sphere that are exposed react, becoming increasingly more opaque, in proportion to the absorbed dose. The polymer sphere is imaged in an optical-CT scanner, which produces a high resolution 3D map of optical attenuation coefficients. Subsequent analysis of the optical attenuation matrix provides information on the spatial distribution of sources in a given area forming a 3D characterization of the area of interest. RadBallTM has no power requirements and can be positioned in tight or hard-to reach locations. The RadBallTM technology has been deployed in a number of technology trials in nuclear waste reprocessing plants at Sellafield in the UK and facilities of the Savannah River National Laboratory (SRNL). This study focuses on the RadBallTM testing and modeling accomplished at SRNL.

  11. RadBall™ Technology Testing and MCNP Modeling of the Tungsten Collimator

    Farfán, Eduardo B.; Foley, Trevor Q.; Coleman, J. Rusty; Jannik, G. Timothy; Holmes, Christopher J.; Oldham, Mark; Adamovics, John; Stanley, Steven J.

    2010-01-01

    The United Kingdom’s National Nuclear Laboratory (NNL) has developed a remote, non-electrical, radiation-mapping device known as RadBall™, which can locate and quantify radioactive hazards within contaminated areas of the nuclear industry. RadBall™ consists of a colander-like outer shell that houses a radiation-sensitive polymer sphere. The outer shell works to collimate radiation sources and those areas of the polymer sphere that are exposed react, becoming increasingly more opaque, in proportion to the absorbed dose. The polymer sphere is imaged in an optical-CT scanner, which produces a high resolution 3D map of optical attenuation coefficients. Subsequent analysis of the optical attenuation matrix provides information on the spatial distribution of sources in a given area forming a 3D characterization of the area of interest. RadBall™ has no power requirements and can be positioned in tight or hard-to reach locations. The RadBall™ technology has been deployed in a number of technology trials in nuclear waste reprocessing plants at Sellafield in the United Kingdom and facilities of the Savannah River National Laboratory (SRNL). This study focuses on the RadBall™ testing and modeling accomplished at SRNL. PMID:21617740

  12. Dbl2 Regulates Rad51 and DNA Joint Molecule Metabolism to Ensure Proper Meiotic Chromosome Segregation.

    Polakova, Silvia; Molnarova, Lucia; Hyppa, Randy W; Benko, Zsigmond; Misova, Ivana; Schleiffer, Alexander; Smith, Gerald R; Gregan, Juraj

    2016-06-01

    To identify new proteins required for faithful meiotic chromosome segregation, we screened a Schizosaccharomyces pombe deletion mutant library and found that deletion of the dbl2 gene led to missegregation of chromosomes during meiosis. Analyses of both live and fixed cells showed that dbl2Δ mutant cells frequently failed to segregate homologous chromosomes to opposite poles during meiosis I. Removing Rec12 (Spo11 homolog) to eliminate meiotic DNA double-strand breaks (DSBs) suppressed the segregation defect in dbl2Δ cells, indicating that Dbl2 acts after the initiation of meiotic recombination. Analyses of DSBs and Holliday junctions revealed no significant defect in their formation or processing in dbl2Δ mutant cells, although some Rec12-dependent DNA joint molecules persisted late in meiosis. Failure to segregate chromosomes in the absence of Dbl2 correlated with persistent Rad51 foci, and deletion of rad51 or genes encoding Rad51 mediators also suppressed the segregation defect of dbl2Δ. Formation of foci of Fbh1, an F-box helicase that efficiently dismantles Rad51-DNA filaments, was impaired in dbl2Δ cells. Our results suggest that Dbl2 is a novel regulator of Fbh1 and thereby Rad51-dependent DSB repair required for proper meiotic chromosome segregation and viable sex cell formation. The wide conservation of these proteins suggests that our results apply to many species. PMID:27304859

  13. Improving societal acceptance of rad waste management policy decisions: an approach based on complex intelligence

    In today's context elaborate public participation exercises are conducted around the world to elicit and incorporate societal risk perceptions into nuclear policy Decision-Making. However, on many occasions, such as in the case of rad waste management, the society remains unconvinced about these decisions. This naturally leads to the questions: are techniques for incorporating societal risk perceptions into the rad waste policy decision making processes sufficiently mature? How could societal risk perceptions and legal normative principles be better integrated in order to render the decisions more equitable and convincing to society? Based on guidance from socio-psychological research this paper postulates that a critical factor for gaining/improving societal acceptance is the quality and adequacy of criteria for option evaluation that are used in the policy decision making. After surveying three rad waste public participation cases, the paper identifies key lacunae in criteria abstraction processes as currently practiced. A new policy decision support model CIRDA: Complex Intelligent Risk Discourse Abstraction model that is based on the heuristic of Risk-Risk Analysis is proposed to overcome these lacunae. CIRDA's functionality of rad waste policy decision making is modelled as a policy decision-making Abstract Intelligent Agent and the agent program/abstraction mappings are presented. CIRDA is then applied to a live (U.K.) rad waste management case and the advantages of this method as compared to the Value Tree Method as practiced in the GB case are demonstrated. (author)

  14. Physical and microstructural characterization of La{sub 0,60}Sr{sub 0,40}Co{sub 0,20}Fe{sub 0,80}O{sub 3-δ} and Ba{sub 0,50}Sr{sub 0,50}Co{sub 0,80}Fe{sub 0,20}O{sub 3-δ} ceramics; Caracterizacao fisica e microestrutural de ceramicas constituidas de La{sub 0,60}Sr{sub 0,40}Co{sub 0,20}Fe{sub 0,80}O{sub 3-δ} e Ba{sub 0,50}Sr{sub 0,50}Co{sub 0,80}Fe{sub 0,20}O{sub 3-δ}

    Bonturim, E.; Vargas, R.A.; Andreoli, M.; Chiba, R.; Seo, E.S.M., E-mail: ebonturim@ipen.br, E-mail: ravargas@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP/CCTM/SOFC), Sao Paulo, SP (Brazil). Centro de Ciencia e Tecnologia de Materiais. Lab. de Insumos e Componentes

    2012-07-01

    The La{sub 0,60}Sr{sub 0,40}Co{sub 0,20}Fe{sub 0,80}O{sub 3-δ} (LSCF) and Ba{sub 0,50}Sr{sub 0,50}Co{sub 0,80}Fe{sub 0,20}O{sub 3-δ} (BSCF) oxides are studied as cathodes in Solid Oxide Fuel Cell. The objective of this study is to characterize physically and microstructural these materials. The LSCF was synthesized by citrate technique and BSCF for citrates-EDTA, processed under the same conditions. The characterizations of ceramics were performed by X-ray diffraction, dilatometry, scanning electron microscopy and apparent density for Archimedes principle. According to the diffraction technique, confirmed the presence of single phases for LSCF to 800 deg C and BSCF to 900 deg C, with orthorhombic and cubic structures, respectively. For dilatometry were determined the sintering temperatures, near of 1050 deg C to BSCF and 1100 deg C to LSCF. The sintered micrographs at 1000, 1050 and 1100 deg C for 2 hours showed homogeneity microstructure, containing porosity and, attacked thermally, a homogeneous distribution of grains. Finally by bulk density, was estimated porosity between 20 and 30%. (author)

  15. Underwater Ranging

    S. P. Gaba

    1984-01-01

    Full Text Available The paper deals with underwater laser ranging system, its principle of operation and maximum depth capability. The sources of external noise and methods to improve signal-to-noise ratio are also discussed.

  16. Sensitization of rad mutants of Dictyostelium discoideum to ultraviolet light by postirradiation treatment with caffeine

    The extent of caffeine sensitization following ultraviolet light irradiation for various UV-sensitive strains and the parental resistant strain are compared. Several features of these results are to be noted. (i) With the exception of the M28 strain, the more sensitive the strain is to UV, the lesser the effect of post-irradiation treatment with caffeine. For example, the D10 with caffeine for the wt parental strain is 0.13 of that with no caffeine, whereas for the three most sensitive strains, γs-13 (radB), HPS73 (rad AradB), and HPS82 (rad AradC), this ratio is about 1.0. The slight desensitizing effect of caffeine with γs-13 is reproducible and was observed previously. (orig./AJ)

  17. Capabilities, Calibration, and Impact of the ISS-RAD Fast Neutron Detector

    Leitgab, Martin

    2015-01-01

    In the current NASA crew radiation health risk assessment framework, estimates for the neutron contributions to crew radiation exposure largely rely on simulated data with sizeable uncertainties due to the lack of experimental measurements inside the ISS. Integrated in the ISS-RAD instrument, the ISS-RAD Fast Neutron Detector (FND) will deploy to the ISS on one of the next cargo supply missions. Together with the ISS-RAD Charged Particle Detector, the FND will perform, for the first time, routine and precise direct neutron measurements inside the ISS between 0.5 and 80 MeV. The measurements will close the NASA Medical Operations Requirement to monitor neutrons inside the ISS and impact crew radiation health risk assessments by reducing uncertainties on the neutron contribution to crew exposure, enabling more efficient mission planning. The presentation will focus on the FND detection mechanism, calibration results and expectations about the FND's interaction with the mixed radiation field inside the ISS.

  18. Initial experience with optical-CT scanning of RadBall Dosimeters

    The RadBall dosimeter is a novel device for providing 3-D information on the magnitude and distribution of contaminant sources of unknown radiation in a given hot cell, glovebox, or contaminated room. The device is presently under evaluation by the National Nuclear Lab (NNL, UK) and the Savannah River National Laboratory (SRNL, US), for application as a diagnostic device for such unknown contaminants in the nuclear industry. A critical component of the technique is imaging the dose distribution recorded in the RadBall using optical-CT scanning. Here we present our initial investigations using the Duke Mid-sized Optical-CT Scanner (DMOS) to image dose distributions deposited in RadBalls exposed to a variety of radiation treatments.

  19. Development and application of the Chinese adult female computational phantom Rad-HUMAN

    Rad-HUMAN is a whole-body numerical phantom of a Chinese adult woman which contains 46 organs and tissues and was created by MCAM6 software using the color photographs of the Chinese Visible Human dataset. This dataset was obtained from a 22-year old Chinese female cadaver judged to represent normal human anatomy as much as possible. The density and elemental composition recommended in the ICRP Publication 89 and in the ICRU report 44 were assigned to the organ and tissue in Rad-HUMAN for radiation protection purpose. The last step was to implement the anatomical data into a Monte Carlo code. Rad-HUMAN contains more than 28.8 billion tiny volume units, which produces an accurately whole-body numerical phantom of a Chinese adult female

  20. Initial experience with optical-CT scanning of RadBall Dosimeters

    Oldham, M.; Clift, C.; Thomas, A.; Farfan, E.; Foley, T.; Jannik, T.; Adamovics J.; Holmes, C.; Stanley, S.

    2010-11-01

    The RadBall dosimeter is a novel device for providing 3-D information on the magnitude and distribution of contaminant sources of unknown radiation in a given hot cell, glovebox, or contaminated room. The device is presently under evaluation by the National Nuclear Lab (NNL, UK) and the Savannah River National Laboratory (SRNL, US), for application as a diagnostic device for such unknown contaminants in the nuclear industry. A critical component of the technique is imaging the dose distribution recorded in the RadBall using optical-CT scanning. Here we present our initial investigations using the Duke Mid-sized Optical-CT Scanner (DMOS) to image dose distributions deposited in RadBalls exposed to a variety of radiation treatments.

  1. BI-RADS update: mammography, breast ultrasound and magnetic resonance imaging of the breast; BI-RADS update: Mammographie, Brustultraschall und Kernspinmammographie

    Saleh, A.; Kurz, K.D.; Moedder, U. [Universitaetsklinikum Duesseldorf (Germany). Inst. fuer Diagnostische Radiologie

    2005-12-01

    The Breast Imaging Reporting and Data System (BI-RADS) is a quality assurance tool in breast evaluation. A breast imaging lexicon, which has been defined for mammography breast ultrasound and magnetic resonance imaging of the breast, standardizes terminology used in reporting findings on breast examinations. Every report ends with the assignment of a final assessment category to describe the risk of malignancy and recommend the action to be taken after the history and results of all breast examinations are taken into account. This article gives a short introduction to breast imaging lexica mammography, breast ultrasound, magnetic resonance of the breast and reviews the literature about the clinical usefulness of the BI-RADS. (orig.)

  2. Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans.

    McClendon, T Brooke; Sullivan, Meghan R; Bernstein, Kara A; Yanowitz, Judith L

    2016-05-01

    Homologous recombination (HR) repairs cytotoxic DNA double-strand breaks (DSBs) with high fidelity. Deficiencies in HR result in genome instability. A key early step in HR is the search for and invasion of a homologous DNA template by a single-stranded RAD-51 nucleoprotein filament. The Shu complex, composed of a SWIM domain-containing protein and its interacting RAD51 paralogs, promotes HR by regulating RAD51 filament dynamics. Despite Shu complex orthologs throughout eukaryotes, our understanding of its function has been most extensively characterized in budding yeast. Evolutionary analysis of the SWIM domain identified Caenorhabditis elegans sws-1 as a putative homolog of the yeast Shu complex member Shu2. Using a CRISPR-induced nonsense allele of sws-1, we show that sws-1 promotes HR in mitotic and meiotic nuclei. sws-1 mutants exhibit sensitivity to DSB-inducing agents and fail to form mitotic RAD-51 foci following treatment with camptothecin. Phenotypic similarities between sws-1 and the two RAD-51 paralogs rfs-1 and rip-1 suggest that they function together. Indeed, we detect direct interaction between SWS-1 and RIP-1 by yeast two-hybrid assay that is mediated by the SWIM domain in SWS-1 and the Walker B motif in RIP-1 Furthermore, RIP-1 bridges an interaction between SWS-1 and RFS-1, suggesting that RIP-1 facilitates complex formation with SWS-1 and RFS-1 We propose that SWS-1, RIP-1, and RFS-1 compose a C. elegans Shu complex. Our work provides a new model for studying Shu complex disruption in the context of a multicellular organism that has important implications as to why mutations in the human RAD51 paralogs are associated with genome instability. PMID:26936927

  3. Enhancing survival of mouse oocytes following chemotherapy or aging by targeting Bax and Rad51.

    Loro L Kujjo

    Full Text Available BACKGROUND: Therapeutic approaches to preserve fertility in females undergoing cancer treatments are currently ineffective. This is partly due to limited knowledge of the molecular mechanisms that injured germ cells elicit to repair damage and survive or to abort repair and activate biochemical pathways leading to death. So far, we know that following spontaneously occurring or drug-induced DNA damage, the efficiency of DNA repair is a critical determinant of the cell's fate. The protein encoded by the Rad51 gene is one of several components recruited for homologous recombination-dependent DNA double-strand break repair in both somatic cells and germ cells. Recently, we showed that microinjection of recombinant Rad51 into AKR/J mouse oocytes decreased the extent of spontaneous DNA double-strand breaks, suppressed apoptosis, and restored the developmental competence in AKR/J embryos. Herein we characterized the nature of chemotherapy-induced lesions in oocytes, and the associated individual components of the DNA damage sensor and repair apparatus. For comparison, we also assessed parallel spontaneous changes in aging oocytes. METHODS: Data collected were derived from: analysis of apoptosis; immunodepletion; oocyte microinjections; immunocytochemistry; immunofluorescence; and CHIP-like assays. RESULTS: Our data show that: (i DNA damage in oocytes can be induced by both chemotherapy and spontaneously by the aging process; (ii oocytes possess the machinery and capability for repairing such DNA damage; (iii Rad51 is a critical player in the repair of both chemotherapy-induced and spontaneously-sustained DNA damage; and (iv in response to damage, oocytes exhibit an inverse functional relationship between presence of Bax and activity of Rad51. CONCLUSION/SIGNIFICANCE: Our results establish Rad51 and/or Bax as potential candidates that can be targeted for development of individualized chemotherapeutic interventions that are effective, but minimal in

  4. Rad59-facilitated acquisition of Y' elements by short telomeres delays the onset of senescence.

    Dmitri Churikov

    2014-11-01

    Full Text Available Telomerase-negative yeasts survive via one of the two Rad52-dependent recombination pathways, which have distinct genetic requirements. Although the telomere pattern of type I and type II survivors is well characterized, the mechanistic details of short telomere rearrangement into highly evolved pattern observed in survivors are still missing. Here, we analyze immediate events taking place at the abruptly shortened VII-L and native telomeres. We show that short telomeres engage in pairing with internal Rap1-bound TG1-3-like tracts present between subtelomeric X and Y' elements, which is followed by BIR-mediated non-reciprocal translocation of Y' element and terminal TG1-3 repeats from the donor end onto the shortened telomere. We found that choice of the Y' donor was not random, since both engineered telomere VII-L and native VI-R acquired Y' elements from partially overlapping sets of specific chromosome ends. Although short telomere repair was associated with transient delay in cell divisions, Y' translocation on native telomeres did not require Mec1-dependent checkpoint. Furthermore, the homeologous pairing between the terminal TG1-3 repeats at VII-L and internal repeats on other chromosome ends was largely independent of Rad51, but instead it was facilitated by Rad59 that stimulates Rad52 strand annealing activity. Therefore, Y' translocation events taking place during presenescence are genetically separable from Rad51-dependent Y' amplification process that occurs later during type I survivor formation. We show that Rad59-facilitated Y' translocations on X-only telomeres delay the onset of senescence while preparing ground for type I survivor formation.

  5. RNA interference targeting silence Rad51 gene sensitizes cancer cells to irradiation

    Objective: To investigate whether RNA interference (RNAi) can targeting silence the Rad51gene thereby increase the radiosensitivity of cancer cells. Methods: Psilencer U6-1.0 vector expressing the short interference RNA (siRNA) silences the endogenous Rad51 gene of HT1080 cell line. RNAi effect was analyzed by Western blot; The radiobiology effect of targeting silencing Rad51 in HT1080 cell line was analyzed by colony forming assay and radiation-induced apoptosis method. Results: All three tested target sequences showed the RNA interference effect. Forty-eight hours after transient transfection, the endogenous Rad51 expression was reduced about 79.8%, 94.3% and 97.4% by sequence 1, 2 and 3, respectively. The radiation-induced Rad51 expression was also suppressed in silenced cells. Colony assay showed the survival fraction to be 80.5% , 78.6% 69.0% and 57.7% compared with control group after ir- radiation at 2, 4, 6 and 8 Gy (P=0.020). The radiation induced apoptosis in silencing group increased 1.03-, 1.43-, 1.19-, 1.29-, 1.33-fo1d 0, 6, 18, 24, and 48 hours after irradiation when compared with the control group (P=0.017). Conclusion: The endogenous expression of Rad51 as well as its radiation- induced up-regulation can be inhibited effectively by RNAi. Our study suggests that RNAi technique be a useful tool in cancer research and radiosensitization studies. (authors)

  6. PI-RADS classification. Structured reporting for MRI of the prostate; PI-RADS-Klassifikation. Strukturiertes Befundungsschema fuer die MRT der Prostata

    Roethke, Matthias; Schlemmer, H.P. [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Abt. fuer Radiologie; Blondin, D. [Universitaetsklinikum Duesseldorf (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Franiel, T. [Charite - Universitaetsmedizin Berlin, Campus Mitte (Germany). Inst. fuer Radiologie

    2013-03-15

    Purpose: To flesh out the ESUR guidelines for the standardized interpretation of multiparametric magnetic resonance imaging (mMRI) for the detection of prostate cancer and to present a graphic reporting scheme for improved communication of findings to urologists. Materials and Methods: The ESUR has recently published a structured reporting system for mMRI of the prostate (PI-RADS). This system involves the use of 5-point Likert scales for grading the findings obtained with different MRI techniques. The mMRI includes T2-weighted MRI, diffusion-weighted imaging, dynamic contrast-enhanced MRI, and MR spectroscopy. In a first step, the fundamentals of technical implementation were determined by consensus, taking into account in particular the German-speaking community. Then, representative images were selected by consensus on the basis of examinations of the three institutions. In addition, scoring intervals for an aggregated PI-RADS score were determined in consensus. Results: The multiparametric methods were discussed critically with regard to implementation and the current status. Criteria used for grading mMRI findings with the PI-RADS classification were concretized by succinct examples. Using the consensus table for aggregated scoring in a clinical setting, a diagnosis of suspected prostate cancer should be made if the PI-RADS score is 4 or higher ({>=} 10 points if 3 techniques are used or {>=} 13 points if 4 techniques are used). Finally, a graphic scheme was developed for communicating mMRI prostate findings. Conclusion: Structured reporting according to the ESUR guidelines contributes to quality assurance by standardizing prostate mMRI, and it facilities the communication of findings to urologists. (orig.)

  7. RadLex - German version: a radiological lexicon for indexing image and report information; RadLex - deutsche Version: Ein radiologisches Lexikon zur Indexierung von Bild- und Befunddaten

    Marwede, D.; Lobsien, D.; Kahn, T. [Universitaetsklinikum Leipzig (Germany). Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie; Daumke, P.; Marko, K.; Schulz, S. [Universitaetsklinikum Freiburg (Germany). Inst. fuer Medizinische Biometrie und Medizinische Informatik

    2009-01-15

    Purpose: Since 2003 the Radiological Society of North America (RSNA) has been developing a lexicon of standardized radiological terms (RadLex) intended to support the structured reporting of imaging observations and the indexing of teaching cases. The aim of this study was to translate the first version of the lexicon (1 - 2007) into German and to implement a language-independent online term browser. Materials and Methods: RadLex version 1 - 2007 contains 6303 terms in nine main categories. Two radiologists independently translated the lexicon using medical dictionaries. Terms translated differently were revised and translated by consensus. For the development of an online term browser, a text processing algorithm called morphosemantic indexing was used which splits up words into small semantic units and compares those units to language-specific subword thesauri. Results: In total 6240 of 6303 terms (99 %) were translated. Of those terms 3965 were German, 1893 were Latin, 359 were multilingual, and 23 were English terms that are also used in German and were therefore maintained. The online term browser supports a language-independent term search in RadLex (German/English) and other common medical terminology (e.g., ICD 10). The term browser displays term hierarchies and translations in different frames and the complexity of the result lists can be adapted by the user. Conclusion: RadLex version 1 - 2007 developed by the RSNA is now available in German and can be accessed online through a term browser with an efficient search function. This is an important precondition for the future comparison of national and international indexed radiological examination results and the interoperability between digital teaching resources. (orig.)

  8. Tfb5 Is Partially Dispensable for Rad26 Mediated Transcription Coupled Nucleotide Excision Repair in Yeast

    Ding, Baojin; Ruggiero, Christine; Chen, Xuefeng; Li, Shisheng

    2007-01-01

    Nucleotide excision repair (NER) is a conserved DNA repair mechanism capable of removing a variety of helix-distorting DNA lesions. A specialized NER pathway, called transcription coupled NER (TC-NER), refers to preferential repair in the transcribed strand of an actively transcribed gene. To be distinguished from TCR-NER, the genome-wide NER process is termed as global genomic NER (GG-NER). In Saccharomyces cerevisiae, GG-NER is dependent on Rad7, whereas TC-NER is mediated by Rad26, the hom...

  9. El radón: ¿riesgo para la salud?

    Juan Miguel Barros Dios

    2011-01-01

    El radón (Rn222) es un gas noble radiactivo que procede directamente del radio (Ra226) cuando este emite una partícula alfa (dos protones y dos neutrones) o núcleo de helio, y que a su vez se transforma en otro elemento radiactivo (Po218) al desprenderse de otra partícula alfa. Desde hace varias décadas se conoce su efecto como factor de riesgo del cáncer primario pulmonar, primero en mineros del uranio y posteriormente en la población general expuesta al radón residencial en hogares construi...

  10. A reliability-risk modelling of nuclear rad-waste facilities

    Rad-waste disposal systems of nuclear power sites are designed and operated to collect, delay, contain, and concentrate radioactive wastes from reactor plant processes such that on-site and off-site exposures to radiation are well below permissible limits. To assist the designer in achieving minimum release/exposure goals, a computerized reliability-risk model has been developed to simulate the rad-waste system. The objectives of the model are to furnish a practical tool for quantifying the effects of changes in system configuration, operation, and equipment, and for the identification of weak segments in the system design. Primarily, the model comprises a marriage of system analysis, reliability analysis, and release-risk assessment. Provisions have been included in the model to permit the optimization of the system design subject to constraints on cost and rad-releases. The system analysis phase involves the preparation of a physical and functional description of the rad-waste facility accompanied by the formation of a system tree diagram. The reliability analysis phase embodies the formulation of appropriate reliability models and the collection of model parameters. Release-risk assessment constitutes the analytical basis whereupon further system and reliability analyses may be warranted. Release-risk represents the potential for release of radioactivity and is defined as the product of an element's unreliability at time, t, and the radioactivity available for release in time interval, Δt. A computer code (RARISK) has been written to simulate the tree diagram of the rad-waste system. Reliability and release-risk results have been generated for cases which examined the process flow paths of typical rad-waste systems, the effects of repair and standby, the variations of equipment failure and repair rates, and changes in system configurations. The essential feature of this model is that a complex system like the rad-waste facility can be easily decomposed into its

  11. Improved Methodology Application for 12-Rad Analysis in a Shielded Facility at SRS

    The DOE Order 420.1 requires establishing 12-rad evacuation zone boundaries and installing Criticality Accident Alarm System (CAAS) per ANS-8.3 standard for facilities having a probability of criticality greater than 10-6 per year. The H-Canyon at the Savannah River Site (SRS) is one of the reprocessing facilities where SRS reactor fuels, research reactor fuels, and other fissile materials are processed and purified using a modified Purex process called H-Modified or HM Process. This paper discusses an improved methodology for 12-rad zone analysis and its implementation within this large shielded facility that has a large variety of criticality sources and scenarios

  12. RadSTraM: Radiological Source Tracking and Monitoring, Phase II Final Report

    Warren, Tracy A [ORNL; Walker, Randy M [ORNL; Hill, David E [ORNL; Gross, Ian G [ORNL; Smith, Cyrus M [ORNL; Abercrombie, Robert K [ORNL

    2008-12-01

    This report focuses on the technical information gained from the Radiological Source Tracking and Monitoring (RadSTraM) Phase II investigation and its implications. The intent of the RadSTraM project was to determine the feasibility of tracking radioactive materials in commerce, particularly International Atomic Energy Agency (IAEA) Category 3 and 4 materials. Specifically, Phase II of the project addressed tracking radiological medical isotopes in commerce. These categories of materials are susceptible to loss or theft but the problem is not being addressed by other agencies.

  13. Mapping of the Gynoecy in Bitter Gourd (Momordica charantia) Using RAD-Seq Analysis

    Hideo Matsumura; Norimichi Miyagi; Naoki Taniai; Mai Fukushima; Kazuhiko Tarora; Ayano Shudo; Naoya Urasaki

    2014-01-01

    Momordica charantia is a monoecious plant of the Cucurbitaceae family that has both male and female unisexual flowers. Its unique gynoecious line, OHB61-5, is essential as a maternal parent in the production of F1 cultivars. To identify the DNA markers for this gynoecy, a RAD-seq (restriction-associated DNA tag sequencing) analysis was employed to reveal genome-wide DNA polymorphisms and to genotype the F2 progeny from a cross between OHB61-5 and a monoecious line. Based on a RAD-seq analysis...

  14. Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1β production

    Roth, Susanne; Rottach, Andrea; Lotz-Havla, Amelie S.; Laux, Verena; Muschaweckh, Andreas; Gersting, Søren W.; Muntau, Ania C.; Hopfner, Karl-Peter; Jin, Lei; Vanness, Katelynd; Petrini, John H.J.; Drexler, Ingo; Leonhardt, Heinrich; Ruland, Jürgen

    2014-01-01

    Double-stranded DNA (dsDNA) in the cytoplasm triggers interleukin-1β (IL-1β) production as an anti-viral host response, and deregulation of the pathways involved can promote inflammatory disease. Here we report a direct cytosolic interaction between the DNA-damage sensor Rad50 and the innate immune adapter CARD9. Dendritic cell transfection with dsDNA or infection with a DNA virus induces the formation of dsDNA-Rad50-CARD9 signaling complexes for NF-κB activation and pro-IL-1β generation. Pri...

  15. Calibration of Big Bottle RAD H2O set-up for radon in water using HDPE bottles

    Glass bottles are generally employed for water sampling because glass is impervious to radon and is not lost during sample storage. On the other hand, glass is fragile and may break, so 1 L High Density PolyEthylene (HDPE) bottles (Thermo Scientific Nalgene) are tested in place of glass vessels employing Big Bottle RAD H2O device (Durridge Company) coupled with RAD7 monitor. The purpose of this calibration is to quantify radon loss during storage in HDPE bottles, evaluate possible radon uptake by known volume of desiccant (Drierite, granular CaSO4) and quantify radon interaction with the rubber and plastic parts of the experimental circuit. These processes have been separately investigated, performing proper experiments for the assessment of their influence on resulting radon data using seven series of solutions at known activity concentrations in the range from 27 to 194 Bq/L. Percent radon loss during storage in 1 L HDPE bottles has been estimated at 0.0045 min−1. Radon absorption by desiccant, expressed as ‘equivalent’ volume of Drierite is 0.673 ± 0.092 L and is somehow independent, within errors, from i) the amount of water already absorbed in Drierite, ii) a recirculation time greater than 30 min and iii) radon concentrations. Radon absorption/desorption from rubber and plastic parts of the experimental device has been assessed as a function of concentration gradient between the inner volume of the circuit and the pores of polymer's. A final algorithm accounting for the above described physical processes has been developed for long runs (2–3 h). A simplified calculation method for short measurements (30 min) is also provided. - Highlights: • Big Bottle RAD H2O set-up for measuring radon in water was calibrated. • Glass bottles were replaced with HDPE vessels because too fragile for water sampling. • Radon diffusion coefficient through HDPE was calculated. • Radon absorption by Drierite and polymers in the setup was quantified.

  16. Prostate MRI based on PI-RADS version 2: how we review and report.

    Steiger, Philipp; Thoeny, Harriet C

    2016-01-01

    Prostate imaging and interpretation is based on prostate imaging reporting and data system version 2 (PI-RADS™ v2) providing clinical guidelines for multiparametric magnetic resonance imaging (mpMRI) of the prostate. PI-RADS™ v2 aims to promote global standardisation, to diminish variation in the acquisition, interpretation and reporting of prostate mpMRI examinations and to improve detection, localisation, and risk stratification in patients with suspected cancer in treatment naïve prostate glands. It does not address detection of recurrence, progression during active surveillance and evaluation of other parts of the body.PI-RADS™ v2 improves and standardises communication between radiologists and urologists to detect or exclude the presence of significant prostate cancer with a high likelihood. Findings on mpMRI are assessed on a 5-point category scale based on the probability that a combination of findings on T2-weighted (T2w) sequences, diffusion-weighted MRI (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) correlates with the presence of a clinically significant prostate cancer at a particular location. PI-RADS assessment categories range from 1 to 5 with 5 being most likely to represent clinically significant prostate cancer. The dominant sequence to detect prostate cancer in the peripheral zone is DWI, whereas for tumour detection in the transition zone T2w is the most important sequence. DCE-MRI has been attributed a minor role and only qualitative assessment with presence or absence of focal enhancement is suggested. Up to four suspicious lesions of category 3, 4 and 5 are assigned on a sector map and the index lesion should be identified. PMID:27067275

  17. Mapping Natural and Man-made Radio Interference at the Moon: Wind Waves RAD2 Data

    MacDowall, R. J.; Hess, R. A.; Kaiser, M. L.; Farrell, W. M.

    2009-12-01

    The lunar surface is frequently identified as a preferred site for large, low-frequency (radio observatories. Compared to ground-based facilities limited to above 10 MHz by ionospheric absorption, the Moon has essentially no ionosphere. Observations of radio sources at frequencies below 100 kHz would be possible. Compared to a free-flying spacecraft constellation, the lunar surface provides a surface for deploying antennas, after which the antenna metrology is not an issue. Also compared to the spacecraft constellation, the moon offers a “backstop” that can block unwanted radio emissions from the sun or, for a far-side array, from man-made transmitters on Earth as well as terrestrial auroral radio emissions. We present an analysis of the Wind Waves RAD2 radio data set for the frequency range 1-14 MHz. These data, acquired from November 1994 through the present, document the radio bursts and terrestrial emissions observed by Wind along a complex trajectory that included passes very close to the Moon. Thus, we can build a statistical “map” of terrestrial radio emissions as a function of local time of the Moon relative to earth, the inclination of the moon’s orbit, and frequency. These data demonstrate that successful radio observations of cosmological sources from anywhere near Earth will be best accomplished by an observatory on the far-side of the Moon. The data also provide statistics regarding interference from solar radio emissions, including variations as a function of the solar cycle, with any observations requiring high sensitivity.

  18. Roles of Rad51 protein in homologous recombination in mammalian cells: relation with repair, replication and cell cycle

    Homologous recombination (HR) is a fundamental process, allowing a faithful repair. In mammalian, MmRAD51, which is the homologue of Saccharomyces cerevisiae ScRAD51 key protein for HR, is an essential gene. This work is based on the characterisation of viable hyper and hypo-recombinant cell lines specifically affected in the Rad51 pathway. By expressing wild type and dominant negative forms of MmRad51, we demonstrated that Rad51 pathway participates to the repair by HR to induced DNA damages. However, inhibition of the Rad 51 pathway does not affect cell viability, spontaneously or after irradiation, whereas, radiation induced HR is inhibited. In the presence of DNA damages during late S and G2/M phase, inhibition of Rad51 pathway induced chromosomal aberrations, leading to a transient arrest in mitosis. This arrest is associated with an increased of cell death. However, a fraction of cells can escape from this transient arrest by forming tetraploid cells, associated with an absence of chromalid separation. Thus, in response to impaired Rad51 pathway, mitotic checkpoints seems to play an essential role. In line with this, we showed that the essential function of Rad51 is p53-dependent, which is in agreement with the role of p53 in tetraploidy inhibition. Our results suggest that the Rad51 protein could participate to the control of mitotic checkpoints and thus to the maintenance of genetic stability. This function could involve other Rad51 partners such as the tumour suppressors BRCA1, BRCA2 and p53. (author)

  19. Diagnostic value of breast ultrasound in mammography BI-RADS 0 and clinically indeterminate or suspicious of malignancy breast lesions

    Dobrosavljević Aleksandar

    2016-01-01

    Full Text Available Background/Aim. Not only that ultrasound makes the difference between cystic and solid changes in breast tissue, as it was the case at the beginning of its use, but it also makes the differential diagnosis in terms of benign-malignant. The aim of this study was to assess the role of sonography in the diagnosis of palpable breast masses according to the American College of Radiology Ultrasonographic Breast Imaging Reporting and Data System (BI-RADS and to correlate the BI-RADS 4 and BI-RADS 5 category with pathohistological findings. Methods. A retrospective study was conducted with the breast sonograms of 30 women presented with palpable breast masses found to be mammography category BI-RADS 0 and ultrasonographic BI-RADS categories 4 and 5. The sonographic categories were correlated with pathohistological findings. Results. Surgical biopsy in 30 masses revealed: malignancy (56.7%, fibroadenoma (26.7%, fibrocystic dysplasia with/without atypia (10%, lipoma (3.3% and intramammary lymph node (3.3%. Correlation between BI-RADS categories and pathohistological findings was found (p < 0.05. All BI-RADS 5 masses were malignant, while in BI-RADS 4A category fibroadenomas dominated. A total of 53.8% of all benign lesions were found in women 49 years of age or younger as compared with 35.3% of all malignancies in this group (p < 0.05. Conclusion. Ultrasonography BI-RADS improved classification of breast masses. The ultrasound BI-RADS 4 (A, B, C and BI-RADS 5 lesions should be worked-up with biopsy.

  20. Rad Hard Imaging Array with Picosecond Timing Project

    National Aeronautics and Space Administration — For a wide range of remote sensing applications, there is a critical need to develop imaging arrays that simultaneously achieve high spatial resolution, high...

  1. Superconducting properties of single crystalline FeTe1-xSex (x = 0, 0.15, 0.25, 0.35, 0.40 and 0.50)

    In this paper we have grown single crystalline samples of Se-doped FeTe compound using self-flux technique and studied the structural and electrical transport properties of the as-grown crystals. The samples have been grown with compositions FeTe1-xSex (x = 0, 0.15, 0.25, 0.35, 0.40 and 0.50). The as-grown samples are then investigated for their structural and superconducting properties by means of X-ray diffraction and physical property measurements. The XRD results of powdered samples reveal a single (tetragonal) phase with space group symmetry P4/nmm for all the samples. The lattice parameters are observed to reduce with increase of Se-doping at Te-site. Highest Hc2(0) (∼180 T) value has been observed for FeTe0.5Se0.5 sample

  2. Alterações clínicolaboratoriais em pacientes com malária por Plasmodium vivax e deficiência de glicose-6-fosfato desidrogenase tratados com 0,50mg/kg/dia de primaquina

    Silva Mônica C.M.; Santos Eliane B.; Costa Elenild G.; S. Filho Manoel G.; Guerreiro João F.; Póvoa Marinete M

    2004-01-01

    O efeito adverso da primaquina na dose de 0,50mg/kg/dia foi investigado em onze pacientes com malária vivax (três com deficiência de glicose-6-fosfato desidrogenase). Alterações clínicas e laboratoriais indicaram hemólise aguda apenas nos enzimopênicos, o que fez com que o tratamento fosse interrompido. Nossos resultados sugerem a necessidade do emprego de um teste de triagem para a deficiência de G6PD em áreas endêmicas de malária vivax a fim de se evitar complicações causadas pelo uso da pr...

  3. Germline variants in MRE11/RAD50/NBN complex genes in childhood leukemia

    The MRE11, RAD50, and NBN genes encode proteins of the MRE11-RAD50-NBN (MRN) complex involved in cellular response to DNA damage and the maintenance of genome stability. In our previous study we showed that the germline p.I171V mutation in NBN may be considered as a risk factor in the development of childhood acute lymphoblastic leukemia (ALL) and some specific haplotypes of that gene may be associated with childhood leukemia. These findings raise important questions about the role of mutations in others genes of the MRN complex in childhood leukemia. The aim of this study was to answer the question whether MRE11 and RAD50 alterations may be associated with childhood ALL or AML. We estimated the frequency of constitutional mutations and polymorphisms in selected regions of MRE11, RAD50, and NBN in the group of 220 children diagnosed with childhood leukemias and controls (n=504/2200). The analysis was performed by specific amplification of region of interest by PCR and followed by multi-temperature single-strand conformation polymorphism (PCR-MSSCP) technique. We performed two molecular tests to examine any potential function of the detected the c.551+19G>A SNP in RAD50 gene. To our knowledge, this is the first analysis of the MRE11, RAD50 and NBN genes in childhood leukemia. The frequency of either the AA genotype or A allele of RAD50-rs17166050 were significantly different in controls compared to leukemia group (ALL+AML) (p<0.0019 and p<0.0019, respectively). The cDNA analysis of AA or GA genotypes carriers has not revealed evidence of splicing abnormality of RAD50 pre-mRNA. We measured the allelic-specific expression of G and A alleles at c.551+19G>A and the statistically significant overexpression of the G allele has been observed. Additionally we confirmed the higher incidence of the p.I171V mutation in the leukemia group (7/220) than among controls (12/2400) (p<0.0001). The formerly reported sequence variants in the RAD50 and MRE11 gene may not constitute a

  4. Design of a 9K illumina BeadChip for polar bears (Ursus maritimus) from RAD and transcriptome sequencing.

    Malenfant, René M; Coltman, David W; Davis, Corey S

    2015-05-01

    Single-nucleotide polymorphisms (SNPs) offer numerous advantages over anonymous markers such as microsatellites, including improved estimation of population parameters, finer-scale resolution of population structure and more precise genomic dissection of quantitative traits. However, many SNPs are needed to equal the resolution of a single microsatellite, and reliable large-scale genotyping of SNPs remains a challenge in nonmodel species. Here, we document the creation of a 9K Illumina Infinium BeadChip for polar bears (Ursus maritimus), which will be used to investigate: (i) the fine-scale population structure among Canadian polar bears and (ii) the genomic architecture of phenotypic traits in the Western Hudson Bay subpopulation. To this end, we used restriction-site associated DNA (RAD) sequencing from 38 bears across their circumpolar range, as well as blood/fat transcriptome sequencing of 10 individuals from Western Hudson Bay. Six-thousand RAD SNPs and 3000 transcriptomic SNPs were selected for the chip, based primarily on genomic spacing and gene function respectively. Of the 9000 SNPs ordered from Illumina, 8042 were successfully printed, and - after genotyping 1450 polar bears - 5441 of these SNPs were found to be well clustered and polymorphic. Using this array, we show rapid linkage disequilibrium decay among polar bears, we demonstrate that in a subsample of 78 individuals, our SNPs detect known genetic structure more clearly than 24 microsatellites genotyped for the same individuals and that these results are not driven by the SNP ascertainment scheme. Here, we present one of the first large-scale genotyping resources designed for a threatened species. PMID:25187336

  5. The Cohesin Subunit Rad21 Is Required for Synaptonemal Complex Maintenance, but Not Sister Chromatid Cohesion, during Drosophila Female Meiosis

    Lehner, Christian F.; Heidmann, Stefan K.

    2014-01-01

    Replicated sister chromatids are held in close association from the time of their synthesis until their separation during the next mitosis. This association is mediated by the ring-shaped cohesin complex that appears to embrace the sister chromatids. Upon proteolytic cleavage of the α-kleisin cohesin subunit at the metaphase-to-anaphase transition by separase, sister chromatids are separated and segregated onto the daughter nuclei. The more complex segregation of chromosomes during meiosis is thought to depend on the replacement of the mitotic α-kleisin cohesin subunit Rad21/Scc1/Mcd1 by the meiotic paralog Rec8. In Drosophila, however, no clear Rec8 homolog has been identified so far. Therefore, we have analyzed the role of the mitotic Drosophila α-kleisin Rad21 during female meiosis. Inactivation of an engineered Rad21 variant by premature, ectopic cleavage during oogenesis results not only in loss of cohesin from meiotic chromatin, but also in precocious disassembly of the synaptonemal complex (SC). We demonstrate that the lateral SC component C(2)M can interact directly with Rad21, potentially explaining why Rad21 is required for SC maintenance. Intriguingly, the experimentally induced premature Rad21 elimination, as well as the expression of a Rad21 variant with destroyed separase consensus cleavage sites, do not interfere with chromosome segregation during meiosis, while successful mitotic divisions are completely prevented. Thus, chromatid cohesion during female meiosis does not depend on Rad21-containing cohesin. PMID:25101996

  6. Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors

    Huiling Xu

    2014-12-01

    Full Text Available Loss of heterozygosity (LOH of the adenomatous polyposis coli (APC gene triggers a series of molecular events leading to intestinal adenomagenesis. Haploinsufficiency of the cohesin Rad21 influences multiple initiating events in colorectal cancer (CRC. We identify Rad21 as a gatekeeper of LOH and a β-catenin target gene and provide evidence that Wnt pathway activation drives RAD21 expression in human CRC. Genome-wide analyses identified Rad21 as a key transcriptional regulator of critical CRC genes and long interspersed element (LINE-1 or L1 retrotransposons. Elevated RAD21 expression tracks with reactivation of L1 expression in human sporadic CRC, implicating cohesin-mediated L1 expression in global genomic instability and gene dysregulation in cancer.

  7. Rad51 Expression in Nasopharyngeal Carcinoma and Its Association with Tumor Reduction: A Preliminary Study in Indonesia

    Cahyanti, Dian; Rachmadi, Lisnawati; Wulani, Vally; Adham, Marlinda

    2016-01-01

    Background: Overexpression of Rad51 protein in many tumor cells has been proven to increase radioresistance and can be related to the resistance of chemosensitivity of tumor cells. This preliminary study was conducted to determine the relationship between the Rad51 expression level in nasopharyngeal carcinoma and the response of the treatment based on the measurement of the tumor reduction. Methods: Thirteen cases of the NPCs were analyzed. The expression levels of the Rad51 were examined from the pretreatment biopsies. Furthermore, tumor reductions were determined based on the change in sum longest diameter of the nasopharyngeal CT-scan before and after therapy. Results: The expression level of the Rad51 was associated with the reduction of tumor mass. The P value was 0.049 and the correlation coefficient was 0.479. Conclusion: The tumor cells Rad51 expression levels may affect the tumor reduction of NPC after the therapy.

  8. RPA and Rad51 constitute a cell intrinsic mechanism to protect the cytosol from self DNA

    Wolf, Christine; Rapp, Alexander; Berndt, Nicole; Staroske, Wolfgang; Schuster, Max; Dobrick-Mattheuer, Manuela; Kretschmer, Stefanie; König, Nadja; Kurth, Thomas; Wieczorek, Dagmar; Kast, Karin; Cardoso, M. Cristina; Günther, Claudia; Lee-Kirsch, Min Ae

    2016-01-01

    Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent type I IFN activation. Mutations in the exonuclease TREX1 cause type I IFN-dependent autoinflammation and autoimmunity. We demonstrate that TREX1 is anchored within the outer nuclear membrane to ensure immediate degradation of ssDNA leaking into the cytosol. In TREX1-deficient fibroblasts, accumulating ssDNA causes exhaustion of RPA and Rad51 resulting in replication stress and activation of p53 and type I IFN. Thus, the ssDNA-binding capacity of RPA and Rad51 constitutes a cell intrinsic mechanism to protect the cytosol from self DNA. PMID:27230542

  9. BI-RADS CATEGORIZATION AND POSITIVE PREDICTIVE VALUE OF MAMMOGRAPHIC FEATURES

    TANG; Rui-ying

    2001-01-01

    [1]American College of Radiology (ACR). Breast imaging reporting and data system (BI-RADS) [M]. 3rd ed. Reston, VA: American College of Radiology, 1998.[2]Laura L, Andrea FA, Fredric BS, et al. The breast imaging reporting and data system: positive predictive value of mammographic features and final assessment categories [J]. AJR 1998; 171:35.[3]Susan GO, Nicole K, Carol R, et al. BI-RADS categorization as a predictor of malignancy [J]. Radiology 1999; 211:845.[4]Jay AB, Phyllis JK, Carey EF. Breast imaging reporting and data system standardized mammography lexicon: observer variability in lesion description [J]. AJR 1996; 166:773.[5]Berg WA, Campassi, Sexton MJ, et al. Analysis of sources of variation in mammographic interpretation [J]. Radiology 1997; 205:447.[6]Daniel BK. Standardized mammography reporting [J]. Radiologic Clinics of North America 1992; 30:257.[7]Jay AB, Phyllis JK, Joseph YL, et al. Breast cancer: prediction with artificial neural network based on BI-RADS standardized lexicon [J]. Radiology 1995; 196:817.[8]Berube M, Curpen B, Ugolini P, et al. Level of suspicion of a mammographic lesion: use of features defined by BI-RADS lexicon and correlation with large core breast biopsy [J]. Can Assoc Radiol J 1998; 49:223.

  10. Suppression of mutagenesis by Rad51D-mediated homologous recombination

    Hinz, J M; Tebbs, R S; Wilson, P F; Nham, P B; Salazar, E P; Nagasawa, H; Urbin, S S; Thompson, L H

    2005-11-15

    Homologous recombinational repair (HRR) restores chromatid breaks arising during DNA replication and prevents chromosomal rearrangements that can occur from the misrepair of such breaks. In vertebrates, five Rad51 paralogs are identified that contribute in a nonessential but critical manner to HRR efficiency. We constructed and characterized a Rad51D knockout cell line in widely studied CHO cells. The rad51d mutant (51D1) displays sensitivity to a wide spectrum of induced DNA damage, indicating the broad relevance of HRR to genotoxicity. Untreated 51D1 cells exhibit {approx}5-fold elevated chromosomal breaks, a 12-fold increased rate of hprt mutation, and 4- to 10-fold increased rates of gene amplification at the dhfr and CAD loci, respectively. These results explicitly show the quantitative importance of HHR in preventing these types genetic alterations, which are associated with carcinogenesis. Thus, HRR copes in an error-free manner with spontaneous DNA damage encountered during DNA replication, and Rad51D is essential for this fidelity.

  11. The Rad9 protein enhances survival and promotes DNA repair following exposure to ionizing radiation

    Following DNA damage cells initiate cell cycle checkpoints to allow time to repair sustained lesions. Rad9, Rad1, and Hus1 proteins form a toroidal complex, termed the 9-1-1 complex, that is involved in checkpoint signaling. 9-1-1 shares high structural similarity to the DNA replication protein proliferating cell nuclear antigen (PCNA) and 9-1-1 has been shown in vitro to stimulate steps of the repair process known as long patch base excision repair. Using a system that allows conditional repression of the Rad9 protein in human cell culture, we show that Rad9, and by extension, the 9-1-1 complex, enhances cell survival, is required for efficient exit from G2-phase arrest, and stimulates the repair of damaged DNA following ionizing radiation. These data provide in vivo evidence that the human 9-1-1 complex participates in DNA repair in addition to its previously described role in DNA damage sensing

  12. VirRAD - The virtual radiopharmacy - a virtual learning community in radiopharmacy

    VirRAD is a new research project funded by the Information Society Technologies programme of the Fifth RTD Framework Programme of the European Union. The aim of VirRAD is to develop an Internet-based virtual learning environment for Radiopharmacy which will facilitate learning and understanding in the speciality at all levels both within and outside the radiopharmaceutical community. The final structure of VirRAD is yet to be decided and will be determined by the needs and desires of its ultimate participants, however it is expected to include multimedia teaching modules for distance learning applications, 3-D simulations of specialised equipment and complex techniques used in radiopharmaceutical preparation and research as well as improved systems of peer-to-peer and student-to-tutor communication and information retrieval. To be as useful and effective as possible VirRAD needs ideas and suggestions from the Nuclear Medicine community. A mechanism for obtaining such input and feedback will be an integral part of the development process

  13. Reactive airways dysfunction syndrome (RADS): guidelines for diagnosis and treatment and insight into likely prognosis.

    Bardana, E J

    1999-12-01

    Reactive airways dysfunction syndrome (RADS) is defined as the sudden onset of asthma following a high level exposure to a corrosive gas, vapor, or fume. This variant of occupational asthma continues to generate controversy regarding the criteria for its diagnosis. There is also some disagreement as to the likely prognosis with this disorder. Currently, the diagnosis requires the assumption of normal premorbid pulmonary physiology and absence of bronchial hyperreactivity. Criteria for the diagnosis of RADS are discussed with a proposal for both major and minor criteria to increase the confidence of an accurate diagnosis. The pathology of RADS involves a primarily lymphocytic inflammatory response with some evidence of subepithelial thickening and fibrosis. Most patients with this condition who survive the short-term exposure to a toxicant recover completely without significant clinical or physiologic sequelae. The issue of low-level RADs remains controversial and problematic as a tenable diagnosis, and will require further careful investigation to evaluate the premise that chronic, low-level toxicants are capable of leading to such a condition. More likely, most of the cases which have been reported represent preexisting asthma and/or expressions of an atopic predisposition. PMID:10619325

  14. Influence of heat treatment temperatures on structural and magnetic properties of Sr{sub 0.50}Ca{sub 0.20}La{sub 0.30}Fe{sub 11.15}Co{sub 0.25}O{sub 19} hexagonal ferrites

    Yang, Yujie; Liu, Xiansong, E-mail: xiansongliu@ahu.edu.cn; Jin, Dali

    2014-09-01

    M-type ferrite Sr{sub 0.50}Ca{sub 0.20}La{sub 0.30}Fe{sub 11.15}Co{sub 0.25}O{sub 19} magnetic powders and magnets were prepared by a ceramic process. The phase identification of magnetic powders was performed by X-ray diffraction. At calcination temperatures ranging from 1170 to 1270 °C, the phase compositions of the magnetic powders consist of M-type hexaferrites together with small amount of impurity phases such as α-Fe{sub 2}O{sub 3}, LaFeO{sub 3} and CoFe{sub 2}O{sub 4}. At calcination temperatures above 1270 °C, single-phase M-type hexaferrites can be obtained. The microstructures of the magnets were investigated by field emission scanning electron microscopy. The particles appear in hexagonal plate-like shape and the particles are distributed homogeneously. The radial shrinkage of the magnets increases with the increase of calcination or sintering temperature. The magnetic properties of the magnets and magnetic powders were measured by a permanent magnetic measure equipment and a vibrating sample magnetometer, respectively. For high remanence, intrinsic coercivity, magnetic induction coercivity and maximum energy product, the optimized calcination and sintering temperatures are 1250 °C and 1190 °C, respectively. - Highlights: • Sr{sub 0.50}Ca{sub 0.20}La{sub 0.30}Fe{sub 11.15}Co{sub 0.25}O{sub 19} hexaferrites were prepared by a ceramic process. • At calcination temperatures above 1270 °C, single-phase M-type hexaferrites are obtained. • The radial shrinkage increases with the increase of calcination or sintering temperature. • The optimized calcination temperature is 1250 °C, the optimized sintering temperature is 1190 °C.

  15. El radón: ¿riesgo para la salud?

    Juan Miguel Barros Dios

    2011-12-01

    Full Text Available El radón (Rn222 es un gas noble radiactivo que procede directamente del radio (Ra226 cuando este emite una partícula alfa (dos protones y dos neutrones o núcleo de helio, y que a su vez se transforma en otro elemento radiactivo (Po218 al desprenderse de otra partícula alfa. Desde hace varias décadas se conoce su efecto como factor de riesgo del cáncer primario pulmonar, primero en mineros del uranio y posteriormente en la población general expuesta al radón residencial en hogares construidos sobre suelos de rocas ricas en uranio (U238, elemento inicial de la cadena de degradación radiactiva de la que procede el radón. Áreas geológicamente constituidas por granitos o pizarras, como son las de gran parte de Galicia y todo el noroeste y oeste de la península ibérica, han sido catalogadas como de alto riesgo de exhalación de radón al interior de edificios y domicilios. En numerosos países de América y Europa existen desde hace varios lustros, políticas de prevención del cáncer pulmonar en aquellas zonas de riesgo basadas en programas de reducción de radón en los domicilios y edificios públicos. Desde finales de los años 80, la radiación alfa procedente del radón y sus descen- dientes de vida media corta han sido clasificados como agentes cancerígenos por la Internacional Agency of Research on Cancer (Lyon, 1988 y el Nacional Research Council (BEIR IV, 1988, constituyendo la segunda causa de cáncer pulmonar después del tabaco, y responsable del 10 al 15 % de todas las muertes por esa neoplasia. Estudios realizados en Galicia confirman esta evidencia, con riesgos de 2 a 3 en expuestos a concentraciones del gas en domicilios y la responsabilidad directa del 9% de todos los casos de cáncer pulmonar del área estudiada y una interacción radón/tabaco que multiplica por 45 el riesgo.

  16. Is the BI-RADS Categorization Valuable for Nonpalpable Breast Lesions in Chinese Women?

    Zhongzhao Wang; Baoning Zhang; Jing Li; Liming Jiang

    2005-01-01

    OBJECTIVE To evaluate the feasibility of the Breast Imaging Reporting and Data System (BI-RADS) in the categorization of nonpalpable breast lesions (NPBLs) and to determine its value in aiding decision-making for biopsy in a Chinese population.METHODS One hundred and seventy-four nonpalpable breast lesions in 155 female patients examined by mammography were retrospectively categorized according to the BI-RAD System, 4th edition, which was established by the American College of Radiology (ACR). All the lesions were diagnosed by a histopathological analysis after mammographically guided wire-localization biopsy.RESULTS The 174 localizations yielded 125 (71.8%) benign lesions and 49 (28.2%) cancers, including 14 (28.6%) ductal carcinomas in situ and 35 (71.4%) invasive cancers. The overall positive predictive value (PPV)for cancer was 28.2% (49/174). After categorization according to the BI-RAD System, there were 12 category 2, 59 category 3, 83 category 4 and 20 category 5 lesions. The PPV for cancer for each category were 0% (0of 12 lesions) in category 2, 3.4% (2 of 59 lesions) in category 3, 37.3%(31 of 83 lesions) in category 4 and 80.0% (16 of 20 lesions) in category 5.CONCLUSION It is concluded that BI-RADS is valuable for the categorization of nonpalpable breast lesions in our Chinese popuiation. This system greatly improved the diagnostic specificity of nonpalpable breast lesions and was feasible in aiding decision-making for biopsy. It is suggested that nonpalpable breast lesions in categories BI-RADS 4 and 5should receive a biopsy because these lesions have a moderate and high positive predictive value for cancer.

  17. Using RAD-seq to recognize sex-specific markers and sex chromosome systems.

    Gamble, Tony

    2016-05-01

    Next-generation sequencing methods have initiated a revolution in molecular ecology and evolution (Tautz et al. ). Among the most impressive of these sequencing innovations is restriction site-associated DNA sequencing or RAD-seq (Baird et al. ; Andrews et al. ). RAD-seq uses the Illumina sequencing platform to sequence fragments of DNA cut by a specific restriction enzyme and can generate tens of thousands of molecular genetic markers for analysis. One of the many uses of RAD-seq data has been to identify sex-specific genetic markers, markers found in one sex but not the other (Baxter et al. ; Gamble & Zarkower ). Sex-specific markers are a powerful tool for biologists. At their most basic, they can be used to identify the sex of an individual via PCR. This is useful in cases where a species lacks obvious sexual dimorphism at some or all life history stages. For example, such tests have been important for studying sex differences in life history (Sheldon ; Mossman & Waser ), the management and breeding of endangered species (Taberlet et al. ; Griffiths & Tiwari ; Robertson et al. ) and sexing embryonic material (Hacker et al. ; Smith et al. ). Furthermore, sex-specific markers allow recognition of the sex chromosome system in cases where standard cytogenetic methods fail (Charlesworth & Mank ; Gamble & Zarkower ). Thus, species with male-specific markers have male heterogamety (XY) while species with female-specific markers have female heterogamety (ZW). In this issue, Fowler & Buonaccorsi () illustrate the ease by which RAD-seq data can generate sex-specific genetic markers in rockfish (Sebastes). Moreover, by examining RAD-seq data from two closely related rockfish species, Sebastes chrysomelas and Sebastes carnatus (Fig. ), Fowler & Buonaccorsi () uncover shared sex-specific markers and a conserved sex chromosome system. PMID:27213697

  18. Effects of the rad52 gene on recombination in Saccharomyces cerevisiae. [Comparison of. gamma. -, uv-induced meiotic and spontaneous mitotic recombination

    Prakash, S.; Prakash, L.; Burke, W.; Montelone, B.A.

    1979-01-01

    Effects of the rad52 mutation in Saccharomyces cerevisiae on meiotic, ..gamma..-ray-induced, uv-induced, and spontaneous mitotic recombination were studied. The rad52/rad52 diploids undergo premeiotic DNA synthesis; sporulation occurs but inviable spores are produced. Intra- and intergenic recombination during meiosis were examined in cells transferred from sporulation medium to vegetative medium at different time intervals. No intragenic recombination was observed at the hisl-1/hisl-315 and trp5-2/trp5-48 heteroalleles. Gene-centromere recombination was also not observed in rad52/rad52 diploids. No ..gamma..-ray-induced intragenic mitotic recombination is seen in rad52/rad52 diploids and uv-induced intragenic recombination is greatly reduced. However, spontaneous mitotic recombination is not similarly affected. The RAD52 gene thus functions in recombination in meiosis and in ..gamma..-ray and uv-induced mitotic recombination but not in spontaneous mitotic recombination.

  19. Enhanced multiferroic properties in (1–y)BiFeO3–yNi0.50Cu0.05Zn0.45Fe2O4 composites

    Multiferroic composites (1–y)BiFeO3–yNi0.50Cu0.05Zn0.45Fe2O4 (y=0.0, 0.1, 0.2, 0.3 and 0.4) are synthesized by the standard solid state reaction method. The X-ray diffraction analysis affirms the formation of both the component phases and also reveals that there is no chemical reaction between them. From the energy-dispersive X-ray spectroscopy study it is observed that the percentage of the elements in the component phases is well consistent with the nominal composition of the composites. Field Emission Scanning Electron Microscopy analysis shows almost homogeneous mixture of the two phases. The real part of the initial permeability increases (up to 67%) and the loss decreases with the ferrite content in the composites which is important in application point of view. Dielectric constant (ε′), loss tangent and AC conductivity are measured as a function of frequency at room temperature. The highest ε′ is obtained for 0.6BiFeO3–0.4Ni0.50Cu0.05Zn0.45Fe2O4 composite. The dielectric dispersion at lower frequency (<105 Hz) is due to the interfacial polarization. The complex impedance spectroscopy is used to correlate between the electrical properties of the studied samples with their microstructures. Two semicircular arcs corresponding to both grain and grain boundary contribution to electrical properties have been observed in all the studied samples. The maximum magnetoelectric voltage coefficient is found to be ∼38 mV cm−1 Oe−1 for the composite with 80% ferroelectric+20% ferrite phases. The present composite might be a promising candidate as multiferroic materials showing effective electric and magnetic properties. - Highlights: • XRD shows coexistance of ferroelectric and ferrimagnetic phases and no third phase. • The multiferroic composites show enhanced initial permeability and low loss. • Dielectric constant exhibits excellent high frequency stability. • Enhanced ME effect (∼38 mVcm−1Oe−1) is observed for 0.8BFO–0.2NCZFO composite

  20. Preparation and Characterization of (K0.5Na0.50.94-2xLi0.06SrxNb0.98Sb0.02O3 Lead-free Piezoelectric Ceramics

    CHU Rui-Qing, HAO Ji-Gong, XU Zhi-Jun, ZANG Guo-Zhong

    2010-07-01

    Full Text Available Lead-free (K0.5Na0.50.94-2xLi0.06SrxNb0.98Sb0.02O3 (KNLSN-Srx; x=0-0.03 piezoelectric ceramics were prepared by conventional solid-state sintering process. The sintering characteristic, the microstructure, dielectric, piezoelectric and ferroelectric properties of KNLSN-Srx ceramics were investigated. XRD results show that all samples exhibite a pure perovskite phase with tetragonal symmetry, indicating that the Sr2+ has diffused into the KNLSN lattices to form a solid solution. The grain size of KNLSN-Srx ceramics was increased with the increasing of Sr-doping level. The proper sintering temperature of KNLSN-Srx ceramics shifted to higher temperature with increasing the content of Sb. Higher d33 and kp, lower tanδ and Qm were obtained as Li, Sr and Sb were added into KNN ceramics. The comprehensive good properties of doped (K0.5Na0.5NbO3 ceramics were obtained when Sr content was 2mol% (d33=130pC/N, kp=34.5%, tanδ=4.2%.

  1. Highly thermostable RadA protein from the archaeon Pyrococcus woesei enhances specificity of simplex and multiplex PCR assays.

    Stefanska, Aleksandra; Gaffke, Lidia; Kaczorowska, Anna-Karina; Plotka, Magdalena; Dabrowski, Slawomir; Kaczorowski, Tadeusz

    2016-05-01

    The radA gene of the hyperthermophilic archaeon Pyrococcus woesei (Thermococcales) was cloned and overexpressed in Escherichia coli. The 1050-bp gene codes for a 349-amino-acid polypeptide with an M r of 38,397 which shows 100 % positional amino acid identity to Pyrococcus furiosus RadA and 27.1 % to the E. coli RecA protein. Recombinant RadA was overproduced in Escherichia coli as a His-tagged fusion protein and purified to electrophoretic homogeneity using a simple procedure consisting of ammonium sulfate precipitation and metal-affinity chromatography. In solution RadA exists as an undecamer (11-mer). The protein binds both to ssDNA and dsDNA. RadA has been found to be highly thermostable, it remains almost unaffected by a 4-h incubation at 94 °C. The addition of the RadA protein to either simplex or multiplex PCR assays, significantly improves the specificity of DNA amplification by eliminating non-specific products. Among applications tested the RadA protein proved to be useful in allelic discrimination assay of HADHA gene associated with long-chain 3-hydroxylacyl-CoA dehydrogenase deficiency that in infancy may lead to hypotonia, serious heart and liver problems and even sudden death. PMID:26337425

  2. Radón y sus efectos en la salud en trabajadores de minas de uranio

    Gonzalo Aicardi-Carrillo

    2015-03-01

    Full Text Available Introducción: El radón es un gas presente en subsuelo, especialmente en minas de uranio, que produce consecuencias sobre la salud, entre las que destaca el cáncer de pulmón. En EEUU es la segunda causa de mortalidad por esta enfermedad. Pese a la fuerte relación causal no existe normativa específica europea de regulación en mineros. Objetivos: Identificar el efecto del radón y sus derivados sobre la salud de los trabajadores de minas de uranio; describir la asociación entre exposición a radón y a otros minerales sobre la salud y asociación entre radón y consumo de tabaco. Metodología: Realizamos una revisión bibliográfica de literatura publicada entre 2007 y 2014, en bases de datos biomédicas, utilizando los criterios de inclusión y exclusión previamente establecidos. Resultados: Se revisan 32 artículos, encontrando un aumento significativo de cáncer pulmonar (SMR-2.03, IC95% 1.96-2.10, incluso a dosis bajas (300-WLM así como otros cánceres (laringe, gástrico, hepático y leucemia y enfermedades cerebrovasculares, controlando posibles factores de confusión (tabaco, silicosis, cuarzo y arsénico no encontrando relación significativa ni sinergias. Conclusión: Existe asociación entre la exposición al radón y cáncer pulmonar en minas de uranio, con un periodo medio de latencia de 20 años, determinado por la dosis de radón y el tiempo de exposición. No se ha demostrado riesgo de desarrollar otros tipos de tumores, y los estudios que lo sugieren son poco consistentes.

  3. Further evidence for the contribution of the RAD51C gene in hereditary breast and ovarian cancer susceptibility.

    Vuorela, Mikko; Pylkäs, Katri; Hartikainen, Jaana M; Sundfeldt, Karin; Lindblom, Annika; von Wachenfeldt Wäppling, Anna; Haanpää, Maria; Puistola, Ulla; Rosengren, Annika; Anttila, Maarit; Kosma, Veli-Matti; Mannermaa, Arto; Winqvist, Robert

    2011-12-01

    RAD51C, a RAD51 paralogue involved in homologous recombination, is a recently established Fanconi anemia and breast cancer predisposing factor. In the initial report, RAD51C mutations were shown to confer a high risk for both breast and ovarian tumors, but most of the replication studies published so far have failed to identify any additional susceptibility alleles. Here, we report a full mutation screening of the RAD51C gene in 147 Finnish familial breast cancer cases and in 232 unselected ovarian cancer cases originating from Finland and Sweden. In addition, in order to resolve whether common RAD51C SNPs are risk factors for breast cancer, we genotyped five tagging single nucleotide polymorphisms, rs12946522, rs304270, rs304283, rs17222691, and rs28363312, all located within the gene, from 993 Finnish breast cancer cases and 871 controls for cancer associated variants. Whereas, none of the studied common SNPs associated with breast cancer susceptibility, mutation analysis revealed two clearly pathogenic alterations. RAD51C c.-13_14del27 was observed in one familial breast cancer case and c.774delT in one unselected ovarian cancer case, thus confirming that RAD51C mutations are implicated in breast and ovarian cancer predisposition, although their overall frequency seems to be low. Independent identification of the very recently reported RAD51C c.774delT mutation in yet another patient originating from Sweden suggests that it might be a recurrent mutation in that population and should be studied further. The reliable estimation of the clinical implications of carrying a defective RAD51C allele still requires the identification of additional mutation positive families. PMID:21750962

  4. Electron dosimetry in irradiation processing with rad-hard diodes

    This work had the aim of the development of dosimetric systems based on Si special diodes, resistant to radiation damage to online monitoring of irradiation processing using 1.5 MeV electrons energy and for relative dosimetry and clinical electron beam scanning within an energy range of 6 MeV up to 21 MeV. The diodes used were produced by Float Zone standard (FZ), Magnetic Czochralski (MCz) and epitaxy growth (EPI) methods. In order to use the diodes as detectors, they were fixed on alumina base to allow the connection of the polarization electrodes and the signals extraction. After the diode assembly on the base, each one was housed in a black acrylic probe with aluminized Mylar® window and LEMO® connector. With the devices operating in photovoltaic mode, the integration of the current signals as a function of irradiation time allowed obtain the charge produced in the sensitive volume of each diode irradiated. The electron accelerator used for high doses irradiation was the DC 1500/25/4 JOB 188 of the 1.5 MeV installed at the Radiation Technology Center of the IPEN/CNEN-SP. The current profile as function of exposure time, the response repeatability, the sensitivity as function of absorbed dose and the dose response curve were studied for each device. In comparison to FZ diode, we observed a greater decrease in the sensitivity for MCz diode, and good repeatability in both cases. Also, the increasing of the charge with the absorbed dose was well fitted by a second order polynomial function. In the EPI diode characterization, this one exhibited repeatability better than CTA dosimeters applied routinely in radiation processing. The above results indicate the potential use of these radiation hardness Si diodes in online dosimetry to high doses applications. For low doses irradiation were used the linear accelerators KD2 and Primus, both manufactured by Siemens and located at Sirio-Libanes Hospital. The diodes responses were evaluated for electron beams within the

  5. Structural and functional characterization of interactions involving the Tfb1 subunit of TFIIH and the NER factor Rad2

    Lafrance-Vanasse, Julien; Arseneault, Geneviève; Cappadocia, Laurent; Chen, Hung-Ta; Legault, Pascale; Omichinski, James G.

    2012-01-01

    The general transcription factor IIH (TFIIH) plays crucial roles in transcription as part of the pre-initiation complex (PIC) and in DNA repair as part of the nucleotide excision repair (NER) machinery. During NER, TFIIH recruits the 3′-endonuclease Rad2 to damaged DNA. In this manuscript, we functionally and structurally characterized the interaction between the Tfb1 subunit of TFIIH and Rad2. We show that deletion of either the PH domain of Tfb1 (Tfb1PH) or several segments of the Rad2 spac...

  6. Studies of the Interaction between Rad52 Protein and the Yeast Single-Stranded DNA Binding Protein RPA

    Hays, Sharon L.; Firmenich, Antoine A.; Massey, Philip; Banerjee, Ronadip; Berg, Paul

    1998-01-01

    The RFA1 gene encodes the large subunit of the yeast trimeric single-stranded DNA binding protein replication protein A (RPA), which is known to play a critical role in DNA replication. A Saccharomyces cerevisiae strain carrying the rfa1-44 allele displays a number of impaired recombination and repair phenotypes, all of which are suppressible by overexpression of RAD52. We demonstrate that a rad52 mutation is epistatic to the rfa1-44 mutation, placing RFA1 and RAD52 in the same genetic pathwa...

  7. Affinity of yeast nucleotide excision repair factor 2, consisting of the Rad4 and Rad23 proteins, for ultraviolet damaged DNA

    Saccharomyces cerevisiae Rad4 and Rad23 proteins are required for the nucleotide excision repair of UV light-damaged DNA. Previous studies have indicated that these two DNA repair proteins are associated in a tight complex, which we refer to as nucleotide excision repair factor 2 (NEF2). In a reconstituted nucleotide excision repair reaction, incision of UV-damaged DNA is dependent on NEF2, indicating a role of NEF2 in an early step of the repair process. NEF2 does not, however, possess an enzymatic activity, and its function in the damage-specific incision reaction has not yet been defined. Here we use a DNA mobility shift assay to demonstrate that NEF2 binds specifically to UV-damaged DNA. Elimination of cyclobutane pyrimidine dimers from the UV-damaged DNA by enzymatic photoreactivation has little effect on the affinity of NEF2 for the DNA, suggesting that NEF2 recognizes the 6-(1, 2)-dihydro-2-oxo-4-pyrimidinyl)-5-methyl-2,4-(1H,3H)-pyrimidinedione photoproducts in the damaged DNA. These results highlight the intricacy of the DNA damage-demarcation reaction during nucleotide excision repair in eukaryotes. (author)

  8. Rad waste characterization certification and tracking in France

    The development of such a far-ranging nuclear program goes hand in hand with effective radwaste management within a consistent regulatory framework. This framework is shortly discussed in this paper that concentrates on the conditions of practical application of the relevant regulations by contributors to the French nuclear fuel cycle who, as waste generators, shall demonstrate that their wastes can be accepted by the Agency in charge of final disposal. The major topics addressed in this paper can be summarized as follows : definition of the requested quality, i.e. of the requirements set on wastes on the basis of safety assessments. achievement of the requested quality through the implementation of adequate methods including waste characterization and the selection of the best-suited waste treatment packaging processes. Verification that the requested quality is effectively obtained through the implementation of a quality assurance program and quality controls. This waste acceptance procedure aims at demonstrating to the French nuclear regulatory authorities and, more importantly, to the public that radioactive waste is being safely managed at all times. For that reason, and because it is such a coherent program, the French LLW certification program can serve as a useful model for the development of similar programs by others.

  9. Melting decontamination and free release of metal waste at Studsvik RadWaste Co. in Sweden

    The Studsvik RadWaste Co. in Sweden was visited on August 29, 2005 by members of radioactive waste and decommissioning subgroup of central safety task force in old Japan Nuclear Cycle Development Institute as 'Overseas investigation'. The visit afforded us the chance to survey melting and decontaminating of metallic waste in this company and the status of free release. Domestic and foreign radioactive metallic waste is accepted in this company after 1987, and the majority of the decontaminated waste have been released freely. In the background of the big effort of this company and the strong leadership of the regulator (SSI: Swedish radiation protection Authority), prosperous operation was able to have been achieved. This survey was done based on 'Free release of radioactive metallic waste in Europe: the free release experience for 17 years at Studsvik RadWaste Co. in Sweden' by Dr. J. Lorenzen. (author)

  10. TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity

    Moudry, Pavel; Watanabe, Kenji; Wolanin, Kamila M; Bartkova, Jirina; Wassing, Isabel E; Watanabe, Sugiko; Strauss, Robert; Troelsgaard Pedersen, Rune; Oestergaard, Vibe H; Lisby, Michael; Andújar-Sánchez, Miguel; Maya-Mendoza, Apolinar; Esashi, Fumiko; Lukas, Jiri; Bartek, Jiri

    2016-01-01

    Topoisomerase IIβ-binding protein 1 (TOPBP1) participates in DNA replication and DNA damage response; however, its role in DNA repair and relevance for human cancer remain unclear. Here, through an unbiased small interfering RNA screen, we identified and validated TOPBP1 as a novel determinant...... whose loss sensitized human cells to olaparib, an inhibitor of poly(ADP-ribose) polymerase. We show that TOPBP1 acts in homologous recombination (HR) repair, impacts olaparib response, and exhibits aberrant patterns in subsets of human ovarian carcinomas. TOPBP1 depletion abrogated RAD51 loading to...... serine 14, a modification required for RAD51 recruitment to chromatin. Overall, our results provide mechanistic insights into TOPBP1's role in HR, with potential clinical implications for cancer treatment....

  11. The evolution of low-mass close binary systems. III. 1.50 M/sub sun/+0.50 M/sub sun/: Unsteady mass loss and shrinking secondaries

    The evolution of a binary system of 1.50 M/sub sun/ and 0.50 M/sub sun/ components with initial separation 3.00 R/sub sun/ is computed. In the computation, both components are followed simultaneously.The more massive component (primary) fills its Roche lobe during core hydrogen burning (case A evolution), and mass transfer quickly grows to a typical thermal time scale rate (approx.1.1 x 10-7 M/sub sun/ yr-1). The primary's rapid decrease in mass and its underluminosity lead to the growth of an abnormally deep surface convection zone, preventing stabilization of the mass loss rate. Runaway (dynamical time scale) mass loss develops, reaching 1.5 x 10-4 M/sub sun/ yr-1. This rate is itself unsteady because of a Bath-type mechanism. Two runaway episodes occur, leaving a 0.67 M/sub sun/+1.33 M/sub sun/ binary still in a semidetached state.The deep convective envelope of the secondary dominates its evolution, leading to contraction in response to accretion, and avoidance of contact. The rapid compression of the secondary's core during dynamical time scale mass transfer causes runaway hydrogen burning, driving large-scale convection which ultimately mixes the star completely.The behavior of the system modeled, and the absence of observational counterparts to it, are interpreted as supporting the fission theory of the origin of close binaries, and as indicating that most W UMa systems have always been contact binaries

  12. RAD tag sequencing as a source of SNP markers in Cynara cardunculus L

    Scaglione Davide

    2012-01-01

    Full Text Available Abstract Background The globe artichoke (Cynara cardunculus L. var. scolymus genome is relatively poorly explored, especially compared to those of the other major Asteraceae crops sunflower and lettuce. No SNP markers are in the public domain. We have combined the recently developed restriction-site associated DNA (RAD approach with the Illumina DNA sequencing platform to effect the rapid and mass discovery of SNP markers for C. cardunculus. Results RAD tags were sequenced from the genomic DNA of three C. cardunculus mapping population parents, generating 9.7 million reads, corresponding to ~1 Gbp of sequence. An assembly based on paired ends produced ~6.0 Mbp of genomic sequence, separated into ~19,000 contigs (mean length 312 bp, of which ~21% were fragments of putative coding sequence. The shared sequences allowed for the discovery of ~34,000 SNPs and nearly 800 indels, equivalent to a SNP frequency of 5.6 per 1,000 nt, and an indel frequency of 0.2 per 1,000 nt. A sample of heterozygous SNP loci was mapped by CAPS assays and this exercise provided validation of our mining criteria. The repetitive fraction of the genome had a high representation of retrotransposon sequence, followed by simple repeats, AT-low complexity regions and mobile DNA elements. The genomic k-mers distribution and CpG rate of C. cardunculus, compared with data derived from three whole genome-sequenced dicots species, provided a further evidence of the random representation of the C. cardunculus genome generated by RAD sampling. Conclusion The RAD tag sequencing approach is a cost-effective and rapid method to develop SNP markers in a highly heterozygous species. Our approach permitted to generate a large and robust SNP datasets by the adoption of optimized filtering criteria.

  13. Rad-Tolerant, Thermally Stable, High-Speed Fiber-Optic Network for Harsh Environments

    Leftwich, Matt; Hull, Tony; Leary, Michael; Leftwich, Marcus

    2013-01-01

    Future NASA destinations will be challenging to get to, have extreme environmental conditions, and may present difficulty in retrieving a spacecraft or its data. Space Photonics is developing a radiation-tolerant (rad-tolerant), high-speed, multi-channel fiber-optic transceiver, associated reconfigurable intelligent node communications architecture, and supporting hardware for intravehicular and ground-based optical networking applications. Data rates approaching 3.2 Gbps per channel will be achieved.

  14. PI-RADS classification. Structured reporting for MRI of the prostate

    Purpose: To flesh out the ESUR guidelines for the standardized interpretation of multiparametric magnetic resonance imaging (mMRI) for the detection of prostate cancer and to present a graphic reporting scheme for improved communication of findings to urologists. Materials and Methods: The ESUR has recently published a structured reporting system for mMRI of the prostate (PI-RADS). This system involves the use of 5-point Likert scales for grading the findings obtained with different MRI techniques. The mMRI includes T2-weighted MRI, diffusion-weighted imaging, dynamic contrast-enhanced MRI, and MR spectroscopy. In a first step, the fundamentals of technical implementation were determined by consensus, taking into account in particular the German-speaking community. Then, representative images were selected by consensus on the basis of examinations of the three institutions. In addition, scoring intervals for an aggregated PI-RADS score were determined in consensus. Results: The multiparametric methods were discussed critically with regard to implementation and the current status. Criteria used for grading mMRI findings with the PI-RADS classification were concretized by succinct examples. Using the consensus table for aggregated scoring in a clinical setting, a diagnosis of suspected prostate cancer should be made if the PI-RADS score is 4 or higher (≥ 10 points if 3 techniques are used or ≥ 13 points if 4 techniques are used). Finally, a graphic scheme was developed for communicating mMRI prostate findings. Conclusion: Structured reporting according to the ESUR guidelines contributes to quality assurance by standardizing prostate mMRI, and it facilities the communication of findings to urologists. (orig.)

  15. Application of RAD-BCG calculator to Hanford's 300 area shoreline characterization dataset

    Antonio, Ernest J.; Poston, Ted M.; Tiller, Brett L.; Patton, Gene W.

    2003-07-01

    Abstract. In 2001, a multi-agency study was conducted to characterize potential environmental effects from radiological and chemical contaminants on the near-shore environment of the Columbia River at the 300 Area of the U.S. Department of Energy’s Hanford Site. Historically, the 300 Area was the location of nuclear fuel fabrication and was the main location for research and development activities from the 1940s until the late 1980s. During past waste handling practices uranium, copper, and other heavy metals were routed to liquid waste streams and ponds near the Columbia River shoreline. The Washington State Department of Health and the Pacific Northwest National Laboratory’s Surface Environmental Surveillance Project sampled various environmental components including river water, riverbank spring water, sediment, fishes, crustaceans, bivalve mollusks, aquatic insects, riparian vegetation, small mammals, and terrestrial invertebrates for analyses of radiological and chemical constituents. The radiological analysis results for water and sediment were used as initial input into the RAD-BCG Calculator. The RAD-BCG Calculator, a computer program that uses an Excel® spreadsheet and Visual Basic® software, showed that maximum radionuclide concentrations measured in water and sediment were lower than the initial screening criteria for concentrations to produce dose rates at existing or proposed limits. Radionuclide concentrations measured in biota samples were used to calculate site-specific bioaccumulation coefficients (Biv) to test the utility of the RAD-BCG-Calculator’s site-specific screening phase. To further evaluate site-specific effects, the default Relative Biological Effect (RBE) for internal alpha particle emissions was reduced by half and the program’s kinetic/allometric calculation approach was initiated. The subsequent calculations showed the initial RAD-BCG Calculator results to be conservative, which is appropriate for screening purposes.

  16. RadLex - German version: a radiological lexicon for indexing image and report information

    Purpose: Since 2003 the Radiological Society of North America (RSNA) has been developing a lexicon of standardized radiological terms (RadLex) intended to support the structured reporting of imaging observations and the indexing of teaching cases. The aim of this study was to translate the first version of the lexicon (1 - 2007) into German and to implement a language-independent online term browser. Materials and Methods: RadLex version 1 - 2007 contains 6303 terms in nine main categories. Two radiologists independently translated the lexicon using medical dictionaries. Terms translated differently were revised and translated by consensus. For the development of an online term browser, a text processing algorithm called morphosemantic indexing was used which splits up words into small semantic units and compares those units to language-specific subword thesauri. Results: In total 6240 of 6303 terms (99 %) were translated. Of those terms 3965 were German, 1893 were Latin, 359 were multilingual, and 23 were English terms that are also used in German and were therefore maintained. The online term browser supports a language-independent term search in RadLex (German/English) and other common medical terminology (e.g., ICD 10). The term browser displays term hierarchies and translations in different frames and the complexity of the result lists can be adapted by the user. Conclusion: RadLex version 1 - 2007 developed by the RSNA is now available in German and can be accessed online through a term browser with an efficient search function. This is an important precondition for the future comparison of national and international indexed radiological examination results and the interoperability between digital teaching resources. (orig.)

  17. Application of RAD-BCG calculator to Hanford's 300 area shoreline characterization dataset

    In 2001, a multi-agency study was conducted to characterize potential environmental effects from radiological and chemical contaminants on the near-shore environment of the Columbia River at the 300 Area of the U.S. Department of Energy's Hanford Site. Historically, the 300 Area was the location of nuclear fuel fabrication and was the main location for research and development activities from the 1940s until the late 1980s. During past waste handling practices uranium, copper, and other heavy metals were routed to liquid waste streams and ponds near the Columbia River shoreline. The Washington State Department of Health and the Pacific Northwest National Laboratory's Surface Environmental Surveillance Project sampled various environmental components including river water, riverbank spring water, sediment, fishes, crustaceans, bivalve mollusks, aquatic insects, riparian vegetation, small mammals, and terrestrial invertebrates for analyses of radiological and chemical constituents. The radiological analysis results for water and sediment were used as initial input into the RAD-BCG Calculator. The RAD-BCG Calculator, a computer program that uses an Excel(regsign) spreadsheet and Visual Basic(regsign) software, showed that maximum radionuclide concentrations measured in water and sediment were lower than the initial screening criteria for concentrations to produce dose rates at existing or proposed limits. Radionuclide concentrations measured in biota samples were used to calculate site-specific bioaccumulation coefficients (Biv) to test the utility of the RAD-BCG-Calculator's site-specific screening phase. To further evaluate site-specific effects, the default Relative Biological Effect (RBE) for internal alpha particle emissions was reduced by half and the program's kinetic/allometric calculation approach was initiated. The subsequent calculations showed the initial RAD-BCG Calculator results to be conservative, which is appropriate for screening purposes.

  18. Online measurement of the BEPCII background using RadFET dosimeters

    To monitor the integral dose deposited in the BESIII electromagnetic calorimeter whose performance degrades due to exposure to the BEPC II background, a 400 nm IMPL RadFET dosimeter-based integral dose online monitor system is built. After calibration with the 60Co source and verification with TLD in the pulse radiation fields, an experiment was arranged to measure the BEPC II background online. The results are presented. (authors)

  19. Initial experience with optical-CT scanning of RadBall Dosimeters

    Oldham, M; Clift, C; Thomas, A.; Farfan, E; Foley, T; Jannik, T; Adamovics, J; Holmes, C.; Stanley, S.

    2010-01-01

    The RadBall dosimeter is a novel device for providing 3-D information on the magnitude and distribution of contaminant sources of unknown radiation in a given hot cell, glovebox, or contaminated room. The device is presently under evaluation by the National Nuclear Lab (NNL, UK) and the Savannah River National Laboratory (SRNL, US), for application as a diagnostic device for such unknown contaminants in the nuclear industry. A critical component of the technique is imaging the dose distributi...

  20. RIVER-RAD: A computer code for simulating the transport of radionuclides in rivers

    A screening-level model, RIVER-RAD, has been developed to assess the potential fate of radionuclides released to rivers. The model is simplified in nature and is intended to provide guidance in determining the potential importance of the surface water pathway, relevant transport mechanisms, and key radionuclides in estimating radiological dose to man. The purpose of this report is to provide a description of the model and a user's manual for the FORTRAN computer code

  1. Semidominant mutations in the yeast Rad51 protein and their relationships with the Srs2 helicase.

    Chanet, R; Heude, M; Adjiri, A; Maloisel, L; Fabre, F

    1996-09-01

    Suppressors of the methyl methanesulfonate sensitivity of Saccharomyces cerevisiae diploids lacking the Srs2 helicase turned out to contain semidominant mutations in Rad5l, a homolog of the bacterial RecA protein. The nature of these mutations was determined by direct sequencing. The 26 mutations characterized were single base substitutions leading to amino acid replacements at 18 different sites. The great majority of these sites (75%) are conserved in the family of RecA-like proteins, and 10 of them affect sites corresponding to amino acids in RecA that are probably directly involved in ATP reactions, binding, and/or hydrolysis. Six mutations are in domains thought to be involved in interaction between monomers; they may also affect ATP reactions. By themselves, all the alleles confer a rad5l null phenotype. When heterozygous, however, they are, to varying degrees, negative semidominant for radiation sensitivity; presumably the mutant proteins are coassembled with wild-type Rad51 and poison the resulting nucleofilaments or recombination complexes. This negative effect is partially suppressed by an SRS2 deletion, which supports the hypothesis that Srs2 reverses recombination structures that contain either mutated proteins or numerous DNA lesions. PMID:8756636

  2. A RAD-based phylogenetics for Orestias fishes from Lake Titicaca.

    Takahashi, Tetsumi; Moreno, Edmundo

    2015-12-01

    The fish genus Orestias is endemic to the Andes highlands, and Lake Titicaca is the centre of the species diversity of the genus. Previous phylogenetic studies based on a single locus of mitochondrial and nuclear DNA strongly support the monophyly of a group composed of many of species endemic to the Lake Titicaca basin (the Lake Titicaca radiation), but the relationships among the species in the radiation remain unclear. Recently, restriction site-associated DNA (RAD) sequencing, which can produce a vast number of short sequences from various loci of nuclear DNA, has emerged as a useful way to resolve complex phylogenetic problems. To propose a new phylogenetic hypothesis of Orestias fishes of the Lake Titicaca radiation, we conducted a cluster analysis based on morphological similarities among fish samples and a molecular phylogenetic analysis based on RAD sequencing. From a morphological cluster analysis, we recognised four species groups in the radiation, and three of the four groups were resolved as monophyletic groups in maximum-likelihood trees based on RAD sequencing data. The other morphology-based group was not resolved as a monophyletic group in molecular phylogenies, and some members of the group were diverged from its sister group close to the root of the Lake Titicaca radiation. The evolution of these fishes is discussed from the phylogenetic relationships. PMID:26291568

  3. Specific absorbed fractions of electrons and photons for Rad-HUMAN phantom using Monte Carlo method

    WANG Wen; CHENG Meng-Yun; LONG Peng-Cheng; HU Li-Qin

    2015-01-01

    The specific absorbed fractions (SAF) for self-and cross-irradiation are effective tools for the internal dose estimation of inhalation and ingestion intakes of radionuclides.A set of SAFs of photons and electrons were calculated using the Rad-HUMAN phantom,which is a computational voxel phantom of a Chinese adult female that was created using the color photographic image of the Chinese Visible Human (CVH) data set by the FDS Team.The model can represent most Chinese adult female anatomical characteristics and can be taken as an individual phantom to investigate the difference of internal dose with Caucasians.In this study,the emission of mono-energetic photons and electrons of 10 keV to 4 MeV energy were calculated using the Monte Carlo particle transport calculation code MCNP.Results were compared with the values from ICRP reference and ORNL models.The results showed that SAF from the Rad-HUMAN have similar trends but are larger than those from the other two models.The differences were due to the racial and anatomical differences in organ mass and inter-organ distance.The SAFs based on the Rad-HUMAN phantom provide an accurate and reliable data for internal radiation dose calculations for Chinese females.

  4. Evaluation of the 2b-RAD method for genomic selection in scallop breeding.

    Dou, Jinzhuang; Li, Xue; Fu, Qiang; Jiao, Wenqian; Li, Yangping; Li, Tianqi; Wang, Yangfan; Hu, Xiaoli; Wang, Shi; Bao, Zhenmin

    2016-01-01

    The recently developed 2b-restriction site-associated DNA (2b-RAD) sequencing method provides a cost-effective and flexible genotyping platform for aquaculture species lacking sufficient genomic resources. Here, we evaluated the performance of this method in the genomic selection (GS) of Yesso scallop (Patinopecten yessoensis) through simulation and real data analyses using six statistical models. Our simulation analysis revealed that the prediction accuracies obtained using the 2b-RAD markers were slightly lower than those obtained using all polymorphic loci in the genome. Furthermore, a small subset of markers obtained from a reduced tag representation (RTR) library presented comparable performance to that obtained using all markers, making RTR be an attractive approach for GS purpose. Six GS models exhibited variable performance in prediction accuracy depending on the scenarios (e.g., heritability, sample size, population structure), but Bayes-alphabet and BLUP-based models generally outperformed other models. Finally, we performed the evaluation using an empirical dataset composed of 349 Yesso scallops that were derived from five families. The prediction accuracy for this empirical dataset could reach 0.4 based on optimal GS models. In summary, the genotyping flexibility and cost-effectiveness make 2b-RAD be an ideal genotyping platform for genomic selection in aquaculture breeding programs. PMID:26754638

  5. Specific absorbed fractions of electrons and photons for Rad-HUMAN phantom using Monte Carlo method

    Wang, Wen; Cheng, Meng-Yun; Long, Peng-Cheng; Hu, Li-Qin

    2015-07-01

    The specific absorbed fractions (SAF) for self- and cross-irradiation are effective tools for the internal dose estimation of inhalation and ingestion intakes of radionuclides. A set of SAFs of photons and electrons were calculated using the Rad-HUMAN phantom, which is a computational voxel phantom of a Chinese adult female that was created using the color photographic image of the Chinese Visible Human (CVH) data set by the FDS Team. The model can represent most Chinese adult female anatomical characteristics and can be taken as an individual phantom to investigate the difference of internal dose with Caucasians. In this study, the emission of mono-energetic photons and electrons of 10 keV to 4 MeV energy were calculated using the Monte Carlo particle transport calculation code MCNP. Results were compared with the values from ICRP reference and ORNL models. The results showed that SAF from the Rad-HUMAN have similar trends but are larger than those from the other two models. The differences were due to the racial and anatomical differences in organ mass and inter-organ distance. The SAFs based on the Rad-HUMAN phantom provide an accurate and reliable data for internal radiation dose calculations for Chinese females. Supported by Strategic Priority Research Program of Chinese Academy of Sciences (XDA03040000), National Natural Science Foundation of China (910266004, 11305205, 11305203) and National Special Program for ITER (2014GB112001)

  6. Role of Rad52 in fractionated irradiation induced signaling in A549 lung adenocarcinoma cells

    Ghosh, Somnath, E-mail: ghosh.barc@gmail.com [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Krishna, Malini, E-mail: malinik00@gmail.com [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India)

    2012-01-03

    The effect of fractionated doses of {gamma}-irradiation (2 Gy per fraction over 5 days), as delivered in cancer radiotherapy, was compared with acute doses of 10 and 2 Gy, in A549 cells. A549 cells were found to be relatively more radioresistant if the 10 Gy dose was delivered as a fractionated regimen. Microarray analysis showed upregulation of DNA repair and cell cycle arrest genes in the cells exposed to fractionated irradiation. There was intense activation of DNA repair pathway-associated genes (DNA-PK, ATM, Rad52, MLH1 and BRCA1), efficient DNA repair and phospho-p53 was found to be translocated to the nucleus of A549 cells exposed to fractionated irradiation. MCF-7 cells responded differently in fractionated regimen. Silencing of the Rad52 gene in fractionated group of A549 cells made the cells radiosensitive. The above result indicated increased radioresistance in A549 cells due to the activation of Rad52 gene.

  7. Role of Rad52 in fractionated irradiation induced signaling in A549 lung adenocarcinoma cells.

    Ghosh, Somnath; Krishna, Malini

    2012-01-01

    The effect of fractionated doses of γ-irradiation (2Gy per fraction over 5 days), as delivered in cancer radiotherapy, was compared with acute doses of 10 and 2Gy, in A549 cells. A549 cells were found to be relatively more radioresistant if the 10Gy dose was delivered as a fractionated regimen. Microarray analysis showed upregulation of DNA repair and cell cycle arrest genes in the cells exposed to fractionated irradiation. There was intense activation of DNA repair pathway-associated genes (DNA-PK, ATM, Rad52, MLH1 and BRCA1), efficient DNA repair and phospho-p53 was found to be translocated to the nucleus of A549 cells exposed to fractionated irradiation. MCF-7 cells responded differently in fractionated regimen. Silencing of the Rad52 gene in fractionated group of A549 cells made the cells radiosensitive. The above result indicated increased radioresistance in A549 cells due to the activation of Rad52 gene. PMID:22001234

  8. A Pictorial Review of Changes in the BI-RADS Fifth Edition.

    Rao, Ajay Aroor; Feneis, Jennifer; Lalonde, Chloe; Ojeda-Fournier, Haydee

    2016-01-01

    Initially developed in 1993, the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) lexicon serves to standardize breast imaging reports, improve communication with referring physicians, and provide a quality assurance tool. The long-awaited BI-RADS fifth edition consolidates, improves, and expands the lexicon for mammography, breast ultrasonography (US), and breast magnetic resonance (MR) imaging. The new edition has increased the number of imaging examples to nearly 600. The breast MR imaging lexicon is significantly expanded since it first appeared in the fourth edition. New terms have been added to the US lexicon to reflect technologic advances. Minor but important changes have been made to the mammography section. Calcification descriptors in the lexicon are now consolidated into two categories: benign and suspicious. The controversial "intermediate concern" grouping has been eliminated, and a table in the lexicon summarizes the literature supporting the recommendation to biopsy such calcifications. New descriptors such as "developing asymmetry" are illustrated, and abstracts are provided to reference their significance. A generous guidance section is included after the lexicon description for each modality. Useful frequently asked questions are succinctly answered, and the literature to support each answer is included in the reference section for each modality. This review article illustrates and highlights changes to the BI-RADS lexicon and provides readers with a general overview to familiarize them with the fifth edition. (©)RSNA, 2016. PMID:27082663

  9. A new e-learning platform for radiology education (RadEd).

    Xiberta, Pau; Boada, Imma

    2016-04-01

    One of the key elements of e-learning platforms is the content provided to the students. Content creation is a time demanding task that requires teachers to prepare material taking into account that it will be accessed on-line. Moreover, the teacher is restricted by the functionalities provided by the e-learning platforms. In contexts such as radiology where images have a key role, the required functionalities are still more specific and difficult to be provided by these platforms. Our purpose is to create a framework to make teacher's tasks easier, specially when he has to deal with contents where images have a main role. In this paper, we present RadEd, a new web-based teaching framework that integrates a smart editor to create case-based exercises that support image interaction such as changing the window width and the grey scale used to render the image, taking measurements on the image, attaching labels to images and selecting parts of the images, amongst others. It also provides functionalities to prepare courses with different topics, exercises and theory material, and also functionalities to control students' work. Different experts have used RadEd and all of them have considered it a very useful and valuable tool to prepare courses where radiological images are the main component. RadEd provides teachers functionalities to prepare more realistic cases and students the ability to make a more specific diagnosis. PMID:26774237

  10. Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1β production.

    Roth, Susanne; Rottach, Andrea; Lotz-Havla, Amelie S; Laux, Verena; Muschaweckh, Andreas; Gersting, Søren W; Muntau, Ania C; Hopfner, Karl-Peter; Jin, Lei; Vanness, Katelynd; Petrini, John H J; Drexler, Ingo; Leonhardt, Heinrich; Ruland, Jürgen

    2014-06-01

    Double-stranded DNA (dsDNA) in the cytoplasm triggers the production of interleukin 1β (IL-1β) as an antiviral host response, and deregulation of the pathways involved can promote inflammatory disease. Here we report a direct cytosolic interaction between the DNA-damage sensor Rad50 and the innate immune system adaptor CARD9. Transfection of dendritic cells with dsDNA or infection of dendritic cells with a DNA virus induced the formation of dsDNA-Rad50-CARD9 signaling complexes for activation of the transcription factor NF-κB and the generation of pro-IL-1β. Primary cells conditionally deficient in Rad50 or lacking CARD9 consequently exhibited defective DNA-induced production of IL-1β, and Card9(-/-) mice had impaired inflammatory responses after infection with a DNA virus in vivo. Our results define a cytosolic DNA-recognition pathway for inflammation and a physical and functional connection between a conserved DNA-damage sensor and the innate immune response to pathogens. PMID:24777530

  11. Small-molecule inhibitors identify the RAD52-ssDNA interaction as critical for recovery from replication stress and for survival of BRCA2 deficient cells

    Hengel, Sarah R; Malacaria, Eva; Folly da Silva Constantino, Laura; Bain, Fletcher E; Diaz, Andrea; Koch, Brandon G; Yu, Liping; Wu, Meng; Pichierri, Pietro; Spies, M Ashley; Spies, Maria

    2016-01-01

    The DNA repair protein RAD52 is an emerging therapeutic target of high importance for BRCA-deficient tumors. Depletion of RAD52 is synthetically lethal with defects in tumor suppressors BRCA1, BRCA2 and PALB2. RAD52 also participates in the recovery of the stalled replication forks. Anticipating that ssDNA binding activity underlies the RAD52 cellular functions, we carried out a high throughput screening campaign to identify compounds that disrupt the RAD52-ssDNA interaction. Lead compounds were confirmed as RAD52 inhibitors in biochemical assays. Computational analysis predicted that these inhibitors bind within the ssDNA-binding groove of the RAD52 oligomeric ring. The nature of the inhibitor-RAD52 complex was validated through an in silico screening campaign, culminating in the discovery of an additional RAD52 inhibitor. Cellular studies with our inhibitors showed that the RAD52-ssDNA interaction enables its function at stalled replication forks, and that the inhibition of RAD52-ssDNA binding acts additively with BRCA2 or MUS81 depletion in cell killing. DOI: http://dx.doi.org/10.7554/eLife.14740.001 PMID:27434671

  12. Rice OsRAD21-2 is Expressed in Actively Dividing Tissues and its Ectopic Expression in Yeast Results in Aberrant Cell Division and Growth

    Chunyan Gong; Tang Li; Qi Li; Longfeng Yan; Tai Wang

    2011-01-01

    Rad21 and its meiotic counterpart Rec8,the key components of the cohesin complex,are essential for sister chromatid cohesion and chromosome segregation in mitosis and meiosis,respectively.In contrast to yeast and vertebrates,which have only two RAD21/REC8 genes,the rice genome encodes four Rad21/Rec8 proteins.Here,we report on the cloning and characterization of OsRAD21-2 from rice (Oryza sativa L.).Phylogenetic analysis of the full-length amino acids showed that OsRad21-2 was grouped into the plant-specific Rad21 subfamily.Semi-quantitative reverse transcription-polymerase chain reaction revealed OsRAD21-2 preferentially expressed in premeiotic flowers.Further RNA in situ hybridization analysis and promoter::β-glucuronidase staining indicated that OsRAD21-2 was mainly expressed in actively dividing tissues including premeiotic stamen,stem intercalary meristem,leaf meristem,and root pericycle.Ectopic expression of OsRAD21-2 in fission yeast resulted in cell growth delay and morphological abnormality.Flow cytometric analysis revealed that the OsRAD21-2-expressed cells were arrested in G2 phase.Our results suggest that OsRad21-2 functions in regulation of cell division and growth.

  13. Diagnostic SNPs for inferring population structure in American mink (Neovison vison) identified through RAD sequencing

    2015-01-01

    Data from: "Diagnostic SNPs for inferring population structure in American mink (Neovison vison) identified through RAD sequencing" in Genomic Resources Notes accepted 1 October 2014 to 30 November 2014....

  14. Acurácia dos achados mamográficos do câncer de mama: correlação da classificação BI-RADS e achados histológicos Accuracy of mammographic findings in breast cancer: correlation between BI-RADS classification and histological findings

    José Hermes Ribas do Nascimento

    2010-04-01

    BI-RADS accuracy in mammography was evaluated. The interobserver agreement was analyzed with the Cohen's kappa (κ test, and the differences between groups were evaluated with the chi-squared test. RESULTS: The present study demonstrated that the mammographic accuracy ranged from 75% to 62% in the differentiation between benign and malignant lesions with the utilization of the BI-RADS classification. Statistically significant interobserver agreement was observed in the description of masses margins (κ= 0.66. A low agreement rate was identified in the description of masses borders (shape (κ= 0.40 and calcifications, both in relation to their distribution (κ= 0.24 and morphology (κ= 0.36. CONCLUSION: The present study demonstrated the BI-RADS accuracy in the differentiation between benign and malignant lesions. The interobserver agreement was poor in the analysis of calcifications morphology and distribution, but a progressive increase in the positive predictive values was observed in the subcategory 4.

  15. A small molecule inhibitor of RAD51 reduces homologous recombination and sensitizes multiple myeloma cells to doxorubicin

    David A. Alagpulinsa

    2014-10-01

    Full Text Available We previously reported high expression of RAD51 and increased homologous recombination (HR rates in multiple myeloma (MM cells, and showed that genomic instability and disease progression are commensurate with HR levels. Moreover, high RAD51 expression in vivo is associated with chemoresistance and poor patient survival. Doxorubicin (DOX is one of the most widely used drug treatments in MM chemotherapy. DOX is cytotoxic because it induces DNA double-strand breaks, which can be repaired by RAD51-mediated HR; activation of this pathway thus contributes to resistance. To investigate the role of RAD51 in MM drug resistance, we assessed the ability of B02, a small-molecule inhibitor of RAD51, to enhance DOX sensitivity of MM cells. Combining low-toxicity doses of DOX and B02 resulted in significant synthetic lethality, observed as increased apoptosis and reduced viability compared to either agent alone, or to the product of their individual effects. In contrast, the combination did not produce significant synergy against normal human CD19+ B cells from peripheral blood. DOX induced RAD51 at both mRNA and protein levels, while arresting cells in S and G2. DOX treatment also increased the number of RAD51 foci, a marker of HR repair, so that the fraction of cells with ≥5 foci rose 4-fold, whereas γH2AX foci rose far less, implying that most new breaks are repaired. When B02 treatment preceded DOX exposure, the induction of RAD51 foci was severely blunted, whereas γH2AX foci rose significantly relative to basal levels or either agent alone. In MM cells carrying a chromosomally integrated reporter of HR repair, DOX increased HR events while B02 inhibition of RAD51 blocked the HR response. These studies demonstrate the crucial role of RAD51 in protecting MM cells from genotoxic agents such as DOX, and suggest that specific inhibition of RAD51 may be an effective means to block DNA repair in MM cells and thus to enhance the efficacy of chemotherapy.

  16. Genetic Interactions Between the Meiosis-Specific Cohesin Components, STAG3, REC8, and RAD21L

    Ayobami Ward

    2016-06-01

    Full Text Available Cohesin is an essential structural component of chromosomes that ensures accurate chromosome segregation during mitosis and meiosis. Previous studies have shown that there are cohesin complexes specific to meiosis, required to mediate homologous chromosome pairing, synapsis, recombination, and segregation. Meiosis-specific cohesin complexes consist of two structural maintenance of chromosomes proteins (SMC1α/SMC1β and SMC3, an α-kleisin protein (RAD21, RAD21L, or REC8, and a stromal antigen protein (STAG1, 2, or 3. STAG3 is exclusively expressed during meiosis, and is the predominant STAG protein component of cohesin complexes in primary spermatocytes from mouse, interacting directly with each α-kleisin subunit. REC8 and RAD21L are also meiosis-specific cohesin components. Stag3 mutant spermatocytes arrest in early prophase (“zygotene-like” stage, displaying failed homolog synapsis and persistent DNA damage, as a result of unstable loading of cohesin onto the chromosome axes. Interestingly, Rec8, Rad21L double mutants resulted in an earlier “leptotene-like” arrest, accompanied by complete absence of STAG3 loading. To assess genetic interactions between STAG3 and α-kleisin subunits RAD21L and REC8, our lab generated Stag3, Rad21L, and Stag3, Rec8 double knockout mice, and compared them to the Rec8, Rad21L double mutant. These double mutants are phenotypically distinct from one another, and more severe than each single knockout mutant with regards to chromosome axis formation, cohesin loading, and sister chromatid cohesion. The Stag3, Rad21L, and Stag3, Rec8 double mutants both progress further into prophase I than the Rec8, Rad21L double mutant. Our genetic analysis demonstrates that cohesins containing STAG3 and REC8 are the main complex required for centromeric cohesion, and RAD21L cohesins are required for normal clustering of pericentromeric heterochromatin. Furthermore, the STAG3/REC8 and STAG3/RAD21L cohesins are the primary

  17. Mrc1 is a replication fork component whose phosphorylation in response to DNA replication stress activates Rad53

    Osborn, Alexander J.; Elledge, Stephen J.

    2003-01-01

    When DNA replication is stalled, a signal transduction pathway is activated that promotes the stability of stalled forks and resumption of DNA synthesis. In budding yeast, this pathway includes the kinases Mec1 and Rad53. Here we report that the Mediator protein Mrc1, which is required for normal DNA replication and for activation of Rad53, is present at replication forks. Mrc1 initially binds early-replicating sequences and moves along chromatin with the replication f...

  18. RAD9 deficiency enhances radiation induced bystander DNA damage and transcriptomal response

    Radiation induced bystander effects are an important component of the overall response of cells to irradiation and are associated with human health risks. The mechanism responsible includes intra-cellular and inter-cellular signaling by which the bystander response is propagated. However, details of the signaling mechanism are not well defined. We measured the bystander response of Mrad9+/+ and Mrad9−/− mouse embryonic stem cells, as well as human H1299 cells with inherent or RNA interference-mediated reduced RAD9 levels after exposure to 1 Gy α particles, by scoring chromosomal aberrations and micronuclei formation, respectively. In addition, we used microarray gene expression analyses to profile the transcriptome of directly irradiated and bystander H1299 cells. We demonstrated that Mrad9 null enhances chromatid aberration frequency induced by radiation in bystander mouse embryonic stem cells. In addition, we found that H1299 cells with reduced RAD9 protein levels showed a higher frequency of radiation induced bystander micronuclei formation, compared with parental cells containing inherent levels of RAD9. The enhanced bystander response in human cells was associated with a unique transcriptomic profile. In unirradiated cells, RAD9 reduction broadly affected stress response pathways at the mRNA level; there was reduction in transcript levels corresponding to genes encoding multiple members of the UVA-MAPK and p38MAPK families, such as STAT1 and PARP1, suggesting that these signaling mechanisms may not function optimally when RAD9 is reduced. Using network analysis, we found that differential activation of the SP1 and NUPR1 transcriptional regulators was predicted in directly irradiated and bystander H1299 cells. Transcription factor prediction analysis also implied that HIF1α (Hypoxia induced factor 1 alpha) activation by protein stabilization in irradiated cells could be a negative predictor of the bystander response, suggesting that local hypoxic stress

  19. Lessons learned from the Radiation measurements of the Mars Science Lab Radiation Assessment Detector (MSL-RAD)

    Reitz, Guenther; Ottolenghi, Andrea

    2016-07-01

    The Radiation Assessment Detector (RAD) was designed to characterize the radiation environment on the Mars surface and to contribute to an improved assessment of radiation risk for a future human mission to Mars. The flight was chosen to cover a period of solar maximum activity to allow besides the measurement of the galactic cosmic rays an intense study of exposures by solar particle events. The Mars Science Laboratory spacecraft (MSL), containing the Curiosity rover, in which RAD was integrated, was launched to Mars on November 26, 2011. Although not part of the mission planning, RAD was operated already during the 253 day and 560 million km cruise to Mars and made the first time detailed measurements of a radiation environment comparable to that inside a future spacecraft carrying humans to Mars and in other deep space missions. Exactly 100 years after the discovery of cosmic rays on August 7, 1912 RAD makes the first observation of the radiation environment on the surface of another planet and is still gathering data until today. Meanwhile the maximum activity of the current solar cycle has been passed and the solar activity is decreasing. Unfortunately the present solar cycle was an unexpected weak cycle. As a matter of fact only very small solar particle events could be observed during the still ongoing RAD measurements. The paper highlights the achievements of RAD by presenting selected data measured during the cruise and on the Mars surface and describes its impact on predictive models for health risks of astronauts during space missions.

  20. Mechanisms for ATM mediated downstream gene BRCA1 and RAD51 in signaling pathway of DNA injury repair

    In order to investigate mechanisms of ATM (Ataxia telangiectasia mutated) genes mediating phosphorylation of BRCA1 (breast cancer gene 1) and its downstream gene RAD51 (DNA damage repair protein 51) in signaling pathway of DNA injury repair, the authors applied immunocoprecipitated and Western blot to observe changes in the expressions of BRCA1 and RAD51 proteins in AT cells, ATM+-AT cells (AT cells transfected with ATM genes) and GM cells (originated from human skin fibroblast, GM 0639) and used as control, after 5, 10 and 20 Gy 60Co γ-ray irradiation at dose rate of 1.0 Gy/min. The irradiated AT cells were analyzed to study interactive action between ATM and BRCA1 protein, BRCA1 and RAD51 protein, and the effect of PI3K inhibitor on ATM phosphorylating, its downstream gene, by immunocoprecipitate and Western blot. No expression bands of BRCA1 were found in ATM+-AT and GM cells of the control. After the irradiation, the BRCA1 and RAD51 were both expressed in GM and ATM cells. The PI3K inhibitor Wortmannin could inhibit the expression of BRCA1 in the AT, ATM+-AT and GM cells. The BRCA1 and RAD proteins were both expressed in ATM+-AT cells and GM cells. Therefore, after the irradiation the phosphorylation of BRCA1 mediated by ATM could further interact with RAD51. This is a cascade in signaling pathway for DNA damage repair and genome stabilization. (authors)

  1. Radon: risk to health? El radón: ¿riesgo para la salud?

    Juan Miguel Barros Dios

    2011-12-01

    Full Text Available Radon (Rn222 is a radioactive noble gas whose origin is Radium (Ra226 when it emits an alpha particle (two protons and two neutrons or a helium nucleus. Rn222 transforms in another radioactive element (Po218 when an alpha particle is emitted. Its carcinogenic effect on the lung was discovered various decades ago, first on uranium miners and later on general population exposed at home to residential radon. The main factor influencing radon concentration in dwellings is the uranium content of the subsoil, since uranium is the first element of the radioactive disintegration chain where radon appears. Geological risk areas of Spain due to their granite and therefore uranium content are Galicia, the Northwest and the West of Spain. Numerous countries of Europe and America have enforced legislation focused to protect population and reduce radon concentration in order to prevent lung cancer appearance. These laws comprise public buildings and private homes. Since the late 80s, alpha radiation generated by radon and its short-life descendents has been classified as carcinogenic agents by the International Agency for Research on Cancer (Lyon, 1988 and the National Research Council (BEIR IV, 1988.El radón (Rn222 es un gas noble radiactivo que procede directamente del radio (Ra226 cuando este emite una partícula alfa (dos protones y dos neutrones o núcleo de helio, y que a su vez se transforma en otro elemento radiactivo (Po218 al desprenderse de otra partícula alfa. Desde hace varias décadas se conoce su efecto como factor de riesgo del cáncer primario pulmonar, primero en mineros del uranio y posteriormente en la población general expuesta al radón residencial en hogares construidos sobre suelos de rocas ricas en uranio (U238, elemento inicial de la cadena de degradación radiactiva de la que procede el radón. Áreas geológicamente constituidas por granitos o pizarras, como son las de gran parte de Galicia y todo el noroeste y oeste de la pen

  2. Structural and electrical properties of (x)Mn0.45Ni0.05Zn0.50Fe2O4 + (1 − x)BaZr0.52Ti0.48O3 multiferroic materials

    Multiferroic (x)Mn0.45Ni0.05Zn0.50Fe2O4 + (1 − x)BaZr0.52Ti0.48O3 materials (where x varies from 0.0 to 0.8 in steps of 0.20) were prepared by the standard solid state reaction method. X-ray diffraction patterns verify the development of tetragonal perovskite structure for ferroelectric and cubic spinel structure for ferrite phase. The frequency and temperature dependent electrical parameters have been investigated to understand the conduction mechanism in these multiferroic materials. The grain effect contributes to the conduction mechanism for the sample containing 0–60% ferrite and both the grain and grain boundary effect contribute to the conduction mechanism for the composite containing 80% ferrite at high temperature. The ac conductivity increases with increasing frequency for the sample x = 0. This is due to the small polaron hopping. For the sample containing 20% ferrite, the frequency independent dc conductivity is observed at low temperature and dominates over a wide frequency range at high temperature region for the sample containing higher percentage of ferrite. The frequency independent dc conductivity is shifted to the frequency dependent ac conductivity, indicating the beginning of the conductivity relaxation phenomenon. This is attributed to the translation of long range polaron hopping to the small range charge carriers. The temperature dependence conductivity indicates that the impurities present in these multiferroic materials are almost minimized and polaron hopping type of conduction mechanism is valid. (papers)

  3. XRCC3 ATPase activity is required for normal XRCC3-Rad51C complex dynamics and homologous recombination

    Yamada, N; Hinz, J; Kopf, V L; Segalle, K; Thompson, L

    2004-02-25

    Homologous recombinational repair is a major DNA repair pathway that preserves chromosomal integrity by removing double-strand breaks, crosslinks, and other DNA damage. In eukaryotic cells, the Rad51 paralogs (XRCC2, XRCC3, Rad51B, Rad51C, and Rad51D) are involved in this process, although their exact functions are largely undetermined. All five paralogs contain ATPase motifs, and XRCC3 appears to exist in a single complex with Rad51C. To begin to examine the function of this Rad51C-XRCC3 complex, we generated mammalian expression vectors that produce human wild-type XRCC3 or mutant XRCC3 with either a non-conservative mutation (K113A) or a conservative mutation (K113R) in the GKT Walker A box of the ATPase motif. The three vectors were independently transfected into Xrcc3-deficient irs1SF CHO cells. Wild-type XRCC3 complemented irs1SF cells, albeit to varying degrees, while ATPase mutants had no complementing activity, even when the mutant protein was expressed at comparable levels to that in wild-type-complemented clones. Because of the mutants' dysfunction, we propose that ATP binding and hydrolyzing activities of XRCC3 are essential. We tested in vitro complex formation by wild-type and mutant XRCC3 with His6-tagged Rad51C upon coexpression in bacteria, nickel affinity purification, and western blotting. Wild-type and K113A mutant XRCC3 formed stable complexes with Rad51C and co-purified with Rad51C, while the K113R mutant did not and was predominantly insoluble. Addition of 5 mM ATP, but not ADP, also abolished complex formation by the wild-type proteins. These results suggest that XRCC3 is likely to regulate the dissociation and formation of Rad51C-XRCC3 complex through ATP binding and hydrolysis, with both processes being essential for the complex's ability to participate in HRR.

  4. Mutation of cysteine-88 in the Saccharomyces cerevisiae RAD6 protein abolishes its ubiquitin-conjugating activity and its various biological functions

    The RAD6 gene of Saccharomyces cerevisiae is required for DNA repair, DNA damage-induced mutagenesis, and sporulation. RAD6 protein is a ubiquitin-conjugating enzyme (E2) that has been shown to attach multiple molecules of ubiquitin to histones H2A and H2B. We have now examined whether the E2 activity of RAD6 is involved in its various biological functions. Since the formation of a thioester adduct between E2 and ubiquitin is necessary for E2 activity, the single cysteine residue (Cys-88) present in RAD6 was changed to alanine or valine. The mutant proteins were overproduced in yeast cells and purified to near homogeneity. We show that the rad6 Ala-88 and rad6 Val-88 mutant proteins lack the capacity for thioester formation with ubiquitin and, as a consequence, are totally devoid of any E2 activity. The rad6 Ala-88 and rad6 Val-88 mutations confer a defect in DNA repair, mutagenesis, and sporulation equivalent to that in the rad6 null allele. We suggest that the biological functions of RAD6 require its E2 activity. (author)

  5. Twist-open mechanism of DNA damage recognition by the Rad4/XPC nucleotide excision repair complex.

    Velmurugu, Yogambigai; Chen, Xuejing; Slogoff Sevilla, Phillip; Min, Jung-Hyun; Ansari, Anjum

    2016-04-19

    DNA damage repair starts with the recognition of damaged sites from predominantly normal DNA. In eukaryotes, diverse DNA lesions from environmental sources are recognized by the xeroderma pigmentosum C (XPC) nucleotide excision repair complex. Studies of Rad4 (radiation-sensitive 4; yeast XPC ortholog) showed that Rad4 "opens" up damaged DNA by inserting a β-hairpin into the duplex and flipping out two damage-containing nucleotide pairs. However, this DNA lesion "opening" is slow (˜5-10 ms) compared with typical submillisecond residence times per base pair site reported for various DNA-binding proteins during 1D diffusion on DNA. To address the mystery as to how Rad4 pauses to recognize lesions during diffusional search, we examine conformational dynamics along the lesion recognition trajectory using temperature-jump spectroscopy. Besides identifying the ˜10-ms step as the rate-limiting bottleneck towards opening specific DNA site, we uncover an earlier ˜100- to 500-μs step that we assign to nonspecific deformation (unwinding/"twisting") of DNA by Rad4. The β-hairpin is not required to unwind or to overcome the bottleneck but is essential for full nucleotide-flipping. We propose that Rad4 recognizes lesions in a step-wise "twist-open" mechanism, in which preliminary twisting represents Rad4 interconverting between search and interrogation modes. Through such conformational switches compatible with rapid diffusion on DNA, Rad4 may stall preferentially at a lesion site, offering time to open DNA. This study represents the first direct observation, to our knowledge, of dynamical DNA distortions during search/interrogation beyond base pair breathing. Submillisecond interrogation with preferential stalling at cognate sites may be common to various DNA-binding proteins. PMID:27035942

  6. Cellular Ubc2/Rad6 E2 ubiquitin-conjugating enzyme facilitates tombusvirus replication in yeast and plants

    Mono- and multi-ubiquitination alters the functions and subcellular localization of many cellular and viral proteins. Viruses can co-opt or actively manipulate the ubiquitin network to support viral processes or suppress innate immunity. Using yeast (Saccharomyces cerevisiae) model host, we show that the yeast Rad6p (radiation sensitive 6) E2 ubiquitin-conjugating enzyme and its plant ortholog, AtUbc2, interact with two tombusviral replication proteins and these E2 ubiquitin-conjugating enzymes could be co-purified with the tombusvirus replicase. We demonstrate that TBSV RNA replication and the mono- and bi-ubiquitination level of p33 is decreased in rad6Δ yeast. However, plasmid-based expression of AtUbc2p could complement both defects in rad6Δ yeast. Knockdown of UBC2 expression in plants also decreases tombusvirus accumulation and reduces symptom severity, suggesting that Ubc2p is critical for virus replication in plants. We provide evidence that Rad6p is involved in promoting the subversion of Vps23p and Vps4p ESCRT proteins for viral replicase complex assembly. - Highlights: • Tombusvirus p33 replication protein interacts with cellular RAD6/Ubc2 E2 enzymes. • Deletion of RAD6 reduces tombusvirus replication in yeast. • Silencing of UBC2 in plants inhibits tombusvirus replication. • Mono- and bi-ubiquitination of p33 replication protein in yeast and in vitro. • Rad6p promotes the recruitment of cellular ESCRT proteins into the tombusvirus replicase

  7. Cellular Ubc2/Rad6 E2 ubiquitin-conjugating enzyme facilitates tombusvirus replication in yeast and plants

    Imura, Yoshiyuki, E-mail: imura@brs.nihon-u.ac.jp; Molho, Melissa; Chuang, Chingkai; Nagy, Peter D., E-mail: pdnagy2@uky.edu

    2015-10-15

    Mono- and multi-ubiquitination alters the functions and subcellular localization of many cellular and viral proteins. Viruses can co-opt or actively manipulate the ubiquitin network to support viral processes or suppress innate immunity. Using yeast (Saccharomyces cerevisiae) model host, we show that the yeast Rad6p (radiation sensitive 6) E2 ubiquitin-conjugating enzyme and its plant ortholog, AtUbc2, interact with two tombusviral replication proteins and these E2 ubiquitin-conjugating enzymes could be co-purified with the tombusvirus replicase. We demonstrate that TBSV RNA replication and the mono- and bi-ubiquitination level of p33 is decreased in rad6Δ yeast. However, plasmid-based expression of AtUbc2p could complement both defects in rad6Δ yeast. Knockdown of UBC2 expression in plants also decreases tombusvirus accumulation and reduces symptom severity, suggesting that Ubc2p is critical for virus replication in plants. We provide evidence that Rad6p is involved in promoting the subversion of Vps23p and Vps4p ESCRT proteins for viral replicase complex assembly. - Highlights: • Tombusvirus p33 replication protein interacts with cellular RAD6/Ubc2 E2 enzymes. • Deletion of RAD6 reduces tombusvirus replication in yeast. • Silencing of UBC2 in plants inhibits tombusvirus replication. • Mono- and bi-ubiquitination of p33 replication protein in yeast and in vitro. • Rad6p promotes the recruitment of cellular ESCRT proteins into the tombusvirus replicase.

  8. Measuring low radium activity concentration in water with RAD7 by means of evaporation

    Kappke, Jaqueline; Marussig, Camila G.T.; Paschuk, Sergei; Zambianchi Junior, Pedro; Correa, Janine N.; Perna, Allan Felipe Nunes; Martin, Aline, E-mail: jaquelinekappke@gmail.com, E-mail: mila_garciatb@hotmail.com, E-mail: spaschuk@gmail.com, E-mail: zambianchi@utfpr.edu.br, E-mail: janine_nicolosi@hotmail.com, E-mail: allan_perna@hotmail.com, E-mail: nocamartin@hotmail.com [Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil)

    2015-07-01

    Preliminary activity measurements of low radium concentration in mineral water by using RAD7 equipment showed high values of statistical errors. Therefore, the need to develop a new protocol for measuring and proofing the evaporation test for radium measurements in water is in place. This study evaluates the possibility of using RAD7 equipment to measure Ra-226 activity in equilibrium with Rn-222 present in water samples. The technique involves evaporation process so as to increase the Ra-226 concentration in the sample in a controlled manner and thus reduce statistical errors. Two samples were compared, 10 L sample of distilled water and a 7.75 L sample of known concentration (0.1 Bq/L). The evaporation was carried out starting with different initial volumes for both samples: 500 mL, 1000 mL, 2000 mL, 4000 mL and a 250 mL sample not subject to evaporation. All samples reached a final volume of approximately 250 mL. After evaporation, the samples were stored for 30 days until secular equilibrium was achieved between Ra-226 and Rn-222. The values obtained, by using RAD7 detector, for distilled water, as expected, are near zero averaging 0.021 ± 0.016 Bq/L. The average value found in the water of known concentration was 0.099 ± 0.011 Bq/L, also close to the expected 0.1 Bq/L. The conclusion is that the application of an evaporation process is efficient and the proposed methodology is a proven alternative to decrease the statistical errors. (author)

  9. MagRad: A code to optimize the operation of superconducting magnets in a radiation environment

    A powerful computational tool, called MagRad, has been developed which optimizes magnet design for operation in radiation fields. Specifically, MagRad has been used for the analysis and design modification of the cable-in-conduit conductors of the TF magnet systems in fusion reactor designs. Since the TF magnets must operate in a radiation environment which damages the material components of the conductor and degrades their performance, the optimization of conductor design must account not only for start-up magnet performance, but also shut-down performance. The degradation in performance consists primarily of three effects: reduced stability margin of the conductor; a transition out of the well-cooled operating regime; and an increased maximum quench temperature attained in the conductor. Full analysis of the magnet performance over the lifetime of the reactor includes: radiation damage to the conductor, stability, protection, steady state heat removal, shielding effectiveness, optimal annealing schedules, and finally costing of the magnet and reactor. Free variables include primary and secondary conductor geometric and compositional parameters, as well as fusion reactor parameters. A means of dealing with the radiation damage to the conductor, namely high temperature superconductor anneals, is proposed, examined, and demonstrated to be both technically feasible and cost effective. Additionally, two relevant reactor designs (ITER CDA and ARIES-II/IV) have been analyzed. Upon addition of pure copper strands to the cable, the ITER CDA TF magnet design was found to be marginally acceptable, although much room for both performance improvement and cost reduction exists. A cost reduction of 10-15% of the capital cost of the reactor can be achieved by adopting a suitable superconductor annealing schedule. In both of these reactor analyses, the performance predictive capability of MagRad and its associated costing techniques have been demonstrated

  10. Assessing the degree of collinearity among the lesion features of the MRI BI-RADS lexicon

    Purpose: To retrospectively assess collinearity among lesion feature of the MRI BI-RADS lexicon. Collinearity denotes a situation in which two or more (independent) variables are correlated to some degree, thus partly conveying the same information. Collinearity may cause problems in the interpretation of logistic regression models. Materials and methods: We analysed the BI-RADS features of 351 lesions in 325 consecutive patients. Patients with biopsy proven breast disease or treated with chemotherapy were excluded. All lesion features were dichotomised into “present” or “not present”. Correlation matrices were generated for mass and non-mass lesions separately, focus lesions were omitted. The phi coefficient was used as measure for correlation. Results: There were 253 mass (175 malignant, 78 benign), 66 non-mass (21 malignant, 45 benign) and 32 focus (5 malignant, 27 benign) lesions among the study population. The strongest inter-subgroup correlations among mass lesion features were: slow initial enhancement with persistent kinetics, phi = 0.64 (0.56–0.71), rapid initial enhancement with washout kinetics, phi = 0.52 (0.43–0.61) and rapid initial enhancement with persistent kinetics, phi = −0.43 (−0.53 to −0.32). The strongest inter-subgroup correlation among non-mass lesion features were: rapid initial enhancement with washout kinetics, phi = 0.51 (0.30–0.67), slow initial enhancement with persistent kinetics, phi = 0.43 (0.21–0.61) and rapid initial enhancement with persistent kinetics, phi = −0.41 (−0.18 to −0.60). Conclusion: There is a noticeable overlap of information, especially between kinetic features and initial enhancement types for both, mass and non-mass lesions. This should be considered when generating logistic regression models with the MRI BI-RADS lesion features.

  11. MagRad: A code to optimize the operation of superconducting magnets in a radiation environment

    Yeaw, C.T.

    1995-12-31

    A powerful computational tool, called MagRad, has been developed which optimizes magnet design for operation in radiation fields. Specifically, MagRad has been used for the analysis and design modification of the cable-in-conduit conductors of the TF magnet systems in fusion reactor designs. Since the TF magnets must operate in a radiation environment which damages the material components of the conductor and degrades their performance, the optimization of conductor design must account not only for start-up magnet performance, but also shut-down performance. The degradation in performance consists primarily of three effects: reduced stability margin of the conductor; a transition out of the well-cooled operating regime; and an increased maximum quench temperature attained in the conductor. Full analysis of the magnet performance over the lifetime of the reactor includes: radiation damage to the conductor, stability, protection, steady state heat removal, shielding effectiveness, optimal annealing schedules, and finally costing of the magnet and reactor. Free variables include primary and secondary conductor geometric and compositional parameters, as well as fusion reactor parameters. A means of dealing with the radiation damage to the conductor, namely high temperature superconductor anneals, is proposed, examined, and demonstrated to be both technically feasible and cost effective. Additionally, two relevant reactor designs (ITER CDA and ARIES-II/IV) have been analyzed. Upon addition of pure copper strands to the cable, the ITER CDA TF magnet design was found to be marginally acceptable, although much room for both performance improvement and cost reduction exists. A cost reduction of 10-15% of the capital cost of the reactor can be achieved by adopting a suitable superconductor annealing schedule. In both of these reactor analyses, the performance predictive capability of MagRad and its associated costing techniques have been demonstrated.

  12. Power Doppler sonography: Anything to add to BI-RADS US in solid breast masses?

    Objective: To evaluate the contribution of power Doppler ultrasonography (PDUS) to breast imaging reporting and data system ultrasonography (BI-RADS US) categorization of solid breast masses. Materials and methods: Totally 94 solid lesions with histopathological results in 49 patients were included in the study. US features of the lesions were classified according to American College of Radiologists (ACR) BI-RADS US lexicon. Lesions were evaluated qualitatively according to their PDUS properties and quantitatively with spectral analysis. Hypervascularity, penetration of vessels into the mass or branching-disordered course and resistivity index values higher than 0.85 were accepted as probable malignant criteria. Results: Fifty-five of 94 lesions were benign (58.5%), while 39 (41.5%) were malignant histopathologically. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of US and PDUS in the diagnosis of malignant lesions were 100%, 58.2%, 62.9%, 100% and 71.8%, 81.8%, 73.7%, 80.4%, respectively. Criteria used for the distinction of malignant and benign lesions like number of vessels (p < 0.05), distribution of tumoral vessels, morphology of vessels and resistivity index values higher than 0.85 showed statistically significant difference (p < 0.001). When sonographic findings were combined with PDUS and spectral analysis findings, sensitivity, specificity, PPV and NPV were 100%, 52.7%, 60% and 100%, respectively. Conclusion: PDUS and spectral analysis have no contribution to BI-RADS US. For the spectral analysis, when RI value is one or greater, malignancy risk significantly increases.

  13. Measuring low radium activity concentration in water with RAD7 by means of evaporation

    Preliminary activity measurements of low radium concentration in mineral water by using RAD7 equipment showed high values of statistical errors. Therefore, the need to develop a new protocol for measuring and proofing the evaporation test for radium measurements in water is in place. This study evaluates the possibility of using RAD7 equipment to measure Ra-226 activity in equilibrium with Rn-222 present in water samples. The technique involves evaporation process so as to increase the Ra-226 concentration in the sample in a controlled manner and thus reduce statistical errors. Two samples were compared, 10 L sample of distilled water and a 7.75 L sample of known concentration (0.1 Bq/L). The evaporation was carried out starting with different initial volumes for both samples: 500 mL, 1000 mL, 2000 mL, 4000 mL and a 250 mL sample not subject to evaporation. All samples reached a final volume of approximately 250 mL. After evaporation, the samples were stored for 30 days until secular equilibrium was achieved between Ra-226 and Rn-222. The values obtained, by using RAD7 detector, for distilled water, as expected, are near zero averaging 0.021 ± 0.016 Bq/L. The average value found in the water of known concentration was 0.099 ± 0.011 Bq/L, also close to the expected 0.1 Bq/L. The conclusion is that the application of an evaporation process is efficient and the proposed methodology is a proven alternative to decrease the statistical errors. (author)

  14. Conservation of the rad21 Schizosaccharomyces pombe DNA double-strand break repair gene in mammals

    Purpose/Objective: Genetic factors are likely to be major determinants of human cellular ionizing radiation sensitivity. DNA double strand breaks (dsbs) are significant ionizing radiation-induced lesions; cellular DNA dsb processing is also important in a number of other contexts. To further the understanding of DNA dsb processing in mammalian cells, we cloned and sequenced mammalian homologs of the rad21 Schizosaccharomyces pombe DNA dsb repair gene. Materials and Methods: The genes were cloned by evolutionary walking, exploiting sequence homology between the yeast and mammalian genes. Results: No major motifs indicative of a particular function were present in the predicted amino acid sequences of the mammalian genes. Alignment of the Rad21 amino acid sequence with its putative homologs showed that similarity was distributed across the length of the proteins, with more highly conserved regions at both termini. The mHR21sp (mouse homolog ofR ad21, S. pombe) and hHR21sp (humanh omolog of Rad21, S. pombe) predicted proteins were 96% identical, whereas the human and S. pombe proteins were 25% identical and 47% similar. RNA blot analysis showed that mHR21sp mRNA was abundant in all adult mouse tissues examined, with highest expression in testis and thymus. In addition to a 3.1kb mRNA transcript in all tissues, an additional 2.2kb transcript was present at a high level in post-meiotic spermatids, white expression of the 3.1kb mRNA in testis was confined to the meiotic compartment. hHR21sp mRNA was cell cycle regulated in human cells, increasing in late S phase to a peak in G2 phase. The level of hHR21sp transcripts was not altered by exposure of normal diploid fibroblasts to 10 Gy ionizing radiation. In situ hybridization showed mHR21sp resided on chromosome 15D3, whereashHR21sp localized to the syntenic 8q24 region. Conclusion: Cloning these novel mammalian genes and characterization of their protein products should contribute to the understanding of cellular DNA dsb

  15. Results from the HiRadMat Primary Beam Line Commissioning

    Hessler, C; Bauche, J; Bestmann, K; Blanco Sancho, J; Conan, N; Cornelis, K; Efthymiopoulos, I; Gaillard, H; Goddard, B; Grenier, D; Gros, G; Habert, A; Jensen, L; Kain, V; Le Godec, G; Meddahi, M; Pelletier, S; Pepinster, P; Puccio, B; Theis, C; Trilhe, P; Vandoni, G; Wenninger, J

    2011-01-01

    The High Radiation to Materials facility (HiRadMat) is a new experimental area at CERN, for studies of the impact of high-intensity pulsed beams on accelerator components and materials. The beam is delivered from the SPS by a new primary beam line, which has been constructed during the 2010/11 winter technical stop. The paper summarizes the construction phase and describes the results from the beam line commissioning in spring 2011. Beam parameter and aperture measurements are presented, as well as steering tests. A special emphasis has been put on the handling of the exceptionally flexible beam line optics in the control system.

  16. RAD KOD KUĆE – ZAKONSKE ODREDBE, KATEGORIJE, PREDNOSTI I NEDOSTACI

    Lipnjak, Gorana

    2012-01-01

    SAŽETAK: U posljednje vrijeme, a u svrhu učinkovitijeg poslovanja, sve se više primjenjuje kategorija rada na izdvojenom radnom mjestu, pretežno kod kuće. Naime, zbog nastojanja poslodavaca da smanje troškove radnog prostora, a s druge strane zahtjeva radnika za što fleksibilnijim načinom rada, takav pristup poslovnim zadacima ima sve više pristaša. U prednosti su svi oni koji su vezani za rad s računalom, budući da su u mogućnosti koristiti se prednostima novih komunikacijskih tehnologija i ...

  17. RadCon: Parameter report focusing on Tropical and Subtropical environments in Australia

    Models to simulate the transfer of radionuclides through air, water and terrestrial ecosystems have been developed and used regularly over the last 20 years. RadCon was developed as a simple model to assess the radiological consequences, as dose, to humans of short-term depositions of radionuclides. Internal exposure via inhalation and ingestion are included in this model as well as external exposure from the passing cloud (cloud shine) and from radioactivity deposited on the ground (ground shine).Initially, the RadCon model will deal with the Australian and South East Asian region but flexibility has been incorporated into the design to allow application in other regions. In a manner similar to a geographic information system, the display of input and output data allows quick access to the results, both numerically and graphically. Coloured concentration gradients, stepping through time, are superimposed on the area of interest to present atmospheric and ground concentrations of the radionuclides and, after the calculations, human dose. The model has portability across computer platforms.This report summarises the parameters and some of the transfer factors underlying the calculations. While the focus was on the tropical and subtropical regions in Australia, for many parameters the values may only have been available for temperate regions, in which case this has been used as the default value. The parameter flexibility is a major aspect of this model and a report to describe the editor has been written (Crawford and Domel, ANSTO/M-129). The aim of this document is to chronologically expand on the formulae and parameter tables presented in the Technical Guide (Crawford et al., ANSTO/E-744, May 2000). The two documents should be read together with the Technical Guide presenting the mathematical computations and this report presenting some of the input values used to calculate the end-point results from the computations. A User Guide to assist in the implementation

  18. Separation of cesium from rad waste solutions with hexacyanoferrate(II) resins of copper and cobalt

    The separation of radiocesium from low and intermediate level waste solutions by ion exchange with potassium cobalt hexacyanoferrate(II) and potassium copper-cobalt hexacyanoferrate(II) loaded resins was studied. The distribution coefficient(Kd) of cesium as a function of sodium ion concentration was determined. High batch capacity of these resins with regards to cesium make them ideal sorbents that can be used in once through mode in the treatment of rad waste solutions. (author). 3 refs., 1 fig., 1 tab

  19. HiRadMat: A high‐energy, pulsed beam, material irradiation facility

    Charitonidis, Nikolaos

    2016-01-01

    HiRadMat is a facility constructed in 2011, designed to provide high-intensity pulsed beams to an irradiation area where different material samples or accelerator components can be tested. The facility, located at the CERN SPS accelerator complex, uses a 440 GeV proton beam with a pulse length up to 7.2 μs and a maximum intensity up to 1E13 protons / pulse. The facility, a unique place for performing state-of-the art beam-to-material experiments, operates under transnational access and welcomes and financially supports, under certain conditions, experimental teams to perform their experiments.

  20. FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51

    Chu, Wai Kit; Payne, Miranda J; Beli, Petra;

    2015-01-01

    leads to hyperrecombination, as well as several phenotypes indicative of an altered response to DNA replication stress. These effects are likely to be mediated by the enhanced nuclear matrix association of the ubiquitylation-resistant RAD51. These data are consistent with FBH1 acting as a negative......Unscheduled homologous recombination (HR) can lead to genomic instability, which greatly increases the threat of neoplastic transformation in humans. The F-box DNA helicase 1 (FBH1) is a 3'-5' DNA helicase with a putative function as a negative regulator of HR. It is the only known DNA helicase to...

  1. www.PedRad.info, the first bilingual case-oriented publication platform for pediatric radiology

    On the Internet, there are few pediatric radiology databases. The most important and complete Web site is PediatricRadiology.com, which provides many radiological links but does not have its own database. We present an Internet project called PedRad.info (also known as Kinderradiologie-Online). The open-source, case-oriented publication platform publishes validated pediatric radiology findings on the Internet. A comparable on-line program, even for adult radiology, does not exist, so this tool is a pioneer in the area of Web-based information technology for medical and radiological communities. (orig.)

  2. Identification of six pathogenic RAD51C mutations via mutational screening of 1228 Danish individuals with increased risk of hereditary breast and/or ovarian cancer

    Jønson, Lars; Ahlborn, Lise B; Steffensen, Ane Y; Djursby, Malene; Ejlertsen, Bent; Timshel, Susanne; Nielsen, Finn C; Gerdes, Anne-Marie; Hansen, Thomas V O

    2016-01-01

    cancer families. We screened the RAD51C gene in 1228 Danish hereditary breast and/or ovarian cancer families by next-generation sequencing analysis. The frequency of the identified variants was examined in the exome sequencing project database and in data from 2000 Danish exomes and the presumed...... identified six pathogenic RAD51C mutations as well as 23 variants of uncertain clinical significance and one benign variant. Together, the study extends our knowledge of the RAD51C mutation spectrum and supports that RAD51C should be included in gene panel testing of individuals with high risk of breast and......Germ-line mutations in the RAD51C gene have recently been identified in families with breast and ovarian cancer and have been associated with an increased risk of ovarian cancer. In this study, we describe the frequency of pathogenic RAD51C mutations identified in Danish breast and/or ovarian...

  3. Radon monitoring in groundwater samples from some areas of northern Rajasthan, India, using a RAD7 detector.

    Rani, Asha; Mehra, Rohit; Duggal, Vikas

    2013-01-01

    Radon monitoring has been increasingly conducted worldwide because of the hazardous effects of radon on the health of human beings. In the present research, groundwater samples were taken from hand pumps at different areas of the districts of SriGanganagar, Hanumangarh, Sikar and Churu in northern Rajasthan. RAD7, an electronic radon detector (Durridge co., USA), was used to estimate the radon concentration in groundwater used for drinking. Radon concentration in the groundwater ranged from 0.5 ± 0.3 Bq l(-1) (Chimanpura) to 85.7±4.9 Bq l(-1)(Khandela) with an average value of 9.03±1.03 Bq l(-1). In 89 % of the samples, radon concentration is well below the allowed maximum contamination level (MCL) of radon concentration in water of 11 Bq l(-1), proposed by US Environmental Protection Agency (USEPA). Only in 11 % of the samples, the recorded values were found to be higher than MCL proposed by USEPA and only in 5 % of the samples, the recorded values were found to be higher than the values between 4 and 40 Bq l(-1) suggested for radon concentration in water for human consumption by the United Nations Scientific Committee on the effect of Atomic Radiation (UNSCEAR). The annual effective dose in stomach and lungs per person was also evaluated in this research. The estimated total annual effective dose of adults ranged from 1.34 to 229.68 µSv y(-1). The total annual effective dose from three locations of the studied area was found to be greater than the safe limit (0.1 mSv y(-1)) recommended by World Health Organization and EU Council. PMID:22826356

  4. High-Resolution Mapping of Homologous Recombination Events in rad3 Hyper-Recombination Mutants in Yeast.

    Sabrina L Andersen

    2016-03-01

    Full Text Available The Saccharomyces cerevisae RAD3 gene is the homolog of human XPD, an essential gene encoding a DNA helicase of the TFIIH complex involved in both nucleotide excision repair (NER and transcription. Some mutant alleles of RAD3 (rad3-101 and rad3-102 have partial defects in DNA repair and a strong hyper-recombination (hyper-Rec phenotype. Previous studies showed that the hyper-Rec phenotype associated with rad3-101 and rad3-102 can be explained as a consequence of persistent single-stranded DNA gaps that are converted to recombinogenic double-strand breaks (DSBs by replication. The systems previously used to characterize the hyper-Rec phenotype of rad3 strains do not detect the reciprocal products of mitotic recombination. We have further characterized these events using a system in which the reciprocal products of mitotic recombination are recovered. Both rad3-101 and rad3-102 elevate the frequency of reciprocal crossovers about 100-fold. Mapping of these events shows that three-quarters of these crossovers reflect DSBs formed at the same positions in both sister chromatids (double sister-chromatid breaks, DSCBs. The remainder reflects DSBs formed in single chromatids (single chromatid breaks, SCBs. The ratio of DSCBs to SCBs is similar to that observed for spontaneous recombination events in wild-type cells. We mapped 216 unselected genomic alterations throughout the genome including crossovers, gene conversions, deletions, and duplications. We found a significant association between the location of these recombination events and regions with elevated gamma-H2AX. In addition, there was a hotspot for deletions and duplications at the IMA2 and HXT11 genes near the left end of chromosome XV. A comparison of these data with our previous analysis of spontaneous mitotic recombination events suggests that a sub-set of spontaneous events in wild-type cells may be initiated by incomplete NER reactions, and that DSCBs, which cannot be repaired by sister

  5. Interrogation of the protein-protein interactions between human BRCA2 BRC repeats and RAD51 reveals atomistic determinants of affinity

    Cole, Daniel J.; Eeson Rajendra; Meredith Roberts-Thomson; Bryn Hardwick; Grahame J. McKenzie; Payne, Mike C.; Ashok R Venkitaraman; Chris-Kriton Skylaris

    2011-01-01

    The breast cancer suppressor BRCA2 controls the recombinase RAD51 in the reactions that mediate homologous DNA recombination, an essential cellular process required for the error-free repair of DNA double-stranded breaks. The primary mode of interaction between BRCA2 and RAD51 is through the BRC repeats, which are ~35 residue peptide motifs that interact directly with RAD51 in vitro. Human BRCA2, like its mammalian orthologues, contains 8 BRC repeats whose sequence and spacing are evolutionar...

  6. Nanoscopic exclusion between Rad51 and 53BP1 after ion irradiation in human HeLa cells

    Reindl, Judith; Drexler, Guido A.; Girst, Stefanie; Greubel, Christoph; Siebenwirth, Christian; Drexler, Sophie E.; Dollinger, Günther; Friedl, Anna A.

    2015-12-01

    Many proteins involved in detection, signalling and repair of DNA double-strand breaks (DSB) accumulate in large number in the vicinity of DSB sites, forming so called foci. Emerging evidence suggests that these foci are sub-divided in structural or functional domains. We use stimulated emission depletion (STED) microscopy to investigate localization of mediator protein 53BP1 and recombination factor Rad51 after irradiation of cells with low linear energy transfer (LET) protons or high LET carbon ions. With a resolution better than 100 nm, STED microscopy and image analysis using a newly developed analyzing algorithm, the reduced product of the differences from the mean, allowed us to demonstrate that with both irradiation types Rad51 occupies spherical regions of about 200 nm diameter. These foci locate within larger 53BP1 accumulations in regions of local 53BP1 depletion, similar to what has been described for the localization of Brca1, CtIP and RPA. Furthermore, localization relative to 53BP1 and size of Rad51 foci was not different after irradiation with low and high LET radiation. As expected, 53BP1 foci induced by low LET irradiation mostly contained one Rad51 focal structure, while after high LET irradiation, most foci contained >1 Rad51 accumulation.

  7. A comprehensive study on the photon energy response of RadFET dosimeters using the PENELOPE Monte Carlo code

    Kahraman, A.; Kaya, S.; Jaksic, A.; Yilmaz, E.

    2015-05-01

    Radiation-sensing Field Effect Transistors (RadFETs or MOSFET dosimeters) with SiO2 gate dielectric have found applications in space, radiotherapy clinics, and high-energy physics laboratories. More sensitive RadFETs, which require modifications in device design, including gate dielectric, are being considered for personal dosimetry applications. This paper presents results of a detailed study of the RadFET energy response simulated with PENELOPE Monte Carlo code. Alternative materials to SiO2 were investigated to develop high-efficiency new radiation sensors. Namely, in addition to SiO2, Al2O3 and HfO2 were simulated as gate material and deposited energy amounts in these layers were determined for photon irradiation with energies between 20 keV and 5 MeV. The simulations were performed for capped and uncapped configurations of devices irradiated by point and extended sources, the surface area of which is the same with that of the RadFETs. Energy distributions of transmitted and backscattered photons were estimated using impact detectors to provide information about particle fluxes within the geometrical structures. The absorbed energy values in the RadFETs material zones were recorded. For photons with low and medium energies, the physical processes that affect the absorbed energy values in different gate materials are discussed on the basis of modelling results. The results show that HfO2 is the most promising of the simulated gate materials.

  8. Genetic polymorphism at codon 546 of the human RAD17 contributes to the risk for esophageal squamous cell carcinoma

    Yasuda, Yukiko; Sakai, Akiko; Ito, Sachio; Mita, Yuichiro; Sonoyama, Takayuki; Tanabe, Shunsuke; Shirakawa, Yasuhiro; Naomoto, Yoshio; Katayama, Hiroshi; Shimizu, Kenji

    2016-01-01

    Human RAD17, a human homolog of the Schizosaccharomyces pombe cell cycle checkpoint gene RAD17, plays a significant role in activating checkpoint signals in response to DNA damage. We evaluated the association of hRAD17 Leu546Arg (rs1045051), a missense single nucleotide polymorphism, with the risk of esophageal squamous cell carcinoma in relation to smoking and alcohol consumption history in 154 esophageal squamous cell carcinoma male patients and 695 cancer-free male controls by a case-control study conducted in Japan. The results showed that the hRAD17 Arg/Arg genotype compared to the Leu/Leu and Leu/Arg genotypes was significantly associated with the risk of the esophageal squamous cell carcinoma with an adjusted odds ratios of 2.22 (95% CI: 1.19-4.16 P=0.013). In stratified studies, the risk of esophageal squamous cell carcinoma was markedly higher in light drinkers (less than 23 g ethanol/day) with the Arg/Arg genotype than in heavy drinkers (excess of 23 g ethanol/day) with the Arg/Arg genotype (OR=2.83, 95% CI: 1.05-7.61, P=0.04). We concluded that the genetic variant of hRAD17 Leu546Arg polymorphism exerts a significant effect on esophageal squamous cell carcinoma risk among Japanese men. PMID:27186329

  9. Space Weather Measurements from the Surface of Mars with the RAD Instrument on the Mars Science Laboratory

    Hassler, Donald M.; Rafkin, Scot; Reitz, Guenther; Koehler, Jan; Posner, Arik; Guo, Jingnan; Ehresmann, Bent; Zeitlin, Cary; Wimmer-Schweingruber, Robert; Matthiä, Daniel

    2016-07-01

    The Radiation Assessment Detector (RAD) is a compact, lightweight energetic particle analyzer currently operating on the surface of Mars as part of the Mars Science Laboratory (MSL) Mission. RAD is providing the first measurements of the energetic particle radiation environment on the surface of another planet due to solar flares, coronal mass ejections (CMEs), and galactic cosmic rays (GCRs). RAD is providing synoptic measurements of the energetic particle environment at a 2nd location in heliosphere (other than near-Earth or L1), and will aid heliospheric modeling over solar cycle. These observations of SEP fluxes are contributing to a solar energetic particle (SEP) event database at Mars and the Martian surface to aid prediction of Solar Particle Events (SPEs), including onset, temporal & size predictions. This presentation will provide an overview of the RAD investigation and present measurements of the solar flare, GCR and radiation environment on the surface of Mars, and discuss the importance of providing broad heliospheric coverage for situational awareness of space weather as we plan to send humans out into deep space and to Mars. RAD is supported by NASA (HEOMD) under JPL subcontract #1273039 to SwRI, and by DLR in Germany under contract with Christian-Albrechts-Universitat (CAU).

  10. First experimental evidence of hydrodynamic tunneling of ultra–relativistic protons in extended solid copper target at the CERN HiRadMat facility

    Schmidt, R.; Grenier, D.; Wollmann, D. [CERN-AB, 1211 Geneva 23 (Switzerland); Blanco Sancho, J. [CERN-AB, 1211 Geneva 23, Switzerland and Ecole Polytechnique Federale de Lausanne, Lausanne (Switzerland); Burkart, F. [CERN-AB, 1211 Geneva 23, Switzerland and Goethe University, Frankfurt (Germany); Tahir, N. A. [GSI Helmholtzzentrum für Schwerionenforschung, Planckstraße 1, 64291 Darmstadt (Germany); Shutov, A. [Institute of Problems of Chemical Physics, Chernogolovka (Russian Federation); Piriz, A. R. [E.T.S.I. Industriales, Universidad de Castilla-La Mancha, 13071 Ciudad Real (Spain)

    2014-08-15

    A novel experiment has been performed at the CERN HiRadMat test facility to study the impact of the 440 GeV proton beam generated by the Super Proton Synchrotron on extended solid copper cylindrical targets. Substantial hydrodynamic tunneling of the protons in the target material has been observed that leads to significant lengthening of the projectile range, which confirms our previous theoretical predictions [N. A. Tahir et al., Phys. Rev. Spec. Top.-Accel. Beams 15, 051003 (2012)]. Simulation results show very good agreement with the experimental measurements. These results have very important implications on the machine protection design for powerful machines like the Large Hadron Collider (LHC), the future High Luminosity LHC, and the proposed huge 80 km circumference Future Circular Collider, which is currently being discussed at CERN. Another very interesting outcome of this work is that one may also study the field of High Energy Density Physics at this test facility.

  11. First experimental evidence of hydrodynamic tunneling of ultra–relativistic protons in extended solid copper target at the CERN HiRadMat facility

    Schmidt, R; Sancho, J Blanco; Burkart, F; Grenier, D; Wollmann, D; Tahir, N A; Shutov, A; Piriz, A R

    2014-01-01

    A novel experiment has been performed at the CERN HiRadMat test facility to study the impact of the 440 GeV proton beam generated by the Super Proton Synchrotron on extended solid copper cylindrical targets. Substantial hydrodynamic tunneling of the protons in the target material has been observed that leads to significant lengthening of the projectile range, which confirms our previous theoretical predictions [N. A. Tahir et al., Phys. Rev. Spec. Top.-Accel. Beams 15, 051003 (2012)]. Simulation results show very good agreement with the experimental measurements. These results have very important implications on the machine protection design for powerful machines like the Large Hadron Collider (LHC), the future High Luminosity LHC, and the proposed huge 80 km circumference Future Circular Collider, which is currently being discussed at CERN. Another very interesting outcome of this work is that one may also study the field of High Energy Density Physics at this test facility.

  12. RadBallTM Technology Testing in the Savannah River Site's Health Physics Instrument Calibration Laboratory

    The UK's National Nuclear Laboratory (NNL) has developed a radiation-mapping device that can locate and quantify radioactive hazards within contaminated areas of the nuclear industry. The device, known as RadBallTM, consists of a colander-like outer collimator that houses a radiation-sensitive polymer sphere. The collimator has over two hundred small holes; thus, specific areas of the polymer sphere are exposed to radiation becoming increasingly more opaque in proportion to the absorbed dose. The polymer sphere is imaged in an optical-CT scanner that produces a high resolution 3D map of optical attenuation coefficients. Subsequent analysis of the optical attenuation data provides information on the spatial distribution of sources in a given area forming a 3D characterization of the area of interest. The RadBallTM technology has been deployed in a number of technology trials in nuclear waste reprocessing plants at Sellafield in the UK and facilities of the Savannah River National Laboratory (SRNL). This paper summarizes the tests completed at SRNL Health Physics Instrument Calibration Laboratory (HPICL).

  13. Mapping of the gynoecy in bitter gourd (Momordica charantia using RAD-seq analysis.

    Hideo Matsumura

    Full Text Available Momordica charantia is a monoecious plant of the Cucurbitaceae family that has both male and female unisexual flowers. Its unique gynoecious line, OHB61-5, is essential as a maternal parent in the production of F1 cultivars. To identify the DNA markers for this gynoecy, a RAD-seq (restriction-associated DNA tag sequencing analysis was employed to reveal genome-wide DNA polymorphisms and to genotype the F2 progeny from a cross between OHB61-5 and a monoecious line. Based on a RAD-seq analysis of F2 individuals, a linkage map was constructed using 552 co-dominant markers. In addition, after analyzing the pooled genomic DNA from monoecious or gynoecious F2 plants, several SNP loci that are genetically linked to gynoecy were identified. GTFL-1, the closest SNP locus to the putative gynoecious locus, was converted to a conventional DNA marker using invader assay technology, which is applicable to the marker-assisted selection of gynoecy in M. charantia breeding.

  14. Atmospheric measurement analysis for the Radiometric Calibration Test Site (RadCaTS)

    Czapla-Myers, Jeffrey

    2015-09-01

    The Radiometric Calibration Test Site (RadCaTS) was developed by the University of Arizona in the early 2000s to collect ground-based data in support of the calibration and validation of Earth-observing sensors. It uses the reflectance-based approach, which requires measurements of the atmosphere and surface reflectance. The measurements are used in MODTRAN to determine the at-sensor radiance for a given time and date. In the traditional reflectance-based approach, on-site personnel use an automated solar radiometer (ASR) to measure the atmospheric attenuation, but in the case of RadCaTS, an AERONET Cimel sun photometer is used to make atmospheric measurements. This work presents a comparison between the Cimel-derived atmospheric characteristics such as aerosol optical depth, the Angstrom exponent, and the columnar water vapor, to those derived using a traditional solar radiometer. The top-of-atmosphere radiance derived using the Cimel and ASR measurements are compared using Landsat 8 OLI bands as a test case for the period 2012-2014 to determine if any biases exist between the two methodologies.

  15. The QSAR study of flavonoid-metal complexes scavenging rad OH free radical

    Wang, Bo-chu; Qian, Jun-zhen; Fan, Ying; Tan, Jun

    2014-10-01

    Flavonoid-metal complexes have antioxidant activities. However, quantitative structure-activity relationships (QSAR) of flavonoid-metal complexes and their antioxidant activities has still not been tackled. On the basis of 21 structures of flavonoid-metal complexes and their antioxidant activities for scavenging rad OH free radical, we optimised their structures using Gaussian 03 software package and we subsequently calculated and chose 18 quantum chemistry descriptors such as dipole, charge and energy. Then we chose several quantum chemistry descriptors that are very important to the IC50 of flavonoid-metal complexes for scavenging rad OH free radical through method of stepwise linear regression, Meanwhile we obtained 4 new variables through the principal component analysis. Finally, we built the QSAR models based on those important quantum chemistry descriptors and the 4 new variables as the independent variables and the IC50 as the dependent variable using an Artificial Neural Network (ANN), and we validated the two models using experimental data. These results show that the two models in this paper are reliable and predictable.

  16. AN EXPERIMENT AT HiRadMat: IRRADIATION OF HIGH-Z MATERIALS

    Blanco Sancho, J; Schmidt, R; Tahir, N A

    2011-01-01

    Calculations of the impact of dense high intensity proton beams into material has been presented in several papers [1, 2, 3]. This paper presents the plans for an experiment to validate the theoretical results. The experiment will be performed at the High Radiation to Materials (HiRadMat) facility at the CERN-SPS. The HiRadMat facility is dedi- cated to shock beam impact experiments. It allows testing of accelerator components, in particular those of LHC, to the impact of high-intensity pulsed beams. This facility will allow to study High Energy Density physics as the en- ergy density will be high enough to create strongly coupled plasma in the core of high-Z materials (copper, tungsten) and to produce strong enough pressure waves to create a density depletion channel along the beam axis (tunneling effect) [4, 5]. The paper introduces the layout of the ex- periment and the instrumentation to detect tunneling of pro- tons through the target as well as the expected results based on simulations.

  17. An Experiment at HiRadMat: Irradiation of high-Z Materials

    Blanco Sancho, J; Schmidt, R; Tahir, N A

    2011-01-01

    Calculations of the impact of dense high intensity proton beams into material has been presented in several papers [1,2,3]. This paper presents the plans for an experiment to validate the theoretical results. The experiment will be performed at the High Radiation to Materials (HiRadMat) facility at the CERN-SPS. The HiRadMat facility is dedicated to shock beam impact experiments. It allows testing of accelerator components, in particular those of LHC, to the impact of high-intensity pulsed beams. This facility will allow to study High Energy Density physics as the energy density will be high enough to create strongly coupled plasma in the core of high-Z materials (copper, tungsten) and to produce strong enough pressure waves to create a density depletion channel along the beam axis (tunneling effect) [4,5]. The paper introduces the layout of the experiment and the instrumentation to detect tunneling of protons through the target as well as the expected results based on simulations.

  18. First Year of Operations in the HiRadMat Irradiation Facility at CERN

    Fabich, A; Conan, N; Cornelis, K; De Paoli, D; Efthymiopoulos, I; Evrard, S; Gaillard, H; Grenard, J L; Lazzaroni, M; Pardons, A; Seraphin, Y; Theis, C; Weiss, K

    2013-01-01

    The HiRadMat facility [1] is designed to provide a test area where the effect of high-intensity pulsed beams on materials or accelerator component assemblies can be studied. The facility is not designed for long-term irradiation studies but rather for single pulse experiments to study the onset of material damage. The designed target is ten experiments per year, with 1015 protons or about 30 high intensity pulses per experiment, thus a total of 1016 protons per year for the whole facility. It is judged that for the majority of the experiments a small number of high intensity pulses would be sufficient in order to investigate the damage to the test samples whilst keeping the activation levels reasonably low such that post-irradiation tests could be performed after a reasonable cool-down period. The HiRadMat facility is situated in the former West Area Neutrino Facility (WANF) target tunnel and is about 35 m below ground. It takes the fast extracted beam from the long straight section LSS6 of SPS, the same use...

  19. A ddRAD Based Linkage Map of the Cultivated Strawberry, Fragaria xananassa.

    Davik, Jahn; Sargent, Daniel James; Brurberg, May Bente; Lien, Sigbjørn; Kent, Matthew; Alsheikh, Muath

    2015-01-01

    The cultivated strawberry (Fragaria ×ananassa Duch.) is an allo-octoploid considered difficult to disentangle genetically due to its four relatively similar sub-genomic chromosome sets. This has been alleviated by the recent release of the strawberry IStraw90 whole genome genotyping array. However, array resolution relies on the genotypes used in the array construction and may be of limited general use. SNP detection based on reduced genomic sequencing approaches has the potential of providing better coverage in cases where the studied genotypes are only distantly related from the SNP array's construction foundation. Here we have used double digest restriction-associated DNA sequencing (ddRAD) to identify SNPs in a 145 seedling F1 hybrid population raised from the cross between the cultivars Sonata (♀) and Babette (♂). A linkage map containing 907 markers which spanned 1,581.5 cM across 31 linkage groups representing the 28 chromosomes of the species. Comparing the physical span of the SNP markers with the F. vesca genome sequence, the linkage groups resolved covered 79% of the estimated 830 Mb of the F. × ananassa genome. Here, we have developed the first linkage map for F. × ananassa using ddRAD and show that this technique and other related techniques are useful tools for linkage map development and downstream genetic studies in the octoploid strawberry. PMID:26398886

  20. RadBallTM Technology Testing in the Savannah River Site's Health Physics Instrument Calibration Laboratory

    Farfán, Eduardo B.; Foley, Trevor Q.; Jannik, G. Timothy; Harpring, Larry J.; Gordon, John R.; Blessing, Ronald; Rusty Coleman, J.; Holmes, Christopher J.; Oldham, Mark; Adamovics, John; Stanley, Steven J.

    2010-11-01

    The UK's National Nuclear Laboratory (NNL) has developed a radiation-mapping device that can locate and quantify radioactive hazards within contaminated areas of the nuclear industry. The device, known as RadBallTM, consists of a colander-like outer collimator that houses a radiation-sensitive polymer sphere. The collimator has over two hundred small holes; thus, specific areas of the polymer sphere are exposed to radiation becoming increasingly more opaque in proportion to the absorbed dose. The polymer sphere is imaged in an optical-CT scanner that produces a high resolution 3D map of optical attenuation coefficients. Subsequent analysis of the optical attenuation data provides information on the spatial distribution of sources in a given area forming a 3D characterization of the area of interest. The RadBallTM technology has been deployed in a number of technology trials in nuclear waste reprocessing plants at Sellafield in the UK and facilities of the Savannah River National Laboratory (SRNL). This paper summarizes the tests completed at SRNL Health Physics Instrument Calibration Laboratory (HPICL).

  1. RadBall Technology Testing in the Savannah River Site's Health Physics Instrument Calibration Laboratory.

    Farfán, Eduardo B; Foley, Trevor Q; Jannik, G Timothy; Harpring, Larry J; Gordon, John R; Blessing, Ronald; Coleman, J Rusty; Holmes, Christopher J; Oldham, Mark; Adamovics, John; Stanley, Steven J

    2010-01-01

    The United Kingdom's National Nuclear Laboratory (NNL) has developed a radiation-mapping device that can locate and quantify radioactive hazards within contaminated areas of the nuclear industry. The device, known as RadBall(™), consists of a colander-like outer collimator that houses a radiation-sensitive polymer sphere. The collimator has over two hundred small holes; thus, specific areas of the polymer sphere are exposed to radiation becoming increasingly more opaque in proportion to the absorbed dose. The polymer sphere is imaged in an optical-CT scanner that produces a high resolution 3D map of optical attenuation coefficients. Subsequent analysis of the optical attenuation data provides information on the spatial distribution of sources in a given area forming a 3D characterization of the area of interest. The RadBall(™) technology has been deployed in a number of technology trials in nuclear waste reprocessing plants at Sellafield in the United Kingdom and facilities of the Savannah River National Laboratory (SRNL). This paper summarizes the tests completed at SRNL Health Physics Instrument Calibration Laboratory (HPICL). PMID:21617738

  2. Specific Absorbed Fractions of Electrons and Photons for Rad-HUMAN Phantom Using Monte Carlo Method

    Wang, Wen; Long, Peng-cheng; Hu, Li-qin

    2014-01-01

    The specific absorbed fractions (SAF) for self- and cross-irradiation are effective tools for the internal dose estimation of inhalation and ingestion intakes of radionuclides. A set of SAFs of photon and electron were calculated using the Rad-HUMAN phantom, a computational voxel phantom of Chinese adult female and created using the color photographic image of the Chinese Visible Human (CVH) data set. The model can represent most of Chinese adult female anatomical characteristics and can be taken as an individual phantom to investigate the difference of internal dose with Caucasians. In this study, the emission of mono-energetic photons and electrons of 10keV to 4MeV energy were calculated using the Monte Carlo particle transport calculation code MCNP. Results were compared with the values from ICRP reference and ORNL models. The results showed that SAF from Rad-HUMAN have the similar trends but larger than those from the other two models. The differences were due to the racial and anatomical differences in o...

  3. RAD sequencing enables unprecedented phylogenetic resolution and objective species delimitation in recalcitrant divergent taxa.

    Herrera, Santiago; Shank, Timothy M

    2016-07-01

    Species delimitations is problematic in many cases due to the difficulty of evaluating predictions from species hypotheses. In many cases delimitations rely on subjective interpretations of morphological and/or DNA data. Species with inadequate genetic resources needed to answer questions regarding evolutionary relatedness and genetic uniqueness are particularly problematic. In this study, we demonstrate the utility of restriction site associated DNA sequencing (RAD-seq) to objectively resolve unambiguous phylogenetic relationships in a recalcitrant group of deep-sea corals with divergences >80 million years. We infer robust species boundaries in the genus Paragorgia by testing alternative delimitation hypotheses using a Bayes Factors delimitation method. We present substantial evidence rejecting the current morphological species delimitation model for the genus and infer the presence of cryptic species associated with environmental variables. We argue that the suitability limits of RAD-seq for phylogenetic inferences cannot be assessed in terms of absolute time, but are contingent on taxon-specific factors. We show that classical taxonomy can greatly benefit from integrative approaches that provide objective tests to species delimitation hypotheses. Our results lead the way for addressing further questions in marine biogeography, community ecology, population dynamics, conservation, and evolution. PMID:26993764

  4. Measurements of the Charged and Neutral Particle Spectra on the Martian Surface with MSL/RAD

    Koehler, Jan

    The Radiation Assessment Detector (RAD) onboard Mars Science Laboratory’s rover Curiosity is the first ever instrument to measure the energetic particle radiation environment on the surface of Mars. Charged particles are a major component of this environment, both galactic cosmic rays propagating to the Martian surface and secondary particles created by interactions of these cosmic rays with the atoms of the Martian atmosphere and soil. Another important factor for determining the biological impact of the Martian surface radiation is the specific contribution of neutrons, which possess a high biological effectiveness. In contrast to charged particles, neutrons and gamma rays are generally only measured indirectly. Their measurement is the result of a complex convolution of the incident particle spectrum with the measurement process. We apply an inversion method to calculate the gamma/neutron spectra from the RAD neutral particle measurements. Here we show first surface measurements of the Martian particle spectra and compare them to theoretical predictions. Measuring the Martian particle spectra is an essential step for determining the mutagenic influences to past or present life at or beneath the Martian surface as well as the radiation hazard for future human exploration, including the shielding design of a potential habitat.

  5. The KYxxL motif in Rad17 protein is essential for the interaction with the 9-1-1 complex.

    Fukumoto, Yasunori; Ikeuchi, Masayoshi; Nakayama, Yuji; Yamaguchi, Naoto

    2016-09-01

    ATR-dependent DNA damage checkpoint is the major DNA damage checkpoint against UV irradiation and DNA replication stress. The Rad17-RFC and Rad9-Rad1-Hus1 (9-1-1) complexes interact with each other to contribute to ATR signaling, however, the precise regulatory mechanism of the interaction has not been established. Here, we identified a conserved sequence motif, KYxxL, in the AAA+ domain of Rad17 protein, and demonstrated that this motif is essential for the interaction with the 9-1-1 complex. We also show that UV-induced Rad17 phosphorylation is increased in the Rad17 KYxxL mutants. These data indicate that the interaction with the 9-1-1 complex is not required for Rad17 protein to be an efficient substrate for the UV-induced phosphorylation. Our data also raise the possibility that the 9-1-1 complex plays a negative regulatory role in the Rad17 phosphorylation. We also show that the nucleotide-binding activity of Rad17 is required for its nuclear localization. PMID:27387238

  6. Modeling the variations of Dose Rate measured by RAD during the first MSL Martian year: 2012-2014

    Guo, Jingnan; Wimmer-Schweingruber, Robert F; Rafkin, Scot; Hassler, Donald M; Posner, Arik; Heber, Bernd; Koehler, Jan; Ehresmann, Bent; Appel, Jan K; Boehm, Eckart; Boettcher, Stephan; Burmeister, Soenke; Brinza, David E; Lohf, Henning; Martin, Cesar; Kahanpaeae, H; Reitz, Guenther

    2015-01-01

    The Radiation Assessment Detector (RAD), on board Mars Science Laboratory's (MSL) rover Curiosity, measures the {energy spectra} of both energetic charged and neutral particles along with the radiation dose rate at the surface of Mars. With these first-ever measurements on the Martian surface, RAD observed several effects influencing the galactic cosmic ray (GCR) induced surface radiation dose concurrently: [a] short-term diurnal variations of the Martian atmospheric pressure caused by daily thermal tides, [b] long-term seasonal pressure changes in the Martian atmosphere, and [c] the modulation of the primary GCR flux by the heliospheric magnetic field, which correlates with long-term solar activity and the rotation of the Sun. The RAD surface dose measurements, along with the surface pressure data and the solar modulation factor, are analysed and fitted to empirical models which quantitatively demonstrate} how the long-term influences ([b] and [c]) are related to the measured dose rates. {Correspondingly we ...

  7. The rad52-Y66A allele alters the choice of donor template during spontaneous chromosomal recombination

    de Mayolo, A.A.; Sunjevaric, I.; Reid, R.;

    2010-01-01

    Spontaneous mitotic recombination is a potential source of genetic changes Such as loss of heterozygosity and chromosome translocations, which may lead to genetic disease. In this study we have used a rad52 hyper-recombination mutant, rad52-Y66A, to investigate the process of spontaneous...... heteroallelic recombination in the yeast Soccharomyces cerevisiae. We find that spontaneous recombination has different genetic requirements, depending on whether the recombination event occurs between chromosomes or between chromosome and plasmid sequences. The hyper-recombination phenotype of the rad52-Y66A......-pass of the window-of-opportunity for sister chromatid recombination normally promoted by MRE11-dependent damage-induced cohesion thereby causing a shift towards interchromosomal recombination....

  8. The Saccharomyces cerevisiae RAD30 gene, a homologue of Escherichia coli dinB and umuC, is DNA damage inducible and functions in a novel error-free postreplication repair mechanism

    Damage-inducible mutagenesis in prokaryotes is largely dependent upon the activity of the UmuD'C-like proteins. Since many DNA repair processes are structurally and/or functionally conserved between prokaryotes and eukaryotes, we investigated the role of RAD30, a previously uncharacterized Saccharomyces cerevisiae DNA repair gene related to the Escherichia coli dinB, umuC and S. cerevisiae REV1 genes, in UV resistance and UV-induced mutagenesis. Similar to its prokaryotic homologues, RAD30 was found to be damage inducible. Like many S. cerevisiae genes involved in error-prone DNA repair, epistasis analysis clearly places RAD30 in the RAD6 group and rad30 mutants display moderate UV sensitivity reminiscent of rev mutants. However, unlike rev mutants, no defect in UV-induced reversion was seen in rad30 strains. While rad6 and rad18 are both epistatic to rad30, no epistasis was observed with rev1, rev3, rev7 or rad5, all of which are members of the RAD6 epistasis group. These findings suggest that RD30 participates in a novel error-free repair pathway dependent on RAD6 and RAD18, but independent of REV1, REV3, REV7 and RAD5. (author)

  9. The BRCA1/BRCA2/Rad51 complex is a prognostic and predictive factor in early breast cancer

    Background and purpose: The breast cancer susceptibility genes BRCA1 and BRCA2 interact with Rad51, one of the central components in the homologous recombination repair pathway. This study evaluates the prognostic and predictive role of BRCA1, BRCA2 and Rad51, individually and as a complex, in breast cancer. Materials and methods: Expression of BRCA1, BRCA2 and Rad51 was investigated using immunohistochemistry in tumours from 224 women with early breast cancer, who were randomised to receive postoperative radiotherapy or adjuvant chemotherapy (CMF). Results: Fifty-three percent (112/212) of the tumours had reduced expression of the BRCA1/BRCA2/Rad51 complex. Low expression correlated to high histologic grade (p = 0.05). Patients with low expression of the complex developed significantly more local recurrences as compared to patients with high expression (RR = 3.20, 95% CI 1.48-6.88, p = 0.003). Expression of the BRCA1/BRCA2/Rad51 complex was an independent prognostic factor in multivariate analysis (p = 0.03). Patients with low expression of the complex responded well to radiotherapy (RR = 0.31, 95% CI 0.14-0.70, p = 0.005), whereas patients with high expression had few local recurrences and no additional benefit from radiotherapy (RR = 1.08, 95% CI 0.40-2.90, p = 0.88). Conclusions: Low expression of the BRCA1/BRCA2/Rad51 complex is a marker of poor prognosis, but predicts good response to radiotherapy in patients with early breast cancer

  10. Mimivirus reveals Mre11/Rad50 fusion proteins with a sporadic distribution in eukaryotes, bacteria, viruses and plasmids

    Ogata Hiroyuki

    2011-09-01

    Full Text Available Abstract Background The Mre11/Rad50 complex and the homologous SbcD/SbcC complex in bacteria play crucial roles in the metabolism of DNA double-strand breaks, including DNA repair, genome replication, homologous recombination and non-homologous end-joining in cellular life forms and viruses. Here we investigated the amino acid sequence of the Mimivirus R555 gene product, originally annotated as a Rad50 homolog, and later shown to have close homologs in marine microbial metagenomes. Results Our bioinformatics analysis revealed that R555 protein sequence is constituted from the fusion of an N-terminal Mre11-like domain with a C-terminal Rad50-like domain. A systematic database search revealed twelve additional cases of Mre11/Rad50 (or SbcD/SbcC fusions in a wide variety of unrelated organisms including unicellular and multicellular eukaryotes, the megaplasmid of a bacterium associated to deep-sea hydrothermal vents (Deferribacter desulfuricans and the plasmid of Clostridium kluyveri. We also showed that R555 homologs are abundant in the metagenomes from different aquatic environments and that they most likely belong to aquatic viruses. The observed phyletic distribution of these fusion proteins suggests their recurrent creation and lateral gene transfers across organisms. Conclusions The existence of the fused version of protein sequences is consistent with known functional interactions between Mre11 and Rad50, and the gene fusion probably enhanced the opportunity for lateral transfer. The abundance of the Mre11/Rad50 fusion genes in viral metagenomes and their sporadic phyletic distribution in cellular organisms suggest that viruses, plasmids and transposons played a crucial role in the formation of the fusion proteins and their propagation into cellular genomes.

  11. SNP discovery in common bean by restriction-associated DNA (RAD) sequencing for genetic diversity and population structure analysis.

    Valdisser, Paula Arielle M R; Pappas, Georgios J; de Menezes, Ivandilson P P; Müller, Bárbara S F; Pereira, Wendell J; Narciso, Marcelo G; Brondani, Claudio; Souza, Thiago L P O; Borba, Tereza C O; Vianello, Rosana P

    2016-06-01

    Researchers have made great advances into the development and application of genomic approaches for common beans, creating opportunities to driving more real and applicable strategies for sustainable management of the genetic resource towards plant breeding. This work provides useful polymorphic single-nucleotide polymorphisms (SNPs) for high-throughput common bean genotyping developed by RAD (restriction site-associated DNA) sequencing. The RAD tags were generated from DNA pooled from 12 common bean genotypes, including breeding lines of different gene pools and market classes. The aligned sequences identified 23,748 putative RAD-SNPs, of which 3357 were adequate for genotyping; 1032 RAD-SNPs with the highest ADT (assay design tool) score are presented in this article. The RAD-SNPs were structurally annotated in different coding (47.00 %) and non-coding (53.00 %) sequence components of genes. A subset of 384 RAD-SNPs with broad genome distribution was used to genotype a diverse panel of 95 common bean germplasms and revealed a successful amplification rate of 96.6 %, showing 73 % of polymorphic SNPs within the Andean group and 83 % in the Mesoamerican group. A slightly increased He (0.161, n = 21) value was estimated for the Andean gene pool, compared to the Mesoamerican group (0.156, n = 74). For the linkage disequilibrium (LD) analysis, from a group of 580 SNPs (289 RAD-SNPs and 291 BARC-SNPs) genotyped for the same set of genotypes, 70.2 % were in LD, decreasing to 0.10 %in the Andean group and 0.77 % in the Mesoamerican group. Haplotype patterns spanning 310 Mb of the genome (60 %) were characterized in samples from different origins. However, the haplotype frameworks were under-represented for the Andean (7.85 %) and Mesoamerican (5.55 %) gene pools separately. In conclusion, RAD sequencing allowed the discovery of hundreds of useful SNPs for broad genetic analysis of common bean germplasm. From now, this approach provides an excellent panel

  12. Preliminary On-Orbit Neutron Dose Equivalent and Energy Spectrum Results from the ISS-RAD Fast Neutron Detector (FND)

    Semones, Edward; Leitgab, Martin

    2016-01-01

    The ISS-RAD instrument was activated on ISS on February 1st, 2016. Integrated in ISS-RAD, the Fast Neutron Detector (FND) performs, for the first time on ISS, routine and precise direct neutron measurements between 0.5 and 8 MeV. Preliminary results for neutron dose equivalent and neutron flux energy distributions from online/on-board algorithms and offline ground analyses will be shown, along with comparisons to simulated data and previously measured neutron spectral data. On-orbit data quality and pre-launch analysis validation results will be discussed as well.

  13. Expression of the denV gene of coliphage T4 in UV-sensitive rad mutants of Saccharomyces cerevisiae

    A plasmid containing the denV gene from bacteriophage T4, under the control of the yeast alcohol dehydrogenase I (ADC1) promoter, conferred a substantial increase in UV resistance in the UV-sensitive Saccharomyces cerevisiae mutants rad1-2 and rad3-2. The UV resistance of the denV+ yeast cells was cell cycle dependent and correlated well with the level of the denV gene product as measured by immunoblotting and by a photoreversal assay for pyrimidine dimer-DNA glycosylase activity

  14. Utjecaj organizacijske kulture, timskog rada i razvoja organizacije na predani rad u organizaciji: posrednička uloga ljudskog kapitala

    Ghorbanhosseini, Masoud

    2013-01-01

    Cilj je ovoga rada napraviti model za određivanje utjecaja organizacijske kulture, timskog rada i razvoja organizacije na predani rad u organizaciji s naglaskom na posredničku ulogu ljudskog kapitala (ljudstva, zaposlenika). Slučajnim je izborom odabrano 266 zaposlenih u Industrijskoj grupi SAFA i oni su odgovorili na pitanja postavljena u istraživanju. Analiza dobivenih podataka je izvršena testom analize načina ponašanja. Rezultati pokazuju da kultura organizacije, timski rad i razvoj organ...

  15. TagDigger: user-friendly extraction of read counts from GBS and RAD-seq data

    Clark, Lindsay V.; Sacks, Erik J.

    2016-01-01

    Background In genotyping-by-sequencing (GBS) and restriction site-associated DNA sequencing (RAD-seq), read depth is important for assessing the quality of genotype calls and estimating allele dosage in polyploids. However, existing pipelines for GBS and RAD-seq do not provide read counts in formats that are both accurate and easy to access. Additionally, although existing pipelines allow previously-mined SNPs to be genotyped on new samples, they do not allow the user to manually specify a su...

  16. Rec2 Interplay with both Brh2 and Rad51 Balances Recombinational Repair in Ustilago maydis

    Kojic, M.; Zhou, Q.; Lisby, M.; Holloman, Willilam K.

    2006-01-01

    prepared from Escherichia coli cells expressing the proteins, we found that Rec2 interacts physically not only with Rad51 and itself but also with Brh2. Transgenic expression of Brh2 in rec2 mutants can effectively restore radiation resistance, but the frequencies of spontaneous Rad51 focus formation and...... missegregation in meiotic products is an indicator of a corrupted process. The results demonstrate that the importance of Rec2 function is not only in stimulating recombination activity but also in ensuring that recombination is properly controlled....

  17. The Rad17 homologue of Arabidopsis is involved in the regulation of DNA damage repair and homologous recombination

    Heitzeberg, F.; Chen, I. P.; Hartung, F.; Orel, N.; Angelis, Karel; Puchta, H.

    2004-01-01

    Roč. 38, č. 6 (2004), s. 954-968. ISSN 0960-7412 R&D Projects: GA MŠk ME 535; GA ČR GA521/01/1418; GA MŠk ME 534 Grant ostatní: European Comunity Grant Agency(XE) QLG2-CT-2001-01397 Institutional research plan: CEZ:AV0Z5038910 Keywords : Arabidopsis * RAD17 * RAD9 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.367, year: 2004

  18. Measurement of radon on Misasa district, Tottori pref. using the PICO-RAD detector and a liquid scintillation spectrometer. 3

    By means of a radon detecting device (Packard Pico-Rad System) using absorbed active charcoal and a liquid scintillation spectrometer, studies on environmental movements of radon and its decay nuclides on Misasa district in Tottori pref. were done continuously on last year. Its minimum detection limits of radon in the air are 1.7Bq/m3 and 0.43Bq/l in the water on counting time of 200 minutes. This method is able to measure conveniently and rapidly on sampling period for 24 hours. (1) Radon concentrations in the air at Misasa environs area on October and November, 1995 were ranged 7.7-59Bq/m3 in outdoor and 13-141Bq/m3 in indoor. On the results measured on Misasa area, 222Rn concentrations on Asahi district located southward from Misasa spa district and Takeda district along Tenjin stream are high, on Kojika district located east-southward from Misasa spa district and Mitoku district are low and outdoor 222Rn concentrations on Ningyo toge neighboring are low level with ranged 12-31Bq/m3. Indoor 222Rn concentrations at Takeda district are about 4 times higher than Kojika district showed the lowest concentration and those of Kojika district are almost similar to those of Higashi Osaka. Indoor 222Rn concentration are higher than outdoor, the mean ratio of indoor to outdoor 222Rn concentration on a few sample of Takeda and Asahi districts (upper stream) are about 2 and those on the other district are shown in low tendency ranged 1-1.3. There are a few difference among some districts. (2) 222Rn concentration variations in a dwelling at Misasa spa district were observed from May to December 1995 in the time course. They are varied in range of 53-121Bq/m3 indoor, 9-50Bq/m3 outdoor and 48-188Bq/m3 in bathroom. (3) 222Rn concentration variations in water samples at Misasa spa district are 91-161Bq/l in hot spring, 2.3-10Bq/l in river water and 14-34Bq/l in well water from May to December 1995. (author)

  19. Space experiment "Cellular Responses to Radiation in Space (CellRad)": Hardware and biological system tests.

    Hellweg, Christine E; Dilruba, Shahana; Adrian, Astrid; Feles, Sebastian; Schmitz, Claudia; Berger, Thomas; Przybyla, Bartos; Briganti, Luca; Franz, Markus; Segerer, Jürgen; Spitta, Luis F; Henschenmacher, Bernd; Konda, Bikash; Diegeler, Sebastian; Baumstark-Khan, Christa; Panitz, Corinna; Reitz, Günther

    2015-11-01

    One factor contributing to the high uncertainty in radiation risk assessment for long-term space missions is the insufficient knowledge about possible interactions of radiation with other spaceflight environmental factors. Such factors, e.g. microgravity, have to be considered as possibly additive or even synergistic factors in cancerogenesis. Regarding the effects of microgravity on signal transduction, it cannot be excluded that microgravity alters the cellular response to cosmic radiation, which comprises a complex network of signaling pathways. The purpose of the experiment "Cellular Responses to Radiation in Space" (CellRad, formerly CERASP) is to study the effects of combined exposure to microgravity, radiation and general space flight conditions on mammalian cells, in particular Human Embryonic Kidney (HEK) cells that are stably transfected with different plasmids allowing monitoring of proliferation and the Nuclear Factor κB (NF-κB) pathway by means of fluorescent proteins. The cells will be seeded on ground in multiwell plate units (MPUs), transported to the ISS, and irradiated by an artificial radiation source after an adaptation period at 0 × g and 1 × g. After different incubation periods, the cells will be fixed by pumping a formaldehyde solution into the MPUs. Ground control samples will be treated in the same way. For implementation of CellRad in the Biolab on the International Space Station (ISS), tests of the hardware and the biological systems were performed. The sequence of different steps in MPU fabrication (cutting, drilling, cleaning, growth surface coating, and sterilization) was optimized in order to reach full biocompatibility. Different coatings of the foil used as growth surface revealed that coating with 0.1 mg/ml poly-D-lysine supports cell attachment better than collagen type I. The tests of prototype hardware (Science Model) proved its full functionality for automated medium change, irradiation and fixation of cells. Exposure of

  20. An attempt to apply the rad-equivalence notion to the biological effects on formaldehyde

    A renewal of interest for formaldehyde (FA) arose three years ago when it was shown that ultraviolet (UV) sensitive bacterial mutants were also sensitive to FA. These mutants are defective either in the exicision of UV induced pyrimidine dimers or in DNA polymerase I. In other words it appears that there is to some extents an overlap in the recognition and repair of UV and FA induced lesions in wild type cells. The genetic effects of this simple molecule on an unicellular eucaryotic organism Saccharomyces cerevisiae which is genetically well known is studied. One of the aim is to establish for several end-points the validity and extent of applicability of the rad-equivalence notion. For comparison some experiments is also performed with mammalian cells cultivated in vitro

  1. RAD-seq derived genome-wide nuclear markers resolve the phylogeny of tunas.

    Díaz-Arce, Natalia; Arrizabalaga, Haritz; Murua, Hilario; Irigoien, Xabier; Rodríguez-Ezpeleta, Naiara

    2016-09-01

    Although species from the genus Thunnus include some of the most commercially important and most severely overexploited fishes, the phylogeny of this genus is still unresolved, hampering evolutionary and traceability studies that could help improve conservation and management strategies for these species. Previous attempts based on mitochondrial and nuclear markers were unsuccessful in inferring a congruent and reliable phylogeny, probably due to mitochondrial introgression events and lack of enough phylogenetically informative markers. Here we infer the first genome-wide nuclear marker-based phylogeny of tunas using restriction site associated DNA sequencing (RAD-seq) data. Our results, derived from phylogenomic inferences obtained from 128 nucleotide matrices constructed using alternative data assembly procedures, support a single Thunnus evolutionary history that challenges previous assumptions based on morphological and molecular data. PMID:27286653

  2. The Final Beam Line Design for the HiRadMat Test Facility

    Hessler, C; Meddahi, M

    2010-01-01

    The High Radiation to Materials facility - hereafter HiRadMat - is designed to allow testing of accelerator components, in particular those of the LHC and its injectors, with the impact of high-intensity pulsed beams. The facility is currently under construction, as an approved CERN project. The installation of the dedicated primary beam line and experimental area is planned during the 2010-2011 technical stop. It will be ready for users after commissioning and some test running in October 2011. A detailed proton beam line design has been performed in order to fulfil the beam parameter specification, in particular the demanding optics flexibility at the test stand location. The studies presented include trajectory correction and aperture studies as well as specifications of magnetic systems, power converters, beam instrumentation and vacuum systems

  3. Proposal to characterise legacy Sellafield ponds using SONAR and RadLine Trade-Mark-Sign

    Reddy, Sarah F., E-mail: s.reddy@lancaster.ac.uk [Engineering Department, Lancaster University, Bailrigg, Lancaster, Lancashire LA1 4YR (United Kingdom); Monk, Stephen D.; Nye, Daniel W.; Colling, Bethany R.; Stanley, Steven J. [Engineering Department, Lancaster University, Bailrigg, Lancaster, Lancashire LA1 4YR (United Kingdom)

    2012-07-15

    Sellafield Nuclear Reprocessing Plant in Cumbria contains storage ponds built in the 1950s which was originally intended to hold spent nuclear fuel for reprocessing, and eventual production of weapons grade plutonium. Parts of the spent fuel have corroded; some are buried under a layer of sediment or intertwined with other debris and removal and destruction of this nuclear waste is not a trivial task due to elevated radiation levels. We propose a system in collaboration with the National Nuclear Laboratory (NNL) to characterise the ponds using a system containing three main parts; an ultrasonic SONAR system used to physically map the pond, scintillator based radiation detector (known as RadLine Trade-Mark-Sign) used to map the pond from a radiation point of view, and bespoke software intended to combine the physical and radiation plots of this environment to create an overall 3D source map.

  4. OSPOSOBLJAVANJE ZA SAMOSTALAN RAD I ZAPOŠLJAVANJE OSOBA S INVALIDITETOM

    Ergović, Jela

    2007-01-01

    U otežanim gospodarskim uvjetima s problemom velike nezaposlenosti u općoj populaciji, osobe s invaliditetom vrlo se teško zapošljavaju. Njihovo obrazovanje i osposobljavanje za rad nije u skladu s potrebama tržišta. Uglavnom se obrazuju (osposobljavaju) za zanimanja koja se više nigdje ne traže, najčešće su informatički neobrazovani, što je u današnjim uvjetima gotovo nepremostiva prepreka zapošljavanju. S gledišta pojedinca, od obrazovanja se očekuje da bude sredstvo za zadovoljenje niza ži...

  5. Application of empore TM strontium rad disks to the analysis of radiostrontium in environmental water samples

    A solid phase extraction method for analyzing radioactive strontium in surface, ground, and drinking waters is presented. Strontium is simply isolated by pulling an acidified sample aliquot through an EmporeTM strontium rad disk with a vacuum, and the disk is subsequently assayed for beta activity. The method is efficient, safe, reliable, and potentially field deployable. Sample preparation and counting source preparation may be condensed into a single procedure, thereby improving efficiency and eliminating many potential sources of laboratory error. Moreover, many of the hazardous chemicals associated with traditional strontium procedures are eliminated. Samples are easily batched, and a one-liter sample may be prepared with as little as 20 min of effort. For a one-liter aqueous sample, up to 3 mg of strontium can be retained by the disks. Chemical and radiometric interferences are discussed. (orig.)

  6. First Results of an Experiment on Advanced Collimator Materials at CERN HiRadMat Facility

    Bertarelli, A; Assmann, R; Berthome, E; Boccone, V; Carra, F; Cerutti, F; Charrondiere, C; Dallocchio, A; Donze, M; Francon, P; Garlasche, M; Gentini, L; Guinchard, M; Mariani, N; Masi, A; Moyret, P; Redaelli, S; Rossi, A; Calderon Cueva, M; Charitonidis, N; Peroni, L; Scapin, M

    2013-01-01

    A comprehensive, first-of-its-kind experiment (HRMT-14) has been recently carried out at CERN HiRadMat facility on six different materials of interest for Beam Intercepting Devices (collimators, targets, dumps). Both traditional materials (Mo, W and Cu alloys) as well as advanced metal/diamond and metal/graphite composites were tested under extreme conditions as to pressure, density and temperature, leading to the development of highly dynamic phenomena as shock-waves, spallation, explosions. Experimental data were acquired, mostly in real time, relying on extensive integrated instrumentation (strain gauges, temperature and vacuum sensors) and on remote acquisition devices (laser Doppler vibrometer and high-speed camera). The experiment was a success under all points of view in spite of the technological challenges and harsh environment. First measurements are in good agreement with results of complex simulations, confirming the effectiveness of the acquisition system and the reliability of advanced numerical...

  7. A 6 device SOI new technology for mixed analog-digital and rad-hard applications

    DMILL technology is being developed for very rad-hard analog-digital applications, such as space and military circuits or as electronics for the future generation of high energy collider (LHC, CERN, Geneva). Both CMOS and junction (JFET and bipolar) transistors are needed. A new process has been integrated, based on a 1.2μm thick silicon film on insulator (SIMOX plus epitaxy), a complete dielectric isolation and low temperature process. The mean feature is that six different components are fabricated on the same wafer, taking into account the 12 volts supply voltage constraint for some analog applications. The first electrical characteristics are presented in this paper. The optimization capabilities of such a hardened CBi-CJ-CMOS technology are discussed

  8. Nova radna zadaća ljekarnika: rad s računalom

    Markotić-Bogavčić, Gordana

    2012-01-01

    Cilj je ovog rada bio utvrditi koliko rad s računalom utječe na promjene vidnih funkcija ljekarnika te na pojavu smetnji na vratnom dijelu kralježnice. U presječnom istraživanju ispitane su vidne funkcije i subjektivne smetnje pri radu 50 ljekarnika (srednja dob 41,8±11 godina), te 56 službenika (srednja dob 36,2±8,6 godina), koji 40 sati tjedno rade na računalu. Pri tome, ljekarnici pretežno stoje, a službenici sjede. Od subjektivnih smetnji pri radu, suzenje očiju i bolovi u vratnoj kraljež...

  9. Rad World -- computer-animated video radiation and hazardous waste-management science curriculum

    The Rad World computer-animated video and curriculum materials were developed through a grant from the Waste-management Education and Research Consortium. The package, which includes a computer-animated video, hands-on activities, and multidisciplinary lessons concerning radiation and hazardous-waste management, was created to approach these subjects in an informative, yet entertaining, manner. The lessons and video, designed to supplement studies of energy and physical science at the middle school and high school level, also implement quality and consistent science education as outlined by the New Mexico Science Standards and Benchmarks (1995). Consistent with the curriculum standards and benchmarks, the curriculum includes library research, collaborative learning, hands-on-science, and discovery learning. Pre- and post-tests are included

  10. Immunochip analysis identifies association of the RAD50/IL13 region with human longevity

    Flachsbart, Friederike; Ellinghaus, David; Gentschew, Liljana;

    2016-01-01

    -wide significant signal (PI mmunochip = 7.01 × 10(-9) ) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PI mmunochip < 5 × 10(-4) for replication in two samples from France......Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls...... seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life....

  11. RAD-seq derived genome-wide nuclear markers resolve the phylogeny of tunas

    Díaz-Arce, Natalia

    2016-06-07

    Although species from the genus Thunnus include some of the most commercially important and most severely overexploited fishes, the phylogeny of this genus is still unresolved, hampering evolutionary and traceability studies that could help improve conservation and management strategies for these species. Previous attempts based on mitochondrial and nuclear markers were unsuccessful in inferring a congruent and reliable phylogeny, probably due to mitochondrial introgression events and lack of enough phylogenetically informative markers. Here we infer the first genome-wide nuclear marker-based phylogeny of tunas using restriction site associated DNA sequencing (RAD-seq) data. Our results, derived from phylogenomic inferences obtained from 128 nucleotide matrices constructed using alternative data assembly procedures, support a single Thunnus evolutionary history that challenges previous assumptions based on morphological and molecular data.

  12. Protective effect of partial shielding on 600 rad γ-irradiated dogs

    For groups with a total of 20 dogs were whole-body exposed to 600 rad of 60Co γ-rays with shieling of head and neck, chest, abdomen, and pelvis, separately, by 10 cm thick lead bricks. All dogs survived, showing some different characteristic features in each group. Peripheral leucocyte counts began to rise on day 9-11 in all groups. In contrast to other groups, the head and neck shielded group showed a much lower incidence of fever despite of signifinicant decrease of leucocytes. The lymphocyte count in the abdomen shielded group was over 1000/mm3 which was higher than those in other groups within 30 days, suggesting less severity of lymphocytic injury in these dogs

  13. Examination of Beryllium Under Intense High Energy Proton Beam at CERN's HiRadMat Facility

    Ammigan, K; Hurh, P; Zwaska, R; Atherton, A; Caretta, O; Davenne, t; Densham, C; Fitton, M; Loveridge, P; O'Dell, J; Roberts, S; Kuksenko, v; Butcher, M; Calviani, M; Guinchard, M; Losito, R

    2015-01-01

    Beryllium is extensively used in various accelerator beam lines and target facilities as material for beam win- dows, and to a lesser extent, as secondary particle produc- tion targets. With increasing beam intensities of future ac- celerator facilities, it is critical to understand the response of beryllium under extreme conditions to avoid compro- mising particle production efficiency by limiting beam pa- rameters. As a result, the planned experiment at CERN’s HiRadMat facility will take advantage of the test facility’s tunable high intensity proton beam to probe and investigate the damage mechanisms of several grades of beryllium. The test matrix will consist of multiple arrays of thin discs of varying thicknesses as well as cylinders, each exposed to increasing beam intensities. Online instrumentations will acquire real time temperature, strain, and vibration data of the cylinders, while Post-Irradiation-Examination (PIE) of the discs will exploit advanced microstructural characteri- zation and imagin...

  14. The influence on rabbit platelet aggregation following γ ray whole-body-irradiation with 400 rads

    In this paper, using the method of turbidmetric technique, changes of rabbit platelet aggregation are observed following γ ray whole-body irradiation with 400 rads. The results indicated that the function of blood platelet aggregation was risen from the first to the fifth day after irradiation, but reduced at the seventh day and markedly at the tenth. It is believed that the early elevation of platelet aggregation may result in increase of adherence and coagulation, and enhance microcirculation disturbances. In addition, a large number of platelets and coagulation factors were consumed, and it might be one of the causes of hemorrhage syndrome after exposure. Dueing early therapy of radiation injury, therefore, it is of benefit for improving the repair of radiation injury to inhibit platelet aggregation

  15. Proposal to characterise legacy Sellafield ponds using SONAR and RadLine™.

    Reddy, Sarah F; Monk, Stephen D; Nye, Daniel W; Colling, Bethany R; Stanley, Steven J

    2012-07-01

    Sellafield Nuclear Reprocessing Plant in Cumbria contains storage ponds built in the 1950s which was originally intended to hold spent nuclear fuel for reprocessing, and eventual production of weapons grade plutonium. Parts of the spent fuel have corroded; some are buried under a layer of sediment or intertwined with other debris and removal and destruction of this nuclear waste is not a trivial task due to elevated radiation levels. We propose a system in collaboration with the National Nuclear Laboratory (NNL) to characterise the ponds using a system containing three main parts; an ultrasonic SONAR system used to physically map the pond, scintillator based radiation detector (known as RadLine™) used to map the pond from a radiation point of view, and bespoke software intended to combine the physical and radiation plots of this environment to create an overall 3D source map. PMID:22698817

  16. Phosphorylation of Rad9 at serine 328 by cyclin A-Cdk2 triggers apoptosis via interfering Bcl-xL.

    Zhuo Zhan

    Full Text Available Cyclin A-Cdk2, a cell cycle regulated Ser/Thr kinase, plays important roles in a variety of apoptoticprocesses. However, the mechanism of cyclin A-Cdk2 regulated apoptosis remains unclear. Here, we demonstrated that Rad9, a member of the BH3-only subfamily of Bcl-2 proteins, could be phosphorylated by cyclin A-Cdk2 in vitro and in vivo. Cyclin A-Cdk2 catalyzed the phosphorylation of Rad9 at serine 328 in HeLa cells during apoptosis induced by etoposide, an inhibitor of topoisomeraseII. The phosphorylation of Rad9 resulted in its translocation from the nucleus to the mitochondria and its interaction with Bcl-xL. The forced activation of cyclin A-Cdk2 in these cells by the overexpression of cyclin A,triggered Rad9 phosphorylation at serine 328 and thereby promoted the interaction of Rad9 with Bcl-xL and the subsequent initiation of the apoptotic program. The pro-apoptotic effects regulated by the cyclin A-Cdk2 complex were significantly lower in cells transfected with Rad9S328A, an expression vector that encodes a Rad9 mutant that is resistant to cyclin A-Cdk2 phosphorylation. These findings suggest that cyclin A-Cdk2 regulates apoptosis through a mechanism that involves Rad9phosphorylation.

  17. The rhp6+ gene of Schizosaccharomyces pombe: a structural and functional homolog of the RAD6 gene from the distantly related yeast Saccharomyces cerevisiae.

    P. Reynolds (Paul); M.H.M. Koken (Marcel); J.H.J. Hoeijmakers (Jan); S. Prakash; L. Prakash

    1990-01-01

    textabstractThe RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin conjugating enzyme and is required for DNA repair, DNA-damage-induced mutagenesis and sporulation. Here, we show that RAD6 and the rhp6+ gene from the distantly related yeast Schizosaccharomyces pombe share a high degree of st

  18. The Breast Imaging Reporting and Data System (BI-RADS) in the Dutch breast cancer screening programme: its role as an assessment and stratification tool

    To assess the suitability of the Breast Imaging Reporting and Data System (BI-RADS) as a quality assessment tool in the Dutch breast cancer screening programme. The data of 93,793 screened women in the Amsterdam screening region (November 2005-July 2006) were reviewed. BI-RADS categories, work-up, age, final diagnosis and final TNM classification were available from the screening registry. Interval cancers were obtained through linkage with the cancer registry. BI-RADS was introduced as a pilot in the Amsterdam region before the nationwide introduction of digital mammography (2009-2010). A total of 1,559 women were referred to hospital (referral rate 1.7 %). Breast cancer was diagnosed in 485 women (detection rate 0.52 %); 253 interval cancers were reported, yielding a programme sensitivity of 66 % and specificity of 99 %. BI-RADS 0 had a lower positive predictive value (PPV, 14.1 %) than BI-RADS 4 (39.1 %) and BI-RADS 5 (92.9 %; P < 0.0001). The number of invasive procedures and tumour size also differed significantly between BI-RADS categories (P < 0.0001). The significant differences in PPV, invasive procedures and tumour size match with stratification into BI-RADS categories. It revealed inter-observer variability between screening radiologists and can thus be used as a quality assessment tool in screening and as a stratification tool in diagnostic work-up. (orig.)

  19. The proviral genome of radiation leukemia virus (RadLV): molecular cloning, restriction analysis and integration sites in tumor cell DNA

    An infectious clone of the linear, unintegrated RadLV provirus was obtained by insertion in the plasmid pBR322. Its restriction map was indistinguishable from that of the majority of the multiple proviral copies, which are found apparently at random sites in the DNA of RadLV-induced rat thymic lymphomas

  20. The recombination protein RAD52 cooperates with the excision repair protein OGG1 for the repair of oxidative lesions in mammalian cells

    de Souza-Pinto, Nadja C; Maynard, Scott; Hashiguchi, Kazunari;

    2009-01-01

    number of protein interactions have been identified for OGG1, while very few appear to have functional consequences. We report here that OGG1 interacts with the recombination protein RAD52 in vitro and in vivo. This interaction has reciprocal functional consequences as OGG1 inhibits RAD52 catalytic...

  1. BNL ALARA Center's development of a computerized radiological assessment and design system (RADS)

    The US Department of Energy's (DOE) Office of Health Physics and Industrial Hygiene sponsored a study of Radiological Engineering Programs at selected DOE contractor facilities. This study was conducted to review, evaluate, and summarize techniques and practices that should be considered in the design phase that reduce dose and the spread of radioactive materials during subsequent construction and operation of DOE radiological facilities. As in a previous study on operational ALARA programs, a variety of good-practice documents will be generated. It is envisioned that these documents will serve as a resource to assist radiological engineers in the process of designing radiological facilities, and in performing radiological safety/ALARA design reviews. This paper presents the features for three good-practice documents and related software applications that are being developed based on the findings of this study. The proposed software called Radiological Assessment and Design System (RADS) will be a menu-driven database and spreadsheet program. It will be designed to provide easy, consistent, and effective implementation of the methodologies described in the three good-practice documents. These documents and the associated RADS software will provide the user with the following three functions: (1) enter dose assessment information and data into computer worksheets and provide printed tables of the results which can then be inserted into safety analysis reports or cost-benefit analyses, (2) perform a wide variety of sorts of radiological design criteria from DOE Orders and produce a checklist of the desired design criteria, and (3) enter cost/benefit data and qualitative rating of attributes for various design alternatives which reduce dose into computer worksheets and provide printed reports of cost-effectiveness results

  2. Areva's Actiflo trademark -Rad water treatment system for the Fukushima nuclear power plant

    In the wake of the March 11th 2011 earthquake and tsunami and the subsequent flooding of several of the Fukushima Daiichi reactor units, Japan and the Japanese utility Tepco faced a crisis situation with incredible challenges. Sea water and later desalted sea water used for open circuit post-accident reactor cooling accumulated in the basements of four reactor buildings as well as in the basements of the turbine buildings on the site. The water had been heavily contaminated due to the fact that it had been in contact with molten fuel assemblies in the reactor cores. The water from flooding and subsequent cooling needed to be collected, along with rainwater. Despite the use of additional water storage systems brought to the site, a shortage of water storage capacity was expected in a 3-month timeframe, especially in view of the coming rain season in Japan. The overall water inventory was estimated at around 110,000 tons with a contamination up to the order of 1 Ci/l (3.7 x 1010 Bq/l). To avoid an over-flow of highly contaminated water into the sea Tepco envisaged establishing a water treatment system. This article focuses on the Actiflo trademark -Rad water treatment project implemented by Areva as part of the Tepco general water treatment scheme. It presents a detailed look at the functional principle of the Actiflo trademark -Rad process, related on-the-fly research and development, an explanation of system implementation challenges and a brief summary of operation results. (orig.)

  3. HLW flowsheet material balance for DWPF rad operation with Tank 51 sludge and ITP Cycle 1 precipitate

    This document presents the details of the Savannah River Plant Flowsheet for the Rad Operation with Tank Sludge and ITP Cycle 1 Precipitate. Topics discussed include: material balance; radiolysis chemistry of tank precipitates; algorithm for ESP washing; chemistry of hydrogen and ammonia generation in CPC; batch sizes for processing feed; and total throughput of a streams during one cycle of operation

  4. radR: an open-source platform for acquiring and analysing data on biological targets observed by surveillance radar

    Matkovich Carolyn

    2010-10-01

    Full Text Available Abstract Background Radar has been used for decades to study movement of insects, birds and bats. In spite of this, there are few readily available software tools for the acquisition, storage and processing of such data. Program radR was developed to solve this problem. Results Program radR is an open source software tool for the acquisition, storage and analysis of data from marine radars operating in surveillance mode. radR takes time series data with a two-dimensional spatial component as input from some source (typically a radar digitizing card and extracts and retains information of biological relevance (i.e. moving targets. Low-level data processing is implemented in "C" code, but user-defined functions written in the "R" statistical programming language can be called at pre-defined steps in the calculations. Output data formats are designed to allow for future inclusion of additional data items without requiring change to C code. Two brands of radar digitizing card are currently supported as data sources. We also provide an overview of the basic considerations of setting up and running a biological radar study. Conclusions Program radR provides a convenient, open source platform for the acquisition and analysis of radar data of biological targets.

  5. The Overexpression of FEN1 and RAD54B May Act as Independent Prognostic Factors of Lung Adenocarcinoma

    Hwang, Jau-Chung; Sung, Wen-Wei; Tu, Hung-Pin; Hsieh, Kun-Chou; Yeh, Chung-Min; Chen, Chih-Jung; Tai, Hui-Chun; Hsu, Chao-Tien; Shieh, Grace S.; Chang, Jan-Gowth; Yeh, Kun-Tu; Liu, Ta-Chih

    2015-01-01

    Synthetic lethality arises when a combination of mutations in two or more genes leads to cell death. However, the prognostic role of concordant overexpression of synthetic lethality genes in protein level rather than a combination of mutations is not clear. In this study, we explore the prognostic role of combined overexpression of paired genes in lung adenocarcinoma. We used immunohistochemical staining to investigate 24 paired genes in 93 lung adenocarcinoma patients and Kaplan-Meier analysis and Cox proportional hazards models to evaluate their prognostic roles. Among 24 paired genes, only FEN1 (Flap endonuclease 1) and RAD54B (RAD54 homolog B) were overexpressed in lung adenocarcinoma patients with poor prognosis. Patients with expression of both FEN1 and RAD54B were prone to have advanced nodal involvement and significantly poor prognosis (HR = 2.35, P = 0.0230). These results suggest that intensive follow up and targeted therapy might improve clinical outcome for patients who show expression of both FEN1 and RAD54B. PMID:26431531

  6. Sds22 participates in Glc7 mediated Rad53 dephosphorylation in MMS-induced DNA damage in Candida albicans.

    Yao, Guangyin; Wan, Junhua; Mu, Chunhua; Liu, Qizheng; Wang, Yue; Sang, Jianli

    2016-08-01

    The protein kinase Rad53 and its orthologs play a fundamental role in regulating the DNA damage checkpoint in eukaryotes. Rad53 is activated by phosphorylation in response to DNA damage and deactivated by dephosphorylation after the damage is repaired. However, the phosphatases involved in Rad53 deactivation are not entirely understood. In this study, by investigating the consequences of overexpressing SDS22, a gene encoding a regulatory subunit of the PP1 phosphatase Glc7, in the human fungal pathogen Candida albicans, we discovered that Sds22 plays an important role in Rad53 dephosphorylation and thus the deactivation of the DNA damage checkpoint. Sds22 cellular levels increase when cells are exposed to DNA damaging agents and decrease after removing the genotoxins. Depletion of Glc7 has similar phenotypes. We provide evidence that Sds2 acts through inhibitory physical association with Glc7. Our findings provide novel insights into the mechanisms for the control of DNA damage checkpoint. Furthermore, SDS22 overexpression reduces C. albicans virulence in a mouse model of systemic infection, suggesting potential targets for developing antifungal drugs. PMID:27328280

  7. Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk

    Orr, Nick; Lemnrau, Alina; Cooke, Rosie;

    2012-01-01

    We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P ...

  8. Small Rad51 and Dmc1 Complexes Often Co-occupy Both Ends of a Meiotic DNA Double Strand Break.

    M Scott Brown

    2015-12-01

    Full Text Available The Eukaryotic RecA-like proteins Rad51 and Dmc1 cooperate during meiosis to promote recombination between homologous chromosomes by repairing programmed DNA double strand breaks (DSBs. Previous studies showed that Rad51 and Dmc1 form partially overlapping co-foci. Here we show these Rad51-Dmc1 co-foci are often arranged in pairs separated by distances of up to 400 nm. Paired co-foci remain prevalent when DSBs are dramatically reduced or when strand exchange or synapsis is blocked. Super-resolution dSTORM microscopy reveals that individual foci observed by conventional light microscopy are often composed of two or more substructures. The data support a model in which the two tracts of ssDNA formed by a single DSB separate from one another by distances of up to 400 nm, with both tracts often bound by one or more short (about 100 nt Rad51 filaments and also by one or more short Dmc1 filaments.

  9. Characterisation of QTL-linked and genome-wide restriction site-associated DNA (RAD markers in farmed Atlantic salmon

    Houston Ross D

    2012-06-01

    Full Text Available Abstract Background Restriction site-associated DNA sequencing (RAD-Seq is a genome complexity reduction technique that facilitates large-scale marker discovery and genotyping by sequencing. Recent applications of RAD-Seq have included linkage and QTL mapping with a particular focus on non-model species. In the current study, we have applied RAD-Seq to two Atlantic salmon families from a commercial breeding program. The offspring from these families were classified into resistant or susceptible based on survival/mortality in an Infectious Pancreatic Necrosis (IPN challenge experiment, and putative homozygous resistant or susceptible genotype at a major IPN-resistance QTL. From each family, the genomic DNA of the two heterozygous parents and seven offspring of each IPN phenotype and genotype was digested with the SbfI enzyme and sequenced in multiplexed pools. Results Sequence was obtained from approximately 70,000 RAD loci in both families and a filtered set of 6,712 segregating SNPs were identified. Analyses of genome-wide RAD marker segregation patterns in the two families suggested SNP discovery on all 29 Atlantic salmon chromosome pairs, and highlighted the dearth of male recombination. The use of pedigreed samples allowed us to distinguish segregating SNPs from putative paralogous sequence variants resulting from the relatively recent genome duplication of salmonid species. Of the segregating SNPs, 50 were linked to the QTL. A subset of these QTL-linked SNPs were converted to a high-throughput assay and genotyped across large commercial populations of IPNV-challenged salmon fry. Several SNPs showed highly significant linkage and association with resistance to IPN, and population linkage-disequilibrium-based SNP tests for resistance were identified. Conclusions We used RAD-Seq to successfully identify and characterise high-density genetic markers in pedigreed aquaculture Atlantic salmon. These results underline the effectiveness of RAD

  10. 心房颤动对慢性心力衰竭伴左室射血分数≥0.50患者预后的临床研究%Impact of atrial fibrillation on prognosis of chronic heart failure patients with left ventricular ejection fraction≥.5

    詹红; TSE Hung-fat; 曹晶茗; LAU Cpu-pak

    2008-01-01

    目的 探讨左室射血分数(LVEF)≥0.50的住院慢性心力衰竭(心衰)患者中心房颤动(房颤)的发生和分布类型,及房颤对此类心衰预后的影响.方法 调查患者417例次,按LVEF<0.50与≥0.50分为两组,根据患者入院前是否有房颤病史分为阵发性房颤、持续性房颤及入院后新发房颤.随后观察并记录严重恶性事件发生情况及因慢性心衰而再人院次数及每两次住院的间隔时间.结果 LVEF<0.50的慢性心衰更多见于男性,一年内心肌梗死的发病率较LVEF≥0.50者高[15.6%(34/218)比8.0%(16/199),P<0.01],且房颤使得患者脑卒中发生率较不伴房颤者明显增高(24.3%(27/111)比8.4%(9/107),P<0.05),急性冠脉综合征、心血管死亡事件例数及死亡数也高于不伴房颤者;在LVEF≥0.50的慢性心衰患者中新发房颤数量较LVEF<0.50者明显增多(51比30,P<0.05),房颤可见伴发在近2/3的患者中,且再入院次数较不伴房颤者增加[(2.78±1.79)次比(2.00±1.35)次,P<0.01],前两次入院间隔时间亦较不伴房颤者缩短[(117±107)d比(154±130)d,P<0.05].结论 房颤更易发生在LVEF≥0.50的慢性心衰患者,导致更短的再入院间隔,强调治疗和管理这类房颤的重要性.%Objective To explore the prevalence, distribution type and impact of atrial fibrillation on prognosis of hospitalized patients with congestive heart failure (CHF) with left ventricular ejection fraction (LVEF)≥ 0.50. Methods The medical records of 417 unselected consecutive patients with CHF were retrospectively reviewed. Patients were categorized as LVEF <0.50 or LVEF≥0.50. And they were also categorized by the past history of atrial fibrillation and divided into three groups: paroxysmal atrial fibrillation, continuous atrial fibrillation and onset of atrial fibrillation after admission. Then the vicious events, the number of readmission due to CHF and the interval between discharge and readmission were observed and

  11. RAD50基因多态性与儿童急性淋巴细胞白血病的相关性%Association between polymorphism of RAD50 gene and acute lymphoid leukemia in children

    李雯; 徐之良

    2015-01-01

    ObjectiveTo investigate the association between single nucleotide polymorphism (SNP) (rs17166050) in RAD50 gene and acute lymphoid leukemia (ALL) in children.MethodsA total of 177 ALL children from Wuhan and surrounding areas and 232 healthy children were selected. The numbers of standard-risk, medium-risk, and high-risk children were 66, 69, and 42, respectively. The genotypes of SNP in RAD50 gene were determined using PCR-RFLP, and the relationship of the RAD50 polymorphism with ALL susceptibility and clinical risk was analyzed.ResultsThe genotype (AA, GA, and GG) distribution of SNP in RAD50 gene showed signiifcant differences between the ALL and control groups (P=0.038), and G allele was signiifcantly associated with ALL susceptibility (OR=1.459, 95%CI: 1.034-2.057,P=0.031). However, the SNP was not associated with the risk stratiifcation of ALL.ConclusionsThe SNP (rs17166050) in RAD50 gene is associated with the susceptibility to ALL in children, but is not associated with the risk stratiifcation of ALL.%目的:探讨RAD50基因的SNP位点(rs17166050)的多态性与我国中部地区儿童急性淋巴细胞白血病(ALL)的相关性。方法177例来自湖北武汉或其周边地区的ALL患儿和232例健康儿童作为研究对象。177例患儿中,标危66例,中危69例,高危42例。利用PCR-RFLP的方法检测RAD50基因SNP位点多态性,研究该多态性与ALL易感性及临床危险度的相关性。结果 ALL组的RAD50基因SNP位点的基因型(AA、GA、GG)分布与对照组相比差异有统计学意义(P=0.038),且G等位基因与ALL易感性显著相关(OR=1.459,95%CI:1.034~2.057,P=0.031);但在ALL组中,该SNP位点的多态性与ALL的危险度不相关。结论 RAD50基因的SNP位点(rs 17166050)的多态性与儿童ALL的易感性相关,但与其危险度分层不具有相关性。

  12. Validity of the breast imaging reporting and data system BI-RADS{sup TM} for clinical mammography in men; Anwendbarkeit des Breast Imaging Reporting and Data System (BI-RADS{sup TM}) auf die klinische Mammographie des Mannes

    Bock, K.; Duda, V.F.; Bonwetsch, C.; Hadji, P.; Schulz, K.D. [Marburg Univ. (Germany). Klinik fuer Gynaekologie, Gynaekologische Endokrinologie und Onkologie; Iwinska-Zelder, J.; Klose, K.J. [Marburg Univ. (Germany). Klinik fuer Diagnostische Radiologie; Rode, G. [Diagnostische Gemeinschaftspraxis Marburg (Germany)

    2001-11-01

    Aim: The implementation of diagnostic standards enhances quality assurance. The American College of Radiology's breast imaging-reporting and data system (BI-RADS{sup TM}) is intended to standardize terminology in the mammography report, the assessment of the findings, and the recommendation af action to be taken. The purpose of this study was to assess the value of the standardized system for clinically apparent male breast tumors. Do the special male anatomy and physiology limit the applicability of an evaluation system designed for female screening mammograms? Methods: 4 investigators with different degrees of experience retrospectively evaluated 160 male mammograms. Our study was based on the 36 cases which could be correlated to histopathological findings: gynecomastia in the majority of cases, but also 4 invasive ductal carcinoma, 1 leiomyosarcoma and 1 ductal carcinoma in situ. Results: Assessment of the mammograms by BI-RADS{sup TM} (3{sup rd} Edition 1998) correctly placed all cases of malignancy into categories 4 and 5 without respect to the investigators's level of experience. Conclusion: Therefore, we conclude that the BI-RADS{sup TM}-classification can successfully be used to classify male mammograms with a high positive predictive value for malignancy. Knowledge of gender-specific imaging characteristics increases the specificity at a constant high level of sensitivity. (orig.) [German] Ziel: In der apparativen Diagnostik dient die Einfuehrung von Standards der Qualitaetssicherung. Das breast imaging-reporting and data system (BI-RADS{sup TM}) des American College of Radiology standardisiert den Sprachgebrauch in der Befundbeschreibung, die Befundbewertung und die resultierenden Empfehlungen in der Mammographie. Unser Interesse galt der Frage, inwieweit dieses System der Kategorisierung von Screening-Mammographien der Frau uebertragbar ist auf klinische Mammographien des Mannes. Begrenzen Anatomie und Physiologie der maennlichen Brustdruese

  13. Low dose radiation effects: an integrative european approach (Risc-Rad Project) coordinated by the Cea

    RISC-RAD (Radiosensitivity of Individuals and Susceptibility to Cancer induced by ionizing Radiations) is an Integrated Project funded by the European Commission under 6. Framework Programme / EURATOM. RISC-RAD started on 1. January 2004 for a duration of four years. Coordinated by Cea (Dr Laure Sabatier), it involves 11 European countries (Austria, Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands, Spain, Sweden and the United Kingdom) and 29 research institutions. Objectives: Exposures to low and protracted doses of ionizing radiation are very frequent in normal living environment, at work places, in industry and in medicine. Effects of these exposures on human health cannot be reliably assessed by epidemiological methods, nor is thoroughly understood by biologists. RISC-RAD project proposes to help bridging the gap of scientific knowledge about these effects. To achieve this goal, a necessary key step is to understand the basic mechanisms by which radiation induces cancer. Studying this multistage process in an integrated way, the project offers a new biological approach characterised by and clear-cut and objective-driven scientific policy: the project is focused on the effects of low doses (less than 100 mSv) and protracted doses of radiation. It aims at identifying new parameters that take into account the differences in radiation responses between individuals. A group of modelers works closely with the experimental teams in order to better quantify the risks associated with low and protracted doses. Research work is divided into five work packages interacting closely with each other. WP1 is dedicated to DNA damage. Ionizing Radiation (IR) produce a broad spectrum of base modifications and DNA strand breaks of different kinds, among which double-strand breaks and 'clustered damage' which is thought to be a major feature in biological effectiveness of IR. The aim of Work Package 1 is to improve understanding of the initial DNA damage induced by

  14. Polymorphisms in RAD51 and their relation with breast cancer in Saudi females

    Tulbah S

    2016-01-01

    Full Text Available Sahar Tulbah,1 Huda Alabdulkarim,2 Mohammad Alanazi,3 Narasimha Reddy Parine,3 Jilani Shaik,3 Akbar Ali Khan Pathan,3 Abdullah Al-Amri,3 Wajahatullah Khan,4 Arjumand Warsy1 1Department of Biochemistry, College of Science, King Saud University, Center of Scientific and Medical Colleges, 2Department of Hematology/Oncology, King Fahad Medical City Hospital, Comprehensive Cancer Center, 3Department of Biochemistry, College of Science, King Saud University, 4Basic Sciences Department, College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia Abstract: The present study aimed at investigating the relationship between rs1801320 (G>C, rs1801321 (G>T, and rs2619681 (C>T RAD51 gene polymorphisms and the risk of breast cancer development in Saudi females. The genotypes were analyzed using TaqMan genotyping assay and polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele frequencies were computed using chi-square or Fisher’s exact test (two-tailed by SPSS 21 software. The results showed that rs1801321G>T GG genotype and G allele frequency were strongly (P<0.0001 related to an elevated risk of breast cancer, while the mutant T allele appeared to provide protection against breast cancer development as observed from the significantly lower (P<0.0001 frequencies of the TT and GT genotypes in cancer patients compared to the healthy controls. The variant rs1801320G>C showed no significant differences in the frequencies of the genotypes and alleles in the patients and the control groups. The CC genotype and C allele frequency of rs2619681 (C>T variant were significantly (P=0.012 higher in cancer patients, whereas the T allele showed a protective effect against cancer development. The frequencies of the three single-nucleotide polymorphisms did not differ in cancer patients with different tumor grades and human epidermal growth factor receptor 2 status (+ or

  15. Functional analysis of the RAD50/MRE11 protein complex through targeted disruption of the murine RAD50 genomic locus: implications for DNA double strand break repair. An astro research fellowship presentation

    Purpose/Objective: The products of the S. cerevisiae genes ScRAD50 and ScMRE11 act in a protein complex and are required for non-homologous end-joining, the predominant mechanism of DNA double strand break (dsb) repair in mammalian cells. Mutation of these genes results in sensitivity to ionizing radiation (IR), a defect in initiation of meiosis, increased and error-prone recombination during mitosis, and overall genomic instability. This resultant phenotype is reminiscent of that seen in mammalian syndromes of genomic instability such as ataxia-telangiectasia and Bloom syndrome, hallmarks of which are radiation sensitivity and predisposition to malignancy. The murine homologues to ScRAD50 and ScMRE11 have recently been identified; both demonstrate impressive primary sequence conservation with their yeast counterparts, and are expected to mediate conserved functions. The roles of muRAD50 in genomic maintenance and in dsb repair will be examined in two parts. The first will include a determination of normal muRAD50 expression patterns. Second, the effects of disruption of the muRAD50 gene will be assessed. A specific targeting event has introduced a conditional murad50 null mutation into the genome of murine embryonic stem (ES) cells. These mutant ES cells are being used to create mutant mice, thus allowing functional characterization of muRAD50 on both the cellular and organismic levels. Such analyses will contribute to the delineation of the mammalian dsb repair pathway and to the cellular response to IR, and will serve as a mammalian model system for genomic instability. Materials and Methods: Wild-type tissue expression patterns and protein-protein interactions were determined by standard biochemical techniques, including immunoprecipitation, polyacrylamide gel electrophoresis, and Western blotting. Molecular cloning techniques were used to create the gene targeting vectors, which were designed to result in either a deletion of exon 1 (equivalent to a null

  16. Studies of DNA repair in Saccharomyces cerevisiae. I. Characterization of a new allele of RAD6. II. Investigation of events in the first cell cycle after DNA damage

    Studies in two independent, but related, areas of DNA repair have been carried out in the eucaryotic yeast, Saccharomyces cerevisiae. The first is the characterization of a new allele in the RAD6 gene suggesting that the gene is multifunctional. The second is the utilization of photoreactivation as a probe of events occurring during the first cell cycle after DNA damage. Strains carrying the new allele, designated rad6-4, of the RAD6 locus are about as sensitive to uv and ionizing radiation as those carrying rad6-1 or rad6-3. Although rad6-4 may well be a missense mutation, the data suggest that the RAD6 gene is multifunctional. One function is necessary to recover from DNA damage in an error-free manner, and the other is concerned with mutagenic processes and sporulation. The loss of photoreversibility (LOP) of ultraviolet induced mutations to arginine independence in an excision defective strain carrying arg4-17 examines the events occurring in the first cell cycle. The post uv protein synthesis causes pyrimidine dimmers to become inaccessible to the photoreactivating enzyme in some unknown manner. There is no evidence indicating whether the normal function of the protein is involved in excision repair, or in one of the two repair processes believed to be inducible; induced mutagenesis or recombinational repair

  17. Affinity purification and partial characterization of a yeast multiprotein complex for nucleotide excision repair using histidine-tagged Rad14 protein

    The nucleotide excision repair (NER) pathway of eukaryotes involves approximately 30 polypeptides. Reconstitution of this pathway with purified components is consistent with the sequential assembly of NER proteins at the DNA lesion. However, recent studies have suggested that NER proteins may be pre-assembled in a high molecular weight complex in the absence of DNA damage. To examine this model further, we have constructed a histidine-tagged version of the yeast DNA damage recognition protein Rad14. Affinity purification of this protein from yeast nuclear extracts resulted in the co-purification of Rad1, Rad7, Rad10, Rad16, Rad23, RPA, RPB1, and TFIIH proteins, whereas none of these proteins bound to the affinity resin in the absence of recombinant Rad14. Furthermore, many of the co-purifying proteins were present in approximately equimolar amounts. Co-elution of these proteins was also observed when the nuclear extract was fractionated by gel filtration, indicating that the NER proteins were associated in a complex with a molecular mass of >1000 kDa prior to affinity chromatography. The affinity purified NER complex catalyzed the incision of UV-irradiated DNA in an ATP-dependent reaction. We conclude that active high molecular weight complexes of NER proteins exist in undamaged yeast cells

  18. Significance of ligand interactions involving Hop2-Mnd1 and the RAD51 and DMC1 recombinases in homologous DNA repair and XX ovarian dysgenesis.

    Zhao, Weixing; Sung, Patrick

    2015-04-30

    The evolutionarily conserved Hop2-Mnd1 complex is a key cofactor for the meiosis-specific recombinase Dmc1. However, emerging evidence has revealed that Hop2-Mnd1 is expressed in somatic tissues, primary human fibroblasts and cell lines, and that it functions in conjunction with the Rad51 recombinase to repair damaged telomeres via the alternate lengthening of telomeres mechanism. Here, we reveal how distinct DNA-binding activities of Hop2-Mnd1 mediate the stabilization of the RAD51-ssDNA presynaptic filament or stimulate the homologous DNA pairing reaction. We have also endeavored to define the interface that governs the assembly of the higher order complex of Hop2-Mnd1 with RAD51. Unexpectedly, we find that ATP enhances the interaction between Hop2-Mnd1 and RAD51, and that both Hop2 and Mnd1 are involved in RAD51 interaction via their C-terminal regions. Importantly, mutations introduced into these Hop2 and Mnd1 domains, including the HOP2 p.del201Glu mutation present in a patient of XX ovarian dysgenesis, diminish the association and functional synergy of Hop2-Mnd1 with both RAD51 and DMC1. Our findings help delineate the intricate manner in which Hop2-Mnd1 engages and functions with RAD51 and DMC1 in mammalian cells and speak to the possible cause of XX ovarian dysgenesis. PMID:25820426

  19. The yeast Shu complex utilizes homologous recombination machinery for error-free lesion bypass via physical interaction with a Rad51 paralogue.

    Xu, Xin; Ball, Lindsay; Chen, Wangyang; Tian, Xuelei; Lambrecht, Amanda; Hanna, Michelle; Xiao, Wei

    2013-01-01

    DNA-damage tolerance (DDT) is defined as a mechanism by which eukaryotic cells resume DNA synthesis to fill the single-stranded DNA gaps left by replication-blocking lesions. Eukaryotic cells employ two different means of DDT, namely translesion DNA synthesis (TLS) and template switching, both of which are coordinately regulated through sequential ubiquitination of PCNA at the K164 residue. In the budding yeast Saccharomyces cerevisiae, the same PCNA-K164 residue can also be sumoylated, which recruits the Srs2 helicase to prevent undesired homologous recombination (HR). While the mediation of TLS by PCNA monoubiquitination has been extensively characterized, the method by which K63-linked PCNA polyubiquitination leads to template switching remains unclear. We recently identified a yeast heterotetrameric Shu complex that couples error-free DDT to HR as a critical step of template switching. Here we report that the Csm2 subunit of Shu physically interacts with Rad55, an accessory protein involved in HR. Rad55 and Rad57 are Rad51 paralogues and form a heterodimer to promote Rad51-ssDNA filament formation by antagonizing Srs2 activity. Although Rad55-Rad57 and Shu function in the same pathway and both act to inhibit Srs2 activity, Shu appears to be dedicated to error-free DDT while the Rad55-Rad57 complex is also involved in double-strand break repair. This study reveals the detailed steps of error-free lesion bypass and also brings to light an intrinsic interplay between error-free DDT and Srs2-mediated inhibition of HR. PMID:24339919

  20. The yeast Shu complex utilizes homologous recombination machinery for error-free lesion bypass via physical interaction with a Rad51 paralogue.

    Xin Xu

    Full Text Available DNA-damage tolerance (DDT is defined as a mechanism by which eukaryotic cells resume DNA synthesis to fill the single-stranded DNA gaps left by replication-blocking lesions. Eukaryotic cells employ two different means of DDT, namely translesion DNA synthesis (TLS and template switching, both of which are coordinately regulated through sequential ubiquitination of PCNA at the K164 residue. In the budding yeast Saccharomyces cerevisiae, the same PCNA-K164 residue can also be sumoylated, which recruits the Srs2 helicase to prevent undesired homologous recombination (HR. While the mediation of TLS by PCNA monoubiquitination has been extensively characterized, the method by which K63-linked PCNA polyubiquitination leads to template switching remains unclear. We recently identified a yeast heterotetrameric Shu complex that couples error-free DDT to HR as a critical step of template switching. Here we report that the Csm2 subunit of Shu physically interacts with Rad55, an accessory protein involved in HR. Rad55 and Rad57 are Rad51 paralogues and form a heterodimer to promote Rad51-ssDNA filament formation by antagonizing Srs2 activity. Although Rad55-Rad57 and Shu function in the same pathway and both act to inhibit Srs2 activity, Shu appears to be dedicated to error-free DDT while the Rad55-Rad57 complex is also involved in double-strand break repair. This study reveals the detailed steps of error-free lesion bypass and also brings to light an intrinsic interplay between error-free DDT and Srs2-mediated inhibition of HR.

  1. Studies of DNA repair in saccharomyces cerevisiae. I. Characterization of a new allele of RAD6. II. Investigation of events in the first cell cycle after DNA damage

    Studies in two independent, but related, areas of DNA repair have been carried out in Saccharomyces cerevisiae; characterization of a new allele in the RAD6 gene which suggests that the gene is multifunctional, and utilization of photoreactivation as a probe of events occurring during the first cell cycle after DNA damage. Strains carrying the new allele, designated rad6-4, are as sensitive to uv and ionizing radiation as those carrying rad6-1 or rad6-3 but, unlike them, are capable of induced mutagenesis and sporulation. Although rad6-4 may well be a missense mutation, the evidence shows that it is unlikely that this phenotype is due to leakiness. Instead, the data suggest that the RAD6 gene is multifunctional. One function is necessary to recover from DNA damage in an error-free manner, and the other is concerned with mutagenic processes and sporulation. Rad6-1 and rad6-3 strains are deficient in both of these functions, while rad6-4 strains are deficient only in the error-free function. The loss of photoreversibility (LOP) of ultraviolet induced mutations to arginine independence in an excision defective strain carrying arg4-17 examines the events occurring in the first cell cycle after DNA damage. LOP is dependent upon de novo protein synthesis. LOP begins immediately after UV irradiation, before semiconservative DNA synthesis takes place, and is complete after four hours in growth medium.There is no evidence indicating whether the normal function of the protein is involved in excision repair, or in one of the two repair processes believed to be inducible; induced mutagenesis or recombinational repair

  2. Diagnostic value of contrast-enhanced ultrasound in BI-RADS4B breast lesions%超声造影对乳腺BI-RADS4B级肿块的诊断价值

    左文思; 冷晓玲; 马富成

    2016-01-01

    目的 评价超声造影对乳腺BI-RADS4B级肿块的鉴别诊断价值.方法 对常规超声检查后诊断为BI-RADS4B级的60例女性患者(共65个肿块,其中恶性44个,良性21个)进行超声造影检查,术后均行病理证实,比较良恶性肿块的超声造影显像特征及其不同区域的血流灌注参数特征.结果 良性组和恶性组在增强顺序、造影模式、造影后范围有无显著增大方面比较差异均具有统计学意义(P0.05);恶性组边缘带的峰值强度明显高于良性组,恶性组边缘的峰值强度、曲线下面积、消除斜率高于其癌旁正常组织,而平均渡越时间、达峰时间低于其癌旁正常组织,差异均有统计学意义(P0.05);良性组边缘带峰值强度、曲线下面积、消除斜率、平均渡越时间、达峰时间与其内部及其癌旁正常组织相比较,差异均无统计学意义(P>0.05).超声造影对BI-RADS4B级恶、良性肿块诊断正确率分别为93.18%(41/44)和76.19%(16/21). 结论 使用超声造影对BI-RADS4B级肿块可以进一步良恶性鉴别,可以提高BI-RADS4B级肿块诊断准确率.%Objective To assess the value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of Breast Imaging Reporting and Data System BI-RADS4B breast lesions. Methods Sixty female patients with 65 breast lesions, including 21 benign lesions (benign group) and 44 malignant lesions (malignant group), were diagnosed as BI-RADS4B by conventional ultrasound examination. All the breast lesions underwent CEUS and postoperative path-ological examination. The imaging features and blood perfusion parameters in different regions of the benign and malig-nant breast tumors were compared. Results The benign group and malignant group showed statistically significant dif-ference in enhancement order, contrast model, and whether the lesion was significantly enlarged after CEUS (P0.05). In CEUS time-intensity curve analysis, the peak intensity (PI) of periphery

  3. Analysis of the synthesis note 99-26 of the CRI-RAD entitled ''evaluation of the CRI-RAD participation to the works of the North Cotentin radioecology group ''

    At the beginning of july 1999, after two years of work, the North Cotentin radioecology group made public its works on the levels of exposure to ionizing radiations of the North Cotentin populations and the associated risk of leukemia. the content of the reports has not been approved by the experts of the CRI-RAD. Their reasons have not been developed. The analysis of this note makes every effort to resume the principle arguments developed in the note. (N.C.)

  4. Interrogation of the Protein-Protein Interactions between Human BRCA2 BRC Repeats and RAD51 Reveals Atomistic Determinants of Affinity

    Cole, Daniel J.; Rajendra, Eeson; Roberts-Thomson, Meredith; Hardwick, Bryn; Grahame J. McKenzie; Payne, Mike C.; Ashok R Venkitaraman; Skylaris, Chris-Kriton

    2011-01-01

    The breast cancer suppressor BRCA2 controls the recombinase RAD51 in the reactions that mediate homologous DNA recombination, an essential cellular process required for the error-free repair of DNA double-stranded breaks. The primary mode of interaction between BRCA2 and RAD51 is through the BRC repeats, which are ∼35 residue peptide motifs that interact directly with RAD51 in vitro. Human BRCA2, like its mammalian orthologues, contains 8 BRC repeats whose sequence and spacing are evolutionar...

  5. A Clamped Be Window for the Dump of the HiRadMat Experiment at CERN

    Delonca, M; Grenier, D; Maglioni, C; Sarrio Martinez, A

    2012-01-01

    At CERN, the High Radiation to Materials facility (HiRadMat) is designed to test accelerator components under the impact of high-intensity pulsed beams and will start operation in 2012. In this frame an LHC TED-type dump was installed at the end of the line, working in nitrogen overpressure, and a 254μm-thick beryllium window was placed as barrier between the inside of the dump and the external atmosphere. Because of the special loading conditions, a clamped window design was especially developed, optimized and implemented, the more standard welded window not being suitable for such loads. Considering then the clamping force and the applied differential pressures, the stresses on the window components were carefully evaluated thanks to empirical as well as numerical models, to guarantee the structural integrity of the beryllium foil. This paper reports on choices and optimizations that led to the final design, presenting also comparative results from different solutions and the detailed results for the adopt...

  6. Unforeseen Consequences of Excluding Missing Data from Next-Generation Sequences: Simulation Study of RAD Sequences.

    Huang, Huateng; Knowles, L Lacey

    2016-05-01

    There is a lack of consensus on how next-generation sequence (NGS) data should be considered for phylogenetic and phylogeographic estimates, with some studies excluding loci with missing data, whereas others include them, even when sequences are missing from a large number of individuals. Here, we use simulations, focusing specifically on RAD (Restriction site Associated DNA) sequences, to highlight some of the unforeseen consequence of excluding missing data from next-generation sequencing. Specifically, we show that in addition to the obvious effects associated with reducing the amount of data used to make historical inferences, the decisions we make about missing data (such as the minimum number of individuals with a sequence for a locus to be included in the study) also impact the types of loci sampled for a study. In particular, as the tolerance for missing data becomes more stringent, the mutational spectrum represented in the sampled loci becomes truncated such that loci with the highest mutation rates are disproportionately excluded. This effect is exacerbated further by factors involved in the preparation of the genomic library (i.e., the use of reduced representation libraries, as well as the coverage) and the taxonomic diversity represented in the library (i.e., the level of divergence among the individuals). We demonstrate that the intuitive appeals about being conservative by removing loci may be misguided. [Next-generation sequencing; phylogenetic; phylogeography; RADseq; RADtags; species delimitation.]. PMID:24996413

  7. Instrument intercomparison in the pulsed neutron fieldsat the CERN HiRadMat facility

    Aza, E; Cassell, C; Charitonidis, N; Harrouch, E; Manessi, G P; Pangallo, M; Perrin, D; Samara, E; Silari, M

    2014-01-01

    An intercomparison of the performances of active neutron detectors was carried out in pulsed neutron fi elds in the new HiRadMat facility at CERN. Five detectors were employed: four of them (two ionization chambers and two rem counters) are routinely employed in the CERN radiation monitoring system, while the fi fth is a novel instrument, called LUPIN, speci fi cally conceived for applications in pulsed neutron fi elds. The measurements were performed in the stray fi eld generated by a proton beam of very short duration with momentum of 440 GeV/c impinging on a dump. The beam intensity was steadily increased during the experiment by more than three orders of magnitude, with an H*(10) due to neutrons at the detector reference positions varying between a few nSv per burst and a few m Sv per burst, whereas the gamma contribution to the total H*(10) was negligible. The aim of the experiment was to evaluate the linearity of the detector response in extreme pulsed conditions as a function of the neutron burst in- t...

  8. A Clamped Be Window for the Dump of the HiRadMat Experiment at CERN

    Delonca, M; Grenier, D; Maglioni, C; Sarrio Martinez, A

    2012-01-01

    At CERN, the High Radiation to Materials facility (HiRadMat) is designed to test accelerator components under the impact of high-intensity pulsed beams and will start operation in 2012. In this frame an LHC TED-type dump was installed at the end of the line, working in nitrogen over-pressure, and a 254μm-thick beryllium window was placed as barrier between the inside of the dump and the external atmosphere. Because of the special loading conditions, a clamped window design was especially developed, optimized and implemented, the more standard welded window not being suitable for such loads. Considering then the clamping force and the applied differential pressures, the stresses on the window components were carefully evaluated thanks to empirical as well as numerical models, to guarantee the structural integrity of the beryllium foil. This paper reports on choices and optimizations that led to the final design, presenting also comparative results from different solutions and the detailed results for the adop...

  9. Computer-aided diagnosis of breast masses using quantified BI-RADS findings.

    Moon, Woo Kyung; Lo, Chung-Ming; Cho, Nariya; Chang, Jung Min; Huang, Chiun-Sheng; Chen, Jeon-Hor; Chang, Ruey-Feng

    2013-07-01

    The information from radiologists was utilized in the proposed computer-aided diagnosis (CAD) for breast tumor classification. The ultrasound (US) database used in this study contained 166 benign and 78 malignant masses. For each mass, six quantitative feature sets were used to describe the radiologists' grading of six Breast Imaging Reporting and Data System (BI-RADS) categories including shape, orientation, margins, lesion boundary, echo pattern, and posterior acoustic features on breast US. The descriptive abilities were between 76% and 82% and the predicted descriptors were then used for tumor classification. Using receiver operating characteristic curve for evaluation, the area under curve (AUC) of the proposed CAD was slightly better than that of a conventional CAD based on the combination of all quantitative features (0.96 vs. 0.93, p=0.18). The partial AUC over 90% sensitivity of the proposed CAD was significantly better than that of the conventional CAD (0.90 vs. 0.76, p<0.05). In conclusion, the computer-aided analysis with qualitative information from radiologists showed a promising result for breast tumor classification. PMID:23639752

  10. Using Next Generation RAD Sequencing to Isolate Multispecies Microsatellites for Pilosocereus (Cactaceae.

    Isabel A S Bonatelli

    Full Text Available Microsatellite markers (also known as SSRs, Simple Sequence Repeats are widely used in plant science and are among the most informative molecular markers for population genetic investigations, but the development of such markers presents substantial challenges. In this report, we discuss how next generation sequencing can replace the cloning, Sanger sequencing, identification of polymorphic loci, and testing cross-amplification that were previously required to develop microsatellites. We report the development of a large set of microsatellite markers for five species of the Neotropical cactus genus Pilosocereus using a restriction-site-associated DNA sequencing (RAD-seq on a Roche 454 platform. We identified an average of 165 microsatellites per individual, with the absolute numbers across individuals proportional to the sequence reads obtained per individual. Frequency distribution of the repeat units was similar in the five species, with shorter motifs such as di- and trinucleotide being the most abundant repeats. In addition, we provide 72 microsatellites that could be potentially amplified in the sampled species and 22 polymorphic microsatellites validated in two populations of the species Pilosocereus machrisii. Although low coverage sequencing among individuals was observed for most of the loci, which we suggest to be more related to the nature of the microsatellite markers and the possible bias inserted by the restriction enzymes than to the genome size, our work demonstrates that an NGS approach is an efficient method to isolate multispecies microsatellites even in non-model organisms.

  11. Cloning, expression, purification, crystallization and preliminary X-ray diffraction data of the Pyrococcus horikoshii RadA intein

    Cloning, expression, purification and X-ray data collection of the RadA intein from the hyperthermophilic archaebacterium P. horikoshii are reported. The RadA intein from the hyperthermophilic archaebacterium Pyrococcus horikoshii was cloned, expressed and purified for subsequent structure determination. The protein crystallized rapidly in several conditions. The best crystals, which diffracted to 1.75 Å resolution, were harvested from drops consisting of 0.1 M HEPES pH 7.5, 3.0 M NaCl and were cryoprotected with Paratone-N before flash-cooling. The collected data were processed in the orthorhombic space group P212121, with unit-cell parameters a = 58.1, b = 67.4, c = 82.9 Å. Molecular replacement with Rosetta using energy- and density-guided structure optimization provided the initial solution, which is currently under refinement

  12. Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy

    Reymer, A.

    2009-07-08

    To get mechanistic insight into the DNA strand-exchange reaction of homologous recombination, we solved a filament structure of a human Rad51 protein, combining molecular modeling with experimental data. We build our structure on reported structures for central and N-terminal parts of pure (uncomplexed) Rad51 protein by aid of linear dichroism spectroscopy, providing angular orientations of substituted tyrosine residues of Rad51-dsDNA filaments in solution. The structure, validated by comparison with an electron microscopy density map and results from mutation analysis, is proposed to represent an active solution structure of the nucleo-protein complex. An inhomogeneously stretched double-stranded DNA fitted into the filament emphasizes the strategic positioning of 2 putative DNA-binding loops in a way that allows us speculate about their possibly distinct roles in nucleo-protein filament assembly and DNA strand-exchange reaction. The model suggests that the extension of a single-stranded DNA molecule upon binding of Rad51 is ensured by intercalation of Tyr-232 of the L1 loop, which might act as a docking tool, aligning protein monomers along the DNA strand upon filament assembly. Arg-235, also sitting on L1, is in the right position to make electrostatic contact with the phosphate backbone of the other DNA strand. The L2 loop position and its more ordered compact conformation makes us propose that this loop has another role, as a binding site for an incoming double-stranded DNA. Our filament structure and spectroscopic approach open the possibility of analyzing details along the multistep path of the strand-exchange reaction.

  13. Effects of gamma irradiation and hot-water treatment on the shelf life and quality of Thai mango cv. Rad

    Preclimacteric mature-green mangoes cv. Rad were irradiated at doses up to 1 kGy after hot water treatment at 55 deg C for 5 min. Irradiation significantly reduced rotting, delayed colour development, preserved quality and extended shelf life. Irradiation injury increased with increasing dose and storage period. In terms of shelf life and quality, a hot-water treatment followed by irradiation at 0.3 kGy was found to be the best combination treatment

  14. RadBall™ Technology Testing in the Savannah River Site’s Health Physics Instrument Calibration Laboratory

    Farfán, Eduardo B.; Foley, Trevor Q.; Jannik, G. Timothy; Harpring, Larry J.; Gordon, John R.; Blessing, Ronald; Coleman, J. Rusty; Holmes, Christopher J.; Oldham, Mark; Adamovics, John; Stanley, Steven J.

    2010-01-01

    The United Kingdom’s National Nuclear Laboratory (NNL) has developed a radiation-mapping device that can locate and quantify radioactive hazards within contaminated areas of the nuclear industry. The device, known as RadBall™, consists of a colander-like outer collimator that houses a radiation-sensitive polymer sphere. The collimator has over two hundred small holes; thus, specific areas of the polymer sphere are exposed to radiation becoming increasingly more opaque in proportion to the abs...

  15. Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2

    Fanconi anemia (FA) is a cancer susceptibility disorder characterized by chromosomal instability and hypersensitivity to DNA cross-linking agents. So far 11 complementation groups have been identified, from which only FA-D1/BRCA2 and FA-J are defective downstream of the central FANCD2 protein as cells from these groups are capable of monoubiquitinating FANCD2. In this study we show that cells derived from patients from the new complementation groups, FA-I, FA-J and FA-L are all proficient in DNA damage induced Rad51 foci formation, making the cells from FA-D1/BRCA2 patients that are defective in this process the sole exception. Although FA-B patient HSC230 was previously reported to also have biallelic BRCA2 mutations, we found normal Rad51 foci formation in cells from this patient, consistent with the recent identification of an X-linked gene being mutated in four unrelated FA-B patients. Thus, our data show that none of the FA proteins, except BRCA2, are required to sequester Rad51 into nuclear foci. Since cells from the FA-D1 and FA-J patient groups are both able to monoubiquitinate FANCD2, the 'Rad51 foci phenotype' provides a convenient assay to distinguish between these two groups. Our results suggest that FANCJ and FANCD1/BRCA2 are part of the integrated FANC/BRCA DNA damage response pathway or, alternatively, that they represent sub-pathways in which only FANCD1/BRCA2 is directly connected to the process of homologous recombination

  16. Genetic variation in the NBS1, MRE11, RAD50 and BLM genes and susceptibility to non-Hodgkin lymphoma

    Gascoyne Randy D; Connors Joseph M; Gallagher Richard P; Lai Agnes S; Leach Stephen; MacArthur Amy C; Schuetz Johanna M; Spinelli John J; Brooks-Wilson Angela R

    2009-01-01

    Abstract Background Translocations are hallmarks of non-Hodgkin lymphoma (NHL) genomes. Because lymphoid cell development processes require the creation and repair of double stranded breaks, it is not surprising that disruption of this type of DNA repair can cause cancer. The members of the MRE11-RAD50-NBS1 (MRN) complex and BLM have central roles in maintenance of DNA integrity. Severe mutations in any of these genes cause genetic disorders, some of which are characterized by increased risk ...

  17. Histo-pathological correlation of BI-RADS 4 lesions on mammography with emphasis on microcalcification patterns.

    F Ismail

    2008-12-01

    Full Text Available A retrospective study of 20 patients with Breast Imaging Reporting and Data System (BI-RADS 4 lesions was undertaken. These patients were classified as BI-RADS 4 lesions due to presence of a mass (clinical or on mammography, architectural distortion and microcalcifications (MC. In some patients, the pattern of MC was benign but there were other features that were suspicious of malignancy. A comparison was made with the histological diagnosis in order to compare the radiological appearance of benign and malignant microcalcification patterns with the final histology. The study design included retrospective analysis of patients with MC on digital mammography who underwent biopsy. An analysis of the histology was then undertaken. Other factors in the history and physical examination were also considered. Results showed that although the study was not statistically significant due to limited study population, interesting trends are determined in assessing calcification patterns using the Breast Imaging Reporting and Data System (BI-RADS classification system, since some lesions that were thought to have benign calcification patterns were actually malignant and vice versa. Further study in this field is required.

  18. Predictive performance of BI-RADS magnetic resonance imaging descriptors in the context of suspicious (category 4) findings*

    de Almeida, João Ricardo Maltez; Gomes, André Boechat; Barros, Thomas Pitangueiras; Fahel, Paulo Eduardo; Rocha, Mário de Seixas

    2016-01-01

    Objective To determine the positive predictive value (PPV) and likelihood ratio for magnetic resonance imaging (MRI) characteristics of category 4 lesions, as described in the Breast Imaging Reporting and Data System (BI-RADS®) lexicon, as well as to test the predictive performance of the descriptors using multivariate analysis and the area under the curve derived from a receiver operating characteristic (ROC) curve. Materials and Methods This was a double-blind review study of 121 suspicious findings from 98 women examined between 2009 and 2013. The terminology was based on the 2013 edition of the BI-RADS. Results Of the 121 suspicious findings, 53 (43.8%) were proven to be malignant lesions, with no significant difference between mass and non-mass enhancement (p = 0.846). The PPVs were highest for masses with a spiculated margin (71%) and round shape (63%), whereas segmental distribution achieved a high PPV (80%) for non-mass enhancement. Kinetic analyses performed poorly, except for type 3 curves applied to masses (PPV of 73%). Logistic regression models were significant for both patterns, although the results were better for masses, particularly when kinetic assessments were included (p = 0.015; pseudo R2 = 0.48; area under the curve = 90%). Conclusion Some BI-RADS MRI descriptors have high PPV and good predictive performance-as demonstrated by ROC curve and multivariate analysis-when applied to BI-RADS category 4 findings. This may allow future stratification of this category.

  19. Ubiquitylation of Rad51d Mediated by E3 Ligase Rnf138 Promotes the Homologous Recombination Repair Pathway

    Han, Deqiang; Liang, Junbo; Lu, Yalan; Xu, Longchang; Miao, Shiying; Lu, Lin-Yu; Song, Wei; Wang, Linfang

    2016-01-01

    Ubiquitylation has an important role as a signal transducer that regulates protein function, subcellular localization, or stability during the DNA damage response. In this study, we show that Ring domain E3 ubiquitin ligases RNF138 is recruited to DNA damage site quickly. And the recruitment is mediated through its Zinc finger domains. We further confirm that RNF138 is phosphorylated by ATM at Ser124. However, the phosphorylation was dispensable for recruitment to the DNA damage site. Our findings also indicate that RAD51 assembly at DSB sites following irradiation is dramatically affected in RNF138-deficient cells. Hence, RNF138 is likely involved in regulating homologous recombination repair pathway. Consistently, efficiency of homologous recombination decreased observably in RNF138-depleted cells. In addition, RNF138-deficient cell is hypersensitive to DNA damage insults, such as IR and MMS. And the comet assay confirmed that RNF138 directly participated in DNA damage repair. Moreover, we find that RAD51D directly interacted with RNF138. And the recruitment of RAD51D to DNA damage site is delayed and unstable in RNF138-depleted cells. Taken together, these results suggest that RNF138 promotes the homologous recombination repair pathway. PMID:27195665

  20. IMPLEMENTASI PEMERINTAHAN YANG BERSIH DALAM KERANGKA RENCANA AKSI DAERAH PEMBERANTASAN KORUPSI (RAD-PK (Studi Di Kabupaten Pemalang

    Muhammad Fauzan

    2012-03-01

    Full Text Available This research related to the implementation of good governance, free from corruption, collusion and nepotism. The approach used in this research is a descriptive qualitative approach. The Location of research conducted in the District of Pemalang. Based on the research results can presented that the District of Pemalang is committed and fully supports the government policy in eradicating corruption. District of Pemalang support to efforts to more information accelerate the eradication of corruption stated in the the Regional Action Plan to Accelerate the Eradication of Corruption (RAD-PK in 2011 -2016 which refers to the Medium Term Development Plan (RPJM District of Pemalang from 2011 to 2016 and the National Action Plan for Eradication of Corruption (RAN-PK and the President of Republic of Indonesia Instruction No. 5 Year 2004 on Accelerating the eradication of corruption. RAD-PK 2011-2016 District of Pemalang is a document that contains an action program that aims to accelerate the eradication of corruption. RAD-PK as a program of action containing concrete measures that have been agreed by the stakeholders in the area, so it has been a commitment of local governments prevention efforts corruption through the development of programs and activities aimed at improving public services and the application of the principles of good governance.

  1. Genetic variation in the NBS1, MRE11, RAD50 and BLM genes and susceptibility to non-Hodgkin lymphoma

    Gascoyne Randy D

    2009-11-01

    Full Text Available Abstract Background Translocations are hallmarks of non-Hodgkin lymphoma (NHL genomes. Because lymphoid cell development processes require the creation and repair of double stranded breaks, it is not surprising that disruption of this type of DNA repair can cause cancer. The members of the MRE11-RAD50-NBS1 (MRN complex and BLM have central roles in maintenance of DNA integrity. Severe mutations in any of these genes cause genetic disorders, some of which are characterized by increased risk of lymphoma. Methods We surveyed the genetic variation in these genes in constitutional DNA of NHL patients by means of gene re-sequencing, then conducted genetic association tests for susceptibility to NHL in a population-based collection of 797 NHL cases and 793 controls. Results 114 SNPs were discovered in our sequenced samples, 61% of which were novel and not previously reported in dbSNP. Although four variants, two in RAD50 and two in NBS1, showed association results suggestive of an effect on NHL, they were not significant after correction for multiple tests. Conclusion These results suggest an influence of RAD50 and NBS1 on susceptibility to diffuse large B-cell lymphoma and marginal zone lymphoma. Larger association and functional studies could confirm such a role.

  2. Development of a Lower-SWaP, RAD-Tolerant, Thermally Stable High Speed Fiber Optics Network for Harsh Environment Applications Project

    National Aeronautics and Space Administration — The proposed Phase I objectives and work plan, carried through to completion, will result in the development of a RAD-tolerant, high-speed, multi-channel fiber...

  3. Sequence analysis of the DNA-repair gene rad51 in the tardigrades Milnesium cf. tardigradum, Hypsibius dujardini and Macrobiotus cf. harmsworthi

    Eliana A. Beltrán-Pardo

    2013-05-01

    Full Text Available Tardigrades are known for being resistant to extreme conditions, including tolerance to ionising and UV radiation in both the hydrated and the dehydrated state. It is known that these factors may cause damage to DNA. It has recently been shown that single and double DNA strand breaks occur when tardigrades are maintained for a long time in the anhydrobiotic state. This may suggest that perhaps tardigrades rely on efficient DNA repair mechanisms. Among all proteins that comprise the DNA repair system, recombinases such as RecA or Rad51 have a very important function: DNA exchange activity. This enzyme is used in the homologous recombination and allows repair of the damaged strand using homologous non-damaged strands as a template. In this study, Rad51 induction was evaluated by western blot in Milnesium cf. tardigradum, after exposure to gamma radiation. The Rad51 protein was highly induced by radiation, when compared to the control. The rad51 genes were searched in three tardigrades: Milnesium cf. tardigradum, Hypsibius dujardini and Macrobiotus cf. harmsworthi. The gene sequences were obtained by preparing and sequencing transcriptome libraries for H. dujardini and M. cf. harmsworthi and designing rad51 degenerate primers specific for M. cf. tardigradum. Comparison of Rad51 putative proteins from tardigrades with other organisms showed that they are highly similar to the corresponding sequence from the nematode Trichinella spiralis. A structure-based sequence alignment from tardigrades and other organisms revealed that putative Rad51 predicted proteins from tardigrades contain the expected motifs for these important recombinases. In a cladogram tree based on this alignment, tardigrades tend to cluster together suggesting that they have selective differences in these genes that make them diverge between species. Predicted Rad51 structures from tardigrades were also compared with crystalline structure of Rad51 in Saccharomyces cerevisiae. These

  4. White Paper Report of the 2011 RAD-AID Conference on International Radiology for Developing Countries: Integrating Multidisciplinary Strategies for Imaging Services in the Developing World

    Everton, Kathryn L.; Mazal, Jonathan; Lexa, Frank; Starikovsky, Anna; Jimenez, Pablo; Jain, Sanjay; DeStigter, Kristen K.; Nathan, Robert; Krebs, Elizabeth; Noble, Vicki; Marks, William,; Hirsh, Richard N.; Short, Brad; Sydnor, Ryan; Timmreck-Jackson, Emily

    2012-01-01

    The 2011 RAD-AID Conference on International Radiology for Developing Countries discussed data, experiences and models pertaining to radiology in the developing world, where widespread shortages of imaging services significantly reduce health care quality and increase health care disparity. This white paper from the 2011 RAD-AID Conference represents consensus advocacy of multidisciplinary strategies to improve planning, accessibility and quality of imaging services in the developing world. C...

  5. Synchronous BI-RADS Category 3 Lesions on Preoperative Ultrasonography in Patients with Breast Cancer: Is Short-Term Follow-Up Appropriate?

    Lee, Seokwon; Jung, Younglae; Bae, Youngtae

    2015-01-01

    Purpose Breast ultrasonography (US) has been widely used in the preoperative examination of patients with breast cancer. Breast Imaging Reporting and Data System (BI-RADS) category 3 (C3) lesions (probably benign) are regarded as having a low probability of malignancy (≤2%). The purposes of this study were to verify the malignancy rates for synchronous BI-RADS C3 lesions in patients with breast cancer and consider appropriate management strategies for these lesions. Methods Between January 20...

  6. Rad51c- and Trp53-double-mutant mouse model reveals common features of homologous recombination-deficient breast cancers.

    Tumiati, M; Munne, P M; Edgren, H; Eldfors, S; Hemmes, A; Kuznetsov, S G

    2016-09-01

    Almost half of all hereditary breast cancers (BCs) are associated with germ-line mutations in homologous recombination (HR) genes. However, the tumor phenotypes associated with different HR genes vary, making it difficult to define the role of HR in BC predisposition. To distinguish between HR-dependent and -independent features of BCs, we generated a mouse model in which an essential HR gene, Rad51c, is knocked-out specifically in epidermal tissues. Rad51c is one of the key mediators of HR and a well-known BC predisposition gene. Here, we demonstrate that deletion of Rad51c invariably requires inactivation of the Trp53 tumor suppressor (TP53 in humans) to produce mammary carcinomas in 63% of female mice. Nonetheless, loss of Rad51c shortens the latency of Trp53-deficient mouse tumors from 11 to 6 months. Remarkably, the histopathological features of Rad51c-deficient mammary carcinomas, such as expression of hormone receptors and luminal epithelial markers, faithfully recapitulate the histopathology of human RAD51C-mutated BCs. Similar to other BC models, Rad51c/p53 double-mutant mouse mammary tumors also reveal a propensity for genomic instability, but lack the focal amplification of the Met locus or distinct mutational signatures reported for other HR genes. Using the human mammary epithelial cell line MCF10A, we show that deletion of TP53 can rescue RAD51C-deficient cells from radiation-induced cellular senescence, whereas it exacerbates their centrosome amplification and nuclear abnormalities. Altogether, our data indicate that a trend for genomic instability and inactivation of Trp53 are common features of HR-mediated BCs, whereas histopathology and somatic mutation patterns are specific for different HR genes. PMID:26820992

  7. Association between the RAD51 135 G>C polymorphism and risk of cancer: a meta-analysis of 19,068 cases and 22,630 controls.

    Wei Wang

    Full Text Available BACKGROUND: RAD51 135G>C can modify promoter activity and the penetrance of BRCA1/2 mutations, which plays vital roles in the etiology of various cancer. To date, previous published data on the association between RAD51 135G>C polymorphism and cancer risk remained controversial. Recent meta-analysis only analyzed RAD51 135G>C polymorphism with breast cancer risk, but the results were also inconsistent. METHODS: A meta-analysis based on 39 case-control studies was performed to investigate the association between cancer susceptibility and RAD51 135G>C. Odds ratios (OR with 95% confidence intervals (CIs were used to assess the association in different inheritance models. Heterogeneity among studies was tested and sensitivity analysis was applied. RESULTS: Overall, no significant association was found between RAD51 135G>C polymorphism and cancer susceptibility in any genetic model. In further stratified analysis, significantly elevated breast cancer risk was observed in BRCA2 mutation carriers (recessive model: OR = 4.88, 95% CI = 1.10-21.67; additive model: OR = 4.92, 95% CI = 1.11-21.83. CONCLUSIONS: This meta-analysis suggests that RAD51 variant 135C homozygote is associated with elevated breast cancer risk among BRCA2 mutation carriers. Moreover, our work also points out the importance of new studies for RAD51 135G>C association in acute myeloid leukemia, especially in Caucasians, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the RAD51 135G>C polymorphism in cancer development.

  8. Rad4 mainly functions in Chk1-mediated DNA damage checkpoint pathway as a scaffold protein in the fission yeast Schizosaccharomyces pombe.

    Ming Yue

    Full Text Available Rad4/Cut5 is a scaffold protein in the Chk1-mediated DNA damage checkpoint in S. pombe. However, whether it contains a robust ATR-activation domain (AAD required for checkpoint signaling like its orthologs TopBP1 in humans and Dpb11 in budding yeast has been incompletely clear. To identify the putative AAD in Rad4, we carried out an extensive genetic screen looking for novel mutants with an enhanced sensitivity to replication stress or DNA damage in which the function of the AAD can be eliminated by the mutations. Two new mutations near the N-terminus were identified that caused significantly higher sensitivities to DNA damage or chronic replication stress than all previously reported mutants, suggesting that most of the checkpoint function of the protein is eliminated. However, these mutations did not affect the activation of Rad3 (ATR in humans yet eliminated the scaffolding function of the protein required for the activation of Chk1. Several mutations were also identified in or near the recently reported AAD in the C-terminus of Rad4. However, all mutations in the C-terminus only slightly sensitized the cells to DNA damage. Interestingly, a mutant lacking the whole C-terminus was found resistant to DNA damage and replication stress almost like the wild type cells. Consistent with the resistance, all known Rad3 dependent phosphorylations of checkpoint proteins remained intact in the C-terminal deletion mutant, indicating that unlike that in Dpb11, the C-terminus of Rad4 does not contain a robust AAD. These results, together with those from the biochemical studies, show that Rad4 mainly functions as a scaffold protein in the Chk1, not the Cds1(CHK2 in humans, checkpoint pathway. It plays a minor role or is functionally redundant with an unknown factor in Rad3 activation.

  9. Development of dosimeters with rad-hard silicon diodes for high dose dosimetry

    In this work we report on results obtained with rad-hard Standard Float Zone (FZ), Diffusion Oxygenated Float Zone (DOFZ) and Magnetic Czochralski (MCz) silicon diodes in gamma radiation processing dosimetry. These p±n-n+ junction devices were manufactured by Okmetic Oyj. (Vantaa, Finland) and processed by the Microelectronics Center of Helsinki University of Technology in the framework of the CERN RD50 Collaboration. The dosimetric probes, based on FZ, DOFZ and M Cz devices, were designed to operate without bias voltage in the direct current mode as on-line radiation dosimeter. The irradiations were performed in the Radiation Technology Center (CTR) at IPEN-CNEN/SP using a 60Co source (Gamma cell 220 - Nordion) with a dose rate around of 2.4 kGy/h. The current response of each diode was measured as a function of the exposure time in steps from 5 kGy up to 50 kGy to achieve a total absorbed dose of 275 kGy. The results obtained showed a significant decrease in the photocurrent generated in all devices for total absorbed doses higher than approximately 25 kGy. To reduce this effect, the samples were pre-irradiated with 60Co gamma rays at 700 kGy in order to saturate the trap production in the diode's sensitive volume. After pre-irradiation, despite of being less sensitive, all devices exhibited more stable photocurrent signals, even for total absorbed doses of 275 kGy. To monitor possible gamma radiation damage effects produced on the diodes, their dynamic leakage current and capacitance were measured as a function of the absorbed dose. (author)

  10. RadWorks Project. ISS REM - to - BIRD - to - HERA: The Evolution of a Technology

    McLeod, Catherine D.

    2015-01-01

    The advancement of particle detectors based on technologies developed for use in high-energy physics applications has enabled the development of a completely new generation of compact low-power active dosimeters and area monitors for use in space radiation environments. One such device, the TimePix, is being developed at CERN, and is providing the technology basis for the most recent line of radiation detection devices being developed by the NASA AES RadWorks project. The most fundamental of these devices, an ISS-Radiation Environment Monitor (REM), is installed as a USB device on ISS where it is monitoring the radiation environment on a perpetual basis. The second generation of this TimePix technology, the BIRD (Battery-operated Independent Radiation Detector), was flown on the NASA EFT-1 flight in December 2014. Data collected by BIRD was the first data made available from the Trapped Belt region of the Earth's atmosphere in over 40 years. The 3rdgeneration of this technology, the HERA (Hybrid Electronic Radiation Assessor), is planned to be integrated into the Orion EM-1, and EM-2 vehicles where it will monitor the radiation environment. For the EM-2 flight, HERA will provide Caution and Warning notification for SPEs as well as real time dose measurements for crew members. The development of this line of radiation detectors provide much greater information and characterization of charged particles in the space radiation environment than has been collected in the past, and in the process provide greater information to inform crew members of radiation related risks, while being very power and mass efficient.

  11. Non-targeted effects of ionising radiation. Proceedings of the RISC-RAD specialised training course

    The training course 'Non-targeted effects of ionising radiation' took place at the STUK, Radiation and Nuclear Safety Authority, Helsinki, Finland 14-16 February 2005. Proceeding of this course is collected in this volume. The idea of the course was to convene a number of scientists leading in the area of non-targeted effects of ionising radiation with the aim to outline their visions for the role of these effects and outline the future directions of radiation research on the basis of their expertise. The course was supported by the RISC-RAD IP FI6R-CT-2003-508842, Euratom specific programme for research and training on nuclear energy, 6th FP of the EC. The main objectives of the training course were: (1) to clarify the mechanisms of non-targeted effects, in particular, bystander effects, genomic instability and adaptive response; (2) to look if and how non-targeted effects modulate the cancer risk in the low dose region, and whether they relate to protective or harmful functions; (3) to clarify if ionising radiation can cause non-cancer diseases or beneficial effects at low and intermediate doses; (4) address the issue of individual susceptibility and other factors modifying non-targeted responses; (5) attempt to assess the relevance of non-targeted effects for radiation protection and to set the scientific basis for a modern, more realistic, radiation safety system; (6) and finally to contribute to the conceptualisation of a new paradigm in radiation biology that would cover both the classical direct (DNA-targeted) and non-targeted (indirect) effects

  12. Ca2+ improves organization of single-stranded DNA bases in human Rad51 filament, explaining stimulatory effect on gene recombination.

    Fornander, Louise H

    2012-02-22

    Human RAD51 protein (HsRad51) catalyses the DNA strand exchange reaction for homologous recombination. To clarify the molecular mechanism of the reaction in vitro being more effective in the presence of Ca(2+) than of Mg(2+), we have investigated the effect of these ions on the structure of HsRad51 filament complexes with single- and double-stranded DNA, the reaction intermediates. Flow linear dichroism spectroscopy shows that the two ionic conditions induce significantly different structures in the HsRad51/single-stranded DNA complex, while the HsRad51/double-stranded DNA complex does not demonstrate this ionic dependence. In the HsRad51/single-stranded DNA filament, the primary intermediate of the strand exchange reaction, ATP/Ca(2+) induces an ordered conformation of DNA, with preferentially perpendicular orientation of nucleobases relative to the filament axis, while the presence of ATP/Mg(2+), ADP/Mg(2+) or ADP/Ca(2+) does not. A high strand exchange activity is observed for the filament formed with ATP/Ca(2+), whereas the other filaments exhibit lower activity. Molecular modelling suggests that the structural variation is caused by the divalent cation interfering with the L2 loop close to the DNA-binding site. It is proposed that the larger Ca(2+) stabilizes the loop conformation and thereby the protein-DNA interaction. A tight binding of DNA, with bases perpendicularly oriented, could facilitate strand exchange.

  13. XRCC2 is Required for the Formation of Rad51 Foci Induced by Ionizing Radiation and DNA Cross-Linking Agent Mitomycin C

    Liu Nan

    2002-01-01

    Full Text Available XRCC2 protein shares weak amino acid sequence similarity with Rad51, which is a central player in homologous recombinational repair (HRR. Rad51 proteins assemble at the sites of HRR and form visible nuclear foci in response to DNA damage. Xrcc2 hamster mutant irs1 cells are incapable of forming Rad51 foci after ionizing irradiation or DNA cross-linking agent mitomycin C treatment, though the Rad51 protein level is normal in the mutant. The defect can be corrected in an XRCC2 transformant. Time course study showed that the irs1 cells primarily lacked the early response (2 hours after irradiation to form small Rad51 foci (type 1 and later response (8 hours after irradiation to form large foci (type 2. These results suggested that XRCC2 is essential for the assembly of the DNA damage-induced Rad51 foci and that XRCC2 may play an important role in the early stage of HRR.

  14. Development of an online, publicly accessible naive Bayesian decision support tool for mammographic mass lesions based on the American College of Radiology (ACR) BI-RADS lexicon

    Benndorf, Matthias; Kotter, Elmar; Langer, Mathias [University Hospital Freiburg, Department of Radiology, Freiburg (Germany); Herda, Christoph [Kantonsspital Graubuenden, Chur (Switzerland); Wu, Yirong; Burnside, Elizabeth S. [University of Wisconsin-Madison School of Medicine and Public Health, Department of Radiology, Madison, WI (United States)

    2015-06-01

    To develop and validate a decision support tool for mammographic mass lesions based on a standardized descriptor terminology (BI-RADS lexicon) to reduce variability of practice. We used separate training data (1,276 lesions, 138 malignant) and validation data (1,177 lesions, 175 malignant). We created naive Bayes (NB) classifiers from the training data with tenfold cross-validation. Our ''inclusive model'' comprised BI-RADS categories, BI-RADS descriptors, and age as predictive variables; our ''descriptor model'' comprised BI-RADS descriptors and age. The resulting NB classifiers were applied to the validation data. We evaluated and compared classifier performance with ROC-analysis. In the training data, the inclusive model yields an AUC of 0.959; the descriptor model yields an AUC of 0.910 (P < 0.001). The inclusive model is superior to the clinical performance (BI-RADS categories alone, P < 0.001); the descriptor model performs similarly. When applied to the validation data, the inclusive model yields an AUC of 0.935; the descriptor model yields an AUC of 0.876 (P < 0.001). Again, the inclusive model is superior to the clinical performance (P < 0.001); the descriptor model performs similarly. We consider our classifier a step towards a more uniform interpretation of combinations of BI-RADS descriptors. We provide our classifier at www.ebm-radiology.com/nbmm/index.html. (orig.)

  15. Development of an online, publicly accessible naive Bayesian decision support tool for mammographic mass lesions based on the American College of Radiology (ACR) BI-RADS lexicon

    To develop and validate a decision support tool for mammographic mass lesions based on a standardized descriptor terminology (BI-RADS lexicon) to reduce variability of practice. We used separate training data (1,276 lesions, 138 malignant) and validation data (1,177 lesions, 175 malignant). We created naive Bayes (NB) classifiers from the training data with tenfold cross-validation. Our ''inclusive model'' comprised BI-RADS categories, BI-RADS descriptors, and age as predictive variables; our ''descriptor model'' comprised BI-RADS descriptors and age. The resulting NB classifiers were applied to the validation data. We evaluated and compared classifier performance with ROC-analysis. In the training data, the inclusive model yields an AUC of 0.959; the descriptor model yields an AUC of 0.910 (P < 0.001). The inclusive model is superior to the clinical performance (BI-RADS categories alone, P < 0.001); the descriptor model performs similarly. When applied to the validation data, the inclusive model yields an AUC of 0.935; the descriptor model yields an AUC of 0.876 (P < 0.001). Again, the inclusive model is superior to the clinical performance (P < 0.001); the descriptor model performs similarly. We consider our classifier a step towards a more uniform interpretation of combinations of BI-RADS descriptors. We provide our classifier at www.ebm-radiology.com/nbmm/index.html. (orig.)

  16. Telemetry Ranging: Concepts

    Hamkins, J.; Kinman, P.; Xie, H.; Vilnrotter, V.; Dolinar, S.

    2015-11-01

    Telemetry ranging is a proposed alternative to conventional two-way ranging for determining the two-way time delay between a Deep Space Station (DSS) and a spacecraft. The advantage of telemetry ranging is that the ranging signal on the uplink is not echoed to the downlink, so that telemetry alone modulates the downlink carrier. The timing information needed on the downlink, in order to determine the two-way time delay, is obtained from telemetry frames. This article describes the phase and timing estimates required for telemetry ranging, and how two-way range is calculated from these estimates. It explains why the telemetry ranging architecture does not require the spacecraft transponder to have a high-frequency or high-quality oscillator, and it describes how a telemetry ranging system can be infused in the Deep Space Network.

  17. Minnesota Pheasant Range

    Minnesota Department of Natural Resources — This dataset delineates the spatial range of wild pheasant populations in Minnesota as of 2002 by dividing the MN state boundary into 2 units: pheasant range and...

  18. Gain ranging amplifier

    A gain ranging amplifier system is provided for use in the acquisition of data. Voltage offset compensation is utilized to correct errors in the gain ranging amplifier system caused by thermal drift and temperature dependent voltage offsets, both of which are associated with amplifiers in the gain ranging amplifier system

  19. The RadGenomics project. Prediction for radio-susceptibility of individuals with genetic predisposition

    The ultimate goal of our project, named RadGenomics, is to elucidate the heterogeneity of the response to ionizing radiation arising from genetic variation among individuals, for the purpose of developing personalized radiation therapy regimens for cancer patients. Cancer patients exhibit patient-to-patient variability in normal tissue reactions after radiotherapy. Several observations support the hypothesis that the radiosensitivity of normal tissue is influenced by genetic factors. The rapid progression of human genome sequencing and the recent development of new technologies in molecular biology are providing new opportunities for elucidating the genetic basis of individual differences in susceptibility to radiation exposure. The development of a sufficiently robust, predictive assay enabling individual dose adjustment would improve the outcome of radiation therapy in patients. Our strategy for identification of DNA polymorphisms that contribute to the individual radiosensitivity is as follows. First, we have been categorizing DNA samples obtained from cancer patients, who have been kindly introduced to us through many collaborators, according to their clinical characteristics including the method and effect of treatment and side effects as scored by toxicity criteria, and also the result of an in vitro radiosensitivity assay, e.g., the micronuclei assay of their lymphocytes. Second, we have identified candidate genes for genotyping mainly by using our custom-designed oligonucleotide array with RNA samples, in which the probes were obtained from more than 40 cancer and 3 fibroblast cell lines whose radiosensitivity level was quite heterogeneous. We have also been studying the modification of proteins after irradiation of cells which may be caused by mainly phosphorylation or dephosphorylation, using mass spectrometry. Genes encoding the modified proteins and/or other proteins with which they interact such as specific protein kinases and phosphatases are also

  20. Gamma and electron high dose dosimetry with rad-hard Si diodes

    In this work the main dosimetric characteristics of rad-hard Float Zone (FZ) and magnetic Czochralski (MCz) diodes to electrons (1.5 MeV) and gamma (60Co) radiation are evaluated. The dosimetric system proposed is based on electrical current measurements due to radiation interactions on the devices. The batch response uniformity was studied for the n-type FZ diodes irradiated with gamma rays. The coefficient of variation of the current measurement was about 1.25% at 5 kGy of accumulated dose. A sensitivity decrease with the increase of the accumulated dose (Total Ionizing Dose - TID) was observed for both FZ and MCz diodes. For gamma irradiation, these effect is more pronounced for n-type or smaller resistivity diodes. Two types of dosimetric probe were used on the electron irradiation procedures, one of them specially designed to avoid the deterioration of the electrical contacts and the diodes metallization. The sensitivity of the preirradiated FZ and MCz diodes fell about 10% and 40%, respectively, during electron irradiation at 1.25 MGy of accumulated dose. The effect of electron radiation damage on the electrical properties of the diodes was studied by the means of leakage current and capacitance measurements as a function of bias voltage. The leakage current increases with the accumulated dose but does not contributes significantly to the current signal, since the diodes are operated in photovoltaic mode, without bias voltage. For the MCz diode no change in the full depletion voltage was observed, which indicates its higher tolerance to radiation-induced damage, as expected. During electron irradiation the temperature increases and in order to determine its influence for the current signals, the leakage current values were extrapolated up to 35 °C. The contribution does not exceed 0.1% for FZ and MCz diodes. The effect of the radiation type, electrons or gamma rays, on the pre dose procedures was analyzed for the FZ n-type device and was observed that the

  1. Telemetry Ranging: Signal Processing

    Hamkins, J.; Kinman, P.; Xie, H.; Vilnrotter, V.; Dolinar, S.

    2016-02-01

    This article describes the details of the signal processing used in a telemetry ranging system in which timing information is extracted from the downlink telemetry signal in order to compute spacecraft range. A previous article describes telemetry ranging concepts and architecture, which are a slight variation of a scheme published earlier. As in that earlier work, the telemetry ranging concept eliminates the need for a dedicated downlink ranging signal to communicate the necessary timing information. The present article describes the operation and performance of the major receiver functions on the spacecraft and the ground --- many of which are standard tracking loops already in use in JPL's flight and ground radios --- and how they can be used to provide the relevant information for making a range measurement. It also describes the implementation of these functions in software, and performance of an end-to-end software simulation of the telemetry ranging system.

  2. Telemetry-Based Ranging

    Hamkins, Jon; Vilnrotter, Victor A.; Andrews, Kenneth S.; Shambayati, Shervin

    2011-01-01

    A telemetry-based ranging scheme was developed in which the downlink ranging signal is eliminated, and the range is computed directly from the downlink telemetry signal. This is the first Deep Space Network (DSN) ranging technology that does not require the spacecraft to transmit a separate ranging signal. By contrast, the evolutionary ranging techniques used over the years by NASA missions, including sequential ranging (transmission of a sequence of sinusoids) and PN-ranging (transmission of a pseudo-noise sequence) whether regenerative (spacecraft acquires, then regenerates and retransmits a noise-free ranging signal) or transparent (spacecraft feeds the noisy demodulated uplink ranging signal into the downlink phase modulator) relied on spacecraft power and bandwidth to transmit an explicit ranging signal. The state of the art in ranging is described in an emerging CCSDS (Consultative Committee for Space Data Systems) standard, in which a pseudo-noise (PN) sequence is transmitted from the ground to the spacecraft, acquired onboard, and the PN sequence is coherently retransmitted back to the ground, where a delay measurement is made between the uplink and downlink signals. In this work, the telemetry signal is aligned with the uplink PN code epoch. The ground station computes the delay between the uplink signal transmission and the received downlink telemetry. Such a computation is feasible because symbol synchronizability is already an integral part of the telemetry design. Under existing technology, the telemetry signal cannot be used for ranging because its arrival-time information is not coherent with any Earth reference signal. By introducing this coherence, and performing joint telemetry detection and arrival-time estimation on the ground, a high-rate telemetry signal can provide all the precision necessary for spacecraft ranging.

  3. The PCNA interaction protein box sequence in Rad54 is an integral part of its ATPase domain and is required for efficient DNA repair and recombination.

    Burgess, Rebecca C; Sebesta, Marek; Sisakova, Alexandra; Marini, Victoria P; Lisby, Michael; Damborsky, Jiri; Klein, Hannah; Rothstein, Rodney; Krejci, Lumir

    2013-01-01

    Rad54 is an ATP-driven translocase involved in the genome maintenance pathway of homologous recombination (HR). Although its activity has been implicated in several steps of HR, its exact role(s) at each step are still not fully understood. We have identified a new interaction between Rad54 and the replicative DNA clamp, proliferating cell nuclear antigen (PCNA). This interaction was only mildly weakened by the mutation of two key hydrophobic residues in the highly-conserved PCNA interaction motif (PIP-box) of Rad54 (Rad54-AA). Intriguingly, the rad54-AA mutant cells displayed sensitivity to DNA damage and showed HR defects similar to the null mutant, despite retaining its ability to interact with HR proteins and to be recruited to HR foci in vivo. We therefore surmised that the PCNA interaction might be impaired in vivo and was unable to promote repair synthesis during HR. Indeed, the Rad54-AA mutant was defective in primer extension at the MAT locus as well as in vitro, but additional biochemical analysis revealed that this mutant also had diminished ATPase activity and an inability to promote D-loop formation. Further mutational analysis of the putative PIP-box uncovered that other phenotypically relevant mutants in this domain also resulted in a loss of ATPase activity. Therefore, we have found that although Rad54 interacts with PCNA, the PIP-box motif likely plays only a minor role in stabilizing the PCNA interaction, and rather, this conserved domain is probably an extension of the ATPase domain III. PMID:24376557

  4. Radiation-induced effects of ATM gene on expressions of BRCA1 and RAD51 detected by laser scanning confocal microscopy

    Objective: To investigate the expressions of BRCA1 and RAD51 proteins in GM, ATM+- AT, and AT cells before and after irradiation by 60Co γ-rays. Methods: The localizations and expressions of BRCA1 and RAD51 proteins in GM, ATM+-AT, AT cells were detected by immunofluorescence staining and laser scanning confocal microscopy after 0 and 10 Gy 60Co γ-ray irradiation. Quantitative analysis was also processed on these proteins. Results: Before irradiation with γ-rays, few expression of RAD51 or BRCA1 protein and no colocalization was observed in GM, ATM+-AT, AT cells, and lowest expression in AT cells. Being irradiated with 10 Gy 60Co γ-rays, the expressions of BRCA1 and RAD51 proteins were increased in GM, ATM+-AT, and AT cells. Colocalized expressions in GM, ATM+-AT cells were observed, but no such expression in AT cells. The expressions of BRCA1 and RAD51 proteins in GM, ATM+-AT cells statistically significantly differed from those in AT cells (P+-AT cells was also statistically significant (P+-AT cells could activate its down stream genes, BRCA1 and RAD51, and could enhance the expressions of and interactions between these two proteins. All these changes are helpful for cell repair following radiation injury. The expressions of BRCA1 and RAD51 proteins were lower in normal GM cells transfected with extrinsic ATM than that in GM cells because the extrinsic ATM gene could not completely compensate the function, partial phosphorylation of down stream gene BRCA1, of intrinsic ATM mutative gene. (authors)

  5. Mapping with RAD (restriction-site associated DNA) markers to rapidly identify QTL for stem rust resistance in Lolium perenne.

    Pfender, W F; Saha, M C; Johnson, E A; Slabaugh, M B

    2011-05-01

    A mapping population was created to detect quantitative trait loci (QTL) for resistance to stem rust caused by Puccinia graminis subsp. graminicola in Lolium perenne. A susceptible and a resistant plant were crossed to produce a pseudo-testcross population of 193 F(1) individuals. Markers were produced by the restriction-site associated DNA (RAD) process, which uses massively parallel and multiplexed sequencing of reduced-representation libraries. Additional simple sequence repeat (SSR) and sequence-tagged site (STS) markers were combined with the RAD markers to produce maps for the female (738 cM) and male (721 cM) parents. Stem rust phenotypes (number of pustules per plant) were determined in replicated greenhouse trials by inoculation with a field-collected, genetically heterogeneous population of urediniospores. The F(1) progeny displayed continuous distribution of phenotypes and transgressive segregation. We detected three resistance QTL. The most prominent QTL (qLpPg1) is located near 41 cM on linkage group (LG) 7 with a 2-LOD interval of 8 cM, and accounts for 30-38% of the stem rust phenotypic variance. QTL were detected also on LG1 (qLpPg2) and LG6 (qLpPg3), each accounting for approximately 10% of phenotypic variance. Alleles of loci closely linked to these QTL originated from the resistant parent for qLpPg1 and from both parents for qLpPg2 and qLpPg3. Observed quantitative nature of the resistance may be due to partial-resistance effects against all pathogen genotypes, or qualitative effects completely preventing infection by only some genotypes in the genetically mixed inoculum. RAD markers facilitated rapid construction of new genetic maps in this outcrossing species and will enable development of sequence-based markers linked to stem rust resistance in L. perenne. PMID:21344184

  6. Charged particle spectra measured during the transit to Mars with the Mars Science Laboratory Radiation Assessment Detector (MSL/RAD)

    Ehresmann, Bent; Hassler, Donald M.; Zeitlin, Cary; Guo, Jingnan; Köhler, Jan; Wimmer-Schweingruber, Robert F.; Appel, Jan K.; Brinza, David E.; Rafkin, Scot C. R.; Böttcher, Stephan I.; Burmeister, Sönke; Lohf, Henning; Martin, Cesar; Böhm, Eckart; Matthiä, Daniel; Reitz, Günther

    2016-08-01

    The Mars Science Laboratory (MSL) started its 253-day cruise to Mars on November 26, 2011. During cruise the Radiation Assessment Detector (RAD), situated on board the Curiosity rover, conducted measurements of the energetic-particle radiation environment inside the spacecraft. This environment consists mainly of galactic cosmic rays (GCRs), as well as secondary particles created by interactions of these GCRs with the spacecraft. The RAD measurements can serve as a proxy for the radiation environment a human crew would encounter during a transit to Mars, for a given part of the solar cycle, assuming that a crewed vehicle would have comparable shielding. The measurements of radiological quantities made by RAD are important in themselves, and, the same data set allow for detailed analysis of GCR-induced particle spectra inside the spacecraft. This provides important inputs for the evaluation of current transport models used to model the free-space (and spacecraft) radiation environment for different spacecraft shielding and different times in the solar cycle. Changes in these conditions can lead to significantly different radiation fields and, thus, potential health risks, emphasizing the need for validated transport codes. Here, we present the first measurements of charged particle fluxes inside a spacecraft during the transit from Earth to Mars. Using data obtained during the last two month of the cruise to Mars (June 11-July 14, 2012), we have derived detailed energy spectra for low-Z particles stopping in the instrument's detectors, as well as integral fluxes for penetrating particles with higher energies. Furthermore, we analyze the temporal changes in measured proton fluxes during quiet solar periods (i.e., when no solar energetic particle events occurred) over the duration of the transit (December 9, 2011-July 14, 2012) and correlate them with changing heliospheric conditions.

  7. A simple method to retrospectively estimate patient dose-area product for chest tomosynthesis examinations performed using VolumeRAD

    Båth, Magnus, E-mail: magnus.bath@vgregion.se; Svalkvist, Angelica [Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg SE-413 45, Sweden and Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg SE-413 45 (Sweden); Söderman, Christina [Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg SE-413 45 (Sweden)

    2014-10-15

    Purpose: The purpose of the present work was to develop and validate a method of retrospectively estimating the dose-area product (DAP) of a chest tomosynthesis examination performed using the VolumeRAD system (GE Healthcare, Chalfont St. Giles, UK) from digital imaging and communications in medicine (DICOM) data available in the scout image. Methods: DICOM data were retrieved for 20 patients undergoing chest tomosynthesis using VolumeRAD. Using information about how the exposure parameters for the tomosynthesis examination are determined by the scout image, a correction factor for the adjustment in field size with projection angle was determined. The correction factor was used to estimate the DAP for 20 additional chest tomosynthesis examinations from DICOM data available in the scout images, which was compared with the actual DAP registered for the projection radiographs acquired during the tomosynthesis examination. Results: A field size correction factor of 0.935 was determined. Applying the developed method using this factor, the average difference between the estimated DAP and the actual DAP was 0.2%, with a standard deviation of 0.8%. However, the difference was not normally distributed and the maximum error was only 1.0%. The validity and reliability of the presented method were thus very high. Conclusions: A method to estimate the DAP of a chest tomosynthesis examination performed using the VolumeRAD system from DICOM data in the scout image was developed and validated. As the scout image normally is the only image connected to the tomosynthesis examination stored in the picture archiving and communication system (PACS) containing dose data, the method may be of value for retrospectively estimating patient dose in clinical use of chest tomosynthesis.

  8. A simple method to retrospectively estimate patient dose-area product for chest tomosynthesis examinations performed using VolumeRAD

    Purpose: The purpose of the present work was to develop and validate a method of retrospectively estimating the dose-area product (DAP) of a chest tomosynthesis examination performed using the VolumeRAD system (GE Healthcare, Chalfont St. Giles, UK) from digital imaging and communications in medicine (DICOM) data available in the scout image. Methods: DICOM data were retrieved for 20 patients undergoing chest tomosynthesis using VolumeRAD. Using information about how the exposure parameters for the tomosynthesis examination are determined by the scout image, a correction factor for the adjustment in field size with projection angle was determined. The correction factor was used to estimate the DAP for 20 additional chest tomosynthesis examinations from DICOM data available in the scout images, which was compared with the actual DAP registered for the projection radiographs acquired during the tomosynthesis examination. Results: A field size correction factor of 0.935 was determined. Applying the developed method using this factor, the average difference between the estimated DAP and the actual DAP was 0.2%, with a standard deviation of 0.8%. However, the difference was not normally distributed and the maximum error was only 1.0%. The validity and reliability of the presented method were thus very high. Conclusions: A method to estimate the DAP of a chest tomosynthesis examination performed using the VolumeRAD system from DICOM data in the scout image was developed and validated. As the scout image normally is the only image connected to the tomosynthesis examination stored in the picture archiving and communication system (PACS) containing dose data, the method may be of value for retrospectively estimating patient dose in clinical use of chest tomosynthesis

  9. Rad51 Nucleoprotein Filament Disassembly Captured Using Fluorescent Plasmodium falciparum SSB as a Reporter for Single-Stranded DNA.

    Davenport, Eric Parker; Harris, Derek F; Origanti, Sofia; Antony, Edwin

    2016-01-01

    Single-stranded DNA binding (SSB) proteins coordinate DNA replication, repair, and recombination and are critical for maintaining genomic integrity. SSB binds to single-stranded DNA (ssDNA) rapidly and with very high affinity making it a useful molecular tool to detect free ssDNA in solution. We have labeled SSB from Plasmodium falciparum (Pf-SSB) with the MDCC (7-diethylamino-3-((((2-maleimidyl)ethyl)amino)-carbonyl)coumarin) fluorophore which yields a four-fold increase in fluorescence upon binding to ssDNA. Pf-SSBMDCC binding to DNA is unaffected by NaCl or Mg2+ concentration and does not display salt-dependent changes in DNA binding modes or cooperative binding on long DNA substrates. These features are unique to Pf-SSB, making it an ideal tool to probe the presence of free ssDNA in any biochemical reaction. Using this Pf-SSBMDCC probe as a sensor for free ssDNA, we have investigated the clearing of preformed yeast Rad51 nucleoprotein filaments by the Srs2 helicase during HR. Our studies provide a rate for the disassembly of the Rad51 filament by full length Srs2 on long ssDNA substrates. Mutations in the conserved 2B domain in the homologous bacterial UvrD, Rep and PcrA helicases show an enhancement of DNA unwinding activity, but similar mutations in Srs2 do not affect its DNA unwinding or Rad51 clearing properties. These studies showcase the utility of the Pf-SSB probe in mechanistic investigation of enzymes that function in DNA metabolism. PMID:27416037

  10. Hodnocení revitalizace Radčického potoka, okr. Plzeň-město

    Tomková, Jana

    2011-01-01

    The initial part of graduation thesis deals with the issue of watercourses’ revitalisation with focus on an urban area. The point of the thesis is to show that the capacity of river-basin in urban area doesn’t have to have only the artificial canals. After that follows a description of flood-protection modification, that was made on the “Radčický brook” in years 2009-2010. The river-basin was strengthened by stone-block pavement during this period of time. The area of interest is situ...

  11. Mms19 protein functions in nucleotide excision repair by sustaining an adequate cellular concentration of the TFIIH component Rad3

    Kou, Haiping; Ying ZHOU; Gorospe, R.M. Charlotte; Wang, Zhigang

    2008-01-01

    Nucleotide excision repair (NER) is a major cellular defense mechanism against DNA damage. We have investigated the role of Mms19 in NER in the yeast Saccharomyces cerevisiae. NER was deficient in the mms19 deletion mutant cell extracts, which was complemented by the NER/transcription factor TFIIH, but not by purified Mms19 protein. In mms19 mutant cells, protein levels of the core TFIIH component Rad3 (XPD homologue) and Ssl2 (XPB homologue) were significantly reduced by up to 3.5- and 2.2-f...

  12. A new parameterization for ice cloud optical properties used in BCC-RAD and its radiative impact

    A new parameterization of the solar and infrared optical properties of ice clouds that considers the multiple habits of ice particles was developed on the basis of a prescribed dataset. First, the fitting formulae of the bulk extinction coefficient, single-scatter albedo, asymmetry factor, and δ-function forward-peak factor at the given 65 wavelengths as a function of effective radius were created for common scenarios, which consider a greater number of wavelengths and are more accurate than those used previously. Then, the band-averaged volume extinction and absorption coefficients, asymmetry factor and forward-peak factor of ice cloud were derived for the BCC-RAD (Beijing Climate Center radiative transfer model) using a parameter reference table. Finally, the newly developed and the original schemes in the BCC-RAD and the commonly used Fu Scheme of ice cloud were all applied to the BCC-RAD. Their influences on radiation calculations were compared using the mid-latitude summer atmospheric profile with ice clouds under no-aerosol conditions, and produced a maximum difference of approximately 30.0 W/m2 for the radiative flux, and 4.0 K/d for the heating rate. Additionally, a sensitivity test was performed to investigate the impact of the ice crystal density on radiation calculations using the three schemes. The results showed that the maximum difference was 68.1 W/m2 for the shortwave downward radiative flux (for the case of perpendicular solar insolation), and 4.2 K/d for the longwave heating rate, indicating that the ice crystal density exerts a significant effect on radiation calculations for a cloudy atmosphere. - Highlights: • A new parameterization of the radiative properties of ice cloud was obtained. • More accurate fitting formulae of them were created for common scenarios. • The band-averaged of them were derived for our radiation model of BCC-RAD. • We found that there exist large differences of results among different ice schemes. • We found

  13. Construction of an SSR and RAD-Marker Based Molecular Linkage Map of Vigna vexillata (L. A. Rich.

    Rusama Marubodee

    Full Text Available Vigna vexillata (L. A. Rich. (tuber cowpea is an underutilized crop for consuming its tuber and mature seeds. Wild form of V. vexillata is a pan-tropical perennial herbaceous plant which has been used by local people as a food. Wild V. vexillata has also been considered as useful gene(s source for V. unguiculata (cowpea, since it was reported to have various resistance gene(s for insects and diseases of cowpea. To exploit the potential of V. vexillata, an SSR-based linkage map of V. vexillata was developed. A total of 874 SSR markers successfully amplified single DNA fragment in V. vexillata among 1,336 SSR markers developed from Vigna angularis (azuki bean, V. unguiculata and Phaseolus vulgaris (common bean. An F2 population of 300 plants derived from a cross between salt resistant (V1 and susceptible (V5 accessions was used for mapping. A genetic linkage map was constructed using 82 polymorphic SSR markers loci, which could be assigned to 11 linkage groups spanning 511.5 cM in length with a mean distance of 7.2 cM between adjacent markers. To develop higher density molecular linkage map and to confirm SSR markers position in a linkage map, RAD markers were developed and a combined SSR and RAD markers linkage map of V. vexillata was constructed. A total of 559 (84 SSR and 475 RAD markers loci could be assigned to 11 linkage groups spanning 973.9 cM in length with a mean distance of 1.8 cM between adjacent markers. Linkage and genetic position of all SSR markers in an SSR linkage map were confirmed. When an SSR genetic linkage map of V. vexillata was compared with those of V. radiata and V. unguiculata, it was suggested that the structure of V. vexillata chromosome was considerably differentiated. This map is the first SSR and RAD marker-based V. vexillata linkage map which can be used for the mapping of useful traits.

  14. Construction of an SSR and RAD-Marker Based Molecular Linkage Map of Vigna vexillata (L.) A. Rich.

    Marubodee, Rusama; Ogiso-Tanaka, Eri; Isemura, Takehisa; Chankaew, Sompong; Kaga, Akito; Naito, Ken; Ehara, Hiroshi; Tomooka, Norihiko

    2015-01-01

    Vigna vexillata (L.) A. Rich. (tuber cowpea) is an underutilized crop for consuming its tuber and mature seeds. Wild form of V. vexillata is a pan-tropical perennial herbaceous plant which has been used by local people as a food. Wild V. vexillata has also been considered as useful gene(s) source for V. unguiculata (cowpea), since it was reported to have various resistance gene(s) for insects and diseases of cowpea. To exploit the potential of V. vexillata, an SSR-based linkage map of V. vexillata was developed. A total of 874 SSR markers successfully amplified single DNA fragment in V. vexillata among 1,336 SSR markers developed from Vigna angularis (azuki bean), V. unguiculata and Phaseolus vulgaris (common bean). An F2 population of 300 plants derived from a cross between salt resistant (V1) and susceptible (V5) accessions was used for mapping. A genetic linkage map was constructed using 82 polymorphic SSR markers loci, which could be assigned to 11 linkage groups spanning 511.5 cM in length with a mean distance of 7.2 cM between adjacent markers. To develop higher density molecular linkage map and to confirm SSR markers position in a linkage map, RAD markers were developed and a combined SSR and RAD markers linkage map of V. vexillata was constructed. A total of 559 (84 SSR and 475 RAD) markers loci could be assigned to 11 linkage groups spanning 973.9 cM in length with a mean distance of 1.8 cM between adjacent markers. Linkage and genetic position of all SSR markers in an SSR linkage map were confirmed. When an SSR genetic linkage map of V. vexillata was compared with those of V. radiata and V. unguiculata, it was suggested that the structure of V. vexillata chromosome was considerably differentiated. This map is the first SSR and RAD marker-based V. vexillata linkage map which can be used for the mapping of useful traits. PMID:26398819

  15. UČINCI MOBINGA NA PRIVREMENU SPRIJEČENOST ZA RAD U MEDICINSKIH SESTARA-TEHNIČARA

    Beganlić, Azijada; Pranjić, Nurka; Brković, Aida; Batić-Mujanović, Olivera; Herenda, Samira

    2009-01-01

    SAŽETAK: Mobing ili psihološko zlostavljanje usmjereno je prema jednom pojedincu koji je stavljen u poziciju u kojoj je bespomoćan i u nemogućnosti da se zaštiti od stalnih maltretirajućih aktivnosti. Mobing ima negativne posljedice na zdravlje zaposlenih, što povećava stopu izostanka s posla zbog bolovanja. Cilj rada je procijeniti učinke mobinga na privremenu spriječenost za rad (apsentizam) u medicinskih tehničara. Prospektivnom studijom poprečnog presjeka analizirali smo stopu prevale...

  16. An attempt to calibrate the UHF strato-tropospheric radar at Arecibo using NexRad radar and disdrometer data

    P. Kafando

    2004-12-01

    Full Text Available The goal of this paper is to present a methodology to calibrate the reflectivity of the UHF Strato-Tropospheric (ST radar located at NAIC in Puerto Rico. The UHF lower relevant altitude is at 5.9km, the melting layer being at around 4.8km. The data used for the calibration came from the observations of clouds, carried out with Strato-Tropospheric dual-wavelength (UHF and VHF radars and a disdrometer; those instruments being located on the NAIC site in Arecibo, Puerto Rico. The National Weather Service operates other instruments like the radiosondes and the NexRad Radar in other sites.

    The proposed method proceeds in two steps. The first consists of the comparison between the NexRad reflectivity and the reflectivity computed from the drop size distributions measured by the disdrometer for one day with a noticeable rainfall rate. In spite of the distance of both instruments, the agreement between the reflectivities of both instruments is enough good to be used as a reference for the UHF ST radar. The errors relative at each data set is found to be 2.75dB for the disdrometer and 4dB for the NexRad radar, following the approach of Hocking et al. (2001. The inadequacy between the two sampled volume is an important contribution in the errors.

    The second step consists of the comparison between the NexRad radar reflectivity and the UHF non-calibrated reflectivity at the 4 altitudes of common observations during one event on 15 October 1998. Similar features are observed and a coefficient is deduced. An offset around 4.7dB is observed and the correlation factor lies between 0.628 and 0.730. According to the errors of the data sets, the precision on the calibration is of the order of 2dB. This method works only when there are precipitation hydrometeors above the NAIC site. However, the result of the calibration could be applied to other data obtained during the campaign, the only

  17. Laser Range Sensors

    K.C. Bahuguna

    2007-11-01

    Full Text Available This paper presents the design aspects of laser range finders and proximity sensors being developed at IRDE for different applications. The principle used in most of the laser range finders is pulse echo or time-of-flight measurement. Optical triangulation is used in proximity sensors while techniques like phase detection and interferometry are employed in instruments for surveying and motion controllers where high accuracy is desired. Most of the laser range finders are designed for ranging non-cooperative targets.

  18. Yeast RAD2, a homolog of human XPG, plays a key role in the regulation of the cell cycle and actin dynamics

    Mi-Sun Kang

    2013-12-01

    Mutations in the human XPG gene cause Cockayne syndrome (CS and xeroderma pigmentosum (XP. Transcription defects have been suggested as the fundamental cause of CS; however, defining CS as a transcription syndrome is inconclusive. In particular, the function of XPG in transcription has not been clearly demonstrated. Here, we provide evidence for the involvement of RAD2, the Saccharomyces cerevisiae counterpart of XPG, in cell cycle regulation and efficient actin assembly following ultraviolet irradiation. RAD2 C-terminal deletion, which resembles the XPG mutation found in XPG/CS cells, caused cell growth arrest, the cell cycle stalling, a defective α-factor response, shortened lifespan, cell polarity defect, and misregulated actin-dynamics after DNA damage. Overexpression of the C-terminal 65 amino acids of Rad2p was sufficient to induce hyper-cell polarization. In addition, RAD2 genetically interacts with TPM1 during cell polarization. These results provide insights into the role of RAD2 in post-UV irradiation cell cycle regulation and actin assembly, which may be an underlying cause of XPG/CS.

  19. RAD18 and associated proteins are immobilized in nuclear foci in human cells entering S-phase with ultraviolet light-induced damage

    Proteins required for translesion DNA synthesis localize in nuclear foci of cells with replication-blocking lesions. The dynamics of this process were examined in human cells with fluorescence-based biophysical techniques. Photobleaching recovery and raster image correlation spectroscopy experiments indicated that involvement in the nuclear foci reduced the movement of RAD18 from diffusion-controlled to virtual immobility. Examination of the mobility of REV1 indicated that it is similarly immobilized when it is observed in nuclear foci. Reducing the level of RAD18 greatly reduced the focal accumulation of REV1 and reduced UV mutagenesis to background frequencies. Fluorescence lifetime measurements indicated that RAD18 and RAD6A or polη only transferred resonance energy when these proteins colocalized in damage-induced nuclear foci, indicating a close physical association only within such foci. Our data support a model in which RAD18 within damage-induced nuclear foci is immobilized and is required for recruitment of Y-family DNA polymerases and subsequent mutagenesis. In the absence of damage these proteins are not physically associated within the nucleoplasm

  20. Suppression of RAD21 Induces Senescence of MDA-MB-231 Human Breast Cancer Cells Through RB1 Pathway Activation Via c-Myc Downregulation.

    Zhu, Shan; Zhao, Li; Li, Yueyang; Hou, Pingfu; Yao, Ruosi; Tan, Jiang; Liu, Dongxu; Han, Liping; Huang, Baiqu; Lu, Jun; Zhang, Yu

    2016-06-01

    Cellular senescence impedes cancer progression by limiting uncontrolled cell proliferation. To identify new genetic events controlling senescence, we performed a small interfering RNA screening human cancer cells and identified a number of targets potentially involved in senescence of MDA-MB-231 human breast cancer cells. Importantly, we showed that knockdown of RAD21 resulted in the appearance of several senescent markers, including enhanced senescence-associated β-galactosidase activity and heterochromatin focus formation, as well as elevated p21 protein levels and RB1 pathway activation. Further biochemical analyses revealed that RAD21 knockdown led to the downregulation of c-Myc and its targets, including CDK4, a negative regulator of RB1, and blockedRB1 phosphorylation (pRB1), and the RB1-mediated transcriptional repression of E2F. Moreover, c-Myc downregulation was partially mediated by proteasome-dependent degradation within promyelocytic leukemia (PML) nuclear bodies, which were found to be highly abundant during RAD21 knockdown-induced senescence. Exogenous c-Myc reconstitution rescued cells from RAD21 silencing-induced senescence. Altogether, data arising from this study implicate a novel function of RAD21 in cellular senescence in MDA-MB-231 cells that is mainly dependent onRB1 pathway activation via c-Myc downregulation. J. Cell. Biochem. 117: 1359-1369, 2016. © 2015 Wiley Periodicals, Inc. PMID:26529363