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Sample records for mcp dxt-rad passive

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

    CERN Document Server

    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...

  2. Extremity dosimetry trial: Devonport royal dockyard

    International Nuclear Information System (INIS)

    Kenyon, R.; Collison, R.

    2008-01-01

    This trial was undertaken to assess extremity dosemeters, which were made available to Devonport Royal Dockyard and determine the most suitable to the site. The trial included operational and laboratory-based exposures. Operational exposures were within a submarine reactor compartment and a waste storage area. Laboratory exposures were undertaken using 241 Am, 137 Cs and 60 Co sources to compare and contrast the dosemeters energy response. In addition, the low dose response and the response if placed in the incorrect orientation were also assessed. Ten passive and two active dosemeters were tested, with three highlighted as the most technically suitable, DSTL Harshaw DXT-RAD, HPA Harshaw EXT-RAD and the AMEC Panasonic UD-807A. The most technically suitable dosemeter was the DSTL Harshaw DXT-RAD, due to good responses within all aspects of the trial and the user's preference for the ring type design. The John Caunt ED2 electronic dosemeter 2 (ED2) also performed well, but suffered radio frequency interference. (authors)

  3. Development and tests of MCP based timing and multiplicity detector for MIPs

    Science.gov (United States)

    Feofilov, G.; Kondratev, V.; Stolyarov, O.; Tulina, T.; Valiev, F.; Vinogradov, L.

    2017-01-01

    We present summary of technological developments and tests of the MCP based large area detector aimed at precise timing and charged particles multiplicity measurements. Results obtained in course of these developments of isochronous (simultaneity) precise signal readout, passive summation of 1 ns signals, fast (1 GHz) front-end electronics, miniature vacuum systems, etc. could be potentially interesting for a number of future applications in different fields.

  4. Fast front-end L0 trigger electronics for ALICE FMD-MCP tests and performance

    CERN Document Server

    Efimov, L G; Kasatkan, V; Klempt, W; Kuts, V; Lenti, V; Platanov, V; Rudge, A; Stolyarov, O I; Tsimbal, F A; Valiev, F F; Villalobos Baillie, O; Vinogradov, L I; Zhigunov, O

    1997-01-01

    We present design details and new measurements of the performance of fast electronics for the Forward Multiplicity Detector for ALICE. These detectors based on sector type Microchannel Plates (MCP) forming several disks gave the very first trigger decision in the experiment (L0). Fast passive summators integrated with the detectors are used for linear summation of up to eight isochronous signal channels from MCP pads belonging to one sector. Two types of microelectronics design thin film summators were produced. We present test results for these summators, working in the frequency range up to 1 Ghz. New low noise preamplifiers have been built to work with these summators. The new design shows a good performance with the usable frequency range extended up to 1 Ghz. An upgrade of the functional scheme for the L0 ALICE pre-trigger design is also presented.Abstract:List of figures Figure 1: ALICE L0 Trigger Front-End Electronics Functional Scheme. Figure 2: UHF design for a fast passive summator based on direct...

  5. Studies of MCP properties

    International Nuclear Information System (INIS)

    Lehmann, A; Britting, A; Eyrich, W; Uhlig, F

    2009-01-01

    Cherenkov detectors of the DIRC type will be used for the particle identification of the PANDA experiment at FAIR. Because of their advantageous properties inside a magnetic field micro-channel plate (MCP) photomultipliers (PMT) are very attractive photon sensors for the two PANDA DIRCs. Various types of MCP-PMTs were investigated. Their gains and their time resolutions were measured as a function of the magnitude and the direction of a magnetic field. It was found that with a pore size of ≤ 10 μm efficient single photon detection is possible even at 2 Tesla if the field direction is close to parallel to the PMT axis. The gain of most of the studied MCP-PMTs remains stable up to a photon density of roughly 1 MHz/cm 2 , while the new Hamamatsu R10754-00-L4 can stand rates of about 10 MHz/cm 2 before the gain starts decreasing. The time resolution of all investigated MCP-PMTs was better than 50 ps (σ). The response of the multi-anode MCP-PMTs was scanned as a function of the position of the photo cathode plane in particular to measure the crosstalk among adjacent pixels. Most of the sensors show a satisfactory behavior.

  6. TOF-SIMA analysis of coating on MCP

    International Nuclear Information System (INIS)

    Luo Chunping; Liang Handong; Sun Dongxu

    2007-01-01

    Microchannel plate (MCP) is a sophisticated electronic optical device. It has advantages of high gain, small size, and low using voltage as a detector. The electronic transmission film on the MCP input plane could effectively avoid the positive ion feedback, and protect the photocathode, eliminate flicker noise, and prolong the lifespan of the device. In conclusion, the different films of the input plane can affect the performance of the MCP. Therefore, there is practical value to study surface coating composition of MCP for understanding the relationship between composition and performance and developing high-powered MCP. In the experiment, TOF-SIMS is used to study the surface coating composition of MCP. The results show that there are some main metal elements such as Si, K, Cr, Ni, Rh, Cs and Pb in the surface of the MCP. (authors)

  7. RAD9, RAD17; RAD24, and RAD53 control one pathway of resistance to γ irradiation in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Koltovaya, N.A.; Nikulushkina, Yu.V.; Roshina, M.P.; Devin, A.B.

    2009-01-01

    Mechanisms for the genetic control of the cell cycle transition (checkpoint control) have been studied in more detail in yeast Saccharomyces cerevisiae. To clarify tho role of the RAD9, RAD17, RAD24, and RAD53 checkpoint genes in cell radioresistance, diploid double mutants were analyzed for cell sensitivity to ionizing radiation. All mutations in combination with rad9Δ were shown to manifest the epistatic type of interaction. Our results suggest that the RAD9, RAD17, RAD24, and RAD53 checkpoint genes belong to a single epistasis group called the RAD9 group and participate in the same pathway. RAD9 and RAD53 have a positive effect on sensitivity to γ irradiation, whereas RAD17 and RAD24 have a negative effect. For haploid interactions between mutations may differ in the case of γ or UV irradiation, mutations - for example, rad9Δ and rad24Δ - were shown to have an additive effect in the first case and epistatic - in the second. The analyzed genes can also participate in minor mechanisms of radioresistance that are relatively independent of the above major mechanism

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

    International Nuclear Information System (INIS)

    Koltovaya, N.A.; Nikulushkina, Yu.V.; Roshchina, M.P.; Devin, A.B.

    2007-01-01

    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

  9. Ion Feedback Suppression Using Inclined MCP Holes in a Single-MCP+Micromegas+Pads Detector

    International Nuclear Information System (INIS)

    Va'vra, J.; Sumiyoshi, T.

    2005-01-01

    We show that the ion backflow to photocathode can be completely suppressed if one uses inclined MCP holes in a presence of magnetic field. The inclined hole angles are chosen to be aligned with the Lorentz electron angle allowing the electron transmission and amplification, while positive ions, traveling along a different angle, are caught on the MCP hole walls. The detector under investigation is a new gaseous detector structure based on a tandem of two parts, a single MCP (Microchannel) plate, a Micromegas with pad readout. We are aiming to develop a gaseous photon detector with the Bialkali photocathode, however, one could use some ideas in the paper for other types of detectors

  10. Ion feedback suppression using inclined MCP holes in a 'single-MCP+micromegas+pads' detector

    International Nuclear Information System (INIS)

    Va'vra, J.; Sumiyoshi, T.

    2005-01-01

    We show that the ion backflow to photocathode can be completely suppressed if one uses inclined MCP holes in the presence of a magnetic field. The inclined hole angles are chosen to be aligned with the Lorentz electron angle allowing the electron transmission and amplification, while positive ions, traveling along a different angle, are caught on the MCP hole walls. The detector under investigation is a new gaseous detector structure based on a tandem of two parts, a single MCP (microchannel plate), a micromegas with pad readout. We are aiming to develop a gaseous photon detector with the Bialkali photocathode, however, one could use some ideas in the paper for other types of detectors

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

    International Nuclear Information System (INIS)

    Calderon, I.L.; Contopoulou, C.R.; Mortimer, R.K.

    1982-01-01

    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

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

    International Nuclear Information System (INIS)

    Veelen, Lieneke R. van; Essers, Jeroen; Rakt, Mandy W.M.M. van de; Odijk, Hanny; Pastink, Albert; Zdzienicka, MaIgorzata Z.; Paulusma, Coen C.; Kanaar, Roland

    2005-01-01

    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

  13. Single ion counting with a MCP (microchannel plate) detector

    Energy Technology Data Exchange (ETDEWEB)

    Tawara, Hiroko; Sasaki, Shinichi; Miyajima, Mitsuhiro [National Lab. for High Energy Physics, Tsukuba, Ibaraki (Japan); Shibamura, Eido

    1996-07-01

    In this study, a single-ion-counting method using alpha-particle-impact ionization of Ar atoms is demonstrated and the preliminary {epsilon}{sub mcp} for Ar ions with incident energies of 3 to 4.7 keV is determined. The single-ion counting by the MCP is aimed to be performed under experimental conditions as follows: (1) A signal from the MCP is reasonably identified as incidence of single Ar-ion. (2) The counting rate of Ar ions is less than 1 s{sup -1}. (3) The incident Ar ions are not focused on a small part of an active area of the MCP, namely, {epsilon}{sub mcp} is determined with respect to the whole active area of the MCP. So far, any absolute detection efficiency has not been reported under these conditions. (J.P.N.)

  14. Lifetime of MCP-PMTs and other performance features

    Science.gov (United States)

    Lehmann, A.; Böhm, M.; Eyrich, W.; Miehling, D.; Pfaffinger, M.; Stelter, S.; Uhlig, F.; Ali, A.; Belias, A.; Dzhygadlo, R.; Gerhardt, A.; Götzen, K.; Kalicy, G.; Krebs, M.; Lehmann, D.; Nerling, F.; Patsyuk, M.; Peters, K.; Schepers, G.; Schmitt, L.; Schwarz, C.; Schwiening, J.; Traxler, M.; Düren, M.; Etzelmüller, E.; Föhl, K.; Hayrapetyan, A.; Kreutzfeld, K.; Merle, O.; Rieke, J.; Schmidt, M.; Wasem, T.; Achenbach, P.; Cardinali, M.; Hoek, M.; Lauth, W.; Schlimme, S.; Sfienti, C.; Thiel, M.

    2018-02-01

    The bar PANDA experiment at FAIR will use DIRC detectors for the separation of hadrons. The compactness of the bar PANDA detector requires the image planes of these detectors to be placed inside the magnetic field of the solenoid. Due to this and other boundary conditions MCP-PMTs were identified as the only suitable photon sensors. Until recently the major obstacle for an application of MCP-PMTs in high rate experiments like bar PANDA were serious aging problems which led to damage at the photo-cathode and a fast declining quantum efficiency as the integrated anode charge (IAC) increased. With new countermeasures against the aging, in particular due to the application of an atomic layer deposition (ALD) technique to coat the MCP pores, the lifetime of MCP-PMTs has meanwhile increased by a factor >50 which is fully sufficient for bar PANDA. The recent results of our long-term lifetime measurements are discussed. New 2-inch MCP-PMT prototypes from Hamamatsu show an encouraging behavior. However, the currently best performing MCP-PMT is a 2-inch PHOTONIS tube with two ALD-layers which reaches an IAC of >16 C/cm2 without any visible sign of aging. In the second part of these proceedings a new data acquisition system of the PADIWA/TRB type is presented which allows a quasi-parallel measurement of many MCP-PMT performance parameters. Especially unwanted effects like dark-count rate, crosstalk, ion after-pulsing, and recoil electrons can be studied in more detail than ever before. Exemplary results for these parameters are shown. The discussed DAQ system will be used for the comprehensive data quality checks of the MCP-PMTs being built into the DIRCs.

  15. Single electron counting using a dual MCP assembly

    International Nuclear Information System (INIS)

    Yang, Yuzhen; Liu, Shulin; Zhao, Tianchi; Yan, Baojun; Wang, Peiliang; Yu, Yang; Lei, Xiangcui; Yang, Luping; Wen, Kaile; Qi, Ming

    2016-01-01

    The gain, pulse height resolution and peak-to-valley ratio of single electrons detected by using a Chevron configured Microchannel Plate (MCP) assembly are studied. The two MCPs are separated by a 280 µm gap and are biased by four electrodes. The purpose of the study is to determine the optimum bias voltage arrangements for single electron counting. By comparing the results of various bias voltage combinations, we conclude that good performance for the electron counting can be achieved by operating the MCP assembly in saturation mode. In addition, by applying a small reverse bias voltage across the gap while adjusting the bias voltages of the MCPs, optimum performance of electron counting can be obtained. - Highlights: • Dual MCPs assembly with four electrodes using different voltage combinations has been investigated for single electron counting. • Both the MCP voltages and the gap voltage can affect the gain, pulse height resolution and P/V ratio. • A high gain of the first stage MCP, a saturation mode of the second stage MCP and an appropriately reverse gap voltage can improve the resolution greatly. • The optimum voltage arrangements is significant for the design of MCP detectors in single electron counting applications.

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

    International Nuclear Information System (INIS)

    Jansen, L.E.T.; Verhage, R.A.; Brouwer, J.

    1998-01-01

    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

  17. Systemic MCP1/CCR2 blockade and leukocyte specific MCP1/CCR2 inhibition affect aortic aneurysm formation differently

    NARCIS (Netherlands)

    de Waard, Vivian; Bot, Ilze; de Jager, Saskia C. A.; Talib, Sara; Egashira, Kensuke; de Vries, Margreet R.; Quax, Paul H. A.; Biessen, Erik A. L.; van Berkel, Theo J. C.

    2010-01-01

    Objective: CCR2, the receptor for monocyte chemoattractant protein 1 (MCP1), is involved in atherosclerosis and abdominal aortic aneurysms (AAAs). Here, we explored the potential beneficial blockade of the MCP1/CCR2 pathway. Methods: We applied an AAA model in aging apolipoprotein E deficient mice

  18. Repair of pyrimidine dimers in radiation-sensitive mutants rad3, rad4, rad6, and rad9 of Saccharomyces cerevisiae. [nicking

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, L [Rochester Univ., N.Y. (USA). Dept. of Radiation Biology and Biophysics; Rochester Univ., N.Y. (USA). School of Medicine and Dentistry)

    1977-10-01

    The ability to remove ultraviolet-induced pyrimidine dimers was examined in four radiation-sensitive mutants of Saccharomyces cerevisiae. The susceptibility of DNA from irradiated cells to nicking by either the T4 uv-endonuclease or an endonuclease activity found in crude extracts of Micrococcus luteus was used to measure the presence of dimers in DNA. The rad3 and rad4 mutants are shown to be defective in dimer excision whereas the rad6 and rad9 mutants are proficient in dimer excision.

  19. Development of MCP transient operation strategy for the SMART-P

    International Nuclear Information System (INIS)

    Yoo, S. E.; Choi, B. S.; Kang, H. O.; Yoon, J. H.; Ji, S. K.

    2003-01-01

    SMART-P MCP(Main Coolant Pump) transient operation strategies are developed. A Modular Modeling System (MMS) computer code is used for the evaluation of the developed operation strategies. In the SMART-P, normal operating modes are classified into MCP high speed(3600 rpm) mode and MCP low speed mode. Also, natural circulation mode is defined as a performance test case. MCP operation transients occur when changing modes from one to another, and system parameters(core power, system pressure, temperature) are having transients. These transients affect on system performance and, in some cases, limit system operation. In this study, MCP operation strategies are developed and obtained acceptable results

  20. MCP-1 expressed by osteoclasts stimulates osteoclastogenesis in an autocrine/paracrine manner

    International Nuclear Information System (INIS)

    Miyamoto, Kana; Ninomiya, Ken; Sonoda, Koh-Hei; Miyauchi, Yoshiteru; Hoshi, Hiroko; Iwasaki, Ryotaro; Miyamoto, Hiroya

    2009-01-01

    Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays a critical role in the recruitment and activation of leukocytes. Here, we describe that multinuclear osteoclast formation was significantly inhibited in cells derived from MCP-1-deficient mice. MCP-1 has been implicated in the regulation of osteoclast cell-cell fusion; however defects of multinuclear osteoclast formation in the cells from mice deficient in DC-STAMP, a seven transmembrane receptor essential for osteoclast cell-cell fusion, was not rescued by recombinant MCP-1. The lack of MCP-1 in osteoclasts resulted in a down-regulation of DC-STAMP, NFATc1, and cathepsin K, all of which were highly expressed in normal osteoclasts, suggesting that osteoclast differentiation was inhibited in MCP-1-deficient cells. MCP-1 alone did not induce osteoclastogenesis, however, the inhibition of osteoclastogenesis in MCP-1-deficient cells was restored by addition of recombinant MCP-1, indicating that osteoclastogenesis was regulated in an autocrine/paracrine manner by MCP-1 under the stimulation of RANKL in osteoclasts.

  1. Associations between Deceased-Donor Urine MCP-1 and Kidney Transplant Outcomes.

    Science.gov (United States)

    Mansour, S G; Puthumana, J; Reese, P P; Hall, I E; Doshi, M D; Weng, F L; Schröppel, B; Thiessen-Philbrook, H; Bimali, M; Parikh, C R

    2017-07-01

    Existing methods to predict recipient allograft function during deceased-donor kidney procurement are imprecise. Understanding the potential renal reparative role for monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in macrophage recruitment after injury, might help predict allograft outcomes. We conducted a sub-study of the multicenter prospective Deceased Donor Study cohort, which evaluated deceased kidney donors from five organ procurement organizations from May 2010 to December 2013. We measured urine MCP-1 (uMCP-1) concentrations from donor samples collected at nephrectomy to determine associations with donor acute kidney injury (AKI), recipient delayed graft function (DGF), 6-month estimated GFR (eGFR), and graft failure. We also assessed perfusate MCP-1 concentrations from pumped kidneys for associations with DGF and 6-month eGFR. AKI occurred in 111 (9%) donors. Median (interquartile range) uMCP-1 concentration was higher in donors with AKI compared to donors without AKI (1.35 [0.41-3.93] ng/ml vs. 0.32 [0.11-0.80] ng/ml, p<0.001). DGF occurred in 756 (31%) recipients, but uMCP-1 was not independently associated with DGF. Higher donor uMCP-1 concentrations were independently associated with higher 6-month eGFR in those without DGF [0.77 (0.10, 1.45) ml/min/1.73m 2 per doubling of uMCP1]. However, there were no independent associations between uMCP-1 and graft failure over a median follow-up of about 2 years. Lastly, perfusate MCP-1 concentrations significantly increased during pump perfusion but were not associated with DGF or 6-month eGFR. Donor uMCP-1 concentrations were modestly associated with higher recipient 6-month eGFR in those without DGF. However, the results suggest that donor uMCP-1 has minimal clinical utility given no associations with graft failure.

  2. Efficiency enhancements for MCP-based beta autoradiography imaging

    CERN Document Server

    Lees, J E

    2002-01-01

    We describe three approaches to increase the beta detection efficiency of microchannel plate detectors for biological beta autoradiography:(a)reversing the microchannel plate (MCP) bias polarity, changing the conventional high negative voltage on the input MCP to a grounded input, (b) a reduction in MCP pore size from 12.5 to 6 mu m, (c) using a CsI coating as an efficient secondary electron emitter. We also present our first measurements of double-tracer ( sup 3 H and sup 1 sup 4 C) imaging using pulse height analysis to distinguish between isotopes.

  3. Combined effects of 1-methyl cyclopropene (1-MCP) and modified ...

    African Journals Online (AJOL)

    1-MCP-treated fruits delayed two different harvest maturity, persimmon fruits flesh firmness, and combination of 1-MCP with MAPA and MAPB reduced the ethylene production rate during storage. Treatment of 1-MCP improved storability of persimmon fruits more effectively than MAP storage. However, the results indicated ...

  4. CCL2/MCP-1 modulation of microglial activation and proliferation

    Directory of Open Access Journals (Sweden)

    Garcia-Bueno Borja

    2011-07-01

    Full Text Available Abstract Background Monocyte chemoattractant protein (CCL2/MCP-1 is a chemokine that attracts cells involved in the immune/inflammatory response. As microglia are one of the main cell types sustaining inflammation in brain, we proposed here to analyze the direct effects of MCP-1 on cultured primary microglia. Methods Primary microglia and neuronal cultures were obtained from neonatal and embryonic Wistar rats, respectively. Microglia were incubated with different concentrations of recombinant MCP-1 and LPS. Cell proliferation was quantified by measuring incorporation of bromodeoxyuridine (BrdU. Nitrite accumulation was measured using the Griess assay. The expression and synthesis of different proteins was measured by RT-PCR and ELISA. Cell death was quantified by measuring release of LDH into the culture medium. Results MCP-1 treatment (50 ng/ml, 24 h did not induce morphological changes in microglial cultures. Protein and mRNA levels of different cytokines were measured, showing that MCP-1 was not able to induce proinflammatory cytokines (IL-1β, IL6, MIP-1α, either by itself or in combination with LPS. A similar lack of effect was observed when measuring inducible nitric oxide synthase (NOS2 expression or accumulation of nitrites in the culture media as a different indicator of microglial activation. MCP-1 was also unable to alter the expression of different trophic factors that were reduced by LPS treatment. In order to explore the possible release of other products by microglia and their potential neurotoxicity, neurons were co-cultured with microglia: no death of neurons could be detected when treated with MCP-1. However, the presence of MCP-1 induced proliferation of microglia, an effect opposite to that observed with LPS. Conclusion These data indicate that, while causing migration and proliferation of microglia, MCP-1 does not appear to directly activate an inflammatory response in this cell type, and therefore, other factors may be

  5. Optimization design of a 20-in. elliptical MCP-PMT

    International Nuclear Information System (INIS)

    Chen, Ping; Tian, Jinshou; Wei, Yonglin; Liu, Hulin; Sai, Xiaofeng; He, Jianping; Chen, Lin; Wang, Xing; Lu, Yu

    2017-01-01

    This paper describes the simulation work for optimizing the newly developed 20-in. elliptical MCP-PMT by enlarging the outside diameters of the two focusing electrodes and the open area of the glass bulb. Effects of biasing voltages applied to the two focusing electrodes and the MCP input facet are studied. With the new design of the 20 in. MCP-PMT, the transit time spread of the prototype can be less than 3 ns and the collection efficiency is as much as the present prototype.

  6. How to prevent ripening blockage in 1-MCP-treated 'Conference' pears.

    Science.gov (United States)

    Chiriboga, Maria-Angeles; Schotsmans, Wendy C; Larrigaudière, Christian; Dupille, Eve; Recasens, Inmaculada

    2011-08-15

    Some European pear varieties treated with 1-methylcyclopropene (1-MCP) often remain 'evergreen', meaning that their ripening process is blocked and does not resume after removal from cold storage. In this work this was confirmed also to be the case in 'Conference' pears. To reverse the blockage of ripening 1-MCP treatments combined with external exogenous ethylene were tested. 1-MCP treatment of 'Conference' pears is very effective in delaying ripening and, more specifically, softening. The same 1-MCP concentration in different experimental years caused a different response. The higher dose of 1-MCP (600 nL L⁻¹) always resulted in irreversible blockage of ripening, whereas the behaviour of fruit receiving a lower dose (300 nL L⁻¹) depended on the year, and this did not depend on maturity at harvest or on storage conditions. Simultaneous exposure to 1-MCP and exogenous ethylene significantly affected fruit ripening, allowing significant softening to occur but at a lower rate compared with control fruit. The application of exogenous ethylene and 1-MCP simultaneously after harvest permitted restoration of the ripening process after storage in 'Conference' pears, extending the possibility of marketing and consumption. Copyright © 2011 Society of Chemical Industry.

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

    International Nuclear Information System (INIS)

    Glassner, B.J.; Mortimer, R.K.

    1994-01-01

    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

  8. Electron optics design of an 8-in. spherical MCP-PMT

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ping, E-mail: chenping@opt.cn [Key Laboratory of Ultra-fast photoelectric Diagnostics Technology, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences, Xi’an 710119 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006, Shanxi (China); Tian, Jinshou [Key Laboratory of Ultra-fast photoelectric Diagnostics Technology, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences, Xi’an 710119 (China); Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006, Shanxi (China); Qian, Sen; Zhao, Tianchi [Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China); Liu, Hulin; Wei, Yonglin; Sai, Xiaofeng; He, Jianping; Wang, Xing; Lu, Yu [Key Laboratory of Ultra-fast photoelectric Diagnostics Technology, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences, Xi’an 710119 (China); Chen, Lin; Guo, Lehui; Pei, Chengquan; Hui, Dandan [Key Laboratory of Ultra-fast photoelectric Diagnostics Technology, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences, Xi’an 710119 (China); University of Chinese Academy of Sciences, Beijing 100049 (China)

    2017-03-11

    This paper discusses the electron optical system of an 8-in. spherical MCP-PMT. The MCP assembly, the supporting pole and the supply voltages are carefully designed to optimize the photoelectron collection efficiency and the transit time spread. Coating the MCP nickel-chromium electrode with an additional high secondary emission material is employed to make a breakthrough on the collection efficiency. With the simulation software CST, the Finite Integration method and the Monte Carlo method are combined to evaluate the collection efficiency, the time properties and the Earth's magnetic field effects. Simulation results show that the photocathode active solid angle is over 3.5 πsr, the average collection efficiency can exceed 95% with the coated MCP and the mean transit time spread is 2.2 ns for a typical electric potential of 500 V applied between the photocathode and the MCP input facet. The prototype and the measured single photoelectron spectrum are also presented.

  9. MCP1 haplotypes associated with protection from pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Owusu-Dabo Ellis

    2011-04-01

    Full Text Available Abstract Background The monocyte chemoattractant protein 1 (MCP-1 is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB case-control study group, associations of the MCP1 -362C and the MCP1 -2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the MCP1 gene in order to determine causal variants or haplotypes genetically and functionally. Results A 14 base-pair deletion in the first MCP1 intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, Pcorrected = 0.00098. Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, Pnominal = 0.00002; adjusted Pglobal = 0.0028. In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the MCP1 mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006. The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB. Conclusions In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the MCP1 -362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91. Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the

  10. Influência do 1-MCP na conservação pós-colheita de rosas cv. Vega Influence of 1-MCP on postharvest conservation of roses cv. Vega

    Directory of Open Access Journals (Sweden)

    Júlia De Pietro

    2010-10-01

    Full Text Available Objetivou-se, neste trabalho, estudar aspectos da fisiologia pós-colheita de rosas cortadas cv. Vega, tratadas com diferentes concentrações de 1-metilcicloropropeno (1-MCP. O experimento foi conduzido em delineamento inteiramente casualizado, em esquema fatorial composto por dois fatores: quatro tratamentos pós-colheita e quatro datas de avaliação (0; 4; 8; 12 dias. As flores foram submetidas aos seguintes tratamentos: 1 Água destilada (controle; 2 1-MCP (100 ppb; 3 1-MCP (250 ppb; 4 1-MCP (500 ppb. Foram realizadas as seguintes avaliações: massa fresca, cor, turgescência, curvatura, taxa respiratória, conteúdo relativo de água, conteúdo de carboidratos solúveis, de redutores e de antocianina. Ao contrário do tratamento controle, todas as concentrações de 1-MCP foram eficientes para retardar a senescência das flores, porém, a concentração de 1-MCP a 500 ppb destacou-se pela melhor manutenção da qualidade, além de prolongar a vida decorativa das hastes até 19 dias.The objective of this work was to study aspects of postharvest physiology of cut roses cv. Vega, treated with different concentrations of 1-metilcloropropene (1-MCP. The experiment was conducted in a complete randomized design composed of two factors: four postharvest treatments and four dates of evaluation (0; 4; 8; 12 days. The following treatments were used: 1 distilled water; 2 1-metilciclopropeno (1-MCP 100 ppb; 3 1-MCP 250 ppb; 4 1-MCP 500 ppb. The following evaluations were made: fresh weight, color, turgor, curvature, respiration rate, relative water content, content of soluble carbohydrates, reducing and anthocyanin. Unlike treatment with distilled water, all concentrations of 1-MCP were effective in delaying the senescence of flowers; however, the concentration of 1-MCP at 500 ppb was highlighted by better maintenance of quality and extended decorate life stem up to 19 days.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Defective thymine dimer excision in radiation-sensitive mutants rad10 and rad16 of Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, L [Rochester Univ., N.Y. (USA). School of Medicine and Dentistry

    1977-04-01

    Two rad mutants of yeast, rad10 and rad16, are shown to be defective in the removal of UV-induced pyrimidine dimers since DNAs obtained from irradiated cells following a post-irradiation incubation in the dark still retain UV-endonuclease-sensitive sites. Both rad10 and rad16 mutants are in the same pathway of excision-repair as the rad1, rad2, rad3, and rad4 mutants.

  13. Rad51-Rad52 mediated maintenance of centromeric chromatin in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Sreyoshi Mitra

    2014-04-01

    Full Text Available Specification of the centromere location in most eukaryotes is not solely dependent on the DNA sequence. However, the non-genetic determinants of centromere identity are not clearly defined. While multiple mechanisms, individually or in concert, may specify centromeres epigenetically, most studies in this area are focused on a universal factor, a centromere-specific histone H3 variant CENP-A, often considered as the epigenetic determinant of centromere identity. In spite of variable timing of its loading at centromeres across species, a replication coupled early S phase deposition of CENP-A is found in most yeast centromeres. Centromeres are the earliest replicating chromosomal regions in a pathogenic budding yeast Candida albicans. Using a 2-dimensional agarose gel electrophoresis assay, we identify replication origins (ORI7-LI and ORI7-RI proximal to an early replicating centromere (CEN7 in C. albicans. We show that the replication forks stall at CEN7 in a kinetochore dependent manner and fork stalling is reduced in the absence of the homologous recombination (HR proteins Rad51 and Rad52. Deletion of ORI7-RI causes a significant reduction in the stalled fork signal and an increased loss rate of the altered chromosome 7. The HR proteins, Rad51 and Rad52, have been shown to play a role in fork restart. Confocal microscopy shows declustered kinetochores in rad51 and rad52 mutants, which are evidence of kinetochore disintegrity. CENP-ACaCse4 levels at centromeres, as determined by chromatin immunoprecipitation (ChIP experiments, are reduced in absence of Rad51/Rad52 resulting in disruption of the kinetochore structure. Moreover, western blot analysis reveals that delocalized CENP-A molecules in HR mutants degrade in a similar fashion as in other kinetochore mutants described before. Finally, co-immunoprecipitation assays indicate that Rad51 and Rad52 physically interact with CENP-ACaCse4 in vivo. Thus, the HR proteins Rad51 and Rad52

  14. Roles for the yeast RAD18 and RAD52 DNA repair genes in UV mutagenesis.

    Science.gov (United States)

    Armstrong, J D; Chadee, D N; Kunz, B A

    1994-11-01

    Experimental evidence indicates that although the Saccharomyces cerevisiae RAD18 and RAD52 genes are not required for nucleotide excision repair, they function in the processing of UV-induced DNA damage in yeast. Conflicting statements regarding the UV mutability of strains deleted for RAD18 prompted us to re-examine the influence of RAD18, and RAD52, on UV mutagenesis. To do so, we characterized mutations induced by UV in SUP4-o, a yeast suppressor tRNA gene. SUP4-o was maintained on a plasmid in isogenic strains that either carried one of two different rad18 deletions (rad18 delta) or had RAD52 disrupted. Both rad18 deletions decreased the frequency of UV-induced SUP4-o mutations to levels close to those for spontaneous mutagenesis in the rad18 delta backgrounds, and prevented a net increase in mutant yield. A detailed analysis of mutations isolated after UV irradiation of one of the rad18 delta strains uncovered little evidence of the specificity features typical for UV mutagenesis in the isogenic repair-proficient (RAD) parent (e.g., predominance of G.C-->A.T transitions). Evidently, UV induction of SUP4-o mutations is highly dependent on the RAD18 gene. Compared to the RAD strain, disruption of RAD52 reduced the frequency and yield of UV mutagenesis by about two-thirds. Closer inspection revealed that 80% of this reduction was due to a decrease in the frequency of G.C-->A.T transitions. In addition, there were differences in the distributions and site specificities of single base-pair substitutions. Thus, RAD52 also participates in UV mutagenesis of a plasmid-borne gene in yeast, but to a lesser extent than RAD18.

  15. Study on MCP-1 related to inflammation induced by biomaterials

    International Nuclear Information System (INIS)

    Ding Tingting; Sun Jiao; Zhang Ping

    2009-01-01

    The study of inflammation is important for understanding the reaction between biomaterials and the human body, in particular, the interaction between biomaterials and immune system. In the current study, rat macrophages were induced by multiple biomaterials with different biocompatibilities, including polyvinyl chloride (PVC) containing 8% of organic tin, a positive control material with cellular toxicity. Human umbilical vein endothelial cells (ECV-304), cultured with PRMI-1640, were detached from cells cultured with the supernatant of macrophages containing TNF-α and IL-1β because of stimulation by biomaterials. The cells were then treated with different biomaterials. Then both TNF-α and IL-1β in macrophages were detected by ELISA. Levels of monocyte chemoattractant protein-1 (MCP-1) were measured by RT-PCR. The results suggested that the expression of TNF-α and IL-1β was elevated by polytetrafluoroethylene (PTFE), polylactic-co-glycolic acid (PLGA) and American NPG alloy (p < 0.001). The level of MCP-1 cultured in supernatant of macrophages was higher than in PRMI-1640 with the same biomaterials. And the exposure to PTFE, PLGA and NPG resulted in the high expression of MCP-1 (p < 0.001) following cytokine stimulation. MCP-1 was also significantly expressed in β-tricalcium phosphate (β-TCP) and calcium phosphate cement samples (CPC) (p < 0.01). Thus, TNF-α, IL-1β and MCP-1 had played an important role in the immune reaction induced by biomaterials and there was a close relationship between the expression of cytokines and biomcompatibility of biomaterials. Furthermore, these data suggested that MCP-1 was regulated by TNF-α and IL-1β, and activated by both cytokines and biomaterials. The data further suggested that the expression of MCP-1 could be used as a marker to indicate the degree of immune reaction induced by biomaterials.

  16. Schizosaccharomyces pombe Rad22A and Rad22B have similar biochemical properties and form multimeric structures

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Femke A.T. de [Department of Toxicogenetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands); Zonneveld, Jose B.M. [Department of Toxicogenetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands); Groot, Anton J. de [Department of Toxicogenetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands); Koning, Roman I. [Department of Molecular Cell Biology, Leiden University Medical Center, Leiden (Netherlands); Zeeland, Albert A. van [Department of Toxicogenetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands); Pastink, Albert [Department of Toxicogenetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)]. E-mail: A.Pastink@lumc.nl

    2007-02-03

    The Saccharomyces cerevisiae Rad52 protein has a crucial role in the repair of DNA double-strand breaks by homologous recombination. In vitro, Rad52 displays DNA binding and strand annealing activities and promotes Rad51-mediated strand exchange. Schizosaccharomyces pombe has two Rad52 homologues, Rad22A and Rad22B. Whereas rad22A deficient strains exhibit severe defects in repair and recombination, rad22B mutants have a much less severe phenotype. To better understand the role of Rad22A and Rad22B in double-strand break repair, both proteins were purified to near homogeneity. Using gel retardation and filter binding assays, binding of Rad22A and Rad22B to short single-stranded DNAs was demonstrated. Binding of Rad22A to double-stranded oligonucleotides or linearized plasmid molecules containing blunt ends or short single-stranded overhangs could not be detected. Rad22B also does not bind efficiently to short duplex oligonucleotides but binds readily to DNA fragments containing 3'-overhangs. Rad22A as well as Rad22B efficiently promote annealing of complementary single-stranded DNAs. In the presence of Rad22A annealing of complementary DNAs is almost 90%. Whereas in reactions containing Rad22B the maximum level of annealing is 60%, most likely due to inhibition of the reaction by duplex DNA. Gel-filtration experiments and electron microscopic analyses indicate self-association of Rad22A and Rad22B and the formation of multimeric structures as has been observed for Rad52 in yeast and man.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Study of the effects of 1-MCP to blueberry under cold storage

    Science.gov (United States)

    Tao, Shenchen; Chu, Huailiang; Chen, Xiaomin; Yuan, Huwei; Qiu, Lingling; Zhao, Liang; Yan, Daoliang; Zheng, Bingsong

    2017-04-01

    Blueberry is one of the thinnest exocarp fruits in the world, which is difficult to keep fresh due to the special structure of its skin. 1-Methlcyclopropene (1-MCP) is able to combine with ethylene(ETH) receptor. In this study we investigated the effect of 1-MCP on rotting rate, weight loss ratio, soluble sugar content, titratable acid content, antioxidant enzyme activities and malondialdehyde (MDA) content in blueberry (Vaccinium corymbosun ‘O Neal’ and ‘North Road’) under cold storage. 1-MCP reduced the rotting rate, weight loss ratio and MDA content, while keeping high-leveled stability in antioxidant enzyme activities, soluble sugar content and titratable acid content. These results showed the role of 1-MCP in alleviating the negative effects of blueberry and suggested that 1-MCP could be used as a preservative for keeping thin exocarp fruit in fresh.

  19. Dosimetric properties of the pocket alarm dosimeter type Alnor RAD 21L, RAD 21H, RAD 22

    International Nuclear Information System (INIS)

    Hauser, M.; Burgkhardt, B.; Piesch, E.

    1981-02-01

    In personnel monitoring pocket dosimeters with build-in alarm devices are increasingly in use. The report presents results of a test performed at Karlsruhe for the pocket dose and alarm meter type Alnor RAD 21L, RAD 21H, RAD 22. The properties investigated are above all linearity and reproducibility of the dose reading as well as of the acoustic alarm indication, dependence of the dose reading on the photon energy, the direction of the radiation incidence, the dose rate, the temperature, operational characteristic of the batteries. (orig.) [de

  20. The MCP-4/MCP-1 ratio in plasma is a candidate circadian biomarker for chronic post-traumatic stress disorder

    Science.gov (United States)

    Dalgard, C; Eidelman, O; Jozwik, C; Olsen, C H; Srivastava, M; Biswas, R; Eudy, Y; Rothwell, S W; Mueller, G P; Yuan, P; Drevets, W C; Manji, H K; Vythlingam, M; Charney, D S; Neumeister, A; Ursano, R J; Jacobowitz, D M; Pollard, H B; Bonne, O

    2017-01-01

    Post-traumatic stress disorder (PTSD) is psychiatric disease, which can occur following exposure to traumatic events. PTSD may be acute or chronic, and can have a waxing and waning course of symptoms. It has been hypothesized that proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF) or plasma might be mediators of the psychophysiological mechanisms relating a history of trauma exposure to changes in behavior and mental health disorders, and medical morbidity. Here we test the cytokine/chemokine hypothesis for PTSD by examining levels of 17 classical cytokines and chemokines in CSF, sampled at 0900 hours, and in plasma sampled hourly for 24 h. The PTSD and healthy control patients are from the NIMH Chronic PTSD and healthy control cohort, initially described by Bonne et al. (2011), in which the PTSD patients have relatively low comorbidity for major depressive disorder (MDD), drug or alcohol use. We find that in plasma, but not CSF, the bivariate MCP4 (CCL13)/ MCP1(CCL2) ratio is ca. twofold elevated in PTSD patients compared with healthy controls. The MCP-4/MCP-1 ratio is invariant over circadian time, and is independent of gender, body mass index or the age at which the trauma was suffered. By contrast, MIP-1β is a candidate biomarker for PTSD only in females, whereas TARC is a candidate biomarker for PTSD only in males. It remains to be discovered whether these disease-specific differences in circadian expression for these specific immune signaling molecules are biomarkers, surrogates, or drivers for PTSD, or whether any of these analytes could contribute to therapy. PMID:28170001

  1. Thioredoxin reductase 1 upregulates MCP-1 release in human endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhen-Bo [Institute of Biophysics, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Beijing (China); Shen, Xun, E-mail: shenxun@sun5.ibp.ac.cn [Institute of Biophysics, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Beijing (China)

    2009-09-04

    To know if thioredoxin reductase 1 (TrxR1) plays a role in antioxidant defense mechanisms against atherosclerosis, effect of TrxR1 on expression/release of monocyte chemoattractant protein (MCP-1) was investigated in activated human endothelial-like EAhy926 cells. The MCP-1 release and expression, cellular generation of reactive oxygen species (ROS), nuclear translocation and DNA-binding activity of NF-{kappa}B subunit p65 were assayed in cells either overexpressing recombinant TrxR1 or having their endogenous TrxR1 knocked down. It was found that overexpression of TrxR1 enhanced, while knockdown of TrxR1 reduced MCP-1 release and expression. Upregulation of MCP-1 by TrxR1 was associated with increasing generation of intracellular ROS generation, enhanced nuclear translocation and DNA-binding activity of NF-{kappa}B. Assay using NF-{kappa}B reporter revealed that TrxR1 upregulated transcriptional activity of NF-{kappa}B. This study suggests that TrxR1 enhances ROS generation, NF-{kappa}B activity and subsequent MCP-1 expression in endothelial cells, and may promote rather than prevent vascular endothelium from forming atherosclerotic plaque.

  2. Associations Between Deceased-Donor Urine MCP-1 and Kidney Transplant Outcomes

    Directory of Open Access Journals (Sweden)

    S.G. Mansour

    2017-07-01

    Discussion: Donor uMCP-1 concentrations were modestly associated with higher recipient 6-month eGFR in those without DGF. However, the results suggest that donor uMCP-1 has minimal clinical utility given no associations with graft failure.

  3. Pós colheita de bananas-maçã submetidas ao 1-MCP e armazenadas á temperatura ambiente Postharvest of 'apple' banana submetted to 1-MCP and storage in room temperature

    Directory of Open Access Journals (Sweden)

    Ana Carla Marque Pinheiro

    2006-04-01

    Full Text Available Bananas da cultivar Maçã foram adquiridas no estádio dois de coloração da casca (verde maturos e submetidas à ação de 1-MCP. O 1-MCP foi aplicado por 12 horas nas seguintes concentrações: 0 (controle, 50, 100, 150, 200 hL.L-1. Após aplicação, os frutos foram armazenados à temperatura ambiente (temperatura média 20ºC ± 1 e umidade relativa 80% ± 5 e avaliados à medida que atingiam os graus 3, 5 e 7 de coloração da casca. O tratamento com 1-MCP atrasou o início do amadurecimento de bananas-maçã armazenadas sob temperatura ambiente, baseado nas primeiras mudanças de coloração da casca. A aplicação de 1-MCP em bananas-maçã, ditou maiores valores de perda de massa e relação polpa/casca (nos graus 5 e 7 de coloração da casca. O 1-MCP, nas doses 100, 150 e 200 hL.L-1 de 1-MCP promoveu desverdecimento desuniforme e tonalidade avermelhada na casca. O tratamento 50 hL.L-1 de 1-MCP é o mais adequado, por promover a extensão da vida pós-colheita de bananas-maçã da cultivar armazenadas sob temperatura ambiente sem afetar a coloração da casca dos frutos, apresentando qualidade, baseando-se na cor da casca, firmeza, acidez titulável, pH e sólidos solúveis, semelhante ao controle.Mature green 'Apple' bananas were submitted to five concentrations of 1-MCP (0, 50, 100, 150 and 200 hL.L-1 for 12 hours. After treatment, the fruits were stored at room temperature (20ºC ± 1 and 80% ± 5 RH and analyzed at 3,5 and 7 color degree of peel. The treatment with 1-MCP delayed the start of the ripening based in the first changes of peel color. The treatment of 'Apple' bananas with 1-MCP promoted higher values of mass loss and pulp/peel ratio (5 and 7 degrees of color peel. The fruits treated with 100, 150 and 200 nL.L-1 of 1-MCP showed heterogeneous degreening and development of red color on the peel. 1-MCP at 50 nL.L-1 was the most appropriated treatment for promoting the extension of postharvest life of 'Apple' bananas stored

  4. MCP-1 Levels are Associated with Cardiac Remodeling but not with Resistant Hypertension.

    Science.gov (United States)

    Ritter, Alessandra Mileni Versuti; Faria, Ana Paula Cabral de; Sabbatini, Andrea; Corrêa, Nathalia Batista; Brunelli, Veridiana; Modolo, Rodrigo; Moreno, Heitor

    2017-04-01

    Hypertension is a chronic, low-grade inflammation process associated with the release of cytokines and development of target organ damage. Deregulated monocyte chemoattractant protein-1 (MCP-1) levels have been associated with high blood pressure and cardiovascular complications; however, the mechanisms involved are complex and not fully understood. This study aimed to compare the levels of MCP-1 in patients with resistant (RH) versus mild-to-moderate (HTN) hypertension and their association with the presence or absence of left ventricular hypertrophy (LVH) in all hypertensive subjects. We enrolled 256 hypertensive subjects: 120 RH and 136 HTN, investigating the relationship between circulating MCP-1 levels and blood pressure, biochemical data, hematologic profile, and cardiac damage within the RH and HTN groups. Plasma MCP-1 levels were measured by ELISA and LVH was assessed by echocardiography. We found no difference in MCP-1 levels between RH and HTN subjects. On the other hand, we encountered lower MCP-1 levels in patients with LVH (105 pg/mL [100 - 260 pg/mL] versus 136 pg/mL (100 - 200 pg/mL), p = 0.005, respectively] compared with those without LVH. A logistic regression model adjusted for body mass index (BMI), age, race, aldosterone levels, and presence of diabetes and RH demonstrated that median levels of MCP-1 (2.55 pg/mL [1.22 - 5.2 pg/mL], p = 0.01) were independently associated with LVH in the entire hypertensive population. Since MCP-1 levels were similar in both RH and HTN subjects and decreased in hypertensive patients with existing LVH, our study suggests a possible downregulation in MCP-1 levels in hypertensive individuals with LVH, regardless of hypertension strata. A hipertensão arterial é um processo crônico de baixo grau inflamatório, associado com liberação de citocinas e desenvolvimento de lesão em órgãos-alvo. A desregulação dos níveis de proteína quimiotática de monócitos-1 (MCP-1) tem sido associada com elevação da press

  5. Melanocyte pigmentation inversely correlates with MCP-1 production and angiogenesis-inducing potential.

    Science.gov (United States)

    Adini, Irit; Adini, Avner; Bazinet, Lauren; Watnick, Randolph S; Bielenberg, Diane R; D'Amato, Robert J

    2015-02-01

    The incidence of certain angiogenesis-dependent diseases is higher in Caucasians than in African Americans. Angiogenesis is amplified in wound healing and cornea models in albino C57 mice compared with black C57 mice. Moreover, mouse and human melanocytes with low pigmentation stimulate endothelial cell (EC) proliferation and migration in vitro more than melanocytes with high pigmentation. This effect is due, in part, to the secretion of an angiogenic protein called fibromodulin (FMOD) from lowly pigmented melanocytes. Herein, we expand upon the mechanism contributing to increased angiogenesis in lighter skin and report that monocyte chemotactic protein-1 (MCP-1) is secreted by nonpigmented mouse melanocytes by 5- to 10-fold more than pigmented melanocytes. MCP-1 protein stimulates EC proliferation and migration in vitro and angiogenesis in vivo. Mechanistic studies determine that FMOD is upstream of MCP-1 and promotes its secretion from both melanocytes and activated ECs via stimulation of NF-κB activity. Mice injected with FMOD-neutralizing antibodies show 2.3-fold decreased levels of circulating MCP-1. Human studies confirmed that, on average, Caucasians have 2-fold higher serum levels of MCP-1 than African Americans. Taken together, this study implicates the FMOD/MCP-1 pathway in the regulation of angiogenesis by local melanocytes and suggests that melanogenic activity may protect against aberrant angiogenic diseases. © FASEB.

  6. Increased MCP-1 gene expression in monocytes of severe OSA patients and under intermittent hypoxia.

    Science.gov (United States)

    Chuang, Li-Pang; Chen, Ning-Hung; Lin, Yuling; Ko, Wen-Shan; Pang, Jong-Hwei S

    2016-03-01

    Obstructive sleep apnea (OSA) is known to be a risk factor of coronary artery disease. Monocyte chemoattractant protein-1 (MCP-1), as a critical factor for monocyte infiltration, is known to play a role in the development of atherosclerosis. This study aimed to investigate the effect of intermittent hypoxia, the hallmark of OSA, on the MCP-1 expression of monocytes. Peripheral blood was sampled from 61 adults enrolled for suspected OSA. RNA was prepared from the isolated monocytes for the analysis of MCP-1. The effect of in vitro intermittent hypoxia on the regulation and function of MCP-1 was investigated on THP-1 monocytic cells and human monocytes. The mRNA and secreted protein levels were investigated by RT/real-time PCR and enzyme-linked immunosorbent assay, respectively. Monocytic MCP-1 gene expression was found to be increased significantly in severe OSA patients. In vitro intermittent hypoxia was demonstrated to increase the mRNA and protein expression levels of MCP-1 dose- and time-dependently in THP-1 monocytic cells. The MCP-1 mRNA expression in monocytes isolated from OSA patient was induced to a much higher level compared to that from normal control. Pre-treatment with inhibitor for p42/44 MAPK or p38 MAPK suppressed the activation of MCP-1 expression by intermittent hypoxia. This is the first study to demonstrate the increase of MCP-1 gene expression in monocytes of severe OSA patients. In addition, monocytic MCP-1 gene expression can be induced under intermittent hypoxia.

  7. Atraso do amadurecimento de banana 'Maçã' pelo 1-MCP, aplicado previamente à refrigeração Ripening delay of 'Apple' banana submitted to 1-MCP, prevoiously applied to refrigeration

    Directory of Open Access Journals (Sweden)

    Gustavo Costa Almeida

    2006-08-01

    Full Text Available O objetivo deste trabalho foi avaliar o efeito de diferentes períodos de exposição da banana 'Maçã' a 50 ppb de 1-MCP (0; 3; 6; 9; 12 e 24 horas sobre sua vida pós-colheita e qualidade. Após exposição ao 1-MCP, os frutos verde-maturos foram armazenados por 30 dias em câmaras com temperatura de 13ºC ± 0,5 e umidade relativa de 95%. Em seguida, as bananas foram armazenadas à temperatura de 20ºC ± 1, até amarelecimento completo da casca. A exposição de banana 'Maçã' a 50 ppb de 1-MCP, por 9 horas, retardou em 7 dias o seu amadurecimento, em comparação a frutos não expostos ao 1-MCP, após 30 dias de armazenamento refrigerado (13ºC, sem prejuízos à sua aparência e composição química. A exposição de banana 'Maçã' a 50 ppb de 1-MCP, por 3 e 6 horas, não estendeu sua vida pós-colheita, tampouco alterou sua composição química. Embora a exposição de banana 'Maçã' a 50 ppb de 1-MCP, por 12 e 24 horas, tenha retardado o seu amadurecimento, promoveu alterações indesejáveis na casca do fruto. Logo, a aplicação de 50 ppb de 1-MCP, por 9 horas, antes da refrigeração, constitui-se numa alternativa viável para prolongar o período de comercialização da banana.The aim of this work was to evaluate 'Apple' banana different periods exposure effect to 50 ppb of 1-MCP (0, 3, 6, 9 and 24 hours on its postharvest life and quality. Mature-green fruits were stored for 30 days in chambers at 13ºC + 0,5 and relative humidity 95%, after exposure to 1-MCP. Then, the bananas were stored at 20ºC + 1 until peel complete yellowing. 'Apple' banana to 50 ppb of 1-MCP exposure during 9 hours delayed in seven days the fruit ripening, comparing to fruit control, after 30 days of cool storage (13ºC, without changing its appearance and chemical composition. The exposure of 'Apple' banana to 50 ppb of 1-MCP for 3 and 6 hours did not extend its postharvest life; neither changed its chemical composition. Although the exposure of

  8. RETARDAMENTO DA MATURAÇÃO DE MAÇÃS 'FUJI' PELO TRATAMENTO COM 1-MCP E MANEJO DA TEMPERATURA DELAYING 'FUJI' APPLE RIPENING BY 1-MCP TREATMENT AND MANAGEMENT OF STORAGE TEMPERATURE

    Directory of Open Access Journals (Sweden)

    LUIZ CARLOS ARGENTA

    2001-08-01

    Full Text Available Maçãs cv. Fuji foram tratadas com 42 mimol·m-3 de 1-metilciclopropeno (1-MCP por 24 h a 20°C, um dia após a colheita, e então armazenadas a 0; 10 ou 20ºC por 70 dias. Tratamento com 1-MCP efetivamente retardou a maturação de maçãs 'Fuji'. 1-MCP reduziu a taxa respiratória dos frutos mantidos a 10 e 20ºC e inibiu a produção de etileno dos frutos mantidos nas três temperaturas de armazenagem. Frutos tratados com 1-MCP e armazenados a 20ºC exibiram taxas respiratórias similares ou inferiores àquelas de frutos-controle armazenados a 10ºC. Quando armazenados a 10 ou 20ºC, frutos tratados com 1-MCP preservaram mais a firmeza da polpa e a acidez titulável e exibiram menor amarelecimento da epiderme que frutos-controle. Entretanto, não houve benefícios significativos do tratamento 1-MCP sobre a conservação da qualidade dos frutos armazenados a 0ºC no período de 70 dias após a colheita. Os resultados indicam que o tratamento com 1-MCP pode ser uma estratégia para o aumento da conservação de maçãs cv. Fuji durante o transporte e a distribuição sob 10 ou 20ºC. O prolongamento da armazenagem a 20ºC por período superior a 40 dias pode ser limitado pelo murchamento dos frutos e desenvolvimento de podridões.'Fuji' apples were treated with 42 mumol·m-3 of 1-methylcyclopropene (1-MCP for 24 h at 20°C then stored at 0, 10 or 20 ºC for 70 days. MCP treatment reduced respiration on fruit held at 10 and 20 ºC and inhibited ethylene production regardless of storage temperature. Treated fruits held at 20ºC presented respiration rate similar to those of untreated fruits held at 10ºC. For fruit held at 10 or 20ºC, MCP treatment inhibited softening, loss of acidity and color changes on fruit surface. However, there was no considerable benefit of 1-MCP treatment on maintenance of fruit quality during short-term (70 days and storage at 0ºC. Results indicated that 1-MCP is an effective mean to delay ripening and to retain

  9. Relationships between serum MCP-1 and subclinical kidney disease: African American-Diabetes Heart Study

    Directory of Open Access Journals (Sweden)

    Murea Mariana

    2012-11-01

    Full Text Available Abstract Background Monocyte chemoattractant protein-1 (MCP-1 plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD were assessed in African Americans (AAs with type 2 diabetes (T2D. Methods Serum MCP-1 concentration, urine albumin:creatinine ratio (ACR, estimated glomerular filtration rate (eGFR, and atherosclerotic calcified plaque (CP in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP. Results Participants were 57% female, with mean ± SD (median age 55.6±9.5 (55.0 years, diabetes duration 10.3±8.2 (8.0 years, urine ACR 149.7±566.7 (14.0 mg/g, CKD-EPI eGFR 92.4±23.3 (92.0 ml/min/1.73m2, MCP-1 262.9±239.1 (224.4 pg/ml, coronary artery CP 280.1±633.8 (13.5, carotid artery CP 47.1±132.9 (0, and aorta CP 1616.0±2864.0 (319.0. Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04 and negatively associated with eGFR (parameter estimate −0.0003, P=0.001. MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes. Conclusions Serum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.

  10. Human RAD18 interacts with ubiquitylated chromatin components and facilitates RAD9 recruitment to DNA double strand breaks.

    Directory of Open Access Journals (Sweden)

    Akiko Inagaki

    Full Text Available RAD18 is an ubiquitin ligase involved in replicative damage bypass and DNA double-strand break (DSB repair processes. We found that RPA is required for the dynamic pattern of RAD18 localization during the cell cycle, and for accumulation of RAD18 at sites of γ-irradiation-induced DNA damage. In addition, RAD18 colocalizes with chromatin-associated conjugated ubiquitin and ubiquitylated H2A throughout the cell cycle and following irradiation. This localization pattern depends on the presence of an intact, ubiquitin-binding Zinc finger domain. Using a biochemical approach, we show that RAD18 directly binds to ubiquitylated H2A and several other unknown ubiquitylated chromatin components. This interaction also depends on the RAD18 Zinc finger, and increases upon the induction of DSBs by γ-irradiation. Intriguingly, RAD18 does not always colocalize with regions that show enhanced H2A ubiquitylation. In human female primary fibroblasts, where one of the two X chromosomes is inactivated to equalize X-chromosomal gene expression between male (XY and female (XX cells, this inactive X is enriched for ubiquitylated H2A, but only rarely accumulates RAD18. This indicates that the binding of RAD18 to ubiquitylated H2A is context-dependent. Regarding the functional relevance of RAD18 localization at DSBs, we found that RAD18 is required for recruitment of RAD9, one of the components of the 9-1-1 checkpoint complex, to these sites. Recruitment of RAD9 requires the functions of the RING and Zinc finger domains of RAD18. Together, our data indicate that association of RAD18 with DSBs through ubiquitylated H2A and other ubiquitylated chromatin components allows recruitment of RAD9, which may function directly in DSB repair, independent of downstream activation of the checkpoint kinases CHK1 and CHK2.

  11. MCP-1 in urine as biomarker of disease activity in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Barbado, Julia; Martin, Debora; Vega, Luisa; Almansa, Raquel; Gonçalves, Lisbeth; Nocito, Mercedes; Jimeno, Antonio; Ortiz de Lejarazu, Raúl; Bermejo-Martin, Jesus F

    2012-11-01

    Conventional clinical parameters are not sensitive or specific enough for detecting ongoing disease activity in the Systemic Lupus Erythematosus (SLE). Measurement of cytokines in urine is an encouraging approach to detection of early flares in this disease. Here we have profiled 27 different cytokines, chemokines and celular growth factors in the urine of 48 patients previously diagnosed of SLE as potential biomarkers of disease activity. Correlation analysis with Bonferroni correction showed that MCP-1 was the only immune mediator which levels in urine correlated directly with the SLE Disease Activity Index 2000 (SLEDAI-2K) score (correlation coefficient, p): MCP-1 (0.45,0.003). MCP-1 correlated inversely with levels of C3 complement protein in serum (-0.50,0.001). MCP-1 showed significant higher levels in patients with severe disease activity in comparison with those exhibiting mild activity. Levels of this chemokine were also higher in patients with severe disease activity in comparison with patients with inactive disease and healthy controls. Areas under receiver operating characteristic curves (AUROC) for detection of severe disease (SLEDAI⩾8) was as follows for MCP-1: [AUROC, (IC95%), p]: [0.81 (0.65-0.96) 0.003]. In addition, MCP-1 showed a good result in the AUROC analysis for detecting renal involvement [0.70 (0.52-0.87) 0.050]. When correlation analysis were repeated excluding those patients with active renal disease (n=14), levels of MCP-1 in urine kept on showing a significant positive association with SLEDAI-2K score. In conclusion, multiplex-based cytokine profiling in urine demonstrated the superiority of MCP-1 over a wide range of cytokines as biomarker of disease activity in SLE. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

    Science.gov (United States)

    Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

    2009-04-01

    Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

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

    International Nuclear Information System (INIS)

    Crawford, J.; Domel, R.U.

    2000-05-01

    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

  14. Optimization of the electron collection efficiency of a large area MCP-PMT for the JUNO experiment

    International Nuclear Information System (INIS)

    Chen, Lin; Tian, Jinshou; Liu, Chunliang; Wang, Yifang; Zhao, Tianchi; Liu, Hulin; Wei, Yonglin; Sai, Xiaofeng; Chen, Ping; Wang, Xing; Lu, Yu; Hui, Dandan; Guo, Lehui; Liu, Shulin; Qian, Sen; Xia, Jingkai; Yan, Baojun; Zhu, Na; Sun, Jianning; Si, Shuguang

    2016-01-01

    A novel large-area (20-inch) photomultiplier tube based on microchannel plate (MCP-PMTs) is proposed for the Jiangmen Underground Neutrino Observatory (JUNO) experiment. Its photoelectron collection efficiency C e is limited by the MCP open area fraction (A open ). This efficiency is studied as a function of the angular (θ), energy (E) distributions of electrons in the input charge cloud and the potential difference (U) between the PMT photocathode and the MCP input surface, considering secondary electron emission from the MCP input electrode. In CST Studio Suite, Finite Integral Technique and Monte Carlo method are combined to investigate the dependence of C e on θ, E and U. Results predict that C e can exceed A open , and are applied to optimize the structure and operational parameters of the 20-inch MCP-PMT prototype. C e of the optimized MCP-PMT is expected to reach 81.2%. Finally, the reduction of the penetration depth of the MCP input electrode layer and the deposition of a high secondary electron yield material on the MCP are proposed to further optimize C e .

  15. Anti-inflammatory effect of resveratrol on TNF-α-induced MCP-1 expression in adipocytes

    International Nuclear Information System (INIS)

    Zhu Jian; Yong Wei; Wu Xiaohong; Yu Ying; Lv Jinghuan; Liu Cuiping; Mao Xiaodong; Zhu Yunxia; Xu Kuanfeng; Han Xiao; Liu Chao

    2008-01-01

    Chronic low-grade inflammation characterized by adipose tissue macrophage accumulation and abnormal cytokine production is a key feature of obesity and type 2 diabetes. Adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, induced by cytokines, has been shown to play an essential role in the early events during macrophage infiltration into adipose tissue. In this study we investigated the effects of resveratrol upon both tumor necrosis factor (TNF)-α-induced MCP-1 gene expression and its underlying signaling pathways in 3T3-L1 adipoctyes. Resveratrol was found to inhibit TNF-α-induced MCP-1 secretion and gene transcription, as well as promoter activity, which based on down-regulation of TNF-α-induced MCP-1 transcription. Nuclear factor (NF)-κB was determined to play a major role in the TNF-α-induced MCP-1 expression. Further analysis showed that resveratrol inhibited DNA binding activity of the NF-κB complex and subsequently suppressed NF-κB transcriptional activity in TNF-α-stimulated cells. Finally, the inhibition of MCP-1 may represent a novel mechanism of resveratrol in preventing obesity-related pathologies

  16. Development of 10×10 Matrix-anode MCP-PMT

    Science.gov (United States)

    Yang, Jie; Li, Yongbin; Xu, Pengxiao; Zhao, Wenjin

    2018-02-01

    10×10 matrix-anode is developed by high-temperature co-fired ceramics (HTCC) technology. Based on the new matrix-anode, a new kind of photon counting imaging detector - 10×10 matrix-anode MCP-PMT is developed, and its performance parameters are tested. HTCC technology is suitable for the MCP-PMT's air impermeability and its baking process. Its response uniformity is better than the metal-ceramic or metal-glass sealing anode, and it is also a promising method to realize a higher density matrix-anode.

  17. MCP characterization at the Cu and Mo Kα x-ray energies

    International Nuclear Information System (INIS)

    Walsh, P.J.; Evans, S.; Schappert, G.T.; Kyrala, G.A.

    1998-03-01

    The authors are investigating the usefulness of microchannel plate (MCP) intensifiers for imaging x-rays at high photon energies, specifically by using filtered X-rays from an electron bombardment source to generate the K α lines of Cu at 8.04 KeV and Mo at 17.5 KeV. These high energy lines are used to measure the resolution of an MCP based intensifier produced at Los Alamos National Laboratory. They have investigated the spot size of a fielded MCP intensifier by observing, on film, the result of single photon excitation of microchannels. Measurement of the spot size was done with visible light microscopy. They report initial results of the spot size distribution in the stripline direction. They have also begun a measurement of the azimuthal anisotropy in the spatial resolution, accentuated at these energies by the inclination of the axis of the MCP channels. They concentrate on an actual ''fielded instrument'' resolution, rather than ideal, for the purpose of analyzing image data captured at the NOVA Laser Facility

  18. Optimization of the electron collection efficiency of a large area MCP-PMT for the JUNO experiment

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lin, E-mail: chenlin@opt.cn [State Key Laboratory of Transient Optics and Photonics, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi’an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Xi’an Jiaotong University, Xi’an 710049 (China); Tian, Jinshou [Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Liu, Chunliang [Xi’an Jiaotong University, Xi’an 710049 (China); Wang, Yifang; Zhao, Tianchi [Institute of High Energy Physics (IHEP) of CAS, Beijing 100049 (China); Liu, Hulin; Wei, Yonglin; Sai, Xiaofeng [Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Chen, Ping [State Key Laboratory of Transient Optics and Photonics, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi’an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Wang, Xing; Lu, Yu [Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Hui, Dandan; Guo, Lehui [State Key Laboratory of Transient Optics and Photonics, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi’an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Liu, Shulin; Qian, Sen; Xia, Jingkai; Yan, Baojun; Zhu, Na [Institute of High Energy Physics (IHEP) of CAS, Beijing 100049 (China); Sun, Jianning; Si, Shuguang [North Night Vision Technology (NNVT) CO., LTD, Nanjing 210110 (China); and others

    2016-08-11

    A novel large-area (20-inch) photomultiplier tube based on microchannel plate (MCP-PMTs) is proposed for the Jiangmen Underground Neutrino Observatory (JUNO) experiment. Its photoelectron collection efficiency C{sub e} is limited by the MCP open area fraction (A{sub open}). This efficiency is studied as a function of the angular (θ), energy (E) distributions of electrons in the input charge cloud and the potential difference (U) between the PMT photocathode and the MCP input surface, considering secondary electron emission from the MCP input electrode. In CST Studio Suite, Finite Integral Technique and Monte Carlo method are combined to investigate the dependence of C{sub e} on θ, E and U. Results predict that C{sub e} can exceed A{sub open}, and are applied to optimize the structure and operational parameters of the 20-inch MCP-PMT prototype. C{sub e} of the optimized MCP-PMT is expected to reach 81.2%. Finally, the reduction of the penetration depth of the MCP input electrode layer and the deposition of a high secondary electron yield material on the MCP are proposed to further optimize C{sub e}.

  19. Aplicação de 1-MCP em caqui 'quioto' armazenado sob refrigeração e atmosfera controlada Effect of 1-MCP applied at different times during cold and Ca storage

    Directory of Open Access Journals (Sweden)

    Auri Brackmann

    2003-04-01

    Full Text Available O objetivo deste trabalho foi de avaliar o efeito do 1-MCP aplicado em diferentes épocas durante o armazenamento refrigerado (AR e em atmosfera controlada (AC sobre a qualidade do caqui cv. Quioto. O delineamento experimental utilizado foi o inteiramente casualizado, com quatro repetições de 30 frutos, e os tratamentos foram os seguintes: armazenamento refrigerado (AR; armazenamento refrigerado(AR + 1-MCP (1000ppb no início do armazenamento; armazenamento refrigerado(AR +1-MCP (1000ppb no final do armazenamento; armazenamento em atmosfera controlada (AC com 1kPa de O2 e AC 5kPa de CO2 e AC com 1kPa de O2 e 5kPa de CO2 + 1-MCP no fim do armazenamento, após 2 meses de armazenamento a -0,5ºC mais 5 dias de exposição dos frutos a 10ºC e 3 dias a 20ºC. No armazenamento refrigerado, o 1-MCP, aplicado tanto no início do armazenamento como no final, proporcionou maior firmeza de polpa. Para os parâmetros: sólidos solúveis totais, podridão e escurecimento da película, não houve diferença estatística entre os tratamentos. Conclui-se que a aplicação de 1-MCP, tanto no início como no final do armazenamento mantém elevada a firmeza de polpa.The objective of this work was to evaluate the effect of 1-MCP applied at different period during the cold storage (CS and in controlled atmosphere (CA on the quality of 'Quioto'. Persimmon. The experimental design was completely randomized with four replications of 30 fruits and the tested treatments were: cold storage (CS, cold storage + 1-MCP (1000ppb in the beginning of the storage, cold storage + 1-MCP (1000ppb in the end of the storage period; storage in controlled atmosphere (CA with 1kPa of O2 and 5kPa of CO2 and 1kPa of O2 and 5kPa of CO2 + 1-MCP in the end of the storage, after 2 months of storage at -0.5ºC, plus 5 days at 10ºC and 3 days at 20ºC. In the cooled storage, the 1-MCP, applied as in the beginning of the storage as in the end of the storage, provided greater pulp firmness

  20. Role of MCP-1 in pleural effusion development in a carrageenan-induced murine model of pleurisy.

    Science.gov (United States)

    Lansley, Sally M; Cheah, Hui Min; Lee, Y C Gary

    2017-05-01

    Exudative pleural effusions affect over 1500 patients per million population each year. The pathobiology of pleural exudate formation remains unclear. Our recent study revealed monocyte chemotactic protein-1 (MCP-1) as a key driver of fibrinolytic-induced exudate effusion while another study found a role for MCP-1 in malignant effusion formation. In the present study, we further evaluated the role of MCP-1 in the development of pleural effusion in a mouse model of acute pleural inflammation. λ-Carrageenan (CAR) was injected into the pleural cavity of CD1 mice and pleural effusion volume measured up to 16 h post-injection. Pleural effusion and serum protein and MCP-1 concentrations were measured and differential cell counts performed in fluids. Mice were also treated with either intraperitoneal (i) anti-MCP-1 antibody or isotype control or (ii) an MCP-1 receptor (CCR2) antagonist or vehicle control 12 h prior to and at the time of CAR injection. Intrapleural CAR induced significant pleural fluid accumulation (300.0 ± 49.9 μL) in mice after 4 h. Pleural fluid MCP-1 concentrations were significantly higher than corresponding serum MCP-1 (144 603 ± 23 204 pg/mL vs 3703 ± 801 pg/mL, P pleural fluid formation was seen both with anti-MCP-1 antibody (median (interquartile range, IQR): 36 (0-168) μL vs controls 290 (70-436) μL; P = 0.02) or CCR2 antagonist (153 (30-222) μL vs controls 240 (151-331) μL, P = 0.0049). Blockade of MCP-1 activity significantly reduced inflammatory pleural effusion formation in a CAR model. Together with recent successes in MCP-1 blockade in other effusion formation models, our data strongly support clinical evaluation of MCP-1 antagonists as a novel approach to pleural fluid management. © 2016 Asian Pacific Society of Respirology.

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

    Lifescience Database Archive (English)

    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

  2. Foreword to the Special Issue on the 11th Specialist Meeting on Microwave Radiometry and Remote Sensing Applications (MicroRad 2010)

    Science.gov (United States)

    Le Vine, David M; Jackson, Thomas J.; Kim, Edward J.; Lang, Roger H.

    2011-01-01

    The Specialist Meeting on Microwave Radiometry and Remote Sensing of the Environment (MicroRad 2010) was held in Washington, DC from March 1 to 4, 2010. The objective of MicroRad 2010 was to provide an open forum to report and discuss recent advances in the field of microwave radiometry, particularly with application to remote sensing of the environment. The meeting was highly successful, with more than 200 registrations representing 48 countries. There were 80 oral presentations and more than 100 posters. MicroRad has become a venue for the microwave radiometry community to present new research results, instrument designs, and applications to an audience that is conversant in these issues. The meeting was divided into 16 sessions (listed in order of presentation): 1) SMOS Mission; 2) Future Passive Microwave Remote Sensing Missions; 3) Theory and Physical Principles of Electromagnetic Models; 4) Field Experiment Results; 5) Soil Moisture and Vegetation; 6) Snow and Cryosphere; 7) Passive/Active Microwave Remote Sensing Synergy; 8) Oceans; 9) Atmospheric Sounding and Assimilation; 10) Clouds and Precipitation; 11) Instruments and Advanced Techniques I; 12) Instruments and Advanced Techniques II; 13) Cross Calibration of Satellite Radiometers; 14) Calibration Theory and Methodology; 15) New Technologies for Microwave Radiometry; 16) Radio Frequency Interference.

  3. Monocyte chemoattractant protein-1 (MCP-1 regulates macrophage cytotoxicity in abdominal aortic aneurysm.

    Directory of Open Access Journals (Sweden)

    Qiwei Wang

    Full Text Available AIMS: In abdominal aortic aneurysm (AAA, macrophages are detected in the proximity of aortic smooth muscle cells (SMCs. We have previously demonstrated in a murine model of AAA that apoptotic SMCs attract monocytes and other leukocytes by producing MCP-1. Here we tested whether infiltrating macrophages also directly contribute to SMC apoptosis. METHODS AND RESULTS: Using a SMC/RAW264.7 macrophage co-culture system, we demonstrated that MCP-1-primed RAWs caused a significantly higher level of apoptosis in SMCs as compared to control macrophages. Next, we detected an enhanced Fas ligand (FasL mRNA level and membrane FasL protein expression in MCP-1-primed RAWs. Neutralizing FasL blocked SMC apoptosis in the co-culture. In situ proximity ligation assay showed that SMCs exposed to primed macrophages contained higher levels of receptor interacting protein-1 (RIP1/Caspase 8 containing cell death complexes. Silencing RIP1 conferred apoptosis resistance to SMCs. In the mouse elastase injury model of aneurysm, aneurysm induction increased the level of RIP1/Caspase 8 containing complexes in medial SMCs. Moreover, TUNEL-positive SMCs in aneurysmal tissues were frequently surrounded by CD68(+/FasL(+ macrophages. Conversely, elastase-treated arteries from MCP-1 knockout mice display a reduction of both macrophage infiltration and FasL expression, which was accompanied by diminished apoptosis of SMCs. CONCLUSION: Our data suggest that MCP-1-primed macrophages are more cytotoxic. MCP-1 appears to modulate macrophage cytotoxicity by increasing the level of membrane bound FasL. Thus, we showed that MCP-1-primed macrophages kill SMCs through a FasL/Fas-Caspase8-RIP1 mediated mechanism.

  4. VIDA COMERCIAL DE PITAHAYA AMARILLA TRATADA CON 1-MCP

    Directory of Open Access Journals (Sweden)

    LILIANA SERNA-COCK

    Full Text Available 1-metilciclopropeno (1-MCP, un inhibidor del etileno, ha sido utilizado para extender la vida comercial de diferentes frutas. El objetivo de este trabajo fue evaluar el efecto de la aplicación de soluciones acuosas de 10, 100 y 200 gL-1 de 1-MCP, con tiempos de exposición de 1, 5 y 10 minutos, sobre la vida comercial de pitahaya amarilla en estado de madurez 4. Durante 15 días de almacenamiento (25 ± 2°C y 75% de humedad relativa, se evaluaron cambios físicos como la pérdida de peso y la aparición de pardeamiento; y se midieron cambios químicos como sólidos solubles, pH, acidez e índice de madurez. Se presentaron diferencias significativas entre los tratamientos. Los resultados demostraron que aplicaciones de 200 gL-1 de 1-MCP durante 10 minutos prolongó por tres días, la vida comercial de la pitahaya amarilla, y redujo cambios en los sólidos solubles y la acidez

  5. 1-MCP pretreatment prevents bud and flower abscission in Dendrobium orchids

    NARCIS (Netherlands)

    Uthaichay, N.; Ketsa, S.; Doorn, van W.G.

    2007-01-01

    Dendrobium orchid inflorescences were treated for 4 h at 25 °C with or without 100¿500 nl/l 1-MCP and were then placed in water at 25 °C to follow abscission. In controls, depending on the experiment, 20¿80% of the floral buds and 0¿20% of the open flowers abscised within 1 week. The 1-MCP

  6. The RadAssessor manual

    Energy Technology Data Exchange (ETDEWEB)

    Seitz, Sharon L.

    2007-02-01

    THIS manual will describe the functions and capabilities that are available from the RadAssessor database and will demonstrate how to retrieve and view its information. You’ll learn how to start the database application, how to log in, how to use the common commands, and how to use the online help if you have a question or need extra guidance. RadAssessor can be viewed from any standard web browser. Therefore, you will not need to install any special software before using RadAssessor.

  7. Roles of C-Terminal Region of Yeast and Human Rad52 in Rad51-Nucleoprotein Filament Formation and ssDNA Annealing.

    Directory of Open Access Journals (Sweden)

    Nilesh V Khade

    Full Text Available Yeast Rad52 (yRad52 has two important functions at homologous DNA recombination (HR; annealing complementary single-strand DNA (ssDNA molecules and recruiting Rad51 recombinase onto ssDNA (recombination mediator activity. Its human homolog (hRAD52 has a lesser role in HR, and apparently lacks mediator activity. Here we show that yRad52 can load human Rad51 (hRAD51 onto ssDNA complexed with yeast RPA in vitro. This is biochemically equivalent to mediator activity because it depends on the C-terminal Rad51-binding region of yRad52 and on functional Rad52-RPA interaction. It has been reported that the N-terminal two thirds of both yRad52 and hRAD52 is essential for binding to and annealing ssDNA. Although a second DNA binding region has been found in the C-terminal region of yRad52, its role in ssDNA annealing is not clear. In this paper, we also show that the C-terminal region of yRad52, but not of hRAD52, is involved in ssDNA annealing. This suggests that the second DNA binding site is required for the efficient ssDNA annealing by yRad52. We propose an updated model of Rad52-mediated ssDNA annealing.

  8. Determination of workplace neutron spectra at a high energy hadron accelerator using active and passive Bonner sphere spectrometers

    International Nuclear Information System (INIS)

    Bedogni, R.; Esposito, A.; Chiti, M.

    2008-01-01

    In the framework of the 2006 experimental benchmark organized at the GSI (Darmstadt, Germany) by the EC CONRAD network, a neutron dosimetry intercomparison was performed in a workplace field around a carbon target hit by 400 MeV/u 12 C ions. The radiation protection group of the INFN-LNF participated to the intercomparison with a Bonner sphere spectrometer equipped with an active 6 LiI(Eu) scintillator and a set of passive detectors, namely MCP-6s (80mgcm -2 )/MCP-7 TLD pairs from TLD Poland. Both active and passive spectrometers, independently tested and calibrated, were used to determine the field and dosimetric quantities in the measurement point. The FRUIT unfolding code, developed at the INFN-LNF radiation protection group, was used to unfold the raw BSS data. This paper compares the results of the active or passive spectrometers, obtaining a satisfactory agreement in terms of both spectrum shape and value of the integral quantities, as the neutron fluence or the ambient dose equivalent. These results allow qualifying the BSS based on TLD pairs as a reliable passive method to be used around high energy particle accelerators even in low dose rate areas. This is particularly useful in those workplaces where the active instruments could be disturbed by the presence of pulsed fields, large photon fluence or electromagnetic noise

  9. Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration in experimental silicosis

    International Nuclear Information System (INIS)

    Liu, Xueting; Fang, Shencun; Liu, Haijun; Wang, Xingang; Dai, Xiaoniu; Yin, Qing; Yun, Tianwei; Wang, Wei; Zhang, Yingming; Liao, Hong; Zhang, Wei; Yao, Honghong; Chao, Jie

    2015-01-01

    Background: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO 2 ). Phagocytosis of SiO 2 in the lung initiates an inflammatory cascade that results in fibroblast proliferation and migration and subsequent fibrosis. Clinical evidence indicates that the activation of alveolar macrophages by SiO 2 produces rapid and sustained inflammation that is characterized by the generation of monocyte chemotactic protein 1 (MCP-1), which induces fibrosis. Pulmonary fibroblast-derived MCP-1 may play a critical role in fibroblast proliferation and migration. Methods and results: Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following results: 1) SiO 2 treatment resulted in the rapid and sustained induction of MCP-1 as well as the elevation of the CC chemokine receptor type 2 (CCR2) protein levels; 2) pretreatment of HPF-a with RS-102895, a specific CCR2 inhibitor, abolished the SiO 2 -induced increase in cell activation and migration in both 2D and 3D culture systems; and 3) RNA interference targeting CCR2 prevented the SiO 2 -induced increase in cell migration. Conclusion: These data demonstrated that the up-regulation of pulmonary fibroblast-derived MCP-1 is involved in pulmonary fibroblast migration induced by SiO 2 . CCR2 was also up-regulated in response to SiO 2 , and this up-regulation facilitated the effect of MCP-1 on fibroblasts. Our study deciphered the link between fibroblast-derived MCP-1 and SiO 2 -induced cell migration. This finding provides novel insight into the potential of MCP-1 in the development of novel therapeutic strategies for silicosis. - Highlights: • Role of pulmonary fibroblast-derived MCP-1 in experimental silicosis was studied. • SiO 2 induced MCP-1 release from cultured human pulmonary fibroblast (HPF-a). • SiO 2 directly activated HPF-a via the MCP-1/CCR2 pathway. • SiO 2 increased HPF-a migration in both 2D and 3D model via the MCP-1/CCR2 pathway. • RNA-i of MCP-1/CCR2

  10. Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration in experimental silicosis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xueting [Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009 (China); Fang, Shencun [Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029 (China); Liu, Haijun [Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing, Jiangsu 210009 (China); Wang, Xingang; Dai, Xiaoniu; Yin, Qing; Yun, Tianwei [Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009 (China); Wang, Wei; Zhang, Yingming [Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029 (China); Liao, Hong [Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing, Jiangsu 210009 (China); Zhang, Wei [Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009 (China); Yao, Honghong [Department of Pharmacology, Medical School of Southeast University, Nanjing, Jiangsu 210009 (China); Chao, Jie, E-mail: chaojie@seu.edu.cn [Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009 (China)

    2015-10-15

    Background: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO{sub 2}). Phagocytosis of SiO{sub 2} in the lung initiates an inflammatory cascade that results in fibroblast proliferation and migration and subsequent fibrosis. Clinical evidence indicates that the activation of alveolar macrophages by SiO{sub 2} produces rapid and sustained inflammation that is characterized by the generation of monocyte chemotactic protein 1 (MCP-1), which induces fibrosis. Pulmonary fibroblast-derived MCP-1 may play a critical role in fibroblast proliferation and migration. Methods and results: Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following results: 1) SiO{sub 2} treatment resulted in the rapid and sustained induction of MCP-1 as well as the elevation of the CC chemokine receptor type 2 (CCR2) protein levels; 2) pretreatment of HPF-a with RS-102895, a specific CCR2 inhibitor, abolished the SiO{sub 2}-induced increase in cell activation and migration in both 2D and 3D culture systems; and 3) RNA interference targeting CCR2 prevented the SiO{sub 2}-induced increase in cell migration. Conclusion: These data demonstrated that the up-regulation of pulmonary fibroblast-derived MCP-1 is involved in pulmonary fibroblast migration induced by SiO{sub 2}. CCR2 was also up-regulated in response to SiO{sub 2}, and this up-regulation facilitated the effect of MCP-1 on fibroblasts. Our study deciphered the link between fibroblast-derived MCP-1 and SiO{sub 2}-induced cell migration. This finding provides novel insight into the potential of MCP-1 in the development of novel therapeutic strategies for silicosis. - Highlights: • Role of pulmonary fibroblast-derived MCP-1 in experimental silicosis was studied. • SiO{sub 2} induced MCP-1 release from cultured human pulmonary fibroblast (HPF-a). • SiO{sub 2} directly activated HPF-a via the MCP-1/CCR2 pathway. • SiO{sub 2} increased HPF-a migration in both 2D and 3D

  11. Regeneration of CFUs in the marrow of mice exposed to 300 rads after having recovered from 950 rads

    International Nuclear Information System (INIS)

    Kedo, A.; Barone, J.; Fried, W.

    1976-01-01

    Exposure to 950 rads 60 Co radiation has been reported to cause long-lasting damage to the hematopoietic stroma (HS), although the size of the CFUs population recovers to pre-irradiation levels. In these studies HS damage was detected only after subcutaneously implanting the femurs of the irradiated mice into syngeneic hosts. To exclude the possibility that what was considered to be HS damage was merely caused by artifacts due to the process of implantation in a new host, the rate of regeneration of CFUs in mice which had recovered from 950 rads prior to receiving 300 rads 60 Co radiation (950 + 300 rads group) was compared with that of mice which received only 300 rads (0 + 300 rads group). The CFUs population in the 950 + 300 rads group grew exponentially for 2 weeks at a rate which did not differ significantly from that of CFUs in the 0 + 300 rads group. However, the rate of CFUs growth reached a plateau before full recovery was achieved in contrast to that in the 0 + 300 rads mice. It was therefore concluded that the incomplete regeneration of CFUs in the marrows of 950 + 300 rads mice was most likely caused by X-irradiation-induced damage to the HS rather than damage to the inherent repopulation potential of the CFUs per se. (author)

  12. The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally?

    Science.gov (United States)

    Yoshimura, Teizo

    2018-01-29

    Macrophages are one of the most abundant leukocyte populations infiltrating tumor tissues and can exhibit both tumoricidal and tumor-promoting activities. In 1989, we reported the purification of monocyte chemoattractant protein-1 (MCP-1) from culture supernatants of mitogen-activated peripheral blood mononuclear cells and tumor cells. MCP-1 is a potent monocyte-attracting chemokine, identical to the previously described lymphocyte-derived chemotactic factor or tumor-derived chemotactic factor, and greatly contributes to the recruitment of blood monocytes into sites of inflammatory responses and tumors. Because in vitro-cultured tumor cells often produce significant amounts of MCP-1, tumor cells are considered to be the main source of MCP-1. However, various non-tumor cells in the tumor stroma also produce MCP-1 in response to stimuli. Studies performed in vitro and in vivo have provided evidence that MCP-1 production in tumors is a consequence of complex interactions between tumor cells and non-tumor cells and that both tumor cells and non-tumor cells contribute to the production of MCP-1. Although MCP-1 production was once considered to be a part of host defense against tumors, it is now believed to regulate the vicious cycle between tumor cells and macrophages that promotes the progression of tumors.Cellular and Molecular Immunology advance online publication, 29 January 2018; doi:10.1038/cmi.2017.135.

  13. Monocyte chemoattractant protein 1 (MCP-1) in temporal arteritis and polymyalgia rheumatica

    DEFF Research Database (Denmark)

    Ellingsen, T; Elling, P; Olson, A

    2000-01-01

    was localised to the vessel wall in patients with TA. In TA, PMR, and healthy controls MCP-1 was quantified by enzyme linked immunosorbent assay (ELISA) in plasma. RESULTS: MCP-1 was localised to the majority of mononuclear cells, some smooth muscle cells, and giant cells in the arterial biopsy specimens from...

  14. Rad and Mubad in Shahnameh of Ferdowsi

    Directory of Open Access Journals (Sweden)

    z Delpazir

    2011-09-01

    However, the important points overlooked by explicators are the relationship between Rad and Mubad (Zoroastrian priest and the reason why these two words have co-occurred so frequently in Shahnameh, the most famous Persian national epic. It seems that Rad in Shahnameh, based on Avesta and Pahlavi texts, is often construed as Sadane or Dastoor that was a high position in ancient Iran’s religious hierarchy. Thus, Rads and Mubads were both considered members of religious communities. This study tries to investigate the role and position of Rads and Mubads and their relationship with one another, based on Shahnameh of Ferdowsi, in three chapters: The etymology of Rad Rad in Shahnameh The relationship between Rads and Mubads.

  15. Cellular Dynamics of Rad51 and Rad54 in Response to Postreplicative Stress and DNA Damage in HeLa Cells.

    Science.gov (United States)

    Choi, Eui-Hwan; Yoon, Seobin; Hahn, Yoonsoo; Kim, Keun P

    2017-02-01

    Homologous recombination (HR) is necessary for maintenance of genomic integrity and prevention of various mutations in tumor suppressor genes and proto-oncogenes. Rad51 and Rad54 are key HR factors that cope with replication stress and DNA breaks in eukaryotes. Rad51 binds to single-stranded DNA (ssDNA) to form the presynaptic filament that promotes a homology search and DNA strand exchange, and Rad54 stimulates the strand-pairing function of Rad51. Here, we studied the molecular dynamics of Rad51 and Rad54 during the cell cycle of HeLa cells. These cells constitutively express Rad51 and Rad54 throughout the entire cell cycle, and the formation of foci immediately increased in response to various types of DNA damage and replication stress, except for caffeine, which suppressed the Rad51-dependent HR pathway. Depletion of Rad51 caused severe defects in response to postreplicative stress. Accordingly, HeLa cells were arrested at the G2-M transition although a small amount of Rad51 was steadily maintained in HeLa cells. Our results suggest that cell cycle progression and proliferation of HeLa cells can be tightly controlled by the abundance of HR proteins, which are essential for the rapid response to postreplicative stress and DNA damage stress.

  16. Simulation of the electron collection efficiency of a PMT based on the MCP coated with high secondary yield material

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lin, E-mail: chenlin@opt.cn [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Xi' an Jiaotong University, Xi' an 710049 (China); Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006 (China); Tian, Jinshou [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006 (China); Zhao, Tianchi [Institute of High Energy Physics (IHEP) of CAS, Beijing 100049 (China); Liu, Chunliang [Xi' an Jiaotong University, Xi' an 710049 (China); Liu, Hulin; Wei, Yonglin; Sai, Xiaofeng [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Chen, Ping [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Wang, Xing; Lu, Yu [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Hui, Dandan [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China)

    2016-11-01

    Owning to the serious loss of photoelectrons striking at the input electrode of traditional microchannel plate (MCP), photoelectron collection efficiency (CE) of photomultiplier tubes based on MCP (MCP-PMTs) fluctuates around the MCP open area fraction and cannot make a breakthrough. Depositing a thin film of high secondary electron yield material on the MCP is proposed as an effective approach to improve the CE. The available simulation and experimental data to validate it, however, is sparse. In our work, a three-dimensional small area MCP model is developed in CST Studio Suite to evaluate the collection efficiencies of PMTs based on the traditional MCP and the coated one, respectively. Results predict that CE of the PMT based on the coated MCP has a significant increase and a better uniformity, which is expected to reach 100%.

  17. Conservação da qualidade de caqui 'Fuyu' em ambiente refrigerado pela combinação de 1-MCP e atmosfera modificada Quality maintenance of 'Fuyu' persimmon in cold storage by combining 1-MCP and modified atmosphere

    Directory of Open Access Journals (Sweden)

    Luiz Carlos Argenta

    2009-06-01

    Full Text Available O presente estudo analisou os efeitos do inibidor da ação do etileno 1-MCP (1-metilciclopropeno, da AM (atmosfera modificada e do oxidante de etileno KMnO4 (permanganato de potássio sobre a qualidade de caqui 'Fuyu' após a armazenagem refrigerada. Os fatores 1-MCP, AM e KMnO4 foram combinados de quatro maneiras, correspondendo aos seguintes tratamentos: T1 Controle + AM + KMnO4;T2 1-MCP + AM + KMnO4; T3 1-MCP + AM, e T4 1-MCP + AA (AA=atmosfera do ar. Frutos maduro-firmes com coloração da casca predominantemente amarela foram colhidos em sete pomares comerciais no nordeste do Estado do Rio Grande do Sul. Parte dos frutos foi exposta a 0.3 µL L-1 de 1-MCP por 12 h em 24 h após a colheita. A seguir, os frutos foram armazenados sob AA ou sob AM induzida por bolsas de polietileno (0,04 mm de espessura, por 20; 40; 60 ou 80 dias a -0,1±0,8ºC. Dois sachês contendo 8,5 g de Alumina-KMnO4foram adicionados em cada uma das bolsas de polietileno dos tratamentos um e dois, antes de elas serem vedadas. Os frutos de cada período de armazenagem refrigerada foram analisados após 0; 3; 6 ou 9 dias de prateleira sob AA a 22±1ºC. O tratamento 1-MCP retardou o amolecimento da polpa, mas não afetou consistentemente o desenvolvimento de 'estrias' e manchas pretas na superfície dos frutos armazenados sob AM contendo KMnO4. A incidência de 'estrias' e manchas pretas em frutos tratados com 1-MCP e armazenados sob AM foi significativamente menor que a de frutos tratados com 1-MCP e armazenados sob AA. Houve efeitos aditivos do 1-MCP e AM na conservação da firmeza e na redução de danos por frio manifestados pela formação de textura gel-firme e manchas translúcidas na casca. O uso de KMnO4 não aumentou a conservação da qualidade dos frutos quando tratados com 1-MCP e armazenados sob AM. O desenvolvimento dos distúrbios da epiderme dependeu do pomar e de períodos de armazenagem e prateleira. No entanto, os benefícios da combinação de 1-MCP e

  18. IP-10, MCP-1, MCP-2, MCP-3, and IL-1RA hold promise as biomarkers for infection with M. tuberculosis in a whole blood based T-cell assay

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Bjerregaard-Andersen, Morten; Rabna, Paulo

    2009-01-01

    and mitogen in the Quantiferon In Tube test tubes. Levels of biomarkers were measured using Luminex and ELISA (IFN-gamma). RESULTS: We found all five new biomarkers were expressed in significantly higher concentrations compared to IFN-gamma. IP-10 and MCP-3 levels in the un-stimulated samples were higher...

  19. MCP/CCR2 signaling is essential for recruitment of mesenchymal progenitor cells during the early phase of fracture healing.

    Directory of Open Access Journals (Sweden)

    Masahiro Ishikawa

    Full Text Available OBJECTIVE: The purpose of this study was to investigate chemokine profiles and their functional roles in the early phase of fracture healing in mouse models. METHODS: The expression profiles of chemokines were examined during fracture healing in wild-type (WT mice using a polymerase chain reaction array and histological staining. The functional effect of monocyte chemotactic protein-1 (MCP-1 on primary mouse bone marrow stromal cells (mBMSCs was evaluated using an in vitro migration assay. MCP-1-/- and C-C chemokine receptor 2 (CCR2-/- mice were fractured and evaluated by histological staining and micro-computed tomography (micro-CT. RS102895, an antagonist of CCR2, was continuously administered in WT mice before or after rib fracture and evaluated by histological staining and micro-CT. Bone graft exchange models were created in WT and MCP-1-/- mice and were evaluated by histological staining and micro-CT. RESULTS: MCP-1 and MCP-3 expression in the early phase of fracture healing were up-regulated, and high levels of MCP-1 and MCP-3 protein expression observed in the periosteum and endosteum in the same period. MCP-1, but not MCP-3, increased migration of mBMSCs in a dose-dependent manner. Fracture healing in MCP-1-/- and CCR2-/- mice was delayed compared with WT mice on day 21. Administration of RS102895 in the early, but not in the late phase, caused delayed fracture healing. Transplantation of WT-derived graft into host MCP-1-/- mice significantly increased new bone formation in the bone graft exchange models. Furthermore, marked induction of MCP-1 expression in the periosteum and endosteum was observed around the WT-derived graft in the host MCP-1-/- mouse. Conversely, transplantation of MCP-1-/- mouse-derived grafts into host WT mice markedly decreased new bone formation. CONCLUSIONS: MCP-1/CCR2 signaling in the periosteum and endosteum is essential for the recruitment of mesenchymal progenitor cells in the early phase of fracture healing.

  20. The New HARSHAW Extremity Dosimeters for Gamma and Beta Ray Monitoring

    International Nuclear Information System (INIS)

    Fellinger, J.; Majewski, M.; Rotunda, J.; Tawi, R.

    1997-01-01

    Large personnel dosimetry services providing extremity monitoring with finger rings based on thermoluminescent detectors have long been looking for a practical method for automated reading including automated identification of the detectors.All existing methods are at least not very suitable for medical applications, particularly for surgery, due to the fact that cold sterilization is usually impossible.Bicron radiation Measurement Products developed in co-operation with the Austrian Research Centre Seibersdorf a new finger ring dosimeter DXT-RAD as a fast and economic solution for fully automated evaluation of extremity dosemeters. (authors)

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

    International Nuclear Information System (INIS)

    Schiestl, R.H.; Prakash, S.; Prakash, L.

    1990-01-01

    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

  2. Coordination of Rad1-Rad10 interactions with Msh2-Msh3, Saw1 and RPA is essential for functional 3' non-homologous tail removal.

    Science.gov (United States)

    Eichmiller, Robin; Medina-Rivera, Melisa; DeSanto, Rachel; Minca, Eugen; Kim, Christopher; Holland, Cory; Seol, Ja-Hwan; Schmit, Megan; Oramus, Diane; Smith, Jessica; Gallardo, Ignacio F; Finkelstein, Ilya J; Lee, Sang Eun; Surtees, Jennifer A

    2018-04-06

    Double strand DNA break repair (DSBR) comprises multiple pathways. A subset of DSBR pathways, including single strand annealing, involve intermediates with 3' non-homologous tails that must be removed to complete repair. In Saccharomyces cerevisiae, Rad1-Rad10 is the structure-specific endonuclease that cleaves the tails in 3' non-homologous tail removal (3' NHTR). Rad1-Rad10 is also an essential component of the nucleotide excision repair (NER) pathway. In both cases, Rad1-Rad10 requires protein partners for recruitment to the relevant DNA intermediate. Msh2-Msh3 and Saw1 recruit Rad1-Rad10 in 3' NHTR; Rad14 recruits Rad1-Rad10 in NER. We created two rad1 separation-of-function alleles, rad1R203A,K205A and rad1R218A; both are defective in 3' NHTR but functional in NER. In vitro, rad1R203A,K205A was impaired at multiple steps in 3' NHTR. The rad1R218A in vivo phenotype resembles that of msh2- or msh3-deleted cells; recruitment of rad1R218A-Rad10 to recombination intermediates is defective. Interactions among rad1R218A-Rad10 and Msh2-Msh3 and Saw1 are altered and rad1R218A-Rad10 interactions with RPA are compromised. We propose a model in which Rad1-Rad10 is recruited and positioned at the recombination intermediate through interactions, between Saw1 and DNA, Rad1-Rad10 and Msh2-Msh3, Saw1 and Msh2-Msh3 and Rad1-Rad10 and RPA. When any of these interactions is altered, 3' NHTR is impaired.

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

    DEFF Research Database (Denmark)

    Rants, Louise Olthaver Juhl

    Homologous recombination (HR) provides a mechanism to restore integrity and maintain stability of the genetic material. HR is a major pathway for repair of DNA double-strand breaks (DSB), recovery of broken replication forks and generation of meiotic crossovers. The defining step in HR is homolog......Homologous recombination (HR) provides a mechanism to restore integrity and maintain stability of the genetic material. HR is a major pathway for repair of DNA double-strand breaks (DSB), recovery of broken replication forks and generation of meiotic crossovers. The defining step in HR...... is homologous strand exchange directed by the RecA-related recombinase Rad51. BRCA2 participates in HR by mediating Rad51 homology-directed repair. Both BRCA2 and Rad51 are essential for HR, DNA repair, and the maintenance of genome stability. In the present study, we seek to understand the mechanism of BRCA2...... with RAD52-mediated repair at sites of CPT-induced DNA damage. The synthetic lethality approach using RAD52 small molecule inhibitors in brca-deficient cancers is a promising therapeutic strategy for cancer treatment....

  4. A mechanistic modelling approach to understand 1-MCP inhibition of ethylene action and quality changes during ripening of apples.

    Science.gov (United States)

    Gwanpua, Sunny George; Verlinden, Bert E; Hertog, Maarten Latm; Nicolai, Bart M; Geeraerd, Annemie H

    2017-08-01

    1-Methylcyclopropene (1-MCP) inhibits ripening in climacteric fruit by blocking ethylene receptors, preventing ethylene from binding and eliciting its action. The objective of the current study was to use mathematical models to describe 1-MCP inhibition of apple fruit ripening, and to provide a tool for predicting ethylene production, and two important quality indicators of apple fruit, firmness and background colour. A model consisting of coupled differential equations describing 1-MCP inhibition of apple ripening was developed. Data on ethylene production, expression of ethylene receptors, firmness, and background colour during ripening of untreated and 1-MCP treated apples were used to calibrate the model. An overall adjusted R 2 of 95% was obtained. The impact of time from harvest to treatment, and harvest maturity on 1-MCP efficacy was modelled. Different hypotheses on the partial response of 'Jonagold' apple to 1-MCP treatment were tested using the model. The model was validated using an independent dataset. Low 1-MCP blocking efficacy was shown to be the most likely cause of partial response for delayed 1-MCP treatment, and 1-MCP treatment of late-picked apples. Time from harvest to treatment was a more important factor than maturity for 1-MCP efficacy in 'Jonagold' apples. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  5. Function of Rad51 paralogs in eukaryotic homologous recombinational repair

    International Nuclear Information System (INIS)

    Liu, N.; Skowronek, K.

    2003-01-01

    Full text: Homologous recombinational repair (HRR) is an important mechanism for maintaining genetic integrity and cancer prevention by accurately repair of DNA double strand breaks induced by environmental insults or occurred in DNA replication. A critical step in HRR is the polymerization of Rad51 on single stranded DNA to form nuclear protein filaments, the later conduct DNA strand paring and exchange between homologous strands. A number of proteins, including replication protein A (RPA), Rad52 and Rad51 paralogs, are suggested to modulate or facilitate the process of Rad51 filament formation. Five Rad51 paralogs, namely XRCC2, XRCC3, Rad51B, Rad51C and Rad51D have been identified in eucaryotic cells. These proteins show distant protein sequence identity to Rad51, to yeast Rad51 paralogs (Rad55 and Rad57) and to each other. Hamster or chicken mutants of Rad51 paralogs exhibit hypersensitivity to a variety of DNA damaging agents, especially cross-linking agents, and are defective in assembly of Rad51 onto HRR site after DNA damage. Recent data from our and other labs showed that Rad51 paralogs constitute two distinct complexes in cell extracts, one contains XRCC2, Rad51B, Rad51C and Rad51D, and the other contains Rad51C and XRCC3. Rad51C is involved in both complexes. Our results also showed that XRCC3-Rad51C complex interacts with Rad51 in vivo. Furthermore, overexpression of Rad52 can partially suppress the hypersensitivity of XRCC2 mutant irs1 to ionizing radiation and corrected the defects in Rad51 focus formation. These results suggest that XRCC2 and other Rad51 paralogs play a mediator function to Rad51 in the early stage of HRR

  6. Characterizations of MCP performance in the hard x-ray range (6–25 keV)

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Ming, E-mail: minwu@sandia.gov; Rochau, Greg [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States); Moy, Ken [Special Technology Laboratories, NSTec, Santa Barbara, California 93111-2335 (United States); Kruschwitz, Craig [National Security Technologies, LLC, Los Alamos Operations, Los Alamos, New Mexico 87544 (United States)

    2014-11-15

    MCP detector performance at hard x-ray energies from 6 to 25 keV was recently investigated using NSLS beamline X15A at BNL. Measurements were made with an NSTec Gen-II (H-CA-65) framing camera, based on a Photonis MCP with ∼10 μm in diameter pores, ∼12 μm center-center spacing, an L/D ratio of 46, and a bias angle of 8°. The MCP characterizations were focused on (1) energy and angle dependent sensitivity, (2) energy and angle dependent spatial resolution, (3) energy dependent gain performance, and (4) energy dependent dynamic range. These measurement corroborated simulation results using a Monte Carlo model that included hard x-ray interactions and the subsequent electron cascade in the MCP.

  7. IL-8 and MCP Gene Expression and Production by LPS-Stimulated Human Corneal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Roni M. Shtein

    2012-01-01

    Full Text Available Purpose. To determine time course of effect of lipopolysaccharide (LPS on production of interleukin-8 (IL-8 and monocyte chemotactic protein (MCP by cultured human corneal stromal cells. Methods. Human corneal stromal cells were harvested from donor corneal specimens, and fourth to sixth passaged cells were used. Cell cultures were stimulated with LPS for 2, 4, 8, and 24 hours. Northern blot analysis of IL-8 and MCP gene expression and ELISA for IL-8 and MCP secretion were performed. ELISA results were analyzed for statistical significance using two-tailed Student's t-test. Results. Northern blot analysis demonstrated significantly increased IL-8 and MCP gene expression after 4 and 8 hours of exposure to LPS. ELISA for secreted IL-8 and MCP demonstrated statistically significant increases (P<0.05 after corneal stromal cell stimulation with LPS. Conclusions. This paper suggests that human corneal stromal cells may participate in corneal inflammation by secreting potent leukocyte chemotactic and activating proteins in a time-dependent manner when exposed to LPS.

  8. Ação do 1-metilciclopropeno (1-MCP na vida de prateleira da banana 'maçã' Action of 1-methylcyclopropene (1-MCP on shelf life of 'apple' banana

    Directory of Open Access Journals (Sweden)

    Ana Carla Marques Pinheiro

    2005-04-01

    Full Text Available Objetivou-se avaliar o efeito do 1-metilciclopropeno (1-MCP, em diferentes concentrações, sobre a vida pós-colheita e sob as variáveis associadas aos atributos de qualidade de banana 'Maçã'. Frutos verde-maturos foram submetidos a cinco concentrações de 1-MCP (0; 50; 100; 150 e 200 etaL.L-1, por 12 horas, e foram analisados durante o amadurecimento sob condição ambiente (20±1ºC e 80±5% UR. O tratamento com 50 etaL.L-1 de 1-MCP atrasou o início do amadurecimento das bananas em aproximadamente 8 dias, baseando-se nas primeiras mudanças de coloração da casca, enquanto os tratamentos 100; 150 e 200 etaL.L-1 atrasaram-no em aproximadamente 10 dias. Observou-se, durante o amadurecimento, o amaciamento dos frutos, associado à conversão de amido em açúcares e ao aumento na solubilização péctica e na atividade da pectinametilesterase (PME e poligalacturonase (PG. A aplicação de 50 etaL.L-1de 1-MCP é a mais adequada por promover a extensão da vida de prateleira de bananas 'Maçã', preservando sua qualidade com base nas análises de açúcares solúveis totais, pectinas total e solúvel, firmeza e aparência externa ao final do armazenamento.The objective of this work was to evaluate the influence of the 1-MCP, at different concentrations, on quality and shelf life of 'Apple' banana. Green mature fruits were submitted to five concentrations of 1-MCP (0, 50, 100, 150 and 200 etaL.L-1, for 12 hours and analyzed during the ripening at room temperature (20ºC ± 1 and 80% ± 5 RH . The 1-MCP at 50 etaL.L-1 delayed, in 8 days, the begining of the ripening, based in the first changes of peel color, whereas 100, 150 and 200 etaL.L-1 treatments delayed the begining of the ripening in 10 days, in comparison to the control. The softening of the fruits, associated to the conversion of starch in sugar and the increasing in the pectic solubilization and activity of pectinmethylsterase and polygalacturonase, was observed during the ripening

  9. Impact of MCP-1 and CCR-2 gene polymorphisms on coronary artery disease susceptibility.

    Science.gov (United States)

    Lin, Hsiu-Ling; Ueng, Kwo-Chang; Hsieh, Yih-Shou; Chiang, Whei-Ling; Yang, Shun-Fa; Chu, Shu-Chen

    2012-09-01

    Coronary artery disease (CAD) was the second leading cause of death during the last 3 years in Taiwan. Smooth muscle cells, monocytes/macrophages, and endothelial cells produce monocyte chemoattractant protein-1 (MCP-1) within atherosclerotic plaques following binding to the chemokine receptor-2 (CCR-2). Previous studies have well-documented the association between MCP-1 expression and susceptibility to, or clinicopathological features, of CAD. This study investigated the relationships between MCP-1-2518A/G and CCR-2-V64I genetic polymorphisms and CAD in the Taiwanese population. A total of 608 subjects, including 392 non-CAD controls and 216 patients with CAD, were recruited and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to evaluate the effects of these two polymorphic variants on CAD. Results indicated a significant association between MCP-1 -2548 gene polymorphism and susceptibility to CAD. GG genotypes (OR = 1.629; 95 % CI = 1.003-2.644), or individuals with at least one G allele (OR = 1.511; 95 % CI = 1.006-2.270), had a higher risk of CAD as compared with AA genotypes. Results also revealed that subjects with at least one A allele of the V64I CCR2 gene polymorphism had significantly increased risk of CAD. G allele in MCP-1-2518 might contribute to higher prevalence of atrial fibrillation in CAD patients (OR = 4.254; p CCR-2 64I gene polymorphisms represent important factors in determining susceptibility to CAD, and the contribution of MCP-1-2518G could be through effects on atrial fibrillation in CAD patients.

  10. Circulating MCP-1 level and вˆј2518 gene polymorphism as a ...

    African Journals Online (AJOL)

    Azza M. Hassan

    that plays an important role in the recruitment of monocytes/macrophages into renal tubulointer- stitium. A biallelic A/G polymorphism at position 2518 in the MCP-1 gene was found ..... minurea, but also with UAE in their type 2 diabetic patients. This is explained by the pivotal role played by increased MCP-. 1 production due ...

  11. RadCat 2.0 User Guide.

    Energy Technology Data Exchange (ETDEWEB)

    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

  12. FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end

    Science.gov (United States)

    Sato, Koichi; Shimomuki, Mayo; Katsuki, Yoko; Takahashi, Daisuke; Kobayashi, Wataru; Ishiai, Masamichi; Miyoshi, Hiroyuki; Takata, Minoru; Kurumizaka, Hitoshi

    2016-01-01

    The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork. PMID:27694619

  13. RadCon: A Radiological Consequences Model

    International Nuclear Information System (INIS)

    Crawford, J.; Domel, R.U.

    2000-05-01

    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

  14. Toward a noncytotoxic glioblastoma therapy: blocking MCP-1 with the MTZ Regimen

    Directory of Open Access Journals (Sweden)

    Salacz ME

    2016-04-01

    Full Text Available Michael E Salacz,1,2 Richard E Kast,3 Najmaldin Saki,4 Ansgar Brüning,5 Georg Karpel-Massler,6 Marc-Eric Halatsch6 1Department of Internal Medicine, 2Department of Neurosurgery, University of Kansas, Kansas City, KS, USA; 3IIAIGC Study Center, Burlington, VT, USA; 4Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 5Molecular Biology Laboratory, University Hospital Munich, Munich, Germany; 6Department of Neurosurgery, University of Ulm, Ulm, Germany Abstract: To improve the prognosis of glioblastoma, we developed an adjuvant treatment directed to a neglected aspect of glioblastoma growth, the contribution of nonmalignant monocyte lineage cells (MLCs (monocyte, macrophage, microglia, dendritic cells that infiltrated a main tumor mass. These nonmalignant cells contribute to glioblastoma growth and tumor homeostasis. MLCs comprise of approximately 10%–30% of glioblastoma by volume. After integration into the tumor mass, these become polarized toward an M2 immunosuppressive, pro-angiogenic phenotype that promotes continued tumor growth. Glioblastoma cells initiate and promote this process by synthesizing 13 kDa MCP-1 that attracts circulating monocytes to the tumor. Infiltrating monocytes, after polarizing toward an M2 phenotype, synthesize more MCP-1, forming an amplification loop. Three noncytotoxic drugs, an antibiotic – minocycline, an antihypertensive drug – telmisartan, and a bisphosphonate – zoledronic acid, have ancillary attributes of MCP-1 synthesis inhibition and could be re-purposed, singly or in combination, to inhibit or reverse MLC-mediated immunosuppression, angiogenesis, and other growth-enhancing aspects. Minocycline, telmisartan, and zoledronic acid – the MTZ Regimen – have low-toxicity profiles and could be added to standard radiotherapy and temozolomide. Re-purposing older drugs has advantages of established safety and low

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

    International Nuclear Information System (INIS)

    Hanly, J.G.; Hassan, J.; Moriarty, M.; Barry, C.; Molony, J.; Casey, E.; Whelan, A.; Feighery, C.; Bresnihan, B.

    1986-01-01

    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

  16. Functional roles for Rad9 in prostate cancer

    International Nuclear Information System (INIS)

    Lieberman, H.B.; Broustas, C.G.

    2012-01-01

    The goal of this work is to understand the mechanistic relationship between high levels of Rad9 protein and prostate cancer. The study is based on several findings suggesting a role for Rad9 in this disease. Rad9 has all the hallmark features of an oncogene or tumor suppressor. It regulates genomic stability, multiple cell cycle checkpoints, apoptosis and DNA repair. In addition, it can transactivate downstream target genes via direct interaction with promoter DNA sequences. We found Rad9 protein levels were very high in prostate cancer cell lines. Furthermore, we examined 52 primary normal prostate and 339 prostate cancer specimens for Rad9 protein by immunohistochemical staining. Statistical significance for Rad9 positive staining versus cancer, and stain intensity versus Stage were tested. We get a p-value of <0.001 when comparing percentage positive by cancer Stage, or stain intensity by cancer Stage. Based on these data, we sought to define the nature of the relationship between Rad9 and prostate cancer. We demonstrate that Rad9 acts as an oncogene in prostate cancer by playing a critical role in tumor formation in a mouse xenograph model. We also show that Rad9 is important for cellular phenotypes essential for metastasis, including tumor cell migration, invasion and resistance to programmed cell death after detachment from extracellular matrix. Therefore, Rad9 is critical for several aspects of prostate tumor progression, and could serve as a novel target for anti-cancer therapy

  17. PI-RADS v2: Current standing and future outlook.

    Science.gov (United States)

    Smith, Clayton P; Türkbey, Barış

    2018-05-01

    The Prostate Imaging-Reporting and Data System (PI-RADS) was created in 2012 to establish standardization in prostate multiparametric magnetic resonance imaging (mpMRI) acquisition, interpretation, and reporting. In hopes of improving upon some of the PI-RADS v1 shortcomings, the PI-RADS Steering Committee released PI-RADS v2 in 2015. This paper reviews the accuracy, interobserver agreement, and clinical outcomes of PI-RADS v2 and comments on the limitations of the current literature. Overall, PI-RADS v2 shows improved sensitivity and similar specificity compared to PI-RADS v1. However, concerns exist regarding interobserver agreement and the heterogeneity of the study methodology.

  18. RadVel: The Radial Velocity Modeling Toolkit

    Science.gov (United States)

    Fulton, Benjamin J.; Petigura, Erik A.; Blunt, Sarah; Sinukoff, Evan

    2018-04-01

    RadVel is an open-source Python package for modeling Keplerian orbits in radial velocity (RV) timeseries. RadVel provides a convenient framework to fit RVs using maximum a posteriori optimization and to compute robust confidence intervals by sampling the posterior probability density via Markov Chain Monte Carlo (MCMC). RadVel allows users to float or fix parameters, impose priors, and perform Bayesian model comparison. We have implemented real-time MCMC convergence tests to ensure adequate sampling of the posterior. RadVel can output a number of publication-quality plots and tables. Users may interface with RadVel through a convenient command-line interface or directly from Python. The code is object-oriented and thus naturally extensible. We encourage contributions from the community. Documentation is available at http://radvel.readthedocs.io.

  19. Development of a dual MCP framing camera for high energy x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Izumi, N., E-mail: izumi2@llnl.gov; Hall, G. N.; Carpenter, A. C.; Allen, F. V.; Cruz, J. G.; Felker, B.; Hargrove, D.; Holder, J.; Lumbard, A.; Montesanti, R.; Palmer, N. E.; Piston, K.; Stone, G.; Thao, M.; Vern, R.; Zacharias, R.; Landen, O. L.; Tommasini, R.; Bradley, D. K.; Bell, P. M. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); and others

    2014-11-15

    Recently developed diagnostic techniques at LLNL require recording backlit images of extremely dense imploded plasmas using hard x-rays, and demand the detector to be sensitive to photons with energies higher than 50 keV [R. Tommasini et al., Phys. Phys. Plasmas 18, 056309 (2011); G. N. Hall et al., “AXIS: An instrument for imaging Compton radiographs using ARC on the NIF,” Rev. Sci. Instrum. (these proceedings)]. To increase the sensitivity in the high energy region, we propose to use a combination of two MCPs. The first MCP is operated in a low gain regime and works as a thick photocathode, and the second MCP works as a high gain electron multiplier. We tested the concept of this dual MCP configuration and succeeded in obtaining a detective quantum efficiency of 4.5% for 59 keV x-rays, 3 times larger than with a single plate of the thickness typically used in NIF framing cameras.

  20. Long Term RadNet Quality Data

    Data.gov (United States)

    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...

  1. Effect of 1-methylcyclopropene (1- MCP) treatment on antioxidant ...

    African Journals Online (AJOL)

    ajl2

    2013-02-13

    Feb 13, 2013 ... of active oxygen-related metabolism of post-harvest Japanese apricot. The results ... a high content of vitamin C (ascorbic acid) and retarding the decrease ..... components analysis of the nfluence of 1-MCP and salicylic acid.

  2. RadGenomics project

    Energy Technology Data Exchange (ETDEWEB)

    Iwakawa, Mayumi; Imai, Takashi; Harada, Yoshinobu [National Inst. of Radiological Sciences, Chiba (Japan). Frontier Research Center] [and others

    2002-06-01

    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)

  3. RadGenomics project

    International Nuclear Information System (INIS)

    Iwakawa, Mayumi; Imai, Takashi; Harada, Yoshinobu

    2002-01-01

    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)

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

    Directory of Open Access Journals (Sweden)

    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

  5. Correlation of RAD51 and radiosensitization of methotrexate

    International Nuclear Information System (INIS)

    Du Liqing; Bai Jianqiang; Liu Qiang; Wang Yan; Zhao Peng; Chen Fenghua; Wang Hong; Fan Feiyue

    2012-01-01

    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)

  6. PAU/RAD: Design and Preliminary Calibration Results of a New L-Band Pseudo-Correlation Radiometer Concept

    Directory of Open Access Journals (Sweden)

    Enric Valencia

    2008-07-01

    Full Text Available The Passive Advanced Unit (PAU for ocean monitoring is a new type of instrument that combines in a single receiver and without time multiplexing, a polarimetric pseudo-correlation microwave radiometer at L-band (PAU-RAD and a GPS reflectometer (PAU-GNSS/R. These instruments in conjunction with an infra-red radiometer (PAU-IR will respectively provide the sea surface temperature and the sea state information needed to accurately retrieve the sea surface salinity from the radiometric measurements. PAU will consist of an array of 4x4 receivers performing digital beamforming and polarization synthesis both for PAU-RAD and PAU-GNSS/R. A concept demonstrator of the PAU instrument with only one receiver has been implemented (PAU-One Receiver or PAU-OR. PAU-OR has been used to test and tune the calibration algorithms that will be applied to PAU. This work describes in detail PAU-OR’s radiometer calibration algorithms and their performance.

  7. Structured reporting platform improves CAD-RADS assessment.

    Science.gov (United States)

    Szilveszter, Bálint; Kolossváry, Márton; Karády, Júlia; Jermendy, Ádám L; Károlyi, Mihály; Panajotu, Alexisz; Bagyura, Zsolt; Vecsey-Nagy, Milán; Cury, Ricardo C; Leipsic, Jonathon A; Merkely, Béla; Maurovich-Horvat, Pál

    2017-11-01

    Structured reporting in cardiac imaging is strongly encouraged to improve quality through consistency. The Coronary Artery Disease - Reporting and Data System (CAD-RADS) was recently introduced to facilitate interdisciplinary communication of coronary CT angiography (CTA) results. We aimed to assess the agreement between manual and automated CAD-RADS classification using a structured reporting platform. Five readers prospectively interpreted 500 coronary CT angiographies using a structured reporting platform that automatically calculates the CAD-RADS score based on stenosis and plaque parameters manually entered by the reader. In addition, all readers manually assessed CAD-RADS blinded to the automatically derived results, which was used as the reference standard. We evaluated factors influencing reader performance including CAD-RADS training, clinical load, time of the day and level of expertise. Total agreement between manual and automated classification was 80.2%. Agreement in stenosis categories was 86.7%, whereas the agreement in modifiers was 95.8% for "N", 96.8% for "S", 95.6% for "V" and 99.4% for "G". Agreement for V improved after CAD-RADS training (p = 0.047). Time of the day and clinical load did not influence reader performance (p > 0.05 both). Less experienced readers had a higher total agreement as compared to more experienced readers (87.0% vs 78.0%, respectively; p = 0.011). Even though automated CAD-RADS classification uses data filled in by the readers, it outperforms manual classification by preventing human errors. Structured reporting platforms with automated calculation of the CAD-RADS score might improve data quality and support standardization of clinical decision making. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  9. Quality management of cut carnation 'Tempo' with 1- MCP

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-19

    Oct 19, 2009 ... carnation 'Tempo' which is an ethylene-sensitive flower, were evaluated. The effects of 1-MCP .... rolling of the petals. Water uptake rate (ml g-1 .... The studies of Chamani (2006) on Rosa 'First red' cut flowers revealed that ...

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

    International Nuclear Information System (INIS)

    Xie, Chen; Wang, Hongwei; Cheng, Hongbin; Li, Jianhua; Wang, Zhi; Yue, Wu

    2014-01-01

    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

  11. CHANGES IN MECHANICAL PROPERTIES OF MINIMALLY-PROCESSED YELLOW PITAHAYA TREATED WITH 1-MCP

    Directory of Open Access Journals (Sweden)

    LILIANA SERNA COCK

    2012-01-01

    Full Text Available Se evaluaron las propiedades mecánicas de esfuerzo del límite de fluencia (sL, modulo de deformación (Ed, esfuerzo de ruptura (sF, y deformación de Hencky en la ruptura (eHF de muestras de pitahaya amarilla mínimamente procesada y tratadas con 200 μgL-1 de 1-MCP durante el almacenamiento a 10±1 °C y 85% de humedad relativa. Las muestras fueron sometidas a pruebas de compresión uniaxial hasta la ruptura. Los resultados mostraron que las muestras tratadas con 1-MCP presentaron los mayores valores del esfuerzo del límite de fluencia, modulo de elasticidad y esfuerzo de ruptura. Esto indica que la aplicación del 1-MCP proporciona mayor firmeza a la fruta y puede representar una alternativa para disminuir cambios indeseables de textura durante el almacenamiento.

  12. 'Diffuse skin browning' in 1-MCP-treated apples: etiology and systems of control.

    Science.gov (United States)

    Larrigaudière, Christian; Vilaplana, Rosa; Recasens, Inmaculada; Soria, Yolanda; Dupille, Eve

    2010-11-01

    'Diffuse skin browning' (DSB) is a physiological disorder that affects Golden Delicious apples treated with 1-methylcyclopropene (1-MCP). Although a very high incidence is found, very little is known about the etiology of this disorder. This study aims to provide an understanding of the causes of this disorder and prevent it. A very high incidence of DSB was found in 1-MCP-treated apples independent of the location of the orchard. Similar to superficial scald, harvest maturity determines the DSB incidence, with the more mature fruit being less sensitive. The 1-MCP dose (156 nL L(-1) or 625 nL L(-1)) and the temperature at which the 1-MCP treatment was applied (0.5 or 20 °C) did not affect the incidence of DSB. Diphenylamine (DPA) treatment did not prevent DSB, contrary to superficial scald. Additionally, controlled atmosphere storage only partially reduced the incidence of DSB, whereas progressive cooling strategies completely inhibited DSB occurrence. A direct correlation was found between the sensitivity of the Golden Delicious clone to russeting and its sensitivity to develop DSB during storage. Our results indicated that DSB and superficial scald are two different disorders involving different oxidative processes. DSB can be prevented by progressive cooling and selection of russeting-resistant clones. 2010 Society of Chemical Industry

  13. RadWorks Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The RadWorks project's overarching objective is the maturation and demonstration of affordable, enabling solutions to the radiation-related challenges presented to...

  14. Three additional genes involved in pyrimidine dimer removal in Saccharomyces cerevisiae: RAD7, RAD14, and MMS19

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, L; Prakash, S

    1979-01-01

    The ability to remove ultraviolet (uv)-induced pyrimidine dimers from the nuclear DNA of yeast was examined in two radiation-sensitive (rad) mutants and one methyl methanesulfonate-sensitive (mms) mutant of the yeast Saccharomyces cerevisiae. The susceptibility of DNA from irradiated cells to nicking by an endonuclease activity prepared from crude extracts of Micrococcus luteus was used to measure the presence of dimers in DNA. The rad7, rad14, and mms19 mutants were found to be defective in their ability to remove uv-induced dimers from nuclear DNA. All three mutants belong to the same episatic group as the other mutants involved in excision-repair. All three mutants show enhanced uv-induced mutations. The rad 14 mutant also shows epistatic interactions with genes in the other two uv repair pathways.

  15. HiRadMat: materials under scrutiny

    CERN Multimedia

    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...

  16. The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis

    Directory of Open Access Journals (Sweden)

    Yuan-kun Xu

    Full Text Available BACKGROUND: Osteoarthritis (OA is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented RESULTS: In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1 and receptor chemokine (C-C motif receptor 2 (CCR2 in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001 and the expression of MMP-13 also increased (P < 0.05. MCP-1 stimulation also induced (or enhanced the apoptosis of OA chondrocytes (P < 0.05. Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13 in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA model CONCLUSIONS: The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis

  17. A Rad53 independent function of Rad9 becomes crucial for genome maintenance in the absence of the Recq helicase Sgs1.

    Directory of Open Access Journals (Sweden)

    Ida Nielsen

    Full Text Available 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 MMS-induced damage. Specifically, we show a strong synergistic functionality between SGS1 and RAD9 for recovery from MMS induced damage and for suppression of gross chromosomal rearrangements, which is not the case for SGS1 and RAD24. Intriguingly, it is a Rad53 independent function of Rad9, which becomes crucial for genome maintenance in the absence of Sgs1. Despite this, our dissection of the MMS checkpoint response reveals parallel, but unequal pathways for Rad53 activation and highlights significant differences between MMS- and hydroxyurea (HU-induced checkpoint responses with relation to the requirement of the Sgs1 interacting partner Topoisomerase III (Top3. Thus, whereas earlier studies have documented a Top3-independent role of Sgs1 for an HU-induced checkpoint response, we show here that upon MMS treatment, Sgs1 and Top3 together define a minor but parallel pathway to that of Rad9.

  18. RadNet Air Quality (Fixed Station) Data

    Data.gov (United States)

    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,...

  19. EFECTO DEL 1-METIL-CICLOPROPENO (1-MCP EN LA MADURACIÓN DE BANANO

    Directory of Open Access Journals (Sweden)

    Kattia Chang-Yuen

    2005-01-01

    Full Text Available Se evaluó la eficacia del 1-metil-ciclopropeno (1-MCP en la maduración del banano (Musa sp Cavendish, aplicado después del empaque en fruta para el mercado de EE.UU. y Europa. Se utilizó fruta de 3 diferentes compañías bananeras; la fruta fue expuesta a 0, 20 y 30 nl l-1 de 1-MCP, por 24 h. Posteriormente, fue sometida a simulación de transporte, según el mercado de destino (7 días EE.UU. y 15 días Europa. Finalizada la simulación se indujo el proceso de maduración con etileno. Las evaluaciones se realizaron cada 2 días, e incluyeron análisis de calidad externa (enfermedades poscosecha y desarrollo de color externo de la cáscara y de calidad interna (oBrix, firmeza, porcentaje de acidez titulable y tasa de produc ción de CO2. Una aplicación de 30 nl l-1 de 1-MCP, generó una ganancia de más de 4 días de vida de anaquel por encima de la fruta control.La apariencia externa y la calidad interna de la fruta no se vio afectada de forma negativa por la exposición al 1-MCP, aunque se recomienda realizar pruebas sensoriales con consumidores en los mercados de destino.

  20. Effects of Triptergium Glycosides on Expressions of MCP- 1 and ...

    African Journals Online (AJOL)

    the pathogenesis of diabetic nephropathy (DN), which is one of the chronic ..... the release of lysosomal enzymes and TGF, increase the ... important roles in the pathogenesis of this disease. Thus, MCP-1 and CTGF are potential targets for ...

  1. Ethylene and 1-MCP regulate major volatile biosynthetic pathways in apple fruit.

    Science.gov (United States)

    Yang, Xiaotang; Song, Jun; Du, Lina; Forney, Charles; Campbell-Palmer, Leslie; Fillmore, Sherry; Wismer, Paul; Zhang, Zhaoqi

    2016-03-01

    The effects of ethylene and 1-methylcyclopropene (1-MCP) on apple fruit volatile biosynthesis and gene expression were investigated. Statistical analysis identified 17 genes that changed significantly in response to ethylene and 1-MCP treatments. Genes encoding branched-chain amino acid aminotransferase (BCAT), aromatic amino acid aminotransferase (ArAT) and amino acid decarboxylases (AADC) were up-regulated during ripening and further enhanced by ethylene treatment. Genes related to fatty acid synthesis and metabolism, including acyl-carrier-proteins (ACPs), malonyl-CoA:ACP transacylase (MCAT), acyl-ACP-desaturase (ACPD), lipoxygenase (LOX), hydroperoxide lyase (HPL), alcohol dehydrogenase (ADH), pyruvate decarboxylase (PDC2), β-oxidation, acyl-CoA synthetase (ACS), enoyl-CoA hydratase (ECHD), acyl-CoA dehydrogenase (ACAD), and alcohol acyltransferases (AATs) also increased during ripening and in response to ethylene treatment. Allene oxide synthase (AOS), alcohol dehydrogenase 1 (ADH1), 3-ketoacyl-CoA thiolase and branched-chain amino acid aminotransferase 2 (BCAT2) decreased in ethylene-treated fruit. Treatment with 1-MCP and ethylene generally produced opposite effects on related genes, which provides evidence that regulation of these genes is ethylene dependent. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  2. Quality management of cut carnation 'Tempo' with 1- MCP | Abadi ...

    African Journals Online (AJOL)

    Quality management of cut carnation 'Tempo' with 1- MCP. ... African Journal of Biotechnology ... time durations (3, 6 and 9 h) on the vaselife, water uptake, loss of fresh weight and chlorophyll index of cut carnation 'Tempo' which is an ...

  3. RadNet Air Data From Sacramento, CA

    Science.gov (United States)

    This page presents radiation air monitoring and air filter analysis data for Sacramento, CA from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  4. RadNet Air Data From Honolulu, HI

    Science.gov (United States)

    This page presents radiation air monitoring and air filter analysis data for Honolulu, HI from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  5. RadNet Air Data From Houston, TX

    Science.gov (United States)

    This page presents radiation air monitoring and air filter analysis data for Houston, TX from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  6. RadNet Air Data From Austin, TX

    Science.gov (United States)

    This page presents radiation air monitoring and air filter analysis data for Austin, TX from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  7. RadNet Air Data From Orlando, FL

    Science.gov (United States)

    This page presents radiation air monitoring and air filter analysis data for Orlando, FL from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  8. Insulin resistance is associated with MCP1-mediated macrophage accumulation in skeletal muscle in mice and humans.

    Directory of Open Access Journals (Sweden)

    David Patsouris

    Full Text Available Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D. However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.

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

    International Nuclear Information System (INIS)

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

    1980-01-01

    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

  10. Conservação pós-colheita de melão Charentais tratado com 1-MCP e armazenado sob refrigeração e atmosfera modificada Postharvest conservation of charentais melons treated with 1-MCP and stored under refrigeration and modified atmosphere

    Directory of Open Access Journals (Sweden)

    Pahlevi A de Souza

    2008-12-01

    Full Text Available Objetivando avaliar a vida útil pós-colheita de melão tipo Charentais (Cucumis melo L. sob refrigeração, tratados com 1-MCP e associado ou não a atmosfera modificada (AM, foram conduzidos dois experimentos em laboratório da Embrapa Agroindústria Tropical, Fortaleza-CE. Os frutos foram provenientes da Agroindústria Nolem Comercial Importadora e Exportadora Ltda, localizada no Agropólo Mossoró Açu-RN. Os frutos foram tratados com 300 e 600 ppb de 1-MCP, em seguida, metade desses frutos foram embalados em filmes plásticos, mantendo-se frutos embalados sem aplicação de 1-MCP nas mesmas condições de armazenamento dos demais. Os melões foram armazenados por 21 dias sendo 14 dias (9±1ºC e 87±5% UR + 7 dias (22±2ºC e 70±5% UR. Em função da aparência externa, a vida útil pós-colheita dos frutos armazenados sob atmosfera modificada, com ou sem tratamento inicial de 1-MCP foi de 21 dias, enquanto que dos frutos tratados inicialmente apenas com 1-MCP foi de 19 dias. A aplicação do 1-MCP proporcionou redução na atividade respiratória e na produção de etileno, e maior retenção da firmeza da polpa, menor perda de massa e melhor aparência externa quando associado a atmosfera modificada. A atmosfera modificada, isoladamente, foi eficiente em reduzir a perda de massa e manter melhor aparência externa.Aiming to evaluate the postharvest shelf life of Charentais melon (Cucumis melo L. stored under refrigeration, the fruits were treated with 1-MCP, associated or not with modified atmosphere (MAP. Two experiments were carried out at the laboratory of Embrapa Agroindústria Tropical in Fortaleza, Brazil, analyzing the chemical and physic quality characteristics. The fruits were obtained at the Agroindústria Nolem Comercial Importadora e Exportadora Ltda, located in Mossoró Açu, Brazil. The fruits were treated with 300 and 600 nL L-1 of 1-MCP, half of those were wrapped in plastic films, which were wrapped without the use of 1

  11. Rad9 Has a Functional Role in Human Prostate Carcinogenesis

    Science.gov (United States)

    Zhu, Aiping; Zhang, Charles Xia; Lieberman, Howard B.

    2013-01-01

    Prostate cancer is currently the most common type of neoplasm found in American men, other than skin cancer, and is the second leading cause of cancer death in males. Because cell cycle checkpoint proteins stabilize the genome, the relationship of one such protein, Rad9, to prostate cancer was investigated. We found that four prostate cancer cell lines (CWR22, DU145, LNCaP, and PC-3), relative to PrEC normal prostate cells, have aberrantly high levels of Rad9 protein. The 3′-end region of intron 2 of Rad9 in DU145 cells is hypermethylated at CpG islands, and treatment with 5′-aza-2′-deoxycytidine restores near-normal levels of methylation and reduces Rad9 protein abundance. Southern blot analyses indicate that PC-3 cells contain an amplified Rad9 copy number. Therefore, we provide evidence that Rad9 levels are high in prostate cancer cells due at least in part to aberrant methylation or gene amplification. The effectiveness of small interfering RNA to lower Rad9 protein levels in CWR22, DU145, and PC-3 cells correlated with reduction of tumorigenicity in nude mice, indicating that Rad9 actively contributes to the disease. Rad9 protein levels were high in 153 of 339 human prostate tumor biopsy samples examined and detectable in only 2 of 52 noncancerous prostate tissues. There was a strong correlation between Rad9 protein abundance and cancer stage. Rad9 protein level can thus provide a biomarker for advanced prostate cancer and is causally related to the disease, suggesting the potential for developing novel diagnostic, prognostic, and therapeutic tools based on detection or manipulation of Rad9 protein abundance. PMID:18316588

  12. Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy

    International Nuclear Information System (INIS)

    Chang, Lihong; Huang, Jiancong; Wang, Kai; Li, Jingjia; Yan, Ruicheng; Zhu, Ling; Ye, Jin; Wu, Xifu; Zhuang, Shimin; Li, Daqing; Zhang, Gehua

    2016-01-01

    The Mre11-Rad50-Nbs1 (MRN) complex is well known for its crucial role in initiating DNA double strand breaks (DSBs) repair pathways to resistant irradiation (IR) injury and thus facilitating radioresistance which severely reduces radiocurability of nasopharyngeal cancer (NPC). Targeting native cellular MRN function would sensitize NPC cells to IR. A recombinant adenovirus containing a mutant Rad50 gene (Ad-RAD50) expressing Rad50 zinc hook domain but lacking the ATPase domain and the Mre11 interaction domain was constructed to disrupt native cellular MRN functions. The effects of Ad-RAD50 on the MRN functions were assessed in NPC cells lines using western blot, co-immunoprecipitation and confocal microscopy analyses. The increased radiosensitivity of transient Ad-RAD50 to IR was examined in NPC cells, including MTT assay, colony formation. The molecular mechanisms of radiosensitization were confirmed by neutral comet assay and western bolts. Nude mice subcutaneous injection, tumor growth curve and TUNEL assay were used to evaluate tumor regression and apoptosis in vivo. Rad50 is remarkably upregulated in NPC cells after IR, implying the critical role of Rad50 in MRN functions. The transient expression of this mutant Rad50 decreased the levels of native cellular Rad50, Mre11 and Nbs1, weakened the interactions among these proteins, abrogated the G2/M arrest induced by DSBs and reduced the DNA repair ability in NPC cells. A combination of IR and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage, prevented proliferation and cell viability. Furthermore, Ad-RAD50 sensitized NPC cells to IR by causing dramatic tumor regression and inducing apoptosis in vivo. Our findings define a novel therapeutic approach to NPC radiosensitization via targeted native cellular Rad50 disruption. The online version of this article (doi:10.1186/s12885-016-2190-8) contains supplementary material, which is available to

  13. RAD51B in Familial Breast Cancer

    OpenAIRE

    Pelttari, L.M.; Khan, S.; et al.,

    2016-01-01

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

  14. RAD51B in familial breast cancer

    OpenAIRE

    Pelttari, LM; Khan, S; Vuorela, M; Kiiski, JI; Vilske, S; Nevanlinna, V; Ranta, S; Schleutker, J; Winqvist, R; Kallioniemi, A; Dörk, T; Bogdanova, NV; Figueroa, J; Pharoah, PDP; Schmidt, MK

    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...

  15. Transmission-Line Readout with Good Time and Space Resolutions for Planacon MCP-PMTs

    CERN Document Server

    Tang, F; Byrum, K; Drake, G; Ertley, C; Frisch, H; Genat, J-F; May, E

    2008-01-01

    With commercially-available multi-anode microchannel plate photomultiplier tubes (MCP-PMT) and electronics, resolutions significantly better than 10 psec have been achieved in small systems with a few readout channels[1,2]. For large-scale time-of-flight systems used in particle physics, which may cover tens of square meters, a solution must be found with a manageable number of electronics channels and low total power consumption on the readout electronics without degrading the system timing resolution. We present here the design of a transmission-line readout for a Photonis Planacon MCP-PMT that has these characteristics. The tube, which is 5 cm square, is characterized by signal pulse rise times in the order of 200 psec and transit time spreads (TTS) in the order of 25 psec[1, 2]. The model 85011-011 MCP has 1024 anode pads laid out in an array of 32 by 32 on the back of the tube. The proposed readout is implemented on a Rogers 4350B printed circuit board with 32 parallel 50-ohm transmission lines on 1.6 mm...

  16. The roles of MCP-1 and protein kinase C delta activation in human eosinophilic leukemia EoL-1 cells.

    Science.gov (United States)

    Lee, Ji-Sook; Yang, Eun Ju; Kim, In Sik

    2009-12-01

    Idiopathic hypereosinophilc syndrome is a disorder associated with clonally eosinophilic proliferation. The importance of FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) in the pathogenesis and classification of HES has been recently reported. In this study, we investigated the contribution of monocyte chemoattractant protein-1 (MCP-1)/CCL2 to chemotactic activity and protein kinase C delta (PKC delta in the human eosinophilic leukemia cell line EoL-1. These cells express CCR2 protein among the CC chemokine receptors (CCR1-5). MCP-1 induces strong migration of EoL-1 cells and the chemotaxis signal in response to MCP-1 involves a G(i)/G(o) protein, phospholipase C (PLC), PKC delta, p38 MAPK and NF-kappaB. MCP-1 activates p38 MAPK via G(i)/G(o) protein, PLC and PKC delta cascade. MCP-1 also induces NF-kappaB translocation and the activation is inhibited by PKC delta activation. The increase in the basal expression and activity of PKC delta in EoL-1 cells, compared to normal eosinophils, inhibits apoptosis in EoL-1 cells. Anti-apoptotic mechanism of PKC delta is related to inhibition of caspase 3 and caspase 9, but not to FIP1L1-PDGFRA. PKC delta functions as an anti-apoptotic molecule, and is involved in EoL-1 cell movement stimulated by MCP-1. This study contributes to an understanding of MCP-1 in eosinophil biology and pathogenic mechanism of eosinophilic disorders.

  17. A novel interation of nucleolin with Rad51

    International Nuclear Information System (INIS)

    De, Ananya; Donahue, Sarah L.; Tabah, Azah; Castro, Nancy E.; Mraz, Naomi; Cruise, Jennifer L.; Campbell, Colin

    2006-01-01

    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. Myocardial production and release of MCP-1 and SDF-1 following myocardial infarction: differences between mice and man

    Directory of Open Access Journals (Sweden)

    Palasubramaniam Dharshan

    2011-09-01

    Full Text Available Abstract Background Stem cell homing to the heart is mediated by the release of chemo-attractant cytokines. Stromal derived factor -1 alpha (SDF-1a and monocyte chemotactic factor 1(MCP-1 are detectable in peripheral blood after myocardial infarction (MI. It remains unknown if they are produced by, and released from, the heart in order to attract stem cells to repair the damaged myocardium. Methods Murine hearts were studied for expression of MCP-1 and SDF-1a at day 3 and day 28 following myocardial infarction to determine whether production is increased following MI. In addition, we studied the coronary artery and coronary sinus (venous blood from patients with normal coronary arteries, stable coronary artery disease (CAD, unstable angina and MI to determine whether these cytokines are released from the heart into the systemic circulation following MI. Results Both MCP-1 and SDF-1a are constitutively produced and released by the heart. MCP-1 mRNA is upregulated following murine experimental MI, but SDF-1a is suppressed. There is less release of SDF-1a into the systemic circulation in patients with all stages of CAD including MI, mimicking the animal model. However MCP-1 release from the human heart following MI is also suppressed, which is the exact opposite of the animal model. Conclusions SDF-1a and MCP-1 release from the human heart are suppressed following MI. In the case of SDF-1a, the animal model appropriately reflects the human situation. However, for MCP-1 the animal model is the exact opposite of the human condition. Human observational studies like this one are paramount in guiding translation from experimental studies to clinical trials.

  19. The association between MCP-1, VEGF polymorphisms and their serum levels in patients with diabetic foot ulcer.

    Science.gov (United States)

    Li, Xiaolei

    2018-06-01

    The purpose of the present study was to investigate distribution of monocyte chemoattractant protein-1 (MCP-1) -2518A/G and vascular endothelial growth factor (VEGF) -634G/C polymorphisms in type 2 diabetes melitus patients (T2DM) presenting diabetic foot ulcer (DFU). Additionally, we evaluated the effects of these 2 polymorphisms on serum levels of MCP-1 and VEGF in the study population.Patients diagnosed with T2DM without or with DFU were recruited in the study. The distribution of MCP-1 -2518A/G and VEGF -634G/C polymorphisms was investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the protein levels of MCP-1 and VEGF. The comparisons of protein levels in DFU patients were performed by student t test according to their genotypes.The frequencies of GG genotype and G allele of MCP-1 -2518A/G was increased in DFU patients, compared with T2DM patients (odds ratio [OR] = 2.60, 95% confidence interval [CI] = 1.23-5.50, P = .011 and OR = 1.72, 95% CI = 1.18-2.50, P = .005, respectively). Moreover, the increased frequency of GG was significantly associated with up-regulated MCP-1 level in DFU patients (P < .001). Analysis for VEGF -634G/C polymorphisms indicated that the prevalence of CC genotype and C allele of the polymorphisms was decreased in DFU patients, compared with T2DM patients (OR = 0.36, 95% CI = 0.17-0.77, P = .008 and OR = 0.63, 95% CI = 0.43-0.91, P = .015, respectively). DFU patients carrying CC genotype had a higher level of VEGF than those with other genotypes (P = .007).MCP-1 -2518A/G and VEGF -634G/C polymorphisms may involve in occurrence and progress of DFU through regulating transcription activity of the genes.

  20. Comparison of clastogen-induced gene expression profiles in wild-type and DNA repair-deficient Rad54/Rad54B cells

    Directory of Open Access Journals (Sweden)

    van Benthem Jan

    2010-01-01

    Full Text Available Abstract Background Previously we found that Rad54/Rad54B cells are more sensitive towards mitomycin C (MMC as compared to wild-type (WT cells. This difference in sensitivity was absent upon exposure to other clastogens like bleomycin (BLM and γ-radiation. In order to get further insight into possible underlying mechanisms, gene expression changes in WT and Rad54/Rad54B MEFs (mouse embryonic fibroblasts after exposure to the clastogens MMC and BLM were investigated. Exposures of these cells to mutagens (N-ac-AAF and ENU and vehicle were taken as controls. Results Most exposures resulted in an induction of DNA damage signaling and apoptosis genes and a reduced expression of cell division genes in cells of both genotypes. As expected, responses to N-ac-AAF were very similar in both genotypes. ENU exposure did not lead to significant gene expression changes in cells of both genotypes, presumably due to its short half-life. Gene expression responses to clastogens, however, showed a genotype-dependent effect for BLM and MMC. MMC treated Rad54/Rad54B MEFs showed no induction of p53-signaling, DNA damage response and apoptosis as seen for all the other treatments. Conclusion These data support our finding that different types of clastogens exist and that responses to these types depend on the DNA repair status of the cells.

  1. Correlation of MCP-4 and high-sensitivity C-reactive protein as a marker of inflammation in obesity and chronic periodontitis.

    Science.gov (United States)

    Pradeep, A R; Kumari, Minal; Kalra, Nitish; Priyanka, N

    2013-03-01

    Obesity is increasing in prevalence worldwide and has emerged as a strong risk factor for periodontal disease. Conversely, the remote effects of periodontal disease on various systemic diseases have been proposed. The aim of this study is to determine the presence of MCP-4 and high sensitivity C reactive protein (hsCRP) levels in gingival crevicular fluid (GCF) and serum in obese and non-obese subjects with chronic periodontitis and to find a correlation between MCP-4 and hsCRP in GCF and serum. Forty subjects (20 males and 20 females) were selected and divided into four groups (10 subjects in each group), based on clinical parameters: group NOH (non-obese healthy), group OH (obese healthy), Group NOCP (non-obese with chronic periodontitis) and group OCP (obese with chronic periodontitis). The levels of serum and GCF MCP-4 were determined by ELISA and hsCRP levels were determined by immunoturbidimetry method. The mean GCF and serum concentration of MCP-4 was highest for group OCP followed by group NOCP, group OH (in GCF); group OH, group NOCP(in serum) and least in group NOH. The mean hsCRP concentration was highest for group OCP followed by group OH, group NOCP and group NOH. A significant positive correlation was found between serum and GCF MCP-4 and hsCRP levels. GCF MCP-4 concentrations increased in periodontal disease compared to health and correlated positively with the severity of disease indicating it as a novel marker of periodontal disease. The serum concentration of MCP-4 was found to be more in obese group as compared to nonobese group indicating it as a marker of obesity. Furthermore, based on the positive correlation of MCP-4 and hsCRP found in this study, it can be proposed that MCP-4 and hsCRP may be the markers linking chronic inflammation in obesity and periodontal disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Molecular anatomy of the recombination mediator function of Saccharomyces cerevisiae Rad52

    DEFF Research Database (Denmark)

    Seong, C.; Sehorn, M.G.; Plate, Iben

    2008-01-01

    A helical filament of Rad51 on single-strand DNA (ssDNA), called the presynaptic filament, catalyzes DNA joint formation during homologous recombination. Rad52 facilitates presynaptic filament assembly, and this recombination mediator activity is thought to rely on the interactions of Rad52...... with Rad51, the ssDNA-binding protein RPA, and ssDNA. The N-terminal region of Rad52, which has DNA binding activity and an oligomeric structure, is thought to be crucial for mediator activity and recombination. Unexpectedly, we find that the C-terminal region of Rad52 also harbors a DNA binding function....... Importantly, the Rad52 C-terminal portion alone can promote Rad51 presynaptic filament assembly. The middle portion of Rad52 associates with DNA-bound RPA and contributes to the recombination mediator activity. Accordingly, expression of a protein species that harbors the middle and C-terminal regions of Rad...

  3. Comparative study of main dosimetric characteristics between the GR-200A and MCP-N LiF (Mg, Cu, P) TLD chips

    International Nuclear Information System (INIS)

    Shen Wenxiu; Tang Kaiyong; Wang Shoushan; Cai Gangang; Zhu Hongying; Lu Min

    1999-01-01

    GR-200A and MCP-N are the same kind of LiF(Mg, Cu, P) chip detectors. The main dosimetric characteristics of two LiF (Mg, Cu, P) chip TLDs (GR-200A made in Solid Dosimetric Detector and Method Laboratory, Beijing, and MCP-N made in Poland) are compared, including glow curve structure, TL sensitivity, anti-moisture, reproducibility, background, detection threshold and photosensitivity. Sensitivity of GR-200a is 1.6 times as much as that of MCP-N. The sensitivity of GR-200A is stable after being used for six times, but the sensitivity of MCP-N dropped 2.8%, and its colour turned from white into light brown. The sensitivity and colour of GR-200A did not vary after being stored for 25 days at 98% RH, by comparison the sensitivity of MCP-N dropped 14%, and its colour turned into light brown. It was found that the GR-200A TLD is superior to the MCP-N TLD in above-mentioned characteristics

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

    International Nuclear Information System (INIS)

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

    1979-01-01

    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

  5. The human MCP-2 gene (SCYA8): Cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2

    Energy Technology Data Exchange (ETDEWEB)

    Van Coillie, E.; Fiten, P.; Van Damme, J.; Opdenakker, G. [Univ. of Leuven (Belgium)] [and others

    1997-03-01

    Monocyte chemotactic proteins (MCPs) form a subfamily of chemokines that recruit leukocytes to sites of inflammation and that may contribute to tumor-associated leukocyte infiltration and to the antiviral state against HIV infection. With the use of degenerate primers that were based on CC chemokine consensus sequences, the known MIP-1{alpha}/LD78{alpha}, MCP-1, and MCP-3 genes and the previously unidentified eotaxin and MCP-2 genes were isolated from a YAC contig from human chromosome 17q11.2. The amplified genomic MCP-2 fragment was used to isolate an MCP-2 cosmid from which the gene sequence was determined. The MCP-2 gene shares with the MCP-1 and MCP-3 genes a conserved intron-exon structure and a coding nucleotide sequence homology of 77%. By Northern blot analysis the 1.0-kb MCP-2 mRNA was predominantly detectable in the small intestine, peripheral blood, heart, placenta, lung, skeletal muscle, ovary, colon, spinal cord, pancreas, and thymus. Transcripts of 1.5 and 2.4 kb were found in the testis, the small intestine, and the colon. The isolation of the MCP-2 gene from the chemokine contig localized it on YAC clones of chromosome 17q11.2, which also contain the eotaxin, MCP-1, MCP-3, and NCC-1/MCP-4 genes. The combination of using degenerate primer PCR and YACs illustrates that novel genes can efficiently be isolated from gene cluster contigs with less redundancy and effort than the isolation of novel ESTs. 42 refs., 5 figs., 2 tabs.

  6. Crystallization and crystallographic analysis of the ligand-binding domain of the Pseudomonas putida chemoreceptor McpS in complex with malate and succinate

    International Nuclear Information System (INIS)

    Gavira, J. A.; Lacal, J.; Ramos, J. L.; García-Ruiz, J. M.; Krell, T.; Pineda-Molina, E.

    2012-01-01

    The crystallization of the ligand-binding domain of the methyl-accepting chemotaxis protein chemoreceptor McpS (McpS-LBD) is reported. Methyl-accepting chemotaxis proteins (MCPs) are transmembrane proteins that sense changes in environmental signals, generating a chemotactic response and regulating other cellular processes. MCPs are composed of two main domains: a ligand-binding domain (LBD) and a cytosolic signalling domain (CSD). Here, the crystallization of the LBD of the chemoreceptor McpS (McpS-LBD) is reported. McpS-LBD is responsible for sensing most of the TCA-cycle intermediates in the soil bacterium Pseudomonas putida KT2440. McpS-LBD was expressed, purified and crystallized in complex with two of its natural ligands (malate and succinate). Crystals were obtained by both the counter-diffusion and the hanging-drop vapour-diffusion techniques after pre-incubation of McpS-LBD with the ligands. The crystals were isomorphous and belonged to space group C2, with two molecules per asymmetric unit. Diffraction data were collected at the ESRF synchrotron X-ray source to resolutions of 1.8 and 1.9 Å for the malate and succinate complexes, respectively

  7. The cross-validated AUC for MCP-logistic regression with high-dimensional data.

    Science.gov (United States)

    Jiang, Dingfeng; Huang, Jian; Zhang, Ying

    2013-10-01

    We propose a cross-validated area under the receiving operator characteristic (ROC) curve (CV-AUC) criterion for tuning parameter selection for penalized methods in sparse, high-dimensional logistic regression models. We use this criterion in combination with the minimax concave penalty (MCP) method for variable selection. The CV-AUC criterion is specifically designed for optimizing the classification performance for binary outcome data. To implement the proposed approach, we derive an efficient coordinate descent algorithm to compute the MCP-logistic regression solution surface. Simulation studies are conducted to evaluate the finite sample performance of the proposed method and its comparison with the existing methods including the Akaike information criterion (AIC), Bayesian information criterion (BIC) or Extended BIC (EBIC). The model selected based on the CV-AUC criterion tends to have a larger predictive AUC and smaller classification error than those with tuning parameters selected using the AIC, BIC or EBIC. We illustrate the application of the MCP-logistic regression with the CV-AUC criterion on three microarray datasets from the studies that attempt to identify genes related to cancers. Our simulation studies and data examples demonstrate that the CV-AUC is an attractive method for tuning parameter selection for penalized methods in high-dimensional logistic regression models.

  8. Physical mapping and cloning of RAD56

    DEFF Research Database (Denmark)

    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...

  9. RAD51B in Familial Breast Cancer

    DEFF Research Database (Denmark)

    Pelttari, Liisa M; Khan, Sofia; Vuorela, Mikko

    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 RAD......51B 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...

  10. Qualidade de caqui 'Rama forte' após armazenamento refrigerado, influenciada pelos tratamentos 1-MCP e/ou CO2

    Directory of Open Access Journals (Sweden)

    João Peterson Pereira Gardin

    2012-12-01

    Full Text Available Avaliaram-se os efeitos dos tratamentos com CO2 e 1-MCP (1-metilciclopropeno sobre a adstringência (índice de tanino, firmeza da polpa e distúrbios da epiderme em caqui 'Rama Forte'. Frutos foram tratados com 1-MCP por 24 h, logo após a colheita e/ou com alto CO2 (70% por 24 ou 48 h, um dia após a colheita ou após o armazenamento refrigerado (AR. Os caquis foram armazenados sob atmosfera modificada a 0 ºC, por 45 dias, e a seguir mantidos a 23 ºC, por 9 dias. Frutos-controle (não tratados com 1-MCP nem com CO2 amoleceram em três dias e perderam aproximadamente 50% da adstringência em 6 dias após o AR. A exposição ao CO2 acelerou a redução da adstringência. Esse efeito do CO2 foi menor em frutos tratados com 1-MCP, especialmente quando o CO2 foi aplicado após o AR, por apenas 24 h. O tratamento com 1-MCP inibiu o amolecimento e a redução da adstringência, especialmente nos frutos não tratados com CO2. O amolecimento de frutos tratados com 1-MCP foi maior quando a exposição ao CO2 ocorreu antes do AR. A combinação dos tratamentos com 1-MCP e alto CO2 reduziu a incidência de podridões e manchas translúcidas, mas não alterou o desenvolvimento de pintas pretas ('estrias'. Os resultados indicam que é possível induzir perda da adstringência sem excessiva perda da firmeza da polpa de caquis 'Rama Forte' após o AR pela associação dos tratamentos com 1-MCP logo após a colheita e alto CO2 após o AR.

  11. Modular Engine Noise Component Prediction System (MCP) Program Users' Guide

    Science.gov (United States)

    Golub, Robert A. (Technical Monitor); Herkes, William H.; Reed, David H.

    2004-01-01

    This is a user's manual for Modular Engine Noise Component Prediction System (MCP). This computer code allows the user to predict turbofan engine noise estimates. The program is based on an empirical procedure that has evolved over many years at The Boeing Company. The data used to develop the procedure include both full-scale engine data and small-scale model data, and include testing done by Boeing, by the engine manufacturers, and by NASA. In order to generate a noise estimate, the user specifies the appropriate engine properties (including both geometry and performance parameters), the microphone locations, the atmospheric conditions, and certain data processing options. The version of the program described here allows the user to predict three components: inlet-radiated fan noise, aft-radiated fan noise, and jet noise. MCP predicts one-third octave band noise levels over the frequency range of 50 to 10,000 Hertz. It also calculates overall sound pressure levels and certain subjective noise metrics (e.g., perceived noise levels).

  12. Resposta da aplicação do 1-MCP em frutos de mamoeiro 'Golden' em diferentes estádios de maturação Responses of 1-MCP applications in 'Golden' papaya fruits on differents maturation stages

    Directory of Open Access Journals (Sweden)

    Maximiliano Silva de Souza

    2009-09-01

    Full Text Available O estudo de fatores que influenciam no processo de amadurecimento é fundamental para o planejamento do processo de comercialização, principalmente em frutos com padrão de respiração climatérico e perecível, como é o caso do mamão. Nesse trabalho, avaliou-se o efeito da aplicação do 1-MCP (1-metilciclopropeno sobre o amadurecimento de frutos de mamoeiro nos estádios 0; 1 e 2 de maturação. O 1-MCP diminui a produção de etileno (≈79% e a taxa respiratória (≈45%, principalmente em frutos no estádio 0 de maturação. O uso deste inibidor da ação do etileno retardou a perda de coloração verde da casca dos frutos, principalmente em frutos nos estádios 0 e 1 de maturação. Houve redução na perda de firmeza do fruto e do mesocarpo nos estádios 1 e 2. Entretanto, em frutos no estádio 0 de maturação, a firmeza do mesocarpo manteve-se alta, o que pode comprometer a aceitação destes frutos pelo consumidor. O teor de sólidos solúveis não foi influenciado pela aplicação do 1-MCP. O efeito do 1-MCP na redução da atividade das enzimas PME e PG foi maior em frutos nos estádios 0 e 1 de maturação em comparação a frutos no estádio 2 de maturação. A atividade da PME demonstrou crescente aumento ao longo do período de armazenamento, porém a atividade da PG permaneceu baixa ao longo dos cinco primeiros dias, com aumento posterior. Os resultados mostraram que a PME exerce influência significativa na perda de firmeza da polpa nos primeiros dias, com atuação posterior da PG. O 1-MCP mostrou-se eficiente em retardar o processo de amadurecimento de frutos de mamoeiro, tornando-se mais eficiente quando associado a estádios de maturação iniciais.The study of factors that influence the process of ripening is critical for planning the marketing process, mainly in standard breathing climacteric and perishing fruits, as it is the case of papaya. In this work it was evaluated the effect of the application of 1-MCP (1

  13. Monte Carlo Simulations of High-speed, Time-gated MCP-based X-ray Detectors: Saturation Effects in DC and Pulsed Modes and Detector Dynamic Range

    International Nuclear Information System (INIS)

    Kruschwitz, Craig; Ming Wu; Moy, Ken; Rochau, Greg

    2008-01-01

    We present here results of continued efforts to understand the performance of microchannel plate (MCP)-based, high-speed, gated, x-ray detectors. This work involves the continued improvement of a Monte Carlo simulation code to describe MCP performance coupled with experimental efforts to better characterize such detectors. Our goal is a quantitative description of MCP saturation behavior in both static and pulsed modes. We have developed a new model of charge buildup on the walls of the MCP channels and measured its effect on MCP gain. The results are compared to experimental data obtained with a short-pulse, high-intensity ultraviolet laser; these results clearly demonstrate MCP saturation behavior in both DC and pulsed modes. The simulations compare favorably to the experimental results. The dynamic range of the detectors in pulsed operation is of particular interest when fielding an MCP-based camera. By adjusting the laser flux we study the linear range of the camera. These results, too, are compared to our simulations

  14. Influence of 1-MCP treatments on eating quality and consumer preferences of ‘Qinmei’ kiwifruit during shelf life

    Science.gov (United States)

    Consumers and growers in China sometime complain that Kiwifruits treated with an ethylene action inhibitor 1-MCP are difficult to ripen and show poor eating quality. This study addresses the quality parameters affecting consumer preferences and reevaluates the necessity of 1-MCP application for stor...

  15. Caffeine inhibits gene conversion by displacing Rad51 from ssDNA

    Science.gov (United States)

    Tsabar, Michael; Mason, Jennifer M.; Chan, Yuen-Ling; Bishop, Douglas K.; Haber, James E.

    2015-01-01

    Efficient repair of chromosomal double-strand breaks (DSBs) by homologous recombination relies on the formation of a Rad51 recombinase filament that forms on single-stranded DNA (ssDNA) created at DSB ends. This filament facilitates the search for a homologous donor sequence and promotes strand invasion. Recently caffeine treatment has been shown to prevent gene targeting in mammalian cells by increasing non-productive Rad51 interactions between the DSB and random regions of the genome. Here we show that caffeine treatment prevents gene conversion in yeast, independently of its inhibition of the Mec1ATR/Tel1ATM-dependent DNA damage response or caffeine's inhibition of 5′ to 3′ resection of DSB ends. Caffeine treatment results in a dosage-dependent eviction of Rad51 from ssDNA. Gene conversion is impaired even at low concentrations of caffeine, where there is no discernible dismantling of the Rad51 filament. Loss of the Rad51 filament integrity is independent of Srs2's Rad51 filament dismantling activity or Rad51's ATPase activity and does not depend on non-specific Rad51 binding to undamaged double-stranded DNA. Caffeine treatment had similar effects on irradiated HeLa cells, promoting loss of previously assembled Rad51 foci. We conclude that caffeine treatment can disrupt gene conversion by disrupting Rad51 filaments. PMID:26019181

  16. Mongoose: Creation of a Rad-Hard MIPS R3000

    Science.gov (United States)

    Lincoln, Dan; Smith, Brian

    1993-01-01

    This paper describes the development of a 32 Bit, full MIPS R3000 code-compatible Rad-Hard CPU, code named Mongoose. Mongoose progressed from contract award, through the design cycle, to operational silicon in 12 months to meet a space mission for NASA. The goal was the creation of a fully static device capable of operation to the maximum Mil-883 derated speed, worst-case post-rad exposure with full operational integrity. This included consideration of features for functional enhancements relating to mission compatibility and removal of commercial practices not supported by Rad-Hard technology. 'Mongoose' developed from an evolution of LSI Logic's MIPS-I embedded processor, LR33000, code named Cobra, to its Rad-Hard 'equivalent', Mongoose. The term 'equivalent' is used to infer that the core of the processor is functionally identical, allowing the same use and optimizations of the MIPS-I Instruction Set software tool suite for compilation, software program trace, etc. This activity was started in September of 1991 under a contract from NASA-Goddard Space Flight Center (GSFC)-Flight Data Systems. The approach affected a teaming of NASA-GSFC for program development, LSI Logic for system and ASIC design coupled with the Rad-Hard process technology, and Harris (GASD) for Rad-Hard microprocessor design expertise. The program culminated with the generation of Rad-Hard Mongoose prototypes one year later.

  17. Temporal cascade of inflammatory cytokines and cell-type populations in monocyte chemotactic protein-1 (MCP-1)-mediated aneurysm healing.

    Science.gov (United States)

    Hoh, Brian L; Fazal, Hanain Z; Hourani, Siham; Li, Mengchen; Lin, Li; Hosaka, Koji

    2018-03-01

    We have previously shown that monocyte chemotactic protein-1 (MCP-1) promotes aneurysm healing. To determine the temporal cascade and durability of aneurysm healing. Murine carotid aneurysms were treated with MCP-1-releasing or poly(lactic-co-glycolic) acid (PLGA)-only coils. Aneurysm healing was assessed by quantitative measurements of intraluminal tissue ingrowth on 5 μm sections by blinded observers. Aneurysm healing occurred in stages characteristic of normal wound healing. The 1st stage (day 3) was characterized by a spike in neutrophils and T cells. The 2nd stage (week 1) was characterized by an influx of macrophages and CD45+ cells significantly greater with MCP-1 than with PLGA (p<0.05). The third stage (week 2-3) was characterized by proliferation of smooth muscle cells and fibroblasts (greater with MCP-1 than with PLGA, p<0.05). The fourth stage (3-6 months) was characterized by leveling off of smooth muscle cells and fibroblasts. M1 macrophages were greater at week 1, whereas M2 macrophages were greater at weeks 2 and 3 with MCP-1 than with PLGA. Interleukin 6 was present early and increased through week 2 (p<0.05 compared with PLGA) then decreased and leveled off through 6 months. Tumour necrosis factor α was present early and remained constant through 6 months. MCP-1 and PLGA treatment had similar rates of tissue ingrowth at early time points, but MCP-1 had a significantly greater tissue ingrowth at week 3 (p<0.05), which persisted for 6 months. The sequential cascade is consistent with an inflammatory model of injury, repair, and remodeling. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. RadNet Air Data From Fort Smith, AR

    Science.gov (United States)

    This page presents radiation air monitoring and air filter analysis data for Fort Smith, AR from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  19. RadNet Air Data From Little Rock, AR

    Science.gov (United States)

    This page presents radiation air monitoring and air filter analysis data for Little Rock, AR from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  20. RadNet Air Data From Mason City, IA

    Science.gov (United States)

    This page presents radiation air monitoring and air filter analysis data for Mason City, IA from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  1. Reach Address Database (RAD)

    Data.gov (United States)

    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,...

  2. Germline RAD51B truncating mutation in a family with cutaneous melanoma

    DEFF Research Database (Denmark)

    Wadt, Karin A W; Aoude, Lauren G; Golmard, Lisa

    2015-01-01

    Known melanoma predisposition genes only account for around 40% of high-density melanoma families. Other rare mutations are likely to play a role in melanoma predisposition. RAD51B plays an important role in DNA repair through homologous recombination, and inactivation of RAD51B has been implicated...... in tumorigenesis. Thus RAD51B is a good candidate melanoma susceptibility gene, and previously, a germline splicing mutation in RAD51B has been identified in a family with early-onset breast cancer. In order to find genetic variants associated with melanoma predisposition, whole-exome sequencing was carried out...... on blood samples from a three-case cutaneous melanoma family. We identified a novel germline RAD51B nonsense mutation, and we demonstrate reduced expression of RAD51B in melanoma cells indicating inactivation of RAD51B. This is only the second report of a germline truncating RAD51B mutation. While...

  3. A 30 ps Timing Resolution for Single Photons with Multi-pixel Burle MCP-PMT

    Energy Technology Data Exchange (ETDEWEB)

    Va' vra, J.; Benitez, J.; Coleman, J.; Leith, D.W.G.S.; Mazaheri, G.; Ratcliff, B.; Schwiening, J.; /SLAC

    2006-07-05

    We have achieved {approx}30 psec single-photoelectron and {approx}12ps for multi-photoelectron timing resolution with a new 64 pixel Burle MCP-PMT with 10 micron microchannel holes. We have also demonstrated that this detector works in a magnetic field of 15kG, and achieved a single-photoelectron timing resolution of better than 60 psec. The study is relevant for a new focusing DIRC RICH detector for particle identification at future Colliders such as the super B-factory or ILC, and for future TOF techniques. This study shows that a highly pixilated MCP-PMT can deliver excellent timing resolution.

  4. Characterization of iminothiosulfine-type ions [HNCS 2] rad +/ rad - and their neutral counterparts by mass spectrometry and computational chemistry

    Science.gov (United States)

    Vivekananda, S.; Raghunath, P.; Bhanuprakash, K.; Srinivas, R.; Trikoupis, Moschoula A.; Terlouw, Johan K.

    2000-12-01

    Electron ionization of rhodanine yields iminothiosulfine ions H- N C- S- Srad + , 1brad + , which readily communicate with the higher energy cyclic isomer H- N CS2rad + , 1arad + . CBS-QB3 and G AUSSIAN-2 model chemistries predict that one electron reduction reverses the stability order but that the (singlet) neutrals remain connected via a negligible energy barrier. Neutralization-reionization (NR) experiments demonstrate that singlet 1a and its heterocumulene isomer 1b are stable species in the gas-phase. However, the co-generated triplet species readily dissociate into 3S2rad + + HNC. Confirmatory experimental evidence comes from charge reversal (CR) and NR experiments on the cyclic anion H- N CS2rad - , 1arad - .

  5. Radiological information management system (RadIMS)

    International Nuclear Information System (INIS)

    Oesterling, R.G.; Marko, S.A.; Tschaeche, A.N.

    1991-01-01

    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

  6. RadCat 3.0 user guide.

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Radiological information management system (RadIMS)

    Energy Technology Data Exchange (ETDEWEB)

    Oesterling, R.G.; Marko, S.A.; Tschaeche, A.N.

    1991-08-19

    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.

  8. Radiological information management system (RadIMS)

    Energy Technology Data Exchange (ETDEWEB)

    Oesterling, R.G.; Marko, S.A.; Tschaeche, A.N.

    1991-08-19

    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.

  9. RadNet Radiological Air Monitoring Network

    International Nuclear Information System (INIS)

    Scott Telofski, J.; Askren, D.R.; Petko, Ch.M.; Fraass, R.G.

    2010-01-01

    The United States Environmental Protection Agency operates a national environmental radiation monitoring program called RadNet. RadNet monitors airborne particulates, precipitation, milk, and drinking water for radiation levels. The primary purpose of the original program in the 1950's and 1960's was to collect and analyze samples in various media to assess the effects of radioactive fallout from above-ground nuclear weapon testing. As above-ground testing diminished in the 1970's, the program, especially the air network, became critical in evaluating effects of other types of nuclear incidents, such as the nuclear reactor accident at Chernobyl, as well as monitoring trends in environmental radioactive contamination. The value of rapid data collection subsequent to such incidents led to the consideration of developing air monitors with radiation detectors and telecommunication equipment for real-time radiation measurement. The strengthened United States homeland security posture after 2001 led to production and installation of the current real-time RadNet air monitors. There are now 118 stationary, continuously operating air monitoring stations and 40 mobile air monitors for site specific monitoring. The stationary air monitors include radiation detectors, meteorological sensors, a high-volume air sampler, and communication devices for hourly data transfers. When unusual levels are detected, scientists download a full sodium iodide detector spectrum for analysis. The real-time data collected by RadNet stationary systems permit rapid identification and quantification of airborne nuclides with sufficient sensitivity to provide critical information to help determine protective actions. The data also may help to rapidly refine long-range radioactive plume models and estimate exposure to the population. This paper provides an overview of the airborne particulate monitoring conducted during above-ground nuclear weapon testing, summarizes the uses of data from the program

  10. Cloning of an E. coli RecA and yeast RAD51 homolog, radA, an allele of the uvsC in Aspergillus nidulans and its mutator effects.

    Science.gov (United States)

    Seong, K Y; Chae, S K; Kang, H S

    1997-04-30

    An E. coli RecA and yeast RAD51 homolog from Aspergillus nidulans, radA, has been cloned by screening genomic and cDNA libraries with a PCR-amplified probe. This probe was generated using primers carrying the conserved sequences of eukaryotic RecA homologs. The deduced amino acid sequence revealed two conserved Walker-A and -B type nucleotide-binding domains and exhibited 88%, 60%, and 53% identity with Mei-3 of Neurospora crassa, rhp51+ of Schizosaccharomyces pombe, and Rad51 of Saccharomyces cerevisiae, respectively. radA null mutants constructed by replacing the whole coding region with a selection marker showed high methyl methanesulfonate (MMS) sensitivity. Heterozygous diploids of radA disruptant with the uvsC114 mutant failed to complement with respect to MMS-sensitivity, indicating that radA is an allele of uvsC. In selecting spontaneous forward selenate resistant mutations, mutator effects were observed in radA null mutants similarly to those shown in uvsC114 mutant strains.

  11. Human RAD50 makes a functional DNA-binding complex.

    Science.gov (United States)

    Kinoshita, Eri; van Rossum-Fikkert, Sari; Sanchez, Humberto; Kertokalio, Aryandi; Wyman, Claire

    2015-06-01

    The MRE11-RAD50-NBS1 (MRN) complex has several distinct functions in DNA repair including important roles in both non-homologous end-joining (NHEJ) and homologous recombination (HR). The biochemical activities of MR(N) have been well characterized implying specific functional roles for the components. The arrangement of proteins in the complex implies interdependence of their biochemical activities making it difficult to separate specific functions. We obtained purified human RAD50 and observed that it binds ATP, undergoes ATP-dependent conformational changes as well as having ATPase activity. Scanning force microscopy analysis clearly showed that RAD50 binds DNA although not as oligomers. RAD50 alone was not functional in tethering DNA molecules. ATP increased formation of RAD50 multimers which were however globular lacking extended coiled coils, in contrast to the MR complex where ATP induced oligomers have obvious coiled coils protruding from a central domain. These results suggest that MRE11 is important in maintaining the structural arrangement of RAD50 in the protein complex and perhaps has a role in reinforcing proper alignment of the coiled coils in the ATP-bound state. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  12. EFECTO DEL EMPAQUE Y DEL 1-MCP SOBRE CARACTERÍSTICAS FÍSICAS, QUÍMICAS Y FISIOLÓGICAS DE PITAHAYA AMARILLA EFEITO DA EMBALAGEM E DO 1-MCP SOB AS PROPRIEDADES QUÍMICAS, FÍSICAS E FISIOLÓGICAS DA PITAHAYA AMARELA EFFECT OF PACKAGING AND 1-MCP ON PHYSICAL, CHEMICAL AND PHYSIOLOGICAL CHARACTERISTICS OF PITAHAYA YELLOW

    Directory of Open Access Journals (Sweden)

    LILIANA SERNA C

    2011-12-01

    Full Text Available En pitahaya amarilla entera con grado de madurez 3, se evaluó el efecto del empaque (canastillas plásticas y cajas de cartón tipo exportación y la aplicación de soluciones acuosas de 1-Metilciclopropeno (200 y 400 µgL-1, sobre la pérdida de peso, firmeza, color, sólidos solubles, acidez titulable, tasa respiratoria y tiempo de vida comercial. Se encontró que en los dos empaques, la aplicación de soluciones acuosas de 200 y 400 µgL-1 de 1-Metilciclopropeno (1-MCP disminuyó los cambios en acidez, tasa respiratoria y color, sin embargo, aumentó la pérdida de peso durante el almacenamiento. El tipo de empaque afectó significativamente la pérdida de peso, los sólidos solubles y el color. La aplicación de 200 µgL-1 de 1-MCP generó menor variación en la luminosidad y en la coloración verde-amarilla en la fruta. Concentraciones de 200 y 400 µgL-1 de 1-MCP y el empaque en canastillas plásticas para mercado local permitieron prolongar el tiempo de vida comercial de la pitahaya amarilla 3 días. Los resultados de este estudio confirman además que la pitahaya amarilla es una fruta climatérica.Na pitahaya amarela inteira com grau tres de madures, foi avallado os efeitos da embalagem (cestos de plástico e caixas de papelão tipo exportação e a aplicação de soluções aquosas de 1-metilciclopropeno (200 e 400 µgL-1 sobre a perda de peso, firmeza, cor, teor de sólidos solúveis totais, acidez, taxa de respiração e tempo de vida comercial. Foi observado que nas duas embalagens, a aplicação de soluções aquosas de 200 e 400 µgL-1 de 1-Metilciclopropeno (1-MCP reduziu as variações na acidez, taxa de respiração e cor, no entanto, aumentou a perda de peso durante o armazenamento. 0 tipo da embalagem afetou significativamente a perda de peso, o teor de sólidos solúveis totais, e acor. A aplicação de 200 µgL-1 de 1-MCP gerou menor variação na luminosidade e na cor verde-amarela no fruto. Concentrações de 200 e 400

  13. Postharvest quality of ‘Galaxy’ apples submitted to the treatment with 1-MCP and different cooling times between harvest and cold storage

    Directory of Open Access Journals (Sweden)

    Crizane Hackbarth

    Full Text Available ABSTRACT: In this research it was evaluated if the use of 1-methylcyclopropene (1-MCP, associated to different cooling times between the harvest and storage, replaces the pre-cooling in ‘Galaxy’ apples. Treatments were arranged in a factorial scheme, combining the following factors: application of 1-MCP (with or without and different times between harvest and cooling (24 hours, 96 hours, 144 hours and 192 hours in 2013; and 24 hours, 48 hours, 144 hours and 240 hours in 2014. After four months of cold storage (1.0±0.2°C/92±5% RH - Relative Humidity were evaluated: flesh firmness, texture, titratable acidity (TA, soluble solids (SS and skin color. Apples treated with 1-MCP showed greater flesh firmness, texture and SS, in both years, and more TA and lower incidence of mealy flesh compared to apples not treated with 1-MCP in 2013. The 1-MCP was effective in maintaining the fruit quality, even with the cooling delay of up to 240 hours. Cooling delay of 192 hours and 240 hours in ‘Galaxy’ apples not treated with 1-MCP should be avoided because it reduces the quality of fruits.

  14. Effect of DPA and 1-MCP on chemical compounds related to superficial scald of Granny Smith apples

    Energy Technology Data Exchange (ETDEWEB)

    Moggia, C.; Moya-Leon, M. A.; Pereira, M.; Yuri, J. A.; Lobos, G. A.

    2010-07-01

    Research was carried out to study the mode of action of diphenylamine (DPA) and 1-methylcyclopropene (1-MCP), on control of superficial scald of Granny Smith apples (Malus domestica Borkh.), and its relation with chemical compounds. Fruit was harvested from a commercial orchard in Chile, 182 and 189 days after full bloom and received the following treatments: DPA (2,000 ppm); 1-MCP (1.2 ppm) and control (no treatment). All fruit was stored for 4 or 6 months at 0 degree centigrade. A completely randomized factorial design was used (2 harvest dates by 3 post harvest treatments). Monthly measurements were made on maturity indices, ethylene production rate (EPR), scald related compounds [a-farnesene (AF), conjugated trienes (CT), total anti-oxidants (AO)], and cell membrane stability. Following 4 and 6 months of storage, plus 7 days at 20 degree centigrade, scald was evaluated. After 6 months, DPA-treated fruit, from both harvests, showed similar firmness, EPR and AO, compared to the control. However, AF and CT were lower, and cell membrane stability higher. Conversely, 1-MCP-treated fruit showed a noticeable EPR suppression and AF inhibition, along with higher firmness, lower CT and AO, compared to the control and DPA. Furthermore, cell membrane stability was superior to that of the control and similar to that of the DPA. Treated fruit (DPA and 1-MCP) showed an important reduction in scald compared to the control. The effect of 1-MCP on the investigated compounds and the reduction in scald, confirms that ethylene plays a major role on its development. (Author) 50 refs.

  15. Protective effect of the LevRad on treat of paracoccidioidomycosis

    International Nuclear Information System (INIS)

    Martins, Estefania M.N.; Andrade, Antero S.R.; Fernandes, Viviane Cristina; Morais, Elis Araujo; Goes, Alfredo M.; Resende, Maria Aparecida de

    2011-01-01

    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)

  16. RAD51 interconnects between DNA replication, DNA repair and immunity.

    Science.gov (United States)

    Bhattacharya, Souparno; Srinivasan, Kalayarasan; Abdisalaam, Salim; Su, Fengtao; Raj, Prithvi; Dozmorov, Igor; Mishra, Ritu; Wakeland, Edward K; Ghose, Subroto; Mukherjee, Shibani; Asaithamby, Aroumougame

    2017-05-05

    RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. We identified a novel role for RAD51 in innate immune response signaling. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and DNA damage. In the absence of RAD51, the unprotected newly replicated genome is degraded by the exonuclease activity of MRE11, and the fragmented nascent DNA accumulates in the cytosol, initiating an innate immune response. Our data suggest that in addition to playing roles in homologous recombination-mediated DNA double-strand break repair and replication fork processing, RAD51 is also implicated in the suppression of innate immunity. Thus, our study reveals a previously uncharacterized role of RAD51 in initiating immune signaling, placing it at the hub of new interconnections between DNA replication, DNA repair, and immunity. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. MCP-1/CCR-2-double-deficiency severely impairs the migration of hematogenous inflammatory cells following transient cerebral ischemia in mice.

    Science.gov (United States)

    Schuette-Nuetgen, Katharina; Strecker, Jan-Kolja; Minnerup, Jens; Ringelstein, E Bernd; Schilling, Matthias

    2012-02-01

    Monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR-2 are known to play a major role in inflammatory responses after cerebral ischemia. Mice deficient in either MCP-1 or CCR-2 have been reported to develop smaller infarct sizes and show decreased numbers of infiltrating inflammatory cells. In the present study we used green fluorescent protein (GFP) transgenic mice to investigate the effect of MCP-1/CCR-2-double deficiency on the recruitment of inflammatory cells in a model of both, mild and severe cerebral ischemia. We show that MCP-1/CCR-2-double deficiency virtually entirely abrogates the recruitment of hematogenous macrophages and significantly reduces neutrophil migration to the ischemic brain 4 and 7 days following focal cerebral ischemia. This argues for a predominant role of the MCP-1/CCR-2 axis in chemotaxis of monocytes despite a wide redundancy in the chemokine-receptor-system. Chemokine analysis revealed that even candidates known to be involved in monocyte and neutrophil recruitment like MIP-1α, CXCL-1, C5a, G-CSF and GM-CSF showed a reduced and delayed or even a lack of relevant compensatory response in MCP-1(-/-)/CCR-2(-/-)-mice. Solely, chemokine receptor 5 (CCR-5) increased early in both, but rose above wildtype levels at day 7 in MCP-1(-/-)/CCR-2(-/-)-animals, which might explain the higher number of activated microglial cells compared to control mice. Our study was, however, not powered to investigate infarct volumes. Further studies are needed to clarify whether these mechanisms of inflammatory cell recruitment might be essential for early infarct development and final infarct size and to evaluate potential therapeutic implications. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-06-01

    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. To compare the Danish dichotomous mammographic density classification system from 1991 to 2001 with the density BI-RADS classifications, in an attempt to validate the Danish classification system. The study sample consisted of 120 mammograms taken in Copenhagen in 1991-2001, which tested false positive, and which were in 2012 re-assessed and classified according to the BI-RADS classification system. We calculated inter-rater agreement between the Danish dichotomous mammographic classification as fatty or mixed/dense and the four-level BI-RADS classification by the linear weighted Kappa statistic. 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). The dichotomous mammographic density classification system utilized in early years of Copenhagen's mammographic screening program (1991-2001) agreed well with the BI-RADS density classification system.

  19. A case-control association study between Obsessive-Compulsive Disorder (OCD and the MCP-1 -2518G/A polymorphism in a Chinese sample Estudo de associação de casos-controle entre Transtorno Obsessivo-Compulsivo (TOC e polimorfismo MCP-1 -2518G/A em uma coorte chinesa

    Directory of Open Access Journals (Sweden)

    Xinhua Zhang

    2012-12-01

    Full Text Available OBJECTIVE: To investigate the association between Obsessive-Compulsive Disorder (OCD and a functional polymorphism of MCP-1 in the Chinese Han population. METHOD: We genotyped and performed a case-control association analysis of the MCP-1 -2518G/A polymorphism in 200 OCD patients and 294 healthy control subjects. RESULTS: There was no significant difference in MCP-1 -2518G/A genotypic and allelic frequencies between OCD cases and controls (x² = 1.123, df = 2, P = 0.57 by genotype; x² = 0.802, df = 1, P = 0.37 by allele. CONCLUSIONS: Our results indicated that MCP-1 -2518G/A may not play a major role in the genetic predisposition of the Chinese Han population to OCD. However, further studies using a larger number of subjects are required to obtain a clear conclusion.OBJETIVO: Investigar a relação entre Transtorno Obsessivo-Compusilvo (TOC e um polimorfismo funcional de MCP-1 na população chinesa de etnia Han. MÉTODOS: Determinamos os genótipos e realizamos uma análise de associações de casos-controle de polimorfismo MCP-1 -2518G/A em 200 indivíduos com TOC e 294 indivíduos saudáveis (controle. RESULTADOS: Não houve diferença significativa no genótipo MCP-1 -2518G/A e nas frequências alélicas entre casos de TOC e controles (x² = 1,123, df = 2, P = 0,57 por genotipo; x² = 0,802, df = 1, P = 0,37 por alelo. CONCLUSÕES: Nossos resultados indicaram que MCP-1 -2518G/A pode não ter grande participação na predisposição genética da etnia Han no que diz respeito ao TOC. Contudo, novos estudos com um maior número de indivíduos são necessários para uma conclusão mais clara.

  20. Qualidade pós-colheita de quivi 'Hayward' tratado com 1-MCP e armazenado sob diferentes atmosferas

    Directory of Open Access Journals (Sweden)

    Marcelo José Vieira

    2012-06-01

    Full Text Available Este trabalho teve por objetivo avaliar o efeito do 1-MCP sobre o amadurecimento e a qualidade pós-colheita de quivi 'Hayward' armazenado sob diferentes atmosferas. Foram conduzidos dois experimentos, com frutos colhidos em pomar comercial localizado em Fraiburgo-SC. No experimento 1, os frutos foram tratados com três doses de 1-MCP (0,0; 0,5 ou 1,0 µL L-1 e armazenados sob atmosfera controlada (AC, contendo 2,0kPa de O2 + 4,5kPa de CO2, a 0ºC ± 0,5ºC, 92 ± 3% UR, e com <40 ηL L-1 de etileno no ambiente, durante 90 e 120 dias, mais sete dias de vida de prateleira a 23ºC. No experimento 2, os frutos foram tratados com 0,0 ou 0,7 µL L-1 de 1-MCP e armazenados sob atmosfera ambiente (AA, contendo 21 kPa de O2 + 0,03 kPa de CO2, a 0 ± 0,5ºC, 90 ± 3% UR, e com 200 a 250 ηL L-1 de etileno no ambiente, durante 30, 60, 90 e 120 dias, mais um e sete dias de vida de prateleira a 23ºC ou AC (contendo 2,0 kPa de O2 + 4,5 kPa de CO2, a 0ºC ± 0,5ºC, 92 ± 3% UR, e com <40 ηL L-1 de etileno no ambiente, durante 60, 90, 120 e 150 dias, mais um e sete dias de vida de prateleira a 23ºC. Os benefícios do tratamento com 1-MCP sobre a conservação da qualidade foram observados tanto para frutos armazenados sob AA quanto sob AC. No experimento 1, não houve diferença entre as doses de 1-MCP de 0,5 e 1,0 µL L-1 sobre o controle do amadurecimento e manutenção da qualidade dos frutos armazenados em AC. No experimento 2, o tratamento com 1-MCP retardou o aumento na taxa de produção de etileno após remoção de câmara fria. A redução da taxa de produção de etileno nos frutos tratados com 1-MCP foi associada ao aumento na conservação da firmeza da polpa sob AC e AA, e redução na incidência de pericarpo translúcido sob AA. O potencial de armazenamento foi aumentado pelo tratamento com 1-MCP em aproximadamente 60 e 30 dias, nos frutos armazenados sob AA e AC, respectivamente.

  1. Interactions among Trypanosoma brucei RAD51 paralogues in DNA repair and antigenic variation

    Science.gov (United States)

    Dobson, Rachel; Stockdale, Christopher; Lapsley, Craig; Wilkes, Jonathan; McCulloch, Richard

    2011-01-01

    Homologous recombination in Trypanosoma brucei is used for moving variant surface glycoprotein (VSG) genes into expression sites during immune evasion by antigenic variation. A major route for such VSG switching is gene conversion reactions in which RAD51, a universally conserved recombinase, catalyses homology-directed strand exchange. In any eukaryote, RAD51-directed strand exchange in vivo is mediated by further factors, including RAD51-related proteins termed Rad51 paralogues. These appear to be ubiquitously conserved, although their detailed roles in recombination remain unclear. In T. brucei, four putative RAD51 paralogue genes have been identified by sequence homology. Here we show that all four RAD51 paralogues act in DNA repair, recombination and RAD51 subnuclear dynamics, though not equivalently, while mutation of only one RAD51 paralogue gene significantly impedes VSG switching. We also show that the T. brucei RAD51 paralogues interact, and that the complexes they form may explain the distinct phenotypes of the mutants as well as observed expression interdependency. Finally, we document the Rad51 paralogues that are encoded by a wide range of protists, demonstrating that the Rad51 paralogue repertoire in T. brucei is unusually large among microbial eukaryotes and that one member of the protein family corresponds with a key, conserved eukaryotic Rad51 paralogue. PMID:21615552

  2. Prolonged exposure to particulate chromate inhibits RAD51 nuclear import mediator proteins.

    Science.gov (United States)

    Browning, Cynthia L; Wise, John Pierce

    2017-09-15

    Particulate hexavalent chromium (Cr(VI)) is a human lung carcinogen and a human health concern. The induction of structural chromosome instability is considered to be a driving mechanism of Cr(VI)-induced carcinogenesis. Homologous recombination repair protects against Cr(VI)-induced chromosome damage, due to its highly accurate repair of Cr(VI)-induced DNA double strand breaks. However, recent studies demonstrate Cr(VI) inhibits homologous recombination repair through the misregulation of RAD51. RAD51 is an essential protein in HR repair that facilitates the search for a homologous sequence. Recent studies show prolonged Cr(VI) exposure prevents proper RAD51 subcellular localization, causing it to accumulate in the cytoplasm. Since nuclear import of RAD51 is crucial to its function, this study investigated the effect of Cr(VI) on the RAD51 nuclear import mediators, RAD51C and BRCA2. We show acute (24h) Cr(VI) exposure induces the proper localization of RAD51C and BRCA2. In contrast, prolonged (120h) exposure increased the cytoplasmic localization of both proteins, although RAD51C localization was more severely impaired. These results correlate temporally with the previously reported Cr(VI)-induced RAD51 cytoplasmic accumulation. In addition, we found Cr(VI) does not inhibit interaction between RAD51 and its nuclear import mediators. Altogether, our results suggest prolonged Cr(VI) exposure inhibits the nuclear import of RAD51C, and to a lesser extent, BRCA2, which results in the cytoplasmic accumulation of RAD51. Cr(VI)-induced inhibition of nuclear import may play a key role in its carcinogenic mechanism since the nuclear import of many tumor suppressor proteins and DNA repair proteins is crucial to their function. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. RAD51B in Familial Breast Cancer.

    Directory of Open Access Journals (Sweden)

    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.

  4. RAD51B in Familial Breast Cancer

    Science.gov (United States)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    Lehmann, P.H.; El-Bassioni, A.A.

    1975-01-01

    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

  7. Changes in quality and biochemical parameters in 'Idared' apples during prolonged shelf life and 1-MCP treatment.

    Science.gov (United States)

    Bizjak, Jan; Slatnar, Ana; Stampar, Franci; Veberic, Robert

    2012-12-01

    In this study, changes in quality and various biochemical parameters of 'Idared' apples during prolonged shelf life period after ultra-low oxygen (ULO) storage were investigated. Additionally, the impact of the postharvest application of 1-methylcyclopropene (1-MCP) on different parameters was evaluated. After the harvest, apples were stored in the ULO storage for 6 months and then exposed to room temperature. Fruit firmness, peel color, and changes in sugars, organic acids and phenolics were monitored during the 3 weeks of shelf life. Malic acid, sugars and firmness decreased at room temperature. However, the color of the apples remained unchanged. The level of citric and ascorbic acid remained constant. Levels of phenolics in the peel increased significantly, whereas remained constant in the pulp of apples. 1-MCP treatment resulted in higher amounts of fructose and glucose, malic acid and greater firmness of apples. However, 1-MCP did not influence the phenolic content, ascorbic acid or color. The results obtained indicate that the content of different health-promoting compounds of apples does not change dramatically at room temperature. At the same time these results suggest that 1-MCP could be useful for maintaining certain quality and biochemical parameters and might extend the shelf life of apples.

  8. Protein dynamics of human RPA and RAD51 on ssDNA during assembly and disassembly of the RAD51 filament.

    Science.gov (United States)

    Ma, Chu Jian; Gibb, Bryan; Kwon, YoungHo; Sung, Patrick; Greene, Eric C

    2017-01-25

    Homologous recombination (HR) is a crucial pathway for double-stranded DNA break (DSB) repair. During the early stages of HR, the newly generated DSB ends are processed to yield long single-stranded DNA (ssDNA) overhangs, which are quickly bound by replication protein A (RPA). RPA is then replaced by the DNA recombinase Rad51, which forms extended helical filaments on the ssDNA. The resulting nucleoprotein filament, known as the presynaptic complex, is responsible for pairing the ssDNA with homologous double-stranded DNA (dsDNA), which serves as the template to guide DSB repair. Here, we use single-molecule imaging to visualize the interplay between human RPA (hRPA) and human RAD51 during presynaptic complex assembly and disassembly. We demonstrate that ssDNA-bound hRPA can undergo facilitated exchange, enabling hRPA to undergo rapid exchange between free and ssDNA-bound states only when free hRPA is present in solution. Our results also indicate that the presence of free hRPA inhibits RAD51 filament nucleation, but has a lesser impact upon filament elongation. This finding suggests that hRPA exerts important regulatory influence over RAD51 and may in turn affect the properties of the assembled RAD51 filament. These experiments provide an important basis for further investigations into the regulation of human presynaptic complex assembly. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment.

    Science.gov (United States)

    Eyboulet, Fanny; Cibot, Camille; Eychenne, Thomas; Neil, Helen; Alibert, Olivier; Werner, Michel; Soutourina, Julie

    2013-12-01

    Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with DNA repair. We identified a functional contact between the Med17 Mediator subunit and Rad2/XPG, the 3' endonuclease involved in nucleotide excision DNA repair. Genome-wide location analyses revealed that Rad2 is associated with RNA polymerase II (Pol II)- and Pol III-transcribed genes and telomeric regions in the absence of exogenous genotoxic stress. Rad2 occupancy of Pol II-transcribed genes is transcription-dependent. Genome-wide Rad2 occupancy of class II gene promoters is well correlated with that of Mediator. Furthermore, UV sensitivity of med17 mutants is correlated with reduced Rad2 occupancy of class II genes and concomitant decrease of Mediator interaction with Rad2 protein. Our results suggest that Mediator is involved in DNA repair by facilitating Rad2 recruitment to transcribed genes.

  10. Liquid and solid rad waste treatment in advanced nuclear power plants. Application to the SBWR design

    International Nuclear Information System (INIS)

    Tielas Reina, M.; Asuar Alonso, O.

    1994-01-01

    Rad waste treatment requirements for the new generation of American advanced passive and evolutionary power plants are listed in the URD (Utility Requirements Document) of the EPRI (Electrical Power Research Institute). These requirements focus on: - Minimization of shipped solid wastes - Minimization of liquid effluents - Simplification of design and operation, with emphasis not only on waste treatment system design but also on general plant design and operation These objectives are aimed at: - Reducing and segregating wastes at source - Minimizing chemical contamination of these wastes System design simplification is completed by providing free space in the building for the use of mobile plants, either for special services not considered in the basic design or to accommodate future technical advances. (Author)

  11. Differential expression and requirements for Schizosaccharomyces pombe RAD52 homologs in DNA repair and recombination

    OpenAIRE

    van den Bosch, Michael; Zonneveld, José B. M.; Vreeken, Kees; de Vries, Femke A. T.; Lohman, Paul H. M.; Pastink, Albert

    2002-01-01

    In fission yeast two RAD52 homologs have been identified, rad22A+ and rad22B+. Two-hybrid experiments and GST pull-down assays revealed physical interaction between Rad22A and Rad22B, which is dependent on the N-terminal regions. Interaction with Rhp51 is dependent on the C-terminal parts of either protein. Both Rad22A and Rad22B also interact with RPA. The expression of rad22B+ in mitotically dividing cells is very low in comparison with rad22A+ but is strongly enhanced after induction of me...

  12. Combined use of serum MCP-1/IL-10 ratio and uterine artery Doppler index significantly improves the prediction of preeclampsia.

    Science.gov (United States)

    Cui, Shihong; Gao, Yanan; Zhang, Linlin; Wang, Yuan; Zhang, Lindong; Liu, Pingping; Liu, Ling; Chen, Juan

    2017-10-01

    Monocyte chemotactic protein-1 (MCP-1, or CCL2) is a member of the chemokine subfamily involved in recruitment of monocytes in inflammatory tissues. IL-10 is a key regulator for maintaining the balance of anti-inflammatory and pro-inflammatory milieu at the feto-maternal interface. Doppler examination has been routinely performed for the monitoring and management of preeclampsia patients. This study evaluates the efficiency of these factors alone, or in combination, for the predication of preeclampsia. The serum levels of MCP-1 and IL-10 in 78 preeclampsia patients and 143 age-matched normal controls were measured. The Doppler ultrasonography was performed and Artery Pulsatility Index (PI) and Resistance Index (RI) were calculated for the same subjects. It was found that while the second-trimester serum MCP-1, IL-10, MCP-1/IL-10 ratio, PI, and RI showed some power in predicting preeclampsia, the combination of MCP-1/IL-10 and PI and RI accomplishes the highest efficiency, achieving an AUC of 0.973 (95% CI, 0.000-1.000, Ppreeclampsia. Future studies using a larger sample can be conducted to construct an algorithm capable of quantitative assessment on the risk of preeclampsia. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. CAD-RADS - a new clinical decision support tool for coronary computed tomography angiography.

    Science.gov (United States)

    Foldyna, Borek; Szilveszter, Bálint; Scholtz, Jan-Erik; Banerji, Dahlia; Maurovich-Horvat, Pál; Hoffmann, Udo

    2018-04-01

    Coronary computed tomography angiography (CTA) has been established as an accurate method to non-invasively assess coronary artery disease (CAD). The proposed 'Coronary Artery Disease Reporting and Data System' (CAD-RADS) may enable standardised reporting of the broad spectrum of coronary CTA findings related to the presence, extent and composition of coronary atherosclerosis. The CAD-RADS classification is a comprehensive tool for summarising findings on a per-patient-basis dependent on the highest-grade coronary artery lesion, ranging from CAD-RADS 0 (absence of CAD) to CAD-RADS 5 (total occlusion of a coronary artery). In addition, it provides suggestions for clinical management for each classification, including further testing and therapeutic options. Despite some limitations, CAD-RADS may facilitate improved communication between imagers and patient caregivers. As such, CAD-RADS may enable a more efficient use of coronary CTA leading to more accurate utilisation of invasive coronary angiograms. Furthermore, widespread use of CAD-RADS may facilitate registry-based research of diagnostic and prognostic aspects of CTA. • CAD-RADS is a tool for standardising coronary CTA reports. • CAD-RADS includes clinical treatment recommendations based on CTA findings. • CAD-RADS has the potential to reduce variability of CTA reports.

  14. MRI for the assessment of malignancy in BI-RADS 4 mammographic microcalcifications.

    Directory of Open Access Journals (Sweden)

    Barbara Bennani-Baiti

    Full Text Available Assess the performance of breast MRI to diagnose breast cancer in BI-RADS 4 microcalcifications detected by mammography.This retrospective, IRB-approved study included 248 consecutive contrast-enhanced breast MRI (1.5T, protocol in accordance with EUSOBI recommendations performed to further diagnose BI-RADS 4 microcalcifications detected at mammography during a 3-year period. Standard of reference had to be established by histopathology. Routine consensus reading results by two radiologists were dichotomized as positive or negative and compared with the reference standard (benign vs malignant to calculate diagnostic parameters.There were 107 malignant and 141 benign microcalcifications. Malignancy rates were 18.3% (23/126 BI-RADS 4a, 41.7% (25/60 BI-RADS 4b and 95% (59/62 BI-RADS 4c. There were 103 true-positive, 116 true-negative, 25 false-positive, and 4 false-negative (one invasive cancer, three DCIS; 2 BI-RADS 4c, 1 BI-RADS 4b on mammography breast MRI findings, effecting a sensitivity, specificity, PPV, and NPV of 96.3% (95%-CI 90.7-99.0%, 82.3% (95%-CI 75.0-88.2%, 80.5% (95%-CI 72.5-87.0% and 96.7% (95%-CI 91.7-99.1%, respectively.MRI is an accurate tool to further diagnose BI-RADS 4a and 4b microcalcifications and may be helpful to avoid unnecessary biopsies in BI-RADS 4a and 4b lesions. BI-RADS 4c microcalcifications should be biopsied irrespective of MRI findings.

  15. RAD52 Facilitates Mitotic DNA Synthesis Following Replication Stress

    DEFF Research Database (Denmark)

    Bhowmick, Rahul; Minocherhomji, Sheroy; Hickson, Ian D

    2016-01-01

    Homologous recombination (HR) is necessary to counteract DNA replication stress. Common fragile site (CFS) loci are particularly sensitive to replication stress and undergo pathological rearrangements in tumors. At these loci, replication stress frequently activates DNA repair synthesis in mitosis...... replication stress at CFS loci during S-phase. In contrast, MiDAS is RAD52 dependent, and RAD52 is required for the timely recruitment of MUS81 and POLD3 to CFSs in early mitosis. Our results provide further mechanistic insight into MiDAS and define a specific function for human RAD52. Furthermore, selective...

  16. Nucleotide sequence, transcript mapping, and regulation of the RAD2 gene of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Madura, K.; Prakash, S.

    1986-01-01

    The authors determined the nucleotide sequence, mapped the 5' and 3' nRNA termini, and examined the regulation of the RAD2 gene of Saccharomyces cerevisiae. A long open reading frame within the RAD2 transcribed region encodes a protein of 1031 amino acids with a calculated molecular weight of 117,847. A disruption of the RAD2 gene that deletes the 78 carboxyl terminal codons results in loss of RAD2 function. The 5' ends of RAD2 mRNA show considerable heterogeneity, mapping 5 to 62 nucleotides upstream of the first ATG codon of the long RAD2 open reading frame. The longest RAD2 transcripts also contain a short open reading frame of 37 codons that precedes and overlaps the 5' end of the long RAD2 open reading frame. The RAD2 3' nRNA end maps 171 nucleotides downstream of the TAA termination codon and 20 nucleotides downstream from a 12-base-pair inverted repeat that might function in transcript termination. Northern blot analysis showed a ninefold increase in steady-state levels of RAD2 mRNA after treatment of yeast cells with UV light. The 5' flanking region of the RAD2 gene contains several direct and inverted repeats and a 44-nuclotide-long purine-rich tract. The sequence T G G A G G C A T T A A found at position - 167 to -156 in the RAD2 gene is similar to at sequence present in the 5' flanking regions of the RAD7 and RAD10 genes

  17. Antifungal activity of 1-methylcyclopropene (1-MCP) against anthracnose (Colletotrichum gloeosporioides) in postharvest mango fruit and its possible mechanisms of action.

    Science.gov (United States)

    Xu, Xiangbin; Lei, Huanhuan; Ma, Xiuyan; Lai, Tongfei; Song, Hongmiao; Shi, Xuequn; Li, Jiangkuo

    2017-01-16

    Anthracnose caused by Colletotrichum gloeosporioides is one of the most important postharvest diseases in mango fruit, often causing huge economic losses. In this study, the effect of 1-methylcyclopropene (1-MCP) against anthracnose in postharvest mango fruit and the mechanisms involved were investigated. 1-MCP induced reactive oxygen species (ROS) generation, damaged the mitochondria and destroyed the integrity of plasma membrane of spores of C. gloeosporioides, significantly suppressing spore germination and mycelial growth of C. gloeosporioides. 1-MCP also decreased the decay incidence and lesion expansion of mango fruit caused by C. gloeosporioides. For the first time this study demonstrated that 1-MCP suppressed anthracnose of postharvest mango fruit by directly inhibiting spore germination and mycelial growth of C. gloeosporioides, thus providing a promising strategy for disease control. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. RADTRAN 6/RadCat 6 user guide.

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Localization of monocyte chemotactic and activating factor (MCAF/MCP-1) in psoriasis

    DEFF Research Database (Denmark)

    Deleuran, M; Buhl, L; Ellingsen, T

    1996-01-01

    in the epidermal pustules in pustular psoriasis. In normals positive staining was observed in all the layers of the epidermis and in a few perivascular cells and blood vessels in the dermis. Where present in normal and diseased skin, eccrine ducts of sweat glands and sebaceous glands stained positive for MCAF......The monocyte chemotactic protein-1 (MCAF) also termed MCP-1, a strong chemotactic factor towards monocytes, is produced by several cell types present in the skin. The in situ presence of MCAF/MCP-1 protein in the skin has, however, not yet been established. Using immunohistochemical techniques we...... have investigated the distribution of MCAF in skin from patients with different types of psoriasis and normal healthy volunteers. We report the novel finding that psoriasis has strong positive immunostaining for MCAF located to all the layers of the epidermis, except the stratum granulosum, in pustular...

  20. Aumento da expressão do MCP-1 coroidal e escleral em modelo experimental de hipercolesterolemia

    Directory of Open Access Journals (Sweden)

    Rogil José de Almeida Torres

    2012-02-01

    Full Text Available OBJETIVO: O objetivo deste trabalho é demonstrar experimentalmente que a dieta rica em colesterol provoca aumento da expressão da MCP-1 na coroide e esclera. MÉTODO: Coelhos New Zealand foram organizados em dois grupos: GN (grupo dieta normal, composto por 8 coelhos (8 olhos, recebeu ração padrão para coelhos, durante 4 semanas; GH (grupo hipercolesterolêmico, composto por 13 coelhos (13 olhos, recebeu dieta rica em colesterol a 1% por 8 semanas. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 8ª semana para o GH e 4ª semana para o GN foi realizada a eutanásia dos animais e os olhos foram submetidos à análise imuno-histoquímica com o anticorpo anti-MCP-1. RESULTADOS: A dieta provocou significativo aumento do colesterol total e triglicerídeos do GH em relação ao GN (p<0,001. Houve significativo aumento da expressão da MCP-1 na coroide e esclera dos animais do GH em relação ao GN (p<0,001. CONCLUSÃO: Este estudo demonstrou que a dieta hipercolesterolêmica em coelhos induz ao aumento da expressão do MCP-1 na coroide e esclera.

  1. BI-RADS: Use in the French radiologic community

    International Nuclear Information System (INIS)

    Stines, Joseph

    2007-01-01

    In the United States, BI-RADS TM (Breast Imaging Reporting and Data System) has been set up as a quality assurance system for better communication between professionals and for the follow-up of breast screening programs. It has become a reference in the field of mammographic imaging and has been adopted by several countries throughout the world. It has been translated in French. The aim of this article is to discuss the difficulties in using it in the French radiologic communities. There are few problems with vocabulary excepted for microcalcifications. BI-RADS TM includes a guidance chapter giving some recommendations for using properly the lexicon. Classification of normal breast remains of concern, as it is difficult to evaluate precisely the content of fat and as the final image is also dependant of technical factors. The main difficulties are related to final classification in BI-RADS TM categories as the lexicon does not explicit which mammographic features should be included in the categories from three to five. In France, a table concerning the classification of mammographic abnormalities has been established by the HAS (former ANAES) which represents the highest scientific health authority in France. There are no major problems for using the BI-RADS TM for US and MRI. BI-RADS TM is suitable for different categories of women and for male and training has an important impact on acceptance and proper use of the lexicon

  2. Positive Predictive Value of BI-RADS Categorization in an Asian Population

    Directory of Open Access Journals (Sweden)

    Yah-Yuen Tan

    2004-07-01

    Full Text Available The Breast Imaging Reporting And Data System (BI-RADS categorization of mammograms is useful in estimating the risk of malignancy, thereby guiding management decisions. However, in Asian women, in whom breast density is increased, the sensitivity of mammography is correspondingly lower. We sought to determine the positive predictive value of BI-RADS categorization for malignancy in our Asian population and, hence, its value in helping us to choose between the various modalities for breast biopsy. We retrospectively reviewed all patients with occult breast lesions detected on mammography or ultrasound who underwent needle-localization open breast biopsy (NLOB in our institution over a 6-year period. There were 470 biopsies in 427 patients; 16% of lesions were malignant. The positive predictive value of BI-RADS 4 and 5 lesions for cancer was 0.27 and 0.84, respectively. While most BI-RADS 5 mass lesions were invasive cancers, the majority of calcifications in this category were in situ carcinomas. We conclude that BI-RADS remains useful in aiding decision-making for biopsy in our Asian population. Based on positive predictive values, we recommend percutaneous breast biopsy for initial evaluation of lesions categorized as BI-RADS 4 or less. For BI-RADS 5 lesions with microcalcifications, open surgical biopsy as a diagnostic and therapeutic procedure may be more appropriate. In the case of a BI-RADS 5 lesion associated with a mass, initial percutaneous biopsy may be useful for diagnosis, followed by a planned single-stage surgical procedure as necessary.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Two micron pore size MCP-based image intensifiers

    Science.gov (United States)

    Glesener, John; Estrera, Joseph

    2010-02-01

    Image intensifiers (I2) have many advantages as detectors. They offer single photon sensitivity in an imaging format, they're light in weight and analog I2 systems can operate for hours on a single AA battery. Their light output is such as to exploit the peak in color sensitivity of the human eye. Until recent developments in CMOS sensors, they also were one of the highest resolution sensors available. The closest all solid state solution, the Texas Instruments Impactron chip, comes in a 1 megapixel format. Depending on the level of integration, an Impactron based system can consume 20 to 40 watts in a system configuration. In further investing in I2 technology, L-3 EOS determined that increasing I2 resolution merited a high priority. Increased I2 resolution offers the system user two desirable options: 1) increased detection and identification ranges while maintaining field-of-view (FOV) or 2) increasing FOV while maintaining the original system resolution. One of the areas where an investment in resolution is being made is in the microchannel plate (MCP). Incorporation of a 2 micron MCP into an image tube has the potential of increasing the system resolution of currently fielded systems. Both inverting and non-inverting configurations are being evaluated. Inverting tubes are being characterized in night vision goggle (NVG) and sights. The non-inverting 2 micron tube is being characterized for high resolution I2CMOS camera applications. Preliminary measurements show an increase in the MTF over a standard 5 micron pore size, 6 micron pitch plate. Current results will be presented.

  5. Regulation of homologous recombination repair protein Rad51 by Ku70

    International Nuclear Information System (INIS)

    Du Liqing; Liu Qiang; Wang Yan; Xu Chang; Cao Jia; Fu Yue; Chen Fenghua; Fan Feiyue

    2013-01-01

    Objective: To explore the regulative effect of non-homologous end joining (NHEJ)protein Ku70 on homologous recombination repair protein Rad51, and to investigate the synergistic mechanism of homologous recombination repair in combination with NHEJ. Methods: Observed Rad51 protein expression after transfect Ku70 small interfering RNA or Ku70 plasmid DNA into tumor cells using Western blot. Results: Expression of Rad51 was obviously reduced after pretreated with Ku70 small interfering RNA. And with the increasing expression of Ku70 protein after transfection of Ku70 plasmid DNA PGCsi3.0-hKu70 into tumor cell lines, the Rad51 protein expression was increased. Conclusion: Ku70 protein has regulating effect on gene expression of Rad51, and it might participate in the collaboration between homologous recombination repair and NHEJ. (authors)

  6. Interdependence of the rad50 hook and globular domain functions.

    Science.gov (United States)

    Hohl, Marcel; Kochańczyk, Tomasz; Tous, Cristina; Aguilera, Andrés; Krężel, Artur; Petrini, John H J

    2015-02-05

    Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end joining, and DNA double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular ATPase domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Differential hRad17 expression by histologic subtype of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Young Jennifer L

    2011-03-01

    Full Text Available Abstract Background In the search for unique ovarian cancer biomarkers, ovarian specific cDNA microarray analysis identified hRad17, a cell cycle checkpoint protein, as over-expressed in ovarian cancer. The aim of this study was to validate this expression. Methods Immunohistochemistry was performed on 72 serous, 19 endometrioid, 10 clear cell, and 6 mucinous ovarian cancers, 9 benign ovarian tumors, and 6 normal ovarian tissue sections using an anti-hRad17 antibody. Western blot analysis and quantitative PCR were performed using cell lysates and total RNA prepared from 17 ovarian cancer cell lines and 6 normal ovarian epithelial cell cultures (HOSE. Results Antibody staining confirmed upregulation of hRad17 in 49.5% of ovarian cancer cases. Immunohistochemistry demonstrated that only 42% of serous and 47% of endometrioid subtypes showed overexpression compared to 80% of clear cell and 100% of mucinous cancers. Western blot confirmed overexpression of hRad17 in cancer cell lines compared to HOSE. Quantitative PCR demonstrated an upregulation of hRad17 RNA by 1.5-7 fold. hRad17 RNA expression differed by subtype. Conclusions hRad17 is over-expressed in ovarian cancer. This over-expression varies by subtype suggesting a role in the pathogenesis of these types. Functional studies are needed to determine the potential role of this protein in ovarian cancer.

  8. Correlation of serum MCP-1 and VE-cadherin levels with neural function and carotid atherosclerosis in patients with acute cerebral infarction

    Directory of Open Access Journals (Sweden)

    Yan-Bing Xi

    2017-05-01

    Full Text Available Objective: To study the correlation of serum monocyte chemoattractant protein-1 (MCP-1 and vascular endothelial cadherin (VE-cadherin levels with neural function and carotid atherosclerosis in patients with acute cerebral infarction. Methods: A total of 78 patients who were diagnosed with acute cerebral infarction in our hospital between May 2013 and August 2016 were selected as pathological group, and 80 healthy volunteers who received physical examination in our hospital during the same period were selected as control group. Serum was collected to determine the levels of MCP-1, VE-cadherin, nerve injury molecules, inflammatory mediators, proteases and their hydrolysate. Results: Serum MCP-1, VE-cadherin, NGB, NSE, S100β, HMGB-1, sCD40L, YKL-40, visfatin, CatK, MMP9 and ICTP levels of pathological group were significantly higher than those of control group; serum MCP-1 and VE-cadherin levels of pathological group were positively correlated with NGB, NSE, S100β, HMGB-1, sCD40L, YKL-40, visfatin, CatK, MMP9 and ICTP levels. Conclusion: Serum MCP-1 and VE-cadherin levels abnormally increase in patients with acute cerebral infarction, and are closely related to the nerve injury and atherosclerosis process.

  9. Increased interreader agreement in diagnosis of hepatocellular carcinoma using an adapted LI-RADS algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Anton S., E-mail: anton.becker@usz.ch; Barth, Borna K.; Marquez, Paulo H.; Donati, Olivio F.; Ulbrich, Erika J.; Karlo, Christoph; Reiner, Cäcilia S.; Fischer, Michael A.

    2017-01-15

    Purpose: To evaluate a simplified Liver Imaging Reporting and Data System (LI-RADS) algorithm to improve interreader agreement while maintaining diagnostic performance for HCC. Materials and methods: MRI scans of 84 cirrhotic patients with 104 distinct liver observations were retrospectively selected to equivocally match each of the LI-RADS grades (LR1-5) using histopathology and imaging follow up as standard of reference. Four independent radiologists categorized all observations as benign (LR1-2) or potentially malignant (LR3-5) and determined LI-RADS based imaging features including observation size, arterial phase hyperenhancement, washout, capsule appearance and threshold growth for LR3-5 observations and timed their readouts. LR3-5 observations were categorized according to the LI-RADS v2014 algorithm and according to a modified LI-RADS (mLI-RADS) version. Diagnostic performance and Interreader agreement were determined for LI-RADS and mLI-RADS using receiver operating characteristics (ROC) and Fleiss’ and Cohen’s Kappa analysis respectively. Results: ROC analysis revealed equal diagnostic performance for LI-RADS and mLI-RADS (area under the ROC curve = 0.91). Interreader agreement was higher using mLI-RADS as compared to current LI-RADS showing an improved overall (κ = 0.53 ± 0.04 vs. 0.45 ± 0.04), and pair-wise agreement between most readers (κ range 0.44-0.62 vs. 0.35-0.60) at a reduced median evaluation time (51 vs. 62 s per observation, p < 0.0001). Conclusion: Focusing on observation size and washout criteria using a modified, stepwise LI-RADS decision tree for LR3-5 observations results in higher interobserver reliability and faster categorization while maintaining diagnostic accuracy.

  10. Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination.

    NARCIS (Netherlands)

    J. Essers (Jeroen); R.W. Hendriks (Rudi); S.M.A. Swagemakers (Sigrid); C. Troelstra (Christine); J. de Wit (Jan); D. Bootsma (Dirk); J.H.J. Hoeijmakers (Jan); R. Kanaar (Roland)

    1997-01-01

    textabstractDouble-strand DNA break (DSB) repair by homologous recombination occurs through the RAD52 pathway in Saccharomyces cerevisiae. Its biological importance is underscored by the conservation of many RAD52 pathway genes, including RAD54, from fungi to humans. We have analyzed the phenotype

  11. Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines

    Science.gov (United States)

    Sulniute, Rima; Palmqvist, Py; Majster, Mirjam; Holm, Cecilia Koskinen; Zwicker, Stephanie; Clark, Reuben; Önell, Sebastian; Johansson, Ingegerd; Lerner, Ulf H.; Lundberg, Pernilla

    2015-01-01

    Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-κΒ pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in

  12. Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2

    Directory of Open Access Journals (Sweden)

    Charo Israel F

    2004-09-01

    Full Text Available Abstract Background Asthma is characterized by type 2 T-helper cell (Th2 inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2 and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma. Methods To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response. Results We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines. Conclusion We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2.

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

    International Nuclear Information System (INIS)

    Du, Liqin; Luo, Yu

    2012-01-01

    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

  14. Characterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes.

    Science.gov (United States)

    Gayarre, Javier; Martín-Gimeno, Paloma; Osorio, Ana; Paumard, Beatriz; Barroso, Alicia; Fernández, Victoria; de la Hoya, Miguel; Rojo, Alejandro; Caldés, Trinidad; Palacios, José; Urioste, Miguel; Benítez, Javier; García, María J

    2017-09-26

    Despite a high prevalence of deleterious missense variants, most studies of RAD51C ovarian cancer susceptibility gene only provide in silico pathogenicity predictions of missense changes. We identified a novel deleterious RAD51C missense variant (p.Arg312Trp) in a high-risk family, and propose a criteria to prioritise RAD51C missense changes qualifying for functional analysis. To evaluate pathogenicity of p.Arg312Trp variant we used sequence homology, loss of heterozygosity (LOH) and segregation analysis, and a comprehensive functional characterisation. To define a functional-analysis prioritisation criteria, we used outputs for the known functionally confirmed deleterious and benign RAD51C missense changes from nine pathogenicity prediction algorithms. The p.Arg312Trp variant failed to correct mitomycin and olaparib hypersensitivity and to complement abnormal RAD51C foci formation according to functional assays, which altogether with LOH and segregation data demonstrated deleteriousness. Prioritisation criteria were based on the number of predictors providing a deleterious output, with a minimum of 5 to qualify for testing and a PredictProtein score greater than 33 to assign high-priority indication. Our study points to a non-negligible number of RAD51C missense variants likely to impair protein function, provides a guideline to prioritise and encourage their selection for functional analysis and anticipates that reference laboratories should have available resources to conduct such assays.

  15. Concentrações de IL-6, TNF-α e MCP-1 em crianças com excesso de massa corporal

    Directory of Open Access Journals (Sweden)

    Juliano Magalhães Guedes

    2015-08-01

    Full Text Available O objetivo desta revisão sistemática foi verificar a relação das concentrações de IL-6, TNF-α e MCP-1 em crianças com excesso de massa corporal. As bases de dados investigadas PUBMED, SciELO, LILACS e Periódico Capes foram consultadas retrospectivamente para os últimos seis anos (2009 a 2014 utilizando combinações de palavras chaves como inflamação, IL-6, TNF-α, MCP-1 combinadas com crianças e escolares. Foram analisados 21 artigos. Foi encontrado associação entre sobrepeso/obesidade com IL-6, TNF-α e MCP-1 em 73,3% (11/15, 80% (12/15 e 60% (3/5 dos estudos que analisaram tais marcadores, respectivamente. Crianças com excesso de massa corporal possuem concentrações elevadas de IL-6, TNF-α e MCP-1 resultando em inflamação sistêmica crônica e aumentando o risco de desenvolvimento de outras doenças cardiovasculares. 

  16. γ radiation dosimetry in Mega rad range using sugar solution

    International Nuclear Information System (INIS)

    Venkataramani, R.; Mehta, S.K.; Soman, S.D.

    1976-01-01

    The formation of malonaldehyde under γ irradiation of solid sucrose and aqueous sucrose, fructose and arabinose solutions has been studied in the Mega rad range. Malonaldehyde (MA) concentration was estimated spectrophotometrically after complexing with 2-thio-barbituric acid. The effect of free radical scavengers (KI and N 2 O) on the yield of MA was investigated. Of the systems studied a 5% aqueous sucrose solution gave a proportional response of MA formation with dose in 0.2 to 5 Mega rad range. A 5% aqueous solution of sucrose prepared from sucrose irradiated in solid state also gave a smooth response of MA yield with dose from 8 to 30 Mega rad. The aqueous and solid sucrose systems together can be conveniently used for dosimetry in the range of 0.2 30 Mega rad. (author)

  17. gamma. radiation dosimetry in Mega rad range using sugar solution

    Energy Technology Data Exchange (ETDEWEB)

    Venkataramani, R; Mehta, S K; Soman, S D [Bhabha Atomic Research Centre, Bombay (India). Health Physics Div.

    1976-09-01

    The formation of malonaldehyde under ..gamma.. irradiation of solid sucrose and aqueous sucrose, fructose and arabinose solutions has been studied in the Mega rad range. Malonaldehyde (MA) concentration was estimated spectrophotometrically after complexing with 2-thio-barbituric acid. The effect of free radical scavengers (KI and N/sub 2/O) on the yield of MA was investigated. Of the systems studied a 5% aqueous sucrose solution gave a proportional response of MA formation with dose in 0.2 to 5 Mega rad range. A 5% aqueous solution of sucrose prepared from sucrose irradiated in solid state also gave a smooth response of MA yield with dose from 8 to 30 Mega rad. The aqueous and solid sucrose systems together can be conveniently used for dosimetry in the range of 0.2 30 Mega rad.

  18. Pseudogenization of the MCP-2/CCL8 chemokine gene in European rabbit (genus Oryctolagus, but not in species of Cottontail rabbit (Sylvilagus and Hare (Lepus

    Directory of Open Access Journals (Sweden)

    van der Loo Wessel

    2012-08-01

    Full Text Available Abstract Background Recent studies in human have highlighted the importance of the monocyte chemotactic proteins (MCP in leukocyte trafficking and their effects in inflammatory processes, tumor progression, and HIV-1 infection. In European rabbit (Oryctolagus cuniculus one of the prime MCP targets, the chemokine receptor CCR5 underwent a unique structural alteration. Until now, no homologue of MCP-2/CCL8a, MCP-3/CCL7 or MCP-4/CCL13 genes have been reported for this species. This is interesting, because at least the first two genes are expressed in most, if not all, mammals studied, and appear to be implicated in a variety of important chemokine ligand-receptor interactions. By assessing the Rabbit Whole Genome Sequence (WGS data we have searched for orthologs of the mammalian genes of the MCP-Eotaxin cluster. Results We have localized the orthologs of these chemokine genes in the genome of European rabbit and compared them to those of leporid genera which do (i.e. Oryctolagus and Bunolagus or do not share the CCR5 alteration with European rabbit (i.e. Lepus and Sylvilagus. Of the Rabbit orthologs of the CCL8, CCL7, and CCL13 genes only the last two were potentially functional, although showing some structural anomalies at the protein level. The ortholog of MCP-2/CCL8 appeared to be pseudogenized by deleterious nucleotide substitutions affecting exon1 and exon2. By analyzing both genomic and cDNA products, these studies were extended to wild specimens of four genera of the Leporidae family: Oryctolagus, Bunolagus, Lepus, and Sylvilagus. It appeared that the anomalies of the MCP-3/CCL7 and MCP-4/CCL13 proteins are shared among the different species of leporids. In contrast, whereas MCP-2/CCL8 was pseudogenized in every studied specimen of the Oryctolagus - Bunolagus lineage, this gene was intact in species of the Lepus - Sylvilagus lineage, and was, at least in Lepus, correctly transcribed. Conclusion The biological function of a gene was often

  19. Characterization of new radiation-sensitive mutant, Escherichia coli K-12 radC102

    International Nuclear Information System (INIS)

    Felzenszwalb, I.; Sargentini, N.J.; Smith, K.C.

    1984-01-01

    A new radiation-sensitive mutant, radC, has been isolated. The radC gene is located at 81.0 min on the Escherichia coli K-12 linkage map. The radC mutation sensitized cells to uv radiation, but unlike most DNA repair mutations, sensitization to X rays was observed only for rich medium-grown cells. For cells grown in rich medium, the radC mutant was normal for γ radiation mutagenesis, but showed less uv-radiation mutagenesis than the wild-type strain; it showed normal amount of X- and uv-radiation-induced DNA degradation, and it wasapprox. =60% deficient in recombination ability. The radC strain was normal for host cell reactivation of γ and uv-irradiated bacteriophage the radC mutation did not sensitize a recA strain, but did sensitize a radA and a polA strain to X and uv radiation and a uvrA strain to uv radiation. Therefore, it is suggested that the radC gene product plays a role in the growth medium-dependent, recA gene-dependent repair of DNA single-strand breaks after X irradiation, and in postreplication repair after uv irradiation

  20. EFECTO DEL 1-METILCICLOPROPENO (1-MCP Y TRATAMIENTO HIDROTÉRMICO SOBRE LA FISIOLOGÍA Y CALIDAD DEL MANGO 'KEITT'

    Directory of Open Access Journals (Sweden)

    J. A. Osuna-García

    2007-01-01

    Full Text Available El objetivo del presente trabajo fue evaluar el efecto del 1-MCP (0 y 300 nl·litro-1 y diferentes niveles de tratamiento hidrotérmico (0, 52 °C por 5 min y 46 °C por 110 min sobre la fisiología y calidad de mango 'Keitt'. Se analizó velocidad de respiración, pérdida de peso, firmeza, color de pulpa, sólidos solubles totales y porcentaje de frutos enfermos. Se encontró que la efectividad del 1-MCP varió acorde al nivel de tratamiento hidrotérmico. En frutos sin hidrotérmico el 1-MCP disminuyó velocidad de respiración, no influyó en la pérdida de peso, mantuvo cuatro veces más la firmeza y retrasó el cambio de color de pulpa y el aumento de los sólidos solubles. Sin embargo, bajo tratamiento hidrotérmico por 5 min el 1-MCP incrementó velocidad de respiración, no influyó en la pérdida de peso, mantuvo dos veces más la firmeza de pulpa, retrasó el desarrollo del color de pulpa y mantuvo sin cambios los sólidos solubles. La efectividad del 1-MCP sobre firmeza y pérdida de peso fue significativamente afectada por el tratamiento hidrotérmico de 110 min, y no tuvo ningún efecto sobre el control de enfermedades, sin embargo, el tratamiento con agua caliente por 5 min redujo en más de 50 % la presencia de frutos enfermos. El 1-MCP en combinación con el tratamiento hidrotérmico de 5 min alargó en cinco días la vida de anaquel de los frutos y podría ser una alternativa viable en mercados que no requieren tratamiento hidrotérmico cuarentenario para el control de mosca de la fruta.

  1. Controlled atmosphere pO2 alters ripening dynamics of 1-MCP treated ‘d’Anjou’ pear (Pyrus communis L.) fruit

    Science.gov (United States)

    Ripening and development of physiological disorders and decay were assessed in ‘d’Anjou’ pear fruit following 1-methylcyclopropene (1-MCP) treatment and cold storage in air or controlled atmosphere (CA). Fruit were exposed after harvest to 0 or 12.6 µmol•L-1 1-MCP and then stored at 0.5 oC in air o...

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

    International Nuclear Information System (INIS)

    El Khoury, Mona; Lalonde, Lucie; David, Julie; Labelle, Maude; Mesurolle, Benoit; Trop, Isabelle

    2015-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. A uniform system for mammographic reporting BI-RADS

    International Nuclear Information System (INIS)

    Masroor, I.; Ahmad, M. N.; Sheikh, M. Y.

    2001-01-01

    Breast image reporting and data system (BI-RADS) is a new system of categorizing and reporting mammographs and mammographic findings recommended by American College of Radiology. The importance of BI-RADS and final assessment categories are discussed. The purpose is to introduce the above-mentioned mammographic reporting system so that it becomes a standard terminology among the medical personnel, involved in the diagnosis and management of breast diseases. (author)

  6. Recovery of deficient homologous recombination in Brca2-depleted mouse cells by wild-type Rad51 expression.

    Science.gov (United States)

    Lee, Shauna A; Roques, Céline; Magwood, Alissa C; Masson, Jean-Yves; Baker, Mark D

    2009-02-01

    The BRCA2 tumor suppressor is important in maintaining genomic stability. BRCA2 is proposed to control the availability, cellular localization and DNA binding activity of the central homologous recombination protein, RAD51, with loss of BRCA2 resulting in defective homologous recombination. Nevertheless, the roles of BRCA2 in regulating RAD51 and how other proteins implicated in RAD51 regulation, such as RAD52 and RAD54 function relative to BRCA2 is not known. In this study, we tested whether defective homologous recombination in Brca2-depleted mouse hybridoma cells could be rectified by expression of mouse Rad51 or the Rad51-interacting mouse proteins, Rad52 and Rad54. In the Brca2-depleted cells, defective homologous recombination can be restored by over-expression of wild-type mouse Rad51, but not mouse Rad52 or Rad54. Correction of the homologous recombination defect requires Rad51 ATPase activity. A sizeable fraction ( approximately 50%) of over-expressed wild-type Rad51 is nuclear localized. The restoration of homologous recombination in the presence of a low (i.e., non-functional) level of Brca2 by wild-type Rad51 over-expression is unexpected. We suggest that Rad51 may access the nuclear compartment in a Brca2-independent manner and when Rad51 is over-expressed, the normal requirement for Brca2 control over Rad51 function in homologous recombination is dispensable. Our studies support loss of Rad51 function as a critical underlying factor in the homologous recombination defect in the Brca2-depleted cells.

  7. RAD51 Is a Selective DNA Repair Target to Radiosensitize Glioma Stem Cells.

    Science.gov (United States)

    King, Harry O; Brend, Tim; Payne, Helen L; Wright, Alexander; Ward, Thomas A; Patel, Karan; Egnuni, Teklu; Stead, Lucy F; Patel, Anjana; Wurdak, Heiko; Short, Susan C

    2017-01-10

    Patients with glioblastoma die from local relapse despite surgery and high-dose radiotherapy. Resistance to radiotherapy is thought to be due to efficient DNA double-strand break (DSB) repair in stem-like cells able to survive DNA damage and repopulate the tumor. We used clinical samples and patient-derived glioblastoma stem cells (GSCs) to confirm that the DSB repair protein RAD51 is highly expressed in GSCs, which are reliant on RAD51-dependent DSB repair after radiation. RAD51 expression and RAD51 foci numbers fall when these cells move toward astrocytic differentiation. In GSCs, the small-molecule RAD51 inhibitors RI-1 and B02 prevent RAD51 focus formation, reduce DNA DSB repair, and cause significant radiosensitization. We further demonstrate that treatment with these agents combined with radiation promotes loss of stem cells defined by SOX2 expression. This indicates that RAD51-dependent repair represents an effective and specific target in GSCs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. OsRAD51C Is Essential for Double Strand Break Repair in Rice Meiosis

    Directory of Open Access Journals (Sweden)

    Ding eTang

    2014-05-01

    Full Text Available RAD51C is one of the RAD51 paralogs that plays an important role in DNA double-strand break repair by homologous recombination. Here, we identified and characterized OsRAD51C, the rice homolog of human RAD51C. The Osrad51c mutant plant is normal in vegetative growth but exhibits complete male and female sterility. Cytological investigation revealed that homologous pairing and synapsis were severely disrupted. Massive chromosome fragmentation occurred during metaphase I in Osrad51c meiocytes, and was fully suppressed by the CRC1 mutation. Immunofluorescence analysis showed that OsRAD51C localized onto the chromosomes from leptotene to early pachytene during prophase I, and that normal loading of OsRAD51C was dependent on OsREC8, PAIR2, and PAIR3. Additionally, ZEP1 did not localize properly in Osrad51c, indicating that OsRAD51C is required for synaptonemal complex assembly. Our study also provided evidence in support of a functional divergence in RAD51C among organisms.

  9. Extracting BI-RADS Features from Portuguese Clinical Texts.

    Science.gov (United States)

    Nassif, Houssam; Cunha, Filipe; Moreira, Inês C; Cruz-Correia, Ricardo; Sousa, Eliana; Page, David; Burnside, Elizabeth; Dutra, Inês

    2012-01-01

    In this work we build the first BI-RADS parser for Portuguese free texts, modeled after existing approaches to extract BI-RADS features from English medical records. Our concept finder uses a semantic grammar based on the BIRADS lexicon and on iterative transferred expert knowledge. We compare the performance of our algorithm to manual annotation by a specialist in mammography. Our results show that our parser's performance is comparable to the manual method.

  10. El radón: ¿riesgo para la salud?

    Directory of Open Access Journals (Sweden)

    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.

  11. Location of RAD51-like protein during meiotic prophase in Eimeria tenella.

    Science.gov (United States)

    Del Cacho, Emilio; Gallego, Margarita; Pagés, Marc; Barbero, José Luís; Monteagudo, Luís; Sánchez-Acedo, Caridad

    2011-05-31

    This study focuses on reporting events in Eimeria tenella oocysts from early to late prophase I in terms of RAD51 protein in association with the synaptonemal complex formed between homologous chromosomes. The aim of the study was the sequential localization of RAD51 protein, which is involved in the repair of double-strand breaks (DSBs) on the eimerian chromosomes as they synapse and desynapse. Structural Maintenance of Chromosome protein SMC3, which plays a role in synaptonemal complex formation, was labeled to identify initiation and progress of chromosome synapsis and desynapsis in parallel with the appearance and disappearance of RAD51 foci. Antibodies directed against RAD51 and cohesin subunit SMC3 proteins were labeled with either fluorescence or colloidal gold to visualize RAD51 protein foci and synaptonemal complexes. RAD51 protein localization during prophase I was studied on meiotic chromosomes spreads obtained from oocysts at different points in time after the start of sporulation. The present findings showed that foci detected with the antibody directed against RAD51 protein first appeared at the pre-leptotene stage before homologous chromosomes began pairing. Subsequently, the foci were detected in association with the lateral elements at the precise sites where synapsis were in progress. These findings lead us to suggest that in E. tenella, homologous chromosome pairing was a DSB-dependent mechanism and reinforced the participation of RAD51 protein in meiotic homology search, alignment and pairing of chromosomes. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Use of equimolar cysteine/ascorbic acids to recover MCP synthesized Ti(Mg) alloy

    CSIR Research Space (South Africa)

    Mushove, T

    2010-10-01

    Full Text Available Dissolution of waste by-products of mechanochemical processing (MCP) synthesis of Ti(Mg) alloy, from TiO2 and 15 wt.% excess Mg, was conducted in equimolar cysteine/ascorbic acids. The synthesized alloy is inherently mixed with MgO and other oxides...

  13. RAD21L, a novel cohesin subunit implicated in linking homologous chromosomes in mammalian meiosis.

    Science.gov (United States)

    Lee, Jibak; Hirano, Tatsuya

    2011-01-24

    Cohesins are multi-subunit protein complexes that regulate sister chromatid cohesion during mitosis and meiosis. Here we identified a novel kleisin subunit of cohesins, RAD21L, which is conserved among vertebrates. In mice, RAD21L is expressed exclusively in early meiosis: it apparently replaces RAD21 in premeiotic S phase, becomes detectable on the axial elements in leptotene, and stays on the axial/lateral elements until mid pachytene. RAD21L then disappears, and is replaced with RAD21. This behavior of RAD21L is unique and distinct from that of REC8, another meiosis-specific kleisin subunit. Remarkably, the disappearance of RAD21L at mid pachytene correlates with the completion of DNA double-strand break repair and the formation of crossovers as judged by colabeling with molecular markers, γ-H2AX, MSH4, and MLH1. RAD21L associates with SMC3, STAG3, and either SMC1α or SMC1β. Our results suggest that cohesin complexes containing RAD21L may be involved in synapsis initiation and crossover recombination between homologous chromosomes.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Radiomic modeling of BI-RADS density categories

    Science.gov (United States)

    Wei, Jun; Chan, Heang-Ping; Helvie, Mark A.; Roubidoux, Marilyn A.; Zhou, Chuan; Hadjiiski, Lubomir

    2017-03-01

    Screening mammography is the most effective and low-cost method to date for early cancer detection. Mammographic breast density has been shown to be highly correlated with breast cancer risk. We are developing a radiomic model for BI-RADS density categorization on digital mammography (FFDM) with a supervised machine learning approach. With IRB approval, we retrospectively collected 478 FFDMs from 478 women. As a gold standard, breast density was assessed by an MQSA radiologist based on BI-RADS categories. The raw FFDMs were used for computerized density assessment. The raw FFDM first underwent log-transform to approximate the x-ray sensitometric response, followed by multiscale processing to enhance the fibroglandular densities and parenchymal patterns. Three ROIs were automatically identified based on the keypoint distribution, where the keypoints were obtained as the extrema in the image Gaussian scale-space. A total of 73 features, including intensity and texture features that describe the density and the parenchymal pattern, were extracted from each breast. Our BI-RADS density estimator was constructed by using a random forest classifier. We used a 10-fold cross validation resampling approach to estimate the errors. With the random forest classifier, computerized density categories for 412 of the 478 cases agree with radiologist's assessment (weighted kappa = 0.93). The machine learning method with radiomic features as predictors demonstrated a high accuracy in classifying FFDMs into BI-RADS density categories. Further work is underway to improve our system performance as well as to perform an independent testing using a large unseen FFDM set.

  16. Manejo da podridão de melão pelo controle do amadurecimento através do 1-mcp, sob duas condições de armazenamento Melon rot management by ripening control whith 1-MCP treatment under two storage conditions

    Directory of Open Access Journals (Sweden)

    Daniel Terao

    2009-06-01

    Full Text Available Objetivou-se neste trabalho avaliar o efeito de 1-MCP (300 nL.L¹ nas alterações fisiológicas que ocorrem durante o amadurecimento do melão, tipo Orange cv. Orange Flesh e sua influência no controle da podridão causada por Fusarium pallidoroseum, em dois ambientes de armazenamento, sem refrigeração (29 ± 1 ºC e umidade relativa de 65 ± 2 % e refrigerado (10 ± 2 ºC e umidade relativa 90 ± 3 % durante 15 dias e nove dias adicionais em condição ambiente. Avaliouse a atividade respiratória, produção de etileno, perda de matéria fresca, cor da casca e da polpa, firmeza da polpa, pH, acidez total titulável, sólidos solúveis totais, açúcares solúveis totais e severidade da doença. O delineamento foi inteiramente casualizado em arranjo fatorial com quatro repetições/tratamento. Frutos tratados com 1-MCP, armazenados em ambiente sem refrigeração, mantiveram firmeza da polpa praticamente inalterada até o 15º dia e quando em refrigeração mantiveram-se inalterados até o final da avaliação aos 24 dias após a colheita, retardando também a abscisão do pedúnculo, uma variável indicativa de maturação. O tratamento com 1-MCP retardou o amadurecimento de frutos controlando a podridão de F. pallidoroseum. Este tratamento também reduziu a respiração, produção, etileno, perda de peso, não influenciando significativamente as variáveis de qualidade do fruto: coloração da casca e polpa dos frutos, teor de sólidos solúveis totais e açúcares solúveis totais durante o período de armazenamento, bem como pH e acidez total titulável nas diferentes condições de armazenamento estudadas. A refrigeração interagiu positivamente com o 1-MCP, aumentando o tempo de conservação e sanidade do melão.The objective of this experiment was to evaluate the effect of 1-replicates. Fruit treated with 1-MCP stored at room temperature MCP (at 300 nL.L-1on de physiological changes occurring during kept the pulp firmness until 15

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Cigarette smoke-related hydroquinone dysregulates MCP-1, VEGF and PEDF expression in retinal pigment epithelium in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Marianne Pons

    2011-02-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of legal blindness in the elderly population. Debris (termed drusen below the retinal pigment epithelium (RPE have been recognized as a risk factor for dry AMD and its progression to wet AMD, which is characterized by choroidal neovascularization (CNV. The underlying mechanism of how drusen might elicit CNV remains undefined. Cigarette smoking, oxidative damage to the RPE and inflammation are postulated to be involved in the pathophysiology of the disease. To better understand the cellular mechanism(s linking oxidative stress and inflammation to AMD, we examined the expression of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1, pro-angiogenic vascular endothelial growth factor (VEGF and anti-angiogenic pigment epithelial derived factor (PEDF in RPE from smoker patients with AMD. We also evaluated the effects of hydroquinone (HQ, a major pro-oxidant in cigarette smoke on MCP-1, VEGF and PEDF expression in cultured ARPE-19 cells and RPE/choroids from C57BL/6 mice.MCP-1, VEGF and PEDF expression was examined by real-time PCR, Western blot, and ELISA. Low levels of MCP-1 protein were detected in RPE from AMD smoker patients relative to controls. Both MCP-1 mRNA and protein were downregulated in ARPE-19 cells and RPE/choroids from C57BL/6 mice after 5 days and 3 weeks of exposure to HQ-induced oxidative injury. VEGF protein expression was increased and PEDF protein expression was decreased in RPE from smoker patients with AMD versus controls resulting in increased VEGF/PEDF ratio. Treatment with HQ for 5 days and 3 weeks increased the VEGF/PEDF ratio in vitro and in vivo.We propose that impaired RPE-derived MCP-1-mediated scavenging macrophages recruitment and phagocytosis might lead to incomplete clearance of proinflammatory debris and infiltration of proangiogenic macrophages which along with increased VEGF/PEDF ratio favoring angiogenesis might promote drusen accumulation and

  19. RadNet Air Quality (Deployable) Data

    Data.gov (United States)

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

    Czech Academy of Sciences Publication Activity Database

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Tracy L Callender

    2016-08-01

    Full Text Available 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.

  3. State of art report for high temperature wear test of SMART MCP and CEDM bearing material

    International Nuclear Information System (INIS)

    Cho, Yong Hu; Lee, Jae Seon; Park, Jin Seok; Kim, Ji Ho; Kim, Jong In

    2000-03-01

    Wear resistance properties of machine elements has been more critical in view of its significant effect on life extension, economics and material saving because it has been recognized that nearly 80 percent of damages of mechanical elements in the friction pairs are due to the material loss by wear. And wear properties have direct influence on the life of a machine in a great extend under extremely severe operating condition. Therefore highly improved wear properties of machine elements operating in such circumstances is heavily required. The purpose of this report is to survey current technology for high temperature wear test in order to establish the test plan for the life evaluation of SMART MCP and CEDM bearing materials. Friction and wear test will be done under high pressure (170 MPa) and high temperature (350 degree C) with water as lubricant to simulate the operating condition of the nuclear power reactor. Because pump type for MCP is selected as the caned motor pump which needs no mechanical sealing, the rotating shaft on which bearing is fully submerged by main coolant with high temperature. So MCP bearing operates without additional lubricant. CEDM is adopted as the ball-screw type with fine controllability. So the driving part is designed as the immersed-in type by main coolant. Therefore the anti-wear and reliability of driving parts are much consequent to guarantee the lifetime and the safety of the whole system. Tribometer adapted to high temperature and pressure circumstance is needed to execute bearing material testing. Test parameters are material, sliding speed, sliding distance and applied load. In order to identify the wear mechanism, optical microscope and surface roughness testers are required. The result of this report will provide an elementary data to develop bearing materials and to estimate bearing lifetime for the bearings of MCP and CEDM in SMART. (author)

  4. Ethylene and 1-MCP affect the postharvest behavior of yellow pitahaya fruits (Selenicereus megalanthus Haw.

    Directory of Open Access Journals (Sweden)

    Yuli Alexandra Deaquiz

    2014-04-01

    Full Text Available The pitahaya or dragon fruit is one of the most representative exotic fruits that Colombia has, with an important, growing international market, but the cultivation and postharvest of this fruit lack sufficient technological support to be more competitive. Therefore, alternatives that provide good-quality products that meet market requirements are very important. Therefore, the objective of this research was to determine the effect of a ripening retardant and ethylene application on the conservation and quality of pitahaya fruits and the possible changes during ripening associated with ethylene, for which a completely randomized design with three treatments was used, corresponding to the application of ethylene (ethephon, 3 mL L-1, 1-methylcyclopropene (1-MCP, 600 mg L-1 and a control, with four replications, for a total of 12 experimental units. The fruits were stored at 18°C with 75% relative humidity. The 1-MCP application significantly decreased the loss of firmness, total soluble solids, loss of fresh mass and respiratory rate. Fruits from the control and ethylene treatment tended toward a climateric respiratory behavior. The total carotenoid content of the fruits was significantly higher in the ethylene application and the control treatment, which was consistent with the color change of the fruits. It can be concluded that the 1-MCP application reduced the ethylene action, slowing the ripening of the dragon fruits.

  5. RadNet: Open network protocol for radiation data

    International Nuclear Information System (INIS)

    Rees, B.; Olson, K.; Beckes-Talcott, J.; Kadner, S.; Wenderlich, T.; Hoy, M.; Doyle, W.; Koskelo, M.

    1998-01-01

    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

  6. Comparison of the Effect of 1-MCP and Low-Pressure Air on Shelflife of Strawberry Fruit (Fragaria ananassa cv. Camarossa

    Directory of Open Access Journals (Sweden)

    B. Modares

    2013-10-01

    Full Text Available Strawberry (Fragaria×ananassa has tasteful, fragrant and nutritious fruits. But, because of delicate texture and high metabolic activities of the fruits at maturity, are very sensitive and easily decayed, and thus have short shelflife. Ethylene is one of the main causes of postharvest fruit losses, which could reduce the shelflife of strawberry. Therefore, an experiment was carried out to examine the effect of 1 µL/L 1-MCP treatment and low-pressure air pretreatment at 0.2 atm in 2 hours on apparent and physicochemical characteristics of strawberry fruit, cultivar Camarossa, during storage in cold store. The study was performed as split plots in time, based on complete randomized design with 3 replications. The results showed that the highest marketability (90%, fruit firmness (7.95 N, titrable organic acids (1.15 g/100 cc, vitamin C (78.13 mg/100 cc and total soluble solids (10.48 % and the lowest amount of apparent decay (13.3 %, acidity (3.63 and taste index (9.04 were obtained in 1-MCP and low-pressure air treatments, which shows the effect of treatments on reducing the rate of biochemical variations in fruit texture. Correlation coefficients between all treatments were significant (P≤0.01. Meanwhile, the positive effect of 1-MCP on appearance and studied physicochemical characteristics was more than low-pressure air pretreatment. Even, the combination of these two treatments had no significant difference with 1-MCp treatment alone. In general, this observation depicts the more positive and significant effect of 1-MCP treatment in delaying the maturity and improving the qualitative traits of strawberry fruits after being stored in cold storage.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  9. Effect of Rad 51 overexpression on chromosomal stability and radiation sensitivity in tumour cells

    International Nuclear Information System (INIS)

    Jend, C.; Stuerzbecher, H.W.; Dikomey, E.; Borgmann, K.

    2004-01-01

    The present study was dedicated to examining the effects of Rad51 overexpression on genomic instability, expressed in terms of chromosomal aberrations in G1 and G2 phases following X-ray irradiation. For this purpose an osteosarcoma cell line (Ui-OS) which shows inducing Rad51 overexpression (UiRad5-2) after stable transfection was compared with an isogenetic line (UiLacZ) which overexpresses beta-galactosidase instead of Rad51 [de

  10. The rad-hard readout system of the BaBar silicon vertex tracker

    Science.gov (United States)

    Re, V.; DeWitt, J.; Dow, S.; Frey, A.; Johnson, R. P.; Kroeger, W.; Kipnis, I.; Leona, A.; Luo, L.; Mandelli, E.; Manfredi, P. F.; Nyman, M.; Pedrali-Noy, M.; Poplevin, P.; Perazzo, A.; Roe, N.; Spencer, N.

    1998-02-01

    This paper discusses the behaviour of a prototype rad-hard version of the chip developed for the readout of the BaBar silicon vertex tracker. A previous version of the chip, implemented in the 0.8 μm HP rad-soft version has been thoroughly tested in the recent times. It featured outstanding noise characteristics and showed that the specifications assumed as target for the tracker readout were met to a very good extent. The next step was the realization of a chip prototype in the rad-hard process that will be employed in the actual chip production. Such a prototype is structurally and functionally identical to its rad-soft predecessor. However, the process parameters being different, and not fully mastered at the time of design, some deviations in the behaviour were to be expected. The reasons for such deviations have been identified and some of them were removed by acting on the points that were left accessible on the chip. Other required small circuit modifications that will not affect the production schedule. The tests done so far on the rad-hard chip have shown that the noise behaviour is very close to that of the rad-soft version, that is fully adequate for the vertex detector readout.

  11. Disparate requirements for the Walker A and B ATPase motifs of human RAD51D in homologous recombination.

    Science.gov (United States)

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

    2006-01-01

    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 (ICLs). 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.

  12. Substantial differences in bias between single-digest and double-digest RAD-seq libraries: A case study.

    Science.gov (United States)

    Flanagan, Sarah P; Jones, Adam G

    2018-03-01

    The trade-offs of using single-digest vs. double-digest restriction site-associated DNA sequencing (RAD-seq) protocols have been widely discussed. However, no direct empirical comparisons of the two methods have been conducted. Here, we sampled a single population of Gulf pipefish (Syngnathus scovelli) and genotyped 444 individuals using RAD-seq. Sixty individuals were subjected to single-digest RAD-seq (sdRAD-seq), and the remaining 384 individuals were genotyped using a double-digest RAD-seq (ddRAD-seq) protocol. We analysed the resulting Illumina sequencing data and compared the two genotyping methods when reads were analysed either together or separately. Coverage statistics, observed heterozygosity, and allele frequencies differed significantly between the two protocols, as did the results of selection components analysis. We also performed an in silico digestion of the Gulf pipefish genome and modelled five major sources of bias: PCR duplicates, polymorphic restriction sites, shearing bias, asymmetric sampling (i.e., genotyping fewer individuals with sdRAD-seq than with ddRAD-seq) and higher major allele frequencies. This combination of approaches allowed us to determine that polymorphic restriction sites, an asymmetric sampling scheme, mean allele frequencies and to some extent PCR duplicates all contribute to different estimates of allele frequencies between samples genotyped using sdRAD-seq versus ddRAD-seq. Our finding that sdRAD-seq and ddRAD-seq can result in different allele frequencies has implications for comparisons across studies and techniques that endeavour to identify genomewide signatures of evolutionary processes in natural populations. © 2017 John Wiley & Sons Ltd.

  13. Stratification of mammographic computerized analysis by BI-RADS categories

    International Nuclear Information System (INIS)

    Lederman, Richard; Leichter, Isaac; Buchbinder, Shalom; Novak, Boris; Bamberger, Philippe; Fields, Scott

    2003-01-01

    The Breast Imaging Reporting and Data System (BI-RADS) was implemented to standardize characterization of mammographic findings. The purpose of the present study was to evaluate in which BI-RADS categories the changes recommended by computerized mammographic analysis are most beneficial. Archival cases including, 170 masses (101 malignant, 69 benign) and 63 clusters of microcalcifications (MCs; 36 malignant, 27 benign), were evaluated retrospectively, using the BI-RADS categories, by several radiologists, blinded to the pathology results. A computerized system then automatically extracted from the digitized mammogram features characterizing mammographic lesions, which were used to classify the lesions. The results of the computerized classification scheme were compared, by receiver operating characteristics (ROC) analysis, to the conventional interpretation. In the ''low probability of malignancy group'' (excluding BI-RADS categories 4 and 5), computerized analysis improved the A z of the ROC curve significantly, from 0.57 to 0.89. In the ''high probability of malignancy group'' (mostly category 5) the computerized analysis yielded an ROC curve with an A z of 0.99. In the ''intermediate probability of malignancy group'' computerized analysis improved the A z significantly, from 0.66 for to 0.83. Pair-wise analysis showed that in the latter group the modifications resulting from computerized analysis were correct in 83% of cases. Computerized analysis has the ability to improve the performance of the radiologists exactly in the BI-RADS categories with the greatest difficulties in arriving at a correct diagnosis. It increased the performance significantly in the problematic group of ''intermediate probability of malignancy'' and pinpointed all the cases with missed cancers in the ''low probability'' group. (orig.)

  14. Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis.

    Science.gov (United States)

    Pan, Y W; Zhou, Z G; Wang, M; Dong, J Q; Du, K P; Li, S; Liu, Y L; Lv, P J; Gao, J B

    2016-11-03

    Early detection and treatment is critically important for lung cancer patients. Inflammatory mediators such as IL-6, IL-10, and MCP-1 participate in lung cancer regulation. CEA, CA125, and ProGRP are commonly used serum tumor markers for lung cancer. In this study, we assessed the sensitivity and specificity of CEA, CA125, and ProGRP when used in combination with IL-6, IL-10, and MCP in lung cancer diagnosis. Serum from three different groups (healthy controls, individuals with high risk for lung cancer, and lung cancer patients) was collected. Electrochemiluminescence was used to detect expressions of CEA, CA125, and ProGRP; ELISA was used to examine serum levels of IL-6, IL-10, and MCP-1. Specificity and sensitivity of single as well as combination markers in lung cancer diagnosis were determined. Results indicated that CEA, CA125, ProGRP, and MCP-1 were significantly up-regulated in lung cancer patients as compared to those in controls and high risk individuals. Higher IL-6 and IL-10 levels were observed in both lung cancer patients and high-risk individuals as compared to those in controls. Highest sensitivity (95.2%) in cancer diagnosis was achieved when all six markers were used. This was followed by a combination of IL-6, IL-10, CEA, CA125, and ProGRP (92.6%). The most sensitive (88.6%). Four-marker combination was composed of IL-6, CEA, CA125, and ProGRP. As the combined usage of CEA, CA125, ProGRP, IL-6, IL-10, and MCP-1 significantly improved sensitivity of lung cancer detection; this biomarker arrangement may be beneficial for early diagnosis, treatment, and prognosis of lung cancer.

  15. RAD51C germline mutations in breast and ovarian cancer cases from high-risk families.

    Directory of Open Access Journals (Sweden)

    Jessica Clague

    Full Text Available BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5' UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non-synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001. Immunoblots of RAD51C-Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene.

  16. Issues in assessing multi-institutional performance of BI-RADS-based CAD systems

    Science.gov (United States)

    Markey, Mia K.; Lo, Joseph Y.

    2005-04-01

    The purpose of this study was to investigate factors that impact the generalization of breast cancer computer-aided diagnosis (CAD) systems that utilize the Breast Imaging Reporting and Data System (BI-RADS). Data sets from four institutions were analyzed: Duke University Medical Center, University of Pennsylvania Medical Center, Massachusetts General Hospital, and Wake Forest University. The latter two data sets are subsets of the Digital Database for Screening Mammography. Each data set consisted of descriptions of mammographic lesions according to the BI-RADS lexicon, patient age, and pathology status (benign/malignant). Models were developed to predict pathology status from the BI-RADS descriptors and the patient age. Comparisons between the models built on data from the different institutions were made in terms of empirical (non-parametric) receiver operating characteristic (ROC) curves. Results suggest that BI-RADS-based CAD systems focused on specific classes of lesions may be more generally applicable than models that cover several lesion types. However, better generalization was seen in terms of the area under the ROC curve than in the partial area index (>90% sensitivity). Previous studies have illustrated the challenges in translating a BI-RADS-based CAD system from one institution to another. This study provides new insights into possible approaches to improve the generalization of BI-RADS-based CAD systems.

  17. Yeast DNA-repair gene RAD14 encodes a zinc metalloprotein with affinity for ultraviolet-damaged DNA

    International Nuclear Information System (INIS)

    Guzder, S.N.; Sung, P.; Prakash, S.; Prakash, L.

    1993-01-01

    Xeroderma pigmentosum (XP) patients suffer from a high incidence of skin cancers due to a defect in excision repair of UV light-damaged DNA. Of the seven XP complementation groups, A--G, group A represents a severe and frequent form of the disease. The Saccharomyces cerevisiae RAD14 gene is a homolog of the XP-A correcting (XPAC) gene. Like XP-A cells, rad14-null mutants are defective in the incision step of excision repair of UV-damaged DNA. The authors have purified RAD14 protein to homogeneity from extract of a yeast strain genetically tailored to overexpress RAD14. As determined by atomic emission spectroscopy, RAD14 contains one zinc atom. They also show in vitro that RAD14 binds zinc but does not bind other divalent metal ions. In DNA mobility-shift assays, RAD14 binds specifically to UV-damaged DNA. Removal of cyclobutane pyrimidine dimers from damaged DNA by enzymatic photoreactivation has no effect on binding, strongly suggesting that RAD14 recognizes pyrimidine(6-4)pyrimidone photoproduct sites. These findings indicate that RAD14 functions in damage recognition during excision repair. 37 refs., 4 figs

  18. Plasma cytokines eotaxin, MIP-1α, MCP-4, and vascular endothelial growth factor in acute lower respiratory tract infection

    DEFF Research Database (Denmark)

    Relster, Mette Marie; Holm, Anette; Pedersen, Court

    2017-01-01

    ), monocyte chemoattractant protein 4 (MCP-4), and vascular endothelial growth factor (VEGF) in 40 patients hospitalized with acute lower respiratory tract infections (LRTI). The cytokines contribute to the pathogenesis of several inflammatory respiratory diseases, indicating a potential as markers for LRTI....... Patients were stratified according to etiology and severity of LRTI, based on baseline C-reactive protein and CURB-65 scores. Using a multiplex immunoassay of plasma, levels of eotaxin and MCP-4 were shown to increase from baseline until day 6 after admission to hospital. The four cytokines were unable...

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    fluorescent protein (GFP) is fully functional in DNA repair and recombination. After induction of DNA double-strand breaks by gamma -irradiation, meiosis, or the HO endonuclease, Rad52-GFP relocalizes from a diffuse nuclear distribution to distinct foci. Interestingly, Rad52 foci are formed almost exclusively...

  20. RadNet (Environmental Radiation Ambient Monitoring System)

    Data.gov (United States)

    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,...

  1. Assay for Human Rad51-Mediated DNA Displacement Loop Formation

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Steven Raynard and Patrick Sung Corresponding author ([]()) ### INTRODUCTION Homologous recombination is an important mechanism for the repair of damaged chromosomes, for preventing the demise of damaged replication forks, and for several other aspects of chromosome metabolism and maintenance. The homologous recombination reaction is mediated by the Rad51 recombinase. In the presence of ATP, Rad51 polymerizes on single-stranded D...

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

    International Nuclear Information System (INIS)

    Mather, S.J.

    2002-01-01

    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

  3. Storage of strawberries (Fragaria ananassa L. cv. ‘Oso Grande’, subjected to 1-MCP - doi: 10.4025/actascitechnol.v34i3.8790

    Directory of Open Access Journals (Sweden)

    Polyanna Alves Silva

    2012-05-01

    Full Text Available This study aimed to investigate the influence of 1 - methylcyclopropene (1-MCP on the substances involved in the softening of strawberry, cultivar Oso Grande, stored at room temperature, from the municipality of Itutinga, State of Minas Gerais. The parameters evaluated were: firmness, total pectin, percentage of solubilization, activities of the enzymes pectinmethylesterase (PME (EC 3.1.1.11 and polygalacturonase (PG (EC 3.2.1.15. It was concluded that 1-MCP delayed the softening of the fruits, since the fruits that were treated with 1-MCP after storage, have shown greater firmness, lower activities of PG and PME, and lower contents of total pectin, soluble pectin and percentage of solubilization. 

  4. The role of Candida albicans homologous recombination factors Rad54 and Rdh54 in DNA damage sensitivity

    Directory of Open Access Journals (Sweden)

    White Theodore C

    2011-09-01

    Full Text Available Abstract Background The fungal pathogen Candida albicans is frequently seen in immune suppressed patients, and resistance to one of the most widely used antifungals, fluconazole (FLC, can evolve rapidly. In recent years it has become clear that plasticity of the Candida albicans genome contributes to drug resistance through loss of heterozygosity (LOH at resistance genes and gross chromosomal rearrangements that amplify gene copy number of resistance associated genes. This study addresses the role of the homologous recombination factors Rad54 and Rdh54 in cell growth, DNA damage and FLC resistance in Candida albicans. Results The data presented here support a role for homologous recombination in cell growth and DNA damage sensitivity, as Candida albicans rad54Δ/rad54Δ mutants were hypersensitive to MMS and menadione, and had an aberrant cell and nuclear morphology. The Candida albicans rad54Δ/rad54Δ mutant was defective in invasion of Spider agar, presumably due to the altered cellular morphology. In contrast, mutation of the related gene RDH54 did not contribute significantly to DNA damage resistance and cell growth, and deletion of either Candida albicans RAD54 or Candida albicans RDH54 did not alter FLC susceptibility. Conclusions Together, these results support a role for homologous recombination in genome stability under nondamaging conditions. The nuclear morphology defects in the rad54Δ/rad54Δ mutants show that Rad54 performs an essential role during mitotic growth and that in its absence, cells arrest in G2. The viability of the single mutant rad54Δ/rad54Δ and the inability to construct the double mutant rad54Δ/rad54Δ rdh54Δ/rdh54Δ suggests that Rdh54 can partially compensate for Rad54 during mitotic growth.

  5. Stratification of mammographic computerized analysis by BI-RADS categories

    Energy Technology Data Exchange (ETDEWEB)

    Lederman, Richard [Department of Radiology, Hadassah University Hospital, Ein Kerem, Jerusalem (Israel); Leichter, Isaac [Department of Electro-Optics, Jerusalem College of Technology, P.O.B. 16031, Jerusalem (Israel); Buchbinder, Shalom [Department of Radiology of The Montefiore Medical Center, The University Hospital for the Albert Einstein College of Medicine, Bronx, New York (United States); Novak, Boris [Department of Applied Mathematics, Jerusalem College of Technology, P.O.B. 16031, Jerusalem 91160 (Israel); Bamberger, Philippe [Department of Electronics, Jerusalem College of Technology, POB 16031, Jerusalem (Israel); Fields, Scott [Department of Radiology, Hadassah University Hospital, Mt. Scopus, Jerusalem (Israel)

    2003-02-01

    The Breast Imaging Reporting and Data System (BI-RADS) was implemented to standardize characterization of mammographic findings. The purpose of the present study was to evaluate in which BI-RADS categories the changes recommended by computerized mammographic analysis are most beneficial. Archival cases including, 170 masses (101 malignant, 69 benign) and 63 clusters of microcalcifications (MCs; 36 malignant, 27 benign), were evaluated retrospectively, using the BI-RADS categories, by several radiologists, blinded to the pathology results. A computerized system then automatically extracted from the digitized mammogram features characterizing mammographic lesions, which were used to classify the lesions. The results of the computerized classification scheme were compared, by receiver operating characteristics (ROC) analysis, to the conventional interpretation. In the ''low probability of malignancy group'' (excluding BI-RADS categories 4 and 5), computerized analysis improved the A{sub z}of the ROC curve significantly, from 0.57 to 0.89. In the ''high probability of malignancy group'' (mostly category 5) the computerized analysis yielded an ROC curve with an A {sub z}of 0.99. In the ''intermediate probability of malignancy group'' computerized analysis improved the A {sub z}significantly, from 0.66 for to 0.83. Pair-wise analysis showed that in the latter group the modifications resulting from computerized analysis were correct in 83% of cases. Computerized analysis has the ability to improve the performance of the radiologists exactly in the BI-RADS categories with the greatest difficulties in arriving at a correct diagnosis. It increased the performance significantly in the problematic group of ''intermediate probability of malignancy'' and pinpointed all the cases with missed cancers in the ''low probability'' group. (orig.)

  6. Nuclear NF-κB p65 in peripheral blood mononuclear cells correlates with urinary MCP-1, RANTES and the severity of type 2 diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Bin Yi

    Full Text Available AIMS: To investigate if nuclear NF-κB p65 expression in ex vivo isolated peripheral blood mononuclear cells correlates with urinary MCP-1 or RANTES and the severity of type 2 diabetic nephropathy. METHODS: According to their urinary albumin-to-creatinine ratio (uACR, 107 patients with type 2 diabetes (eGFR >60 ml/min were divided into normal albuminuria group (DN0 group, 38 cases, microalbuminuria group (DN1 group, 38 cases, and macroalbuminuria group (DN2 group, 31 cases, compared with matched healthy normal control group (NC group, 30 cases. Nuclear NF-κB p65 protein expression levels in peripheral blood mononuclear cells were detected by western blotting. Real-time quantitative polymerase chain reaction was used to detect NF-κB p65 mRNA expression and ELISA assay was used to detect the levels of urinary MCP-1 and RANTES. RESULTS: Nuclear NF-κB p65 protein and NF-κB p65 mRNA expression levels in peripheral blood mononuclear cells, urinary MCP-1/Cr and RANTES/Cr were all significantly higher in all diabetes groups as compared with NC group. In particular, the increase of nuclear NF-κB p65 protein and NF-κB p65 mRNA expressions, urinary MCP-1/Cr and RANTES/Cr all correlated with the severity of type 2 diabetic nephropathy as indicated by the increase in uACR. Pearson correlation analysis indicated that both urinary MCP-1/Cr and RANTES/Cr were positively correlated with nuclear NF-κB p65 protein or NF-κB p65 mRNA levels. Stepwise multiple regression analysis showed that nuclear NF-κB p65 protein or NF-κB p65 mRNA was an independent variable for urinary MCP-1/Cr, and MCP-1/Cr and RANTES/Cr were two independent variables for uACR. CONCLUSION: Our research demonstrates that nuclear NF-κB p65 protein and mRNA expressions in ex vivo isolated peripheral blood mononuclear cells well correlate with urinary MCP-1/Cr, RANTES/Cr and the severity of type 2 diabetic nephropathy.

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

    DEFF Research Database (Denmark)

    Moudry, Pavel; Watanabe, Kenji; Wolanin, Kamila M.

    2016-01-01

    to chromatin and formation of RAD51 foci, but without affecting the upstream HR steps of DNA end resection and RPA loading. Furthermore, TOPBP1 BRCT domains 7/8 are essential for RAD51 foci formation. Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase-mediated phosphorylation of RAD51...

  8. Analysis of Dextromethorphan and Dextrorphan in Skeletal Remains Following Differential Microclimate Exposure: Comparison of Acute vs. Repeated Drug Exposure.

    Science.gov (United States)

    Morrison, Lucas M; Unger, Kirk A; Watterson, James H

    2017-07-01

    Analysis of dextromethorphan (DXM) and its metabolite dextrorphan (DXT) in skeletal remains of rats following acute (ACU, 75 mg/kg, IP, n = 10) or three repeated (REP, 25 mg/kg, IP, n = 10, 40-min interval) doses of DXM is described. Following dosing and euthanasia, rats decomposed outdoors to skeleton in two different microclimate environments (n = 5 ACU and n = 5 REP at each site): Site A (shaded forest microenvironment) and Site B (rocky substrate exposed to direct sunlight, 600 m from Site A). Two drug-free rats at each site served as negative controls. Skeletal elements (vertebrae, ribs, pelvic girdles, femora, tibiae, skulls and scapulae) were recovered, pulverized and underwent methanolic microwave assisted extraction (MAE). Extracts were analyzed by GC-MS following clean-up by solid-phase extraction (SPE). Drug levels, expressed as mass-normalized response ratios and the ratios of DXT and DXM levels (RRDXT/RRDXM) were compared between drug exposures, microclimate sites, and across skeletal elements. DXM levels differed significantly (P < 0.05) between corresponding bone elements across exposure groups (5/7-site A; 4/7-site B), but no significant differences in DXT levels were observed between corresponding elements. RRDXT/RRDXM differed significantly (P < 0.05) between corresponding bone elements across exposure groups (6/7-site A; 5/7-site B). No significant differences were observed in levels of DXM, DXT or RRDXT/RRDXM between corresponding elements from either group between sites. When data from all bone elements was pooled, levels of DXM and RRDXT/RRDXM differed significantly between exposure groups at each site, while those of DXT did not. For both exposure groups, comparison of pooled data between sites showed no significant differences in levels of DXM, DXT or RRDXT/RRDXM. Different decomposition microclimates did not impede the discrimination of DXM exposure patterns from the analyses of DXM, DXT and RRDXT/RRDXM in bone samples. © The Author 2017

  9. Spatially and Temporally Regulated NRF2 Gene Therapy Using Mcp-1 Promoter in Retinal Ganglion Cell Injury

    Directory of Open Access Journals (Sweden)

    Kosuke Fujita

    2017-06-01

    Full Text Available Retinal ganglion cell degeneration triggered by axonal injury is believed to underlie many ocular diseases, including glaucoma and optic neuritis. In these diseases, retinal ganglion cells are affected unevenly, both spatially and temporally, such that healthy and unhealthy cells coexist in different patterns at different time points. Herein, we describe a temporally and spatially regulated adeno-associated virus gene therapy aiming to reduce undesired off-target effects on healthy retinal neurons. The Mcp-1 promoter previously shown to be activated in stressed retinal ganglion cells following murine optic nerve injury was combined with the neuroprotective intracellular transcription factor Nrf2. In this model, Mcp-1 promoter-driven NRF2 expression targeting only stressed retinal ganglion cells showed efficacy equivalent to non-selective cytomegalovirus promoter-driven therapy for preventing cell death. However, cytomegalovirus promoter-mediated NRF2 transcription induced cellular stress responses and death of Brn3A-positive uninjured retinal ganglion cells. Such undesired effects were reduced substantially by adopting the Mcp-1 promoter. Combining a stress-responsive promoter and intracellular therapeutic gene is a versatile approach for specifically targeting cells at risk of degeneration. This strategy may be applicable to numerous chronic ocular and non-ocular conditions.

  10. Rad9 contribution to radiosensitivity and the G2 checkpoint in a DT40 cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kumano, Tomoyasu [Kanazawa Univ. (Japan). Graduate School of Medical Science

    2002-12-01

    In fission yeast, the rad9 (radiation sensitive) gene was cloned from a mutant that is sensitive to ionizing radiation, ultraviolet and hydroxyurea. This gene has also been shown to be required for a DNA damage checkpoint. Orthologues of the rad9 gene have recently been identified in higher eukaryote cells including human. Here we generated Rad9 knockout (Rad9-/-) cells from the chicken B lymphocyte line DT40 to examine the role of Rad9 in higher eukaryotes. First we isolated a part of the chicken Rad9 gene which was 54% identical with human Rad9 at the amino acid sequence level. Next we isolated genomic clones, determined exons and introns, and constructed targeting vectors designed to disrupt exon 1-3 of the chicken Rad9 gene by replacement with a drug-resistant gene. Successful targeted integration was verified by Southern blot analysis and the disruption of the Rad9 gene was confirmed by reverse transcription polymerase chain reaction (RT-PCR). To analyze the radiosensitivity of these Rad9-/- cells, we monitored the clonogenic survival after various degrees of X-ray irradiation. Rad9-/- cells were more sensitive to X-rays than wild type cells at all dosages. However, these cells were less sensitive than ATM knockout (ATM-/-) cells that are known to be X-ray sensitive and that showed a defective checkpoint control. In contrast, Rad9-/- cells were markedly more sensitive to ultraviolet and hydroxyruea. In addition, we assessed the G2 checkpoint by measurement of the mitotic index that is the fraction of the accumulating number of cells in mitosis at various times after X-ray irradiation. While the number of mitotic wild type cells did not increase until 2 hrs after X-ray irradiation, the number of mitotic Rad9-/- cells showed an increase similar to that of ATM-/- cells. These results suggest that just as in fission yeast, in higher eukaryotes Rad9 also contributes to X-ray, ultraviolet and hydroxyurea sensitivity, and plays an important role in the G2 checkpoint

  11. Rad9 contribution to radiosensitivity and the G2 checkpoint in a DT40 cell line

    International Nuclear Information System (INIS)

    Kumano, Tomoyasu

    2002-01-01

    In fission yeast, the rad9 (radiation sensitive) gene was cloned from a mutant that is sensitive to ionizing radiation, ultraviolet and hydroxyurea. This gene has also been shown to be required for a DNA damage checkpoint. Orthologues of the rad9 gene have recently been identified in higher eukaryote cells including human. Here we generated Rad9 knockout (Rad9-/-) cells from the chicken B lymphocyte line DT40 to examine the role of Rad9 in higher eukaryotes. First we isolated a part of the chicken Rad9 gene which was 54% identical with human Rad9 at the amino acid sequence level. Next we isolated genomic clones, determined exons and introns, and constructed targeting vectors designed to disrupt exon 1-3 of the chicken Rad9 gene by replacement with a drug-resistant gene. Successful targeted integration was verified by Southern blot analysis and the disruption of the Rad9 gene was confirmed by reverse transcription polymerase chain reaction (RT-PCR). To analyze the radiosensitivity of these Rad9-/- cells, we monitored the clonogenic survival after various degrees of X-ray irradiation. Rad9-/- cells were more sensitive to X-rays than wild type cells at all dosages. However, these cells were less sensitive than ATM knockout (ATM-/-) cells that are known to be X-ray sensitive and that showed a defective checkpoint control. In contrast, Rad9-/- cells were markedly more sensitive to ultraviolet and hydroxyruea. In addition, we assessed the G2 checkpoint by measurement of the mitotic index that is the fraction of the accumulating number of cells in mitosis at various times after X-ray irradiation. While the number of mitotic wild type cells did not increase until 2 hrs after X-ray irradiation, the number of mitotic Rad9-/- cells showed an increase similar to that of ATM-/- cells. These results suggest that just as in fission yeast, in higher eukaryotes Rad9 also contributes to X-ray, ultraviolet and hydroxyurea sensitivity, and plays an important role in the G2 checkpoint

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

    International Nuclear Information System (INIS)

    Mosor, Maria; Ziółkowska-Suchanek, Iwona; Nowicka, Karina; Dzikiewicz-Krawczyk, Agnieszka; Januszkiewicz–Lewandowska, Danuta; Nowak, Jerzy

    2013-01-01

    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

  13. Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.

    Directory of Open Access Journals (Sweden)

    Malathesha Ganachari

    2010-01-01

    Full Text Available We previously reported that the -2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the -1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the -2518 MCP-1 genotype GG and the -1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1.

  14. Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.

    Science.gov (United States)

    Ganachari, Malathesha; Ruiz-Morales, Jorge A; Gomez de la Torre Pretell, Juan C; Dinh, Jeffrey; Granados, Julio; Flores-Villanueva, Pedro O

    2010-01-25

    We previously reported that the -2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB) in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the -1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC) analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the -2518 MCP-1 genotype GG and the -1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1.

  15. Mars science laboratory radiation assessment detector (MSL/RAD) modeling workshop proceedings

    Science.gov (United States)

    Hassler, Donald M.; Norbury, John W.; Reitz, Günther

    2017-08-01

    The Radiation Assessment Detector (RAD) (Hassler et al., 2012; Zeitlin et al., 2016) onboard the Mars Science Laboratory (MSL) Curiosity rover (Grotzinger et al., 2012) is a sophisticated charged and neutral particle radiation analyzer developed by an international team of scientists and engineers from Southwest Research Institute in Boulder, Colorado as the leading institution, the University of Kiel and the German Aerospace Center in Cologne, Germany. RAD is a compact, powerful instrument capable of distinguishing between ionizing particles and neutral particles and providing neutron, gamma, and charged particle spectra from protons to iron as well as absorbed dose measurements in tissue-equivalent material. During the 6 month cruise to Mars, inside the MSL spacecraft, RAD served as a proxy to validate models of the radiation levels expected inside a spacecraft that future astronauts might experience (Zeitlin et al., 2013). RAD was turned on one day after the landing on August 7, 2012, exactly 100 years to the day after the discovery of cosmic rays on Earth by Victor Hess. These measurements are the first of their kind on the surface of another planet (Hassler et al., 2014), and the radiation data collected by RAD on the surface of Mars will inform projections of crew health risks and the design of protective surface habitats and other countermeasures for future human missions in the coming decades.

  16. Resolving RAD51C function in late stages of homologous recombination

    Directory of Open Access Journals (Sweden)

    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.

  17. Dynamic changes in Rad51 distribution on chromatin during meiosis in male and female vertebrates.

    Science.gov (United States)

    Ashley, T; Plug, A W; Xu, J; Solari, A J; Reddy, G; Golub, E I; Ward, D C

    1995-10-01

    Antibodies against human Rad51 protein were used to examine the distribution of Rad51 on meiotic chromatin in mouse spermatocytes and oocytes as well as chicken oocytes during sequential stages of meiosis. We observed the following dynamic changes in distribution of Rad51 during meiosis: (1) in early leptotene nuclei there are multiple, apparently randomly distributed, foci that by late leptonema become organized into tracks of foci. (2) These foci persist into zygonema, but most foci are now localized on Rad51-positive axes that correspond to lateral elements of the synaptonemal complex. As homologs synapse foci from homologous axes fuse. The distribution and involvement of Rad51 foci as contact points between homologs suggest that they may be components to early recombination nodules. (3) As pachynema progresses the number of foci drops dramatically; the temporal occurrence (mice) and physical and numerical distribution of foci on axes (chickens) suggest that they may be a component of late recombination nodules. (4) In early pachynema there are numerous Rad51 foci on the single axis of the X (mouse spermatocytes) or the Z (chicken oocytes) chromosomes that neither pair, nor recombine. (5) In late pachynema in mouse spermatocytes, but not oocytes, the Rad51 signal is preferentially enhanced at both ends of all the bivalents. As bivalents in spermatocytes, but not oocytes, begin to desynapse at diplonema they are often held together at these Rad51-positive termini. These observations parallel observations that recombination rates are exceptionally high near chromosome ends in male but not female eutherian mammals. (6) From diakinesis through metaphase I, Rad51 protein is detected as low-intensity fluorescent doublets that localize with CREST-specific antigens (kinetochores), suggesting that Rad51 participates, at least as a structural component of the materials involved, in sister kinetochore cohesiveness. Finally, the changes in Rad51 distribution during meiosis

  18. NeuRad detector prototype pulse shape study

    Science.gov (United States)

    Muzalevsky, I.; Chudoba, V.; Belogurov, S.; Kiselev, O.; Bezbakh, A.; Fomichev, A.; Krupko, S.; Slepnev, R.; Kostyleva, D.; Gorshkov, A.; Ovcharenko, E.; Schetinin, V.

    2018-04-01

    The EXPERT setup located at the Super-FRS facility, the part of the FAIR complex in Darmstadt, Germany, is intended for investigation of properties of light exotic nuclei. One of its modules, the high granularity neutron detector NeuRad assembled from a large number of the scintillating fiber is intended for registration of neutrons emitted by investigated nuclei in low-energy decays. Feasibility of the detector strongly depends on its timing properties defined by the spatial distribution of ionization, light propagation inside the fibers, light emission kinetics and transition time jitter in the multi-anode photomultiplier tube. The first attempt of understanding the pulse formation in the prototype of the NeuRad detector by comparing experimental results and Monte Carlo (MC) simulations is reported in this paper.

  19. Development of high integrity containers for rad-waste treatment

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yung Chul; Cho, Myung Sug; Jung, Yun Sub [Korea Electric Power Corp. (KEPCO), Taejon (Korea, Republic of). Research Center

    1995-12-31

    Nuclear power plants are generating rad waste such as solid wastes, concentrated liquid wastes, spent resins and spent filters, and various types of imported containers which have different specifications and material properties are employed to handle the rad wastes according to facility characteristics of the plants or the type of wastes. These containers are stored at the intermediate storage facilities at the plant site due to the construction delay of permanent disposal site, and the additional construction of storage and disposal sites become more difficult with increase of the numbers and the operation time of the plants. In order to solve these difficulties, rad wastes volume reduction facilities such as High Pressure Compression Facility or Drying Facility are being installed and use of High Integrity Containers(HIC) are increasing. Therefore, we decide quality and technology standards required for the HIC, and then develop the HIC which satisfies the standards with new composite material called Steel Fiber Polymer Impregnated Concrete(SFPIC) (author). 84 refs., 118 figs.

  20. Development of high integrity containers for rad-waste treatment

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yung Chul; Cho, Myung Sug; Jung, Yun Sub [Korea Electric Power Corp. (KEPCO), Taejon (Korea, Republic of). Research Center

    1996-12-31

    Nuclear power plants are generating rad waste such as solid wastes, concentrated liquid wastes, spent resins and spent filters, and various types of imported containers which have different specifications and material properties are employed to handle the rad wastes according to facility characteristics of the plants or the type of wastes. These containers are stored at the intermediate storage facilities at the plant site due to the construction delay of permanent disposal site, and the additional construction of storage and disposal sites become more difficult with increase of the numbers and the operation time of the plants. In order to solve these difficulties, rad wastes volume reduction facilities such as High Pressure Compression Facility or Drying Facility are being installed and use of High Integrity Containers(HIC) are increasing. Therefore, we decide quality and technology standards required for the HIC, and then develop the HIC which satisfies the standards with new composite material called Steel Fiber Polymer Impregnated Concrete(SFPIC) (author). 84 refs., 118 figs.

  1. Rad GTPase is essential for the regulation of bone density and bone marrow adipose tissue in mice.

    Science.gov (United States)

    Withers, Catherine N; Brown, Drew M; Byiringiro, Innocent; Allen, Matthew R; Condon, Keith W; Satin, Jonathan; Andres, Douglas A

    2017-10-01

    The small GTP-binding protein Rad (RRAD, Ras associated with diabetes) is the founding member of the RGK (Rad, Rem, Rem2, and Gem/Kir) family that regulates cardiac voltage-gated Ca 2+ channel function. However, its cellular and physiological functions outside of the heart remain to be elucidated. Here we report that Rad GTPase function is required for normal bone homeostasis in mice, as Rad deletion results in significantly lower bone mass and higher bone marrow adipose tissue (BMAT) levels. Dynamic histomorphometry in vivo and primary calvarial osteoblast assays in vitro demonstrate that bone formation and osteoblast mineralization rates are depressed, while in vitro osteoclast differentiation is increased, in the absence of Rad. Microarray analysis revealed that canonical osteogenic gene expression (Runx2, osterix, etc.) is not altered in Rad -/- calvarial osteoblasts; instead robust up-regulation of matrix Gla protein (MGP, +11-fold), an inhibitor of extracellular matrix mineralization and a protein secreted during adipocyte differentiation, was observed. Strikingly, Rad deficiency also resulted in significantly higher marrow adipose tissue levels in vivo and promoted spontaneous in vitro adipogenesis of primary calvarial osteoblasts. Adipogenic differentiation of wildtype calvarial osteoblasts resulted in the loss of endogenous Rad protein, further supporting a role for Rad in the control of BMAT levels. These findings reveal a novel in vivo function for Rad and establish a role for Rad signaling in the complex physiological control of skeletal homeostasis and bone marrow adiposity. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Reynolds, P.; Weber, S.; Prakash, L.

    1985-01-01

    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

  3. Arabidopsis rad23-4 gene is required for pollen development under ...

    African Journals Online (AJOL)

    Nucleotide excision repair (NER) is a highly conserved DNA repair pathway for correcting DNA lesions that cause distortion of the double helical structure. The protein heterodimer Rad23 is involved in recognition and binding to such lesions. Here, we showed that rad23-4 (AT5g38470) was expressed in the roots, mature ...

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

    International Nuclear Information System (INIS)

    Eckardt-Schupp, F.; Siede, W.; Game, J.C.

    1987-01-01

    The moderately UV- and X-ray-sensitive mutant of Saccharomyces cerevisiae originally designated r 1 /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

  5. NARAC Dispersion Model Product Integration With RadResponder

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. RadNet-Air Near Real Time Data

    Data.gov (United States)

    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...

  7. How and how much does RAD-seq bias genetic diversity estimates?

    Science.gov (United States)

    Cariou, Marie; Duret, Laurent; Charlat, Sylvain

    2016-11-08

    RAD-seq is a powerful tool, increasingly used in population genomics. However, earlier studies have raised red flags regarding possible biases associated with this technique. In particular, polymorphism on restriction sites results in preferential sampling of closely related haplotypes, so that RAD data tends to underestimate genetic diversity. Here we (1) clarify the theoretical basis of this bias, highlighting the potential confounding effects of population structure and selection, (2) confront predictions to real data from in silico digestion of full genomes and (3) provide a proof of concept toward an ABC-based correction of the RAD-seq bias. Under a neutral and panmictic model, we confirm the previously established relationship between the true polymorphism and its RAD-based estimation, showing a more pronounced bias when polymorphism is high. Using more elaborate models, we show that selection, resulting in heterogeneous levels of polymorphism along the genome, exacerbates the bias and leads to a more pronounced underestimation. On the contrary, spatial genetic structure tends to reduce the bias. We confront the neutral and panmictic model to "ideal" empirical data (in silico RAD-sequencing) using full genomes from natural populations of the fruit fly Drosophila melanogaster and the fungus Shizophyllum commune, harbouring respectively moderate and high genetic diversity. In D. melanogaster, predictions fit the model, but the small difference between the true and RAD polymorphism makes this comparison insensitive to deviations from the model. In the highly polymorphic fungus, the model captures a large part of the bias but makes inaccurate predictions. Accordingly, ABC corrections based on this model improve the estimations, albeit with some imprecisions. The RAD-seq underestimation of genetic diversity associated with polymorphism in restriction sites becomes more pronounced when polymorphism is high. In practice, this means that in many systems where

  8. Muscle glycogen depletion following 75-km of cycling is not linked to increased muscle IL-6, IL-8, and MCP-1 mRNA expression and protein content

    Directory of Open Access Journals (Sweden)

    David Christopher Nieman

    2016-09-01

    Full Text Available The cytokine response to heavy exertion varies widely for unknown reasons, and this study evaluated the relative importance of glycogen depletion, muscle damage, and stress hormone changes on blood and muscle cytokine measures. Cyclists (N=20 participated in a 75-km cycling time trial (168±26.0 min, with blood and vastus lateralis muscle samples collected before and after. Muscle glycogen decreased 77.2±17.4%, muscle IL-6, IL-8, and MCP-1 mRNA increased 18.5±2.8-, 45.3±7.8-, and 8.25±1.75-fold, and muscle IL-6, IL-8, and MCP-1 protein increased 70.5±14.1%, 347±68.1%, and 148±21.3%, respectively (all, P<0.001. Serum myoglobin and cortisol increased 32.1±3.3 to 242±48.3 mg/mL, and 295±27.6 to 784±63.5 nmol/L, respectively (both P<0.001. Plasma IL-6, IL-8, and MCP-1 increased 0.42±0.07 to 18.5±3.8, 4.07±0.37 to 17.0±1.8, and 96.5±3.7 to 240±21.6 pg/mL, respectively (all P<0.001. Increases in muscle IL-6, IL-8, and MCP-1 mRNA were unrelated to any of the outcome measures. Muscle glycogen depletion was related to change in plasma IL-6 (r=0.462, P=0.040, with change in myoglobin related to plasma IL-8 (r=0.582, P=0.007 and plasma MCP-1 (r=0.457, P=0.043, and muscle MCP-1 protein (r=0.588, P=0.017; cortisol was related to plasma IL-8 (r=0.613, P=0.004, muscle IL-8 protein (r=0.681, P=0.004, and plasma MCP-1 (r=0.442, P=0.050. In summary, this study showed that muscle IL-6, IL-8, and MCP-1 mRNA expression after 75-km cycling was unrelated to glycogen depletion and muscle damage, with change in muscle glycogen related to plasma IL-6, and changes in serum myoglobin and cortisol related to the chemotactic cytokines IL-8 and MCP-1.

  9. Performance and precision of double digestion RAD (ddRAD) genotyping in large multiplexed datasets of marine fish species

    DEFF Research Database (Denmark)

    Maroso, F.; Hillen, J E J; Pardo, B. G.

    2018-01-01

    ; (ii) the discrepancy between expected and observed tag length and coverage; (iii) the performances of reference based vs. de novo approaches; (iv) the sources of potential genotyping errors of the library preparation/bioinformatics protocol, by comparing technical replicates. Our results showed use...... a standardized protocol. A common bioinformatics pipeline based on STACKS was established, with and without the use of a reference genome. We performed analyses throughout the production and analysis of ddRAD data in order to explore (i) the loss of information due to heterogeneous raw read number across samples...... of downstream analysis carried out with ddRAD vs single SNP allele specific assay genotypes provided information about the levels of genotyping imprecision that can have a significant impact on allele frequency estimations and population assignment. The results and insights presented here will help to select...

  10. p115 RhoGEF activates the Rac1 GTPase signaling cascade in MCP1 chemokine-induced vascular smooth muscle cell migration and proliferation.

    Science.gov (United States)

    Singh, Nikhlesh K; Janjanam, Jagadeesh; Rao, Gadiparthi N

    2017-08-25

    Although the involvement of Rho proteins in the pathogenesis of vascular diseases is well studied, little is known about the role of their upstream regulators, the Rho guanine nucleotide exchange factors (RhoGEFs). Here, we sought to identify the RhoGEFs involved in monocyte chemotactic protein 1 (MCP1)-induced vascular wall remodeling. We found that, among the RhoGEFs tested, MCP1 induced tyrosine phosphorylation of p115 RhoGEF but not of PDZ RhoGEF or leukemia-associated RhoGEF in human aortic smooth muscle cells (HASMCs). Moreover, p115 RhoGEF inhibition suppressed MCP1-induced HASMC migration and proliferation. Consistent with these observations, balloon injury (BI) induced p115 RhoGEF tyrosine phosphorylation in rat common carotid arteries, and siRNA-mediated down-regulation of its levels substantially attenuated BI-induced smooth muscle cell migration and proliferation, resulting in reduced neointima formation. Furthermore, depletion of p115 RhoGEF levels also abrogated MCP1- or BI-induced Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling, which, as we reported previously, is involved in vascular wall remodeling. Our findings also show that protein kinase N1 (PKN1) downstream of Rac1-cyclin D1/CDK6 and upstream of CDK4-PAK1 in the p115 RhoGEF-Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling axis is involved in the modulation of vascular wall remodeling. Of note, we also observed that CCR2-G i/o -Fyn signaling mediates MCP1-induced p115 RhoGEF and Rac1 GTPase activation. These findings suggest that p115 RhoGEF is critical for MCP1-induced HASMC migration and proliferation in vitro and for injury-induced neointima formation in vivo by modulating Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. AOPPs Induce MCP-1 Expression by Increasing ROS-Mediated Activation of the NF-κB Pathway in Rat Mesangial Cells: Inhibition by Sesquiterpene Lactones

    Directory of Open Access Journals (Sweden)

    Jian-Cheng Wang

    2013-12-01

    Full Text Available Background: Monocyte chemoattractant protein-1 (MCP-1 plays an important role in extracellular matrix accumulation through macrophage recruitment and activation in the development and progression of diabetic nephropathy. Therefore, this study examined whether advanced oxidation protein products (AOPPs are involved in nuclear factor-κB (NF-κB activation and MCP-1 mRNA and protein expression in mesangial cells (MCs and evaluated the effects of derivatives of sesquiterpene lactones (SLs on AOPP-induced renal damage. Methods: MCP-1 mRNA and protein expression in MCs were determined by quantitative real-time PCR and ELISA, respectively. The level of intracellular reactive oxygen species (ROS was determined by flow cytometry. The protein expression of tubulin, P47, NF-κB p65, phospho-NF-κB p65, IκB, phospho-IκB, IKKß and phospho-IKKß was evaluated by Western blot. Results: AOPPs caused oxidative stress in MCs and activated the NF-κB pathway by inducing IκBa phosphorylation and degradation. Inhibition of ROS by SOD (ROS inhibitor blocked the AOPP-mediated NF-κB pathway. Moreover, the inhibition of AOPP-induced overproduction of MCP-1 mRNA and protein was associated with inhibition of IκBa degradation by SLs. Conclusion: AOPPs induce MCP-1 expression by activating the ROS/NF-κB pathway and can be inhibited by SLs. These findings may provide a novel approach to treat inflammatory and immune renal diseases, including diabetic nephropathy.

  12. RadShield: semiautomated shielding design using a floor plan driven graphical user interface.

    Science.gov (United States)

    DeLorenzo, Matthew C; Wu, Dee H; Yang, Kai; Rutel, Isaac B

    2016-09-08

    The purpose of this study was to introduce and describe the development of RadShield, a Java-based graphical user interface (GUI), which provides a base design that uniquely performs thorough, spatially distributed calculations at many points and reports the maximum air-kerma rate and barrier thickness for each barrier pursuant to NCRP Report 147 methodology. Semiautomated shielding design calculations are validated by two approaches: a geometry-based approach and a manual approach. A series of geometry-based equations were derived giv-ing the maximum air-kerma rate magnitude and location through a first derivative root finding approach. The second approach consisted of comparing RadShield results with those found by manual shielding design by an American Board of Radiology (ABR)-certified medical physicist for two clinical room situations: two adjacent catheterization labs, and a radiographic and fluoroscopic (R&F) exam room. RadShield's efficacy in finding the maximum air-kerma rate was compared against the geometry-based approach and the overall shielding recommendations by RadShield were compared against the medical physicist's shielding results. Percentage errors between the geometry-based approach and RadShield's approach in finding the magnitude and location of the maximum air-kerma rate was within 0.00124% and 14 mm. RadShield's barrier thickness calculations were found to be within 0.156 mm lead (Pb) and 0.150 mm lead (Pb) for the adjacent catheteriza-tion labs and R&F room examples, respectively. However, within the R&F room example, differences in locating the most sensitive calculation point on the floor plan for one of the barriers was not considered in the medical physicist's calculation and was revealed by the RadShield calculations. RadShield is shown to accurately find the maximum values of air-kerma rate and barrier thickness using NCRP Report 147 methodology. Visual inspection alone of the 2D X-ray exam distribution by a medical physicist may not

  13. Tomosynthesis in the Diagnostic Setting: Changing Rates of BI-RADS Final Assessment over Time.

    Science.gov (United States)

    Raghu, Madhavi; Durand, Melissa A; Andrejeva, Liva; Goehler, Alexander; Michalski, Mark H; Geisel, Jaime L; Hooley, Regina J; Horvath, Laura J; Butler, Reni; Forman, Howard P; Philpotts, Liane E

    2016-10-01

    Purpose To evaluate the effect of tomosynthesis in diagnostic mammography on the Breast Imaging Reporting and Data System (BI-RADS) final assessment categories over time. Materials and Methods This retrospective study was approved by the institutional review board. The authors reviewed all diagnostic mammograms obtained during a 12-month interval before (two-dimensional [2D] mammography [June 2, 2010, to June 1, 2011]) and for 3 consecutive years after (tomosynthesis year 1 [2012], tomosynthesis year 2 [2013], and tomosynthesis year 3 [2014]) the implementation of tomosynthesis. The requirement to obtain informed consent was waived. The rates of BI-RADS final assessment categories 1-5 were compared between the 2D and tomosynthesis groups. The positive predictive values after biopsy (PPV3) for BI-RADS category 4 and 5 cases were compared. The mammographic features (masses, architectural distortions, calcifications, focal asymmetries) of lesions categorized as probably benign (BI-RADS category 3) and those for which biopsy was recommended (BI-RADS category 4 or 5) were reviewed. The χ(2) test was used to compare the rates of BI-RADS final assessment categories 1-5 between the two groups, and multivariate logistic regression analysis was performed to compare all diagnostic studies categorized as BI-RADS 3-5. Results There was an increase in the percentage of cases reported as negative or benign (BI-RADS category 1 or 2) with tomosynthesis (58.7% with 2D mammography vs 75.8% with tomosynthesis at year 3, P tomosynthesis at year 3, P tomosynthesis (8.0% with 2D mammography vs 7.8% with tomosynthesis at year 3, P = .2), there was a significant increase in the PPV3 (29.6% vs 50%, respectively; P tomosynthesis use. Conclusion Tomosynthesis in the diagnostic setting resulted in progressive shifts in the BI-RADS final assessment categories over time, with a significant increase in the proportion of studies classified as normal, a continued decrease in the rate of studies

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

    DEFF Research Database (Denmark)

    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 Rad...

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

    International Nuclear Information System (INIS)

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

    1979-01-01

    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

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

    Science.gov (United States)

    Ward, Ayobami; Hopkins, Jessica; Mckay, Matthew; Murray, Steve; Jordan, Philip W

    2016-06-01

    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 cohesins required for

  17. Characterization of nanoDot optically stimulated luminescence detectors and high-sensitivity MCP-N thermoluminescent detectors in the 40-300 kVp energy range.

    Science.gov (United States)

    Poirier, Yannick; Kuznetsova, Svetlana; Villarreal-Barajas, Jose Eduardo

    2018-01-01

    To investigate empirically the energy dependence of the detector response of two in vivo luminescence detectors, LiF:Mg,Cu,P (MCP-N) high-sensitivity TLDs and Al 2 O 3 :C OSLDs, in the 40-300-kVp energy range in the context of in vivo surface dose measurement. As these detectors become more prevalent in clinical and preclinical in vivo measurements, knowledge of the variation in the empirical dependence of the measured response of these detectors across a wide spectrum of beam qualities is important. We characterized a large range of beam qualities of three different kilovoltage x-ray units: an Xstrahl 300 Orthovoltage unit, a Precision x-Ray X-RAD 320ix biological irradiator, and a Varian On-Board Imaging x-ray unit. The dose to water was measured in air according to the AAPM's Task Group 61 protocol. The OSLDs and TLDs were irradiated under reference conditions on the surface of a water phantom to provide full backscatter conditions. To assess the change in sensitivity in the long term, we separated the in vivo dosimeters of each type into an experimental and a reference group. The experimental dosimeters were irradiated using the kilovoltage x-ray units at each beam quality used in this investigation, while the reference group received a constant 10 cGy irradiation at 6 MV from a Varian clinical linear accelerator. The individual calibration of each detector was verified in cycles where both groups received a 10 cGy irradiation at 6 MV. The nanoDot OSLDs were highly reproducible, with ±1.5% variation in response following >40 measurement cycles. The TLDs lost ~20% of their signal sensitivity over the course of the study. The relative light output per unit dose to water of the MCP-N TLDs did not vary with beam quality for beam qualities with effective energies <50 keV (~150 kVp/6 mm Al). At higher energies, they showed a reduced (~75-85%) light output per unit dose relative to 6 MV x rays. The nanoDot OSLDs exhibited a very strong (120

  18. RAD51 and RTEL1 compensate telomere loss in the absence of telomerase.

    Science.gov (United States)

    Olivier, Margaux; Charbonnel, Cyril; Amiard, Simon; White, Charles I; Gallego, Maria E

    2018-03-16

    Replicative erosion of telomeres is naturally compensated by telomerase and studies in yeast and vertebrates show that homologous recombination can compensate for the absence of telomerase. We show that RAD51 protein, which catalyzes the key strand-invasion step of homologous recombination, is localized at Arabidopsis telomeres in absence of telomerase. Blocking the strand-transfer activity of the RAD51 in telomerase mutant plants results in a strikingly earlier onset of developmental defects, accompanied by increased numbers of end-to-end chromosome fusions. Imposing replication stress through knockout of RNaseH2 increases numbers of chromosome fusions and reduces the survival of these plants deficient for telomerase and homologous recombination. This finding suggests that RAD51-dependent homologous recombination acts as an essential backup to the telomerase for compensation of replicative telomere loss to ensure genome stability. Furthermore, we show that this positive role of RAD51 in telomere stability is dependent on the RTEL1 helicase. We propose that a RAD51 dependent break-induced replication process is activated in cells lacking telomerase activity, with RTEL1 responsible for D-loop dissolution after telomere replication.

  19. Rad-hard embedded computers for nuclear robotics

    International Nuclear Information System (INIS)

    Giraud, A.; Joffre, F.; Marceau, M.; Robiolle, M.; Brunet, J.P.; Mijuin, D.

    1993-01-01

    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

  20. Increased cerebrospinal fluid levels of cytokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Martínez, H R; Escamilla-Ocañas, C E; Camara-Lemarroy, C R; González-Garza, M T; Moreno-Cuevas, J; García Sarreón, M A

    2017-10-10

    Neuroinflammation has recently been described in amyotrophic lateral sclerosis (ALS). However, the precise role of such proinflammatory cytokines as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) in ALS has not yet been determined. In this study, we determined cerebrospinal fluid (CSF) MCP-1 and MIP-1β levels and assessed their association with the duration and severity of ALS. Concentrations of MCP-1 and MIP-1β were determined in the CSF of 77 patients diagnosed with ALS and 13 controls. Cytokine levels were analysed in relation to ALS duration (12months) and severity (30points on the ALS Functional Rating Scale administered at hospital admission). Higher CSF MIP-1β (10.68pg/mL vs. 4.69pg/mL, P<.0001) and MCP-1 (234.89pg/mL vs. 160.95pg/mL, P=.011) levels were found in the 77 patients with ALS compared to controls. There were no differences in levels of either cytokine in relation to disease duration or severity. However, we did observe a significant positive correlation between MIP-1β and MCP-1 in patients with ALS. The increase in MIP-1β and MCP-1 levels suggests that these cytokines may have a synergistic effect on ALS pathogenesis. However, in our cohort, no association was found with either the duration or the clinical severity of the disease. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Early Postoperative Low Expression of RAD50 in Rectal Cancer Patients Associates with Disease-Free Survival

    Directory of Open Access Journals (Sweden)

    Vincent Ho

    2017-11-01

    Full Text Available Background: Molecular biomarkers have the potential to predict response to the treatment of rectal cancer. In this study, we aimed to evaluate the prognostic and clinicopathological implication of RAD50 (DNA repair protein RAD50 homolog expression in rectal cancer. Methods: A total of 266 rectal cancer patients who underwent surgery and received chemo- and radiotherapy between 2000 and 2011 were involved in the study. Postoperative RAD50 expression was determined by immunohistochemistry in surgical samples (n = 266. Results: Using Kaplan–Meier survival analysis, we found that low RAD50 expression in postoperative samples was associated with worse disease free survival (p = 0.001 and overall survival (p < 0.001 in early stage/low-grade tumors. In a comparison of patients with low vs. high RAD50 expression, we found that low levels of postoperative RAD50 expression in rectal cancer tissues were significantly associated with perineural invasion (p = 0.002. Conclusion: Expression of RAD50 in rectal cancer may serve as a prognostic biomarker for long-term survival of patients with perineural invasion-positive tumors and for potential use in early stage and low-grade rectal cancer assessment.

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

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

    Hodge, Rebecca; Hellmann, Sophie Sell; von Euler-Chelpin, My

    2014-01-01

    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...... dichotomous mammographic density classification system from 1991 to 2001 with the density BI-RADS classifications, in an attempt to validate the Danish classification system. MATERIAL AND METHODS: The study sample consisted of 120 mammograms taken in Copenhagen in 1991-2001, which tested false positive......, and which were in 2012 re-assessed and classified according to the BI-RADS classification system. We calculated inter-rater agreement between the Danish dichotomous mammographic classification as fatty or mixed/dense and the four-level BI-RADS classification by the linear weighted Kappa statistic. RESULTS...

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

    International Nuclear Information System (INIS)

    Lambert, S.

    2001-01-01

    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) [fr

  5. Effects of postharvest application of 1-MCP and postcutting dip treatment on the quality and nutritional properties of fresh-cut kiwifruit.

    Science.gov (United States)

    Antunes, Maria D C; Dandlen, Susana; Cavaco, Ana M; Miguel, Graça

    2010-05-26

    Consumption of minimally processed fruit and vegetables has increased significantly in the past few years due to the consumers' life style. The aim of this study was to evaluate the effect of treatment with ascorbic acid or calcium chloride on the quality parameters of fresh-cut kiwifruit prepared from fruit previously stored for 3 months, either treated or not treated with 1-methylcyclopropene (1-MCP) before storage. Harvested fruit were treated with 1 microL L(-1) 1-MCP for 20 h at room temperature ( approximately 20 degrees C) (MCP) or had no treatment (C) and were then stored at 0 degrees C. After 3 months, fruit were removed from storage, peeled, and cut longitudinally in quarters, dipped in 2% ascorbic acid (Asc), 2% calcium chloride (Ca), or just water (cont), and kept at 2 degrees C for 8 days. Measurements of firmness, soluble solids content (SSC) ( degrees Brix), color (CIE L*, a*, b*), electrolyte leakage, sugars, organic acids, total phenolics, and antioxidant activity (DPPH and ABTS) were performed at 0, 4, and 8 days. A taste panel was performed on the seventh shelf life day. It was shown that whole MCP-treated kiwifruit kept better than the control through the 3 months storage, this effect being lost through the fresh-cut shelf life period. Furthermore, the postcut dip on 2% CaCl(2) was effective on delaying softening and browning of fresh-cut kiwifruit, which were also the fruit preferred by panelists. Both ascorbic acid and CaCl(2) were effective on preserving or improving nutritional properties (phenolics, ascorbic acid, DPPH, and ABTS) mainly in the first 4 days of shelf life. The CaCl(2) had a further beneficial effect until 8 shelf life days. It is suggested that CaCl(2) is better in keeping overall quality through 8 days of shelf life at 2 degrees C in fresh-cut kiwifruit followed by Asc, and 1-MCP has negligible effect in the conditions of this experiment.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Huiling Xu

    2014-12-01

    Full Text Available Summary: 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. : Rad21 holds the cohesin complex together as part of its role in chromosome partitioning and DNA repair. Xu et al. identify Rad21 as a key mediator of Apc gene heterozygous loss, the event initiating intestinal tumorigenesis. The subsequent activation of the Wnt pathway further induces Rad21, global gene dysregulation, chromosome instability, and pervasive retrotransposon activation.

  8. EFECTO DEL 1-METILCICLOPROPENO (1-MCP SOBRE LA FISIOLOGÍA Y CALIDAD DE FRUTOS DE JACA (Artocarpus heterophyllus Lam.

    Directory of Open Access Journals (Sweden)

    M. Mata-Montes de Oca

    2007-01-01

    Full Text Available Debido a sus características de color y sabor de pulpa, la demanda de fruta de jaca se ha incrementado considerablemente. La mayoría de la producción de Nayarit es exportada a los Estados Unidos de Norteamérica. Sin embargo, debido a su corta vida de anaquel y susceptibilidad al daño por frío la fruta es exportada vía aérea con altos costos de flete. Se reporta que el 1-Metilciclopropeno (1-MCP retarda el proceso de madurez, alarga la vida de anaquel y mantiene la calidad de varios frutales, así que el objetivo de este estudio fue evaluar el efecto del 1-MCP sobre la fisiología y calidad del fruto de jaca almacenado a 20 ºC. Las frutas fueron cosechadas en madurez fisiológica, lavadas y tratadas con 1-MCP a 100 y 300 nl·litro-1 en cámaras selladas por 12 h a 20 ± 1 ºC; 85 ± 5 % de HR manteniendo un testigo sin tratar. Las variables evaluadas fueron: velocidad de respiración y de producción de etileno, sólidos solubles totales, acidez titulable, firmeza de la pulpa y de la fruta entera, color en la pulpa y pérdida de peso. El 1-MCP no afectó la mayoría de las variables de calidad pero retrasó significativamente la velocidad de respiración y la producción de etileno así como el ablandamiento de la pulpa, lo que permitió prolongar la vida de anaquel hasta por ocho y 12 días a 100 y 300 nl·litro-1, respectivamente.

  9. Conservatism in SRS Criticality Alarm System 12 Rad Zone Calculations - How Much is Enough?

    International Nuclear Information System (INIS)

    Yates, K.R.

    2002-01-01

    Savannah River Site (SRS) uses two methods (i.e., Approximate Method and MCNP) of calculating the 12-rad zone. The reasons for the two-tier approach are described in Ref. 1 and 2. Lately, there have been occasions in which the use of either the Approximate Method (AM) or MCNP3 calculations indicated potential facility impacts. For example, one or both methods may indicate that a 12-rad zone extends outside of relatively thick shielding, or extends to the roof of a facility, or extends through shielding to part of a stairwell. In such cases, a criticality alarm system may have to be installed to protect workers in a small, localized area from a potential dose that is not substantially greater than 12 rad in air. But, is the potential dose really greater than 12 rad in air? A subcommittee was appointed to look into the two 12-rad zone calculation methods for the purpose of identifying items contributing to over-conservatism and under-conservatism, and to recommend a path forward

  10. Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks.

    Science.gov (United States)

    Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia; Evangelou, Konstantinos; Da-Ré, Caterina; Huber, Florian; Padayachy, Laura; Tardy, Sebastien; Nicati, Noemie L; Barriot, Samia; Ochs, Fena; Lukas, Claudia; Lukas, Jiri; Gorgoulis, Vassilis G; Scapozza, Leonardo; Halazonetis, Thanos D

    2016-12-15

    Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, a gene dispensable for normal development in mice, was among the top hits. In cells in which fork collapse was induced by oncogenes or chemicals, the Rad52 protein localized to DRS foci. Depletion of Rad52 by siRNA or knockout of the gene by CRISPR/Cas9 compromised restart of collapsed forks and led to DNA damage in cells experiencing DRS. Furthermore, in cancer-prone, heterozygous APC mutant mice, homozygous deletion of the Rad52 gene suppressed tumor growth and prolonged lifespan. We therefore propose that mammalian RAD52 facilitates repair of collapsed DNA replication forks in cancer cells. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. Checkpoint Kinase Rad53 Couples Leading- and Lagging-Strand DNA Synthesis under Replication Stress.

    Science.gov (United States)

    Gan, Haiyun; Yu, Chuanhe; Devbhandari, Sujan; Sharma, Sushma; Han, Junhong; Chabes, Andrei; Remus, Dirk; Zhang, Zhiguo

    2017-10-19

    The checkpoint kinase Rad53 is activated during replication stress to prevent fork collapse, an essential but poorly understood process. Here we show that Rad53 couples leading- and lagging-strand synthesis under replication stress. In rad53-1 cells stressed by dNTP depletion, the replicative DNA helicase, MCM, and the leading-strand DNA polymerase, Pol ε, move beyond the site of DNA synthesis, likely unwinding template DNA. Remarkably, DNA synthesis progresses further along the lagging strand than the leading strand, resulting in the exposure of long stretches of single-stranded leading-strand template. The asymmetric DNA synthesis in rad53-1 cells is suppressed by elevated levels of dNTPs in vivo, and the activity of Pol ε is compromised more than lagging-strand polymerase Pol δ at low dNTP concentrations in vitro. Therefore, we propose that Rad53 prevents the generation of excessive ssDNA under replication stress by coordinating DNA unwinding with synthesis of both strands. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair.

    Science.gov (United States)

    Cukras, Scott; Lee, Euiho; Palumbo, Emily; Benavidez, Pamela; Moldovan, George-Lucian; Kee, Younghoon

    2016-10-01

    USP1 deubiquitinating enzyme and its stoichiometric binding partner UAF1 play an essential role in promoting DNA homologous recombination (HR) repair in response to various types of DNA damaging agents. Deubiquitination of FANCD2 may be attributed to the key role of USP1-UAF1 complex in regulating HR repair, however whether USP1-UAF1 promotes HR repair independently of FANCD2 deubiquitination is not known. Here we show evidence that the USP1-UAF1 complex has a FANCD2-independent function in promoting HR repair. Proteomic search of UAF1-interacting proteins revealed that UAF1 associates with RAD51AP1, a RAD51-interacting protein implicated in HR repair. We show that UAF1 mediates the interaction between USP1 and RAD51AP1, and that depletion of USP1 or UAF1 led to a decreased stability of RAD51AP1. Protein interaction mapping analysis identified some key residues within RAD51AP1 required for interacting with the USP1-UAF1 complex. Cells expressing the UAF1 interaction-deficient mutant of RAD51AP1 show increased chromosomal aberrations in response to Mitomycin C treatment. Moreover, similar to the RAD51AP1 depleted cells, the cells expressing UAF1-interaction deficient RAD51AP1 display persistent RAD51 foci following DNA damage exposure, indicating that these factors regulate a later step during the HR repair. These data altogether suggest that the USP1-UAF1 complex promotes HR repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1.

  13. RadNet Real-Time Monitoring Spectrometry Data Inventory

    Data.gov (United States)

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Rhizoma coptidis Inhibits LPS-Induced MCP-1/CCL2 Production in Murine Macrophages via an AP-1 and NFB-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Andrew Remppis

    2010-01-01

    Full Text Available Introduction. The Chinese extract Rhizoma coptidis is well known for its anti-inflammatory, antioxidative, antiviral, and antimicrobial activity. The exact mechanisms of action are not fully understood. Methods. We examined the effect of the extract and its main compound, berberine, on LPS-induced inflammatory activity in a murine macrophage cell line. RAW 264.7 cells were stimulated with LPS and incubated with either Rhizoma coptidis extract or berberine. Activation of AP-1 and NFB was analyzed in nuclear extracts, secretion of MCP-1/CCL2 was measured in supernatants. Results. Incubation with Rhizoma coptidis and berberine strongly inhibited LPS-induced monocyte chemoattractant protein (MCP-1 production in RAW cells. Activation of the transcription factors AP-1 and NFB was inhibited by Rhizoma coptidis in a dose- and time-dependent fashion. Conclusions. Rhizoma coptidis extract inhibits LPS-induced MCP-1/CCL2 production in vitro via an AP-1 and NFB-dependent pathway. Anti-inflammatory action of the extract is mediated mainly by its alkaloid compound berberine.

  16. Cloning of human and mouse genes homologous to RAD52, a yeast gene involved in DNA repair and recombination.

    NARCIS (Netherlands)

    D.F.R. Muris; O.Y. Bezzubova (Olga); J-M. Buerstedde; K. Vreeken; A.S. Balajee; C.J. Osgood; C. Troelstra (Christine); J.H.J. Hoeijmakers (Jan); K. Ostermann; H. Schmidt (Henning); A.T. Natarajan; J.C.J. Eeken; P.H.M. Lohmann (Paul); A. Pastink (Albert)

    1994-01-01

    textabstractThe RAD52 gene of Saccharomyces cerevisiae is required for recombinational repair of double-strand breaks. Using degenerate oligonucleotides based on conserved amino acid sequences of RAD52 and rad22, its counterpart from Schizosaccharomyces pombe, RAD52 homologs from man and mouse were

  17. Performance of the RAD-57 pulse CO-oximeter compared with standard laboratory carboxyhemoglobin measurement.

    Science.gov (United States)

    Touger, Michael; Birnbaum, Adrienne; Wang, Jessica; Chou, Katherine; Pearson, Darion; Bijur, Polly

    2010-10-01

    We assess agreement between carboxyhemoglobin levels measured by the Rad-57 signal extraction pulse CO-oximeter (RAD), a Food and Drug Administration-approved device for noninvasive bedside measurement, and standard laboratory arterial or venous measurement in a sample of emergency department (ED) patients with suspected carbon monoxide poisoning. The study was a cross-sectional cohort design using a convenience sample of adult and pediatric ED patients in a Level I trauma, burn, and hyperbaric oxygen referral center. Measurement of RAD carboxyhemoglobin was performed simultaneously with blood sampling for laboratory determination of carboxyhemoglobin level. The difference between the measures for each patient was calculated as laboratory carboxyhemoglobin minus carboxyhemoglobin from the carbon monoxide oximeter. The limits of agreement from a Bland-Altman analysis are calculated as the mean of the differences between methods ±1.96 SDs above and below the mean. Median laboratory percentage carboxyhemoglobin level was 2.3% (interquartile range 1 to 8.5; range 0% to 38%). The mean difference between laboratory carboxyhemoglobin values and RAD values was 1.4% carboxyhemoglobin (95% confidence interval [CI] 0.2% to 2.6%). The limits of agreement of differences of measurement made with the 2 devices were -11.6% and 14.4% carboxyhemoglobin. This range exceeded the value of ±5% carboxyhemoglobin defined a priori as clinically acceptable. RAD correctly identified 11 of 23 patients with laboratory values greater than 15% carboxyhemoglobin (sensitivity 48%; 95% CI 27% to 69%). There was one case of a laboratory carboxyhemoglobin level less than 15%, in which the RAD device gave a result greater than 15% (specificity of RAD 96/97=99%; 95% CI 94% to 100%). In the range of carboxyhemoglobin values measured in this sample, the level of agreement observed suggests RAD measurement may not be used interchangeably with standard laboratory measurement. Copyright © 2010 American

  18. Rad51 expression levels predict synthetic lethality and metastatic potential in high grade breast cancers

    International Nuclear Information System (INIS)

    Wiegmans, A.P.; Al-Ejeh, F.; Khanna, K.K.

    2012-01-01

    Among women with breast cancer, 30-40% will develop metastatic disease and only achieve an overall survival of less than 5 years. Despite new-targeted therapy, breast tumors that harbour similar histology or molecular phenotype differ in their response to treatment. To uncover potential new therapeutic targets and improve outcome, we performed data mining of cancer micro array databases. We found that high expression of the homologous recombination protein, RAD51, was significantly associated with high-grade breast cancer, aggressive subtypes and increased risk of metastasis. We confirmed using immunohistochemistry that RAD5 1 was highly expressed in metastatic tumours and high-grade triple negative, HER2+ and luminal-B tumours. This provided a rationale for targeting RAD5 1 in high-grade, therapy-resistant breast cancers. Here, we report for the first time preclinical evaluation of RAD5 1 as a therapeutic target. We found that, in-vitro high RAD5 expressing cell lines were resistant to PARP inhibitor while knockdown reversed this resistance. In-vivo, knockdown of RAD5 1 inhibited metastatic progression using a syngeneic breast cancer model and the seeding of human xenografts to distant sites, including brain and lung. Concurrent PARP inhibition reduced primary tumor growth and delayed metastasis supporting synthetic lethality in-vivo. Together these insights provide pre-clinical data demonstrating RAD5 1 as a new biomarker and potential therapeutic target against aggressive metastatic breast cancer. (author)

  19. PI-RADS v2 and ADC values: is there room for improvement?

    Science.gov (United States)

    Jordan, Eric J; Fiske, Charles; Zagoria, Ronald; Westphalen, Antonio C

    2018-03-17

    To determine the diagnostic accuracy of ADC values in combination with PI-RADS v2 for the diagnosis of clinically significant prostate cancer (CS-PCa) compared to PI-RADS v2 alone. This retrospective study included 155 men whom underwent 3-Tesla prostate MRI and subsequent MR/US fusion biopsies at a single non-academic center from 11/2014 to 3/2016. All scans were performed with a surface coil and included T2, diffusion-weighted, and dynamic contrast-enhanced sequences. Suspicious findings were classified using Prostate Imaging Reporting and Data System (PI-RADS) v2 and targeted using MR/US fusion biopsies. Mixed-effect logistic regression analyses were used to determine the ability of PIRADS v2 alone and combined with ADC values to predict CS-PCa. As ADC categories are more practical in clinical situations than numeric values, an additional model with ADC categories of ≤ 800 and > 800 was performed. A total of 243 suspicious lesions were included, 69 of which were CS-PCa, 34 were Gleason score 3+3 PCa, and 140 were negative. The overall PIRADS v2 score, ADC values, and ADC categories are independent statistically significant predictors of CS-PCa (p values or categories is better discrimination of PI-RADS v2 4 lesions. ADC values and categories help to diagnose CS-PCa when lesions are assigned a PI-RADS v2 score of 4.

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    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...... 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...... cells with RAD51 sense or antisense constructs and measured the VP16 resistance. Finally, we measured VP16-induced DSBs in the 17 SCLC cell lines. Two cell lines exhibited a multidrug-resistant phenotype. In the other SCLC cell lines, the cellular VP16 resistance was positively correlated with the RAD51...

  1. Requirement of Sequences outside the Conserved Kinase Domain of Fission Yeast Rad3p for Checkpoint Control

    Science.gov (United States)

    Chapman, Carolyn Riley; Evans, Sarah Tyler; Carr, Antony M.; Enoch, Tamar

    1999-01-01

    The fission yeast Rad3p checkpoint protein is a member of the phosphatidylinositol 3-kinase-related family of protein kinases, which includes human ATMp. Mutation of the ATM gene is responsible for the disease ataxia-telangiectasia. The kinase domain of Rad3p has previously been shown to be essential for function. Here, we show that although this domain is necessary, it is not sufficient, because the isolated kinase domain does not have kinase activity in vitro and cannot complement a rad3 deletion strain. Using dominant negative alleles of rad3, we have identified two sites N-terminal to the conserved kinase domain that are essential for Rad3p function. One of these sites is the putative leucine zipper, which is conserved in other phosphatidylinositol 3-kinase-related family members. The other is a novel motif, which may also mediate Rad3p protein–protein interactions. PMID:10512862

  2. Proto-jet configurations in RADs orbiting a Kerr SMBH: symmetries and limiting surfaces

    Science.gov (United States)

    Pugliese, D.; Stuchlík, Z.

    2018-05-01

    Ringed accretion disks (RADs) are agglomerations of perfect-fluid tori orbiting around a single central attractor that could arise during complex matter inflows in active galactic nuclei. We focus our analysis to axi-symmetric accretion tori orbiting in the equatorial plane of a supermassive Kerr black hole; equilibrium configurations, possible instabilities, and evolutionary sequences of RADs were discussed in our previous works. In the present work we discuss special instabilities related to open equipotential surfaces governing the material funnels emerging at various regions of the RADs, being located between two or more individual toroidal configurations of the agglomerate. These open structures could be associated to proto-jets. Boundary limiting surfaces are highlighted, connecting the emergency of the jet-like instabilities with the black hole dimensionless spin. These instabilities are observationally significant for active galactic nuclei, being related to outflows of matter in jets emerging from more than one torus of RADs orbiting around supermassive black holes.

  3. Oak Ridge Reservation Environmental Protection Rad Neshaps Radionuclide Inventory Web Database and Rad Neshaps Source and Dose Database.

    Science.gov (United States)

    Scofield, Patricia A; Smith, Linda L; Johnson, David N

    2017-07-01

    The U.S. Environmental Protection Agency promulgated national emission standards for emissions of radionuclides other than radon from US Department of Energy facilities in Chapter 40 of the Code of Federal Regulations (CFR) 61, Subpart H. This regulatory standard limits the annual effective dose that any member of the public can receive from Department of Energy facilities to 0.1 mSv. As defined in the preamble of the final rule, all of the facilities on the Oak Ridge Reservation, i.e., the Y-12 National Security Complex, Oak Ridge National Laboratory, East Tennessee Technology Park, and any other U.S. Department of Energy operations on Oak Ridge Reservation, combined, must meet the annual dose limit of 0.1 mSv. At Oak Ridge National Laboratory, there are monitored sources and numerous unmonitored sources. To maintain radiological source and inventory information for these unmonitored sources, e.g., laboratory hoods, equipment exhausts, and room exhausts not currently venting to monitored stacks on the Oak Ridge National Laboratory campus, the Environmental Protection Rad NESHAPs Inventory Web Database was developed. This database is updated annually and is used to compile emissions data for the annual Radionuclide National Emission Standards for Hazardous Air Pollutants (Rad NESHAPs) report required by 40 CFR 61.94. It also provides supporting documentation for facility compliance audits. In addition, a Rad NESHAPs source and dose database was developed to import the source and dose summary data from Clean Air Act Assessment Package-1988 computer model files. This database provides Oak Ridge Reservation and facility-specific source inventory; doses associated with each source and facility; and total doses for the Oak Ridge Reservation dose.

  4. Rad10 exhibits lesion-dependent genetic requirements for recruitment to DNA double-strand breaks in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Moore, Destaye M; Karlin, Justin; González-Barrera, Sergio

    2009-01-01

    In the yeast Saccharomyces cerevisiae, the Rad1-Rad10 protein complex participates in nucleotide excision repair (NER) and homologous recombination (HR). During HR, the Rad1-Rad10 endonuclease cleaves 3' branches of DNA and aberrant 3' DNA ends that are refractory to other 3' processing enzymes. ...

  5. Breast Density Estimation with Fully Automated Volumetric Method: Comparison to Radiologists' Assessment by BI-RADS Categories.

    Science.gov (United States)

    Singh, Tulika; Sharma, Madhurima; Singla, Veenu; Khandelwal, Niranjan

    2016-01-01

    The objective of our study was to calculate mammographic breast density with a fully automated volumetric breast density measurement method and to compare it to breast imaging reporting and data system (BI-RADS) breast density categories assigned by two radiologists. A total of 476 full-field digital mammography examinations with standard mediolateral oblique and craniocaudal views were evaluated by two blinded radiologists and BI-RADS density categories were assigned. Using a fully automated software, mean fibroglandular tissue volume, mean breast volume, and mean volumetric breast density were calculated. Based on percentage volumetric breast density, a volumetric density grade was assigned from 1 to 4. The weighted overall kappa was 0.895 (almost perfect agreement) for the two radiologists' BI-RADS density estimates. A statistically significant difference was seen in mean volumetric breast density among the BI-RADS density categories. With increased BI-RADS density category, increase in mean volumetric breast density was also seen (P BI-RADS categories and volumetric density grading by fully automated software (ρ = 0.728, P BI-RADS density category by two observers showed fair agreement (κ = 0.398 and 0.388, respectively). In our study, a good correlation was seen between density grading using fully automated volumetric method and density grading using BI-RADS density categories assigned by the two radiologists. Thus, the fully automated volumetric method may be used to quantify breast density on routine mammography. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  6. DMC1 functions in a Saccharomyces cerevisiae meiotic pathway that is largely independent of the RAD51 pathway

    International Nuclear Information System (INIS)

    Dresser, M.E.; Ewing, D.J.; Conrad, M.N.; Dominguez, A.M.; Barstead, R.; Jiang, H.; Kodadek, T.

    1997-01-01

    Meiotic recombination in the yeast Saccharomyces cerevisiae requires two similar recA-like proteins, Dmc1p and Rad51p. A screen for dominant meiotic mutants provided DMC1-G126D, a dominant allele mutated in the conserved ATP-binding site (specifically, the A-loop motif) that confers a null phenotype. A recessive null allele, dmc1-K69E, was isolated as an intragenic suppressor of DMC1-G126D. Dmc1-K69Ep, unlike Dmc1p, does not interact homotypically in a two-hybrid assay, although it does interact with other fusion proteins identified by two-hybrid screen with Dmc1p. Dmc1p, unlike Rad51p, does not interact in the two-hybrid assay with Rad52p or Rad54p. However, Dmc1p does interact with Tid1p, a Rad54p homologue, with Tid4p, a Rad16p homologue, and with other fusion proteins that do not interact with Rad51p, suggesting that Dmc1p and Rad51p function in separate, though possibly overlapping, recombinational repair complexes. Epistasis analysis suggests that DMC1 and RAD51 function in separate pathways responsible for meiotic recombination. Taken together, our results are consistent with a requirement for DMC1 for meiosis-specific entry of DNA double-strand break ends into chromatin. Interestingly, the pattern on CHEF gels of chromosome fragments that result from meiotic DNA double-strand break formation is different in DMC1 mutant strains from that seen in rad50S strains. (author)

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

    International Nuclear Information System (INIS)

    Wu, Yican; Cheng, Mengyun; Wang, Wen; Fan, Yanchang; Zhao, Kai; He, Tao; Pei, Xi; Shang, Leiming; Chen, Chaobin; Long, Pengcheng; Cao, Ruifen; Wang, Guozhong; Zhou, Shaoheng; Yu, Shengpeng; Hu, Liqin; Zeng, Q.

    2013-01-01

    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

  8. The Effect of Post-Resistance Exercise Amino Acids on Plasma MCP-1 and CCR2 Expression

    Directory of Open Access Journals (Sweden)

    Adam J. Wells

    2016-07-01

    Full Text Available The recruitment and infiltration of classical monocytes into damaged muscle is critical for optimal tissue remodeling. This study examined the effects of an amino acid supplement on classical monocyte recruitment following an acute bout of lower body resistance exercise. Ten resistance-trained men (24.7 ± 3.4 years; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm ingested supplement (SUPP or placebo (PL immediately post-exercise in a randomized, cross-over design. Blood samples were obtained at baseline (BL, immediately (IP, 30-min (30P, 1-h (1H, 2-h (2H, and 5-h (5H post-exercise to assess plasma concentrations of monocyte chemoattractant protein 1 (MCP-1, myoglobin, cortisol and insulin concentrations; and expressions of C-C chemokine receptor-2 (CCR2, and macrophage-1 antigen (CD11b on classical monocytes. Magnitude-based inferences were used to provide inferences on the true effects of SUPP compared to PL. Changes in myoglobin, cortisol, and insulin concentrations were similar between treatments. Compared to PL, plasma MCP-1 was “very likely greater” (98.1% likelihood effect in SUPP at 2H. CCR2 expression was “likely greater” at IP (84.9% likelihood effect, “likely greater” at 1H (87.7% likelihood effect, “very likely greater” at 2H (97.0% likelihood effect, and “likely greater” at 5H (90.1% likelihood effect in SUPP, compared to PL. Ingestion of SUPP did not influence CD11b expression. Ingestion of an amino acid supplement immediately post-exercise appears to help maintain plasma MCP-1 concentrations and augment CCR2 expression in resistance trained men.

  9. Role of teh Rad52 Amino-terminal DNA Binding Activity in DNA Strand Capture in Homologous Recombination

    DEFF Research Database (Denmark)

    Shi, Idina; Hallwyl, Swee Chuang Lim; Seong, Changhyun

    2009-01-01

    Saccharomyces cerevisiae Rad52 protein promotes homologous recombination by nucleating the Rad51 recombinase onto replication protein A-coated single-stranded DNA strands and also by directly annealing such strands. We show that the purified rad52-R70A mutant protein, with a compromised amino-ter...

  10. 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

    International Nuclear Information System (INIS)

    Yao, Michelle S.; Bladl, Anthony R.; Petrini, John H.J.

    1997-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Yugoslav central disposal system or rad waste materials: necessity and justification of construction

    International Nuclear Information System (INIS)

    Peric, A.; Plecas, I.; Pavlovic, R.

    1995-01-01

    Decision on searching for the location and the choice of appropriate type of system for final disposal of low and intermediate level rad waste materials should be made urgently in Yugoslavia. capacities for further storing of such waste materials on the site of the Vinca Institute will be full in the next few years, following the trend of present rad waste generation and delivery. Selection of the location and type of the disposal system in Yugoslavia is of crucial importance from the point of view of conservation of environment quality level and enabling permanent control of disposed immobilized rad waste materials and its impact on the environment. (author)

  13. Breast imaging reporting and data system (BI-RADS) or French 'classification ACR'

    International Nuclear Information System (INIS)

    Dilhuydy, Marie Helene

    2007-01-01

    Summary: The American College of Radiology Task Force on Breast Cancer published in 2003 Fourth edition of BI-RADS for Mammography. It is a lexicon of mammography terms including illustrations of each feature described, followed by a reporting format with assessment categories according to the degree of concern. The aim is to reduce inconsistencies in mammography reports and recommendations for assessment, to facilitate outcome monitoring and to allow each radiologist to audit his own mammography practice. In France, the Societe Francaise de Radiologie acquired the rights to translate BI-RADS, word for word and without adaptation or influence. The last edition was published in 2004. Simultaneously, French Haute Autorite de Sante and National Committee for Breast Cancer Screening proposed to all community practice mammography facilities a classification of detected abnormalities stating more clearly than BI-RADS do which feature has to be included in such and such assessment category and how to manage it. This 'classification ACR' is adapted from BI-RADS but strongly influenced by the context of the French nationwide screening programme, and by European recommendations to limitate undesirable risks of screening such as false positive and overdiagnosis. The differences between the two systems are discussed

  14. p53 is involved in clearance of ionizing radiation-induced RAD51 foci in a human colon cancer cell line

    International Nuclear Information System (INIS)

    Orre, Lukas M.; Stenerloew, Bo; Dhar, Sumeer; Larsson, Rolf; Lewensohn, Rolf; Lehtioe, Janne

    2006-01-01

    We have investigated p53-related differences in cellular response to DNA damaging agents, focusing on p53s effects on RAD51 protein level and sub-cellular localization post exposure to ionizing radiation. In a human colon cancer cell line, HCT116 and its isogenic p53-/- subcell line we show here p53-independent RAD51 foci formation but interestingly the resolution of RAD51 foci showed clear p53 dependence. In p53 wt cells, but not in p53-/- cells, RAD51 protein level decreased 48 h post irradiation and fluorescence immunostaining showed resolution of RAD51 foci and relocalization of RAD51 to nucleoli at time points corresponding to the decrease in RAD51 protein level. Both cell lines rejoined DNA double strand breaks efficiently with similar kinetics and p53 status did not influence sensitivity to DNA damaging agents. We suggest that p53 has a role in RAD51 clearance post DSB repair and that nucleoli might be sites of RAD51 protein degradation

  15. The host response to the probiotic Escherichia coli strain Nissle 1917: Specific up-regulation of the proinflammatory chemokine MCP-1

    Directory of Open Access Journals (Sweden)

    Ukena Sya N

    2005-12-01

    Full Text Available Abstract Background The use of live microorganisms to influence positively the course of intestinal disorders such as infectious diarrhea or chronic inflammatory conditions has recently gained increasing interest as a therapeutic alternative. In vitro and in vivo investigations have demonstrated that probiotic-host eukaryotic cell interactions evoke a large number of responses potentially responsible for the effects of probiotics. The aim of this study was to improve our understanding of the E. coli Nissle 1917-host interaction by analyzing the gene expression pattern initiated by this probiotic in human intestinal epithelial cells. Methods Gene expression profiles of Caco-2 cells treated with E. coli Nissle 1917 were analyzed with microarrays. A second human intestinal cell line and also pieces of small intestine from BALB/c mice were used to confirm regulatory data of selected genes by real-time RT-PCR and cytometric bead array (CBA to detect secretion of corresponding proteins. Results Whole genome expression analysis revealed 126 genes specifically regulated after treatment of confluent Caco-2 cells with E. coli Nissle 1917. Among others, expression of genes encoding the proinflammatory molecules monocyte chemoattractant protein-1 ligand 2 (MCP-1, macrophage inflammatory protein-2 alpha (MIP-2α and macrophage inflammatory protein-2 beta (MIP-2β was increased up to 10 fold. Caco-2 cells cocultured with E. coli Nissle 1917 also secreted high amounts of MCP-1 protein. Elevated levels of MCP-1 and MIP-2α mRNA could be confirmed with Lovo cells. MCP-1 gene expression was also up-regulated in mouse intestinal tissue. Conclusion Thus, probiotic E. coli Nissle 1917 specifically upregulates expression of proinflammatory genes and proteins in human and mouse intestinal epithelial cells.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Efficient repair of DNA double strand breaks and interstrand cross-links requires the homologous recombination (HR) pathway, a potentially error-free process that utilizes a homologous sequence as a repair template. A key player in HR is RAD51, the eukaryotic ortholog of bacterial RecA protein. RAD......51 can polymerize on DNA to form a nucleoprotein filament that facilitates both the search for the homologous DNA sequences and the subsequent DNA strand invasion required to initiate HR. Because of its pivotal role in HR, RAD51 is subject to numerous positive and negative regulatory influences...... 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...

  17. Rhizoma Coptidis Inhibits LPS-Induced MCP-1/CCL2 Production in Murine Macrophages via an AP-1 and NFκB-Dependent Pathway

    Science.gov (United States)

    Remppis, Andrew; Bea, Florian; Greten, Henry Johannes; Buttler, Annette; Wang, Hongjie; Zhou, Qianxing; Preusch, Michael R.; Enk, Ronny; Ehehalt, Robert; Katus, Hugo; Blessing, Erwin

    2010-01-01

    Introduction. The Chinese extract Rhizoma coptidis is well known for its anti-inflammatory, antioxidative, antiviral, and antimicrobial activity. The exact mechanisms of action are not fully understood. Methods. We examined the effect of the extract and its main compound, berberine, on LPS-induced inflammatory activity in a murine macrophage cell line. RAW 264.7 cells were stimulated with LPS and incubated with either Rhizoma coptidis extract or berberine. Activation of AP-1 and NFκB was analyzed in nuclear extracts, secretion of MCP-1/CCL2 was measured in supernatants. Results. Incubation with Rhizoma coptidis and berberine strongly inhibited LPS-induced monocyte chemoattractant protein (MCP)-1 production in RAW cells. Activation of the transcription factors AP-1 and NFκB was inhibited by Rhizoma coptidis in a dose- and time-dependent fashion. Conclusions. Rhizoma coptidis extract inhibits LPS-induced MCP-1/CCL2 production in vitro via an AP-1 and NFκB-dependent pathway. Anti-inflammatory action of the extract is mediated mainly by its alkaloid compound berberine. PMID:20652055

  18. Significance and Application of Digital Breast Tomosynthesis for the BI-RADS Classification of Breast Cancer.

    Science.gov (United States)

    Cai, Si-Qing; Yan, Jian-Xiang; Chen, Qing-Shi; Huang, Mei-Ling; Cai, Dong-Lu

    2015-01-01

    Full-field digital mammography (FFDM) with dense breasts has a high rate of missed diagnosis, and digital breast tomosynthesis (DBT) could reduce organization overlapping and provide more reliable images for BI-RADS classification. This study aims to explore application of COMBO (FFDM+DBT) for effect and significance of BI-RADS classification of breast cancer. In this study, we selected 832 patients who had been treated from May 2013 to November 2013. Classify FFDM and COMBO examination according to BI-RADS separately and compare the differences for glands in the image of the same patient in judgment, mass characteristics display and indirect signs. Employ Paired Wilcoxon rank sum test was used in 79 breast cancer patients to find differences between two examine methods. The results indicated that COMBO pattern is able to observe more details in distribution of glands when estimating content. Paired Wilcoxon rank sum test showed that overall classification level of COMBO is higher significantly compared to FFDM to BI-RADS diagnosis and classification of breast (PBI-RADS classification in breast cancer in clinical.

  19. The Molecular Basis of Double-Strand DNA Break Repair: The Critical Structure of the RAD52/RPA Complex

    National Research Council Canada - National Science Library

    Jackson, Dobra

    2001-01-01

    .... RAD52 has specific interactions with RAD51, RPA and DNA (1,2,3). The binding of RAD52 to ends of double-strand breaks has been found to be a key initiation step to DNA repair by homologous recombination...

  20. RAD50 germline mutations are associated with poor survival in BRCA1/2-negative breast cancer patients.

    Science.gov (United States)

    Fan, Cong; Zhang, Juan; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

    2018-05-04

    RAD50 is a highly conserved DNA double-strand break (DSB) repair gene. However, the associations between RAD50 germline mutations and the survival and risk of breast cancer have not been fully elucidated. Here, we aimed to investigate the clinical impact of RAD50 germline mutations in a large cohort of unselected breast cancer patients. In this study, RAD50 germline mutations were determined using next-generation sequencing in 7657 consecutive unselected breast cancer patients without BRCA1/2 mutations. We also screened for RAD50 recurrent mutations (L719fs, K994fs, and H1269fs) in 5000 healthy controls using Sanger sequencing. We found that 26 out of 7657 (0.34%) patients had RAD50 pathogenic mutations, and 16 patients carried one of the three recurrent mutations (L719fs, n=6 cases; K994fs, n=5 cases; and H1269fs, n=5 cases); the recurrent mutation rate was 0.21%. The frequency of the three recurrent mutations in the 5000 healthy controls was 0.18% (9/5000). These mutations did not confer an increased risk of breast cancer in the studied patients [odds ratios (OR), 1.16; 95% confidence interval (CI), 0.51-2.63; P = 0.72]. Nevertheless, multivariate analysis revealed that RAD50 pathogenic mutations were an independent unfavourable predictor of recurrence-free survival (RFS) [adjusted hazard ratio (HR) 2.66; 95% CI, 1.18-5.98; P=0.018] and disease-specific survival (DSS) (adjusted HR 4.36; 95% CI, 1.58-12.03; P=0.004) in the entire study cohort. Our study suggested that RAD50 germline mutations are not associated with an increased risk of breast cancer, but patients with RAD50 germline mutations have unfavourable survival compared with patients without these mutations. This article is protected by copyright. All rights reserved. © 2018 UICC.

  1. Food Irradiation Is Done in Grays, not Rads

    International Nuclear Information System (INIS)

    Strom, Daniel J.

    2002-01-01

    One federal agency has chosen to use exclusively modern SI units of radiation dose in its regulations: the FDA. While not exactly hot news, this bold move by a U.S. government agency on November 26, 1997, should be noted by those who wish to encourage the switch from curies, working level months, rads, rems, and roentgens to becquerels, joule hours per cubic meter, grays, sieverts, and coulombs per kilogram. The regulation is 21 CFR 179, Irradiation in the Production, Processing, and Handling of Food. Specifically, 21 CFR 179.26 (b) 8. permits meat irradiation up to 4.5 kGy for refrigerated meat and 7.0 kGy for frozen meat. Prior to the 1997 addition, radiation doses had been quoted in grays (kGy) with rad (Mrad) values in parentheses. In the 1997 addition, the Mrads disappeared

  2. The KYxxL motif in Rad17 protein is essential for the interaction with the 9–1–1 complex

    Energy Technology Data Exchange (ETDEWEB)

    Fukumoto, Yasunori, E-mail: fukumoto@faculty.chiba-u.jp [Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan); Ikeuchi, Masayoshi; Nakayama, Yuji [Department of Biochemistry & Molecular Biology, Kyoto Pharmaceutical University, Kyoto 607-8414 (Japan); Yamaguchi, Naoto, E-mail: nyama@faculty.chiba-u.jp [Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan)

    2016-09-02

    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. - Highlights: • We have identified a conserved KYxxL motif in Rad17 protein. • The KYxxL motif is crucial for the interaction with the 9–1–1 complex. • The KYxxL motif is dispensable or inhibitory for UV-induced Rad17 phosphorylation. • Nucleotide binding of Rad17 is required for its nuclear localization.

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

    International Nuclear Information System (INIS)

    Sung, P.; Prakash, S.; Prakash, L.

    1990-01-01

    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)

  4. Prokaryotic expression and in vitro functional analysis of IL-1β and MCP-1 from guinea pig.

    Science.gov (United States)

    Dirisala, Vijaya R; Jeevan, Amminikutty; Ly, Lan H; McMurray, David N

    2013-06-01

    The Guinea pig (Cavia porcellus) is an excellent animal model for studying human tuberculosis (TB) and also for a number of other infectious and non-infectious diseases. One of the major roadblocks in effective utilization of this animal model is the lack of readily available immunological reagents. In order to address this issue, guinea pig interleukin 1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) were efficiently cloned and expressed in a prokaryotic expression vector, and the expressed proteins in soluble form from both the genes were confirmed by N-terminal sequencing. The biological activity of recombinant guinea pig IL-1β was demonstrated by its ability to drive proliferation in thymocytes, and the recombinant guinea pig MCP-1 exhibited chemotactic activity for guinea pig resident peritoneal macrophages. These biologically active recombinant guinea pig proteins will facilitate an in-depth understanding of the role they play in the immune responses of the guinea pig to TB and other diseases.

  5. 222Rn Determination In Drinking Waters - RAD7 And LSC Technique Comparison

    International Nuclear Information System (INIS)

    Todorovic, N.; Stojkovic, I.; Nikolov, J.; Tenjovic, B.

    2015-01-01

    A procedure for the determination of 222Rn in environmental water samples using liquid scintillation counting (LSC) was applied and optimized. For radon determination in drinking water from groundwater and surface water sources by LSC, the EPA Method 913.0 was used. A minimum detectable activity of 0.029 Bq L-1 in a 20 mL glass vial (10 mL water sample mixed with 10 mL of liquid scintillation cocktail) has been achieved during 300 minutes of measurement time. The procedure was compared with RAD7 radon detector measurements. Factors that affect the measurement accuracy and precision of RAD7 radon detector are the sampling technique, sample concentration, sample size, counting time, temperature, relative humidity and background effects. The minimal detectable activity (MDA) for RAD7 technique was found to be 0.1 Bq/L. From obtained results of 222Rn measurements in 15 water samples with different 222Rn activities, correlation between the two techniques applied for measurements of 222Rn in water samples (A less than 400 Bq/L) was determined. There is reasonable agreement (within statistical uncertainties) between the various techniques in most cases, while disagreements most likely come from systematic uncertainties associated with sampling procedures. Discrepancy in determined activities between the two techniques becomes more evident with increased 222Rn activities in water. LSC technique gives in general higher activity concentrations for about 30 percent than RAD7 spectrometer. The interpretation of shown results could be that RAD7 is not properly calibrated for higher activities, since USA reference level of 222Rn concentrations in water is only 11.1 Bq/L (US EPA, Proposed Radon in Drinking Water Regulation). (author).

  6. The role of Rad 51 protein in radioresistance of spheroid model of Du 145 prostate carcinoma cell line

    International Nuclear Information System (INIS)

    Taghizadeh, M.; Khoei, S.; Nikoofar, A. R.; Ghamsari, L.; Goliaei, B.

    2009-01-01

    Rad 51 is a protein with critical role in double strand break repair. Down-regulation of this protein has a significant effect in radiosensitivity of some cell lines like prostate carcinoma. Compared to monolayer cell culture model, the spheroids are more resistant to radiation. The aim of the current study was to determine the Rad 51 protein level in Du 145 spheroids, and monolayer cells before and after exposure to gamma irradiation. Materials and Methods: In the present study, western blot was used to determine the level of Rad 51 protein in Du 145 cell line grown as monolayer and spheroid. Results: Western blot analysis showed that in the spheroid cells, Rad 51 had an elevated level before and after radiation in comparison with monolayer cells. Higher doses of radiation induced elevated expression of Rad 51 protein in both culture models.The level of at protein after exposure to gamma rays had been time-dependent. Conclusion: Rad 51 might act as a mediator of radiation resistance in tumor cells. Repression of Rad 51 activity could be a prominent strategy to overcome radiation resistance of tumors.

  7. Could ultrasonic elastography help the diagnosis of small (≤2 cm) breast cancer with the usage of sonographic BI-RADS classification?

    International Nuclear Information System (INIS)

    Zhi, Hui; Xiao, Xiao-yun; Ou, Bing; Zhong, Wen-jing; Zhao, Zi-zhuo; Zhao, Xin-bao; Yang, Hai-yun; Luo, Bao-ming

    2012-01-01

    Objectives: To evaluate the additive value of ultrasound strain elastography (USE) to BI-RADS for the differentiation of benign and malignant breast small lesions. Methods: Breast masses (≤2 cm) with histological diagnosis examined by ultrasonography and USE in our department from April 2004 to December 2009 were reviewed. Conventional B-mode ultrasound findings were classified according to the BI-RADS classification. USE findings were classified according to the 5-point scale. Histological diagnosis was used as the reference standard. Results: 401 (246 benign (61.3%), 155 malignant (38.7%)) from 370 consecutive patients were included in the study. Sensitivity and specificity were 90.3%, 68.3% for BI-RADS; 72.3%, 91.9% for USE. The sensitivity of BI-RADS was better than that of USE (P < 0.05), while the specificity of USE was better than that of BI-RADS (P < 0.05). A revised BI-RADS combined with USE results was proposed in this study. Sensitivity and specificity were 83.9% and 87.8% for revised BI-RADS. The diagnostic performance of revised BI-RADS was better than BI-RADS (P < 0.05). Conclusions: USE could give BI-RADS some help in the differentiation of benign and malignant breast small lesions. The addition of elastography to BI-RADS could improve the diagnostic performance in <2 cm lesions.

  8. Extreme Temperature, Rad-Hard Power Management ASIC, Phase I

    Data.gov (United States)

    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...

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

    International Nuclear Information System (INIS)

    Roethke, Matthias; Schlemmer, H.P.; Blondin, D.; Franiel, T.

    2013-01-01

    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.)

  10. El gas radón como contaminante atmosférico

    Directory of Open Access Journals (Sweden)

    Luis Santiago Quindós Poncela

    2010-12-01

    Full Text Available En este trabajo se abordan distintos aspectos acerca de la problemática del radón en viviendas. Este gas de origen natural se encuentra prácticamente en la totalidad de los suelos de la corteza terrestre debido a la presencia de uranio y radio en la composición de los mismos. En función de factores arquitectónicos y de hábitos de ocupación de la vivienda pueden alcanzarse concentraciones elevadas del gas en interiores. En estas situaciones existe un incremento cuantificable del riesgo de desarrollar cáncer de pulmón en los habitantes de la vivienda. En los últimos años, las mejoras metodológicas en la realización de estudios epidemiológicos han conducido a la obtención de evidencias científicas de la relación entre la presencia de radón en interiores y el riesgo de cáncer de pulmón. Esta relación, encontrada hace años en trabajadores de minas de uranio, ha sido corroborada en el caso del radón residencial a la luz de los metaanálisis realizados recientemente a partir de estudios epidemiológicos agrupados. Durante los últimos 25 años se han realizado más de 6.000 medidas de radón en interiores. Se presentan los principales resultados de las mayores campañas de medida llevadas a cabo, así como los criterios recientemente establecidos por el Consejo de Seguridad Nuclear acerca de los niveles de intervención en viviendas y lugares de trabajo.

  11. Rad54 and Mus81 cooperation promotes DNA damage repair and restrains chromosome missegregation

    DEFF Research Database (Denmark)

    Ghamrasni, S El; Cardoso, R; Li, L

    2016-01-01

    . The inefficient repair of DNA double-strand breaks (DSBs) in Rad54(-/-)Mus81(-/-) cells was accompanied by elevated levels of chromosome missegregation and cell death. Perhaps as a consequence, tumor incidence in Rad54(-/-)Mus81(-/-) mice remained comparable to that in Mus81(-/-) mice. Our study highlights...

  12. Rad-hard Smallsat / CubeSat Avionics Board, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — VORAGO will design a rad-hard Smallsat / CubeSat Avionics single board that has the necessary robustness needed for long duration missions in harsh mission...

  13. Identification of a breast cancer family double heterozygote for RAD51C and BRCA2 gene mutations

    DEFF Research Database (Denmark)

    Ahlborn, Lise B; Steffensen, Ane Y; Jønson, Lars

    2015-01-01

    for mutations in the RAD51C and BRCA2 genes. The RAD51C missense mutation p.Arg258His has previously been identified in a homozygous state in a patient with Fanconi anemia. This mutation is known to affect the DNA repair function of the RAD51C protein. The BRCA2 p.Leu3216Leu synonymous mutation has not been...

  14. Rad-hard embedded computers for nuclear robotics

    International Nuclear Information System (INIS)

    Giraud, A.; Joffre, F.; Marceau, M.; Robiolle, M.; Brunet, J.P.; Mijuin, D.

    1994-01-01

    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

  15. A simple ionizing radiation spectrometer/dosimeter based on radiation sensing field effect transistors (RadFETs)

    International Nuclear Information System (INIS)

    Moreno, D.J.; Hughes, R.C.; Jenkins, M.W.; Drumm, C.R.

    1997-01-01

    This paper reports on the processing steps in a silicon foundry leading to improved performance of the Radiation Sensing Field Effect Transistor (RadFET) and the use of multiple RadFETs in a handheld, battery operated, combination spectrometer/dosimeter

  16. MicroCameras and Photometers (MCP) on board the TARANIS satellite

    Science.gov (United States)

    Farges, T.; Hébert, P.; Le Mer-Dachard, F.; Ravel, K.; Gaillac, S.

    2017-12-01

    TARANIS (Tool for the Analysis of Radiations from lightNing and Sprites) is a CNES micro satellite. Its main objective is to study impulsive transfers of energy between the Earth atmosphere and the space environment. It will be sun-synchronous at an altitude of 700 km. It will be launched in 2019 for at least 2 years. Its payload is composed of several electromagnetic instruments in different wavelengths (from gamma-rays to radio waves including optical). TARANIS instruments are currently in calibration and qualification phase. The purpose is to present the MicroCameras and Photometers (MCP) design, to show its performances after its recent characterization and at last to discuss the scientific objectives and how we want to answer it with the MCP observations. The MicroCameras, developed by Sodern, are dedicated to the spatial description of TLEs and their parent lightning. They are able to differentiate sprite and lightning thanks to two narrow bands ([757-767 nm] and [772-782 nm]) that provide simultaneous pairs of images of an Event. Simulation results of the differentiation method will be shown. After calibration and tests, the MicroCameras are now delivered to the CNES for integration on the payload. The Photometers, developed by Bertin Technologies, will provide temporal measurements and spectral characteristics of TLEs and lightning. There are key instrument because of their capability to detect on-board TLEs and then switch all the instruments of the scientific payload in their high resolution acquisition mode. Photometers use four spectral bands in the [170-260 nm], [332-342 nm], [757-767 nm] and [600-900 nm] and have the same field of view as cameras. The on-board TLE detection algorithm remote-controlled parameters have been tuned before launch using the electronic board and simulated or real events waveforms. After calibration, the Photometers are now going through the environmental tests. They will be delivered to the CNES for integration on the

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

    Science.gov (United States)

    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. © 2016 John Wiley & Sons Ltd.

  18. The rad2 mutation affects the molecular nature of UV and acridine-mustard-induced mutations in the ADE2 gene of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Ivanov, E.L.; Kovaltzova, S.V.; Kassinova, G.V.; Gracheva, L.M.; Korolev, V.G.; Zakharov, I.A.

    1986-01-01

    The authors have studied the molecular nature of ade2 mutations induced by UV light and bifunctional acridine-mustard (BAM) in wild-type (RAD) and in excision-deficient (rad2) strains of the yeast, Saccharomyces cerevisiae. In the RAD strain, UV causes 45% GC → AT transitions among all mutations; in the rad2 strain this value is 77%. BAM was shown to be highly specific for frameshift mutagenesis: 60% frameshifts in the RAD strain, and as many as 84% frameshifts in the rad2 strain were induced. Therefore, the rad2 mutation affects the specificity of UV- and BAM-induced mutagenesis in yeast. Experimental data agree with the view that the majority of mutations in the RAD strain are induced by a prereplicative mechanism, whereas mutations in the rad2 strain are predominantly postreplicative events. (Auth.)

  19. Folic Acid Supplementation Delays Atherosclerotic Lesion Development by Modulating MCP1 and VEGF DNA Methylation Levels In Vivo and In Vitro

    Science.gov (United States)

    Cui, Shanshan; Li, Wen; Lv, Xin; Wang, Pengyan; Gao, Yuxia; Huang, Guowei

    2017-01-01

    The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells. We analyzed atherosclerotic lesion histology, folate concentration, homocysteine concentration, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and DNA methyltransferase activity, as well as monocyte chemotactic protein-1 (MCP1) and vascular endothelial growth factor (VEGF) expression and promoter methylation. Folic acid reduced atherosclerotic lesion size in ApoE knockout mice. The underlying folic acid protective mechanism appears to operate through regulating the normal homocysteine state, upregulating the SAM: SAH ratio, elevating DNA methyltransferase activity and expression, altering MCP1 and VEGF promoter methylation, and inhibiting MCP1 and VEGF expression. We conclude that folic acid supplementation effectively prevented atherosclerosis by modifying DNA methylation through the methionine cycle, improving DNA methyltransferase activity and expression, and thus changing the expression of atherosclerosis-related genes. PMID:28475147

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

    International Nuclear Information System (INIS)

    Imura, Yoshiyuki; Molho, Melissa; Chuang, Chingkai; Nagy, Peter D.

    2015-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Influence of different inhibitors on the activity of the RAD54 dependent step of DNA repair in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Siede, W.; Obermaier, S.; Eckhardt, F.

    1985-01-01

    The recombinagenic pathway of DNA repair in yeast was characterized by the effect of different inhibitors on the temperature-dependent survival after ..gamma..-irradiation in haploid cells of the thermoconditional mutant rad54-3. Blocking protein synthesis with cycloheximide in replicating cells caused partial inhibition of the RAD54 dependent function but some repair activity remained detectable. This indicates that ..gamma..-rays can induce RAD54 activity above some constitutive level of function. Inhibition of DNA replication by hydroxyurea efficiently blocked the RAD54 dependent function in stationary-phase cells but not in logarithmic-phase cells. In logarithmic-phase cells, the authors found a strong inhibitory effect of caffeine on the RAD54 mediated repair process.

  3. Differentiation of prostatitis and prostate cancer using the Prostate Imaging-Reporting and Data System (PI-RADS).

    Science.gov (United States)

    Meier-Schroers, Michael; Kukuk, Guido; Wolter, Karsten; Decker, Georges; Fischer, Stefan; Marx, Christian; Traeber, Frank; Sprinkart, Alois Martin; Block, Wolfgang; Schild, Hans Heinz; Willinek, Winfried

    2016-07-01

    To determine if prostate cancer (PCa) and prostatitis can be differentiated by using PI-RADS. 3T MR images of 68 patients with 85 cancer suspicious lesions were analyzed. The findings were correlated with histopathology. T2w imaging (T2WI), diffusion weighted imaging (DWI), dynamic contrast enhancement (DCE), and MR-Spectroscopy (MRS) were acquired. Every lesion was given a single PI-RADS score for each parameter, as well as a sum score and a PI-RADS v2 score. Furthermore, T2-morphology, ADC-value, perfusion type, citrate/choline-level, and localization were evaluated. 44 of 85 lesions showed PCa (51.8%), 21 chronic prostatitis (24.7%), and 20 other benign tissue such as hyperplasia or fibromuscular tissue (23.5%). The single PI-RADS score for T2WI, DWI, DCE, as well as the aggregated score including and not including MRS, and the PI-RADS v2-score were all significantly higher for PCa than for prostatitis or other tissue (pprostatitis than for other tissue (p=0.029 and p=0.020), whereas the other parameters were not different. Prostatitis usually presented borderline pathological PI-RADS scores, showed restricted diffusion with ADC≥900mm(2)/s in 100% of cases, was more often indistinctly hypointense on T2WI (66.7%), and localized in the transitional zone (57.1%). An ADC≥900mm(2)/s achieved the highest predictive value for prostatitis (AUC=0.859). Prostatitis can be differentiated from PCa using PI-RADS, since all available parameters are more distinct in cases of cancer. However, there is significant overlap between prostatitis and other benign findings, thus PI-RADS is only suitable to a limited extent for the primary assessment of prostatitis. Restricted diffusion with ADC≥900mm(2)/s is believed to be a good indicator for prostatitis. MRS can help to distinguish between prostatitis and other tissue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Phosphorylation of Rad9 at serine 328 by cyclin A-Cdk2 triggers apoptosis via interfering Bcl-xL.

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    with 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...

  6. TRPV1 and the MCP-1/CCR2 Axis Modulate Post-UTI Chronic Pain.

    Science.gov (United States)

    Rosen, John M; Yaggie, Ryan E; Woida, Patrick J; Miller, Richard J; Schaeffer, Anthony J; Klumpp, David J

    2018-05-08

    The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas capsazepine treatment of mice at two weeks following SΦ874 infection did not reduce chronic allodynia. TRPV1-deficient mice did not develop chronic allodynia either. Similar results were found using novelty-suppressed feeding (NSF) to assess depressive behavior associated with neuropathic pain. Imaging of reporter mice also revealed induction of MCP-1 and CCR2 expression in sacral dorsal root ganglia following SΦ874 infection. Treatment with a CCR2 receptor antagonist at two weeks post-infection reduced chronic allodynia. Taken together, these results suggest that TRPV1 has a role in the establishment of post-UTI chronic pain, and CCR2 has a role in maintenance of post-UTI chronic pain.

  7. Preservação dos atributos físicos de frutos de atemoia cv. Gefner com o uso de 1-MCP e atmosfera modificad

    Directory of Open Access Journals (Sweden)

    Gláucia Michelle Cosme Silva

    2014-12-01

    Full Text Available O interesse comercial pela atemoia vem aumentando cada vez mais no Brasil. O aumento da atividade respiratória, acompanhado por modificações rápidas na composição física dos frutos podem inviabilizar sua distribuição a mercados distantes. Neste contexto, objetivou-se com o presente trabalho avaliar os atributos físicos em frutos de atemoia tratados com 1-metilciclopropeno (1-MCP e atmosfera modificada associados à refrigeração. O experimento foi instalado em delineamento experimental inteiramente casualizado, em esquema fatorial 4x5, sendo quatro concentrações de 1-MCP (0; 200; 400 e 600 ŋL L-¹ e cinco períodos de avaliação após a colheita, em intervalo de cinco dias, com quatro repetições e quatro frutos por unidade experimental. As atemoias foram colhidas em pomar comercial, no município de Matias Cardoso-MG, no estádio de maturação fisiológica, lavadas, sanitizadas e secas ao ar, depois tratadas com as concentrações de 1-MCP por oito horas, em temperatura ambiente. Logo após, quatro frutos foram dispostos em bandejas de poliestireno expandido. Alguns permaneceram sem membrana, enquanto outros foram embalados com membrana plástica de PEBD 16µm. As variáveis avaliadas nos frutos foram: perda de biomassa fresca, firmeza, concentração de CO2, etileno e coloração da casca. O uso da atmosfera modificada e do 1-MCP, associados ou não, foi eficiente no atraso do amadurecimento dos frutos, permitindo a conservação de sua qualidade física. Frutos tratados com 1-MCP apresentaram-se mais firmes, além da preservação da coloração, verificada através da luminosidade, cromaticidade e ângulo Hueº, que se mostraram superiores quando comparados aos frutos não tratados.

  8. Usefulness of combined use of contrast-enhanced ultrasound and TI-RADS classification for the differentiation of benign from malignant lesions of thyroid nodules.

    Science.gov (United States)

    Zhang, Yan; Zhou, Ping; Tian, Shuang-Ming; Zhao, Yong-Feng; Li, Jia-Le; Li, Lan

    2017-04-01

    To study the thyroid image reporting and data system (TI-RADS) classification and the contrast-enhanced ultrasound (CEUS) enhancement pattern of thyroid nodules, and to determine whether combined use of both methods is helpful in the diagnosis of thyroid nodules. A total of 319 thyroid nodules in 246 patients were assessed with TI-RADS, CEUS and a combination of both methods. The diagnostic performance of TI-RADS, CEUS and a combination of both methods was compared. The accuracy in the diagnosis of thyroid nodules was 90.3 % for TI-RADS, 90.0 % for CEUS and 96.0 % for a combination of both methods respectively. A statistically significant difference was not observed in the diagnostic accuracy of CEUS and TI-RADS (P > 0.05). However, a significant difference was observed between a combination of both methods and either alone (P TI-RADS classifications of 4a and 4b thyroid nodules compared with TI-RADS alone (P  0.05). The improved TI-RADS, when combined with CEUS, could significantly improve the diagnostic accuracy for thyroid nodules, especially for TI-RADS class-4 thyroid nodules. • TI-RADS can be used as the primary diagnostic standard for thyroid nodules • CEUS can be used as an important complement to TI-RADS • The improved TI-RADS can significantly improve the qualitative diagnostic accuracy.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

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

    1984-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  12. Diffracted X-ray tracking: new system for single molecular detection with X-rays

    CERN Document Server

    Sasaki, Y C; Adachi, S; Suzuki, Y; Yagi, N

    2001-01-01

    We propose a new X-ray methodology for direct observations of the behaviors of single molecular units in real time and real space. This new system, which we call Diffracted X-ray Tracking (DXT), monitors the Brownian motions of a single molecular unit by observations of X-ray diffracted spots from a nanocrystal, tightly bound to the individual single molecular unit in bio-systems. DXT does not determine any translational movements, but only orientational movements.

  13. Diffracted X-ray tracking: new system for single molecular detection with X-rays

    International Nuclear Information System (INIS)

    Sasaki, Y.C.; Okumura, Y.; Adachi, S.; Suzuki, Y.; Yagi, N.

    2001-01-01

    We propose a new X-ray methodology for direct observations of the behaviors of single molecular units in real time and real space. This new system, which we call Diffracted X-ray Tracking (DXT), monitors the Brownian motions of a single molecular unit by observations of X-ray diffracted spots from a nanocrystal, tightly bound to the individual single molecular unit in bio-systems. DXT does not determine any translational movements, but only orientational movements

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

    International Nuclear Information System (INIS)

    Calas, M.J.G.; Almeida, R.M.V.R.; Gutfilen, B.; Pereira, W.C.A.

    2010-01-01

    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.

  15. RadMAP: The Radiological Multi-sensor Analysis Platform

    International Nuclear Information System (INIS)

    Bandstra, Mark S.; Aucott, Timothy J.; Brubaker, Erik; Chivers, Daniel H.; Cooper, Reynold J.; Curtis, Joseph C.; Davis, John R.; Joshi, Tenzing H.; Kua, John; Meyer, Ross; Negut, Victor; Quinlan, Michael; Quiter, Brian J.; Srinivasan, Shreyas; Zakhor, Avideh; Zhang, Richard; Vetter, Kai

    2016-01-01

    The variability of gamma-ray and neutron background during the operation of a mobile detector system greatly limits the ability of the system to detect weak radiological and nuclear threats. The natural radiation background measured by a mobile detector system is the result of many factors, including the radioactivity of nearby materials, the geometric configuration of those materials and the system, the presence of absorbing materials, and atmospheric conditions. Background variations tend to be highly non-Poissonian, making it difficult to set robust detection thresholds using knowledge of the mean background rate alone. The Radiological Multi-sensor Analysis Platform (RadMAP) system is designed to allow the systematic study of natural radiological background variations and to serve as a development platform for emerging concepts in mobile radiation detection and imaging. To do this, RadMAP has been used to acquire extensive, systematic background measurements and correlated contextual data that can be used to test algorithms and detector modalities at low false alarm rates. By combining gamma-ray and neutron detector systems with data from contextual sensors, the system enables the fusion of data from multiple sensors into novel data products. The data are curated in a common format that allows for rapid querying across all sensors, creating detailed multi-sensor datasets that are used to study correlations between radiological and contextual data, and develop and test novel techniques in mobile detection and imaging. In this paper we will describe the instruments that comprise the RadMAP system, the effort to curate and provide access to multi-sensor data, and some initial results on the fusion of contextual and radiological data.

  16. RadMAP: The Radiological Multi-sensor Analysis Platform

    Energy Technology Data Exchange (ETDEWEB)

    Bandstra, Mark S., E-mail: msbandstra@lbl.gov [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Aucott, Timothy J. [Department of Nuclear Engineering, University of California Berkeley, CA (United States); Brubaker, Erik [Sandia National Laboratory, Livermore, CA (United States); Chivers, Daniel H.; Cooper, Reynold J. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Curtis, Joseph C. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Department of Nuclear Engineering, University of California Berkeley, CA (United States); Davis, John R. [Department of Nuclear Engineering, University of California Berkeley, CA (United States); Joshi, Tenzing H.; Kua, John; Meyer, Ross; Negut, Victor; Quinlan, Michael; Quiter, Brian J. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Srinivasan, Shreyas [Department of Nuclear Engineering, University of California Berkeley, CA (United States); Department of Electrical Engineering and Computer Science, University of California Berkeley, CA (United States); Zakhor, Avideh; Zhang, Richard [Department of Electrical Engineering and Computer Science, University of California Berkeley, CA (United States); Vetter, Kai [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Department of Nuclear Engineering, University of California Berkeley, CA (United States)

    2016-12-21

    The variability of gamma-ray and neutron background during the operation of a mobile detector system greatly limits the ability of the system to detect weak radiological and nuclear threats. The natural radiation background measured by a mobile detector system is the result of many factors, including the radioactivity of nearby materials, the geometric configuration of those materials and the system, the presence of absorbing materials, and atmospheric conditions. Background variations tend to be highly non-Poissonian, making it difficult to set robust detection thresholds using knowledge of the mean background rate alone. The Radiological Multi-sensor Analysis Platform (RadMAP) system is designed to allow the systematic study of natural radiological background variations and to serve as a development platform for emerging concepts in mobile radiation detection and imaging. To do this, RadMAP has been used to acquire extensive, systematic background measurements and correlated contextual data that can be used to test algorithms and detector modalities at low false alarm rates. By combining gamma-ray and neutron detector systems with data from contextual sensors, the system enables the fusion of data from multiple sensors into novel data products. The data are curated in a common format that allows for rapid querying across all sensors, creating detailed multi-sensor datasets that are used to study correlations between radiological and contextual data, and develop and test novel techniques in mobile detection and imaging. In this paper we will describe the instruments that comprise the RadMAP system, the effort to curate and provide access to multi-sensor data, and some initial results on the fusion of contextual and radiological data.

  17. Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy

    KAUST Repository

    Reymer, A.; Frykholm, K.; Morimatsu, K.; Takahashi, M.; Norden, B.

    2009-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

    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

  20. Results From the First 118 GHz Passive Microwave Observations Over Antarctica

    Science.gov (United States)

    McAllister, R.; Gallaher, D. W.; Gasiewski, A. J.; Periasamy, L.; Belter, R.; Hurowitz, M.; Hosack, W.; Sanders, B. T.

    2017-12-01

    Cooperation between the University of Colorado (Center for Environmental Technology, National Snow and Ice Data Center, and Colorado Space Grant Consortium) and the private corporation Orbital Micro Systems (OMS) has resulted in a highly miniturized passive microwave sensor. This sensor was successfully flown over Antarctica in onboard NASA's DC-8 in Operation Ice Bridge (OIB) in October / November of 2016. Data was collected from the "MiniRad" 8 channel miniaturized microwave sensor, which operated as both a sounder and an imager. The non-calibrated observation included both high and low altitude observations over clouds, sea, ice, ice sheets, and mountains as well as terrain around Tierra del Fuego. Sample results and their significance will be discussed. The instrument is in a form factor suitable for deployment in cubesats and will be launched into orbit next year. Commercial deployments by OMS in a constellation configuration will shortly follow.

  1. Rad-hard Location and Attitude Module (R-LAM), Phase I

    Data.gov (United States)

    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. Measurement of 2-5 keV x-ray emission from laser-target interactions by using fluor-MCP and CsI-XRD detectors

    International Nuclear Information System (INIS)

    Lee, P.H.Y.; Tirsell, K.G.; Leipelt, G.R.; Laird, W.B.

    1981-01-01

    For inertial confinement fusion plasma diagnostics, x-ray diode (XRD) detectors using conventional cathodes are not sensitive enough to measure x-rays above approx. 1.5 keV. However, for laser driver fusion targets, x-rays in the range of 2 to 5 keV are important because of their mobility in the target. We have successfully used fluor-microchannel plate (MCP) detectors to obtain absolute x-ray measurements in the 2 to 5 keV range. Recent data obtained from experiments on the Shiva laser system are presented. In addition, designs for a variety of channels in the range using fluor-MCP and CsI-XRD's above 1.5 keV will be discussed

  3. Nonvolatile Rad-Hard Holographic Memory

    Science.gov (United States)

    Chao, Tien-Hsin; Zhou, Han-Ying; Reyes, George; Dragoi, Danut; Hanna, Jay

    2001-01-01

    We are investigating a nonvolatile radiation-hardened (rad-hard) holographic memory technology. Recently, a compact holographic data storage (CHDS) breadboard utilizing an innovative electro-optic scanner has been built and demonstrated for high-speed holographic data storage and retrieval. The successful integration of this holographic memory breadboard has paved the way for follow-on radiation resistance test of the photorefractive (PR) crystal, Fe:LiNbO3. We have also started the investigation of using two-photon PR crystals that are doubly doped with atoms of iron group (Ti, Cr, Mn, Cu) and of rare-earth group (Nd, Tb) for nonvolatile holographic recordings.

  4. Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.

    Directory of Open Access Journals (Sweden)

    Kazuko Ino

    Full Text Available Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP(+CD45(- cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4. Because the vast majority of EGFP(+CD45(- cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs. EGFP(+ PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1 and angiotensin II (Ang II increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2 and Ang II type 1 receptor (AT1R, were expressed on Ly6C(high monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+F4/80(+CCR2(+ monocytic cells and EGFP(+ PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+ bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+ PaSCs in injured mice. We propose that CCR2(+ monocytes migrate into the pancreas possibly via the

  5. Photodetachment and UV-Vis spectral properties of Cl2rad -·nHO clusters: Extrapolation to bulk

    Science.gov (United States)

    Pathak, A. K.; Mukherjee, T.; Maity, D. K.

    2008-03-01

    Vertical detachment energy (VDE) and UV-Vis spectra of Cl2rad -·nHO clusters ( n = 1-11) are reported based on first principle electronic structure calculations. VDE of the hydrated clusters are calculated following second order Moller-Plesset perturbation (MP2) as well as coupled cluster theory with 6-311++G(d,p) set of basis function. The excess electron in these hydrated clusters is mainly localized over the solute Cl atoms. A linear relationship is obtained for VDE vs. ( n + 2.6) -1/3 and bulk VDE of Cl2rad - aqueous solution is calculated as 10.61 eV at CCSD(T) level of theory. UV-Vis spectra of these hydrated clusters are calculated applying CI with single electron (CIS) excitation procedure. Simulated UV-Vis spectra of Cl2rad -·10HO cluster is noted to be in excellent agreement with the reported spectra of Cl2rad - (aq) system, λmax for Cl2rad -·11HO system is calculated to be red shifted though.

  6. Fundamental studies of passivity and passivity breakdown

    International Nuclear Information System (INIS)

    Macdonald, D.D.; Urquidi-Macdonald, M.; Song, H.; Biaggio-Rocha, S.; Searson, P.

    1991-11-01

    This report summarizes the findings of our fundamental research program on passivity and passivity breakdown. During the past three and one half years in this program (including the three year incrementally-funded grant prior to the present grant), we developed and experimentally tested various physical models for the growth and breakdown of passive films on metal surfaces. These models belong to a general class termed ''point defects models'' (PDMs), in which the growth and breakdown of passive films are described in terms of the movement of anion and cation vacancies

  7. Medullary thyroid carcinoma: Application of Thyroid Imaging Reporting and Data System (TI-RADS) Classification.

    Science.gov (United States)

    Yun, Gabin; Kim, Yeo Koon; Choi, Sang Il; Kim, Ji-Hoon

    2018-04-21

    To evaluate the applicability of ultrasound (US)-based Thyroid Imaging Reporting and Data System (TI-RADS) for evaluating medullary thyroid carcinoma (MTC). US images and medical records of patients with cytopathology-confirmed MTC between June 2003 and November 2016 were retrospectively reviewed. Four independent reviewers (two experienced and two inexperienced radiologists) evaluated 57 pre-operative US images of patients with MTC for shape, composition, echogenicity, margin, calcification of the MTC nodules, and categorized the nodules using TI-RADS classification. Weighted Kappa statistics was used to determine the inter-observer agreement of TI-RADS. Univariate and multivariate analyses were performed to assess US findings associated with lymph node metastasis. Ninety-five percent of nodules were classified as either high suspicion (68%) or intermediate suspicion (26%). The overall inter-rater agreement was good (Kappa 0.84, agreement 91.52%), and inexperienced reviewers also showed good agreements with the most experienced reviewer (weighted Kappa 0.73 and 0.81). According to the univariate analysis, TI-RADS category 5, shape, microcalcification, and extrathyroid extension were significantly associated with lymph node metastasis in MTC patients (p = 0.003, 0.008, 0.001, and 0.021, respectively). As per the multivariate analysis, the presence of microcalcification and the irregular shape of the nodule were significantly associated with metastatic lymph nodes in MTC patients (odds ratio, 26.6; 95% CI, 2.7-263.7, p = 0.005, odds ratio, 14.7; 95% CI, 1.3-170, p = 0.031, respectively). TI-RADS is applicable for the evaluation of MTC nodules with good inter-observer agreement.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination

    DEFF Research Database (Denmark)

    Gao, Min; Wei, Wei; Li, Ming Hua

    2014-01-01

    resection as well as RPA and Mre11 loading is unaffected by Ago2 or Dicer depletion, suggesting that Ago2 very likely functions directly in mediating Rad51 accumulation at DSBs. Taken together, our findings suggest that guided by diRNAs, Ago2 can promote Rad51 recruitment and/or retention at DSBs...

  11. Down-regulation of Rad51 activity during meiosis in yeast prevents competition with Dmc1 for repair of double-strand breaks.

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2014-01-01

    Full Text Available Interhomolog recombination plays a critical role in promoting proper meiotic chromosome segregation but a mechanistic understanding of this process is far from complete. In vegetative cells, Rad51 is a highly conserved recombinase that exhibits a preference for repairing double strand breaks (DSBs using sister chromatids, in contrast to the conserved, meiosis-specific recombinase, Dmc1, which preferentially repairs programmed DSBs using homologs. Despite the different preferences for repair templates, both Rad51 and Dmc1 are required for interhomolog recombination during meiosis. This paradox has recently been explained by the finding that Rad51 protein, but not its strand exchange activity, promotes Dmc1 function in budding yeast. Rad51 activity is inhibited in dmc1Δ mutants, where the failure to repair meiotic DSBs triggers the meiotic recombination checkpoint, resulting in prophase arrest. The question remains whether inhibition of Rad51 activity is important during wild-type meiosis, or whether inactivation of Rad51 occurs only as a result of the absence of DMC1 or checkpoint activation. This work shows that strains in which mechanisms that down-regulate Rad51 activity are removed exhibit reduced numbers of interhomolog crossovers and noncrossovers. A hypomorphic mutant, dmc1-T159A, makes less stable presynaptic filaments but is still able to mediate strand exchange and interact with accessory factors. Combining dmc1-T159A with up-regulated Rad51 activity reduces interhomolog recombination and spore viability, while increasing intersister joint molecule formation. These results support the idea that down-regulation of Rad51 activity is important during meiosis to prevent Rad51 from competing with Dmc1 for repair of meiotic DSBs.

  12. Raman-Activated Droplet Sorting (RADS) for Label-Free High-Throughput Screening of Microalgal Single-Cells.

    Science.gov (United States)

    Wang, Xixian; Ren, Lihui; Su, Yetian; Ji, Yuetong; Liu, Yaoping; Li, Chunyu; Li, Xunrong; Zhang, Yi; Wang, Wei; Hu, Qiang; Han, Danxiang; Xu, Jian; Ma, Bo

    2017-11-21

    Raman-activated cell sorting (RACS) has attracted increasing interest, yet throughput remains one major factor limiting its broader application. Here we present an integrated Raman-activated droplet sorting (RADS) microfluidic system for functional screening of live cells in a label-free and high-throughput manner, by employing AXT-synthetic industrial microalga Haematococcus pluvialis (H. pluvialis) as a model. Raman microspectroscopy analysis of individual cells is carried out prior to their microdroplet encapsulation, which is then directly coupled to DEP-based droplet sorting. To validate the system, H. pluvialis cells containing different levels of AXT were mixed and underwent RADS. Those AXT-hyperproducing cells were sorted with an accuracy of 98.3%, an enrichment ratio of eight folds, and a throughput of ∼260 cells/min. Of the RADS-sorted cells, 92.7% remained alive and able to proliferate, which is equivalent to the unsorted cells. Thus, the RADS achieves a much higher throughput than existing RACS systems, preserves the vitality of cells, and facilitates seamless coupling with downstream manipulations such as single-cell sequencing and cultivation.

  13. Simulation of the GCR spectrum in the Mars curiosity rover's RAD detector using MCNP6

    Science.gov (United States)

    Ratliff, Hunter N.; Smith, Michael B. R.; Heilbronn, Lawrence

    2017-08-01

    The paper presents results from MCNP6 simulations of galactic cosmic ray (GCR) propagation down through the Martian atmosphere to the surface and comparison with RAD measurements made there. This effort is part of a collaborative modeling workshop for space radiation hosted by Southwest Research Institute (SwRI). All modeling teams were tasked with simulating the galactic cosmic ray (GCR) spectrum through the Martian atmosphere and the Radiation Assessment Detector (RAD) on-board the Curiosity rover. The detector had two separate particle acceptance angles, 4π and 30 ° off zenith. All ions with Z = 1 through Z = 28 were tracked in both scenarios while some additional secondary particles were only tracked in the 4π cases. The MCNP6 4π absorbed dose rate was 307.3 ± 1.3 μGy/day while RAD measured 233 μGy/day. Using the ICRP-60 dose equivalent conversion factors built into MCNP6, the simulated 4π dose equivalent rate was found to be 473.1 ± 2.4 μSv/day while RAD reported 710 μSv/day.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Masimo Rad-57 Pulse CO-Oximeter for noninvasive carboxyhemoglobin measurement.

    Science.gov (United States)

    Suner, Selim; McMurdy, John

    2009-03-01

    Noninvasive methods of body fluid chemical measurement have been expanding. New technologies are enabling the quantification of different compounds in the blood and interstitial tissues. One example of this is the pulse oximeter, which has facilitated the measurement of oxyhemoglobin rapidly and reliably without the requirement of blood-draws. The Masimo Rad-57 Pulse CO-Oximeter expanded the capabilities of pulse-oximetry to include measurements of carboxyhemoglobin and methemoglobin. This innovation has revolutionized the paradigm for detection of patients with CO poisoning. Previously, clinicians relied on historical information and patient signs and symptoms pointing to the possibility of CO exposure or toxicity. Only then would a blood test be ordered to measure carboxyhemoglobin levels. Since the presentation of CO poisoning is nonspecific and overlaps with many other conditions, and since the presence of environmental CO is often unknown, the detection of this condition was only possible in cases where the presence of CO was obvious or where the symptoms were severe. We now know, from studies conducted using the Rad-57, the only US FDA-approved device for noninvasive measurement of SpCO, that there are a significant number of patients who experience CO exposure but are nonsymptomatic. The Rad-57 provides a clinical justification for screening in the healthcare setting to identify patients with significant CO exposure who would otherwise be undetected.

  16. PI-RADS version 2: what you need to know

    International Nuclear Information System (INIS)

    Barrett, T.; Turkbey, B.; Choyke, P.L.

    2015-01-01

    Prostate cancer is the second most prevalent cancer in men worldwide and its incidence is expected to double by 2030. Multi-parametric magnetic resonance imaging (MRI) incorporating anatomical and functional imaging has now been validated as a means of detecting and characterising prostate tumours and can aid in risk stratification and treatment selection. The European Society of Urogenital Radiology (ESUR) in 2012 established the Prostate Imaging—Reporting and Data System (PI-RADS) guidelines aimed at standardising the acquisition, interpretation and reporting of prostate MRI. Subsequent experience and technical developments have highlighted some limitations, and a joint steering committee formed by the American College of Radiology, ESUR, and the AdMeTech Foundation have recently announced an updated version of the proposals. We summarise the main proposals of PI-RADS version 2, explore the evidence behind the recommendations, and highlight key differences for the benefit of those already familiar with the original.

  17. Acorrelation study between histological results and thyroid ultrasound findings. The TI-RADS classification.

    Science.gov (United States)

    García-Moncó Fernández, Carlos; Serrano-Moreno, Clara; Donnay-Candil, Sergio; Carrero-Alvaro, Juan

    2018-04-01

    There are several classifications based on thyroid ultrasound for selecting suspected malignant thyroid nodules. The Thyroid Imaging Reporting and Data System (TI-RADS) classification proposed by Horvath in 2009 includes 6 categories. To assess the sensitivity of the TI-RADS classification for diagnosing thyroid nodules. A retrospective study of all patients who underwent thyroidectomy at our hospital (n=263) from September 2013 to December 2015. After thyroidectomy, histological results were correlated to the ultrasound findings reported. Of the 263 study patients, 75 (28.5%) were diagnosed with thyroid cancer and 188 (71.5%) with benign disease. Correlation of histological results with preoperative ultrasound reports showed an initial sensitivity of 65%. After excluding 15 patients diagnosed with occult microcarcinoma, sensitivity increased to 81.6%. The ultrasound images from 11 false negatives cases were then reassessed by a radiologist who knew histological diagnosis and reclassified 10 of them as TI-RADS≥4. This procedure could have increased sensitivity up to 98.3%. Although the sensitivity initially found in our study using the TI-RADS scale was relatively low, the value markedly improved when patients with occult microcarcinoma were excluded. Thus, use of the TI-RADS scale would allow for an adequate selection of patients amenable to fine needle aspiration of the nodule. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    becomes crucial for genome maintenance in the absence of Sgs1. Despite this, our dissection of the MMS checkpoint response reveals parallel, but unequal pathways for Rad53 activation and highlights significant differences between MMS- and hydroxyurea (HU)-induced checkpoint responses with relation...

  19. Quantitative comparison of mutagenic hazards: rad-equivalences

    International Nuclear Information System (INIS)

    1980-01-01

    The present situation concerning the problem of estimating genetic risks associated with the exposure of living beings, including man, to chemical compounds present in the environment is defined. Since these compounds affect the genetic material of cells by reactions similar to those produced by radiations, attempts have been made to establish rad-equivalences for some of these substances. This idea is discussed through the different publications mentioned [fr

  20. Analysis of Dextromethorphan and Dextrorphan in Skeletal Remains Following Decomposition in Different Microclimate Conditions.

    Science.gov (United States)

    Unger, K A; Watterson, J H

    2016-10-01

    The effects of decomposition microclimate on the distribution of dextromethorphan (DXM) and dextrorphan (DXT) in skeletonized remains of rats acutely exposed to DXM were examined. Animals (n = 10) received DXM (75 mg/kg, i.p.), were euthanized 30 min post-dose and immediately allowed to decompose at either Site A (shaded forest microenvironment on a grass-covered soil substrate) or Site B (rocky substrate exposed to direct sunlight, 600 m from Site A). Ambient temperature and relative humidity were automatically recorded 3 cm above rats at each site. Skeletal elements (vertebral columns, ribs, pelvic girdles, femora, tibiae, humeri and scapulae) were harvested, and analyzed using microwave assisted extraction, microplate solid phase extraction, and GC/MS. Drug levels, expressed as mass-normalized response ratios, and the ratios of DXT and DXM levels were compared across bones and between microclimate sites. No significant differences in DXT levels or metabolite/parent ratios were observed between sites or across bones. Only femoral DXM levels differed significantly between microclimate sites. For pooled data, microclimate was not observed to significantly affect analyte levels, nor the ratio of levels of DXT and DXM. These data suggest that microclimate conditions do not influence DXM and metabolite distribution in skeletal remains. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Diagnostic value of coustic radiation force impulse for BI-RADS category 4 breast lesions of different sizes.

    Science.gov (United States)

    Wu, Rong

    2018-04-14

    To determine the diagnostic value of combined conventional ultrasound (US) and acoustic radiation force impulse (ARFI) imaging for the differential diagnosis of BI-RADS category 4 breast lesions of different sizes. From April 2013 to January 2015, 283 patients (with a total of 292 breast lesions) who underwent US and ARFI examination were included in this retrospective study. The SWV for the lesion and adjacent normal breast tissue were measured and the SWV ratio was calculated. VTI grade was also assessed. The lesions were separated into three groups on the basis of size, and two combinations of ARFI parameters (SWV + VTI and SWV ratio + VTI) were applied to reassess the BI-RADS categories. Diagnoses were confirmed by pathological examination after biopsy or surgery. ROC analysis was performed to assess the diagnostic efficiency of each method. The Z test was used to compare the difference between AUC of the two methods. Significant improvement was seen in the diagnostic performance of US with the use of the ARFI parameters SWV + VTI (77/179 [43.0%] of BI-RADS category 4A breast lesions were downgraded) and SWV ratio + VTI (64/179 [35.8%] of BI-RADS category 4A breast lesions were downgraded, including two malignant cases that were misdiagnosed as benign) (P BI-RADS category 4 breast lesions. The combination of SWV ratio + VTI can improve BI-RADS classification of small lesions (<10 mm size).

  2. The Medicago truncatula GRAS protein RAD1 supports arbuscular mycorrhiza symbiosis and Phytophthora palmivora susceptibility.

    Science.gov (United States)

    Rey, Thomas; Bonhomme, Maxime; Chatterjee, Abhishek; Gavrin, Aleksandr; Toulotte, Justine; Yang, Weibing; André, Olivier; Jacquet, Christophe; Schornack, Sebastian

    2017-12-16

    The roots of most land plants are colonized by symbiotic arbuscular mycorrhiza (AM) fungi. To facilitate this symbiosis, plant genomes encode a set of genes required for microbial perception and accommodation. However, the extent to which infection by filamentous root pathogens also relies on some of these genes remains an open question. Here, we used genome-wide association mapping to identify genes contributing to colonization of Medicago truncatula roots by the pathogenic oomycete Phytophthora palmivora. Single-nucleotide polymorphism (SNP) markers most significantly associated with plant colonization response were identified upstream of RAD1, which encodes a GRAS transcription regulator first negatively implicated in root nodule symbiosis and recently identified as a positive regulator of AM symbiosis. RAD1 transcript levels are up-regulated both in response to AM fungus and, to a lower extent, in infected tissues by P. palmivora where its expression is restricted to root cortex cells proximal to pathogen hyphae. Reverse genetics showed that reduction of RAD1 transcript levels as well as a rad1 mutant are impaired in their full colonization by AM fungi as well as by P. palmivora. Thus, the importance of RAD1 extends beyond symbiotic interactions, suggesting a general involvement in M. truncatula microbe-induced root development and interactions with unrelated beneficial and detrimental filamentous microbes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  3. Indexing thoracic CT reports using a preliminary version of a standardized radiological lexicon (RadLex).

    Science.gov (United States)

    Marwede, Dirk; Schulz, Thomas; Kahn, Thomas

    2008-12-01

    To validate a preliminary version of a radiological lexicon (RadLex) against terms found in thoracic CT reports and to index report content in RadLex term categories. Terms from a random sample of 200 thoracic CT reports were extracted using a text processor and matched against RadLex. Report content was manually indexed by two radiologists in consensus in term categories of Anatomic Location, Finding, Modifier, Relationship, Image Quality, and Uncertainty. Descriptive statistics were used and differences between age groups and report types were tested for significance using Kruskal-Wallis and Mann-Whitney Test (significance level <0.05). From 363 terms extracted, 304 (84%) were found and 59 (16%) were not found in RadLex. Report indexing showed a mean of 16.2 encoded items per report and 3.2 Finding per report. Term categories most frequently encoded were Modifier (1,030 of 3,244, 31.8%), Anatomic Location (813, 25.1%), Relationship (702, 21.6%) and Finding (638, 19.7%). Frequency of indexed items per report was higher in older age groups, but no significant difference was found between first study and follow up study reports. Frequency of distinct findings per report increased with patient age (p < 0.05). RadLex already covers most terms present in thoracic CT reports based on a small sample analysis from one institution. Applications for report encoding need to be developed to validate the lexicon against a larger sample of reports and address the issue of automatic relationship encoding.

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

    International Nuclear Information System (INIS)

    Rao, Suman

    2008-01-01

    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)

  5. Affinity purification and partial characterization of a yeast multiprotein complex for nucleotide excision repair using histidine-tagged Rad14 protein

    International Nuclear Information System (INIS)

    Rodriguez, K.; Talamantez, J.; Huang, W.; Reed, S.H.; Wang, Z.; Chen, L.; Feaver, W.J.; Friedberg, E.C.; Tomkinson, A.E.

    1998-01-01

    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

  6. The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus

    DEFF Research Database (Denmark)

    Torres-Rosell, Jordi; Sunjevaric, Ivana; De Piccoli, Giacomo

    2007-01-01

    at an extranucleolar site. The nucleolar exclusion of Rad52 recombination foci entails Mre11 and Smc5-Smc6 complexes and depends on Rad52 SUMO (small ubiquitin-related modifier) modification. Remarkably, mutations that abrogate these activities result in the formation of Rad52 foci within the nucleolus and cause r...

  7. Chemokine MCP1/CCL2 and RANTES/CCL5 gene polymorphisms influence Henoch–Schönlein purpura susceptibility and severity

    Directory of Open Access Journals (Sweden)

    Hsin-Hui Yu

    2015-04-01

    Conclusion: Our results support the fact that chemokines play important roles in the pathogenesis of HSP. MCP1/CCL2 gene polymorphisms were associated with susceptibility for HSP. RANTES/CCL5 gene polymorphisms may be related to disease severity and HSP nephritis.

  8. Tousled-like kinase-dependent phosphorylation of Rad9 plays a role in cell cycle progression and G2/M checkpoint exit.

    Directory of Open Access Journals (Sweden)

    Ryan Kelly

    Full Text Available Genomic integrity is preserved by checkpoints, which act to delay cell cycle progression in the presence of DNA damage or replication stress. The heterotrimeric Rad9-Rad1-Hus1 (9-1-1 complex is a PCNA-like clamp that is loaded onto DNA at structures resulting from damage and is important for initiating and maintaining the checkpoint response. Rad9 possesses a C-terminal tail that is phosphorylated constitutively and in response to cell cycle position and DNA damage. Previous studies have identified tousled-like kinase 1 (TLK1 as a kinase that may modify Rad9. Here we show that Rad9 is phosphorylated in a TLK-dependent manner in vitro and in vivo, and that T355 within the C-terminal tail is the primary targeted residue. Phosphorylation of Rad9 at T355 is quickly reduced upon exposure to ionizing radiation before returning to baseline later in the damage response. We also show that TLK1 and Rad9 interact constitutively, and that this interaction is enhanced in chromatin-bound Rad9 at later stages of the damage response. Furthermore, we demonstrate via siRNA-mediated depletion that TLK1 is required for progression through S-phase in normally cycling cells, and that cells lacking TLK1 display a prolonged G2/M arrest upon exposure to ionizing radiation, a phenotype that is mimicked by over-expression of a Rad9-T355A mutant. Given that TLK1 has previously been shown to be transiently inactivated upon phosphorylation by Chk1 in response to DNA damage, we propose that TLK1 and Chk1 act in concert to modulate the phosphorylation status of Rad9, which in turn serves to regulate the DNA damage response.

  9. Effects of Roux-en-Y Gastric Bypass on Fasting and Postprandial Levels of the Inflammatory Markers YKL-40 and MCP-1 in Patients with Type 2 Diabetes and Glucose Tolerant Subjects

    Directory of Open Access Journals (Sweden)

    Stine Brinkløv Thomsen

    2013-01-01

    Full Text Available Background. The inflammatory markers YKL-40 and monocyte chemoattractant protein-1 (MCP-1 are elevated in morbidly obese patients and decline after weight loss. The objective of our study was to investigate the possible changes of YKL-40 and MCP-1, in both the fasting and the postprandial states, following Roux-en-Y gastric bypass (RYGB in subjects with type 2 diabetes (T2D and normal glucose tolerance (NGT. Methods. Ten obese patients with T2D and 10 subjects with NGT were examined in the fasting state and after a standard meal prior to and after (1 week, 3 months, and 1 year RYGB. Results. Fasting state MCP-1 levels decreased after RYGB in both groups (P values < 0.0001 whereas fasting YKL-40 levels were unchanged (P values ≥ 0.120. Postprandial MCP-1 levels showed a tendency towards a decrease on most study days; however, the changes were only significant at 1 week (P=0.001 and 1 yr (P<0.0001 in the T2D group and at 3 mo after RYGB in the NGT group (P=0.009. YKL-40 levels showed a slight, postprandial suppression on all study days in the T2D group (all P values ≤ 0.021. Conclusions. Fasting MCP-1 levels, but not YKL-40 levels, decrease after RYGB in subjects with T2D and NGT. Postprandial changes of inflammatory markers are discrete and inconsistent.

  10. Simple rules for ultrasonographic subcategorization of BI-RADS{sup ®}-US 4 breast masses

    Energy Technology Data Exchange (ETDEWEB)

    Jales, Rodrigo Menezes, E-mail: rodrigoj@hotmail.com [Department of Obstetrics and Gynecology, Faculty of Medical Sciences, State University of Campinas – Unicamp, Campinas, São Paulo (Brazil); Sarian, Luís Otavio, E-mail: luis.sarian@gmail.com [Department of Obstetrics and Gynecology, Faculty of Medical Sciences, State University of Campinas – Unicamp, Campinas, São Paulo (Brazil); Torresan, Renato, E-mail: torresan@terra.com.br [Department of Obstetrics and Gynecology, Faculty of Medical Sciences, State University of Campinas – Unicamp, Campinas, São Paulo (Brazil); Marussi, Emílio Francisco, E-mail: efmarussi@uol.com.br [Department of Obstetrics and Gynecology, Faculty of Medical Sciences, State University of Campinas – Unicamp, Campinas, São Paulo (Brazil); Álvares, Beatriz Regina, E-mail: alvaresb@terra.com.br [Department of Radiology, Faculty of Medical Sciences, State University of Campinas – Unicamp, Campinas, São Paulo (Brazil); Derchain, Sophie, E-mail: derchain@fcm.unicamp.br [Department of Obstetrics and Gynecology, Faculty of Medical Sciences, State University of Campinas – Unicamp, Campinas, São Paulo (Brazil)

    2013-08-15

    Objectives: To evaluate an objective method for ultrasonographic (US) subcategorization of BI-RADS{sup ®}-US 4 breast masses based on clear and simple rules in order for woman to benefit from a more complete and homogeneous breast mass analysis. Methods: In this cross-sectional study, we selected 330 women, with 339 US breast masses, classified as BI-RADS{sup ®}-US 4. Three physicians experienced in breast imaging independently reviewed all US images, assessing mass shape, margins, orientation, echo texture and vascularity. These experts further subdivided the masses into subcategories 4a, 4b and 4c, according to simple US rules. Inter-observer agreement was calculated for US features categories and for final subcategory assessment. We also estimated the positive predictive value (PPV) for BI-RADS{sup ®}-US subcategories 4a, 4b and 4c assigned by each of the three observers. Results: Pathological examination of all masses confirmed 144 (42%) malignant and 195 (58%) benign tumors. Moderate agreement was obtained for mass shape, margins, vascularity and for final BI-RADS{sup ®}-US 4 subcategory. Substantial agreement was obtained for the description of mass orientation and echo texture. The PPV for subcategories 4a, 4b and 4c were, 17%, 45% and 85%, respectively, for the first observer and 20%, 38% and 79% and 17%, 40% and 85% for the other two observers. Conclusion: Standardization of a US subcategorization of BI-RADS{sup ®}-US 4 breast masses seems to be feasible, with substantial inter-observer agreement and progressive increase in the PPV in the subcategories 4a, 4b and 4c, provided that clear and simple classification rules are defined.

  11. Interobserver variability of ultrasound elastography and the ultrasound BI-RADS lexicon of breast lesions.

    Science.gov (United States)

    Park, Chang Suk; Kim, Sung Hun; Jung, Na Young; Choi, Jae Jung; Kang, Bong Joo; Jung, Hyun Seouk

    2015-03-01

    Elastographpy is a newly developed noninvasive imaging technique that uses ultrasound (US) to evaluate tissue stiffness. The interpretation of the same elastographic images may be variable according to reviewers. Because breast lesions are usually reported according to American College of Radiology Breast Imaging and Data System (ACR BI-RADS) lexicons and final category, we tried to compare observer variability between lexicons and final categorization of US BI-RADS and the elasticity score of US elastography. From April 2009 to February 2010, 1356 breast lesions in 1330 patients underwent ultrasound-guided core biopsy. Among them, 63 breast lesions in 55 patients (mean age, 45.7 years; range, 21-79 years) underwent both conventional ultrasound and elastography and were included in this study. Two radiologists independently performed conventional ultrasound and elastography, and another three observers reviewed conventional ultrasound images and elastography videos. Observers independently recorded the elasticity score for a 5-point scoring system proposed by Itoh et al., BI-RADS lexicons and final category using ultrasound BI-RADS. The histopathologic results were obtained and used as the reference standard. Interobserver variability was evaluated. Of the 63 lesions, 42 (66.7 %) were benign, and 21 (33.3 %) were malignant. The highest value of concordance among all variables was achieved for the elasticity score (k = 0.59), followed by shape (k = 0.54), final category (k = 0.48), posterior acoustic features (k = 0.44), echogenecity and orientation (k = 0.43). The least concordances were margin (k = 0.26), lesion boundary (k = 0.29) and calcification (k = 0.3). Elasticity score showed a higher level of interobserver agreement for the diagnosis of breast lesions than BI-RADS lexicons and final category.

  12. Phenolic excipients of insulin formulations induce cell death, pro-inflammatory signaling and MCP-1 release

    Directory of Open Access Journals (Sweden)

    Claudia Weber

    2015-01-01

    Insulin solutions displayed cytotoxic and pro-inflammatory potential caused by phenol or m-cresol. We speculate that during insulin pump therapy phenol and m-cresol might induce cell death and inflammatory reactions at the infusion site in vivo. Inflammation is perpetuated by release of MCP-1 by activated monocytic cells leading to enhanced recruitment of inflammatory cells. To minimize acute skin complications caused by phenol/m-cresol accumulation, a frequent change of infusion sets and rotation of the infusion site is recommended.

  13. Characterization of RAD4 gene required for ultraviolet-induced excision repair of Saccharomyces cerevisiae propagated in Escherichia coli without inactivation

    International Nuclear Information System (INIS)

    Choi, I.S.; Kim, J.B.; Lee, K.N.; Park, S.D.

    1990-01-01

    The previously isolated RAD4 gene designated as pPC1 from the genomic library of Saccharomyces cerevisiae appeared to propagate in Escherichia coli and yet retained its complementing activity of rad4 mutants without inactivation. The subcloned RAD4 gene was found to be localized within a 2.5 kb DNA fragment flanking Bg/II and BamHI sites in the insert DNA, and was shown to have the same restriction map as a yeast chromosomal DNA, as determined by Southern hybridization. Tetrad analysis and pulse-field chromosome mapping have revealed that the cloned RAD4 gene can be mapped and integrated into the yeast chromosome V, the actual site of this gene. DNA-tRNA hybridization has shown that the isolated RAD4 gene did not contain a suppressor tRNA gene. These results have indicated that the pPC1 is a functional RAD4 gene playing a unique role involved in the nucleotide excision repair of yeast without any genetic change during amplification in E. coli. (author)

  14. Passive solar technology

    Energy Technology Data Exchange (ETDEWEB)

    Watson, D

    1981-04-01

    The present status of passive solar technology is summarized, including passive solar heating, cooling and daylighting. The key roles of the passive solar system designer and of innovation in the building industry are described. After definitions of passive design and a summary of passive design principles are given, performance and costs of passive solar technology are discussed. Passive energy design concepts or methods are then considered in the context of the overall process by which building decisions are made to achieve the integration of new techniques into conventional design. (LEW).

  15. Human CST Facilitates Genome-wide RAD51 Recruitment to GC-Rich Repetitive Sequences in Response to Replication Stress.

    Science.gov (United States)

    Chastain, Megan; Zhou, Qing; Shiva, Olga; Fadri-Moskwik, Maria; Whitmore, Leanne; Jia, Pingping; Dai, Xueyu; Huang, Chenhui; Ye, Ping; Chai, Weihang

    2016-08-02

    The telomeric CTC1/STN1/TEN1 (CST) complex has been implicated in promoting replication recovery under replication stress at genomic regions, yet its precise role is unclear. Here, we report that STN1 is enriched at GC-rich repetitive sequences genome-wide in response to hydroxyurea (HU)-induced replication stress. STN1 deficiency exacerbates the fragility of these sequences under replication stress, resulting in chromosome fragmentation. We find that upon fork stalling, CST proteins form distinct nuclear foci that colocalize with RAD51. Furthermore, replication stress induces physical association of CST with RAD51 in an ATR-dependent manner. Strikingly, CST deficiency diminishes HU-induced RAD51 foci formation and reduces RAD51 recruitment to telomeres and non-telomeric GC-rich fragile sequences. Collectively, our findings establish that CST promotes RAD51 recruitment to GC-rich repetitive sequences in response to replication stress to facilitate replication restart, thereby providing insights into the mechanism underlying genome stability maintenance. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. It should be indicate a biopsy for BI-RADS 3 mammogram?

    Directory of Open Access Journals (Sweden)

    Anahi Ofelia Vera San Miguel

    2016-12-01

    Full Text Available Background: Worldwide, mammography is the imaging method most commonly used for early detection of breast cancer, decisive for prior to the onset of symptoms diagnosed. The malignancy that is recorded more frequently in women is breast cancer, regarded worldwide as a major public health problem. By implementing the BI-RADS manual seeks to standardize mammographic report. Objective: To determine the radiographic and anatomic-pathologic concordance of mammographic findings in women of thirty years and more, who consulted in the Hospital Central del Instituto de Previsión Social- Paraguay, during the first semester of 2015. Materials and Methods: We performed a cross-sectional, retrospective study. The variables age, reasons for seeing a doctor, mammographic findings, histopathological diagnoses obtained from breast biopsy and reporting BI-RADS were studied. Results: The sample consisted of 138 women. The age range of the patients was 30 to 89 years, with an average of 55 years. The annual routine check represented the most frequent reason for consultation (52.0%. 71.0% of the findings corresponded to dense nodules, and they were 75.0% malignancies. Conclusion: The agreement was moderate with Kappa index. In patients with BI-RADS 3, there were found 30.62% malignancies, so it is suggested to consider from this level for pathological study.

  17. Loss of the homologous recombination gene rad51 leads to Fanconi anemia-like symptoms in zebrafish.

    Science.gov (United States)

    Botthof, Jan Gregor; Bielczyk-Maczyńska, Ewa; Ferreira, Lauren; Cvejic, Ana

    2017-05-30

    RAD51 is an indispensable homologous recombination protein, necessary for strand invasion and crossing over. It has recently been designated as a Fanconi anemia (FA) gene, following the discovery of two patients carrying dominant-negative mutations. FA is a hereditary DNA-repair disorder characterized by various congenital abnormalities, progressive bone marrow failure, and cancer predisposition. In this report, we describe a viable vertebrate model of RAD51 loss. Zebrafish rad51 loss-of-function mutants developed key features of FA, including hypocellular kidney marrow, sensitivity to cross-linking agents, and decreased size. We show that some of these symptoms stem from both decreased proliferation and increased apoptosis of embryonic hematopoietic stem and progenitor cells. Comutation of p53 was able to rescue the hematopoietic defects seen in the single mutants, but led to tumor development. We further demonstrate that prolonged inflammatory stress can exacerbate the hematological impairment, leading to an additional decrease in kidney marrow cell numbers. These findings strengthen the assignment of RAD51 as a Fanconi gene and provide more evidence for the notion that aberrant p53 signaling during embryogenesis leads to the hematological defects seen later in life in FA. Further research on this zebrafish FA model will lead to a deeper understanding of the molecular basis of bone marrow failure in FA and the cellular role of RAD51.

  18. Effects of Roux-en-Y Gastric Bypass on Fasting and Postprandial Levels of the Inflammatory Markers YKL-40 and MCP-1 in Patients with Type 2 Diabetes and Glucose Tolerant Subjects

    DEFF Research Database (Denmark)

    Thomsen, Stine Brinkløv; Rathcke, Camilla Noelle; Jørgensen, Nils Bruun

    2013-01-01

    Background. The inflammatory markers YKL-40 and monocyte chemoattractant protein-1 (MCP-1) are elevated in morbidly obese patients and decline after weight loss. The objective of our study was to investigate the possible changes of YKL-40 and MCP-1, in both the fasting and the postprandial states......, following Roux-en-Y gastric bypass (RYGB) in subjects with type 2 diabetes (T2D) and normal glucose tolerance (NGT). Methods. Ten obese patients with T2D and 10 subjects with NGT were examined in the fasting state and after a standard meal prior to and after (1 week, 3 months, and 1 year) RYGB. Results....... Fasting state MCP-1 levels decreased after RYGB in both groups (P values...

  19. The recombination protein RAD52 cooperates with the excision repair protein OGG1 for the repair of oxidative lesions in mammalian cells

    DEFF Research Database (Denmark)

    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...... knockdown, and mouse cells lacking the protein via gene knockout showed increased sensitivity to oxidative stress. Moreover, cells depleted of RAD52 show higher accumulation of oxidized bases in their genome than cells with normal levels of RAD52. Our results indicate that RAD52 cooperates with OGG1...... to repair oxidative DNA damage and enhances the cellular resistance to oxidative stress. Our observations suggest a coordinated action between these proteins that may be relevant when oxidative lesions positioned close to strand breaks impose a hindrance to RAD52 catalytic activities....

  20. Mouse Rad9b is essential for embryonic development and promotes resistance to DNA damage

    Science.gov (United States)

    Leloup, Corinne; Hopkins, Kevin M.; Wang, Xiangyuan; Zhu, Aiping; Wolgemuth, Debra J.; Lieberman, Howard B.

    2010-01-01

    RAD9 participates in promoting resistance to DNA damage, cell cycle checkpoint control, DNA repair, apoptosis, embryogenesis, and regulation of transcription. A paralogue of RAD9 (named RAD9B) has been identified. To define the function of mouse Rad9b (Mrad9b), embryonic stem (ES) cells with a targeted gene deletion were constructed and used to generate Mrad9b mutant mice. Mrad9b−/− embryos are resorbed after E7.5 while some of the heterozygotes die between E12.5 and a few days after birth. Mrad9b is expressed in embryonic brain and Mrad9b+/− embryos exhibit abnormal neural tube closure. Mrad9b−/− mouse embryonic fibroblasts are not viable. Mrad9b−/− ES cells are more sensitive to gamma rays and mitomycin C than Mrad9b+/+ controls, but show normal gamma-ray-induced G2/M checkpoint control. There is no evidence of spontaneous genomic instability in Mrad9b−/− cells. Our findings thus indicate that Mrad9b is essential for embryonic development and mediates resistance to certain DNA damaging agents. PMID:20842695

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Ghandhi, Shanaz A; Ponnaiya, Brian; Panigrahi, Sunil K; Hopkins, Kevin M; Cui, Qingping; Hei, Tom K; Amundson, Sally A; Lieberman, Howard B

    2014-01-01

    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

  3. 2b-RAD genotyping for population genomic studies of Chagas disease vectors: Rhodnius ecuadoriensis in Ecuador.

    Directory of Open Access Journals (Sweden)

    Luis E Hernandez-Castro

    2017-07-01

    Full Text Available Rhodnius ecuadoriensis is the main triatomine vector of Chagas disease, American trypanosomiasis, in Southern Ecuador and Northern Peru. Genomic approaches and next generation sequencing technologies have become powerful tools for investigating population diversity and structure which is a key consideration for vector control. Here we assess the effectiveness of three different 2b restriction site-associated DNA (2b-RAD genotyping strategies in R. ecuadoriensis to provide sufficient genomic resolution to tease apart microevolutionary processes and undertake some pilot population genomic analyses.The 2b-RAD protocol was carried out in-house at a non-specialized laboratory using 20 R. ecuadoriensis adults collected from the central coast and southern Andean region of Ecuador, from June 2006 to July 2013. 2b-RAD sequencing data was performed on an Illumina MiSeq instrument and analyzed with the STACKS de novo pipeline for loci assembly and Single Nucleotide Polymorphism (SNP discovery. Preliminary population genomic analyses (global AMOVA and Bayesian clustering were implemented. Our results showed that the 2b-RAD genotyping protocol is effective for R. ecuadoriensis and likely for other triatomine species. However, only BcgI and CspCI restriction enzymes provided a number of markers suitable for population genomic analysis at the read depth we generated. Our preliminary genomic analyses detected a signal of genetic structuring across the study area.Our findings suggest that 2b-RAD genotyping is both a cost effective and methodologically simple approach for generating high resolution genomic data for Chagas disease vectors with the power to distinguish between different vector populations at epidemiologically relevant scales. As such, 2b-RAD represents a powerful tool in the hands of medical entomologists with limited access to specialized molecular biological equipment.

  4. 2b-RAD genotyping for population genomic studies of Chagas disease vectors: Rhodnius ecuadoriensis in Ecuador.

    Science.gov (United States)

    Hernandez-Castro, Luis E; Paterno, Marta; Villacís, Anita G; Andersson, Björn; Costales, Jaime A; De Noia, Michele; Ocaña-Mayorga, Sofía; Yumiseva, Cesar A; Grijalva, Mario J; Llewellyn, Martin S

    2017-07-01

    Rhodnius ecuadoriensis is the main triatomine vector of Chagas disease, American trypanosomiasis, in Southern Ecuador and Northern Peru. Genomic approaches and next generation sequencing technologies have become powerful tools for investigating population diversity and structure which is a key consideration for vector control. Here we assess the effectiveness of three different 2b restriction site-associated DNA (2b-RAD) genotyping strategies in R. ecuadoriensis to provide sufficient genomic resolution to tease apart microevolutionary processes and undertake some pilot population genomic analyses. The 2b-RAD protocol was carried out in-house at a non-specialized laboratory using 20 R. ecuadoriensis adults collected from the central coast and southern Andean region of Ecuador, from June 2006 to July 2013. 2b-RAD sequencing data was performed on an Illumina MiSeq instrument and analyzed with the STACKS de novo pipeline for loci assembly and Single Nucleotide Polymorphism (SNP) discovery. Preliminary population genomic analyses (global AMOVA and Bayesian clustering) were implemented. Our results showed that the 2b-RAD genotyping protocol is effective for R. ecuadoriensis and likely for other triatomine species. However, only BcgI and CspCI restriction enzymes provided a number of markers suitable for population genomic analysis at the read depth we generated. Our preliminary genomic analyses detected a signal of genetic structuring across the study area. Our findings suggest that 2b-RAD genotyping is both a cost effective and methodologically simple approach for generating high resolution genomic data for Chagas disease vectors with the power to distinguish between different vector populations at epidemiologically relevant scales. As such, 2b-RAD represents a powerful tool in the hands of medical entomologists with limited access to specialized molecular biological equipment.

  5. Chemistry of the oxophosphinidene ligand. 2. Reactivity of the anionic complexes [MCp{P(O)R*}(CO)(2)](-) (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3)) toward electrophiles based on elements different from carbon.

    Science.gov (United States)

    Alonso, María; Alvarez, M Angeles; García, M Esther; Ruiz, Miguel A; Hamidov, Hayrullo; Jeffery, John C

    2010-12-20

    The anionic oxophosphinidene complexes (H-DBU)[MCp{P(O)R*}(CO)(2)] (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3); Cp = η(5)-C(5)H(5), DBU = 1,8-diazabicyclo [5.4.0] undec-7-ene) displayed multisite reactivity when faced with different electrophilic reagents. The reactions with the group 14 organochloride compounds ER(4-x)Cl(x) (E = Si, Ge, Sn, Pb) led to either phosphide-like, oxophosphinidene-bridged derivatives [MCp{P(OE')R*}(CO)(2)] (E' = SiMe(3), SiPh(3), GePh(3), GeMe(2)Cl) or to terminal oxophosphinidene complexes [MCp{P(O)R*}(CO)(2)(E')] (E' = SnPh(3), SnPh(2)Cl, PbPh(3); Mo-Pb = 2.8845(4) Å for the MoPb compound). A particular situation was found in the reaction with SnMe(3)Cl, this giving a product existing in both tautomeric forms, with the phosphide-like complex [MCp{P(OSnMe(3))R*}(CO)(2)] prevailing at room temperature and the tautomer [MCp{P(O)R*}(CO)(2)(SnMe(3))] being the unique species present below 203 K in dichloromethane solution. The title anions also showed a multisite behavior when reacting with transition-metal based electrophiles. Thus, the reactions with the complexes [M'Cp(2)Cl(2)] (M' = Ti, Zr) gave phosphide-like derivatives [MCp{P(OM')R*}(CO)(2)] (M = Mo, M' = TiCp(2)Cl, ZrCp(2)Cl; M = W, M' = ZrCp(2)Cl), displaying a bridging κ(1),κ(1)-P,O- oxophosphinidene ligand connecting MCp(CO)(2) and M'Cp(2)Cl metal fragments (W-P = 2.233(1) Å, O-Zr = 2.016(4) Å for the WZr compound]. In contrast, the reactions with the complex [AuCl{P(p-tol)(3)}] gave the metal-metal bonded derivatives trans-[MCp{P(O)R*}(CO)(2){AuP(p-tol)(3)}] (M = Mo, W; Mo-Au = 2.7071(7) Å). From all the above results it was concluded that the terminal oxophosphinidene complexes are preferentially formed under conditions of orbital control, while charge-controlled reactions tend to give derivatives with the electrophilic fragment bound to the oxygen atom of the oxophosphinidene ligand (phosphide-like, oxophosphinidene-bridged derivatives).

  6. VEGF 936C > T Polymorphism and Association of BI-RADS Score in Women with Suspected Breast Cancer

    Directory of Open Access Journals (Sweden)

    M. Wehrschuetz

    2009-01-01

    Full Text Available Purpose Vascular endothelial growth factor (VEGF is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumors. A 936C> T polymorphism in the VEGF gene has been associated with reduced VEGF plasma levels. Purpose of the present study was to analyze the potential association between VEGF genotype and radiological appearance of breast lesions by mammography. Materials and Methods Fifty two women with 54 suspected breast lesions were analyzed by the use of mammography with the standard breast imaging reporting and data systems (BI-RADS. Germline VEGF genotype was determined in all subjects by allele-specific digestion of amplification products. An open biopsy was performed on all lesions. Results VEGF CC, CT and TT genotypes were found in 41 (79%, 9 (17% and 2 (4% patients. By mammography 26, 16 and 12 suspected breast lesions were classified as BI-RADS scores 3, 4 and 5, respectively. Both carriers of the TT genotype were classified as BI-RADS 5, whereas among CT or CC carriers, BI-RADS scores 3, 4 and 5 were found in 26, 16 and 10 subjects (P T polymorphism seems to be associated with a high BI-RADS score in women with suspicious breast lesions.

  7. Analysis of the temporal expression of chemokines and chemokine receptors during experimental granulomatous inflammation: role and expression of MIP-1α and MCP-1

    Science.gov (United States)

    Carollo, Maria; Hogaboam, Cory M; Kunkel, Stephen L; Delaney, Stephen; Christie, Mark I; Perretti, Mauro

    2001-01-01

    Chemokine expression and function was monitored in an experimental model of granulomatous tissue formation after injection of croton oil in complete Freund's adjuvant (CO/CFA) into mouse dorsal air-pouches up to 28 days. In the first week, mast cell degranulation and leukocyte influx (mononuclear cell, MNC, and polymorphonuclear cell, PMN) were associated with CXCR2, KC and macrophage inflammatory protein (MIP)-2 mRNA expression, as determined by TaqMan® reverse transcriptase-polymerase chain reaction. KC (∼400 pg mg protein−1, n=12) and MIP-2 (∼800 pg mg protein−1, n=12) proteins peaked at day 7, together with myeloperoxidase (MPO) activity. Highest MIP-1α (>1 ng mg protein−1, n=12) levels were measured at day 3. After day 7, a gradual increase in CCR2 and CCR5 mRNA, monocyte chemoattractant protein (MCP)-1 mRNA and protein expression was measured. MCP-1 protein peaked at day 21 (∼150 pg mg protein−1, n=12) and was predominantly expressed by mast cells. A gradual increase in N-acetyl-β-D-glucosaminidase (NAG) activity (maximal at 28 days) was also measured. An antiserum against MIP-1α did not modify the inflammatory response measured at day 7 (except for a 50% reduction in MIP-1α levels), but provoked a significant increase in MPO, NAG and MCP-1 levels as measured at day 21 (n=6, Pvalues (n=8, P<0.05). In conclusion, we have shown that CO/CFA initiates a complex inflammatory reaction in which initial expression of MIP-1α serves a protective role whereas delayed expression of MCP-1 seems to have a genuine pro-inflammatory role. PMID:11704636

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

    Data.gov (United States)

    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...

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

    Science.gov (United States)

    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

    2016-05-27

    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.

  10. Final disposal of the rad waste materials - question of the nuclear energy implementation and application perspectives

    International Nuclear Information System (INIS)

    Plecas, I.

    1995-01-01

    Two main problems that are denying and slowing down the development of nuclear energy are safe work of the nuclear power facilities (NEF) and disposal of the radioactive waste materials, produced from the NEF and infrastructure facilities of the nuclear fuel cycle (NFC). Although nowadays worldwide knowledge, based on the 45 year of experiences in handling the radioactive waste materials, do not treat the problems of final disposal of the rad waste materials as a task of the primary importance in NFC, this subject still engage experts from this field of investigations, especially in the countries that developed all aspects of the nuclear fuel cycle. Techniques for final disposal of low and intermediate level rad waste materials, are well known and are in state of implementation. The importance of the fundamental safety principles, implemented in the IAEA documents, concerning handling, treatment and final disposal of the rad waste materials, is presented. Future usage of nuclear energy, taking into account all the facts that are dealing with problems of the rad waste materials produced in the NFC, can be a reality. (author.)

  11. Physical, chemical and sensory changes of refrigerated yellow pitahaya treated preharvest with 1-MCP

    OpenAIRE

    Liliana Serna Cock; Laura Sofía Torres Valenzuela; Alfredo Ayala Aponte

    2013-01-01

    El efecto de la aplicación de soluciones acuosas de 0, 200 y 400 mg L de 1-metilciclopropeno (1-MCP) en pitahaya amarilla en precosecha (Selenicereus megalanthus Haw) fue evaluado. Se midieron los cambios en pérdida de peso, cambio total de la coloración, azucares totales, acidez titulable, ácido ascórbico y análisis sensorial. La pitahaya fue almacenada bajo refrigeración (10°C y 85% de humedad relativa por 29 días). Dos tipos de empaque (Cajas para exportación y canastillas plá...

  12. Ultrasonographic characteristics and BI-RADS-US classification of BRCA1 mutation-associated breast cancer in Guangxi, China.

    Science.gov (United States)

    Li, Cheng; Liu, Junjie; Wang, Sida; Chen, Yuanyuan; Yuan, Zhigang; Zeng, Jian; Li, Zhixian

    2015-01-01

    To retrospectively analyze and compare the ultrasonographic characteristics and BI-RADS-US classification between patients with BRCA1 mutation-associated breast cancer and those without BRCA1 gene mutation in Guangxi, China. The study was performed in 36 lesions from 34 BRCA1 mutation-associated breast cancer patients. A total of 422 lesions from 422 breast cancer patients without BRCA1 mutations served as control group. The comparison of the ultrasonographic features and BI-RADS-US classification between two the groups were reviewed. More complex inner echo was disclosed in BRCA1 mutation-associated breast cancer patients (x(2) = 4.741, P = 0.029). The BI-RADS classification of BRCA1 mutation-associated breast cancer was lower (U = 6094.0, P = 0.022). BRCA1 mutation-associated breast cancer frequently displays as microlobulated margin and complex echo. It also shows more benign characteristics in morphology, and the BI-RADS classification is prone to be underestimated.

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

    International Nuclear Information System (INIS)

    Malik, M. F. I.; Rabaiee, N. A.; Jaafar, M. S.

    2015-01-01

    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. RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination.

    Science.gov (United States)

    Inano, Shojiro; Sato, Koichi; Katsuki, Yoko; Kobayashi, Wataru; Tanaka, Hiroki; Nakajima, Kazuhiro; Nakada, Shinichiro; Miyoshi, Hiroyuki; Knies, Kerstin; Takaori-Kondo, Akifumi; Schindler, Detlev; Ishiai, Masamichi; Kurumizaka, Hitoshi; Takata, Minoru

    2017-06-01

    RFWD3 is a recently identified Fanconi anemia protein FANCW whose E3 ligase activity toward RPA is essential in homologous recombination (HR) repair. However, how RPA ubiquitination promotes HR remained unknown. Here, we identified RAD51, the central HR protein, as another target of RFWD3. We show that RFWD3 polyubiquitinates both RPA and RAD51 in vitro and in vivo. Phosphorylation by ATR and ATM kinases is required for this activity in vivo. RFWD3 inhibits persistent mitomycin C (MMC)-induced RAD51 and RPA foci by promoting VCP/p97-mediated protein dynamics and subsequent degradation. Furthermore, MMC-induced chromatin loading of MCM8 and RAD54 is defective in cells with inactivated RFWD3 or expressing a ubiquitination-deficient mutant RAD51. Collectively, our data reveal a mechanism that facilitates timely removal of RPA and RAD51 from DNA damage sites, which is crucial for progression to the late-phase HR and suppression of the FA phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Evidence that a recombinationless strain, rad 51, of Saccharomyces cerevisiae lacks the budding cell resistance to γ-rays

    International Nuclear Information System (INIS)

    Hama-Inaba, Hiroko; Saeki, Tetsuya

    1975-01-01

    The radiosensitivities of a wild-type and x-ray sensitive mutant, rad 51 (defective in genetic recombination) of Saccharomyces cerevisiae to γ-rays were compared, using non-synchronized and partially synchronized cultures. The rad 51 cells, either haploid or diploid, showed only very small changes in radiosensitivity during cell growth, whereas the wild-type cells, especially haploid, showed the well-known budding resistance. The heterozygous (wild/rad 51) diploid cells showed in a survival curve a remarkable budding resistance and sigmoidal inactivation kinetics similar to those of wild-type homozygous diploid cells. (author)

  16. RIVER-RAD, Radionuclide Transport in Surface Waters

    International Nuclear Information System (INIS)

    1996-01-01

    1 - Description of program or function: RIVER-RAD assesses 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. 2 - Method of solution: A compartmental linear transfer model is used in RIVER-RAD. The river system model in the code is divided into reaches (compartments) of equal size, each with a sediment compartment below it. The movement of radionuclides is represented by a series of transfers between the reaches, and between the water and sediment compartments of each reach. Within each reach (for both the water and sediment compartments), the radionuclides are assumed to be uniformly mixed. Upward volatilization is allowed from the water compartment, and the transfer of radionuclides between the reaches is determined by the flow rate of the river. Settling and resuspension velocities determine the transfer of absorbed radionuclides between the water and sediment compartments. Radioactive decay and decay-product buildup are incorporated into all transport calculations for all radionuclide chains specified by the user. Each nuclide may have unique input and removal rates. Volatilization and radiological decay are considered as linear rate constants in the model. 3 - Restrictions on the complexity of the problem: None noted

  17. MCP-1, ICAM-1 and VCAM-1 are present in early aneurysmal dilatation in experimental rats

    International Nuclear Information System (INIS)

    Jun Fan; Hao-Tong; Jing Di; Fang Liu; Hai-Hua Zhao; Shu-Ling Bai; Xiang Li; Linlin Zhong

    2010-01-01

    Recent studies have suggested that inflammation actively participates in ascending aortic aneurysm formation. The aim of the present study was to evaluate the expression changes of adhesion molecules and MMPs in an experimental model of ascending aortic aneurysm induced by ascending aorta banding in Wistar rats. Twelve rats developed aortic dilation after ascending aorta banding treatment, while nine normal animals underwent surgery without banding were used as controls. Light microscope and scanning electron microscope showed that the wall of the ascending aorta became disorganized as well as infiltration by inflammatory cells in aneurysmal rats. By using immunohistochemical techniques, a significant increase in the immunostaining of MCP-1 was observed in the aneurysmal wall as compared to the normal aortic wall. Under similar experimental conditions, we also found that the immunostaining of ICAM-1 and VCAM-1 was markedly increased in the aneurysmal wall. In addition, gelatin zymo graphic analysis showed that the expression and activities of MMP-2 and MMP-9 were remarkably enhanced in the ascending aorta of ascending aortic aneurysmal rats as compared to normal rats. These results demonstrate that MCP-1, ICAM-1 and VCAM-1 are involved in the pathogenesis of ascending aortic aneurysm and an increase in the immunostaining and activity of MMP-2 and MMP-9 may promote the progression of ascending aortic aneurysm. (authors)

  18. PEG-albumin plasma expansion increases expression of MCP-1 evidencing increased circulatory wall shear stress: an experimental study.

    Directory of Open Access Journals (Sweden)

    C Makena Hightower

    Full Text Available Treatment of blood loss with plasma expanders lowers blood viscosity, increasing cardiac output. However, increased flow velocity by conventional plasma expanders does not compensate for decreased viscosity in maintaining vessel wall shear stress (WSS, decreasing endothelial nitric oxide (NO production. A new type of plasma expander using polyethylene glycol conjugate albumin (PEG-Alb causes supra-perfusion when used in extreme hemodilution and is effective in treating hemorrhagic shock, although it is minimally viscogenic. An acute 40% hemodilution/exchange-transfusion protocol was used to compare 4% PEG-Alb to Ringer's lactate, Dextran 70 kDa and 6% Hetastarch (670 kDa in unanesthetized CD-1 mice. Serum cytokine analysis showed that PEG-Alb elevates monocyte chemotactic protein-1 (MCP-1, a member of a small inducible gene family, as well as expression of MIP-1α, and MIP-2. MCP-1 is specific to increased WSS. Given the direct link between increased WSS and production of NO, the beneficial resuscitation effects due to PEG-Alb plasma expansion appear to be due to increased WSS through increased perfusion and blood flow rather than blood viscosity.

  19. Stereotactic vacuum core biopsy of clustered microcalcifications classified as BI-RADS{sup TM} type 3; Stereotaktische Vakuumstanzbiopsie zur Abklaerung von gruppiertem Mikrokalk der Kategorie BI-RADS{sup TM} 3

    Energy Technology Data Exchange (ETDEWEB)

    Obenauer, S.; Fischer, U.; Baum, F.; Dammert, S.; Grabbe, E. [Goettingen Univ. (Germany). Abt. fuer Roentgendiagnostik; Fuezesi, L. [Goettingen Univ. (Germany). Zentrum Pathologie

    2001-08-01

    Purpose: Evaluation of stereotactic vacuum core biopsy of clustered microcalcifications categorized as BI-RADS{sup TM} 3. Material and methods: 86 patients with microcalcification BI-RADS{sup TM} 3 (probably benign, <3% malignant) underwent a stereotactic vacuum core biopsy (Mammotome, Fa. Ethicon Endo-Surgery Breast Care) using a digital stereotactic unit (Mammotest, Fa. Fischer Imaging). The removal of the calcifications was judged by two radiologists in consensus and classified as complete (100%), major (55-99%) or incomplete (<50%). Results: 4/86 patients could not be evaluated by vacuum core biopsy due to the localization of the microcalcifications close to the skin or lack of detection. In 40/82 cases a complete, in 38/82 a major, and in 4/82 an incomplete removal was achieved. Histology revealed 67 cases of fibrocystic changes, 4 papillomas, 4 fibroadenomas, 4 cases of atypical ductal hyperplasia (ADH), and 3 ductal carcinomas in situ (DCIS), one of these with a minimal-invasive tumor component. Patients with ADH were advised to undergo surgical biopsy. Histology revealed complete removal. 7 patients had complications or side-effects. Conclusions: Percutaneous vacuum core biopsy is a reliable minimal-invasive diagnostic method to come to the final diagnosis in patients with clustered microcalcifications categorized BI-RADS{sup TM} 3. However, if malignancy is proven (about 4% of our cases) an open biopsy is necessary. (orig.) [German] Zielsetzung: Evaluation der stereotaktischen Vakuumstanzbiopsie bei gruppierten Mikrokalzifikationen vom Typ BI-RADS{sup TM}3. Material und Methodik: Gruppiert angeordneter Mikrokalk der Kategorie BI-RADS{sup TM} 3 (wahrscheinlich benigne, <3% maligne) wurde bei 86 Patientinnen mit einer stereotaktischen Vakuumstanzbiopsie (Mammotome{sup circledR}, Fa. Ethicon Endo-Surgery Breast Care) an einem digitalen Stereotaxietisch (Mammotest, Fa. Fischer Imaging) abgeklaert. Das Ausmass der bioptisch entfernten Kalizifkationen wurde von

  20. Rapid, autonomous analysis of He spectra I: Overview of the RadID program, user experience, and structure

    Energy Technology Data Exchange (ETDEWEB)

    Gosnell, Thomas B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Chavez, Joseph R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Rowland, Mark S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Wong, James L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2014-02-26

    RadID is a new gamma-ray spectrum analysis program for rapid screening of HPGe gamma-ray data to reveal the presence of radionuclide signatures. It is an autonomous, rule-based heuristic system that can identify well over 200 radioactive sources with particular interest in uranium and plutonium characteristics. It executes in about one second. RadID does not require knowledge of the detector efficiency, the source-to-detector distance, or the geometry of the inspected radiation source—including any shielding. In this first of a three-document series we sketch the RadID program’s origin, its minimal requirements, the user experience, and the program operation.

  1. A dedicated BI-RADS training programme: Effect on the inter-observer variation among screening radiologists

    International Nuclear Information System (INIS)

    Timmers, J.M.H.; Doorne-Nagtegaal, H.J. van; Verbeek, A.L.M.; Heeten, G.J. den; Broeders, M.J.M.

    2012-01-01

    Introduction: The Breast Imaging Reporting and Data System (BI-RADS) was introduced in the Dutch breast cancer screening programme to improve communication between medical specialists. Following introduction, a substantial variation in the use of the BI-RADS lexicon for final assessment categories was noted among screening radiologists. We set up a dedicated training programme to reduce this variation. This study evaluates whether this programme was effective. Materials and methods: Two comparable test sets were read before and after completion of the training programme. Each set contained 30 screening mammograms of referred women selected from screening practice. The sets were read by 25 experienced and 30 new screening radiologists. Cohen's kappa (κ) was used to calculate the inter-observer agreement. The BI-RADS 2003 version was implemented in the screening programme as the BI-RADS 2008 version requires the availability of diagnostic work-up, and this is unavailable. Results: The inter-observer agreement of all participating radiologists (n = 55) with the expert panel increased from a pre-training κ-value of 0.44 to a post-training κ-value of 0.48 (p = 0.14). The inter-observer agreement of the new screening radiologists (n = 30) with the expert panel increased from κ = 0.41 to κ = 0.50 (p = 0.01), whereas there was no difference in agreement among the 25 experienced radiologists (from κ = 0.48 to κ = 0.46, p = 0.60). Conclusion: Our training programme in the BI-RADS lexicon resulted in a significant improvement of agreement among new screening radiologists. Overall, the agreement among radiologists was moderate (guidelines Landis and Koch). This is in line with results found in the literature

  2. Simulation of the GCR spectrum in the Mars curiosity rover's RAD detector using MCNP6.

    Science.gov (United States)

    Ratliff, Hunter N; Smith, Michael B R; Heilbronn, Lawrence

    2017-08-01

    The paper presents results from MCNP6 simulations of galactic cosmic ray (GCR) propagation down through the Martian atmosphere to the surface and comparison with RAD measurements made there. This effort is part of a collaborative modeling workshop for space radiation hosted by Southwest Research Institute (SwRI). All modeling teams were tasked with simulating the galactic cosmic ray (GCR) spectrum through the Martian atmosphere and the Radiation Assessment Detector (RAD) on-board the Curiosity rover. The detector had two separate particle acceptance angles, 4π and 30 ° off zenith. All ions with Z = 1 through Z = 28 were tracked in both scenarios while some additional secondary particles were only tracked in the 4π cases. The MCNP6 4π absorbed dose rate was 307.3 ± 1.3 µGy/day while RAD measured 233 µGy/day. Using the ICRP-60 dose equivalent conversion factors built into MCNP6, the simulated 4π dose equivalent rate was found to be 473.1 ± 2.4 µSv/day while RAD reported 710 µSv/day. Copyright © 2017 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

  3. SNP discovery in common bean by restriction-associated DNA (RAD) sequencing for genetic diversity and population structure analysis.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  5. Rad50S alleles of the Mre11 complex: questions answered and questions raised.

    Science.gov (United States)

    Usui, Takehiko; Petrini, John H J; Morales, Monica

    2006-08-15

    We find that Rad50S mutations in yeast and mammals exhibit constitutive PIKK (PI3-kinase like kinase)-dependent signaling [T. Usui, H. Ogawa, J.H. Petrini, A DNA damage response pathway controlled by Tel1 and the Mre11 complex. Mol. Cell 7 (2001) 1255-1266.; M. Morales, J.W. Theunissen, C.F. Kim, R. Kitagawa, M.B. Kastan, J.H. Petrini, The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev. 19 (2005) 3043-4354.]. The signaling depends on Mre11 complex functions, consistent with its role as a DNA damage sensor. Rad50S is distinct from hypomorphic mutations of Mre11 and Nbs1 in mammals [M. Morales, J.W. Theunissen, C.F. Kim, R. Kitagawa, M.B. Kastan, J.H. Petrini, The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev. 19 (2005) 3043-3054.; J.P. Carney, R.S. Maser, H. Olivares, E.M. Davis, Le M. Beau, J.R. Yates, III, L. Hays, W.F. Morgan, J.H. Petrini, The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93 (1998) 477-486.; G.S. Stewart, R.S. Maser, T. Stankovic, D.A. Bressan, M.I. Kaplan, N.G. Jaspers, A. Raams, P.J. Byrd, J.H. Petrini, A.M. Taylor, The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99 (1999) 577-587.; B.R. Williams, O.K. Mirzoeva, W.F. Morgan, J. Lin, W. Dunnick, J.H. Petrini, A murine model of nijmegen breakage syndrome. Curr. Biol. 12 (2002) 648-653.; J.W. Theunissen, M.I. Kaplan, P.A. Hunt, B.R. Williams, D.O. Ferguson, F.W. Alt, J.H. Petrini, Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice. Mol. Cell 12 (2003) 1511-1523.] and the Mre11 complex deficiency in yeast [T. Usui, H. Ogawa, J.H. Petrini, A DNA damage response

  6. Comparison of Performance Characteristics of American College of Radiology TI-RADS, Korean Society of Thyroid Radiology TIRADS, and American Thyroid Association Guidelines.

    Science.gov (United States)

    Middleton, William D; Teefey, Sharlene A; Reading, Carl C; Langer, Jill E; Beland, Michael D; Szabunio, Margaret M; Desser, Terry S

    2018-05-01

    The American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) provides guidelines to practitioners who interpret sonographic examinations of thyroid nodules. The purpose of this study is to compare the ACR TI-RADS system with two other well-established guidelines. The ACR TI-RADS, the Korean Society of Thyroid Radiology (KSThR) Thyroid Imaging Reporting and Data System (TIRADS), and the American Thyroid Association guidelines were compared using 3422 thyroid nodules for which pathologic findings were available. The composition, echogenicity, margins, echogenic foci, and size of the nodules were assessed to determine whether a recommendation would be made for fine-needle aspiration or follow-up sonography when each system was used. The biopsy yield of malignant findings, the yield of follow-up, and the percentage of malignant and benign nodules that would be biopsied were determined for all nodules and for nodules 1 cm or larger. The percentage of nodules that could not be classified was 0%, 3.9%, and 13.9% for the ACR TI-RADS, KSThR TIRADS, and ATA guidelines, respectively. The biopsy yield of malignancy was 14.2%, 10.2%, and 10.0% for nodules assessed by the ACR TI-RADS, KSThR TIRADS, and ATA guidelines, respectively. The percentage of malignant nodules that were biopsied was 68.2%, 78.7%, and 75.9% for the ACR TI-RADS, the KSThR TIRADS, and the ATA guidelines, respectively, whereas the percentage of malignant nodules that would be either biopsied or followed was 89.2% for the ACR TI-RADS. The percentage of benign nodules that would be biopsied was 47.1%, 79.7%, and 78.1% for the ACR TI-RADS, the KSThR TIRADS, and the ATA guidelines, respectively. The percentage of benign nodules that would be either biopsied or followed was 65.2% for the ACR TI-RADS. The ACR TI-RADS performs well when compared with other well-established guidelines.

  7. First ultrasound diagnosis of BI-RADS 3 lesions in young patients: Can 6-months follow-up be sufficient to assess stability?

    Energy Technology Data Exchange (ETDEWEB)

    Marcon, Magda, E-mail: magda.marcon@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich (Switzerland); Frauenfelder, Thomas, E-mail: thomas.frauenfelder@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich (Switzerland); Becker, Anton S., E-mail: anton.becker@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich (Switzerland); Dedes, Konstantin J., E-mail: Konstantin.dedes@usz.ch [Department of Gynecology, University Hospital Zurich (Switzerland); Boss, Andreas, E-mail: andreas.boss@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich (Switzerland)

    2017-04-15

    Objectives: To evaluate the outcome of repeated short-term follow-up with ultrasound in no high-risk young patients with a BI-RADS3 lesion at first examination. Methods: In this IRB-approved study 492 women, aged 18–34 years (mean ± standard deviation, 28 ± 4.5 years) with first breast ultrasound examination in 2012–2014 were retrospectively evaluated. Inclusion criteria were: at least one BI-RADS3 lesion and (a) biopsy/surgical excision or (b) follow-up of at least 18 months (including a 6-month follow-up). BI-RADS category assigned during follow-up and pathologic findings in cases undergoing biopsy/surgical excision were collected. At the 6- and 18-month follow-up the recommended biopsy rates (RBR) and the corresponding positive predictive value (PPV) were calculated. Results: In 97 patients, 151 BI-RADS3 lesions were identified. Biopsy/surgical excision was initially performed in 25/151 (16.5%) lesions. After 6-month, category was downgraded to BI-RADS1/2 in 23/126 (15.3%) and upgraded to BI-RADS4 in 9/126 lesions (7.1%). Pathological diagnosis of these lesions was fibroadenoma in 5 and benign phyllodes tumor in 4 cases (RBR 7%, PPV{sub bio} 44.4%). After 18-month one lesion was classified BI-RADS4 and pathological diagnosis was fibroadenoma (RBR 1.1%, PPV{sub bio} 0%). Conclusions: Our preliminary data show that follow-up imaging performed after 18 months from a first BI-RADS3 diagnosis does not affect clinical treatment and 6-month follow-up may be sufficient to assess the stability of probably benign lesions.

  8. First ultrasound diagnosis of BI-RADS 3 lesions in young patients: Can 6-months follow-up be sufficient to assess stability?

    International Nuclear Information System (INIS)

    Marcon, Magda; Frauenfelder, Thomas; Becker, Anton S.; Dedes, Konstantin J.; Boss, Andreas

    2017-01-01

    Objectives: To evaluate the outcome of repeated short-term follow-up with ultrasound in no high-risk young patients with a BI-RADS3 lesion at first examination. Methods: In this IRB-approved study 492 women, aged 18–34 years (mean ± standard deviation, 28 ± 4.5 years) with first breast ultrasound examination in 2012–2014 were retrospectively evaluated. Inclusion criteria were: at least one BI-RADS3 lesion and (a) biopsy/surgical excision or (b) follow-up of at least 18 months (including a 6-month follow-up). BI-RADS category assigned during follow-up and pathologic findings in cases undergoing biopsy/surgical excision were collected. At the 6- and 18-month follow-up the recommended biopsy rates (RBR) and the corresponding positive predictive value (PPV) were calculated. Results: In 97 patients, 151 BI-RADS3 lesions were identified. Biopsy/surgical excision was initially performed in 25/151 (16.5%) lesions. After 6-month, category was downgraded to BI-RADS1/2 in 23/126 (15.3%) and upgraded to BI-RADS4 in 9/126 lesions (7.1%). Pathological diagnosis of these lesions was fibroadenoma in 5 and benign phyllodes tumor in 4 cases (RBR 7%, PPV bio 44.4%). After 18-month one lesion was classified BI-RADS4 and pathological diagnosis was fibroadenoma (RBR 1.1%, PPV bio 0%). Conclusions: Our preliminary data show that follow-up imaging performed after 18 months from a first BI-RADS3 diagnosis does not affect clinical treatment and 6-month follow-up may be sufficient to assess the stability of probably benign lesions.

  9. Congenital Mirror Movements Due to RAD51: Cosegregation with a Nonsense Mutation in a Norwegian Pedigree and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Oriane Trouillard

    2016-11-01

    Full Text Available Background: Autosomal dominant congenital mirror movements (CMM is a neurodevelopmental disorder characterized by early onset involuntary movements of one side of the body that mirror intentional movements on the contralateral side; these persist throughout life in the absence of other neurological symptoms. The main culprit genes responsible for this condition are RAD51 and DCC. This condition has only been reported in a few families, and the molecular mechanisms linking RAD51 mutations and mirror movements (MM are poorly understood. Methods: We collected demographic, clinical, and genetic data of a new family with CMM due to a truncating mutation of RAD51. We reviewed the literature to identify all reported patients with CMM due to RAD51 mutations. Results: We identified a heterozygous nonsense mutation c.760C>T (p.Arg254∗ in eight subjects: four with obvious and disabling MM, and four with a mild phenotype. Including our new family, we identified 32 patients from 6 families with CMM linked to RAD51 variants. Discussion: Our findings further support the involvement of RAD51 in CMM pathogenesis. Possible molecular mechanisms involved in CMM pathogenesis are discussed.

  10. 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

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, J. P. [NIH, Bethesda, MD. (United States); Levine, A. S.; Woodgate, R.

    1997-12-15

    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)

  11. Compositional properties of passivity

    NARCIS (Netherlands)

    Kerber, Florian; van der Schaft, Arjan

    2011-01-01

    The classical passivity theorem states that the negative feedback interconnection of passive systems is again passive. The converse statement, - passivity of the interconnected system implies passivity of the subsystems -, turns out to be equally valid. This result implies that among all feasible

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

    International Nuclear Information System (INIS)

    Marwede, D.; Lobsien, D.; Kahn, T.; Daumke, P.; Marko, K.; Schulz, S.

    2009-01-01

    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.)

  13. Relative contributions of decay accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 in the protection of melanocytes from homologous complement

    NARCIS (Netherlands)

    Venneker, G. T.; Vodegel, R. M.; Okada, N.; Westerhof, W.; Bos, J. D.; Asghar, S. S.

    1998-01-01

    Complement regulatory molecules, membrane cofactor protein (MCP), decay accelerating factor (DAF) and CD59, protect body cells from autologous complement. They have wide tissue distribution but nothing is known about the expression of these molecules on human melanocytes. Since melanocytes are lysed

  14. Failure to induce a DNA repair gene, RAD54, in Saccharomyces cerevisiae does not affect DNA repair or recombination phenotypes

    International Nuclear Information System (INIS)

    Cole, G.M.; Mortimer, R.K.

    1989-01-01

    The Saccharomyces cerevisiae RAD54 gene is transcriptionally regulated by a broad spectrum of DNA-damaging agents. Induction of RAD54 by DNA-damaging agents is under positive control. Sequences responsible for DNA damage induction (the DRS element) lie within a 29-base-pair region from -99 to -70 from the most proximal transcription start site. This inducible promoter element is functionally separable from a poly(dA-dT) region immediately downstream which is required for constitutive expression. Deletions which eliminate induction of RAD54 transcription by DNA damage but do not affect constitutive expression have no effect on growth or survival of noninducible strains relative to wild-type strains in the presence of DNA-damaging agents. The DRS element is also not required for homothallic mating type switching, transcriptional induction of RAD54 during meiosis, meiotic recombination, or spontaneous or X-ray-induced mitotic recombination. We find no phenotype for a lack of induction of RAD54 message via the damage-inducible DRS, which raises significant questions about the physiology of DNA damage induction in S. cerevisiae

  15. Packaging Effects on RadFET Sensors for High Energy Physics Experiments

    CERN Document Server

    Mekki, J; Glaser, M; Guatelli, S; Moll, M; Pia, M G; Ravotti, F

    2009-01-01

    RadFETs in customized chip carrier packages are installed in the LHC Experiments as radiation monitors. The package influence on the dose measurement in the complex LHC radiation environment is evaluated using Geant4 simulations and experimental data.

  16. The MCP-1, CCL-5 and SDF-1 chemokines as pro-inflammatory markers in generalized anxiety disorder and personality disorders.

    Science.gov (United States)

    Ogłodek, Ewa A; Szota, Anna M; Just, Marek J; Moś, Danuta M; Araszkiewicz, Aleksander

    2015-02-01

    The co-occurrence of generalized anxiety disorder and personality disorders suggests the existence of association between the neurobiological predispositions leading to the development of these disorders and activation of cytokine system. Pro-inflammatory chemokines such as CCL-5/RANTES (regulated upon activation normal T cell expressed and secreted) and CXCL12/SDF-1 (stromal derived factor) play an important role in immune response. A total of 160 participants were enrolled in the study, 120 of whom comprised the study group (people with the dual diagnosis of personality disorder and generalized anxiety disorder). The mean age was 41.4 ± 3.5 years (range: 20-44 years). The control group consisted of 40 healthy individuals in the mean age of 40.8 ± 3.1 years (range: 20-43 years). A blood sample was collected from each participant and the plasma levels of the CCL-2/MCP-1 (monocyte chemoattractant protein-1), RANTES and SDF-1 chemokines were determined by ELISA. Increased levels of MCP-1 and SDF-1 were found both in women and in men versus the control group for all types of personality disorders. The levels of CCL-5 in men were significantly increased versus the control group and significantly higher in women than in men. Neither women nor men with avoidant or obsessive-compulsive personality disorder showed any significant differences in MCP-1 or SFD-1 levels. In subjects with borderline personality disorder, the levels of the study chemokines were higher in women than in men. Our study has shown the need for determination of proinflammatory interleukins which are considered as biomarkers of personality disorders and generalized anxiety disorders. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. The Saccharomyces cerevisiae RAD18 gene encodes a protein that contains potential zinc finger domains for nucleic acid binding and a putative nucleotide binding sequence

    Energy Technology Data Exchange (ETDEWEB)

    Jones, J.S.; Prakash, L. (Univ. of Rochester School of Medicine, NY (USA)); Weber, S. (Kodak Research Park, Rochester, NY (USA))

    1988-07-25

    The RAD18 gene of Saccharomyces cerevisiae is required for postreplication repair of UV damaged DNA. The authors have isolated the RAD18 gene, determined its nucleotide sequence and examined if deletion mutations of this gene show different or more pronounced phenotypic effects than the previously described point mutations. The RAD18 gene open reading frame encodes a protein of 487 amino acids, with a calculated molecular weight of 55,512. The RAD18 protein contains three potential zinc finger domains for nucleic acid binding, and a putative nucleotide binding sequence that is present in many proteins that bind and hydrolyze ATP. The DNA binding and nucleotide binding activities could enable the RAD18 protein to bind damaged sites in the template DNA with high affinity. Alternatively, or in addition, RAD18 protein may be a transcriptional regulator. The RAD18 deletion mutation resembles the previously described point mutations in its effects on viability, DNA repair, UV mutagenesis, and sporulation.

  19. Identification of a deoxyribonuclease controlled by the rad52 gene of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Chow, T.Y.K.; Resnick, M.A.

    1983-01-01

    We have examined deoxyribonuclease levels in extracts of wild-type and rad52 mutants and have observed no significant differences. However, major differences were observed when we employed anti-serum raised against a purified single strand DNA-binding endoexonuclease from Neurospora crassa. As much as sixty percent of the alkaline deoxyribonuclease in wild-type extracts exhibited immunocrossreactivity, whereas none was found in extracts from rad52 strains. This DNase activity was also followed through meiosis; maximum activity was observed in wild-type cells, at a time corresponding to an early stage of premeiotic DNA-synthesis and commitment to recombination. 14 references, 4 figures, 1 table

  20. Fission yeast shelterin regulates DNA polymerases and Rad3(ATR kinase to limit telomere extension.

    Directory of Open Access Journals (Sweden)

    Ya-Ting Chang

    2013-11-01

    Full Text Available Studies in fission yeast have previously identified evolutionarily conserved shelterin and Stn1-Ten1 complexes, and established Rad3(ATR/Tel1(ATM-dependent phosphorylation of the shelterin subunit Ccq1 at Thr93 as the critical post-translational modification for telomerase recruitment to telomeres. Furthermore, shelterin subunits Poz1, Rap1 and Taz1 have been identified as negative regulators of Thr93 phosphorylation and telomerase recruitment. However, it remained unclear how telomere maintenance is dynamically regulated during the cell cycle. Thus, we investigated how loss of Poz1, Rap1 and Taz1 affects cell cycle regulation of Ccq1 Thr93 phosphorylation and telomere association of telomerase (Trt1(TERT, DNA polymerases, Replication Protein A (RPA complex, Rad3(ATR-Rad26(ATRIP checkpoint kinase complex, Tel1(ATM kinase, shelterin subunits (Tpz1, Ccq1 and Poz1 and Stn1. We further investigated how telomere shortening, caused by trt1Δ or catalytically dead Trt1-D743A, affects cell cycle-regulated telomere association of telomerase and DNA polymerases. These analyses established that fission yeast shelterin maintains telomere length homeostasis by coordinating the differential arrival of leading (Polε and lagging (Polα strand DNA polymerases at telomeres to modulate Rad3(ATR association, Ccq1 Thr93 phosphorylation and telomerase recruitment.

  1. Brca2 C-terminus interacts with Rad51 and contributes to nuclear forcus formation in double-strand break repair of DNA

    International Nuclear Information System (INIS)

    Ochiai, Kazuhiko; Morimatsu, Masami; Yoshikawa, Yasunaga; Syuto, Bunei; Hashizume, Kazuyoshi

    2004-01-01

    In humans and mice, the interaction between the breast cancer susceptibility protein, Brca2, and Rad51 recombinase is essential for DNA repair by homologous recombination, the failure of this process can predispose to cancer. Cells with mutated Brca2 are hypersensitive to ionizing radiation (IR) and exhibit defective DNA repair. Using yeast and mammalian two-hybrid assays, we demonstrate that canine Rad51 protein interacts specifically with the C-terminus of canine Brca2. In support of the biological significance of this interaction, we found that radiation-induced focus formation of Rad51 in COS-7 cells was compromised by forced expression of the C-terminus of canine Brca2. A similar result was obtained for the murine C-terminus. These data suggest that the C-terminal domain of canine Brca2 functions to bind Rad51 and that this domain contributes to the IR-induced assembly of the Rad51 complex in vivo. (author)

  2. Relationship between genetic polymorphisms in MCP-1, CCR-2, and non-small-cell lung cancer in the Han nationality of Northern China.

    Science.gov (United States)

    Yang, L; Wang, J; Li, F-G; Han, M; Chang, X-J; Wang, Z-T

    2015-04-22

    Lung cancer is a common malignant tumor worldwide and is now the leading cause of cancer-related deaths. Monocyte chemoattractant protein 1 (MCP-1) and its receptor chemokine receptor 2 (CCR-2) are important chemokines. We examined the polymorphisms of 338 unrelated patients with non-small cell lung carcinoma (NSCLC) and 200 unrelated healthy controls of Han nationality in Northern China using polymerase chain reaction-restriction fragment length polymorphism. We found a significant increase in the frequency of the MCP-1 AA genotype [0.293 vs 0.195, odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.13-2.60] and a significant decrease in the frequency of the GG genotype (0.290 vs 0.41, OR = 0.64, 95%CI = 0.47-0.87) in NSCLC patients compared to controls. The frequencies of AA-ww (0.151 vs 0.090, P = 0.041, OR = 1.80, 95%CI = 1.33-2.43) and AA-wm (0.136 vs 0.080, P = 0.049, OR = 1.81, 95%CI = 1.01-3.27) were higher in lung cancer patients than in healthy controls; the frequency of GG-wm (0.121 vs 0.190, P = 0.030, OR = 0.60, 95%CI = 0.38-0.95) was lower in lung cancer patients than in healthy controls. Based on these results, the polymorphism in MCP-1 may be correlated with the development of NSCLC in the Han nationality of Northern China. However, the polymorphism in CCR-2 is not involved in NSCLC.

  3. Identification of Rad23-4 gene required for pollen development in ...

    African Journals Online (AJOL)

    雨林木风

    2012-05-31

    May 31, 2012 ... in ultraviolet (UV)-B–treated rad23-4 mutants. Compared with the wild type ... discovered in yeast (Guzder et al., 1998). Recent studies showed that ... UV-B irradiation can induce accumulations of anthocyanin in the plants.

  4. Radionuclide field lysimeter experiment (RadFLEx): geochemical and hydrological data for SRS performance assessments

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Powell, B. [Clemson Univ., SC (United States); Barber, K. [Clemson Univ., SC (United States); Devol, T. [Clemson Univ., SC (United States); Dixon, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Erdmann, B. [Clemson Univ., SC (United States); Maloubier, M. [Clemson Univ., SC (United States); Martinez, N. [Clemson Univ., SC (United States); Montgomery, D. [Clemson Univ., SC (United States); Peruski, K. [Clemson Univ., SC (United States); Roberts, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Witmer, M. [Clemson Univ., SC (United States)

    2017-12-12

    The SRNL Radiological Field Lysimeter Experiment (RadFLEx) is a one-of-a-kind test bed facility designed to study radionuclide geochemical processes in the Savannah River Site (SRS) vadose zone at a larger spatial scale (from grams to tens of kilograms of sediment) and temporal scale (from months to decade) than is readily afforded through laboratory studies. RadFLEx is a decade-long project that was initiated on July 5, 2012 and is funded by six different sources. The objective of this status report is as follows: 1) to report findings to date that have an impact on SRS performance assessment (PA) calculations, and 2) to provide performance metrics of the RadFLEx program. The PA results are focused on measurements of transport parameters, such as distribution coefficients (Kd values), solubility, and unsaturated flow values. As this is an interim report, additional information from subsequent research may influence our interpretation of current results. Research related to basic understanding of radionuclide geochemistry in these vadose zone soils and other source terms are not described here but are referenced for the interested reader.

  5. Poster - 24: Characterization of the energy dependence of high-sensitivity MCP-N TLD and Al2O3:C OSLD in-vivo dosimetry systems for 40–100 kVp energies

    Energy Technology Data Exchange (ETDEWEB)

    Poirier, Yannick; Kuznetsova, Svetlana; Barajas, Eduardo Villarreal [Tom Baker Cancer Centre, Calgary AB, University of Calgary, Calgary AB, Tom Baker Cancer Center/University of Calgary, Calgary AB (Canada)

    2016-08-15

    Purpose: To characterize the energy dependence of high-sensitivity MCP-N TLD and Al{sub 2}O{sub 3}:C OSLD dosimetry systems at low (40–100 kVp) energies for in-vivo dosimetry. Methods: We assessed the variation of response with energy of two detectors in the 40–100 kVp energy range: high-sensitivity MCP-N TLDs (LiF:Mg,Cu,P) and OSLDs (Al{sub 2}O{sub 3}:C). The detectors were irradiated with an XRad 320ix biological irradiator under reference conditions. The delivered dose was 10 cGy for 7 beam qualities ranging from 40–100 kVp, 1.7–4.0 mm Al, and effective energies 26.9–37.9 keV. Both sets of detectors were also irradiated under reference conditions at 6 MV using a Varian Clinac 21Ex to assess the change in response from high-energy beams. Results: The MCP-N high-sensitivity TLDs were relatively insensitive to energies in the kV range, as their response varied by ±5%, i.e. well within the reproducibility limits of these detectors. However, the OSLDs exhibited a linearly-decreasing response with energy with a response 18.7% higher at 40 kVp than at 100 kVp for the same nominal dose. Compared to the 6 MV beams used in conventional radiotherapy, OSLDs responded 3.3–3.9 times higher depending on beam quality while the MCP-N TLD response was unchanged within experimental uncertainty. Conclusions: Unlike the more commonly used TLD-100, the high-sensitivity MCP-N TLDs exhibit little to no energy response. OSLDs are shown to be highly energy-dependent, both from MV to kV and within the kV range.

  6. The charged particle radiation environment on Mars measured by MSL/RAD from November 15, 2015 to January 15, 2016.

    Science.gov (United States)

    Ehresmann, Bent; Zeitlin, Cary J; Hassler, Donald M; Matthiä, Daniel; Guo, Jingnan; 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; Reitz, Günther

    2017-08-01

    The Radiation Assessment Detector (RAD) on board the Mars Science Laboratory (MSL) Curiosity rover has been measuring the radiation environment in Gale crater on Mars since August, 2012. These first in-situ measurements provide an important data set for assessing the radiation-associated health risks for future manned missions to Mars. Mainly, the radiation field on the Martian surface stems from Galactic Cosmic Rays (GCRs) and secondary particles created by the GCRs' interactions with the Martian atmosphere and soil. RAD is capable of measuring differential particle fluxes for lower-energy ions and isotopes of hydrogen and helium (up to hundreds of MeV/nuc). Additionally, RAD also measures integral particle fluxes for higher energies of these ions. Besides providing insight on the current Martian radiation environment, these fluxes also present an essential input for particle transport codes that are used to model the radiation to be encountered during future manned missions to Mars. Comparing simulation results with actual ground-truth measurements helps to validate these transport codes and identify potential areas of improvements in the underlying physics of these codes. At the First Mars Radiation Modeling Workshop (June 2016 in Boulder, CO), different groups of modelers were asked to calculate the Martian surface radiation environment for the time of November 15, 2015 to January 15, 2016. These model results can then be compared with in-situ measurements of MSL/RAD conducted during the same time frame. In this publication, we focus on presenting the charged particle fluxes measured by RAD between November 15, 2015 and January 15, 2016, providing the necessary data set for the comparison to model outputs from the modeling workshop. We also compare the fluxes to initial GCR intensities, as well as to RAD measurements from an earlier time period (August 2012 to January 2013). Furthermore, we describe how changes and updates in RAD on board processing and the on

  7. Influence of promoting blood circulation to remove blood stasis combined with laparoscopy on serum MCP-1, RANTES, oxidative stress and hormones in infertile patients with endometriosis

    Directory of Open Access Journals (Sweden)

    Xiao-Sha Zhang

    2017-11-01

    Full Text Available Objective: To observe the influence of promoting blood circulation to remove blood stasis combined with laparoscopy on serum MCP-1, RANTES, oxidative stress and hormones in infertile patients with endometriosis. Methods: A total of 60 infertile patients with endometriosis were randomly divided into observation group (30 cases and control group (30 cases. Observation group: promoting blood circulation to remove blood stasis combined with laparoscopy; control group: patients were treated only by laparoscopy. Recording and comparing the levels of MCP-1, RANTES, oxidative stress and hormones before and after treatment. Results: (1 Before treatment, there was no statistically significant difference in the serum MCP-1, RANTES, AOPP, MDA, SOD, levels between the two groups. After treatment, compared with the same group before treatment, the serum RANTES, AOPP, MDA levels of the two groups were significantly lower, the serum SOD level of the two groups were significantly higher, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups. (2 Before treatment, there was no statistically significant difference in the serum FSH, LH, E2, P, PRL levels between the two groups. After treatment, compared with the same group before treatment, the serum FSH, LH, P, PRL levels of the two groups were significantly higher, the serum E2 level of the two groups were significantly lower, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups. Conclusion: Promoting blood circulation to remove blood stasis combined with laparoscopy for infertile patients with endometriosis can reduce the levels of serum MCP-1, RANTES, oxidative stress, hormones and be beneficial to protect their uterine function.

  8. Minocycline enhances mitomycin C-induced cytotoxicity through down-regulating ERK1/2-mediated Rad51 expression in human non-small cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Wang, Tai-Jing; Chang, Po-Yuan; Syu, Jhan-Jhang; Chen, Jyh-Cheng; Chen, Chien-Yu; Jian, Yun-Ting; Jian, Yi-Jun; Zheng, Hao-Yu; Chen, Wen-Ching; Lin, Yun-Wei

    2015-10-01

    Minocycline is a semisynthetic tetracycline derivative; it has anti-inflammatory and anti-cancer effects distinct from its antimicrobial function. However, the molecular mechanism of minocycline-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. Our previous studies have shown that the MKK1/2-ERK1/2 signal pathway maintains the expression of Rad51 in NSCLC cells. In this study, minocycline treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1975. Treatment with minocycline decreased Rad51 mRNA and protein levels through MKK1/2-ERK1/2 inactivation. Furthermore, expression of constitutively active MKK1 (MKK1-CA) vectors significantly rescued the decreased Rad51 protein and mRNA levels in minocycline-treated NSCLC cells. However, combined treatment with MKK1/2 inhibitor U0126 and minocycline further decreased the Rad51 expression and cell viability of NSCLC cells. Knocking down Rad51 expression by transfection with small interfering RNA of Rad51 enhanced the cytotoxicity and cell growth inhibition of minocycline. Mitomycin C (MMC) is typically used as a first or second line regimen to treat NSCLC. Compared to a single agent alone, MMC combined with minocycline resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-ERK1/2, and reduced Rad51 protein levels. Overexpression of MKK1-CA or Flag-tagged Rad51 could reverse the minocycline and MMC-induced synergistic cytotoxicity. These findings may have implications for the rational design of future drug regimens incorporating minocycline and MMC for the treatment of NSCLC. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. RAD51 potentiates synergistic effects of chemotherapy with PCI-24781 and cis-diamminedichloroplatinum on gastric cancer

    Science.gov (United States)

    He, Wei-Ling; Li, Yu-Huang; Hou, Wei-Jian; Ke, Zun-Fu; Chen, Xin-Lin; Lu, Li-Ya; Cai, Shi-Rong; Song, Wu; Zhang, Chang-Hua; He, Yu-Long

    2014-01-01

    AIM: To explore the efficacy of PCI-24781, a broad-spectrum, hydroxamic acid-derived histone deacetylase inhibitor, in the treatment of gastric cancer (GC). METHODS: With or without treatment of PCI-24781 and/or cis-diamminedichloroplatinum (CDDP), GC cell lines were subjected to functional analysis, including cell growth, apoptosis and clonogenic assays. Chromatin immunoprecipitation and luciferase reporter assays were used to determine the interacting molecules and the activity of the enzyme. An in vivo study was carried out in GC xenograft mice. Cell culture-based assays were represented as mean ± SD. ANOVA tests were used to assess differences across groups. All pairwise comparisons between tumor weights among treatment groups were made using the Tukey-Kramer method for multiple comparison adjustment to control experimental-wise type I error rates. Significance was set at P PCI-24781 significantly reduced the growth of the GC cells, enhanced cell apoptosis and suppressed clonogenicity, and these effects synergized with the effects of CDDP. PCI-24781 modulated the cell cycle and significantly reduced the expression of RAD51, which is related to homologous recombination. Depletion of RAD51 augmented the biological functions of PCI-24781, CDDP and the combination treatment, whereas overexpressing RAD51 had the opposite effects. Increased binding of the transcription suppressor E2F4 on the RAD51 promoter appeared to play a major role in these processes. Furthermore, significant suppression of tumor growth and weight in vivo was obtained following PCI-24781 treatment, which synergized with the anticancer effect of CDDP. CONCLUSION: These data suggest that RAD51 potentiates the synergistic effects of chemotherapy with PCI-24781 and CDDP on GC. PMID:25110436

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

    International Nuclear Information System (INIS)

    Ghosh, Somnath; Krishna, Malini

    2012-01-01

    The effect of fractionated doses of γ-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.

  11. RadCon Occurrence Reporting Simplified

    International Nuclear Information System (INIS)

    Denham, D. H.

    1999-01-01

    This narrative and accompanying diagrams provide a simplified summary of the RadCon Occurrence Reporting criteria to allow Environmental Restoration Contractor (ERC) staff to efficiently recognize occurrences and to effectively initiate the implementation of the requirements of U.S. Department of Energy (DOE) Order 232.1A, Occurrence Reporting and Processing of Operations Information, and of the ERC criteria defined in BHI-MA-02, ERC Project Procedures, Procedure 2.6, ''Occurrence Investigation and Reporting.'' These directives promote timely identification, categorization, notification, and reporting to DOE and ERC management of reportable occurrences at DOE-owned or -operated facilities that could (1) affect health and safety of the public, (2) seriously impact the intended purpose of DOE facilities, (3) adversely affect the credibility of DOE, or (4) have a noticeable adverse effect on the environment

  12. Radiological assessment of breast density by visual classification (BI-RADS) compared to automated volumetric digital software (Quantra): implications for clinical practice.

    Science.gov (United States)

    Regini, Elisa; Mariscotti, Giovanna; Durando, Manuela; Ghione, Gianluca; Luparia, Andrea; Campanino, Pier Paolo; Bianchi, Caterina Chiara; Bergamasco, Laura; Fonio, Paolo; Gandini, Giovanni

    2014-10-01

    This study was done to assess breast density on digital mammography and digital breast tomosynthesis according to the visual Breast Imaging Reporting and Data System (BI-RADS) classification, to compare visual assessment with Quantra software for automated density measurement, and to establish the role of the software in clinical practice. We analysed 200 digital mammograms performed in 2D and 3D modality, 100 of which positive for breast cancer and 100 negative. Radiological density was assessed with the BI-RADS classification; a Quantra density cut-off value was sought on the 2D images only to discriminate between BI-RADS categories 1-2 and BI-RADS 3-4. Breast density was correlated with age, use of hormone therapy, and increased risk of disease. The agreement between the 2D and 3D assessments of BI-RADS density was high (K 0.96). A cut-off value of 21% is that which allows us to best discriminate between BI-RADS categories 1-2 and 3-4. Breast density was negatively correlated to age (r = -0.44) and positively to use of hormone therapy (p = 0.0004). Quantra density was higher in breasts with cancer than in healthy breasts. There is no clear difference between the visual assessments of density on 2D and 3D images. Use of the automated system requires the adoption of a cut-off value (set at 21%) to effectively discriminate BI-RADS 1-2 and 3-4, and could be useful in clinical practice.

  13. Intermittent pneumatic leg compressions acutely upregulate VEGF and MCP-1 expression in skeletal muscle.

    Science.gov (United States)

    Roseguini, Bruno T; Mehmet Soylu, S; Whyte, Jeffrey J; Yang, H T; Newcomer, Sean; Laughlin, M Harold

    2010-06-01

    Application of intermittent pneumatic compressions (IPC) is an extensively used therapeutic strategy in vascular medicine, but the mechanisms by which this method works are unclear. We tested the hypothesis that acute application (150 min) of cyclic leg compressions in a rat model signals upregulation of angiogenic factors in skeletal muscle. To explore the impact of different pressures and frequency of compressions, we divided rats into four groups as follows: 120 mmHg (2 s inflation/2 s deflation), 200 mmHg (2 s/2 s), 120 mmHg (4 s/16 s), and control (no intervention). Blood flow and leg oxygenation (study 1) and the mRNA expression of angiogenic mediators in the rat tibialis anterior muscle (study 2) were assessed after a single session of IPC. In all three groups exposed to the intervention, a modest hyperemia (approximately 37% above baseline) between compressions and a slight, nonsignificant increase in leg oxygen consumption (approximately 30%) were observed during IPC. Compared with values in the control group, vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) mRNA increased significantly (P < 0.05) only in rats exposed to the higher frequency of compressions (2 s on/2 s off). Endothelial nitric oxide synthase, matrix metalloproteinase-2, and hypoxia-inducible factor-1alpha mRNA did not change significantly following the intervention. These findings show that IPC application augments the mRNA content of key angiogenic factors in skeletal muscle. Importantly, the magnitude of changes in mRNA expression appeared to be modulated by the frequency of compressions such that a higher frequency (15 cycles/min) evoked more robust changes in VEGF and MCP-1 compared with a lower frequency (3 cycles/min).

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

    Directory of Open Access Journals (Sweden)

    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

  15. Mimivirus reveals Mre11/Rad50 fusion proteins with a sporadic distribution in eukaryotes, bacteria, viruses and plasmids

    Directory of Open Access Journals (Sweden)

    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.

  16. Updates from the MSL-RAD Experiment on the Mars Curiosity Rover

    Science.gov (United States)

    Zeitlin, Cary

    2015-01-01

    The MSL-RAD instrument continues to operate flawlessly on Mars. As of this writing, some 1040 sols (Martian days) of data have been successfully acquired. Several improvements have been made to the instrument's configuration, particularly aimed at enabling the analysis of neutral-particle data. The dose rate since MSL's landing in August 2012 has remained remarkably stable, reflecting the unusual and very weak solar maximum of Cycle 24. Only a few small SEP events have been observed by RAD, which is shielded by the Martian atmosphere. Gale Crater, where Curiosity landed, is 4.4 km below the mean surface of Mars, and the column depth of atmosphere above is approximately 20 g/sq cm, which provides significant attenuation of GCR heavy ions and SEPs. Recent analysis results will be presented, including updated estimates of the neutron contributions to dose and dose equivalent in cruise and on the surface of Mars.

  17. Ca2+ improves organization of single-stranded DNA bases in human Rad51 filament, explaining stimulatory effect on gene recombination.

    KAUST Repository

    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.

  18. Small Rad51 and Dmc1 Complexes Often Co-occupy Both Ends of a Meiotic DNA Double Strand Break.

    Directory of Open Access Journals (Sweden)

    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.

  19. Double-digest RAD sequencing using Ion Proton semiconductor platform (ddRADseq-ion) with nonmodel organisms.

    Science.gov (United States)

    Recknagel, Hans; Jacobs, Arne; Herzyk, Pawel; Elmer, Kathryn R

    2015-11-01

    Research in evolutionary biology involving nonmodel organisms is rapidly shifting from using traditional molecular markers such as mtDNA and microsatellites to higher throughput SNP genotyping methodologies to address questions in population genetics, phylogenetics and genetic mapping. Restriction site associated DNA sequencing (RAD sequencing or RADseq) has become an established method for SNP genotyping on Illumina sequencing platforms. Here, we developed a protocol and adapters for double-digest RAD sequencing for Ion Torrent (Life Technologies; Ion Proton, Ion PGM) semiconductor sequencing. We sequenced thirteen genomic libraries of three different nonmodel vertebrate species on Ion Proton with PI chips: Arctic charr Salvelinus alpinus, European whitefish Coregonus lavaretus and common lizard Zootoca vivipara. This resulted in ~962 million single-end reads overall and a mean of ~74 million reads per library. We filtered the genomic data using Stacks, a bioinformatic tool to process RAD sequencing data. On average, we obtained ~11,000 polymorphic loci per library of 6-30 individuals. We validate our new method by technical and biological replication, by reconstructing phylogenetic relationships, and using a hybrid genetic cross to track genomic variants. Finally, we discuss the differences between using the different sequencing platforms in the context of RAD sequencing, assessing possible advantages and disadvantages. We show that our protocol can be used for Ion semiconductor sequencing platforms for the rapid and cost-effective generation of variable and reproducible genetic markers. © 2015 John Wiley & Sons Ltd.

  20. RAD18 and associated proteins are immobilized in nuclear foci in human cells entering S-phase with ultraviolet light-induced damage

    International Nuclear Information System (INIS)

    Watson, Nicholas B.; Nelson, Eric; Digman, Michelle; Thornburg, Joshua A.; Alphenaar, Bruce W.; McGregor, W. Glenn

    2008-01-01

    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

  1. Curcumin enhances the mitomycin C-induced cytotoxicity via downregulation of MKK1/2-ERK1/2-mediated Rad51 expression in non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Ko, Jen-Chung; Tsai, Min-Shao; Weng, Shao-Hsing; Kuo, Ya-Hsun; Chiu, Yu-Fan; Lin, Yun-Wei

    2011-01-01

    Curcumin (diferuloylmethane), a major active component of turmeric (Curcuma longa), has been reported to suppress the proliferation of a wide variety of tumor cells. Rad51 is a key protein in the homologous recombination (HR) pathway of DNA double-strand break repair, and HR represents a novel target for cancer therapy. A high expression of Rad51 has been reported in chemo- or radio-resistant carcinomas. Therefore, in the current study, we will examine whether curcumin could enhance the effects of mitomycin C (MMC), a DNA interstrand cross-linking agent, to induce cytotoxicity by decreasing Rad51 expression. Exposure of two human non-small lung cancer (NSCLC) cell lines (A549 and H1975) to curcumin could suppress MMC-induced MKK1/2-ERK1/2 signal activation and Rad51 protein expression. Enhancement of ERK1/2 activation by constitutively active MKK1/2 (MKK1/2-CA) increased Rad51 protein levels in curcumin and MMC co-treated human lung cells. Moreover, the synergistic cytotoxic effect induced by curcumin combined with MMC was decreased by MKK1-CA-mediated enhancement of ERK1/2 activation by a significant degree. In contrast, MKK1/2 inhibitor, U0126 was shown to augment the cytotoxicity of curcumin and MMC through downregulation of ERK1/2 activation and Rad51 expression. Depletion of endogenous Rad51 expression by siRad51 RNA transfection significantly enhanced MMC and/or curcumin induced cell death and cell growth inhibition. In contrast, an overexpression of Rad51 protected lung cancer cells from synergistic cytotoxic effects induced by curcumin and MMC. We concluded that Rad51 inhibition may be an additional action mechanism for enhancing the chemosensitization of MMC by curcumin in NSCLC. - Highlights: → Curcumin downregulates MKK-ERK-mediated Rad51 expression. → Curcumin enhances mitomycin C-induced cytotoxicity. → Rad51 protects cells from cytotoxic effects induced by curcumin and mitomycin C. → Rad51 inhibition enhances the chemosensitization of

  2. 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

    DEFF Research Database (Denmark)

    Burgess, Rebecca C; Sebesta, Marek; Sisakova, Alexandra

    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...

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

    DEFF Research Database (Denmark)

    Kojic, Milorad; Mao, Ninghui; Zhou, Qingwen

    2008-01-01

    A single Rad52-related protein is evident by blast analysis of the Ustilago maydis genome database. Mutants created by disruption of the structural gene exhibited few discernible defects in resistance to UV, ionizing radiation, chemical alkylating or cross-linking agents. No deficiency was noted...

  4. Radioresistance of chordoma cells is associated with the ATM/ATR pathway, in which RAD51 serves as an important downstream effector.

    Science.gov (United States)

    Zhang, Chao; Wang, Bing; Li, Lei; Li, Yawei; Li, Pengzhi; Lv, Guohua

    2017-09-01

    Surgery followed by radiotherapy is the standard treatment for chordomas, which are a rare but low-grade type of bone cancer arising from remnants of the embryonic notochord. However, disease recurrence following radiotherapy is common, most likely due to endogenous DNA repair mechanisms that promote cell survival upon radiation strikes. The ataxia telangiectasia mutated/ataxia telangiectasia mutated and Rad3 related (ATM/ATR)-mediated pathway has a critical role in DNA repair mechanisms; however, it has rarely been investigated in chordomas. In the present study, the expression of signal molecules related to the ATM/ATR pathway in chordoma tissues and adjacent normal tissues were initially examined using immunohistochemistry and western blot analysis. Chordoma U-CH1 and U-CH2 cells were subsequently used to investigate cell responses to ionizing radiation and the potential protective actions mediated by the ATM/ATR pathway. Phosphorylated (p)-ATM, p-ATR, γ-H2A histone family, member X (H2AX) and RAD51 were significantly upregulated in chordoma tissues relative to adjacent normal tissues (PATM, γ-H2AX and RAD51 expression in U-CH1 cells (PATM, p-ATR and RAD51 levels in U-CH2 cells (PATM/ATR pathway, in which RAD51 serves as an important downstream effector. Thus, RAD51 presents a promising therapeutic target for improving the outcome of radiotherapy treatment in chordomas.

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

    Science.gov (United States)

    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 (2.5-20 μM) 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Caffeine stabilizes Cdc25 independently of Rad3 in S chizosaccharomyces pombe contributing to checkpoint override

    Science.gov (United States)

    Alao, John P; Sjölander, Johanna J; Baar, Juliane; Özbaki-Yagan, Nejla; Kakoschky, Bianca; Sunnerhagen, Per

    2014-01-01

    Cdc25 is required for Cdc2 dephosphorylation and is thus essential for cell cycle progression. Checkpoint activation requires dual inhibition of Cdc25 and Cdc2 in a Rad3-dependent manner. Caffeine is believed to override activation of the replication and DNA damage checkpoints by inhibiting Rad3-related proteins in both S chizosaccharomyces pombe and mammalian cells. In this study, we have investigated the impact of caffeine on Cdc25 stability, cell cycle progression and checkpoint override. Caffeine induced Cdc25 accumulation in S . pombe independently of Rad3. Caffeine delayed cell cycle progression under normal conditions but advanced mitosis in cells treated with replication inhibitors and DNA-damaging agents. In the absence of Cdc25, caffeine inhibited cell cycle progression even in the presence of hydroxyurea or phleomycin. Caffeine induces Cdc25 accumulation in S . pombe by suppressing its degradation independently of Rad3. The induction of Cdc25 accumulation was not associated with accelerated progression through mitosis, but rather with delayed progression through cytokinesis. Caffeine-induced Cdc25 accumulation appears to underlie its ability to override cell cycle checkpoints. The impact of Cdc25 accumulation on cell cycle progression is attenuated by Srk1 and Mad2. Together our findings suggest that caffeine overrides checkpoint enforcement by inducing the inappropriate nuclear localization of Cdc25. PMID:24666325

  7. Wallac automatic alarm dosimeter type RAD21

    International Nuclear Information System (INIS)

    Burgess, P. H.; Iles, W.J.

    1980-02-01

    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.)

  8. Ca2+ improves organization of single-stranded DNA bases in human Rad51 filament, explaining stimulatory effect on gene recombination.

    KAUST Repository

    Fornander, Louise H; Frykholm, Karolin; Reymer, Anna; Renodon-Corniè re, Axelle; Takahashi, Masayuki; Nordé n, Bengt

    2012-01-01

    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

  9. Differential RPA-1 and RAD-51 recruitment in vivo throughout the C. elegans germline, as revealed by laser microirradiation.

    Science.gov (United States)

    Koury, Emily; Harrell, Kailey; Smolikove, Sarit

    2018-01-25

    Studies of the repair pathways associated with DNA double strand breaks (DSBs) are numerous, and provide evidence for cell-cycle specific regulation of homologous recombination (HR) by the regulation of its associated proteins. Laser microirradiation is a well-established method to examine in vitro kinetics of repair and allows for live-imaging of DSB repair from the moment of induction. Here we apply this method to whole, live organisms, introducing an effective system to analyze exogenous, microirradiation-induced breaks in the Caenorhabditis elegans germline. Through this method we observed the sequential kinetics of the recruitment of ssDNA binding proteins RPA-1 and RAD-51 in vivo. We analyze these kinetics throughout different regions of the germline, and thus throughout a range of developmental stages of mitotic and meiotic nuclei. Our analysis demonstrates a largely conserved timing of recruitment of ssDNA binding proteins to DSBs throughout the germline, with a delay of RAD-51 recruitment at mid-pachytene nuclei. Microirradiated nuclei are viable and undergo a slow kinetics of resolution. We observe RPA-1 and RAD-51 colocalization for hours post-microirradiation throughout the germline, suggesting that there are mixed RPA-1/RAD-51 filaments. Finally, through live imaging analysis we observed RAD-51 foci movement with low frequency of coalescence. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Riesgos vinculados a la exposición al radón

    Directory of Open Access Journals (Sweden)

    Juan Miguel Barros Dios

    2010-12-01

    Full Text Available Se comentan las diferentes evidencias científicas de que el radón y sus descendientes de vida media corta son responsables de la aparición de un número no desdeñable de cánceres de pulmón entre la población expuesta en domicilios y edificios públicos (exposición laboral. Asimismo, se traza una pequeña aproximación al camino recorrido por este conocimiento y su difícil aceptación por parte de las diferentes Administraciones de numerosos países y, en concreto, de España, así como las diversas investigaciones que el Grupo Galego do Radon y el Laboratorio de Radón de Galicia, del Área de Salud Pública, de la Universidad de Santiago de Compostela, llevan aportando a ese conocimiento científico. Por último, se valoran las escasas iniciativas legislativas sobre el problema en España.

  11. The accuracy of the SONOBREAST statistical model in comparison to BI-RADS for the prediction of malignancy in solid breast nodules detected at ultrasonography.

    Science.gov (United States)

    Paulinelli, Regis R; Oliveira, Luis-Fernando P; Freitas-Junior, Ruffo; Soares, Leonardo R

    2016-01-01

    The objective of the present study was to compare the accuracy of SONOBREAST for the prediction of malignancy in solid breast nodules detected at ultrasonography with that of the BI-RADS system and to assess the agreement between these two methods. This prospective study included 274 women and evaluated 500 breast nodules detected at ultrasonography. The probability of malignancy was calculated based on the SONOBREAST model, available at www.sonobreast.com.br, and on the BI-RADS system, with results being compared with the anatomopathology report. The lesions were considered suspect in 171 cases (34.20%), according to both SONOBREAST and BI-RADS. Agreement between the methods was perfect, as shown by a Kappa coefficient of 1 (pBI-RADS proved identical insofar as sensitivity (95.40%), specificity (78.69%), positive predictive value (48.54%), negative predictive value (98.78%) and accuracy (81.60%) are concerned. With respect to the categorical variables (BI-RADS categories 3, 4 and 5), the area under the receiver operating characteristic (ROC) curve was 94.41 for SONOBREAST (range 92.20-96.62) and 89.99 for BI-RADS (range 86.60-93.37). The accuracy of the SONOBREAST model is identical to that found with BI-RADS when the same parameters are used with respect to the cut-off point at which malignancy is suspected. Regarding the continuous probability of malignancy with BI-RADS categories 3, 4 and 5, SONOBREAST permits a more precise and individualized evaluation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. RadSim: a program to simulate individual particle interactions for educational purposes

    International Nuclear Information System (INIS)

    Verhaegen, Frank; Palefsky, Steven; DeBlois, Francois

    2006-01-01

    A program was developed, RadSim, which can be used to simulate certain individual interactions of photons, electrons, positrons and alpha particles with a single atom for educational purposes. The program can be run in two modes: manual and simulated. In the manual mode, an individual particle undergoing a specified interaction with a target atom can be simulated, which essentially comes down to a graphical evaluation of kinematic equations. In the simulated mode, a preset number of identical particles are allowed to undergo a specified interaction type with a target atom. The exit channel of the interaction is sampled from probability distributions using Monte Carlo methods. The incoming and outgoing particles are visualized and the frequency distribution of the kinematic variables of the exit channel is displayed graphically. It has to be emphasized that RadSim was mainly developed for educational purposes. (note)

  13. Comparison of Visual Assessment of Breast Density in BI-RADS 4th and 5th Editions With Automated Volumetric Measurement.

    Science.gov (United States)

    Youk, Ji Hyun; Kim, So Jung; Son, Eun Ju; Gweon, Hye Mi; Kim, Jeong-Ah

    2017-09-01

    The purpose of this study was to compare visual assessments of mammographic breast density by radiologists using BI-RADS 4th and 5th editions in correlation with automated volumetric breast density measurements. A total of 337 consecutive full-field digital mammographic examinations with standard views were retrospectively assessed by two radiologists for mammographic breast density according to BI-RADS 4th and 5th editions. Fully automated measurement of the volume of fibroglandular tissue and total breast and percentage breast density was performed with a commercially available software program. Interobserver and intraobserver agreement was assessed with kappa statistics. The distributions of breast density categories for both editions of BI-RADS were compared and correlated with volumetric data. Interobserver agreement on breast density category was moderate to substantial (κ = 0.58-0.63) with use of BI-RADS 4th edition and substantial (κ = 0.63-0.66) with use of the 5th edition but without significant difference between the two editions. For intraobserver agreement between the two editions, the distributions of density category were significantly different (p density data, including percentage breast density, were significantly different among density categories (p density assessment had good correlation with visual assessment for both editions of BI-RADS.

  14. Passive film growth on carbon steel and its nanoscale features at various passivating potentials

    International Nuclear Information System (INIS)

    Li, Yuan; Cheng, Y. Frank

    2017-01-01

    Highlights: • Imaged the topography of passivated steel at various film-forming potentials. • Characterized the nanoscale features of passive films. • Determined the composition of passive films formed at various potentials. - Abstract: In this work, the passivation and topographic sub-structure of passive films on a carbon steel in a carbonate/bicarbonate solution was characterized by electrochemical measurements, atomic force microscopy and X-ray photoelectron spectroscopy. When passivating at a potential near the active-passive transition, the film contains the mixture of Fe_3O_4, Fe_2O_3 and FeOOH, with numerous nanoscale features. As the film-forming potential shifts positively, the passive film becomes more compact and the nanoscale features disappear. When the film is formed at a passive potential where the oxygen evolution is enabled, the content of FeOOH in the film increases, resulting in an amorphous topography and reduced corrosion resistance.

  15. Prolongamento da vida pós-colheita de bananas-maçã submetidas ao 1-metilciclopropeno (1-MCP - qualidade sensorial e física Extension of postharvest life of 'Apple1 banana subjected to1-methylcyclopropene (1-MCP - sensory and physical quality

    Directory of Open Access Journals (Sweden)

    Ana Carla Marques Pinheiro

    2010-03-01

    Full Text Available Objetivou-se avaliar o efeito do 1-metilciclopropeno (1-MCP sobre a qualidade e extensão da vida pós-colheita de bananas-maçã. Frutas no grau 2 de coloração da casca foram tratadas com 50 nL.L-1 de 1-MCP durante 0 (controle, 6, 9, 12 e 24 horas. Posteriormente, foram armazenadas sob condição ambiente: 22± 2 ºC 85± 5% UR. Avaliaram-se as características sensoriais: aparência dos frutos no grau 4 (frutos mais verdes que amarelos e grau 7 (frutos amarelos com pontuações marrons de coloração da casca; descasque, aroma, sabor, firmeza da polpa e aspecto global nos frutos no grau 7, utilizando-se um teste de aceitabilidade através de escala hedônica de 9 pontos; e ainda a intenção de compra nos frutos nos graus 4 e 7, através de escala de 5 pontos. Avaliou-se também, visualmente, a extensão da vida pós-colheita, e, instrumentalmente, a coloração da casca e firmeza da polpa. Conclui-se que a aplicação de 50 nL.L-1 por um período de 12 horas é a mais adequada, pois promove extensão na vida pós-colheita de bananas-maçã, armazenadas em temperatura ambiente, em aproximadamente 11 dias, sem alterar a qualidade sensorial, a intenção de compra, coloração da casca e firmeza dos frutos quando maduros, comparados ao controle.The objective of this work was to evaluate the effect of 1-methylcyclopropene (1-MCP on the quality and extension of postharvest life of 'Apple1 banana. The fruit, at degree 2 of peel color was treated with 50 nL.L-1 of 1-MCP for 0 (control, 6, 9, 12 and 24 hours. Next, It was stored at room temperature: 22± 2 ºC 85± 5 per cent RH. The following sensory characteristics were evaluated: appearance of the fruit at degree 4 (greener than yellow and degree 7 (yellow with brown spots of peel color; peeling, aroma, flavor, firmness of pulp and global aspect of the fruit at degree 7, using a test of acceptability using the 9-point hedonic scale and also the intention of buying the fruit at degrees 4 and 7

  16. Pir51, a Rad51-interacting protein with high expression in aggressive lymphoma, controls mitomycin C sensitivity and prevents chromosomal breaks

    Energy Technology Data Exchange (ETDEWEB)

    Henson, Sarah E. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Tsai, Shih-Chang [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Malone, Cindy Sue [Department of Biology, California State University Northridge, Northridge, CA 91330 (United States); Soghomonian, Shahe V. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Ouyang, Yan [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Wall, Randolph [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Molecular Biology Institute and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Marahrens, York [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States) and Molecular Biology Institute and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States)]. E-mail: YMarahrens@mednet.ucla.edu; Teitell, Michael A. [Molecular Biology Institute and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States) and Department of Pathology and Laboratory Medicine, California NanoSystems Institute, and Institute for Stem Cell Biology and Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States)]. E-mail: mteitell@ucla.edu

    2006-10-10

    Pir51, a protein of unknown function that interacts with Rad51, was identified in a screen for genes that were highly expressed in aggressive mantle cell lymphoma (MCL) versus indolent small lymphocytic lymphoma (SLL) patient samples. We show that Pir51 is a nuclear protein expressed in a variety of cell types and that its expression is regulated during the cell cycle in a pattern nearly identical to Rad51. Also similar to Rad51, Pir51 levels did not change in response to a variety of DNA damaging agents. siRNA depletion of Pir51 did not reduce homologous recombination repair (HRR), but sensitized cells to mitomycin C (MMC)-induced DNA crosslinking and resulted in elevated levels of double-strand breaks (DSBs) in metaphase chromosome spreads and reduced colony formation. Therefore, Pir51 maintains genomic integrity and potentially connects the early response to DNA crosslinks, orchestrated by the ATR kinase and Fanconi Anemia (FA) proteins, to later stages of Rad51-dependent repair. Our results provide the first example of a Rad51-binding protein that influences DNA crosslink repair without affecting homologous recombination repair.

  17. Pir51, a Rad51-interacting protein with high expression in aggressive lymphoma, controls mitomycin C sensitivity and prevents chromosomal breaks

    International Nuclear Information System (INIS)

    Henson, Sarah E.; Tsai, Shih-Chang; Malone, Cindy Sue; Soghomonian, Shahe V.; Ouyang, Yan; Wall, Randolph; Marahrens, York; Teitell, Michael A.

    2006-01-01

    Pir51, a protein of unknown function that interacts with Rad51, was identified in a screen for genes that were highly expressed in aggressive mantle cell lymphoma (MCL) versus indolent small lymphocytic lymphoma (SLL) patient samples. We show that Pir51 is a nuclear protein expressed in a variety of cell types and that its expression is regulated during the cell cycle in a pattern nearly identical to Rad51. Also similar to Rad51, Pir51 levels did not change in response to a variety of DNA damaging agents. siRNA depletion of Pir51 did not reduce homologous recombination repair (HRR), but sensitized cells to mitomycin C (MMC)-induced DNA crosslinking and resulted in elevated levels of double-strand breaks (DSBs) in metaphase chromosome spreads and reduced colony formation. Therefore, Pir51 maintains genomic integrity and potentially connects the early response to DNA crosslinks, orchestrated by the ATR kinase and Fanconi Anemia (FA) proteins, to later stages of Rad51-dependent repair. Our results provide the first example of a Rad51-binding protein that influences DNA crosslink repair without affecting homologous recombination repair

  18. Machine learning-based analysis of MR radiomics can help to improve the diagnostic performance of PI-RADS v2 in clinically relevant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing [CFDA, Center for Medical Device Evaluation, Beijing (China); Wu, Chen-Jiang; Zhang, Jing; Wang, Xiao-Ning; Zhang, Yu-Dong [First Affiliated Hospital with Nanjing Medical University, Department of Radiology, Nanjing, Jiangsu Province (China); Bao, Mei-Ling [First Affiliated Hospital with Nanjing Medical University, Department of Pathology, Nanjing (China)

    2017-10-15

    To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 [95% CI 0.923-0.976]) than PI-RADS (Az: 0.878 [0.834-0.914], p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 [0.945-0.988] vs. 0.940 [0.905-0.965], p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 [0.960-0.995]) and PCa versus TZ (Az: 0.968 [0.940-0.985]). Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa. (orig.)

  19. Machine learning-based analysis of MR radiomics can help to improve the diagnostic performance of PI-RADS v2 in clinically relevant prostate cancer

    International Nuclear Information System (INIS)

    Wang, Jing; Wu, Chen-Jiang; Zhang, Jing; Wang, Xiao-Ning; Zhang, Yu-Dong; Bao, Mei-Ling

    2017-01-01

    To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 [95% CI 0.923-0.976]) than PI-RADS (Az: 0.878 [0.834-0.914], p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 [0.945-0.988] vs. 0.940 [0.905-0.965], p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 [0.960-0.995]) and PCa versus TZ (Az: 0.968 [0.940-0.985]). Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa. (orig.)

  20. Passive film growth on carbon steel and its nanoscale features at various passivating potentials

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan; Cheng, Y. Frank, E-mail: fcheng@ucalgary.ca

    2017-02-28

    Highlights: • Imaged the topography of passivated steel at various film-forming potentials. • Characterized the nanoscale features of passive films. • Determined the composition of passive films formed at various potentials. - Abstract: In this work, the passivation and topographic sub-structure of passive films on a carbon steel in a carbonate/bicarbonate solution was characterized by electrochemical measurements, atomic force microscopy and X-ray photoelectron spectroscopy. When passivating at a potential near the active-passive transition, the film contains the mixture of Fe{sub 3}O{sub 4}, Fe{sub 2}O{sub 3} and FeOOH, with numerous nanoscale features. As the film-forming potential shifts positively, the passive film becomes more compact and the nanoscale features disappear. When the film is formed at a passive potential where the oxygen evolution is enabled, the content of FeOOH in the film increases, resulting in an amorphous topography and reduced corrosion resistance.