RAD51B in Familial Breast Cancer.

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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.

RAD51B in Familial Breast Cancer

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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

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

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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.

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

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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.

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

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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

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

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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.

Differential RPA-1 and RAD-51 recruitment in vivo throughout the C. elegans germline, as revealed by laser microirradiation.

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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.

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

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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.

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)

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

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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.

Enhancement of the RAD51 Recombinase Activity by the Tumor Suppressor PALB2

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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.

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....

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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.

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.

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.

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

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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.

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

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...

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.

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

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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

Pir51, a Rad51-interacting protein with high expression in aggressive lymphoma, controls mitomycin C sensitivity and prevents chromosomal breaks

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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.

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

Small Rad51 and Dmc1 Complexes Often Co-occupy Both Ends of a Meiotic DNA Double Strand Break.

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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.

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.

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

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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.

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

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...

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

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.

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...

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

Recruitment of RecA homologs Dmc1p and Rad51p to the double-strand break repair site initiated by meiosis-specific endonuclease VDE (PI-SceI).

Science.gov (United States)

Fukuda, Tomoyuki; Ohya, Yoshikazu

2006-02-01

During meiosis, VDE (PI-SceI), a homing endonuclease in Saccharomyces cerevisiae, introduces a double-strand break (DSB) at its recognition sequence and induces homologous recombinational repair, called homing. Meiosis-specific RecA homolog Dmc1p, as well as mitotic RecA homolog Rad51p, acts in the process of meiotic recombination, being required for strand invasion and exchange. In this study, recruitment of Dmc1p and Rad51p to the VDE-induced DSB repair site is investigated by chromatin immunoprecipitation assay. It is revealed that Dmc1p and Rad51p are loaded to the repair site in an independent manner. Association of Rad51p requires other DSB repair proteins of Rad52p, Rad55p, and Rad57p, while loading of Dmc1p is facilitated by the different protein, Sae3p. Absence of Tid1p, which can bind both RecA homologs, appears specifically to cause an abnormal distribution of Dmc1p. Lack of Hop2, Mnd1p, and Sae1p does not impair recruitment of both RecA homologs. These findings reveal the discrete functions of each strand invasion protein in VDE-initiated homing, confirm the similarity between VDE-initiated homing and Spo11p-initiated meiotic recombination, and demonstrate the availability of VDE-initiated homing for the study of meiotic recombination.

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...

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)

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.

Simultaneous ATM/BRCA1/RAD51 expression variations associated with prognostic factors in Iranian sporadic breast cancer patients.

Science.gov (United States)

Hallajian, Zeinab; Mahjoubi, Frouzandeh; Nafissi, Nahid

2017-07-01

DNA double-strand breaks (DSBs) as a serious lesion are repaired by non-homologous end-joining and homologous recombination pathways. ATM, BRCA1, RAD51 genes are involved in HR pathways. While some studies have revealed individual expression changes of these genes in different types of cancer, there are limited studies attempting to evaluate correlation of expression variations of these genes in breast cancer pathogenesis. This study aimed to determine RAD51, ATM and BRCA1 gene expression level and its association with clinicopathological factors in fresh breast cancer tissues. Moreover, this study evaluates potential correlations among expression levels of these genes. 50 breast cancer tissues were collected and examined for BRCA1, RAD51 and ATM gene expression by Real Time PCR. Expression changes were analyzed with REST software version 2009. mRNA expression was reduced in all these three genes when compared with β-Actin as a control gene (P value  ATM, BRCA1 and RAD51 gene down expression (P value  ATM with stage (P value  < 0.05), necrosis (P value  < 0.05), perineural invasion (P value  < 0.05), vascular invasion (P value  < 0.01), malignancy (P value  ≤ 0.001), PR (P value  < 0.05) and ER status (P value  < 0.01). In addition, there was a significant association between down expression of BRCA1 with Ki67 (P value  ≤ 0.001). Moreover, there was a significant association between down expression of RAD51 with lymph node involvement (P value  < 0.01), auxiliary lymph node metastasis (P value  = 0.01), age (P = 0.001), grade (P value  < 0.05) and PR status (P value  < 0.05). This study suggests association between expression changes in several DSB repair genes in a common functional pathway in breast cancer and the significant association between abnormal expression of these genes and important clinical prognostic factors.

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.

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.

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.

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)

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.

HELQ promotes RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis

DEFF Research Database (Denmark)

Adelman, Carrie A.; Lolo, Rafal L.; Birkbak, Nicolai Juul

2013-01-01

Repair of interstrand crosslinks (ICLs) requires the coordinated action of the intra-S-phase checkpoint and the Fanconi anaemia pathway, which promote ICL incision, translesion synthesis and homologous recombination (reviewed in refs 1, 2). Previous studies have implicated the 3'-5' superfamily 2......, phenotype than the null, indicative of haploinsufficiency. We establish that HELQ interacts directly with the RAD51 paralogue complex BCDX2 and functions in parallel to the Fanconi anaemia pathway to promote efficient homologous recombination at damaged replication forks. Thus, our results reveal a critical...

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

Identification of the meiotic toolkit in diatoms and exploration of meiosis-specific SPO11 and RAD51 homologs in the sexual species Pseudo-nitzschia multistriata and Seminavis robusta.

Science.gov (United States)

Patil, Shrikant; Moeys, Sara; von Dassow, Peter; Huysman, Marie J J; Mapleson, Daniel; De Veylder, Lieven; Sanges, Remo; Vyverman, Wim; Montresor, Marina; Ferrante, Maria Immacolata

2015-11-14

Sexual reproduction is an obligate phase in the life cycle of most eukaryotes. Meiosis varies among organisms, which is reflected by the variability of the gene set associated to the process. Diatoms are unicellular organisms that belong to the stramenopile clade and have unique life cycles that can include a sexual phase. The exploration of five diatom genomes and one diatom transcriptome led to the identification of 42 genes potentially involved in meiosis. While these include the majority of known meiosis-related genes, several meiosis-specific genes, including DMC1, could not be identified. Furthermore, phylogenetic analyses supported gene identification and revealed ancestral loss and recent expansion in the RAD51 family in diatoms. The two sexual species Pseudo-nitzschia multistriata and Seminavis robusta were used to explore the expression of meiosis-related genes: RAD21, SPO11-2, RAD51-A, RAD51-B and RAD51-C were upregulated during meiosis, whereas other paralogs in these families showed no differential expression patterns, suggesting that they may play a role during vegetative divisions. An almost identical toolkit is shared among Pseudo-nitzschia multiseries and Fragilariopsis cylindrus, as well as two species for which sex has not been observed, Phaeodactylum tricornutum and Thalassiosira pseudonana, suggesting that these two may retain a facultative sexual phase. Our results reveal the conserved meiotic toolkit in six diatom species and indicate that Stramenopiles share major modifications of canonical meiosis processes ancestral to eukaryotes, with important divergences in each Kingdom.

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)

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.

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.

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

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.

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

Homologous Recombination Repair Signaling in Chemical Carcinogenesis: Prolonged Particulate Hexavalent Chromium Exposure Suppresses the Rad51 Response in Human Lung Cells

Science.gov (United States)

Qin, Qin; Xie, Hong; Wise, Sandra S.; Browning, Cynthia L.; Thompson, Kelsey N.; Holmes, Amie L.; Wise, John Pierce

2014-01-01

The aim of this study was to focus on hexavalent chromium, [Cr(VI)], a chemical carcinogen and major public health concern, and consider its ability to impact DNA double strand break repair. We further focused on particulate Cr(VI), because it is the more potent carcinogenic form of Cr(VI). DNA double strand break repair serves to protect cells against the detrimental effects of DNA double strand breaks. For particulate Cr(VI), data show DNA double strand break repair must be overcome for neoplastic transformation to occur. Acute Cr(VI) exposures reveal a robust DNA double strand break repair response, however, longer exposures have not been considered. Using the comet assay, we found longer exposures to particulate zinc chromate induced concentration-dependent increases in DNA double strand breaks indicating breaks were occurring throughout the exposure time. Acute (24 h) exposure induced DNA double strand break repair signaling by inducing Mre11 foci formation, ATM phosphorylation and phosphorylated ATM foci formation, Rad51 protein levels and Rad51 foci formation. However, longer exposures reduced the Rad51 response. These data indicate a major chemical carcinogen can simultaneously induce DNA double strand breaks and alter their repair and describe a new and important aspect of the carcinogenic mechanism for Cr(VI). PMID:25173789

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.

Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy

KAUST Repository

Reymer, A.

2009-07-08

To get mechanistic insight into the DNA strand-exchange reaction of homologous recombination, we solved a filament structure of a human Rad51 protein, combining molecular modeling with experimental data. We build our structure on reported structures for central and N-terminal parts of pure (uncomplexed) Rad51 protein by aid of linear dichroism spectroscopy, providing angular orientations of substituted tyrosine residues of Rad51-dsDNA filaments in solution. The structure, validated by comparison with an electron microscopy density map and results from mutation analysis, is proposed to represent an active solution structure of the nucleo-protein complex. An inhomogeneously stretched double-stranded DNA fitted into the filament emphasizes the strategic positioning of 2 putative DNA-binding loops in a way that allows us speculate about their possibly distinct roles in nucleo-protein filament assembly and DNA strand-exchange reaction. The model suggests that the extension of a single-stranded DNA molecule upon binding of Rad51 is ensured by intercalation of Tyr-232 of the L1 loop, which might act as a docking tool, aligning protein monomers along the DNA strand upon filament assembly. Arg-235, also sitting on L1, is in the right position to make electrostatic contact with the phosphate backbone of the other DNA strand. The L2 loop position and its more ordered compact conformation makes us propose that this loop has another role, as a binding site for an incoming double-stranded DNA. Our filament structure and spectroscopic approach open the possibility of analyzing details along the multistep path of the strand-exchange reaction.

Design of potent inhibitors of human RAD51 recombinase based on BRC motifs of BRCA2 protein: modeling and experimental validation of a chimera peptide.

KAUST Repository

Nomme, Julian; Renodon-Corniè re, Axelle; Asanomi, Yuya; Sakaguchi, Kazuyasu; Stasiak, Alicja Z; Stasiak, Andrzej; Norden, Bengt; Tran, Vinh; Takahashi, Masayuki

2010-01-01

We have previously shown that a 28-amino acid peptide derived from the BRC4 motif of BRCA2 tumor suppressor inhibits selectively human RAD51 recombinase (HsRad51). With the aim of designing better inhibitors for cancer treatment, we combined an in silico docking approach with in vitro biochemical testing to construct a highly efficient chimera peptide from eight existing human BRC motifs. We built a molecular model of all BRC motifs complexed with HsRad51 based on the crystal structure of the BRC4 motif-HsRad51 complex, computed the interaction energy of each residue in each BRC motif, and selected the best amino acid residue at each binding position. This analysis enabled us to propose four amino acid substitutions in the BRC4 motif. Three of these increased the inhibitory effect in vitro, and this effect was found to be additive. We thus obtained a peptide that is about 10 times more efficient in inhibiting HsRad51-ssDNA complex formation than the original peptide.

Design of potent inhibitors of human RAD51 recombinase based on BRC motifs of BRCA2 protein: modeling and experimental validation of a chimera peptide.

KAUST Repository

Nomme, Julian

2010-08-01

We have previously shown that a 28-amino acid peptide derived from the BRC4 motif of BRCA2 tumor suppressor inhibits selectively human RAD51 recombinase (HsRad51). With the aim of designing better inhibitors for cancer treatment, we combined an in silico docking approach with in vitro biochemical testing to construct a highly efficient chimera peptide from eight existing human BRC motifs. We built a molecular model of all BRC motifs complexed with HsRad51 based on the crystal structure of the BRC4 motif-HsRad51 complex, computed the interaction energy of each residue in each BRC motif, and selected the best amino acid residue at each binding position. This analysis enabled us to propose four amino acid substitutions in the BRC4 motif. Three of these increased the inhibitory effect in vitro, and this effect was found to be additive. We thus obtained a peptide that is about 10 times more efficient in inhibiting HsRad51-ssDNA complex formation than the original peptide.

Caffeine suppresses homologous recombination through interference with RAD51-mediated joint molecule formation

Science.gov (United States)

Zelensky, Alex N.; Sanchez, Humberto; Ristic, Dejan; Vidic, Iztok; van Rossum-Fikkert, Sari E.; Essers, Jeroen; Wyman, Claire; Kanaar, Roland

2013-01-01

Caffeine is a widely used inhibitor of the protein kinases that play a central role in the DNA damage response. We used chemical inhibitors and genetically deficient mouse embryonic stem cell lines to study the role of DNA damage response in stable integration of the transfected DNA and found that caffeine rapidly, efficiently and reversibly inhibited homologous integration of the transfected DNA as measured by several homologous recombination-mediated gene-targeting assays. Biochemical and structural biology experiments revealed that caffeine interfered with a pivotal step in homologous recombination, homologous joint molecule formation, through increasing interactions of the RAD51 nucleoprotein filament with non-homologous DNA. Our results suggest that recombination pathways dependent on extensive homology search are caffeine-sensitive and stress the importance of considering direct checkpoint-independent mechanisms in the interpretation of the effects of caffeine on DNA repair. PMID:23666627

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...

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)

ATM/ATR-mediated phosphorylation of PALB2 promotes RAD51 function

DEFF Research Database (Denmark)

Ahlskog, Johanna K; Larsen, Brian D; Achanta, Kavya

2016-01-01

DNA damage activates the ATM and ATR kinases that coordinate checkpoint and DNA repair pathways. An essential step in homology-directed repair (HDR) of DNA breaks is the formation of RAD51 nucleofilaments mediated by PALB2-BRCA2; however, roles of ATM and ATR in this critical step of HDR are poor...... function, as the PALB2-dependent checkpoint response is normal in cells expressing the phospho-deficient PALB2 mutant. Collectively, our findings highlight a critical importance of PALB2 phosphorylation as a novel regulatory step in genome maintenance after genotoxic stress....

CRISPR Technology Reveals RAD(51)-ical Mechanisms of Repair in Roundworms: An Educational Primer for Use with "Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans".

Science.gov (United States)

Turcotte, Carolyn A; Andrews, Nicolas P; Sloat, Solomon A; Checchi, Paula M

2016-11-01

The mechanisms cells use to maintain genetic fidelity via DNA repair and the accuracy of these processes have garnered interest from scientists engaged in basic research to clinicians seeking improved treatment for cancer patients. Despite the continued advances, many details of DNA repair are still incompletely understood. In addition, the inherent complexity of DNA repair processes, even at the most fundamental level, makes it a challenging topic. This primer is meant to assist both educators and students in using a recent paper, "Promotion of homologous recombination by SWS-1 in complex with RAD-51 paralogs in Caenorhabditis elegans," to understand mechanisms of DNA repair. The goals of this primer are to highlight and clarify several key techniques utilized, with special emphasis on the clustered, regularly interspaced, short palindromic repeats technique and the ways in which it has revolutionized genetics research, as well as to provide questions for deeper in-class discussion. Copyright © 2016 by the Genetics Society of America.

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...

Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2

Energy Technology Data Exchange (ETDEWEB)

Godthelp, Barbara C. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Wiegant, Wouter W. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Waisfisz, Quinten [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Medhurst, Annette L. [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Arwert, Fre [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Joenje, Hans [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands) and Department of Molecular Cell Genetics, Collegium Medicum, N. Copernicus University, Bydgoszcz (Poland)]. E-mail: m.z.zdzienicka@lumc.nl

2006-02-22

Fanconi anemia (FA) is a cancer susceptibility disorder characterized by chromosomal instability and hypersensitivity to DNA cross-linking agents. So far 11 complementation groups have been identified, from which only FA-D1/BRCA2 and FA-J are defective downstream of the central FANCD2 protein as cells from these groups are capable of monoubiquitinating FANCD2. In this study we show that cells derived from patients from the new complementation groups, FA-I, FA-J and FA-L are all proficient in DNA damage induced Rad51 foci formation, making the cells from FA-D1/BRCA2 patients that are defective in this process the sole exception. Although FA-B patient HSC230 was previously reported to also have biallelic BRCA2 mutations, we found normal Rad51 foci formation in cells from this patient, consistent with the recent identification of an X-linked gene being mutated in four unrelated FA-B patients. Thus, our data show that none of the FA proteins, except BRCA2, are required to sequester Rad51 into nuclear foci. Since cells from the FA-D1 and FA-J patient groups are both able to monoubiquitinate FANCD2, the 'Rad51 foci phenotype' provides a convenient assay to distinguish between these two groups. Our results suggest that FANCJ and FANCD1/BRCA2 are part of the integrated FANC/BRCA DNA damage response pathway or, alternatively, that they represent sub-pathways in which only FANCD1/BRCA2 is directly connected to the process of homologous recombination.

Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2

International Nuclear Information System (INIS)

Godthelp, Barbara C.; Wiegant, Wouter W.; Waisfisz, Quinten; Medhurst, Annette L.; Arwert, Fre; Joenje, Hans; Zdzienicka, Malgorzata Z.

2006-01-01

Fanconi anemia (FA) is a cancer susceptibility disorder characterized by chromosomal instability and hypersensitivity to DNA cross-linking agents. So far 11 complementation groups have been identified, from which only FA-D1/BRCA2 and FA-J are defective downstream of the central FANCD2 protein as cells from these groups are capable of monoubiquitinating FANCD2. In this study we show that cells derived from patients from the new complementation groups, FA-I, FA-J and FA-L are all proficient in DNA damage induced Rad51 foci formation, making the cells from FA-D1/BRCA2 patients that are defective in this process the sole exception. Although FA-B patient HSC230 was previously reported to also have biallelic BRCA2 mutations, we found normal Rad51 foci formation in cells from this patient, consistent with the recent identification of an X-linked gene being mutated in four unrelated FA-B patients. Thus, our data show that none of the FA proteins, except BRCA2, are required to sequester Rad51 into nuclear foci. Since cells from the FA-D1 and FA-J patient groups are both able to monoubiquitinate FANCD2, the 'Rad51 foci phenotype' provides a convenient assay to distinguish between these two groups. Our results suggest that FANCJ and FANCD1/BRCA2 are part of the integrated FANC/BRCA DNA damage response pathway or, alternatively, that they represent sub-pathways in which only FANCD1/BRCA2 is directly connected to the process of homologous recombination

Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament.

KAUST Repository

Fornander, Louise H

2013-12-03

The Swi5-Sfr1 heterodimer protein stimulates the Rad51-promoted DNA strand exchange reaction, a crucial step in homologous recombination. To clarify how this accessory protein acts on the strand exchange reaction, we have analyzed how the structure of the primary reaction intermediate, the Rad51/single-stranded DNA (ssDNA) complex filament formed in the presence of ATP, is affected by Swi5-Sfr1. Using flow linear dichroism spectroscopy, we observe that the nucleobases of the ssDNA are more perpendicularly aligned to the filament axis in the presence of Swi5-Sfr1, whereas the bases are more randomly oriented in the absence of Swi5-Sfr1. When using a modified version of the natural protein where the N-terminal part of Sfr1 is deleted, which has no affinity for DNA but maintained ability to stimulate the strand exchange reaction, we still observe the improved perpendicular DNA base orientation. This indicates that Swi5-Sfr1 exerts its activating effect through interaction with the Rad51 filament mainly and not with the DNA. We propose that the role of a coplanar alignment of nucleobases induced by Swi5-Sfr1 in the presynaptic Rad51/ssDNA complex is to facilitate the critical matching with an invading double-stranded DNA, hence stimulating the strand exchange reaction.

Reconstitution of DNA strand exchange mediated by Rhp51 recombinase and two mediators.

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Yumiko Kurokawa

2008-04-01

Full Text Available In the fission yeast Schizosaccharomyces pombe, genetic evidence suggests that two mediators, Rad22 (the S. pombe Rad52 homolog and the Swi5-Sfr1 complex, participate in a common pathway of Rhp51 (the S. pombe Rad51 homolog-mediated homologous recombination (HR and HR repair. Here, we have demonstrated an in vitro reconstitution of the central step of DNA strand exchange during HR. Our system consists entirely of homogeneously purified proteins, including Rhp51, the two mediators, and replication protein A (RPA, which reflects genetic requirements in vivo. Using this system, we present the first robust biochemical evidence that concerted action of the two mediators directs the loading of Rhp51 onto single-stranded DNA (ssDNA precoated with RPA. Dissection of the reaction reveals that Rad22 overcomes the inhibitory effect of RPA on Rhp51-Swi5-Sfr1-mediated strand exchange. In addition, Rad22 negates the requirement for a strict order of protein addition to the in vitro system. However, despite the presence of Rad22, Swi5-Sfr1 is still essential for strand exchange. Importantly, Rhp51, but neither Rad22 nor the Swi5-Sfr1 mediator, is the factor that displaces RPA from ssDNA. Swi5-Sfr1 stabilizes Rhp51-ssDNA filaments in an ATP-dependent manner, and this stabilization is correlated with activation of Rhp51 for the strand exchange reaction. Rad22 alone cannot activate the Rhp51 presynaptic filament. AMP-PNP, a nonhydrolyzable ATP analog, induces a similar stabilization of Rhp51, but this stabilization is independent of Swi5-Sfr1. However, hydrolysis of ATP is required for processive strand transfer, which results in the formation of a long heteroduplex. Our in vitro reconstitution system has revealed that the two mediators have indispensable, but distinct, roles for mediating Rhp51 loading onto RPA-precoated ssDNA.

Cloning, sequencing, disruption and phenotypic analysis of uvsC, an Aspergillus nidulans homologue of yeast RAD51.

Science.gov (United States)

van Heemst, D; Swart, K; Holub, E F; van Dijk, R; Offenberg, H H; Goosen, T; van den Broek, H W; Heyting, C

1997-05-01

We have cloned the uvsC gene of Aspergillus nidulans by complementation of the A. nidulans uvsC114 mutant. The predicted protein UVSC shows 67.4% sequence identity to the Saccharomyces cerevisiae Rad51 protein and 27.4% sequence identity to the Escherichia coli RecA protein. Transcription of uvsC is induced by methyl-methane sulphonate (MMS), as is transcription of RAD51 of yeast. Similar levels of uvsC transcription were observed after MMS induction in a uvsC+ strain and the uvsC114 mutant. The coding sequence of the uvsC114 allele has a deletion of 6 bp, which results in deletion of two amino acids and replacement of one amino acid in the translation product. In order to gain more insight into the biological function of the uvsC gene, a uvsC null mutant was constructed, in which the entire uvsC coding sequence was replaced by a selectable marker gene. Meiotic and mitotic phenotypes of a uvsC+ strain, the uvsC114 mutant and the uvsC null mutant were compared. The uvsC null mutant was more sensitive to both UV and MMS than the uvsC114 mutant. The uvsC114 mutant arrested in meiotic prophase-I. The uvsC null mutant arrested at an earlier stage, before the onset of meiosis. One possible interpretation of these meiotic phenotypes is that the A. nidulans homologue of Rad51 of yeast has a role both in the specialized processes preceding meiosis and in meiotic prophase I.

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...

Icotinib hydrochloride enhances chemo- and radiosensitivity by inhibiting EGFR signaling and attenuating RAD51 expression and function in Hela S3 cells

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Wang X

2018-03-01

Full Text Available Xuanxuan Wang, Yanjun Gu, Hai Liu, Liming Shi, Xiaonan Sun Department of Radiation Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China Background: Radiotherapy and cisplatin-based chemotherapy are currently considered as standard treatments employed for advanced cervical cancer (CC. However, patients with local recurrence or distant metastasis continue to have poor outcomes. EGFR overexpression correlated with chemo/radioresistance, and disease failure has been well proved in the previous studies. Hence, the aim of this study was to explore the therapeutic efficacy and underlying mechanism of the sensitization to radiation or cisplatin of icotinib hydrochloride (IH, a high-selective EGFR tyrosine kinase inhibitor (TKI, in the Hela S3 human CC cell line.Methods: Cell proliferation was measured with cell counting kit-8 (CCK-8 assay. Flow cytometry analysis was performed to examine cell cycle distribution and apoptosis. The phosphorylation of EGFR and its downstream signaling molecules were measured by Western blot analysis. γ-H2AX foci and RAD51 foci in the cellular nucleus were visualized using immunofluoresence staining. Expression levels of RAD51 in the whole cells and subceullar fractions were detected to demonstrate the impact of IH on DNA repair. Results: IH can significantly inhibit cell proliferation, redistribute cell cycle, enhance apoptosis and impair DNA damage response of Hela S3 cells following radiation or cisplatin treatment through suppressing the activation of the EGFR signaling pathway and attenuating the expression and function of homologous recombination (HR protein RAD51.Conclusion: This study suggests that IH is a potential sensitizer in radiotherapy and cisplatin-based chemotherapy for CC and RAD51 may serve as a prognosis biomarker for this combination treatment. Keywords: icotinib hydrochloride, cervical cancer, EGFR, radiotherapy, chemotherapy

C. elegans ring finger protein RNF-113 is involved in interstrand DNA crosslink repair and interacts with a RAD51C homolog.

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Hyojin Lee

Full Text Available The Fanconi anemia (FA pathway recognizes interstrand DNA crosslinks (ICLs and contributes to their conversion into double-strand DNA breaks, which can be repaired by homologous recombination. Seven orthologs of the 15 proteins associated with Fanconi anemia are functionally conserved in the model organism C. elegans. Here we report that RNF-113, a ubiquitin ligase, is required for RAD-51 focus formation after inducing ICLs in C. elegans. However, the formation of foci of RPA-1 or FCD-2/FANCD2 in the FA pathway was not affected by depletion of RNF-113. Nevertheless, the RPA-1 foci formed did not disappear with time in the depleted worms, implying serious defects in ICL repair. As a result, RNF-113 depletion increased embryonic lethality after ICL treatment in wild-type worms, but it did not increase the ICL-induced lethality of rfs-1/rad51C mutants. In addition, the persistence of RPA-1 foci was suppressed in doubly-deficient rnf-113;rfs-1 worms, suggesting that there is an epistatic interaction between the two genes. These results lead us to suggest that RNF-113 and RFS-1 interact to promote the displacement of RPA-1 by RAD-51 on single-stranded DNA derived from ICLs.

A miR-590/Acvr2a/Rad51b Axis Regulates DNA Damage Repair during mESC Proliferation

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Qidong Liu

2014-12-01

Full Text Available Embryonic stem cells (ESCs enable rapid proliferation that also causes DNA damage. To maintain genomic stabilization during rapid proliferation, ESCs must have an efficient system to repress genotoxic stress. Here, we show that withdrawal of leukemia inhibitory factor (LIF, which maintains the self-renewal capability of mouse ESCs (mESCs, significantly inhibits the cell proliferation and DNA damage of mESCs and upregulates the expression of miR-590. miR-590 promotes single-strand break (SSB and double-strand break (DSB damage repair, thus slowing proliferation of mESCs without influencing stemness. miR-590 directly targets Activin receptor type 2a (Acvr2a to mediate Activin signaling. We identified the homologous recombination-mediated repair (HRR gene, Rad51b, as a downstream molecule of the miR-590/Acvr2a pathway regulating the SSB and DSB damage repair and cell cycle. Our study shows that a miR-590/Acvr2a/Rad51b signaling axis ensures the stabilization of mESCs by balancing DNA damage repair and rapid proliferation during self-renewal.

Lingering single-strand breaks trigger Rad51-independent homology-directed repair of collapsed replication forks in the polynucleotide kinase/phosphatase mutant of fission yeast.

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Arancha Sanchez

2017-09-01

Full Text Available The DNA repair enzyme polynucleotide kinase/phosphatase (PNKP protects genome integrity by restoring ligatable 5'-phosphate and 3'-hydroxyl termini at single-strand breaks (SSBs. In humans, PNKP mutations underlie the neurological disease known as MCSZ, but these individuals are not predisposed for cancer, implying effective alternative repair pathways in dividing cells. Homology-directed repair (HDR of collapsed replication forks was proposed to repair SSBs in PNKP-deficient cells, but the critical HDR protein Rad51 is not required in PNKP-null (pnk1Δ cells of Schizosaccharomyces pombe. Here, we report that pnk1Δ cells have enhanced requirements for Rad3 (ATR/Mec1 and Chk1 checkpoint kinases, and the multi-BRCT domain protein Brc1 that binds phospho-histone H2A (γH2A at damaged replication forks. The viability of pnk1Δ cells depends on Mre11 and Ctp1 (CtIP/Sae2 double-strand break (DSB resection proteins, Rad52 DNA strand annealing protein, Mus81-Eme1 Holliday junction resolvase, and Rqh1 (BLM/WRN/Sgs1 DNA helicase. Coupled with increased sister chromatid recombination and Rad52 repair foci in pnk1Δ cells, these findings indicate that lingering SSBs in pnk1Δ cells trigger Rad51-independent homology-directed repair of collapsed replication forks. From these data, we propose models for HDR-mediated tolerance of persistent SSBs with 3' phosphate in pnk1Δ cells.

Specific inhibition of Wee1 kinase and Rad51 recombinase: A strategy to enhance the sensitivity of leukemic T-cells to ionizing radiation-induced DNA double-strand breaks

International Nuclear Information System (INIS)

Havelek, Radim; Cmielova, Jana; Kralovec, Karel; Bruckova, Lenka; Bilkova, Zuzana; Fousova, Ivana; Sinkorova, Zuzana; Vavrova, Jirina; Rezacova, Martina

2014-01-01

Highlights: • Pre-treatment with the inhibitors increased the sensitivity of Jurkat cells to irradiation. • Combining both inhibitors together resulted in a G2 cell cycle arrest abrogation in Jurkat. • Jurkat cells pre-treated with inhibitors were positive for γH2AX foci 24 h upon irradiation. • Pre-treatment with Rad51 RI-1 had no effect on apoptosis induction in MOLT-4 cells. • When dosed together, the combination decreased MOLT-4 cell survival. - Abstract: Present-day oncology sees at least two-thirds of cancer patients receiving radiation therapy as a part of their anticancer treatment. The objectives of the current study were to investigate the effects of the small molecule inhibitors of Wee1 kinase II (681641) and Rad51 (RI-1) on cell cycle progression, DNA double-strand breaks repair and apoptosis following ionizing radiation exposure in human leukemic T-cells Jurkat and MOLT-4. Pre-treatment with the Wee1 681641 or Rad51 RI-1 inhibitor alone increased the sensitivity of Jurkat cells to irradiation, however combining both inhibitors together resulted in a further enhancement of apoptosis. Jurkat cells pre-treated with inhibitors were positive for γH2AX foci 24 h upon irradiation. MOLT-4 cells were less affected by inhibitors application prior to ionizing radiation exposure. Pre-treatment with Rad51 RI-1 had no effect on apoptosis induction; however Wee1 681641 increased ionizing radiation-induced cell death in MOLT-4 cells

Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament.

KAUST Repository

Fornander, Louise H; Renodon-Corniè re, Axelle; Kuwabara, Naoyuki; Ito, Kentaro; Tsutsui, Yasuhiro; Shimizu, Toshiyuki; Iwasaki, Hiroshi; Nordé n, Bengt; Takahashi, Masayuki

2013-01-01

The Swi5-Sfr1 heterodimer protein stimulates the Rad51-promoted DNA strand exchange reaction, a crucial step in homologous recombination. To clarify how this accessory protein acts on the strand exchange reaction, we have analyzed how the structure

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.

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

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.

Mimivirus reveals Mre11/Rad50 fusion proteins with a sporadic distribution in eukaryotes, bacteria, viruses and plasmids

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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.

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.

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

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

Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype

DEFF Research Database (Denmark)

Figueroa, Jonine D; Garcia-Closas, Montserrat; Humphreys, Manjeet

2011-01-01

A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer As...

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...

Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype

DEFF Research Database (Denmark)

Figueroa, Jonine D; Garcia-Closas, Montserrat; Humphreys, Manjeet

2011-01-01

for tumors of lower grade (case-only P= 6.7 × 10(-3)) and lobular histology (case-only P= 0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling......A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer......10483813 (r(2)= 0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11...

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...

Localization of recombination proteins and Srs2 reveals anti-recombinase function in vivo

DEFF Research Database (Denmark)

Burgess, Rebecca C; Lisby, Michael; Altmannova, Veronika

2009-01-01

, and surprisingly, can form in the absence of Rad52 mediation. However, these Rad51 foci do not represent repair-proficient filaments, as determined by recombination assays. Antagonistic roles for Rad52 and Srs2 in Rad51 filament formation are also observed in vitro. Furthermore, we provide evidence that Srs2......Homologous recombination (HR), although an important DNA repair mechanism, is dangerous to the cell if improperly regulated. The Srs2 "anti-recombinase" restricts HR by disassembling the Rad51 nucleoprotein filament, an intermediate preceding the exchange of homologous DNA strands. Here, we...... removes Rad51 indiscriminately from DNA, while the Rad52 protein coordinates appropriate filament reformation. This constant breakdown and rebuilding of filaments may act as a stringent quality control mechanism during HR....

Structure of the hDmc1-ssDNA filament reveals the principles of its architecture.

Directory of Open Access Journals (Sweden)

Andrei L Okorokov

Full Text Available In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1, a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active and compressed (inactive. However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds DNA nucleoprotein filaments, the extended (active state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers

Accuracy of CESM versus conventional mammography and ultrasound in evaluation of BI-RADS 3 and 4 breast lesions with pathological correlation

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Maha Helal

2017-09-01

Full Text Available Aim: Assess accuracy of contrast enhanced spectral mammography (CESM versus conventional mammography and ultrasound in evaluation of BI-RADS 3 and 4 breast lesions with pathological correlation. Patients and methods: Thirty female patients with 35 breast lesions diagnosed by conventional imaging as BI-RADS 3 and 4, presented to Women’s Imaging Unit of Radiology Department between January and December 2015, age ranged from 23 to 70 years. All patients underwent conventional mammography and ultrasound then CESM. Results: Patients divided into two groups, benign and malignant lesions group according to histological analysis. Mammography results that malignant lesions detected in 18/35 (51.4% while benign lesions 17/35 (48.6%. Ultrasound revealed 27/35 (77.1% lesions were malignant and 8/35 (22.9% lesions benign. But CESM, revealed 25/35 (71.4% lesions were malignant & 10/35 (28.6% lesions benign. Among 7 patients with multifocal/ multi-centric histologically proven malignant lesions, all detected by CESM 7/7 cases (100% versus 2/7 cases (28.6% and 6/7 cases (85.7% detected by mammography and ultrasound respectively. Based on, CESM had 95.2% sensitivity and 82.9% diagnostic accuracy. Conclusion: CESM has better diagnostic accuracy than mammography alone and mammography plus ultrasound. CESM has 82.9% diagnostic accuracy in comparison to 51.4% for mammography and 77.1% for ultrasound. Keywords: Breast lesions, CESM, BI-RADS lexicon

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.

The role of the Mre11–Rad50–Nbs1 complex in double-strand break repair—facts and myths

International Nuclear Information System (INIS)

Takeda, Shunichi; Hoa, Nguyen Ngoc; Sasanuma, Hiroyuki

2016-01-01

Homologous recombination (HR) initiates double-strand break (DSB) repair by digesting 5′-termini at DSBs, the biochemical reaction called DSB resection, during which DSBs are processed by nucleases to generate 3′ single-strand DNA. Rad51 recombinase polymerizes along resected DNA, and the resulting Rad51–DNA complex undergoes homology search. Although DSB resection by the Mre11 nuclease plays a critical role in HR in Saccharomyces cerevisiae, it remains elusive whether DSB resection by Mre11 significantly contributes to HR-dependent DSB repair in mammalian cells. Depletion of Mre11 decreases the efficiency of DSB resection only by 2- to 3-fold in mammalian cells. We show that although Mre11 is required for efficient HR-dependent repair of ionizing-radiation–induced DSBs, Mre11 is largely dispensable for DSB resection in both chicken DT40 and human TK6 B cell lines. Moreover, a 2- to 3-fold decrease in DSB resection has virtually no impact on the efficiency of HR. Thus, although a large number of researchers have reported the vital role of Mre11-mediated DSB resection in HR, the role may not explain the very severe defect in HR in Mre11-deficient cells, including their lethality. We here show experimental evidence for the additional roles of Mre11 in (i) elimination of chemical adducts from DSB ends for subsequent DSB repair, and (ii) maintaining HR intermediates for their proper resolution

In Vivo Delivery of miR-34a Sensitizes Lung Tumors to Radiation Through RAD51 Regulation

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Maria Angelica Cortez

2015-01-01

Full Text Available MiR-34a, an important tumor-suppressing microRNA, is downregulated in several types of cancer; loss of its expression has been linked with unfavorable clinical outcomes in non-small-cell lung cancer (NSCLC, among others. MiR-34a represses several key oncogenic proteins, and a synthetic mimic of miR-34a is currently being tested in a cancer trial. However, little is known about the potential role of miR-34a in regulating DNA damage response and repair. Here, we demonstrate that miR-34a directly binds to the 3’ untranslated region of RAD51 and regulates homologous recombination, inhibiting double-strand-break repair in NSCLC cells. We further demonstrate the therapeutic potential of miR-34a delivery in combination with radiotherapy in mouse models of lung cancer. Collectively, our results suggest that administration of miR-34a in combination with radiotherapy may represent a novel strategy for treating NSCLC.

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

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

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.

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

Sensing Conformational Changes in DNA upon Ligand Binding Using QCM-D. Polyamine Condensation and Rad51 Extension of DNA Layers

KAUST Repository

Sun, Lu

2014-10-16

© 2014 American Chemical Society. Biosensors, in which binding of ligands is detected through changes in the optical or electrochemical properties of a DNA layer confined to the sensor surface, are important tools for investigating DNA interactions. Here, we investigate if conformational changes induced in surface-attached DNA molecules upon ligand binding can be monitored by the quartz crystal microbalance with dissipation (QCM-D) technique. DNA duplexes containing 59-184 base pairs were formed on QCM-D crystals by stepwise assembly of synthetic oligonucleotides of designed base sequences. The DNA films were exposed to the cationic polyamines spermidine and spermine, known to condense DNA molecules in bulk experiments, or to the recombination protein Rad51, known to extend the DNA helix. The binding and dissociation of the ligands to the DNA films were monitored in real time by measurements of the shifts in resonance frequency (Δf) and in dissipation (ΔD). The QCM-D data were analyzed using a Voigt-based model for the viscoelastic properties of polymer films in order to evaluate how the ligands affect thickness and shear viscosity of the DNA layer. Binding of spermine shrinks all DNA layers and increases their viscosity in a reversible fashion, and so does spermidine, but to a smaller extent, in agreement with its lower positive charge. SPR was used to measure the amount of bound polyamines, and when combined with QCM-D, the data indicate that the layer condensation leads to a small release of water from the highly hydrated DNA films. The binding of Rad51 increases the effective layer thickness of a 59bp film, more than expected from the know 50% DNA helix extension. The combined results provide guidelines for a QCM-D biosensor based on ligand-induced structural changes in DNA films. The QCM-D approach provides high discrimination between ligands affecting the thickness and the structural properties of the DNA layer differently. The reversibility of the film

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

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.

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

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.

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.

Protein dynamics during presynaptic complex assembly on individual ssDNA molecules

Science.gov (United States)

Gibb, Bryan; Ye, Ling F.; Kwon, YoungHo; Niu, Hengyao; Sung, Patrick; Greene, Eric C.

2014-01-01

Homologous recombination is a conserved pathway for repairing double–stranded breaks, which are processed to yield single–stranded DNA overhangs that serve as platforms for presynaptic complex assembly. Here we use single–molecule imaging to reveal the interplay between Saccharomyce cerevisiae RPA, Rad52, and Rad51 during presynaptic complex assembly. We show that Rad52 binds RPA–ssDNA and suppresses RPA turnover, highlighting an unanticipated regulatory influence on protein dynamics. Rad51 binding extends the ssDNA, and Rad52–RPA clusters remain interspersed along the presynaptic complex. These clusters promote additional binding of RPA and Rad52. Together, our work illustrates the spatial and temporal progression of RPA and Rad52 association with the presynaptic complex, and reveals a novel RPA–Rad52–Rad51–ssDNA intermediate, which has implications for understanding how the activities of Rad52 and RPA are coordinated with Rad51 during the later stages recombination. PMID:25195049

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.

CRA-1 uncovers a double-strand break-dependent pathway promoting the assembly of central region proteins on chromosome axes during C. elegans meiosis.

Science.gov (United States)

Smolikov, Sarit; Schild-Prüfert, Kristina; Colaiácovo, Mónica P

2008-06-06

The synaptonemal complex (SC), a tripartite proteinaceous structure that forms between homologous chromosomes during meiosis, is crucial for faithful chromosome segregation. Here we identify CRA-1, a novel and conserved protein that is required for the assembly of the central region of the SC during C. elegans meiosis. In the absence of CRA-1, central region components fail to extensively localize onto chromosomes at early prophase and instead mostly surround the chromatin at this stage. Later in prophase, central region proteins polymerize along chromosome axes, but for the most part fail to connect the axes of paired homologous chromosomes. This defect results in an inability to stabilize homologous pairing interactions, altered double-strand break (DSB) repair progression, and a lack of chiasmata. Surprisingly, DSB formation and repair are required to promote the polymerization of the central region components along meiotic chromosome axes in cra-1 mutants. In the absence of both CRA-1 and any one of the C. elegans homologs of SPO11, MRE11, RAD51, or MSH5, the polymerization observed along chromosome axes is perturbed, resulting in the formation of aggregates of the SC central region proteins. While radiation-induced DSBs rescue this polymerization in cra-1; spo-11 mutants, they fail to do so in cra-1; mre-11, cra-1; rad-51, and cra-1; msh-5 mutants. Taken together, our studies place CRA-1 as a key component in promoting the assembly of a tripartite SC structure. Moreover, they reveal a scenario in which DSB formation and repair can drive the polymerization of SC components along chromosome axes in C. elegans.

Multiple instances of paraphyletic species and cryptic taxa revealed by mitochondrial and nuclear RAD data for Calandrella larks (Aves: Alaudidae).

Science.gov (United States)

Stervander, Martin; Alström, Per; Olsson, Urban; Ottosson, Ulf; Hansson, Bengt; Bensch, Staffan

2016-09-01

The avian genus Calandrella (larks) was recently suggested to be non-monophyletic, and was divided into two genera, of which Calandrella sensu stricto comprises 4-5 species in Eurasia and Africa. We analysed mitochondrial cytochrome b (cytb) and nuclear Restriction-site Associated DNA (RAD) sequences from all species, and for cytb we studied 21 of the 22 recognised subspecies, with the aim to clarify the phylogenetic relationships within the genus and to compare large-scale nuclear sequence patterns with a widely used mitochondrial marker. Cytb indicated deep splits among the currently recognised species, although it failed to support the interrelationships among most of these. It also revealed unexpected deep divergences within C. brachydactyla, C. blanfordi/C. erlangeri, C. cinerea, and C. acutirostris. It also suggested that both C. brachydactyla and C. blanfordi, as presently circumscribed, are paraphyletic. In contrast, most of the many subspecies of C. brachydactyla and C. cinerea were unsupported by cytb, although two populations of C. cinerea were found to be genetically distinct. The RAD data corroborated the cytb tree (for the smaller number of taxa analysed) and recovered strongly supported interspecific relationships. However, coalescence analyses of the RAD data, analysed in SNAPP both with and without an outgroup, received equally strong support for two conflicting topologies. We suggest that the tree rooted with an outgroup - which is not recommended for SNAPP - is more trustworthy, and suggest that the reliability of analyses performed without any outgroup species should be thoroughly evaluated. We also demonstrate that degraded museum samples can be phylogenetically informative in RAD analyses following careful bioinformatic treatment. We note that the genus Calandrella is in need of taxonomic revision. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Schizosaccharomyces pombe Mms1 channels repair of perturbed replication into Rhp51 independent homologous recombination

DEFF Research Database (Denmark)

Vejrup-Hansen, Rasmus; Mizuno, Ken'Ichi; Miyabe, Izumi

2011-01-01

-like protein, Rtt101/Cul8, a potential paralog of Cullin 4. We performed epistasis analysis between ¿mms1 and mutants of pathways with known functions in genome integrity, and measured the recruitment of homologous recombination proteins to blocked replication forks and recombination frequencies. We show that......-specific replication fork barrier and that, in a ¿mms1 strain, Rad22(Rad52) and RPA recruitment to blocked forks are reduced, whereas Rhp51 recruitment is unaffected. In addition, Mms1 appears to specifically promote chromosomal rearrangements in a recombination assay. These observations suggest that Mms1 acts...... is particularly important when a single strand break is converted into a double strand break during replication. Genetic data connect Mms1 to a Mus81 and Rad22(Rad52) dependent, but Rhp51 independent, branch of homologous recombination. This is supported by results demonstrating that Mms1 is recruited to a site...

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.

Polymerization of nitrogen in cesium azide under modest pressure

Energy Technology Data Exchange (ETDEWEB)

Wang, Xiaoli, E-mail: use126126@126.com, E-mail: lijianfu@lyu.edu.cn [Institute of Condensed Matter Physics, Linyi University, Linyi 276005 (China); Beijing Computational Science Research Center, Beijing 100084 (China); State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun 130012 (China); Li, Jianfu, E-mail: use126126@126.com, E-mail: lijianfu@lyu.edu.cn [Institute of Condensed Matter Physics, Linyi University, Linyi 276005 (China); Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); Zhu, Hongyang [State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun 130012 (China); Chen, Li [Institute of Condensed Matter Physics, Linyi University, Linyi 276005 (China); Lin, Haiqing [Beijing Computational Science Research Center, Beijing 100084 (China)

2014-07-28

Alkali metal azides can be used as starting materials in the synthesis of polymeric nitrogen, a potential high-energy-density material. The structural evolutionary behaviors of nitrogen in CsN{sub 3} have been studied up to 200 GPa using particle swarm optimization structure search combining with density functional theory. Three stable new phases with C2/m, P2{sub 1}/m, and P-1 structure at pressure of 6, 13, and 51 GPa are identified for the first time. The phase transition to chain like structure (P-1 phase) occurs at a modest pressure 51 GPa, the azide ions N{sub 3}{sup −} (linear chains of three N atoms with covalent bonds and interact weakly with each other) begin to show remarkable polymeric N properties in the CsN{sub 3} system. Throughout the stable pressure range, the structure is metallic and consists of N atoms in sp{sup 2} hybridizations. Our study completes the structural evolution of CsN{sub 3} under pressure and reveals that the introduced Cs atoms are responsible for the decreased synthesis pressure comparing to pure molecular nitrogen under compression.

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.

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

Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients with Gastric Cancer

Science.gov (United States)

Sahasrabudhe, Ruta; Lott, Paul; Bohorquez, Mabel; Toal, Ted; Estrada, Ana P.; Suarez, John J.; Brea-Fernández, Alejandro; Cameselle-Teijeiro, José; Pinto, Carla; Ramos, Irma; Mantilla, Alejandra; Prieto, Rodrigo; Corvalan, Alejandro; Norero, Enrique; Alvarez, Carolina; Tapia, Teresa; Carvallo, Pilar; Gonzalez, Luz M.; Cock-Rada, Alicia; Solano, Angela; Neffa, Florencia; Valle, Adriana Della; Yau, Chris; Soares, Gabriela; Borowsky, Alexander; Hu, Nan; He, Li-Ji; Han, Xiao-You; Taylor, Philip R.; Goldstein, Alisa M.; Torres, Javier; Echeverry, Magdalena; Ruiz-Ponte, Clara; Teixeira, Manuel R.; Carvajal Carmona, Luis G.

2016-01-01

Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer. PMID:28024868

Molecular weights distribution and temperature effects in the styrene polymerization initiated with gamma rays

International Nuclear Information System (INIS)

Burillo, G.; Martinez, R.

1979-01-01

The polymerization of styrene irradiated in a 60 CO source to 18 0 C temperature and to 70 0 C temperature was studied, in order to reduce the irradiation time raising the polymerization rate and looking for a highest molecular weight. The radiation doses used were from 0.2 to 33.26 Mrad, at the rate of 56 rad/sec, the percent of polymerization and the molecular weight formed were determined, the results indicate one highest molecular weight of 132,700 when the radiation dose of 20 Mrad and the temperature of 20 0 C were used, and one of 395,000 when the irradiation is carried out to 70 0 C. (author)

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.

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

Radiation-induced emulsion polymerization of tetrafluoroethylene

International Nuclear Information System (INIS)

Suwa, Takeshi

1979-10-01

The radiation-induced emulsifier-free emulsion polymerization of tetrafluoroethylene (TFE) has been studied at initial pressure 2 - 25 kg/cm 2 and temperature 30 0 - 110 0 C for dose rate 0.57 x 10 4 - 3.0 x 10 4 rad/hr. Polytetrafluoroethylene (PTFE), a hydrophobic polymer, forms as a stable latex in the absence of an emulsifier. Stability of the latex is governed by the dose rate/TFE pressure ratio; it increases with sufficient TFE monomer. PTFE particles produced in this polymerization system are stable due to the carboxyl end groups and adsorption of OH - and HF on the particles. PTFE latex of molecular weight higher than 2 x 10 7 is obtained by addition of a radical scavenger such as hydroquinone. The molecular weight of PTFE can be measured from the heat of crystallization conveniently with high reliability, which was found in the course of study on the melting and crystallization behavior. (author)

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.

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)

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...

Single Turnover at Molecular Polymerization Catalysts Reveals Spatiotemporally Resolved Reactions.

Science.gov (United States)

Easter, Quinn T; Blum, Suzanne A

2017-10-23

Multiple active individual molecular ruthenium catalysts have been pinpointed within growing polynorbornene, thereby revealing information on the reaction dynamics and location that is unavailable through traditional ensemble experiments. This is the first single-turnover imaging of a molecular catalyst by fluorescence microscopy and allows detection of individual monomer reactions at an industrially important molecular ruthenium ring-opening metathesis polymerization (ROMP) catalyst under synthetically relevant conditions (e.g. unmodified industrial catalyst, ambient pressure, condensed phase, ca. 0.03 m monomer). These results further establish the key fundamentals of this imaging technique for characterizing the reactivity and location of active molecular catalysts even when they are the minor components. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

Three new genetic loci (R1210C in CFH, variants in COL8A1 and RAD51B are independently related to progression to advanced macular degeneration.

Directory of Open Access Journals (Sweden)

Johanna M Seddon

Full Text Available To assess the independent impact of new genetic variants on conversion to advanced stages of AMD, controlling for established risk factors, and to determine the contribution of genes in predictive models.In this prospective longitudinal study of 2765 individuals, 777 subjects progressed to neovascular disease (NV or geographic atrophy (GA in either eye over 12 years. Recently reported genetic loci were assessed for their independent effects on incident advanced AMD after controlling for 6 established loci in 5 genes, and demographic, behavioral, and macular characteristics. New variants which remained significantly related to progression were then added to a final multivariate model to assess their independent effects. The contribution of genes to risk models was assessed using reclassification tables by determining risk within cross-classified quintiles for alternative models.THREE NEW GENETIC VARIANTS WERE SIGNIFICANTLY RELATED TO PROGRESSION: rare variant R1210C in CFH (hazard ratio (HR 2.5, 95% confidence interval [CI] 1.2-5.3, P = 0.01, and common variants in genes COL8A1 (HR 2.0, 95% CI 1.1-3.5, P = 0.02 and RAD51B (HR 0.8, 95% CI 0.60-0.97, P = 0.03. The area under the curve statistic (AUC was significantly higher for the 9 gene model (.884 vs the 0 gene model (.873, P = .01. AUC's for the 9 vs 6 gene models were not significantly different, but reclassification analyses indicated significant added information for more genes, with adjusted odds ratios (OR for progression within 5 years per one quintile increase in risk score of 2.7, P<0.001 for the 9 vs 6 loci model, and OR 3.5, P<0.001 for the 9 vs. 0 gene model. Similar results were seen for NV and GA.Rare variant CFH R1210C and common variants in COL8A1 and RAD51B plus six genes in previous models contribute additional predictive information for advanced AMD beyond macular and behavioral phenotypes.

Protein dynamics during presynaptic complex assembly on individual ssDNA molecules

OpenAIRE

Gibb, Bryan; Ye, Ling F.; Kwon, YoungHo; Niu, Hengyao; Sung, Patrick; Greene, Eric C.

2014-01-01

Homologous recombination is a conserved pathway for repairing double?stranded breaks, which are processed to yield single?stranded DNA overhangs that serve as platforms for presynaptic complex assembly. Here we use single?molecule imaging to reveal the interplay between Saccharomyce cerevisiae RPA, Rad52, and Rad51 during presynaptic complex assembly. We show that Rad52 binds RPA?ssDNA and suppresses RPA turnover, highlighting an unanticipated regulatory influence on protein dynamics. Rad51 b...

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

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.

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

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

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

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.

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.

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...

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)

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)

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

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.

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

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

Epidermal growth factor receptor (EGFR mutation status and Rad51 determine the response of glioblastoma (GBM to multimodality therapy with cetuximab, temozolomide and radiation

Directory of Open Access Journals (Sweden)

Phyllis Rachelle Wachsberger

2013-02-01

Full Text Available Purpose: EGFR amplification and mutation (i.e., EGFRvIII are found in 40% of primary GBM tumors and are believed to contribute to tumor development and therapeutic resistance. This study was designed to investigate how EGFR mutational status modulates response to multimodality treatment with cetuximab, an anti-EGFR inhibitor, the chemotherapeutic agent, temozolamide (TMZ and radiation therapy (RT Methods and Materials: In vitro and in vivo experiments were performed on two isogenic U87 GBM cell lines: one overexpressing wildtype EGFR (U87wtEGFR and the other overexpressing EGFRvIII (U87EGFRvIII. Results: Xenografts harboring EGFRvIII were more sensitive to TMZ alone and TMZ in combination with RT and/or cetuximab than xenografts expressing wtEGFR. In vitro experiments demonstrated that U87EGFRvIII-expressing tumors appear to harbor defective DNA homologous recombination repair in the form of Rad51 processing, Conclusions: The difference in sensitivity between EGFR-expressing and EGFRvIII-expressing tumors to combined modality treatment may help in the future tailoring of GBM therapy to subsets of patients expressing more or less of the EGFR mutant.

Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability

DEFF Research Database (Denmark)

Galanos, Panagiotis; Pappas, George; Polyzos, Alexander

2018-01-01

. Consequently, fewer single nucleotide substitutions (SNSs) occur, while formation of highly deleterious DNA double-strand breaks (DSBs) is enhanced, crafting a characteristic mutational signature landscape. Guided by the mutational signatures formed, we find that the DSBs are repaired by Rad52-dependent break...

Molecular Pathways

Science.gov (United States)

Lok, Benjamin H.; Powell, Simon N.

2012-01-01

The Rad52 protein was largely ignored in humans and other mammals when the mouse knockout revealed a largely “no-effect” phenotype. However, using synthetic lethal approaches to investigate context dependent function, new studies have shown that Rad52 plays a key survival role in cells lacking the function of the BRCA1-BRCA2 pathway of homologous recombination. Biochemical studies also showed significant differences between yeast and human Rad52, in which yeast Rad52 can promote strand invasion of RPA-coated single-stranded DNA in the presence of Rad51, but human Rad52 cannot. This results in the paradox of how is human Rad52 providing Rad51 function: presumably there is something missing in the biochemical assays that exists in-vivo, but the nature of this missing factor is currently unknown. Recent studies have suggested that Rad52 provides back-up Rad51 function for all members of the BRCA1-BRCA2 pathway, suggesting that Rad52 may be a target for therapy in BRCA pathway deficient cancers. Screening for ways to inhibit Rad52 would potentially provide a complementary strategy for targeting BRCA-deficient cancers in addition to PARP inhibitors. PMID:23071261

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...

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.

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.

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.

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...

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

An integrated in silico approach to analyze the involvement of single amino acid polymorphisms in FANCD1/BRCA2-PALB2 and FANCD1/BRCA2-RAD51 complex.

Science.gov (United States)

Doss, C George Priya; Nagasundaram, N

2014-11-01

Fanconi anemia (FA) is an autosomal recessive human disease characterized by genomic instability and a marked increase in cancer risk. The importance of FANCD1 gene is manifested by the fact that deleterious amino acid substitutions were found to confer susceptibility to hereditary breast and ovarian cancers. Attaining experimental knowledge about the possible disease-associated substitutions is laborious and time consuming. The recent introduction of genome variation analyzing in silico tools have the capability to identify the deleterious variants in an efficient manner. In this study, we conducted in silico variation analysis of deleterious non-synonymous SNPs at both functional and structural level in the breast cancer and FA susceptibility gene BRCA2/FANCD1. To identify and characterize deleterious mutations in this study, five in silico tools based on two different prediction methods namely pathogenicity prediction (SIFT, PolyPhen, and PANTHER), and protein stability prediction (I-Mutant 2.0 and MuStab) were analyzed. Based on the deleterious scores that overlap in these in silico approaches, and the availability of three-dimensional structures, structure analysis was carried out with the major mutations that occurred in the native protein coded by FANCD1/BRCA2 gene. In this work, we report the results of the first molecular dynamics (MD) simulation study performed to analyze the structural level changes in time scale level with respect to the native and mutated protein complexes (G25R, W31C, W31R in FANCD1/BRCA2-PALB2, and F1524V, V1532F in FANCD1/BRCA2-RAD51). Analysis of the MD trajectories indicated that predicted deleterious variants alter the structural behavior of BRCA2-PALB2 and BRCA2-RAD51 protein complexes. In addition, statistical analysis was employed to test the significance of these in silico tool predictions. Based on these predictions, we conclude that the identification of disease-related SNPs by in silico methods, in combination with MD

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,...

Radiation-induced polymerization of water-saturated styrene in a wide range of dose rate

International Nuclear Information System (INIS)

Takezaki, J.; Okada, T.; Sakurada, I.

1978-01-01

Radiation-induced polymerization of water-saturated styrene (water content 3.5 x 10 -2 mole/liter) was carried out in a wide range of dose rate between 1.2 x 10 3 and 1.8 x 10 7 rad/sec, and compared with the polymerization of the moderately dried styrene (water content 3.2 x 10 -3 mole/liter). Molecular weight distribution curves of the polymerization products showed that they were generally consisted of four parts, namely, oligomers, radical, cationic, and super polymers. Contributions of the four constituents to the polymerization and the number average degrees of polymerization (DP) of the four kinds of polymers were calculated by the graphical analysis of the curves. The rate of radical polymerization and DP of radical polymers are independent of the water content; the dose rate dependences of the polymerization rate and DP agree with the well known square root and inverse square root laws, respectively, of the radical polymerization of styrene. The rate of ionic polymerization is directly proportional to the dose rate, but it decreases, at a given dose rate, inversely proportional to the water content of styrene. DP of ionic polymer is independent of the dose rate but decreases with increasing water content. The super polymer of DP about 10 4 is not formed in the case of the moderately dried styrene. G values for the initiating radical and ion formation are calculated to be independently of the dose rate and water content, 0.66 and 0.027, respectively. It was suggested that oligomer was formed in the early stage by the interaction of cation with anion and only those cations which had survived underwent polymerization. 10 figures, 4 tables

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.

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.

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.

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.

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.

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

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

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

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)

Detection of Salmonella typhi utilizing bioconjugated fluorescent polymeric nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Jain, Swati, E-mail: swatijain.iitd@gmail.com; Chattopadhyay, Sruti, E-mail: sruticiitd@gmail.com; Jackeray, Richa; Abid, Zainul; Singh, Harpal, E-mail: harpal2000@yahoo.com [Centre for Biomedical Engineering, Indian Institute of Technology-Delhi (India)

2016-05-15

Present work demonstrates effective utilization of functionalized polymeric fluorescent nanoparticles as biosensing probe for the detection of Salmonella typhi bacteria on modified polycarbonate (PC) filters in about 3 h. Antibody modified-PC membranes were incubated with contaminated bacterial water for selective capturing which were detected by synthesized novel bioconjugate probe. Core–shell architecture of polymeric nanoparticles endows them with aqueous stabilization and keto-enolic functionalities making them usable for covalently linking S. typhi antibodies without any crosslinker or activator. Bradford analysis revealed that one nanoparticle has an average of 3.51 × 10{sup −19} g or 21 × 10{sup 4} bound S. typhi Ab molecules. Analysis of the regions of interest (ROI) in fluorescent micrographs of modified fluoroimmunoassay showed higher detection sensitivity of 5 × 10{sup 2} cells/mL due to signal amplification unlike conventional naked dye FITC-Ab conjugate. Fluorescence of pyrene dye remained same on immobilization of biomolecules and nanoparticles showed stable fluorescent intensity under prolong exposure to laser owing to protective polymeric layer allowing accurate identification of bacteria. Surface-functionalized PC matrix and fluorescent label NPs permit covalent interactions among biomolecules enhancing signal acquisitions showing higher detection efficiency as compared to conventional microtiter plate-based system. Our novel immunoassay has the potential to be explored as rapid detection method for identifying S. typhi contaminations in water.Graphical Abstract.

Detection of Salmonella typhi utilizing bioconjugated fluorescent polymeric nanoparticles

International Nuclear Information System (INIS)

Jain, Swati; Chattopadhyay, Sruti; Jackeray, Richa; Abid, Zainul; Singh, Harpal

2016-01-01

Present work demonstrates effective utilization of functionalized polymeric fluorescent nanoparticles as biosensing probe for the detection of Salmonella typhi bacteria on modified polycarbonate (PC) filters in about 3 h. Antibody modified-PC membranes were incubated with contaminated bacterial water for selective capturing which were detected by synthesized novel bioconjugate probe. Core–shell architecture of polymeric nanoparticles endows them with aqueous stabilization and keto-enolic functionalities making them usable for covalently linking S. typhi antibodies without any crosslinker or activator. Bradford analysis revealed that one nanoparticle has an average of 3.51 × 10"−"1"9 g or 21 × 10"4 bound S. typhi Ab molecules. Analysis of the regions of interest (ROI) in fluorescent micrographs of modified fluoroimmunoassay showed higher detection sensitivity of 5 × 10"2 cells/mL due to signal amplification unlike conventional naked dye FITC-Ab conjugate. Fluorescence of pyrene dye remained same on immobilization of biomolecules and nanoparticles showed stable fluorescent intensity under prolong exposure to laser owing to protective polymeric layer allowing accurate identification of bacteria. Surface-functionalized PC matrix and fluorescent label NPs permit covalent interactions among biomolecules enhancing signal acquisitions showing higher detection efficiency as compared to conventional microtiter plate-based system. Our novel immunoassay has the potential to be explored as rapid detection method for identifying S. typhi contaminations in water.Graphical Abstract

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.

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

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...

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.

Some regularities of separate and simultaneous radiation polymerization of vinyl acetate and acrylonitrile in adsorption layer on aerosil surface

International Nuclear Information System (INIS)

Mund, S.L.; Bruk, M.A.; Abkin, A.D.

1976-01-01

The kinetics has been studied of initial stage radiation copolymerization and separate radiation polymerization of aerosil adsorbed vinylacetate (VA) and acrylonitrile (AN). The monomers were irradiated using a Co 60 gamma source or a RUP-400 X-ray unit. Infrared spectroscopy, nuclear magnetic resonance and gravimetry were used in the study. It has been found that in the dose rate interval studied (over 60-450 rad./sec) the break of kinetic chains during the polymerization of VA and its mixtures with AN is due to the reaction of degenerate transfer of the chains to the surface hydroxyl groups. When AN is polymerized, biomolecular break of chains prevails. The effective activation energy of polymerization is 1.5 kcal/mol for VA and 2.5 kcal/mol for AN. The order of polymerization rates by the concentration of adsorbed monomers at 50 deg, as well as by the irradiation dose rate is equal to 1 and 1 for VA and 3/2 and 0.7 for AN, respectively. The calculated values of copolymerization constants coincide with those characteristic of their radical polymerization in liquid phase. Isotherms for adsorption of VA and AN on aerosil at 30, 50 and 70 deg have been studied [ru

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.

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.

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.

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,...

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

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 - .

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

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.

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.

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.

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

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.

Experimental conditions affecting the kinetics of aqueous HCN polymerization as revealed by UV-vis spectroscopy.

Science.gov (United States)

Marín-Yaseli, Margarita R; Moreno, Miguel; de la Fuente, José L; Briones, Carlos; Ruiz-Bermejo, Marta

2018-02-15

HCN polymerization is one of the most important and fascinating reactions in prebiotic chemistry, and interest in HCN polymers in the field of materials science is growing. However, little is known about the kinetics of the HCN polymerization process. In the present study, a first approach to the kinetics of two sets of aqueous HCN polymerizations, from NH 4 CN and NaCN, at middle temperatures between 4 and 38°C, has been carried out. For each series, the presence of air and salts in the reaction medium has been systematically explored. A previous kinetic analysis was conducted during the conversion of the insoluble black HCN polymers obtained as gel fractions in these precipitation polymerizations for a reaction of one month, where a limit conversion was achieved at the highest polymerization temperature. The kinetic description of the gravimetric data for this complex system shows a clear change in the linear dependence with the polymerization temperature for the reaction from NH 4 CN, besides a relevant catalytic effect of ammonium, in comparison with those data obtained from the NaCN series. These results also demonstrated the notable influence of air, oxygen, and the saline medium in HCN polymer formation. Similar conclusions were reached when the sol fractions were monitored by UV-vis spectroscopy, and a Hill type correlation was used to describe the polymerization profiles obtained. This technique was chosen because it provides an easy, prompt and fast method to follow the evolution of the liquid or continuous phase of the process under study. Copyright © 2017 Elsevier B.V. All rights reserved.

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)

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.

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

The effects of polymeric plutonium on erythrocyte survival in mice, (1)

International Nuclear Information System (INIS)

Joshima, Hisamasa; Kashima, Masatoshi; Matsuoka, Osamu

1976-01-01

The changes in erythrocyte counts, hematocrit, hemoglobin, reticulocyte counts and erythrocyte survival following an intravenous injection of polymeric 239 Pu at the dose level of 15 μCi/kg, 10 μCi/kg and 5 μCi/kg were studied in CF no. 1 male mice in order to investigate the possible pathogenesis of anemia produced by irradiation of polymeric plutonium. The administration of 15 μCi/kg and 10 μCi/kg of polymeric plutonium produced anemia but 5 μCi/kg had no significant effect. Studies with 51 Cr labelled erythrocyte showed a moderate reduction in survival of erythrocyte following a single intraveneous injection of polymeric plutonium. Not only the intracorpuscular effect but also extracorpuscular effect of polymeric plutonium was considered to lead to a reduction in erythrocyte survival, but no clear dose relationship could be observed between the reduction of survival and either intracorpuscular effect or extracorpuscular effect. Although the most important pathogenesis of anemia produced by polymeric plutonium is supposed to be a decreased erythropoiesis, it was believed that both qualitatively impaired erythropoiesis and abnormal erythrocyte destruction might also play some role in the occurrence of anemia. (auth.)

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.

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.

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...

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

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.

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

International Nuclear Information System (INIS)

Jansson, Kristina; Warringer, Jonas; Farewell, Anne; Park, Han-Oh; Hoe, Kwang-Lae; Kim, Dong-Uk; Hayles, Jacqueline; Sunnerhagen, Per

2008-01-01

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

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

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

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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.

Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52

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Chin-Chuan Chen

2017-12-01

Full Text Available Effective DNA repair enables cancer cells to survive DNA damage induced by chemotherapeutic or radiotherapeutic treatments. Therefore, inhibiting DNA repair pathways is a promising therapeutic strategy for increasing the efficacy of such treatments. In this study, we found that dihydrocoumarin (DHC, a flavoring agent, causes deficiencies in double-stand break (DSB repair and prolonged DNA damage checkpoint recovery in yeast. Following DNA damage, Rad52 recombinase was revealed to be inhibited by DHC, which results in deficiencies in DSB repair and prolonged DNA damage checkpoint recovery. The deletion of RPD3, a class I histone deacetylase (HDAC, was found to mimic DHC-induced suppression of Rad52 expression, suggesting that the HDAC inhibitor activity of DHC is critical to DSB repair and DNA damage sensitivity. Overall, our findings delineate the regulatory mechanisms of DHC in DSB repair and suggest that it might potentially be used as an inhibitor of the DNA repair pathway in human cells.

Interdependence of the rad50 hook and globular domain functions.

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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.

Differential hRad17 expression by histologic subtype of ovarian cancer

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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.

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

Sensitization of Tumor to 212Pb Radioimmunotherapy by Gemcitabine Involves Initial Abrogation of G2 Arrest and Blocked DNA Damage Repair by Interference With Rad51

International Nuclear Information System (INIS)

Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.

2013-01-01

Purpose: To elucidate the mechanism of the therapeutic efficacy of targeted α-particle radiation therapy using 212 Pb-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers. Methods and Materials: Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by 212 Pb-TCMC-trastuzumab and compared with controls. Results: Treatment with 212 Pb-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). 212 Pb-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation, resulting in apoptosis. 212 Pb-TCMC-trastuzumab treatment after gemcitabine pretreatment caused depression of DNA synthesis, DNA double-strand breaks, accumulation of unrepaired DNA, and down-regulation of Rad51 protein, indicating that DNA damage repair was blocked. In addition, modification in the chromatin structure of p21 may be associated with transcriptionally repressed chromatin states, indicating that the open structure was delayed at earlier time points. Conclusion: These findings suggest that the cell-killing efficacy of 212 Pb-TCMC-trastuzumab after gemcitabine pretreatment may be associated with abrogation of the G2/M checkpoint, inhibition of DNA damage repair, and chromatin remodeling

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)

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.

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

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

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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.

Multiple sex-associated regions and a putative sex chromosome in zebrafish revealed by RAD mapping and population genomics.

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Jennifer L Anderson

Full Text Available Within vertebrates, major sex determining genes can differ among taxa and even within species. In zebrafish (Danio rerio, neither heteromorphic sex chromosomes nor single sex determination genes of large effect, like Sry in mammals, have yet been identified. Furthermore, environmental factors can influence zebrafish sex determination. Although progress has been made in understanding zebrafish gonad differentiation (e.g. the influence of germ cells on gonad fate, the primary genetic basis of zebrafish sex determination remains poorly understood. To identify genetic loci associated with sex, we analyzed F(2 offspring of reciprocal crosses between Oregon *AB and Nadia (NA wild-type zebrafish stocks. Genome-wide linkage analysis, using more than 5,000 sequence-based polymorphic restriction site associated (RAD-tag markers and population genomic analysis of more than 30,000 single nucleotide polymorphisms in our *ABxNA crosses revealed a sex-associated locus on the end of the long arm of chr-4 for both cross families, and an additional locus in the middle of chr-3 in one cross family. Additional sequencing showed that two SNPs in dmrt1 previously suggested to be functional candidates for sex determination in a cross of ABxIndia wild-type zebrafish, are not associated with sex in our AB fish. Our data show that sex determination in zebrafish is polygenic and that different genes may influence sex determination in different strains or that different genes become more important under different environmental conditions. The association of the end of chr-4 with sex is remarkable because, unique in the karyotype, this chromosome arm shares features with known sex chromosomes: it is highly heterochromatic, repetitive, late replicating, and has reduced recombination. Our results reveal that chr-4 has functional and structural properties expected of a sex chromosome.

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)

Split dose recovery studies using homologous recombination deficient gene knockout chicken B lymphocyte cells

International Nuclear Information System (INIS)

Rao, B.S.S.; Tano, Kaori; Utsumi, Hiroshi; Takeda, Shunichi

2007-01-01

To understand the role of proteins involved in double strand breaks (DSB) repair modulating sublethal damage (SLD) recovery, chicken B lymphoma (DT 40) cell lines either proficient or deficient in RAD52, XRCC2, XRCC3, RAD51C and RAD51D were subjected to fractionated irradiation and their survival curves charted. Survival curves of both WT DT40 and RAD52 -/- cells had a big shoulder while all the other cells exhibited small shoulders. However, at the higher doses of radiation, RAD51C -/- cells displayed hypersensitivity comparable to the data obtained for the homologous recombination deficient RAD54 -/- cells. Repair of SLD was measured as an increase in survival after a split dose irradiation with an interval of incubation between the radiation doses. All the cell lines (parental DT40 and genetic knockout cell lines viz., RAD52 -/- , XRCC2 -/- XRCC3 -/- RAD51C -/- and RAD51D -/- ) used in this study demonstrated a typical split-dose recovery capacity with a specific peak, which varied depending on the cell type. The maximum survival of WT DT40 and RAD52 -/- was reached at about 1-2 hours after the first dose of radiation and then decreased to a minimum thereafter (5 h). The increase in the survival peaked once again by about 8 hours. The survival trends observed in XRCC2 -/- , XRCC3 -/- , RAD51C -/- and RAD51D -/- knockout cells were also similar, except for the difference in the initial delay of a peak survival for RAD51D -/- and lower survival ratios. The second phase of increase in the survival in these cell lines was much slower in XRCC2 -/- , XRCC3 -/- , RAD51C -/- nd RAD51D -/- and further delayed when compared with that of RAD52 -/- and parental DT40 cells suggesting a dependence on their cell cycle kinetics. This study demonstrates that the participation of RAD52, XRCC2, XRCC3, RAD51C and RAD51D in the DSB repair via homologous recombination is of less importance in comparison to RAD54, as RAD54 deficient cells demonstrated complete absence of SLD recovery

Validation of the fifth edition BI-RADS ultrasound lexicon with comparison of fourth and fifth edition diagnostic performance using video clips

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Jung Hyun Yoon

2016-10-01

Full Text Available Purpose The aim of this study was to evaluate the positive predictive value (PPV and the diagnostic performance of the ultrasonographic descriptors in the fifth edition of BI-RADS, comparing with the fourth edition using video clips. Methods From September 2013 to July 2014, 80 breast masses in 74 women (mean age, 47.5±10.7 years from five institutions of the Korean Society of Breast Imaging were included. Two radiologists individually reviewed the static and video images and analyzed the images according to the fourth and fifth edition of BI-RADS. The PPV of each descriptor was calculated and diagnostic performances between the fourth and fifth editions were compared. Results Of the 80 breast masses, 51 (63.8% were benign and 29 (36.2% were malignant. Suspicious ultrasonographic features such as irregular shape, non-parallel orientation, angular or spiculated margins, and combined posterior features showed higher PPV in both editions (all P0.05. The area under the receiver operating characteristics curve was higher in the fourth edition (0.708 to 0.690, without significance (P=0.416. Conclusion The fifth edition of the BI-RADS ultrasound lexicon showed comparable performance to the fourth edition and can be useful in the differential diagnosis of breast masses using ultrasonography.

Constructing Functional Ionic Membrane Surface by Electrochemically Mediated Atom Transfer Radical Polymerization

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Fen Ran

2016-01-01

Full Text Available The sodium polyacrylate (PAANa contained polyethersulfone membrane that was fabricated by preparation of PES-NH2 via nonsolvent phase separation method, the introduction of bromine groups as active sites by grafting α-Bromoisobutyryl bromide, and surface-initiated electrochemically atom transfer radical polymerization (SI-eATRP of sodium acrylate (AANa on the surface of PES membrane. The polymerization could be controlled by reaction condition, such as monomer concentration, electric potential, polymerization time, and modifier concentration. The membrane surface was uniform when the monomer concentration was 0.9 mol/L, the electric potential was −0.12 V, the polymerization time was 8 h, and the modifier concentration was 2 wt.%. The membrane showed excellent hydrophilicity and blood compatibility. The water contact angle decreased from 84° to 68° and activated partial thromboplastin increased from 51 s to 84 s after modification of the membranes.

Comparative expression profiling of AtRAD5B and AtNDL1: Hints towards a role in G protein mediated signaling.

Science.gov (United States)

Khatri, Nisha; Singh, Swati; Hakim, Nasmeen; Mudgil, Yashwanti

2017-11-01

Arabidopsis AtRAD5B encodes for a putative helicase of the class SWItch/Sucrose Non-Fermentable (SWI/SNF) ATPases. We identified AtRAD5B as an interactor of N-MYC DOWNREGULATED-LIKE1 (AtNDL1) in a yeast two-hybrid screen. AtNDL1 is a G protein signaling component which regulates auxin transport and gradients together with GTP binding protein beta 1 (AGB1). Auxin gradients are known to recruit SWI/SNF remodeling complexes to the chromatin and regulate expression of genes involved in flower and leaf formation. In current study, a comparative spatial and temporal co-expression/localization analysis of AtNDL1, AGB1 with AtRAD5B was carried out in order to explore the possibility of their coexistence in a common signaling network. Translational fusion (GUS) of AtNDL1 and AtRAD5B in seedlings and reproductive organs revealed that both shared similar expression patterns with the highest expression observed in male reproductive organs. Moreover, they shared similar domains of localization in roots, suggesting their potential functioning together in reproductive and root development processes. This study predicts the existence of a signaling network involving AtNDL1, AGB1 with AtRAD5B. Copyright © 2017 Elsevier B.V. All rights reserved.

The tumor suppressor homolog in fission yeast, myh1{sup +}, displays a strong interaction with the checkpoint gene rad1{sup +}

Energy Technology Data Exchange (ETDEWEB)

Jansson, Kristina; Warringer, Jonas; Farewell, Anne [Department of Cell and Molecular Biology, Lundberg Laboratory, Goeteborg University, P.O. Box 462, Goeteborg SE-405 30 (Sweden); Park, Han-Oh [Bioneer Corporation, 49-3, Munpyeong-dong, Daedeok-gu, Daejon 306-220 (Korea, Republic of); Hoe, Kwang-Lae; Kim, Dong-Uk [Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yusong, Daejeon (Korea, Republic of); Hayles, Jacqueline [Cell Cycle Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln' s Inn Fields, London WC2A 3PX (United Kingdom); Sunnerhagen, Per [Department of Cell and Molecular Biology, Lundberg Laboratory, Goeteborg University, P.O. Box 462, Goeteborg SE-405 30 (Sweden)], E-mail: per.sunnerhagen@cmb.gu.se

2008-09-26

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

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

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.

El radón: ¿riesgo para la salud?

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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.

Mapping of the gynoecy in bitter gourd (Momordica charantia using RAD-seq analysis.

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Hideo Matsumura

Full Text Available Momordica charantia is a monoecious plant of the Cucurbitaceae family that has both male and female unisexual flowers. Its unique gynoecious line, OHB61-5, is essential as a maternal parent in the production of F1 cultivars. To identify the DNA markers for this gynoecy, a RAD-seq (restriction-associated DNA tag sequencing analysis was employed to reveal genome-wide DNA polymorphisms and to genotype the F2 progeny from a cross between OHB61-5 and a monoecious line. Based on a RAD-seq analysis of F2 individuals, a linkage map was constructed using 552 co-dominant markers. In addition, after analyzing the pooled genomic DNA from monoecious or gynoecious F2 plants, several SNP loci that are genetically linked to gynoecy were identified. GTFL-1, the closest SNP locus to the putative gynoecious locus, was converted to a conventional DNA marker using invader assay technology, which is applicable to the marker-assisted selection of gynoecy in M. charantia breeding.

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

Science.gov (United States)

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

2014-01-01

Momordica charantia is a monoecious plant of the Cucurbitaceae family that has both male and female unisexual flowers. Its unique gynoecious line, OHB61-5, is essential as a maternal parent in the production of F1 cultivars. To identify the DNA markers for this gynoecy, a RAD-seq (restriction-associated DNA tag sequencing) analysis was employed to reveal genome-wide DNA polymorphisms and to genotype the F2 progeny from a cross between OHB61-5 and a monoecious line. Based on a RAD-seq analysis of F2 individuals, a linkage map was constructed using 552 co-dominant markers. In addition, after analyzing the pooled genomic DNA from monoecious or gynoecious F2 plants, several SNP loci that are genetically linked to gynoecy were identified. GTFL-1, the closest SNP locus to the putative gynoecious locus, was converted to a conventional DNA marker using invader assay technology, which is applicable to the marker-assisted selection of gynoecy in M. charantia breeding. PMID:24498029

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

DEFF Research Database (Denmark)

Song, Honglin; Dicks, Ed; Ramus, Susan J

2015-01-01

Screening Study (UK_FOCSS) after quality-control analysis. RESULTS: In the case-control study, we identified predicted deleterious mutations in 28 EOC cases (0.82%) compared with three controls (0.11%; P

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.

Sensitization of Tumor to {sup 212}Pb Radioimmunotherapy by Gemcitabine Involves Initial Abrogation of G2 Arrest and Blocked DNA Damage Repair by Interference With Rad51

Energy Technology Data Exchange (ETDEWEB)

Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E. [Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Brechbiel, Martin W., E-mail: martinwb@mail.nih.gov [Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

2013-03-15

Purpose: To elucidate the mechanism of the therapeutic efficacy of targeted α-particle radiation therapy using {sup 212}Pb-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers. Methods and Materials: Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by {sup 212}Pb-TCMC-trastuzumab and compared with controls. Results: Treatment with {sup 212}Pb-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). {sup 212}Pb-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation, resulting in apoptosis. {sup 212}Pb-TCMC-trastuzumab treatment after gemcitabine pretreatment caused depression of DNA synthesis, DNA double-strand breaks, accumulation of unrepaired DNA, and down-regulation of Rad51 protein, indicating that DNA damage repair was blocked. In addition, modification in the chromatin structure of p21 may be associated with transcriptionally repressed chromatin states, indicating that the open structure was delayed at earlier time points. Conclusion: These findings suggest that the cell-killing efficacy of {sup 212}Pb-TCMC-trastuzumab after gemcitabine pretreatment may be associated with abrogation of the G2/M checkpoint, inhibition of DNA damage repair, and chromatin remodeling.

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.

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...

Using a butterflyfish genome as a general tool for RAD-Seq studies in specialized reef fish

KAUST Repository

DiBattista, Joseph; Saenz Agudelo, Pablo; Piatek, Marek J.; Wang, Xin; Aranda, Manuel; Berumen, Michael L.

2017-01-01

Data from a large-scale restriction site associated DNA (RAD-Seq) study of nine butterflyfish species in the Red Sea and Arabian Sea provided a means to test the utility of a recently published draft genome (Chaetodon austriacus) and assess apparent bias in this method of isolating nuclear loci. We here processed double-digest restriction-site (ddRAD) associated DNA sequencing data to identify single nucleotide polymorphism (SNP) markers and their associated function with and without our reference genome to see if it improves the quality of RAD-Seq markers. Our analyses indicate (1) a modest gap between the number of non-annotated versus annotated SNPs across all species, (2) an advantage of using genomic resources for closely related but not distantly related butterflyfish species based on the ability to assign putative gene function to SNPs, and (3) an enrichment of genes among sister butterflyfish taxa related to calcium transmembrane transport and binding. The latter result highlights the potential for this approach to reveal insights into adaptive mechanisms in populations inhabiting challenging coral reef environments such as the Red Sea, Arabian Sea, and Arabian Gulf with further study.

Using a butterflyfish genome as a general tool for RAD-Seq studies in specialized reef fish

KAUST Repository

DiBattista, Joseph

2017-02-25

Data from a large-scale restriction site associated DNA (RAD-Seq) study of nine butterflyfish species in the Red Sea and Arabian Sea provided a means to test the utility of a recently published draft genome (Chaetodon austriacus) and assess apparent bias in this method of isolating nuclear loci. We here processed double-digest restriction-site (ddRAD) associated DNA sequencing data to identify single nucleotide polymorphism (SNP) markers and their associated function with and without our reference genome to see if it improves the quality of RAD-Seq markers. Our analyses indicate (1) a modest gap between the number of non-annotated versus annotated SNPs across all species, (2) an advantage of using genomic resources for closely related but not distantly related butterflyfish species based on the ability to assign putative gene function to SNPs, and (3) an enrichment of genes among sister butterflyfish taxa related to calcium transmembrane transport and binding. The latter result highlights the potential for this approach to reveal insights into adaptive mechanisms in populations inhabiting challenging coral reef environments such as the Red Sea, Arabian Sea, and Arabian Gulf with further study.

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

Polymerization of impregnated monomer in wood by microwave irradiation

International Nuclear Information System (INIS)

Kawase, Kaoru; Hayakawa, Kiyoshi

1976-01-01

The manufacturing of a wood-plastic combination (WPC) by irradiation of microwave (2,450 and 915 +- 50 MHz) or gamma-ray was carried out. After the impregnation of dry woods (Hinoki: Chamaecyparis obtusa Endl., Buna: Acer mono Maxim., and Kaede: Fagus crenata Blume) with the mixture of the vinyl monomers and chemical reagents, the monomer in wood was polymerized by irradiation. In case of polymerization with microwave (2,450 MHz) the effect of oxygen was not recognized, but in the case of gamma-ray the rate of polymerization remarkably decreased in the presence of oxygen. The polymerization of various monomers was carried out also in the air, and the conversions of styrene, methyl-, ethyl-, n-propyl-, and n-butyl-methacrylate were 51.8 -- 89.1%, but that of vinyl acetate was lower (4.3 -- 8.2%). The conversion of monomers with irradiation of 915 MHz microwave was very low (2.6 -- 33.5%). The conversion of monomers increased when toluylene diisocyanate was added in the monomers. The percentage of extraction with hot benzene of WPC (chip) decreased by the addition of toluylene diisocyanate. It was concluded from C.H.N. analyses that the reaction took place among the wood, toluylene diisocyanate and methyl methacrylate. (auth.)

Radiation Induced Polymerization of Pyrrole

International Nuclear Information System (INIS)

Sarada Idris; Ratnam, C.T.; Ahmad Ashrif Abu Bakar

2016-01-01

We demonstrate the polymerization of pyrrole by gamma irradiation. The pyrrole films were exposed to gamma ray from cobalt 60 source at doses ranging from 0 to 150 kGy. The films were subjected to structural and morphological analyses by using FTIR, SEM and AFM techniques. Similar studies were also made on pristine pyrrole film which serve as control. Results revealed that pyrrole has been successfully polymerized through irradiation induced reactions. The SEM images depicted the formation of cauliflower shape upon gamma irradiation. The structural changes of pyrrole also evidenced by FTIR spectra. Surface topography and roughness of pyrrole before and after gamma irradiation found to show significant differences. (author)

Click polymerization for the synthesis of reduction-responsive polymeric prodrug

Science.gov (United States)

Zhang, Xiaojin; Wang, Hongquan; Dai, Yu

2018-05-01

Click polymerization is a powerful polymerization technique for the construction of new macromolecules with well-defined structures and multifaceted functionalities. Here, we synthesize reduction-responsive polymeric prodrug PEG- b-(PSS- g-MTX)- b-PEG containing disulfide bonds and pendant methotrexate (MTX) via two-step click polymerization followed by conjugating MTX to pendant hydroxyl. MTX content in polymeric prodrug is 13.5%. Polymeric prodrug is able to form polymeric micelles by self-assembly in aqueous solution. Polymeric micelles are spherical nanoparticles with tens of nanometers in size. Of note, polymeric micelles are reduction-responsive due to disulfide bonds in the backbone of PEG- b-(PSS- g-MTX)- b-PEG and could release pendant drugs in the presence of the reducing agents such as dl-dithiothreitol (DTT).

Pulsed-laser polymerization in compartmentalized liquids. 1. Polymerization in vesicles

NARCIS (Netherlands)

Jung, M.; Casteren, van I.A.; Monteiro, M.J.; Herk, van A.M.; German, A.L.

2000-01-01

Polymerization in vesicles is a novel type of polymerization in heterogeneous media, leading to parachute-like vesicle-polymer hybrid morphologies. To explore the kinetics of vesicle polymerizations and to learn more about the actual locus of polymerization we applied the pulsed-laser polymerization

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

Acetone-induced Polymerization of 3-Aminopropyltrimethoxysilane (APTMS) as Revealed by NMR Spectroscopy - Revisited.

Czech Academy of Sciences Publication Activity Database

Schraml, Jan; Korec, S.; Krump, M.; Čermák, Jan

2015-01-01

Roč. 53, č. 2 (2015), s. 154-159 ISSN 0749-1581 Institutional support: RVO:67985858 Keywords : NMR * polymerization * 3-aminopropyltrimethoxysilane Subject RIV: CC - Organic Chemistry Impact factor: 1.226, year: 2015

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.

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

BI-RADS categorisation of 2708 consecutive nonpalpable breast lesions in patients referred to a dedicated breast care unit

International Nuclear Information System (INIS)

Hamy, A.S.; Giacchetti, S.; Cuvier, C.; Perret, F.; Bonfils, S.; Charveriat, P.; Hocini, H.; Espie, M.; Albiter, M.; Bazelaire, C. de; Roquancourt, A. de

2012-01-01

To determine the malignancy rate of nonpalpable breast lesions, categorised according to the Breast Imaging Reporting and Data System (BI-RADS) classification in the setting of a Breast Care Unit. All nonpalpable breast lesions from consecutive patients referred to a dedicated Breast Care Unit were prospectively reviewed and classified into 5 BI-RADS assessment categories (0, 2, 3, 4, and 5). A total of 2708 lesions were diagnosed by mammography (71.6%), ultrasound (8.7%), mammography and ultrasound (19.5%), or MRI (0.2%). The distribution of the lesions by BI-RADS category was: 152 in category 0 (5.6%), 56 in category 2 (2.1%), 742 in category 3 (27.4%), 1523 in category 4 (56.2%) and 235 in category 5 (8.7%). Histology revealed 570 malignant lesions (32.9%), 152 high-risk lesions (8.8%), and 1010 benign lesions (58.3%). Malignancy was detected in 17 (2.3%) category 3 lesions, 364 (23.9%) category 4 lesions and 185 (78.7%) category 5 lesions. Median follow-up was 36.9 months. This pragmatic study reflects the assessment and management of breast impalpable abnormalities referred for care to a specialized Breast Unit. Multidisciplinary evaluation with BI-RADS classification accurately predicts malignancy, and reflects the quality of management. This assessment should be encouraged in community practice appraisal. (orig.)

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.

Validation of the fifth edition BI-RADS ultrasound lexicon with comparison of fourth and fifth edition diagnostic performance using video clips

International Nuclear Information System (INIS)

Yoon, Jung Hyun; Kim, Min Jung; Lee, Hye Sun; Kim, Sung Hun; Youk, Ji Hyun; Jeong, Sun Hye; Kim, You Me

2016-01-01

The aim of this study was to evaluate the positive predictive value (PPV) and the diagnostic performance of the ultrasonographic descriptors in the fifth edition of BI-RADS, comparing with the fourth edition using video clips. From September 2013 to July 2014, 80 breast masses in 74 women (mean age, 47.5±10.7 years) from five institutions of the Korean Society of Breast Imaging were included. Two radiologists individually reviewed the static and video images and analyzed the images according to the fourth and fifth edition of BI-RADS. The PPV of each descriptor was calculated and diagnostic performances between the fourth and fifth editions were compared. Of the 80 breast masses, 51 (63.8%) were benign and 29 (36.2%) were malignant. Suspicious ultrasonographic features such as irregular shape, non-parallel orientation, angular or spiculated margins, and combined posterior features showed higher PPV in both editions (all P<0.05). No significant differences were found in the diagnostic performances between the two editions (all P>0.05). The area under the receiver operating characteristics curve was higher in the fourth edition (0.708 to 0.690), without significance (P=0.416). The fifth edition of the BI-RADS ultrasound lexicon showed comparable performance to the fourth edition and can be useful in the differential diagnosis of breast masses using ultrasonography

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.

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.)

In situ electron-beam polymerization stabilized quantum dot micelles.

Science.gov (United States)

Travert-Branger, Nathalie; Dubois, Fabien; Renault, Jean-Philippe; Pin, Serge; Mahler, Benoit; Gravel, Edmond; Dubertret, Benoit; Doris, Eric

2011-04-19

A polymerizable amphiphile polymer containing PEG was synthesized and used to encapsulate quantum dots in micelles. The quantum dot micelles were then polymerized using a "clean" electron beam process that did not require any post-irradiation purification. Fluorescence spectroscopy revealed that the polymerized micelles provided an organic coating that preserved the quantum dot fluorescence better than nonpolymerized micelles, even under harsh conditions. © 2011 American Chemical Society

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.

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

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...

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,...

Research regarding biodegradable properties of food polymeric products under microorganism activity

Science.gov (United States)

Opran, Constantin; Lazar, Veronica; Fierascu, Radu Claudiu; Ditu, Lia Mara

2018-02-01

Aim of this research is the structural analysis by comparison of the biodegradable properties of two polymeric products made by non-biodegradable polymeric material (polypropylene TIPPLEN H949 A) and biodegradable polymeric material (ECOVIO IS 1335), under microorganism activity in order to give the best solution for the manufacture of food packaging biodegradable products. It presents the results of experimental determinations on comparative analysis of tensile strength for the two types of polymers. The sample weight variations after fungal biodegradation activity revealed that, after 3 months, there are no significant changes in polymeric substratum for non-biodegradable polymeric. The microscopically analysis showed that the fungal filaments did not strongly adhered on the non-biodegradable polymeric material, instead, both filamentous fungi strains adhered and covered the surface of the biodegradable sample with germinated filamentous conidia. The spectral analysis of polymer composition revealed that non-biodegradable polymer polypropylene spectra are identical for control and for samples that were exposed to fungal activity, suggesting that this type of sample was not degraded by the fungi strains. Instead, for biodegradable polymer sample, it was observed significant structural changes across multiple absorption bands, suggesting enzyme activity manifested mainly by Aspergillus niger strain. Structural analysis of interdisciplinary research results, lead, to achieving optimal injection molded technology emphasizing technological parameters, in order to obtain food packaging biodegradable products.

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

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.

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.)

An Asymmetric Runaway Domain Swap Antithrombin Dimer as a Key Intermediate for Polymerization Revealed by Hydrogen/Deuterium-Exchange Mass Spectrometry

DEFF Research Database (Denmark)

Trelle, Morten Beck; Pedersen, Shona H; Østerlund, Eva Christina

2017-01-01

Antithrombin deficiency is associated with increased risk of venous thrombosis. In certain families, this condition is caused by pathogenic polymerization of mutated antithrombin in the blood. To facilitate future development of pharmaceuticals against antithrombin polymerization, an improved und...... strongly supports a β4A-β5A β-hairpin runaway domain swap mechanism for antithrombin polymerization. HDX-MS thus holds exceptional promise as an enabling analytical technique in the efforts toward future pharmacological intervention with protein polymerization and associated diseases....

Simulation of aerosol radiative properties with the ORISAM-RAD model during a pollution event (ESCOMPTE 2001)

Science.gov (United States)

Mallet, M.; Pont, V.; Liousse, C.; Roger, J. C.; Dubuisson, P.

The aim of this study is to present the organic and inorganic spectral aerosol module-radiative (ORISAM-RAD) module, allowing the 3D distribution of aerosol radiative properties (aerosol optical depth, single scattering albedo and asymmetry parameter) from the ORISAM module. In this work, we test ORISAM-RAD for one selected day (24th June) during the ESCOMPTE (expérience sur site pour contraindre les modèles de pollution atmosphérique et de transport d'emissions) experiment for an urban/industrial aerosol type. The particle radiative properties obtained from in situ and AERONET observations are used to validate our simulations. In a first time, simulations obtained from ORISAM-RAD indicate high aerosol optical depth (AOD)˜0.50-0.70±0.02 (at 440 nm) in the aerosol pollution plume, slightly lower (˜10-20%) than AERONET retrievals. In a second time, simulations of the single scattering albedo ( ωo) have been found to well reproduce the high spatial heterogeneities observed over this domain. Concerning the asymmetry parameter ( g), ORISAM-RAD simulations reveal quite uniform values over the whole ESCOMPTE domain, comprised between 0.61±0.01 and 0.65±0.01 (at 440 nm), in excellent agreement with ground based in situ measurements and AERONET retrievals. Finally, the outputs of ORISAM-RAD have been used in a radiative transfer model in order to simulate the diurnal direct radiative forcing at different locations (urban, industrial and rural). We show that anthropogenic aerosols strongly decrease surface solar radiation, with diurnal mean surface forcings comprised between -29.0±2.9 and -38.6±3.9 W m -2, depending on the sites. This decrease is due to the reflection of solar radiations back to space (-7.3±0.8<Δ FTOA<-12.3±1.2 W m -2) and to its absorption into the aerosol layer (21.1±2.1<Δ FATM<26.3±2.6 W m -2). These values are found to be consistent with those measured at local scale.

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

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

Radiation response in vitro of fibroblasts from a Fanconi anemia patient with marked clinical radiosensitivity

Energy Technology Data Exchange (ETDEWEB)

Djuzenova, C.; Flentje, M. [Dept. of Radiotherapy, Univ. of Wuerzburg, Wuerzburg (Germany); Plowman, P.N. [Radiotherapy/Clinical Oncology, St. Bartholomew' s Hospital, London (United Kingdom)

2004-12-01

Background: fanconi anemia (FA) is an autosomal recessive chromosome instability disorder characterized by progressive pancytopenia and cancer susceptibility. The risks of radiation therapy in FA patients who have cancer remain to be investigated. Recently, Marcou et al. (2001) reported a case of severe clinical radiosensitivity in a female FA patient with a tonsillar squamous cell carcinoma treated by radiotherapy. By contrast, her in vitro irradiated skin fibroblasts revealed nearly normal radiosensitivity as determined by the colony survival assay. Material and methods: in view of this discrepancy, the radiation response of this particular FA fibroblast strain (designated 425BR) was further analyzed in the present study by means of the alkaline single-cell gel electrophoresis (Comet) assay, and also by the cytochalasin-blocked micronuclei (MN) test. In addition, the expression levels of DNA repair proteins, hMre11, Rad50, and Rad51, were investigated using Western blot and foci immunofluorescence staining. Results: the Comet assay revealed that the initial DNA fragmentation in irradiated FA cells was two times higher and the DNA rejoining process was three times slower than that in control (1BR3) fibroblasts. Moreover, although the baseline level of MNs was lower in FA cells than in controls, the FA fibroblasts were more prone (about two times) to MN production than control cells when irradiated with 2-4 Gy. Western blot analysis of the DNA repair proteins (hMre11, Rad50, and Rad51) did not reveal any abnormalities in protein expression levels or their migration patterns in the fibroblasts derived from an FA patient either before or after irradiation. At the same time, in vitro irradiated cells from the FA patient exhibited a significantly reduced number of nuclei with focally concentrated DNA repair Rad51 protein than in control cells. Conclusion: the increased DNA damage and MN induction in irradiated FA fibroblasts, and the reduction of the formation of DNA

Radiation response in vitro of fibroblasts from a Fanconi anemia patient with marked clinical radiosensitivity

International Nuclear Information System (INIS)

Djuzenova, C.; Flentje, M.; Plowman, P.N.

2004-01-01

Background: fanconi anemia (FA) is an autosomal recessive chromosome instability disorder characterized by progressive pancytopenia and cancer susceptibility. The risks of radiation therapy in FA patients who have cancer remain to be investigated. Recently, Marcou et al. (2001) reported a case of severe clinical radiosensitivity in a female FA patient with a tonsillar squamous cell carcinoma treated by radiotherapy. By contrast, her in vitro irradiated skin fibroblasts revealed nearly normal radiosensitivity as determined by the colony survival assay. Material and methods: in view of this discrepancy, the radiation response of this particular FA fibroblast strain (designated 425BR) was further analyzed in the present study by means of the alkaline single-cell gel electrophoresis (Comet) assay, and also by the cytochalasin-blocked micronuclei (MN) test. In addition, the expression levels of DNA repair proteins, hMre11, Rad50, and Rad51, were investigated using Western blot and foci immunofluorescence staining. Results: the Comet assay revealed that the initial DNA fragmentation in irradiated FA cells was two times higher and the DNA rejoining process was three times slower than that in control (1BR3) fibroblasts. Moreover, although the baseline level of MNs was lower in FA cells than in controls, the FA fibroblasts were more prone (about two times) to MN production than control cells when irradiated with 2-4 Gy. Western blot analysis of the DNA repair proteins (hMre11, Rad50, and Rad51) did not reveal any abnormalities in protein expression levels or their migration patterns in the fibroblasts derived from an FA patient either before or after irradiation. At the same time, in vitro irradiated cells from the FA patient exhibited a significantly reduced number of nuclei with focally concentrated DNA repair Rad51 protein than in control cells. Conclusion: the increased DNA damage and MN induction in irradiated FA fibroblasts, and the reduction of the formation of DNA

Radiation-induced in-source polymerization of acrylonitrile in urea canal complex

International Nuclear Information System (INIS)

Yoshii, Fumio; Abe, Toshihiko; Kobayashi, Yasushi.

1975-01-01

Effect of reaction conditions on the radiation-induced in-source polymerization of acrylonitrile in urea canal complex and the properties of obtained polyacrylonitriles were investigated. The results were discussed in comparison with previously reported of the post-polymerization experiments. 1) Rate of polymerization and viscosity (eta sub(sp)/C) were the highest when the molar ratio of acrylonitrile to urea in canal complex was unity. Similar results were also obtained in the post-polymerization. However, eta sub(sp)/C exhibited different behavior on polymerization time in comparison with post-polymerization. 2) The initial rate (Rsub(p)) of polymerization is proportional to the dose rate (I) at low dose rate, but at high dose rates (above 2x10 5 r/hr) makes Rsub(p) proportional to Isup(0.5). 3) Molecular weight distribution become broader with increasing polymerization time and is broad as compared with those obtained by the post-polymerization. G-value of initiation of polymerization decreased with increasing polymerization time. These value was larger than the that obtained in the post-polymerization. 4) The stereoregularity of the polyacrylonitriles was independent of the molar ratio of acrylonitrile to urea in the canal complex and conversion. 5) The appearance of the polyacrylonitriles observed by the scanning electron microscope changed from curled string to extended one as the polymerization proceed. 6) Infrared spectrum revealed the ketenimine and cyclization structure in the polyacrylonitriles obtained below -100 0 C. The content of these abnormal structures increased with increasing conversion. (auth.)

Suspicious breast calcifications undergoing stereotactic biopsy in women ages 70 and over: Breast cancer incidence by BI-RADS descriptors.

Science.gov (United States)

Grimm, Lars J; Johnson, David Y; Johnson, Karen S; Baker, Jay A; Soo, Mary Scott; Hwang, E Shelley; Ghate, Sujata V

2017-06-01

To determine the malignancy rate overall and for specific BI-RADS descriptors in women ≥70 years who undergo stereotactic biopsy for calcifications. We retrospectively reviewed 14,577 consecutive mammogram reports in 6839 women ≥70 years to collect 231 stereotactic biopsies of calcifications in 215 women. Cases with missing images or histopathology and calcifications associated with masses, distortion, or asymmetries were excluded. Three breast radiologists determined BI-RADS descriptors by majority. Histology, hormone receptor status, and lymph node status were correlated with BI-RADS descriptors. There were 131 (57 %) benign, 22 (10 %) atypia/lobular carcinomas in situ, 55 (24 %) ductal carcinomas in situ (DCIS), and 23 (10 %) invasive diagnoses. Twenty-seven (51 %) DCIS cases were high-grade. Five (22 %) invasive cases were high-grade, two (9 %) were triple-negative, and three (12 %) were node-positive. Malignancy was found in 49 % (50/103) of fine pleomorphic, 50 % (14/28) of fine linear, 25 % (10/40) of amorphous, 20 % (3/15) of round, 3 % (1/36) of coarse heterogeneous, and 0 % (0/9) of dystrophic calcifications. Among women ≥70 years that underwent stereotactic biopsy for calcifications only, we observed a high rate of malignancy. Additionally, coarse heterogeneous calcifications may warrant a probable benign designation. • Cancer rates of biopsied calcifications in women ≥70 years are high • Radiologists should not dismiss suspicious calcifications in older women • Coarse heterogeneous calcifications may warrant a probable benign designation.

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.

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.

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.

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.

Separation of time scales in one-dimensional directed nucleation-growth processes

Science.gov (United States)

Pierobon, Paolo; Miné-Hattab, Judith; Cappello, Giovanni; Viovy, Jean-Louis; Lagomarsino, Marco Cosentino

2010-12-01

Proteins involved in homologous recombination such as RecA and hRad51 polymerize on single- and double-stranded DNA according to a nucleation-growth kinetics, which can be monitored by single-molecule in vitro assays. The basic models currently used to extract biochemical rates rely on ensemble averages and are typically based on an underlying process of bidirectional polymerization, in contrast with the often observed anisotropic polymerization of similar proteins. For these reasons, if one considers single-molecule experiments, the available models are useful to understand observations only in some regimes. In particular, recent experiments have highlighted a steplike polymerization kinetics. The classical model of one-dimensional nucleation growth, the Kolmogorov-Avrami-Mehl-Johnson (KAMJ) model, predicts the correct polymerization kinetics only in some regimes and fails to predict the steplike behavior. This work illustrates by simulations and analytical arguments the limitation of applicability of the KAMJ description and proposes a minimal model for the statistics of the steps based on the so-called stick-breaking stochastic process. We argue that this insight might be useful to extract information on the time and length scales involved in the polymerization kinetics.

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

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 ...

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

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.

Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry.

Science.gov (United States)

Zhao, Weixing; Vaithiyalingam, Sivaraja; San Filippo, Joseph; Maranon, David G; Jimenez-Sainz, Judit; Fontenay, Gerald V; Kwon, Youngho; Leung, Stanley G; Lu, Lucy; Jensen, Ryan B; Chazin, Walter J; Wiese, Claudia; Sung, Patrick

2015-07-16

The tumor suppressor BRCA2 is thought to facilitate the handoff of ssDNA from replication protein A (RPA) to the RAD51 recombinase during DNA break and replication fork repair by homologous recombination. However, we find that RPA-RAD51 exchange requires the BRCA2 partner DSS1. Biochemical, structural, and in vivo analyses reveal that DSS1 allows the BRCA2-DSS1 complex to physically and functionally interact with RPA. Mechanistically, DSS1 acts as a DNA mimic to attenuate the affinity of RPA for ssDNA. A mutation in the solvent-exposed acidic domain of DSS1 compromises the efficacy of RPA-RAD51 exchange. Thus, by targeting RPA and mimicking DNA, DSS1 functions with BRCA2 in a two-component homologous recombination mediator complex in genome maintenance and tumor suppression. Our findings may provide a paradigm for understanding the roles of DSS1 in other biological processes. Copyright © 2015 Elsevier Inc. All rights reserved.

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...

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

The C. elegans DSB-2 protein reveals a regulatory network that controls competence for meiotic DSB formation and promotes crossover assurance.

Directory of Open Access Journals (Sweden)

Simona Rosu

Full Text Available For most organisms, chromosome segregation during meiosis relies on deliberate induction of DNA double-strand breaks (DSBs and repair of a subset of these DSBs as inter-homolog crossovers (COs. However, timing and levels of DSB formation must be tightly controlled to avoid jeopardizing genome integrity. Here we identify the DSB-2 protein, which is required for efficient DSB formation during C. elegans meiosis but is dispensable for later steps of meiotic recombination. DSB-2 localizes to chromatin during the time of DSB formation, and its disappearance coincides with a decline in RAD-51 foci marking early recombination intermediates and precedes appearance of COSA-1 foci marking CO-designated sites. These and other data suggest that DSB-2 and its paralog DSB-1 promote competence for DSB formation. Further, immunofluorescence analyses of wild-type gonads and various meiotic mutants reveal that association of DSB-2 with chromatin is coordinated with multiple distinct aspects of the meiotic program, including the phosphorylation state of nuclear envelope protein SUN-1 and dependence on RAD-50 to load the RAD-51 recombinase at DSB sites. Moreover, association of DSB-2 with chromatin is prolonged in mutants impaired for either DSB formation or formation of downstream CO intermediates. These and other data suggest that association of DSB-2 with chromatin is an indicator of competence for DSB formation, and that cells respond to a deficit of CO-competent recombination intermediates by prolonging the DSB-competent state. In the context of this model, we propose that formation of sufficient CO-competent intermediates engages a negative feedback response that leads to cessation of DSB formation as part of a major coordinated transition in meiotic prophase progression. The proposed negative feedback regulation of DSB formation simultaneously (1 ensures that sufficient DSBs are made to guarantee CO formation and (2 prevents excessive DSB levels that could

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...

Evaluation of metal-polymeric fixed partial prosthesis using optical coherence tomography

Science.gov (United States)

Sinescu, C.; Negrutiu, M. L.; Duma, V. F.; Marcauteanu, C.; Topala, F. I.; Rominu, M.; Bradu, A.; Podoleanu, A. Gh.

2013-11-01

Metal-Polymeric fixed partial prosthesis is the usual prosthetic treatment for many dental patients. However, during the mastication the polymeric component of the prosthesis is fractured and will be lost. This fracture is caused by the material defects or by the fracture lines trapped inside the esthetic components of the prosthesis. This will finally lead to the failure of the prosthetic treatment. Nowadays, there is no method of identification and forecast for the materials defects of the polymeric materials. The aim of this paper is to demonstrate the capability of Optical Coherence Tomography (OCT) as a non-invasive clinical method that can be used for the evaluation of metal-polymeric fixed partial prostheses. Twenty metal-polymeric fixed partial prostheses were used for this study. The esthetic component of the prostheses has been Adoro (Ivoclar). Optical investigations of the metal prostheses have revealed no material defects or fracture lines. All the prostheses were temporary cemented in the oral cavities of the patients for six month. The non-invasive method used for the investigations was OCT working in Time Domain mode at 1300 nm. The evaluations of the prostheses were performed before and after their cementation in the patient mouths. All the imagistic results were performed in 2D and than in 3D, after the reconstruction. The results obtained after the OCT evaluation allowed for the identification of 4 metal-polymeric fixed partial prostheses with material defects immediately after finishing the technological procedures. After 6 month in the oral environment other 3 fixed partial prostheses revealed fracture lines. In conclusion, OCT proved to be a valuable tool for the noninvasive evaluation of the metal-polymeric fixed partial prostheses.

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

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...

Radical-Mediated Enzymatic Polymerizations

Science.gov (United States)

Zavada, Scott R.; Battsengel, Tsatsral; Scott, Timothy F.

2016-01-01

Polymerization reactions are commonly effected by exposing monomer formulations to some initiation stimulus such as elevated temperature, light, or a chemical reactant. Increasingly, these polymerization reactions are mediated by enzymes―catalytic proteins―owing to their reaction efficiency under mild conditions as well as their environmental friendliness. The utilization of enzymes, particularly oxidases and peroxidases, for generating radicals via reduction-oxidation mechanisms is especially common for initiating radical-mediated polymerization reactions, including vinyl chain-growth polymerization, atom transfer radical polymerization, thiol–ene step-growth polymerization, and polymerization via oxidative coupling. While enzyme-mediated polymerization is useful for the production of materials intended for subsequent use, it is especially well-suited for in situ polymerizations, where the polymer is formed in the place where it will be utilized. Such polymerizations are especially useful for biomedical adhesives and for sensing applications. PMID:26848652

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

Upgrades of the RadMon V6 and its Integration on a Nanosatellite for the Analysis and the Comparative Study of the CHARM and Low Earth Orbit Environments

CERN Document Server

AUTHOR|(CDS)2080738; PERONNARD Paul, CERN

Radiation fields in the CERN accelerator complex are characterized by mixed particles with broad energy ranges. A Radiation Monitoring System, called "RadMon", was developed for the distributed, on-line measurement of the complex radiation fields and their effect on the electronics installed in areas with a harsh radiation environment. The most recent version of the RadMon revealed a critical issue soon after deployment in the tunnel and the experimental areas. Multiple Cell Upsets (MCUs) arising from microlatchup events started showing up on the SRAM-based particle flux sensors equipped by the system, ultimately affecting the measurement and resulting in corrupted data and accuracy losses. A study of the generation of this effect was performed, and a solution using an on-line detection and correction algorithm embedded on an FPGA, was evaluated and implemented on the RadMon device. Furthermore, in the framework of the project CELESTA, a feasibility study was carried out to validate the adaptation of the RadM...

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

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

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.

Homologous recombination contributes to the repair of DNA double-strand breaks induced by high-energy iron ions

Energy Technology Data Exchange (ETDEWEB)

Zafar, Faria; Seidler, Sara B.; Kronenberg, Amy; Schild, David; Wiese, Claudia

2010-06-29

To test the contribution of homologous recombinational repair (HRR) in repairing DNA damaged sites induced by high-energy iron ions, we used: (1) HRR-deficient rodent cells carrying a deletion in the RAD51D gene and (2) syngeneic human cells impaired for HRR by RAD51D or RAD51 knockdown using RNA interference. We show that in response to iron ions, HRR contributes to cell survival in rodent cells, and that HRR-deficiency abrogates RAD51 foci formation. Complementation of the HRR defect by human RAD51D rescues both enhanced cytotoxicity and RAD51 foci formation. For human cells irradiated with iron ions, cell survival is decreased, and, in p53 mutant cells, the levels of mutagenesis are increased when HRR is impaired. Human cells synchronized in S phase exhibit more pronounced resistance to iron ions as compared with cells in G1 phase, and this increase in radioresistance is diminished by RAD51 knockdown. These results implicate a role for RAD51-mediated DNA repair (i.e. HRR) in removing a fraction of clustered lesions induced by charged particle irradiation. Our results are the first to directly show the requirement for an intact HRR pathway in human cells in ensuring DNA repair and cell survival in response to high-energy high LET radiation.

Homologous recombination contributes to the repair of DNA double-strand breaks induced by high-energy iron ions

International Nuclear Information System (INIS)

Zafar, Faria; Seidler, Sara B.; Kronenberg, Amy; Schild, David; Wiese, Claudia

2010-01-01

To test the contribution of homologous recombinational repair (HRR) in repairing DNA damaged sites induced by high-energy iron ions, we used: (1) HRR-deficient rodent cells carrying a deletion in the RAD51D gene and (2) syngeneic human cells impaired for HRR by RAD51D or RAD51 knockdown using RNA interference. We show that in response to iron ions, HRR contributes to cell survival in rodent cells, and that HRR-deficiency abrogates RAD51 foci formation. Complementation of the HRR defect by human RAD51D rescues both enhanced cytotoxicity and RAD51 foci formation. For human cells irradiated with iron ions, cell survival is decreased, and, in p53 mutant cells, the levels of mutagenesis are increased when HRR is impaired. Human cells synchronized in S phase exhibit more pronounced resistance to iron ions as compared with cells in G1 phase, and this increase in radioresistance is diminished by RAD51 knockdown. These results implicate a role for RAD51-mediated DNA repair (i.e. HRR) in removing a fraction of clustered lesions induced by charged particle irradiation. Our results are the first to directly show the requirement for an intact HRR pathway in human cells in ensuring DNA repair and cell survival in response to high-energy high LET radiation.

Elektroaktive polymerer

DEFF Research Database (Denmark)

West, K.

Traditionelt tænker vi på polymerer (plastik) som elektrisk isolerende materialer - det som er udenpå ledningerne. I dag kender vi imidlertid også polymerer med intrinsisk elektrisk ledningsevne, og plast er på vej ind i anvendelser, der tidligereudelukkende var baseret på metaller og uorganiske...... halvledere. Hertil kommer, at en del af de ledende polymerer kan stimuleres til at skifte mellem en ledende og en halvledende tilstand, hvorved de ændret både form og farve. I foredraget gives der enrække eksempler på anvendelse af polymerer som elektriske komponenter - rækkende fra polymer elektronik over...

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

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...

Perfusion impairments in children with reactive attachment disorder (RAD) on 99mTc-ECD brain SPECT: comparison with MR findings

International Nuclear Information System (INIS)

Yoo, Y. H.; Sin, E. J.; Cheon, K. A.; Yoon, M. J.; Lee, J. D.; Jeon, T. J.

2002-01-01

This study aimed to reveal that severe disturbance of attachment relationship with primary care-giver can affect functional and anatomical brain development by measuring cerebral perfusion on 99m Tc-ECD brain SPECT and correlative MRI. We included 18 children aged 31 to 76 months who met the diagnostic criteria of RAD as defined in DSM-IV and ICD-10 and SSP and CARS. 99m Tc-ECD SPECT was performed using CERASPECT. MRI was performed in all patients. SPECT data were visually assessed. 15 of 18 children had abnormal perfusion on SPECT, revealing decreased perfusion of Lt.thalamus (7/15) and Rt.thalamus (3/15), and bilateral thalami (5/15). Perfusion of basal ganglia was decreased in 8 children. Decreased perfusion of Lt. parietal area was seen in 2. Whereas, all patients had normal MR findings. Perfusion abnormalities involving thalamus, BG in most children with RAD were found in this study. These results suggest that brain development of infant could be impeded by severe pathologic care and early nurturing environment would be important for normal development

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.

Platinum porphyrins as ionophores in polymeric membrane electrodes

DEFF Research Database (Denmark)

Lvova, Larisa; Verrelli, Giorgio; Nardis, Sara

2011-01-01

A comparative study of Pt(II)- and Pt(IV)-porphyrins as novel ionophores for anion-selective polymeric membrane electrodes is performed. Polymeric membranes of different compositions, prepared by varying plasticizers, cationic and anionic additives and Pt porphyrins, have been examined...... within the electrode membranes, while those based on Pt(IV)TPPCl2 operate via a mixed mode carrier mechanism, evidencing also a partial reduction of the starting ionophore to Pt(II)TPP. Spectrophotometric measurements of thin polymeric films indicate that no spontaneous formation of hydroxide ion bridged...... porphyrin dimers occurs in the membrane plasticized both with high or low dielectric constant plasticizer, due to a low oxophilicity of central Pt. The computational study of various anion–Pt(IV)TPPCl2 complex formation by means of semi-empirical and density functional theory (DFT) methods revealed a good...

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.

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

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.

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.

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...

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

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

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.

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

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.

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.

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. ...

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.

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

The polymeric nanofilm of triazinedithiolsilane fabricated by self-assembled technique on copper surface. Part 2: Characterization of composition and morphology

International Nuclear Information System (INIS)

Wang, Yabin; Liu, Zhong; Huang, Yudong; Qi, Yutai

2015-01-01

Highlights: • The chemical reactions between copper and triazinedithiolsilane were revealed. • The structure of triazinedithiolsilane's polymeric nanofilm was demonstrated. • The morphology and microstructure of the polymeric nanofilm was observed. - Abstract: In the first part, a novel design route for metal protection against corrosion was proposed, and a class of triazinedithiolsilane compounds was conceived as protector for copper. The protective capability of the polymeric nanofilm, fabricated by self-assembling one representative (abbreviated as TESPA) of triazinedithiolsilane compounds onto copper surface, has been investigated and evaluated by electrochemical tests. The results show that the polymeric nanofilm significantly inhibits copper corrosion. This study, on the one hand, concentrates on the chemical composition of the TESPA polymeric nanofilm by means of X-ray photoelectron spectroscopy (XPS). The XPS results reveal that the chemical bonds between copper and TESPA monomers, three dimensional disulfide units and siloxane networks are responsible for the satisfactory protection of TESPA polymeric nanofilm against copper corrosion. On the other hand, scanning electron microscope (SEM) and energy-dispersive spectroscopy (EDS) are utilized to reveal the morphology and the uniformity of the TESPA polymeric nanofilm. The SEM-EDS results demonstrate that the copper surfaces are uniformly covered with TESPA self-assembled monolayer and the polymeric nanofilm. The TESPA-covered copper surfaces turn out to be smoother than that of the bare copper surface.

Histologic work-up of non-palpable breast lesions classified as probably benign at initial mammography and/or ultrasound (BI-RADS category 3).

Science.gov (United States)

Gruber, R; Jaromi, S; Rudas, M; Pfarl, G; Riedl, C C; Flöry, D; Graf, O; Sickles, E A; Helbich, T H

2013-03-01

To determine the accuracy of a probably benign assessment of non-palpable breast lesions (BI-RADS category 3) at mammography and/or ultrasound with immediate histological work-up. Stereotactic or ultrasound guided core needle breast biopsy (NBB) was performed to evaluate 288 lesions, which were prospectively assessed as BI-RADS category 3. Imaging findings included 195 masses, 73 calcification cases, 16 focal asymmetries, and four architectural distortion cases. After NBB, patients underwent either open surgical biopsy (OSB) (n=204) or mammographic follow-up (n=84) for at least 24 months. Histological results of NBB were compared with those of OSB. Three of the 288 lesions (1.0%) proved to be malignant at histological work-up, two of them were ductal carcinoma in situ (DCIS) and one of them was an invasive carcinoma. NBB revealed invasive carcinoma in 1/288 (0.35%) and atypical ductal hyperplasia (ADH) in 13/288 (4.5%) lesions. OSB revealed DCIS in 2/204 (1%) and invasive carcinoma in 1/204 (0.5%) lesions. The two DCIS were underestimated as ADH by NBB. The remaining 285 (99%) lesions proved to be benign at OSB or remained stable during follow-up. Confirmed by tissue diagnosis, the low likelihood of malignancy of prospectively assessed probably benign lesions is below the 2% threshold established for BI-RADS category 3. Imaging follow-up is a safe and effective alternative to immediate histological work-up for such lesions. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hydrophobic Coatings on Cotton Obtained by in Situ Plasma Polymerization of a Fluorinated Monomer in Ethanol Solutions.

Science.gov (United States)

Molina, Ricardo; Teixidó, Josep Maria; Kan, Chi-Wai; Jovančić, Petar

2017-02-15

Plasma polymerization using hydrophobic monomers in the gas phase is a well-known technology to generate hydrophobic coatings. However, synthesis of functional hydrophobic coatings using plasma technology in liquids has not yet been accomplished. This work is consequently focused on polymerization of a liquid fluorinated monomer on cotton fabric initiated by atmospheric plasma in a dielectric barrier discharge configuration. Functional hydrophobic coatings on cotton were successfully achieved using in situ atmospheric plasma-initiated polymerization of fluorinated monomer dissolved in ethanol. Gravimetric measurements reveal that the amount of polymer deposited on cotton substrates can be modulated with the concentration of monomer in ethanol solution, and cross-linking reactions occur during plasma polymerization of a fluorinated monomer even without the presence of a cross-linking agent. FTIR and XPS analysis were used to study the chemical composition of hydrophobic coatings and to get insights into the physicochemical processes involved in plasma treatment. SEM analysis reveals that at high monomer concentration, coatings possess a three-dimensional pattern with a characteristic interconnected porous network structure. EDX analysis reveals that plasma polymerization of fluorinated monomers takes place preferentially at the surface of cotton fabric and negligible polymerization takes place inside the cotton fabric. Wetting time measurements confirm the hydrophobicity of cotton coatings obtained although equilibrium moisture content was slightly decreased. Additionally, the abrasion behavior and resistance to washing of plasma-coated cotton has been evaluated.

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

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)

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

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.

Nonlinear viscoelasticity of pre-compressed layered polymeric composite under oscillatory compression

KAUST Repository

Xu, Yangguang

2018-05-03

Describing nonlinear viscoelastic properties of polymeric composites when subjected to dynamic loading is essential for development of practical applications of such materials. An efficient and easy method to analyze nonlinear viscoelasticity remains elusive because the dynamic moduli (storage modulus and loss modulus) are not very convenient when the material falls into nonlinear viscoelastic range. In this study, we utilize two methods, Fourier transform and geometrical nonlinear analysis, to quantitatively characterize the nonlinear viscoelasticity of a pre-compressed layered polymeric composite under oscillatory compression. We discuss the influences of pre-compression, dynamic loading, and the inner structure of polymeric composite on the nonlinear viscoelasticity. Furthermore, we reveal the nonlinear viscoelastic mechanism by combining with other experimental results from quasi-static compressive tests and microstructural analysis. From a methodology standpoint, it is proved that both Fourier transform and geometrical nonlinear analysis are efficient tools for analyzing the nonlinear viscoelasticity of a layered polymeric composite. From a material standpoint, we consequently posit that the dynamic nonlinear viscoelasticity of polymeric composites with complicated inner structures can also be well characterized using these methods.

Radiation chemistry of polymeric system

International Nuclear Information System (INIS)

Machi, Sueo; Ishigaki, Isao

1978-01-01

Among wide application of radiation in the field of polymer chemistry, practices of polymerization, graft polymerization, bridging, etc. are introduced hereinafter. As for the radiation sources of radiation polymerization, in addition to the 60 Co-γ ray with long permeation distance which has been usually applied, electron beam accelerators with high energy, large current and high reliability have come to be produced, and the liquid phase polymerization by electron beam has attracted attention industrially. Concerning polymerizing reactions, explanations were given to electron beam polymerization under high dose rate, the polymerization in supercooling state or under high pressure, and emulsifying polymerization. As for radiation bridging, radiation is applied for the bridging of hydrogel, acceleration of bridging and improvement of radiation resistance. It is also utilized for reforming membranes by graft polymerization, and synthesis of polymers for medical use. Application of fixed enzymes in the medical field has been investigated by fixing various enzymes by low temperature γ-ray polymerization with glassy monomers such as HEMA. (Kobatake, H.)

Pressure-induced polymerization of P(CN){sub 3}

Energy Technology Data Exchange (ETDEWEB)

Gou, Huiyang, E-mail: hgou@ciw.edu, E-mail: tstrobel@ciw.edu; Kim, Duck Young; Strobel, Timothy A., E-mail: hgou@ciw.edu, E-mail: tstrobel@ciw.edu [Geophysical Laboratory, Carnegie Institution of Washington, 5251 Broad Branch Road, NW, Washington, DC 20015 (United States); Yonke, Brendan L. [NRC Postdoctoral Associate, Naval Research Laboratory, 4555 Overlook Ave., SW, Washington, DC 20375 (United States); Epshteyn, Albert [Naval Research Laboratory, 4555 Overlook Ave., SW, Washington, DC 20375 (United States); Smith, Jesse S. [High Pressure Collaborative Access Team, Geophysical Laboratory, Carnegie Institution of Washington, Argonne, Illinois 60439 (United States)

2015-05-21

Motivated to explore the formation of novel extended carbon-nitrogen solids via well-defined molecular precursor pathways, we studied the chemical reactivity of highly pure phosphorous tricyanide, P(CN){sub 3}, under conditions of high pressure at room temperature. Raman and infrared (IR) spectroscopic measurements reveal a series of phase transformations below 10 GPa, and several low-frequency vibrational modes are reported for the first time. Synchrotron powder X-ray diffraction measurements taken during compression show that molecular P(CN){sub 3} is highly compressible, with a bulk modulus of 10.0 ± 0.3 GPa, and polymerizes into an amorphous solid above ∼10.0 GPa. Raman and IR spectra, together with first-principles molecular-dynamics simulations, show that the amorphization transition is associated with polymerization of the cyanide groups into CN bonds with predominantly sp{sup 2} character, similar to known carbon nitrides, resulting in a novel phosphorous carbon nitride (PCN) polymeric phase, which is recoverable to ambient pressure.

Molecular Determinants of Radio Resistance in Prostate Cancer

Science.gov (United States)

2005-08-01

Pathway Gene Accession # Ratio H/N Ratio Hypoxia/Normoxla (Log,) NER ERCCt NM001983 1.3 BER APE,2 NM_014481 1.0 MMR PMS2 NM_000535 1.3 HR RAD51...cross-complementing group 1; APEX2, apurinic!apyrimidinic endonuclease/redox factor 2; PMS2 , postmeiotic segregation increased 2; RAD51, RAD51 homolog

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

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.

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)

Immunochip analysis identifies association of the RAD50/IL13 region with human longevity.

Science.gov (United States)

Flachsbart, Friederike; Ellinghaus, David; Gentschew, Liljana; Heinsen, Femke-Anouska; Caliebe, Amke; Christiansen, Lene; Nygaard, Marianne; Christensen, Kaare; Blanché, Hélène; Deleuze, Jean-François; Derbois, Céline; Galan, Pilar; Büning, Carsten; Brand, Stephan; Peters, Anette; Strauch, Konstantin; Müller-Nurasyid, Martina; Hoffmann, Per; Nöthen, Markus M; Lieb, Wolfgang; Franke, Andre; Schreiber, Stefan; Nebel, Almut

2016-06-01

Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls. First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip-wide significant signal (PI mmunochip  = 7.01 × 10(-9) ) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PI mmunochip  association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant in a meta-analysis of the combined French and Danish data after adjusting for multiple testing. In a meta-analysis of all three samples, rs2706372 reached a P-value of PI mmunochip+Repl  = 5.42 × 10(-7) (OR = 1.20; 95% CI = 1.12-1.28). SNP rs2706372 is located in the extended RAD50/IL13 region. RAD50 seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Three new genetic loci (R1210C in CFH, variants in COL8A1 and RAD51B) are independently related to progression to advanced macular degeneration.

Science.gov (United States)

Seddon, Johanna M; Reynolds, Robyn; Yu, Yi; Rosner, Bernard

2014-01-01

To assess the independent impact of new genetic variants on conversion to advanced stages of AMD, controlling for established risk factors, and to determine the contribution of genes in predictive models. In this prospective longitudinal study of 2765 individuals, 777 subjects progressed to neovascular disease (NV) or geographic atrophy (GA) in either eye over 12 years. Recently reported genetic loci were assessed for their independent effects on incident advanced AMD after controlling for 6 established loci in 5 genes, and demographic, behavioral, and macular characteristics. New variants which remained significantly related to progression were then added to a final multivariate model to assess their independent effects. The contribution of genes to risk models was assessed using reclassification tables by determining risk within cross-classified quintiles for alternative models. THREE NEW GENETIC VARIANTS WERE SIGNIFICANTLY RELATED TO PROGRESSION: rare variant R1210C in CFH (hazard ratio (HR) 2.5, 95% confidence interval [CI] 1.2-5.3, P = 0.01), and common variants in genes COL8A1 (HR 2.0, 95% CI 1.1-3.5, P = 0.02) and RAD51B (HR 0.8, 95% CI 0.60-0.97, P = 0.03). The area under the curve statistic (AUC) was significantly higher for the 9 gene model (.884) vs the 0 gene model (.873), P = .01. AUC's for the 9 vs 6 gene models were not significantly different, but reclassification analyses indicated significant added information for more genes, with adjusted odds ratios (OR) for progression within 5 years per one quintile increase in risk score of 2.7, Padvanced AMD beyond macular and behavioral phenotypes.

ANIONIC POLYMERIZATION OF ALKYL METHACRYLATES INITIATED BY nBuCu(NCy2)Li

Institute of Scientific and Technical Information of China (English)

Bing-yong Han; Jian-guo Liang; Jian-min Lu; Feng An; Wan-tai Yang

2009-01-01

Anionic polymerization of methyl methacrylate (MMA), n-butyl methacrylate (nBMA) and glycidyl methacrylate (GMA) initiated by nBuCu(NCy2)Li (1) in tetrahydrofuran (THF) at -50℃ to -10℃ was investigated. It was found that the polymerization of MMA and nBMA initiated by 1 proceeded quantitatively in THF to afford PMMA and PBMA with polydispersity index 1.15-1.30 and nearly 100% initiator efficiencies at -10℃. The molecular weights increased linearly with the ratio of [monomer]/[1]. However, a post-polymerization experiment carried out on this system revealed a double polymer peak by GPC when fresh monomer was added after an interval of 10 rain. Polymerization of styrene could be initiated by 1, but the initiator efficiency was low.

Identification of Laying-Related SNP Markers in Geese Using RAD Sequencing.

Directory of Open Access Journals (Sweden)

ShiGang Yu

Full Text Available Laying performance is an important economical trait of goose production. As laying performance is of low heritability, it is of significance to develop a marker-assisted selection (MAS strategy for this trait. Definition of sequence variation related to the target trait is a prerequisite of quantitating MAS, but little is presently known about the goose genome, which greatly hinders the identification of genetic markers for the laying traits of geese. Recently developed restriction site-associated DNA (RAD sequencing is a possible approach for discerning large-scale single nucleotide polymorphism (SNP and reducing the complexity of a genome without having reference genomic information available. In the present study, we developed a pooled RAD sequencing strategy for detecting geese laying-related SNP. Two DNA pools were constructed, each consisting of equal amounts of genomic DNA from 10 individuals with either high estimated breeding value (HEBV or low estimated breeding value (LEBV. A total of 139,013 SNP were obtained from 42,291,356 sequences, of which 18,771,943 were for LEBV and 23,519,413 were for HEBV cohorts. Fifty-five SNP which had different allelic frequencies in the two DNA pools were further validated by individual-based AS-PCR genotyping in the LEBV and HEBV cohorts. Ten out of 55 SNP exhibited distinct allele distributions in these two cohorts. These 10 SNP were further genotyped in a goose population of 492 geese to verify the association with egg numbers. The result showed that 8 of 10 SNP were associated with egg numbers. Additionally, liner regression analysis revealed that SNP Record-111407, 106975 and 112359 were involved in a multiplegene network affecting laying performance. We used IPCR to extend the unknown regions flanking the candidate RAD tags. The obtained sequences were subjected to BLAST to retrieve the orthologous genes in either ducks or chickens. Five novel genes were cloned for geese which harbored the

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).

Survival and growth of yeast without telomere capping by Cdc13 in the absence of Sgs1, Exo1, and Rad9.

Directory of Open Access Journals (Sweden)

Hien-Ping Ngo

2010-08-01

Full Text Available Maintenance of telomere capping is absolutely essential to the survival of eukaryotic cells. Telomere capping proteins, such as Cdc13 and POT1, are essential for the viability of budding yeast and mammalian cells, respectively. Here we identify, for the first time, three genetic modifications that allow budding yeast cells to survive without telomere capping by Cdc13. We found that simultaneous inactivation of Sgs1, Exo1, and Rad9, three DNA damage response (DDR proteins, is sufficient to allow cell division in the absence of Cdc13. Quantitative amplification of ssDNA (QAOS was used to show that the RecQ helicase Sgs1 plays an important role in the resection of uncapped telomeres, especially in the absence of checkpoint protein Rad9. Strikingly, simultaneous deletion of SGS1 and the nuclease EXO1, further reduces resection at uncapped telomeres and together with deletion of RAD9 permits cell survival without CDC13. Pulsed-field gel electrophoresis studies show that cdc13-1 rad9Delta sgs1Delta exo1Delta strains can maintain linear chromosomes despite the absence of telomere capping by Cdc13. However, with continued passage, the telomeres of such strains eventually become short and are maintained by recombination-based mechanisms. Remarkably, cdc13Delta rad9Delta sgs1Delta exo1Delta strains, lacking any Cdc13 gene product, are viable and can grow indefinitely. Our work has uncovered a critical role for RecQ helicases in limiting the division of cells with uncapped telomeres, and this may provide one explanation for increased tumorigenesis in human diseases associated with mutations of RecQ helicases. Our results reveal the plasticity of the telomere cap and indicate that the essential role of telomere capping is to counteract specific aspects of the DDR.

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.

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...

Facile synthesis of porous graphene-like carbon nitride nanosheets with high surface area and enhanced photocatalytic activity via one-step catalyst-free solution self-polymerization

Science.gov (United States)

Wu, Shikai; Wen, Shengwu; Xu, Xinmei; Huang, Guozhi; Cui, Yifan; Li, Jinyu; Qu, Ailan

2018-04-01

Porous graphite carbon nitride nanosheets (g-C3N4) are achieved via one-step catalyst-free solution self-polymerization from a single melamine precursor. The resultant porous g-C3N4 nanosheets with the best photodegradation capacity provided the surface area of 669.15 m2/g, which is superior to the surface area of any other porous g-C3N4 reported. Results showed enhanced adsorption and degradation capacity of methyl orange (MO) under UV-visible light irradiation (λ > 350 nm) compared to bulk g-C3N4. The MO oxidation of the porous g-C3N4 nanosheets is driven mostly by the participation of holes, and secondly by rad O2- and rad OH radicals. This approach shed lights on porous g-C3N4 production simply by self-polycondensation of single functional monomer. It also provided a low-cost and eco-friendly method to facilely mass-produce g-C3N4 nanosheets with high surface area for many potential applications.

Twin screw extruders as polymerization reactors for a free radical homo polymerization

NARCIS (Netherlands)

Ganzeveld, K.J.; Janssen, L.P.B.M.

The bulk polymerization of n-butylmethacrylate was investigated in a counter-rotating twin screw extruder. It appeared that the gel effect, occurring with bulk polymerizations, affected the polymerization progress very strongly. Due to this effect the conversion of the reaction is independent of the

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.)

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.

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...

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...

Mechanocatalytic polymerization and cross-linking in a polymeric matrix

NARCIS (Netherlands)

Jakobs, R.T.M.; Ma, Shuang; Sijbesma, R.P.

2013-01-01

A latent olefin metathesis catalyst, bearing two polymeric NHC ligands, was embedded in a semicrystalline polymer matrix containing cyclic olefins. The catalyst was activated by straining the solid material under compression, resulting in polymerization and cross-linking reactions of the monomers in

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

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

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.

Chelating polymeric membranes

KAUST Repository

Peinemann, Klaus-Viktor; Villalobos Vazquez de la Parra, Luis Francisco; Hilke, Roland

2015-01-01

microporous chelating polymeric membrane. Embodiments include, but are not limited to, microporous chelating polymeric membranes, device comprising the membranes, and methods of using and making the same.

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.)

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

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.

Cellular radiation effects and hyperthermia cell cycle kinetics of radiation sensitive mutants of saccharomyces cerevisiae after x-irradiation and hyperthermia

International Nuclear Information System (INIS)

Fingerhut, R.; Kiefer, J.; Otto, F.

1983-01-01

Radiosensitive mutants rad2, rad9, and rad51 of Saccharomyces cerevisiae were X-irradiated with 120 Gy or 60 Gy, heated at 50 0 C for 30 min or treated with a combination of both and incubated in nutrient medium at 30 0 C. Cell number, percentage of budding cells, and cell cycle progression were determined in 45-min intervals. Cell cycle kinetics were investigated by flow cytofluorometry. Hyperthermia leads mainly to a lengthening of G1, whereas X-rays arrest cells of the rad2 and rad9 mutant in G2 and the rad51 - mutant additionaly in a state with DNA contents above G2. Cell division dealy is influenced by oxygen in all strains but to a lesser extent in the rad2 mutant. The effect of the combined treatment appears to be merely additive in the rad2 and rad9 mutant while the rad51 mutant is sensitized to X-irradiation by hyperthermia. No selective action of hyperthermia on hypoxic cells was found. (orig.)

The Fanconi Anemia BRCA Pathway as a Predictor of Benefit from Bevacizumab in a Large Phase-3 Clinical Trial in Ovarian Cancer

Science.gov (United States)

2014-10-01

FAM175A (3), PMS2 (2), and MLH1 (1). Consistent with their role as ovarian cancer susceptibility genes, BRIP1, RAD51C, and RAD51D were significantly...ATM (11), RAD51C (10), NBN (9), TP53 (6), BARD1 (4), MSH6 (4), FAM175A (3), PMS2 (2), and MLH1 (1). Consistent with their role as ovarian cancer

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.

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.

Synthesis, Characterization and Bulk Properties of Amphiphilic Copolymers Containing Fluorinated Methacrylates from Sequential Copper-Mediated Radical Polymerization

DEFF Research Database (Denmark)

Hansen, Natanya Majbritt Louie; Gerstenberg, Michael; Haddleton, David M.

2008-01-01

acrylate (MEA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA) by Atom Transfer Radical Polymerization. A kinetic study of the 3FM homopolymerization initiated with ethyl bromoisobutyrate and Cu(I)Br/N-(n-propyl)-2-pyridylmethanimine reveals a living/ controlled polymerization in the range 80...

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.

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.

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

Combination of prostate imaging reporting and data system (PI-RADS) score and prostate-specific antigen (PSA) density predicts biopsy outcome in prostate biopsy naïve patients.

Science.gov (United States)

Washino, Satoshi; Okochi, Tomohisa; Saito, Kimitoshi; Konishi, Tsuzumi; Hirai, Masaru; Kobayashi, Yutaka; Miyagawa, Tomoaki

2017-02-01

To assess the value of the Prostate Imaging Reporting and Data System (PI-RADS) scoring system, for prostate multi-parametric magnetic resonance imaging (mpMRI) to detect prostate cancer, and classical parameters, such as prostate-specific antigen (PSA) level, prostate volume and PSA density, for predicting biopsy outcome in biopsy naïve patients who have suspected prostate cancer. Patients who underwent mpMRI at our hospital, and who had their first prostate biopsy between July 2010 and April 2014, were analysed retrospectively. The prostate biopsies were taken transperineally under transrectal ultrasonography guidance. In all, 14 cores were biopsied as a systematic biopsy in all patients. Two cognitive fusion-targeted biopsy cores were added for each lesion in patients who had suspicious or equivocal lesions on mpMRI. The PI-RADS scoring system version 2.0 (PI-RADS v2) was used to describe the MRI findings. Univariate and multivariate analyses were performed to determine significant predictors of prostate cancer and clinically significant prostate cancer. In all, 288 patients were analysed. The median patient age, PSA level, prostate volume and PSA density were 69 years, 7.5 ng/mL, 28.7 mL, and 0.26 ng/mL/mL, respectively. The biopsy results were benign, clinically insignificant, and clinically significant prostate cancer in 129 (45%), 18 (6%) and 141 (49%) patients, respectively. The multivariate analysis revealed that PI-RADS v2 score and PSA density were independent predictors for prostate cancer and clinically significant prostate cancer. When PI-RADS v2 score and PSA density were combined, a PI-RADS v2 score of ≥4 and PSA density ≥0.15 ng/mL/mL, or PI-RADS v2 score of 3 and PSA density of ≥0.30 ng/mL/mL, was associated with the highest clinically significant prostate cancer detection rates (76-97%) on the first biopsy. Of the patients in this group with negative biopsy results, 22% were subsequently diagnosed as prostate cancer. In contrast, a PI-RADS

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.)

Self-Assembled Polymeric Micellar Nanoparticles as Nanocarriers for Poorly Soluble Anticancer Drug Ethaselen

Directory of Open Access Journals (Sweden)

Yang Zhuoli

2009-01-01

Full Text Available Abstract A series of monomethoxy poly(ethylene glycol-poly(lactide (mPEG-PLA diblock copolymers were synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and delivery of a promising anticancer drug ethaselen. Ethaselen was efficiently encapsulated into the micelles by the dialysis method, and the solubility of ethaselen in water was remarkably increased up to 82 μg/mL before freeze-drying. The mean diameter of ethaselen-loaded micelles ranged from 51 to 98 nm with a narrow size distribution and depended on the length of PLA block. In vitro hemolysis study indicated that mPEG-PLA copolymers and ethaselen-loaded polymeric micelles had no hemolytic effect on the erythrocyte. The enhanced antitumor efficacy and reduced toxic effect of ethaselen-loaded polymeric micelle when compared with ethaselen-HP-β-CD inclusion were observed at the same dose in H22human liver cancer cell bearing mouse models. These suggested that mPEG-PLA polymeric micelle nanoparticles had great potential as nanocarriers for effective solubilization of poorly soluble ethaselen and further reducing side effects and toxicities of the drug.

Radiation-Induced Polymerization of Butyl Acrylate for Recovery of Organic Solvents

International Nuclear Information System (INIS)

Kattan, M.; Al-Kassiri, H.

2011-01-01

Radiation-induced polymerization of butyl acrylate using 60 Co gamma rays has been investigated under different conditions, such as irradiation dose (0-130 kGy), dose rate (10 kGy/h), and temperature (25-70 degree C). A linear relationship between conversion and temperature of irradiation was found. The activation energy (E) of 9.37 kJ/mol was obtained from kinetic analysis of the result from the polymerization at 10 kGy/h. Thermal properties were examined using differential scanning calorimetry and thermal gravimetric analysis. Efficient extraction of organic solvents including chloroform, chlorobenzene, carbon tetrachloride, benzene, styrene was revealed by the swelling and releasing measurements. These results indicate the feasibility of applying this polymer, which was prepared by radiation-induced polymerization, to management of organic wastes in the field of environment. (author)

Radiation-Induced Polymerization of Butyl Acrylate for Recovery of Organic Solvents

International Nuclear Information System (INIS)

Kattan, M.; Al-kassiri, H.

2010-01-01

Radiation-induced polymerization of butyl acrylate (BAc) using 60 Co gamma rays has been investigated under different conditions such as irradiation dose (0-130 kGy), dose rate (10 kGy/h) and temperature (25-70 C). A linear relationship between conversion and temperature of irradiation was found. The activation energy (E) of 9.37 kJ/mol was obtained from kinetic analysis of the result from the polymerization at 10 kGy/h. Thermal properties. were examined using differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). Efficient extraction of organic solvents including chloroform, chlorobenzene, carbon tetrachloride, benzene, styrene was revealed by the swelling and releasing measurements. These results indicate the feasibility of applying this polymer, which was prepared by radiation-induced polymerization, to management of organic wastes in the field of environment. (author)

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.

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.

Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells.

Science.gov (United States)

Browning, Cynthia L; Qin, Qin; Kelly, Deborah F; Prakash, Rohit; Vanoli, Fabio; Jasin, Maria; Wise, John Pierce

2016-09-01

Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels and Rad51 mislocalization to the cytoplasm. The response of proteins involved in Rad51 nuclear import and nucleofilament formation displayed varying responses to prolonged Cr(VI) exposure. BRCA2 formed nuclear foci after prolonged Cr(VI) exposure, while Rad51C foci formation was suppressed. These results suggest that particulate Cr(VI), a major chemical carcinogen, inhibits HR repair by targeting Rad51, causing DNA double strand breaks to be repaired by a low fidelity, Rad51-independent repair pathway. These results further enhance our understanding of the underlying mechanism of Cr(VI)-induced chromosome instability and thus, carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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.

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

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...

Antifouling coatings via plasma polymerization and atom transfer radical polymerization on thin film composite membranes for reverse osmosis

Science.gov (United States)

Hirsch, Ulrike; Ruehl, Marco; Teuscher, Nico; Heilmann, Andreas

2018-04-01

A major drawback to otherwise highly efficient membrane-based desalination techniques like reverse osmosis (RO) is the susceptibility of the membranes to biofouling. In this work, a combination of plasma activation, plasma bromination and surface-initiated atom transfer radical polymerization (si-ATRP) of hydrophilic and zwitterionic monomers, namely hydroxyethyl methacrylate (HEMA), 2-methacryloyloxyethyl phosphorylcholine (MPC) and [2-(methacryloyloxy)ethyl]-dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), was applied to generate non-specific, anti-adhesive coatings on thin film composite (TFC) membranes. The antifouling effect of the coatings was shown by short-time batch as well as long-time steady state cultivation experiments with the microorganism Pseudomonas fluorescens. It could be shown that plasma functionalization and polymerization is possible on delicate thin film composite membranes without restricting their filtration performance. All modified membranes showed an increased resistance towards the adhesion of Pseudomonas fluorescens. On average, the biofilm coverage was reduced by 51.4-12.6% (for HEMA, SBMA, and MPC), the highest reduction was monitored for MPC with a biofilm reduction by 85.4%. The hydrophilic coatings applied did not only suppress the adhesion of Pseudomonas fluorescens, but also significantly increase the permeate flux of the membranes relative to uncoated membranes. The stability of the coatings was however not ideal and will have to be improved for future commercial use.

The rem mutations in the ATP-binding groove of the Rad3/XPD helicase lead to Xeroderma pigmentosum-Cockayne syndrome-like phenotypes.

Science.gov (United States)

Herrera-Moyano, Emilia; Moriel-Carretero, María; Montelone, Beth A; Aguilera, Andrés

2014-12-01

The eukaryotic TFIIH complex is involved in Nucleotide Excision Repair and transcription initiation. We analyzed three yeast mutations of the Rad3/XPD helicase of TFIIH known as rem (recombination and mutation phenotypes). We found that, in these mutants, incomplete NER reactions lead to replication fork breaking and the subsequent engagement of the homologous recombination machinery to restore them. Nevertheless, the penetrance varies among mutants, giving rise to a phenotype gradient. Interestingly, the mutations analyzed reside at the ATP-binding groove of Rad3 and in vivo experiments reveal a gain of DNA affinity upon damage of the mutant Rad3 proteins. Since mutations at the ATP-binding groove of XPD in humans are present in the Xeroderma pigmentosum-Cockayne Syndrome (XP-CS), we recreated rem mutations in human cells, and found that these are XP-CS-like. We propose that the balance between the loss of helicase activity and the gain of DNA affinity controls the capacity of TFIIH to open DNA during NER, and its persistence at both DNA lesions and promoters. This conditions NER efficiency and transcription resumption after damage, which in human cells would explain the XP-CS phenotype, opening new perspectives to understand the molecular basis of the role of XPD in human disease.

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.

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.

Optical investigations of various polymeric materials used in dental technology

Science.gov (United States)

Negrutiu, Meda Lavinia; Sinescu, Cosmin; Topala, Florin Ionel; Ionita, Ciprian; Goguta, Luciana; Marcauteanu, Corina; Rominu, Mihai; Podoleanu, Adrian Gh.

2011-10-01

Dental prosthetic restorations have to satisfy high stress as well as aesthetic requirements. In order to avoid deficiencies of dental prostheses, several alternative systems and procedures were imagined, directly related to the material used and also to the manufacturing technology. Increasing the biomechanical comportment of polymeric materials implies fiber reinforcing. The different fibers reinforcing products made very difficult the evaluation of their performances and biomechanical properties analysis. There are several known methods which are used to assess the quality of dental prostheses, but most are invasive. These lead to the destruction of the samples and often no conclusion could be drawn in the investigated areas of interest. Using a time domain en-face OCT system, we have recently demonstrated real time thorough evaluation of quality of various dental treatments. The aim of this study was to assess the quality of various polymeric materials used in dental technology and to validate the en face OCT imagistic evaluation of polymeric dental prostheses by using scanning electron microscopy (SEM) and microcomputer tomography (μCT). SEM investigations evidenced the nonlinear aspect of the interface between the polymeric material and the fiber reinforcement and materials defects in some samples. The results obtained by microCT revealed also some defects inside the polymeric materials and at the interfaces with the fiber reinforcement. The advantages of the OCT method consist in non-invasiveness and high resolution. In addition, en face OCT investigations permit visualization of the more complex stratified structure at the interface between the polymeric material and the fiber reinforcement.

Polymeric micelles for drug targeting.

Science.gov (United States)

Mahmud, Abdullah; Xiong, Xiao-Bing; Aliabadi, Hamidreza Montazeri; Lavasanifar, Afsaneh

2007-11-01

Polymeric micelles are nano-delivery systems formed through self-assembly of amphiphilic block copolymers in an aqueous environment. The nanoscopic dimension, stealth properties induced by the hydrophilic polymeric brush on the micellar surface, capacity for stabilized encapsulation of hydrophobic drugs offered by the hydrophobic and rigid micellar core, and finally a possibility for the chemical manipulation of the core/shell structure have made polymeric micelles one of the most promising carriers for drug targeting. To date, three generations of polymeric micellar delivery systems, i.e. polymeric micelles for passive, active and multifunctional drug targeting, have arisen from research efforts, with each subsequent generation displaying greater specificity for the diseased tissue and/or targeting efficiency. The present manuscript aims to review the research efforts made for the development of each generation and provide an assessment on the overall success of polymeric micellar delivery system in drug targeting. The emphasis is placed on the design and development of ligand modified, stimuli responsive and multifunctional polymeric micelles for drug targeting.

Polymerization Using Phosphazene Bases

KAUST Repository

Zhao, Junpeng

2015-09-01

In the recent rise of metal-free polymerization techniques, organic phosphazene superbases have shown their remarkable strength as promoter/catalyst for the anionic polymerization of various types of monomers. Generally, the complexation of phosphazene base with the counterion (proton or lithium cation) significantly improves the nucleophilicity of the initiator/chain end resulting in highly enhanced polymerization rates, as compared with conventional metalbased initiating systems. In this chapter, the general features of phosphazenepromoted/catalyzed polymerizations and the applications in macromolecular engineering (synthesis of functionalized polymers, block copolymers, and macromolecular architectures) are discussed with challenges and perspectives being pointed out.

Phosphazene-promoted anionic polymerization

KAUST Repository

Zhao, Junpeng

2014-01-01

In the recent surge of metal-free polymerization techniques, phosphazene bases have shown their remarkable potential as organic promoters/catalysts for the anionic polymerization of various types of monomers. By complexation with the counterion (e.g. proton or lithium cation), phosphazene base significantly improve the nucleophilicity of the initiator/chain-end resulting in rapid and usually controlled anionic/quasi-anionic polymerization. In this review, we will introduce the general mechanism, i.e. in situ activation (of initiating sites) and polymerization, and summarize the applications of such a mechanism on macromolecular engineering toward functionalized polymers, block copolymers and complex macromolecular architectures.

The Aspergillus uvsH gene encodes a product homologous to yeast RAD18 and Neurospora UVS-2.

Science.gov (United States)

Yoon, J H; Lee, B J; Kang, H S

1995-07-28

The uvsH DNA repair gene of Aspergillus nidulans has been cloned by complementation of the uvsH77 mutation with a cosmid library containing genomic DNA inserts from a wild-type strain. Methylmethane sulfonate (MMS)-resistant transformants were obtained on medium containing 0.01% MMS, to which uvsH mutants exhibit high sensitivity. Retransformation of uvsH77 mutants with the rescued cosmids from the MMS-resistant transformants resulted in restoration of both UV and MMS resistance to wild-type levels. Nucleotide sequence analysis of the genomic DNA and cDNA of the uvsH gene shows that it has an open reading frame (ORF) of 1329 bp, interrupted by two introns of 51 and 61 bp. A 2.4 kb transcript of the uvsH gene was detected by Northern blot analysis. Primer extension analysis revealed that transcription starts at 31 bp upstream from the translation initiation codon. This gene encodes a predicted polypeptide of 443 amino acids, which has two unique zinc finger motifs. The proposed polypeptide displays 39% identity to the Neurospora crassa UVS-2 protein and 24% identity to the Saccharomyces cerevisiae RAD18 protein. The sequence similarity is particularly high in three domains. One zinc finger (RING finger) motif is located in the first domain close to the N-terminus. The other zinc finger motif is in the second domain. In the third domain, the mutation sites in both the uvsH77 and uvsH304 alleles were identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterizing the Hypermutated Subtype of Advanced Prostate Cancer as a Predictive Biomarker for Precision Medicine

Science.gov (United States)

2016-10-01

instability, MSI, MLH1, MSH2, MSH6, PMS2 , metastasis, precision medicine 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...hypermutation, hyper-mutation, microsatellite instability, MSI, MLH1, MSH2, MSH6, PMS2 , metastasis, precision medicine Colin Pritchard MD, PhD 2015-2016 Year 2...BRCC3 BRIP1 CHEK1 CHEK2 FAM175A MLH1 MRE11A MSH2 MSH6 NBN PALB2 PMS2 PRSS1 PTEN RAD50 RAD51B RAD51C RAD51D RBBP8 TP53 TP53BP1 XRCC2 Additional

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.

Conducting Polymeric Materials

DEFF Research Database (Denmark)

Hvilsted, Søren

2016-01-01

The overall objective of this collection is to provide the most recent developments within the various areas of conducting polymeric materials. The conductivity of polymeric materials is caused by electrically charged particles, ions, protons and electrons. Materials in which electrons...