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Sample records for radiation sensitive genetically

  1. Radiation-sensitive genetically susceptible pediatric sub-populations

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    Kleinerman, Ruth A. [National Cancer Institute, NIH, DHHS, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Rockville, MD (United States)

    2009-02-15

    Major advances in pediatric cancer treatment have resulted in substantial improvements in survival. However, concern has emerged about the late effects of cancer therapy, especially radiation-related second cancers. Studies of childhood cancer patients with inherited cancer syndromes can provide insights into the interaction between radiation and genetic susceptibility to multiple cancers. Children with retinoblastoma (Rb), neurofibromatosis type 1 (NF1), Li-Fraumeni syndrome (LFS), and nevoid basal cell carcinoma syndrome (NBCCS) are at substantial risk of developing radiation-related second and third cancers. A radiation dose-response for bone and soft-tissue sarcomas has been observed in hereditary Rb patients, with many of these cancers occurring in the radiation field. Studies of NF1 patients irradiated for optic pathway gliomas have reported increased risks of developing another cancer associated with radiotherapy. High relative risks for second and third cancers were observed for a cohort of 200 LFS family members, especially children, possibly related to radiotherapy. Children with NBCCS are very sensitive to radiation and develop multiple basal cell cancers in irradiated areas. Clinicians following these patients should be aware of their increased genetic susceptibility to multiple primary malignancies enhanced by sensitivity to ionizing radiation. (orig.)

  2. Temperature-sensitive mutants of fowl plague virus: isolation and genetic characterization. [UV radiation

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    Almond, J.W.; McGeoch, D.; Barry, R.D.

    1979-01-30

    Forty-nine temperature-sensitive mutants of fowl plague virus (FPV) strain Rostock and four ts mutants of FPV-strain Dobson were isolated by utilizing two methods of plaque screening, after either spontaneous or chemically induced mutagenesis. Twenty-nine of the FPV-Rostock mutants were further characterized by genetic recombination studies and were found to fall into six high frequency recombination groups. The genome segment carrying the ts mutation in each group was identified by analyzing the gene composition of ts/sup +/ recombinants generated from crosses between representatives of each group and ts mutants of FPV-Dobson. It was concluded that the six groups correspond to mutations in six different genome segments, namely, those coding for the P/sub 1/, P/sub 2/, P/sub 3/, HA, NP, and NS proteins.

  3. Individual radiation sensitivity (gender, age, genetic disposition). Consequences for radiation protection; Individuelle Strahlenempfindlichkeit (Geschlecht-Alter-genetische Disposition). Konsequenzen fuer den Strahlenschutz?

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    Streffer, C. [Universitaetsklinikum Essen (Germany)

    2013-07-01

    The effects of ionising radiation on human health is influenced by a number of physiological and molecular biological factors. This is also valid for the causation of stochastic radiation effects especially the causation of cancer. Several epidemiological studies have resulted with respect to the total rate of solid cancers that women are more sensitive than men by a factor of 1.6 to 2.0. For leukaemia this is not the case. The largest studies come from the investigations on the survivors of the atomic bombs in Hiroshima and Nagasaki. But also studies on the population of the Techa River (Southeast Urals) yield such data. The analyses of single cancer localizations come to different results with respect to the dependence on the sex. Secondary cancers after radiotherapy for cancer treatment show also higher rates in women than in men. A similar situation is observed with respect to the dependence of cancer rate on age. The total rate of solid cancers is highest with children and decreases with increasing age. The effects are very different again with single cancer localizations. An especially strong age dependence was observed for thyroid cancer. Increasingly individuals have been found who are especially radiosensitive on the basis of their genetic disposition also with respect to the causation of cancer. Mechanisms and possibilities to trace these individuals are discussed. It is also discussed whether and to which extent these data should have consequences for the practical radiological protection. (orig.)

  4. X-ray survival characteristics and genetic analysis for nine saccharomyces deletion mutants that show altered radiation sensitivity

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    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2004-01-07

    The availability of a genome-wide set of Saccharomyces deletion mutants provides a chance to identify all the yeast genes involved in DNA repair. Using X-rays, we are screening these mutants to identify additional genes that show increased sensitivity to the lethal effects of ionizing radiation. For each mutant identified as sensitive, we are confirming that the sensitivity phenotype co-segregates with the deletion allele and are obtaining multipoint survival-versus-dose assays in at least two haploid and one homozygous diploid strains. We present data for deletion mutants involving the genes DOT1, MDM20, NAT3, SPT7, SPT20, GCN5, HFI1, DCC1 and VID21/EAF1, and discuss their potential roles in repair. Eight of these genes have a clear radiation-sensitive phenotype when deleted, but the ninth, GCN5, has at most a borderline phenotype. None of the deletions confer substantial sensitivity to ultra-violet radiation, although one or two may confer marginal sensitivity. The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein. We find that histone H3 mutants (supplied by K. Struhl) in which this residue is replaced by other amino-acids are also X-ray sensitive, seeming to confirm that methylation of the lysine-79 residue is required for effective repair of radiation damage.

  5. Radiation Sensitization in Cancer Therapy.

    Science.gov (United States)

    Greenstock, Clive L.

    1981-01-01

    Discusses various aspects of radiation damage to biological material, including free radical mechanisms, radiation sensitization and protection, tumor hypoxia, mechanism of hypoxic cell radiosensitization, redox model for radiation modification, sensitizer probes of cellular radiation targets, pulse radiolysis studies of free radical kinetics,…

  6. X-ray survival characteristics and genetic analysis for nineSaccharomyces deletion mutants that affect radiation sensitivity

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    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2006-07-21

    We examine ionizing radiation (IR) sensitivity and epistasisrelationships of several Saccharomyces mutants affectingpost-translational modifications of histones H2B and H3. Mutantsbre1delta, lge1delta, and rtf1delta, defective in histone H2B lysine 123ubiquitination, show IR sensitivity equivalent to that of the dot1deltamutant that we reported on earlier, consistent with published findingsthat Dot1p requires H2B K123 ubiquitination to fully methylate histone H3K79. This implicates progressive K79 methylation rather thanmono-methylation in IR resistance. The set2delta mutant, defective in H3K36 methylation, shows mild IR sensitivity whereas mutants that abolishH3 K4 methylation resemble wild type. The dot1delta, bre1delta, andlge1delta mutants show epistasis for IR sensitivity. The paf1deltamutant, also reportedly defective in H2B K123 ubiquitination, confers nosensitivity. The rad6delta, rad51null, rad50delta, and rad9deltamutations are epistatic to bre1? and dot1delta, but rad18delta andrad5delta show additivity with bre1delta, dot1delta, and each other. Thebre1delta rad18delta double mutant resembles rad6delta in sensitivity;thus the role of Rad6p in ubiquitinating H2B accounts for its extrasensitivity compared to rad18delta. We conclude that IR resistanceconferred by BRE1 and DOT1 is mediated through homologous recombinationalrepair, not postreplication repair, and confirm findings of a G1checkpoint role for the RAD6/BRE1/DOT1 pathway.

  7. Individual radiation sensitivity: implications in medical practice

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    Gisone, P.; Dubner, D.; Perez, M.D.R.; Michelin, S.; Di Giogio, M. [Autoridad Regulatoria Nuclear, Buenos Aires (Argentina); Bourguignon, M. [Direction Generale de la Surete Nucleaire et de la Radioprotection, Paris (France)

    2006-07-01

    Important advances in radiotherapy and nuclear medicine towards better treatment modalities and safer applications have taken place in recent years. Progress in medical imaging, better tumour targeting and optimization of radiation delivery have allowed for dose escalation and improved patient outcome. However, the tolerance of normal tissues constitutes the limiting factor for dose escalation in therapeutical uses of ionizing radiation (IR). Patients vary considerably in their normal tissue response to IR even after similar treatments. As many as 5% of cancer patients develop severe effects to external radiation therapy in normal tissues within the treatment field: they may include acute effects such as erythema and desquamation of the exposed skin and mucosa that appear during or directly after radiotherapy, late effects developed months or years later, such as fibrosis and telangiectasia and cancer induction. Several patient and treatment related factors are known to influence the variability of side effects, however up to a 70% of the total variance of normal tissue radiation response remained unexplained. Thus, individual sensitivity to IR, i.e. hypersensitivity to carcinogenic risks (stochastic effects) and hypersensitivity to deterministic effects, is becoming an important issue in oncology and raises questions regarding the underlying mechanisms. The mechanisms of DNA repair, the signalling pathways involved in radiation sensitivity and non-targeted effects are key aspects, essential to understanding radiation effects at genetic level. Moreover, human genetic diseases that combine higher incidence of cancer and hypersensitivity to IR are associated with defects in cell response to DNA damage. Therefore, much interest has raised during the last years in the developing of predictive tests capable to detect in advance such hypersensitive conditions. The goal of this presentation is to review the possible mechanisms involved in genetic and epigenetic

  8. Radiation-induced Genomic Instability and Radiation Sensitivity

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    Varnum, Susan M.; Sowa, Marianne B.; Kim, Grace J.; Morgan, William F.

    2013-01-19

    The obvious relationships between reactive oxygen and nitrogen species, mitochondrial dysfunction, inflammatory type responses and reactive chemokines and cytokines suggests a general stress response induced by ionizing radiation most likely leads to the non-targeted effects described after radiation exposure. We argue that true bystander effects do not occur in the radiation therapy clinic. But there is no question that effects outside the target volume do occur. These “out of field effects” are considered very low dose effects in the context of therapy. So what are the implications of non-targeted effects on radiation sensitivity? The primary goal of therapy is to eradicate the tumor. Given the genetic diversity of the human population, lifestyle and environment factors it is likely some combination of these will influence patient outcome. Non-targeted effects may contribute to a greater or lesser extent. But consider the potential situation involving a partial body exposure due to a radiation accident or radiological terrorism. Non-targeted effects suggest that the tissue at risk for demonstrating possible detrimental effects of radiation exposure might be greater than the volume actually irradiated.

  9. SEM probe of IC radiation sensitivity

    Science.gov (United States)

    Gauthier, M. K.; Stanley, A. G.

    1979-01-01

    Scanning Electron Microscope (SEM) used to irradiate single integrated circuit (IC) subcomponent to test for radiation sensitivity can localize area of IC less than .03 by .03 mm for determination of exact location of radiation sensitive section.

  10. How Sensitive Is Genetic Data?

    Science.gov (United States)

    Sariyar, Murat; Suhr, Stephanie; Schlünder, Irene

    2017-09-07

    The rising demand to use genetic data for research goes hand in hand with an increased awareness of privacy issues related to its use. Using human genetic data in a legally compliant way requires an examination of the legal basis as well as an assessment of potential disclosure risks. Focusing on the relevant legal framework in the European Union, we discuss open questions and uncertainties around the handling of genetic data in research, which can result in the introduction of unnecessary hurdles for data sharing. First, we discuss defining features and relative disclosure risks of some DNA-related biomarkers, distinguishing between the risk for disclosure of (1) the identity of an individual, (2) information about an individual's health and behavior, including previously unknown phenotypes, and (3) information about an individual's blood relatives. Second, we discuss the European legal framework applicable to the use of DNA-related biomarkers in research, the implications of including both inherited and acquired traits in the legal definition, as well as the issue of "genetic exceptionalism"-the notion that genetic information has inherent characteristics that require different considerations than other health and medical information. Finally, by mapping the legal to specific technical definitions, we draw some initial conclusions concerning how sensitive different types of "genetic data" may actually be. We argue that whole genome sequences may justifiably be considered "exceptional" and require special protection, whereas other genetic data that do not fulfill the same criteria should be treated in a similar manner to other clinical data. This kind of differentiation should be reflected by the law and/or other governance frameworks as well as agreed Codes of Conduct when using the term "genetic data."

  11. Ionizing radiation and genetic risks

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    Sankaranarayanan, K. [Department of Toxicogenetics, Leiden University Medical Centre, Sylvius Laboratories, Wassenaarseweg 72, 2333 AL Leiden (Netherlands)]. E-mail: sankaran@lumc.nl; Wassom, J.S. [YAHSGS, LLC, Richland, WA 99352 (United States); Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37830 (United States)

    2005-10-15

    Recent estimates of genetic risks from exposure of human populations to ionizing radiation are those presented in the 2001 report of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). These estimates incorporate two important concepts, namely, the following: (1) most radiation-induced mutations are DNA deletions, often encompassing multiple genes, but only a small proportion of the induced deletions is compatible with offspring viability; and (2) the viability-compatible deletions induced in germ cells are more likely to manifest themselves as multi-system developmental anomalies rather than as single gene disorders. This paper: (a) pursues these concepts further in the light of knowledge of mechanisms of origin of deletions and other rearrangements from two fields of contemporary research: repair of radiation-induced DNA double-strand breaks (DSBs) in mammalian somatic cells and human molecular genetics; and (b) extends them to deletions induced in the germ cell stages of importance for radiation risk estimation, namely, stem cell spermatogonia in males and oocytes in females. DSB repair studies in somatic cells have elucidated the roles of two mechanistically distinct pathways, namely, homologous recombination repair (HRR) that utilizes extensive sequence homology and non-homologous end-joining (NHEJ) that requires little or no homology at the junctions. A third process, single-strand annealing (SSA), which utilizes short direct repeat sequences, is considered a variant of HRR. HRR is most efficient in late S and G{sub 2} phases of the cell cycle and is a high fidelity mechanism. NHEJ operates in all cell cycle phases, but is especially important in G{sub 1}. In the context of radiation-induced DSBs, NHEJ is error-prone. SSA is also an error-prone mechanism and its role is presumably similar to that of HRR. Studies in human molecular genetics have demonstrated that the occurrence of large deletions, duplications or other

  12. DNA repair and radiation sensitivity in mammalian cells

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    Chen, D.J.C.; Stackhouse, M. [Los Alamos National Lab., NM (United States); Chen, D.S. [Rochester Univ., NY (United States). Dept. of Radiation Oncology

    1993-02-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  13. DNA repair and radiation sensitivity in mammalian cells

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    Chen, D.J.C.; Stackhouse, M. (Los Alamos National Lab., NM (United States)); Chen, D.S. (Rochester Univ., NY (United States). Dept. of Radiation Oncology)

    1993-01-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  14. Longitudinal Genetic Analysis of Anxiety Sensitivity

    Science.gov (United States)

    Zavos, Helena M. S.; Gregory, Alice M.; Eley, Thalia C.

    2012-01-01

    Anxiety sensitivity is associated with both anxiety and depression and has been shown to be heritable. Little, however, is known about the role of genetic influence on continuity and change of symptoms over time. The authors' aim was to examine the stability of anxiety sensitivity during adolescence. By using a genetically sensitive design, the…

  15. Sensitizing Osteosarcoma to Radiation Therapy

    Science.gov (United States)

    Mamo, Tewodros Kebede

    Several strategies to enhance the effects of radiation therapy are being explored for various cancers, with multiple molecular pathways and physical approaches suggested to play a role. One approach to improve the effectiveness of radiation therapy in tumors is the use of radiosensitizing molecules. Among the key radiosensitizing molecules being explored in various cancers include pharmacologic inhibitors of DNA repair and gold nanoparticles that physically enhance the amount of radiation deposited inside cancer cells. The main goal of this thesis is to explore the role of DNA repair inhibition as a radiosensitizing strategy for osteosarcoma cells. Additionally, the thesis investigates the effects of particle size in the application of gold nanoparticles in osteosarcoma cells to help identify the key parameters relevant to choosing an effective gold nanoparticle-based radiosensitizer.

  16. Genetics Home Reference: warfarin sensitivity

    Science.gov (United States)

    ... SA, Patel M, Martis S, Lubitz SA, van der Zee S, Yoo C, Edelmann L, Halperin JL, Desnick RJ. ... or Free article on PubMed Central van der Zee SA, Halperin JL. Anticoagulant therapy: warfarin sensitivity genotyping ...

  17. Protection Strategy of Sensitive Body Organs in Radiation Therapy

    OpenAIRE

    Abolfath, Ramin M.; Papiez, Lech

    2009-01-01

    In this paper, we investigate protection strategies of sensitive body anatomy against the irradiation to the cancerous moving tumors in intensity modulated radiation therapy. Inspired by optimization techniques developed in statistical physics and dynamical systems, we deploy a method based on variational principles and formulate an efficient genetic algorithm which enable us to search for global minima in a complex landscape of irradiation dose delivered to the radiosensitive organs at risk....

  18. Protection Strategy of Sensitive Body Organs in Radiation Therapy

    CERN Document Server

    Abolfath, Ramin M

    2009-01-01

    In this paper, we investigate protection strategies of sensitive body anatomy against the irradiation to the cancerous moving tumors in intensity modulated radiation therapy. Inspired by optimization techniques developed in statistical physics and dynamical systems, we deploy a method based on variational principles and formulate an efficient genetic algorithm which enable us to search for global minima in a complex landscape of irradiation dose delivered to the radiosensitive organs at risk. We take advantage of the internal motion of body anatomy during radiation therapy to reduce the unintentional delivery of the radiation to sensitive organs. We show that the accurate optimization of the control parameters, compare to the conventional IMRT and widely used delivery based on static anatomy assumption, leads to a significant reduction of the dose delivered to the organs at risk.

  19. The quantitative genetics of disgust sensitivity.

    Science.gov (United States)

    Sherlock, James M; Zietsch, Brendan P; Tybur, Joshua M; Jern, Patrick

    2016-02-01

    [Correction Notice: An Erratum for this article was reported in Vol 16(1) of Emotion (see record 2015-57029-001). In the article, the name of author Joshua M. Tybur was misspelled as Joshua M. Tyber. All versions of this article have been corrected.] Response sensitivity to common disgust elicitors varies considerably among individuals. The sources of these individual differences are largely unknown. In the current study, we use a large sample of female identical and nonidentical twins (N = 1,041 individuals) and their siblings (N = 170) to estimate the proportion of variation due to genetic effects, the shared environment, and other (residual) sources across multiple domains of disgust sensitivity. We also investigate the genetic and environmental influences on the covariation between the different disgust domains. Twin modeling revealed that approximately half of the variation in pathogen, sexual, and moral disgust is due to genetic effects. An independent pathways twin model also revealed that sexual and pathogen disgust sensitivity were influenced by unique sources of genetic variation, while also being significantly affected by a general genetic factor underlying all 3 disgust domains. Moral disgust sensitivity, in contrast, did not exhibit domain-specific genetic variation. These findings are discussed in light of contemporary evolutionary approaches to disgust sensitivity.

  20. Genetic susceptibility to radiation: which impact on medical practice?

    Energy Technology Data Exchange (ETDEWEB)

    Alapetite, C.; Cosset, J.M. [Institut Curie, Dept. de Radiotherapie, 75 - Paris (France); Bourguignon, M.H.; Masse, R. [Office de Protection contre les Rayonnements Ionisants, 78 - le Vesinet (France)

    2001-07-01

    Recent progress especially in the field of gene identification and expression have raised more attention on genetic susceptibility to cancer possibly enhanced by radiations. Radiation therapists are mostly concerned by this question since hypersensitive patients may suffer from adverse effects in normal tissues following a standard radiation therapy and normally sensitive patients could benefit from higher doses of radiations for a better cure of their malignant tumors. Although only a small percentage of individuals are 'hypersensitive' to radiation effects, all medical specialists using ionising radiations should be aware of these new progress in medical knowledge. The present paper reviews the main pathologies (diseases, syndromes...) known or strongly suspected to be associated with a hypersensitivity to ionizing radiations. Then the main tests capable to detect in advance such pathologies are analyzed and compared. Finally guidelines are provided, especially to the radiation therapists to limit the risk of severe complications (or even deaths) for these specific subset of patients suffering from a genetic disorder with a susceptibility to radiations. (author)

  1. Final Technical Report for the grant entitled "Genetic Factors Affecting Susceptibility to Low-Dose Radiation"

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William, F., Ph.D., D.Sc.

    2006-11-22

    The goal of this proposal was to test the hypothesis that mice heterozygous for the Nijmegen Breakage Syndrome (NBS1) gene are genetically susceptible to low doses of ionizing radiation. The rationale for this is that patients with NBS are radiation sensitive, because of defects in cellular responses to radiation induced genetic damage and haploinsufficiency at this genetic locus provides the potential for genetic susceptibility to low doses of ionizing radiation. Wild type and heterozygous NBS1 mice were irradiated and followed over their lifetime for radiation induced genomic instability, carcinogenesis and non-specific life shortening. No differences in cytogenetic damage, cancer induction or life span were observed between the hypomorphic mice indicating that genetic imbalance at the NBS1 loci does not modulate low dose radiation sensitivity.

  2. Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Skiöld, Sara [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Azimzadeh, Omid [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Merl-Pham, Juliane [Research Unit Protein Science, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg (Germany); Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet [Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm (Sweden); Tapio, Soile [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Harms-Ringdahl, Mats [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Haghdoost, Siamak, E-mail: Siamak.Haghdoost@su.se [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden)

    2015-06-15

    Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy.

  3. Radiation sensitivity of different citric pectins

    Energy Technology Data Exchange (ETDEWEB)

    Inamura, Patricia Y.; Mastro, Nelida L. del [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: patyoko@yahoo.com; nlmastro@ipen.br

    2007-07-01

    Pectic substances are important soluble polysaccharides of plant origin of considerable interest for food industry as gelling agent and stabilizer in jams, fruit jellies, yogurt drinks and lactic acid beverages. Polysaccharides can be degraded by ionizing radiation due to the free radical induced scission of the glycosidic bonds. Viscosity methods had been used to determine the efficiency of hydroxyl radical induced chain breaks generation in macromolecules. In the present work samples of pectin with different degree of methoxylation were employed in order to study their radiation sensitivity by means of viscosity measurements. Samples of citric pectin 1% solutions were irradiated with gamma rays at different doses, ranging from 0 to 15 kGy, using a {sup 60}Co Gammacell 220 (AECL), dose rate about 2 kGy/h. After irradiation the viscosity was measured on the viscometer Brookfield model LV-DVIII at 50, 60 and 70 deg C within a period of 48h. Pectin viscosity with high degree of methoxylation decreased sharply with the radiation dose remaining almost constant from 10 kGy. Pectin with low degree of methoxylation presented initially higher values of viscosity and the radiation induced decrease was also pronounced. Viscosity measurements decreased with the increase of the temperature applied for both kind of samples. The effect of radiation induced chain breaks generation in pectin molecules was evident through the viscosity reduction of irradiated pectin solutions although the viscosity presented diverse values depending of the degree of methoxylation of carboxyl groups in the backbone of polysaccharide macromolecules. (author)

  4. Radiation sensitivity basidiospore and mycelium in pleurotus ostreatus

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Keun; Chang, Hwa Hyoung [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1999-06-01

    To assess the effects of gamma-ray (Co-60) on radiation sensitivity and genetic similarity of the vasidiospore and mycelium in oyster mushroom, Pleurotus ostreatus, the D{sub 10} values and RAPD patterns were analysed. Three strains were isolated from basidiospores (PO-B1, -B2, and -B3 from 2 kGy irradiation group0 and five strains from mycelia (PO-M1, -M2 from 1 kGy, PO-M3 from 2 kGy, and PO-M4 and -M5 from 2+1 kGy irradiation group). The D{sub 10} values of extracellular chitinases of them were generally higher than those of the control. By the gamma-ray radiation, 22-25% of genetic similarities were changed in the basidiospore strains and 23-36% of them in the mycelium strains. From these results, it seems that the basidiospore could be more radio-resistant than the mycelium of P. ostreatus and that the genetic similarity of the mycelium of P. ostreatus could be changed easier than that of the basidiospore by the gamma-ray radiation. (author). 22 refs., 2 figs., 3 tabs.

  5. High sensitive radiation detector for radiology dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Valente, M.; Malano, F. [Instituto de Fisica Enrique Gaviola, Oficina 102 FaMAF - UNC, Av. Luis Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina); Molina, W.; Vedelago, J., E-mail: valente@famac.unc.edu.ar [Laboratorio de Investigaciones e Instrumentacion en Fisica Aplicada a la Medicina e Imagenes por Rayos X, Laboratorio 448 FaMAF - UNC, Ciudad Universitaria, 5000 Cordoba (Argentina)

    2014-08-15

    Fricke solution has a wide range of applications as radiation detector and dosimetry. It is particularly appreciated in terms of relevant comparative advantages, like tissue equivalence when prepared in aqueous media like gel matrix, continuous mapping capability, dose rate recorded and incident direction independence as well as linear dose response. This work presents the development and characterization of a novel Fricke gel system, based on modified chemical compositions making possible its application in clinical radiology. Properties of standard Fricke gel dosimeter for high dose levels are used as starting point and suitable chemical modifications are introduced and carefully investigated in order to attain high resolution for low dose ranges, like those corresponding to radiology interventions. The developed Fricke gel radiation dosimeter system achieves the expected typical dose dependency, actually showing linear response in the dose range from 20 up to 4000 mGy. Systematic investigations including several chemical compositions are carried out in order to obtain a good enough dosimeter response for low dose levels. A suitable composition among those studied is selected as a good candidate for low dose level radiation dosimetry consisting on a modified Fricke solution fixed to a gel matrix containing benzoic acid along with sulfuric acid, ferrous sulfate, xylenol orange and ultra-pure reactive grade water. Dosimeter samples are prepared in standard vials for its in phantom irradiation and further characterization by spectrophotometry measuring visible light transmission and absorbance before and after irradiation. Samples are irradiated by typical kV X-ray tubes and calibrated Farmer type ionization chamber is used as reference to measure dose rates inside phantoms in at vials locations. Once sensitive material composition is already optimized, dose-response curves show significant improvement regarding overall sensitivity for low dose levels. According to

  6. Development of a radiation-sensitive indicator

    Science.gov (United States)

    Abdel-Fattah, A. A.; El-Kelany, M.; Abdel-Rehim, F.

    1996-10-01

    A poly(vinyl alcohol) (PVA) film containing acid-sensitive dye (bromophenol red, BPR) and water soluble chlorine-containing substance [CCl 3COONa or chloral hydrate (CCl 3CH(OH) 2, 2,2,2-trichloroethan-1,1-diol)] may be useful as a radiation-sensitive indicator. The acid-sensitive dye in the film changes its color from violet to pale yellow by irradiation due to the consequent lowering of the pH of the film caused by the HCl generated from the radiolysis of the Cl-containing substance. This film can be used as a dosimeter in a relatively low dose range up to 5 kGy. This response range makes this film useful in some food irradiation, pasteurization and water purification applications. The effects of temperature and relative humidity during irradiation and post-irradiation storage on the response of the film are discussed. It is inexpensive, does not require toxic solvents in preparation and easy to prepare in a laboratory.

  7. Radiation sensitivity of hyperthermal composting microorganisms

    Science.gov (United States)

    Choi, Jong-Il; Yoon, Min-Chul; Kim, Jae-Hun; Yamashita, Masamichi; Kim, Geun Joong; Lee, Ju-Woon

    In the space station and vehicles designed for long human mission, high-temperature compost is a promising technology for decomposing organic waste and producing the fertilizers. In space, the microorganisms could have the changed biological activities or even be mutated by ionizing irradiation. Therefore, in this study, the effect of gamma irradiation on the sensitivity of bacteria in hyperthermal composting was investigated. The sequence analysis of the amplified 16s rDNA genes and amoA gene were used for the identification of composting microorganisms. Viability of microorganisms in compost soil after gamma irradiation was directly visualized with LIVE/DEAD Baclight viability kit. The dominant bacterial genera are Weissella cibaria and Leuconostoc sp. and fungus genera are Metschnikowia bicuspidate and Pichia guilliermondii, respectively. By the gamma irradiation up to the dose of 1 kGy, the microbial population was not changed. Also, the enzyme activities of amylase and cellulose were sustained by the gamma irradiation. These results show that these hyperthermia microorganisms might have the high resistance to gamma radiation and could be used for agriculture in the Space Station.

  8. Sensitivity of transient synchrotron radiation to tokamak plasma parameters

    Energy Technology Data Exchange (ETDEWEB)

    Fisch, N.J.; Kritz, A.H.

    1988-12-01

    Synchrotron radiation from a hot plasma can inform on certain plasma parameters. The dependence on plasma parameters is particularly sensitive for the transient radiation response to a brief, deliberate, perturbation of hot plasma electrons. We investigate how such a radiation response can be used to diagnose a variety of plasma parameters in a tokamak. 18 refs., 13 figs.

  9. Thermal radiosensitization in radiation-sensitive mutant mouse leukemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Toshikazu (Hiroshima Univ. (Japan). School of Dentistry)

    1994-06-01

    This study investigated thermal, radiation, and combined thermal radiation sensitization of mouse leukemic cells, L5178Y, and radiation-sensitive mutant cells, LX830. Radiation sensitivity (D[sub 0]) values were 0.41 Gy for LX830 and 1.39 Gy for L5178Y, with the ratio of D[sub 0] values in LX830 to in L5178Y being 3.4. Thus, LX830 was more radiosensitive than L5178Y. LX830 showed no shouldered survival curves. Although sublethal damage (SLD) repair was seen to the almost same degree in both LX830 and L5178Y, potential lethal damage (PLD) repair was scarcely observed in LX830. Both cell lines were similar in thermal sensitivity (T[sub 0]). Eosine staining suggested that cell killing due to hyperthermia had occurred in the interphase in both LX830 and L5178Y. L5178Y showed thermal sensitivity low in the G1 phase and high in the S phase; on the contrary, LX830 showed it high in the G1 phase and low in the S phase. Thermal radiosensitization was similar in both cell lines, although there was a great difference in radiation sensitivity between the cell lines. The difference in radiation sensitivity (D[sub 0]) between L5178Y and LX830 became small when radiation was given at the time of the maximum thermal resistance. This seemed to contribute to a decrease in radiation sensitivity in LX830. It can be concluded that thermal radiosensitization depends on thermal sensitivity and that radiation sensitivity decreases in radiation-sensitive cells when exposed to irradiation at the time of thermal resistance. (N.K.).

  10. Hemochromatosis heterozygotes may constitute a radiation-sensitive subpopulation.

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, R G.(GEORGE A GRANT INC); Morris, James E.(BATTELLE (PACIFIC NW LAB)); Anderson, Larry E.(BATTELLE (PACIFIC NW LAB))

    1999-12-01

    A primary mechanism of radiation-induced DNA damage is by generation of free radicals. Chronically increased oxidative stress from elevated body iron may increase radiation sensitivity by decreasing cellular oxygen radical scavenging capability. Hemochromatosis heterozygotes have elevated body iron. Low-level radiation sensitization by iron may be particularly pertinent for risk of breast cancer. Since ten percent of the population appears to be heterozygous for the hemochromatosis gene, a radiosensitizing effect would have pervasive implications.

  11. Genetic variation in resistance to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ayala, F.J.

    1992-01-01

    Results of an investigation of the gene coding for Cu, Zn superoxide dismutase (Sod) in Drosophila melanogaster seeking to understand the enzyme's role in cell protection against ionizing radiation are reported. Components of the investigation include molecular characterization of the gene; measuring the response of different genotypes to increasing levels of radiation; and investigation of the processes that maintain the Sod polymorphism in populations. While two alleles, S and F, are commonly found at the Sod locus in natural populations of D. melanogaster we have isolated from a natural population a null (CA1) mutant that yields only 3.5% of normal SOD activity. The S, F, and CA1 alleles provide a model system to investigate SOD-dependent radioresistance, because each allele yields different levels of SOD, so that S > F >> CAl. The radioprotective effects of SOD can be established by showing protective effects for the various genotypes that correspond to those inequalities. Because the allele variants studied are derived from natural populations, the proposed investigation avoids problems that arise when mutants obtained my mutagenesis are used. Moreover, each allele is studied in multiple genetic backgrounds, so that we correct for effects attributable to other loci by randomizing these effects.

  12. Genetics of allergy and allergic sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Sparks, Rachel; Waage, Johannes

    2015-01-01

    Our understanding of the specific genetic lesions in allergy has improved in recent years due to identification of common risk variants from genome-wide association studies (GWAS) and studies of rare, monogenic diseases. Large-scale GWAS have identified novel susceptibility loci and provided...... information about shared genetics between allergy, related phenotypes and autoimmunity. Studies of monogenic diseases have elucidated critical cellular pathways and protein functions responsible for allergy. These complementary approaches imply genetic mechanisms involved in Th2 immunity, T...

  13. Radiation sensitivity modification by chemotherapeutic agents

    Energy Technology Data Exchange (ETDEWEB)

    Hetzel, F.W.; Brown, M.; Kaufman, N.; Bicher, H.I.

    1981-01-01

    Three chemotherapeutic agents, chlorambucil, mustargen, and BCNU-409962, being investigated for their possible clinical use in conjunction with radiation therapy have been shown in vitro to dramatically affect the characteristics of standard radiation survival curves (in V79 cells and spheroids). The agent mustargen, at a concentration of 0.25 microgram/ml administered 1 hour prior to 9-MeV-electron exposure, had a significant effect in reducing D0. The 165-rad D0 observed in control curves was reduced to 105 rads in the presence of drug. One hour preincubation with BCNU (prior to radiation exposure) at a concentration of 3.0 microgram/ml was found to dramatically reduce the initial shoulder region with n number values for drug curves approximately one-half those seen for controls. No effect is seen when chlorambucil is combined with radiation in exponential or confluent cultures but an enhancement ratio of 1.8 is found when intact spheroids are pretreated with this drug.

  14. Genetic variation in normal tissue toxicity induced by ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Popanda, Odilia, E-mail: o.popanda@dkfz.de [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Marquardt, Jens Uwe [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Chang-Claude, Jenny [Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Schmezer, Peter [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2009-07-10

    Radiotherapy is an important weapon in the treatment of cancer, but adverse reactions developing in the co-irradiated normal tissue can be a threat for patients. Early reactions might disturb the usual application schedule and limit the radiation dose. Late appearing and degenerative reactions might reduce or destroy normal tissue function. Genetic markers conferring the ability to identify hyper-sensitive patients in advance would considerably improve therapy. Association studies on genetic variation and occurrence of side effects should help to identify such markers. This survey includes published studies and novel data from our own laboratory. It illustrates the presence of candidate polymorphisms in genes involved in the cellular response to irradiation which could be used as predictive markers for radiosensitivity in breast or prostate cancer patients. For other tumor types such as head and neck cancers or brain tumors, the available data are much more limited. In any case, further validation of these markers is needed in large patient cohorts with systematically recorded data on side effects and patient characteristics. Genetic variation contributing to radiosensitivity should be screened on a broader basis using newly developed, more comprehensive approaches such as genome-wide association studies.

  15. On the instability effects in radiation-sensitive chalcogenide glasses

    Energy Technology Data Exchange (ETDEWEB)

    Balitska, V. [Lviv State University for Vital Activity Safety, 35 Kleparivska str., Lviv, UA-79007 (Ukraine); Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine); Kovalskiy, A. [Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine); International Materials Institute for New Functionality in Glass, Lehigh University, 5 East Packer Avenue, Bethlehem, PA 18015-3195 (United States); Shpotyuk, O. [Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine); International Materials Institute for New Functionality in Glass, Lehigh University, 5 East Packer Avenue, Bethlehem, PA 18015-3195 (United States)], E-mail: shpotyuk@novas.lviv.ua; Vakiv, M. [Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine)

    2007-04-15

    The features of application of radiation-sensitive media based on chalcogenide glasses of As-Ge-S system for registration of high-energy {gamma}-radiation are analysed. It is shown that compositional features of the observed time-instability effect should be taken into account in order to ensure a higher accuracy of the developed dosimeters.

  16. Sensitivity of oysters (Crassostrea Brasiliana) to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mattiolo Marchese, S.R. [Brazilian Navy Technology Center, Sao Paulo (Brazil); Mastro, N.L. del [Inst. of Nuclear and Energy Researches IPEN-CNEN/SP, Sao Paulo (Brazil)

    1997-12-31

    Various foods including oysters, crabs and shrimps have been shown to be possible transmitters of Vibrio ssp. Irradiation of sea-foods is being considered an alternative to intervention measures in Public Health against food borne diseases. The aim of this work was to establish, the radiation resistance of the oysters Crassostrea brasiliana. The oysters were irradiated with Co-60 radiation with doses of 0, 1.5, 3 and 6 kGy. Survival curves as a function of time showed that 100% of the oysters irradiated with doses of 3 kGy survived at least 6 days. 100% those irradiated with 6 kGy survived 3 days. The obtained results are auspicious considering that a dose of 2 kGy is already effective in the diminishing of the microbial load on oysters. (author). 5 refs, 5 figs, 1 tab.

  17. Physical determinants of radiation sensitivity in bacterial spores

    Energy Technology Data Exchange (ETDEWEB)

    Powers, E.L.

    1982-01-01

    Several factors modifying radiation sensitivity in dry bacterial spores are described and discussed. Vacuum inducing the loss of critical structural water, very low dose rates of radiation from which the cell may recover, radiations of high linear energy transfer, and the action of temperature over long periods of time on previously irradiated cells are recognized from extensive laboratory work as important in determining survival of spores exposed to low radiation doses at low temperatures for long periods of time. Some extensions of laboratory work are proposed.

  18. Effect of troglitazone on radiation sensitivity in cervix cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    An, Zheng Zhe; Liu, Xian Guang; Song, Hye Jin; Choi, Chi Hwan; Kim, Won Dong; Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of); Yu, Jae Ran [Konkuk University College of Medicine, Chungju (Korea, Republic of)

    2012-06-15

    Troglitazone (TRO) is a peroxisome proliferator-activated receptor {gamma} (PPAR{gamma} ) agonist. TRO has antiproliferative activity on many kinds of cancer cells via G1 arrest. TRO also increases Cu{sup 2+}/Zn{sup 2+} -superoxide dismutase (CuZnSOD) and catalase. Cell cycle, and SOD and catalase may affect on radiation sensitivity. We investigated the effect of TRO on radiation sensitivity in cancer cells in vitro. Three human cervix cancer cell lines (HeLa, Me180, and SiHa) were used. The protein expressions of SOD and catalase, and catalase activities were measured at 2-10 {mu}M of TRO for 24 hours. Cell cycle was evaluated with flow cytometry. Reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate. Cell survival by radiation was measured with clonogenic assay. By 5 {mu}M TRO for 24 hours, the mRNA, protein expression and activity of catalase were increased in all three cell lines. G0- G1 phase cells were increased in HeLa and Me180 by 5 {mu}M TRO for 24 hours, but those were not increased in SiHa. By pretreatment with 5 {mu}M TRO radiation sensitivity was increased in HeLa and Me180, but it was decreased in SiHa. In Me180, with 2 {mu}M TRO which increased catalase but not increased G0-G1 cells, radiosensitization was not observed. ROS produced by radiation was decreased with TRO. TRO increases radiation sensitivity through G0-G1 arrest or decreases radiation sensitivity through catalasemediated ROS scavenging according to TRO dose or cell types. The change of radiation sensitivity by combined with TRO is not dependent on the PPAR {gamma} expression level.

  19. Effect of troglitazone on radiation sensitivity in cervix cancer cells.

    Science.gov (United States)

    An, Zhengzhe; Liu, Xianguang; Song, Hyejin; Choi, Chihwan; Kim, Won-Dong; Yu, Jae-Ran; Park, Woo-Yoon

    2012-06-01

    Troglitazone (TRO) is a peroxisome proliferator-activated receptor γ (PPARγ) agonist. TRO has antiproliferative activity on many kinds of cancer cells via G1 arrest. TRO also increases Cu(2+)/Zn(2+)-superoxide dismutase (CuZnSOD) and catalase. Cell cycle, and SOD and catalase may affect on radiation sensitivity. We investigated the effect of TRO on radiation sensitivity in cancer cells in vitro. Three human cervix cancer cell lines (HeLa, Me180, and SiHa) were used. The protein expressions of SOD and catalase, and catalase activities were measured at 2-10 µM of TRO for 24 hours. Cell cycle was evaluated with flow cytometry. Reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate. Cell survival by radiation was measured with clonogenic assay. By 5 µM TRO for 24 hours, the mRNA, protein expression and activity of catalase were increased in all three cell lines. G0-G1 phase cells were increased in HeLa and Me180 by 5 µM TRO for 24 hours, but those were not increased in SiHa. By pretreatment with 5 µM TRO radiation sensitivity was increased in HeLa and Me180, but it was decreased in SiHa. In Me180, with 2 µM TRO which increased catalase but not increased G0-G1 cells, radiosensitization was not observed. ROS produced by radiation was decreased with TRO. TRO increases radiation sensitivity through G0-G1 arrest or decreases radiation sensitivity through catalase-mediated ROS scavenging according to TRO dose or cell types. The change of radiation sensitivity by combined with TRO is not dependent on the PPARγ expression level.

  20. Radiation sensitive devices and systems for detection of radioactive materials and related methods

    Science.gov (United States)

    Kotter, Dale K

    2014-12-02

    Radiation sensitive devices include a substrate comprising a radiation sensitive material and a plurality of resonance elements coupled to the substrate. Each resonance element is configured to resonate responsive to non-ionizing incident radiation. Systems for detecting radiation from a special nuclear material include a radiation sensitive device and a sensor located remotely from the radiation sensitive device and configured to measure an output signal from the radiation sensitive device. In such systems, the radiation sensitive device includes a radiation sensitive material and a plurality of resonance elements positioned on the radiation sensitive material. Methods for detecting a presence of a special nuclear material include positioning a radiation sensitive device in a location where special nuclear materials are to be detected and remotely interrogating the radiation sensitive device with a sensor.

  1. Genetic effects of radiation. [Extrapolation of mouse data to man

    Energy Technology Data Exchange (ETDEWEB)

    Selby, P.B.

    1976-01-01

    Data are reviewed from studies on the genetic effects of x radiation in mice and the extrapolation of the findings for estimating genetic hazards in man is discussed. Data are included on the frequency of mutation induction following acute or chronic irradiation of male or female mice at various doses and dose rates.

  2. Mutagen sensitivity: a genetic predisposition factor for cancer.

    Science.gov (United States)

    Wu, Xifeng; Gu, Jian; Spitz, Margaret R

    2007-04-15

    Mutagen sensitivity, measured by quantifying the chromatid breaks induced by mutagens in short-term cultures of peripheral blood lymphocytes, has been used as an indirect measure of DNA repair capacity. Numerous epidemiologic studies have suggested that mutagen sensitivity is a cancer susceptibility factor for a variety of epithelial cancers. A recent classic twin study examined systematically the role of genetic and environmental factors on the mutagen sensitivity phenotype and provided compelling evidence that mutagen sensitivity is highly heritable. A new prospective analysis provides further support to the notion that mutagen sensitivity increases the risk of cancer. In this review, we briefly summarize nearly two decades of epidemiologic and genetic studies linking mutagen sensitivity and cancer risk. The evidence is becoming increasingly convincing that mutagen sensitivity is a risk factor for cancer development.

  3. Multipurpose High Sensitivity Radiation Detector: Terradex

    Energy Technology Data Exchange (ETDEWEB)

    Alpat, Behcet [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy)]. E-mail: behcet.alpat@pg.infn.it; Aisa, Damiano [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Bizzarri, Marco [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Blasko, Sandor [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Esposito, Gennaro [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Farnesini, Lucio [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Fiori, Emmanuel [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Papi, Andrea [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Postolache, Vasile [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Renzi, Francesca [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Ionica, Romeo [Politecnica University of Bucarest, Splaiul Indipendentei, Bucharest (Romania); Manolescu, Florentina [Space Science Institute of Bucharest, Maugurele, Bucharest (Romania); Ozkorucuklu, Suat [Suleyman Demirel Universitesi, Isparta (Turkey); Denizli, Haluk [Abant Izzet Baysal Universitesi, Bolu (Turkey); Tapan, Ilhan [Uludag Universitesi, Bursa (Turkey); Ercan Pilicer [Uludag Universitesi, Bursa (Turkey); Egidi, Felice [SITE Technology, Carsoli (Italy); Moretti, Cesare [SITE Technology, Carsoli(AQ) (Italy); Dicola, Luca [SITE Technology, Carsoli(AQ) (Italy)

    2007-05-11

    Terradex project aims to realise an accurate and programmable multiparametric tool which will measure relevant physical quantities such as observation time, energy and type of all decay products of three naturally occurring decay chains of uranium and thorium series present in nature as well as the decay products of man-made radioactivity. The measurements described in this work are based on the performance tests of the first version of an instrument that is designed to provide high counting accuracy, by introducing self-triggering, delayed time-coincidence technique, of products of a given decay chain. In order to qualify the technique and to calibrate the Terradex, a {sup 222}Rn source is used. The continuous and accurate monitoring of radon concentration in air is realised by observing the alpha and beta particles produced by the decay of {sup 222}Rn and its daughters and tag each of them with a precise occurrence time. The validity of delayed coincident technique by using the state of the art electronics with application of novel data sampling and analysis methods are discussed. The flexibility of sampling protocols and the advantages of online calibration capability to achieve the highest level of precision in natural and man-made radiation measurements are also described.

  4. Differential sensitivity of Chironomus and human hemoglobin to gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gaikwad, Pallavi S. [Stress Biology Research Laboratory, Department of Zoology, Savitribai Phule University, Pune, 411007 (India); Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Panicker, Lata [Solid State Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Mohole, Madhura; Sawant, Sangeeta [Bioinformatics Center, Savitribai Phule Pune University, Pune, 411007 (India); Mukhopadhyaya, Rita [Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Nath, Bimalendu B., E-mail: bbnath@gmail.com [Stress Biology Research Laboratory, Department of Zoology, Savitribai Phule University, Pune, 411007 (India)

    2016-08-05

    Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study. -- Highlights: •Comparison of radiation tolerant Chironomus Hb and radiation sensitive Human Hb. •Amino acid composition of midge and human heme confer differential hydrophobicity. •Heme pocket of evolutionarily ancient midge Hb provide gamma radiation resistivity.

  5. Acoustic design sensitivity analysis of structural sound radiation

    Institute of Scientific and Technical Information of China (English)

    许智生

    2009-01-01

    This paper presents an acoustic design sensitivity(ADS)analysis on sound radiation of structures by using the boundary element method(BEM).We calculated the velocity distribution of the thin plate by analytical method and the surface sound pressure by Rayleigh integral,and expressed the sound radiation power of the structure in a positive definite quadratic form of the Hermitian with an impedance matrix.The ADS analysis of the plate was thus translated into the analysis of structure dynamic sensitivity and ...

  6. Bacterial inactivation by solar ultraviolet radiation compared with sensitivity to 254 nm radiation.

    Science.gov (United States)

    Coohill, Thomas P; Sagripanti, Jose-Luis

    2009-01-01

    Our goal was to derive a quantitative factor that would allow us to predict the solar sensitivity of vegetative bacterial cells to natural solar radiation from the wealth of data collected for cells exposed to UVC (254 nm) radiation. We constructed a solar effectiveness spectrum for inactivation of vegetative bacterial cells by combining the available action spectra for vegetative cell killing in the solar range with the natural sunlight spectrum that reaches the ground. We then analyzed previous studies reporting the effects of solar radiation on vegetative bacterial cells and on bacterial spores. Although UVC-sensitive cells were also more sensitive to solar radiation, we found no absolute numerical correlation between the relative solar sensitivity of vegetative cells and their sensitivity to 254 nm radiation. The sensitivity of bacterial spores to solar exposure during both summer and winter correlated closely to their UVC sensitivity. The estimates presented here should make it possible to reasonably predict the time it would take for natural solar UV to kill bacterial spores or with a lesser degree of accuracy, vegetative bacterial cells after dispersion from an infected host or after an accidental or intentional release.

  7. Radiation sensitivity of pine wood nematodes in woodchips

    Energy Technology Data Exchange (ETDEWEB)

    Eichholz, G.G.; Bogdanov, A.A. (Georgia Inst. of Tech., Atlanta, GA (USA)); Dwinell, L.D. (Forest Service, Athens, GA (USA). Forestry Sciences Lab.)

    1991-01-01

    The radiation sensitivity of pine wood nematodes has been tested over a range of dose values with a cesium-137 irradiator. Lethal doses were found to lie in a range above 6-8 kGy, too high to make this an economically attractive means of deinfestation for commercial woodchips. (author).

  8. Multiparametric assessment of radiation effects for the individual radiation sensitivity estimation; Multiparametrische Erfassung von Strahlenwirkungen zur Abschaetzung der individuellen Strahlenempfindlichkeit

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    The effects of low dose irradiation are highly relevant for radiation protection in the public. The sensitivity to clastogenic and tumorigenic effects of ionizing radiation (IR) varies considerably amongst individuals. Examples for genetically determined enhanced sensitivity are well known in some hereditary diseases: patients with chromosomal instability syndromes, Ataxia telangiectasia (A-T), Nijmegen Breakage Syndrome (NBS) and Bloom Syndrome (BS) show strongly enhanced sensitivity towards IR, severe immunodeficiencies, and a high incidence for developing leukemias and lymphomas. This obvious coincidence of enhanced radiosensitivity and tumor risk, and the frequently observed enhanced radiosensitivity of genetically non-defined tumor patients indicate that tumor patients may constitute a subpopulation with enriched genetical predisposition for enhanced radiosensitivity. Furthermore, a subpopulation of radiosensitive individuals may be part of the probably inconspicuous total population. For example, individuals heterozygous for the above mentioned genes (and possibly some other genes) show enhanced radiosensitivity if compared with the normal population. In general, heterozygous carriers of those hereditary deficiencies are clinically inconspicuous, but due an haploinsufficiency their tumour risk may be enhanced. This has been shown for mice carrying an heterozygous Nbs1 mutation (J.-Q. Wang, Lyon, pers. Communication). Our findings concerning enhanced radiation-induced chromosomal aberrations in heterozygous Nbs1 cell lines support this notion. The identification of high risk groups with enhanced radiosensitivity is therefore an important task for radioprotection. This project aimed at establishing a procedure which allows to test various cellular parameters as indicators for effects of radiation. A standard protocol for the isolation and cryoconservation of primary blood cells was developed. DNA repair analysis (Comet Assay) and radiation-induced apoptosis

  9. Intrauterine and genetic factors in early childhood sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus

    2010-01-01

    The allergy-associated (atopic) diseases; asthma, eczema and rhinoconjunctivitis, are the most common chronic diseases in childhood. A large number of environmental and genetic risk factors have been suggested, but still our understanding of the underlying disease mechanisms and etiologies...... of opportunity” for prevention. The aim of this thesis was to increase the understanding of sensitization in early life. We studied indicators of sensitization in the newborn, and early development of sensitization and disease associated with a newly discovered genetic risk factor. Such insight may increase our...... and identifying the environmental risk factors interacting with this genetic susceptibility and the age at which intervention should be initiated. We found a FLG-associated pattern of atopic disease in early childhood characterized by early onset of eczema, early onset of asthma with severe exacerbations...

  10. Intrauterine and genetic factors in early childhood sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus

    2010-01-01

    predictive value of elevated cord blood IgE found in recent studies. Future studies should control for materno-fetal transfer of IgE or preferably use other markers of atopy. Variation in the gene coding for the skin barrier protein filaggrin (FLG) is the strongest known genetic risk factor for eczema. FLG......The allergy-associated (atopic) diseases; asthma, eczema and rhinoconjunctivitis, are the most common chronic diseases in childhood. A large number of environmental and genetic risk factors have been suggested, but still our understanding of the underlying disease mechanisms and etiologies...... of opportunity” for prevention. The aim of this thesis was to increase the understanding of sensitization in early life. We studied indicators of sensitization in the newborn, and early development of sensitization and disease associated with a newly discovered genetic risk factor. Such insight may increase our...

  11. The Effect of Genetic Polymorphism upon Antineoplastic Sensitivity

    Institute of Scientific and Technical Information of China (English)

    Jun Liang

    2006-01-01

    In clinical practice, patients undergoing chemotherapy display prominent individual differences, adverse reactions and sensitivity to antineoplastic therapy. Those differences are caused by individual genetic polymorphism of related genes. Genetic variation can induce distinct alterations of drug-metabolizing enzymes, drug transporters, drug targets and DNA repair enzymes and thereby influence the ability of the drugs to reach their target sites. This article reviews in detail the potential interactions mentioned above.

  12. Sensitivity to Radiation-Induced Cancer in Hemochromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Bull. Richard J.; Anderson, Larry E.

    2000-06-01

    The objectives of this pilot project using HFE-knockout homozygotes and heterozygotes are to (1) determine whether the knock-out mice have greater sensitivity to radiation-induced cancer of the colon, liver and breast, (2) establish the dependence of this sensitivity on the accumulation of iron, (3) determine the extent to which cell replication and apoptosis occur in these target tissues with varying iron load, and (4) correlate the increases in sensitivity with changes in insulin-related signaling in tumors and normal tissue from each target organ. Three experimental designs will be used in the pilot project. The sequence of experiments is designed to first explore the influence of iron load on the response and demonstrate that HFE knockout mice are more sensitive than the wild type to radiation-induced cancer in one or more of three target tissues (liver, colon and breast). The dose response relationships with a broader set of radiation doses will be explored in the second experiment. The final experiment is designed to explore the extent to which heterozygotes display the increased susceptibility to cancer induction and to independently assess the importance of iron load to the initiation versus promotion of tumors.

  13. Gamma response study of radiation sensitive MOSFETs for their use as gamma radiation sensor

    Science.gov (United States)

    Srivastava, Saurabh; Aggarwal, Bharti; Singh, Arvind; Kumar, A. Vinod; Topkar, Anita

    2016-05-01

    Continuous monitoring of gamma dose is important in various fields like radiation therapy, space-related research, nuclear energy programs and high energy physics experiment facilities. The present work is focused on utilization of radiation-sensitive Metal-Oxide-Semiconductor Field Effect Transistors (MOSFETs) to monitor gamma radiation doses. Static characterization of these detectors was performed to check their expected current-voltage relationship. Threshold voltage and transconductance per unit gate to source voltage (K factor) were calculated from the experimental data. The detector was exposed to gamma radiation in both, with and without gate bias voltage conditions, and change in threshold voltage was monitored at different gamma doses. The experimental data was fitted to obtain equation for dependence of threshold voltage on gamma dose. More than ten times increase in sensitivity was observed in biased condition (+3 V) compared to the unbiased case.

  14. Nonverbal Sensitivity: Consequences for Learning and Satisfaction in Genetic Counseling

    Science.gov (United States)

    Roter, D. L.; Erby, L. H.; Hall, J. A.; Larson, S.; Ellington, L.; Dudley, W.

    2008-01-01

    Purpose: This study aims to explore the role of interactants' nonverbal sensitivity, anxiety and sociodemographic characteristics in learning and satisfaction within the genetic counseling context. Design/methodology/approach: This is a combined simulation and analogue study. Simulations were videotaped with 152 prenatal and cancer genetic…

  15. Understanding the Science-Learning Environment: A Genetically Sensitive Approach

    Science.gov (United States)

    Haworth, Claire M. A.; Davis, Oliver S. P.; Hanscombe, Ken B.; Kovas, Yulia; Dale, Philip S.; Plomin, Robert

    2013-01-01

    Previous studies have shown that environmental influences on school science performance increase in importance from primary to secondary school. Here we assess for the first time the relationship between the science-learning environment and science performance using a genetically sensitive approach to investigate the aetiology of this link. 3000…

  16. In-Space Radiator Shape Optimization using Genetic Algorithms

    Science.gov (United States)

    Hull, Patrick V.; Kittredge, Ken; Tinker, Michael; SanSoucie, Michael

    2006-01-01

    Future space exploration missions will require the development of more advanced in-space radiators. These radiators should be highly efficient and lightweight, deployable heat rejection systems. Typical radiators for in-space heat mitigation commonly comprise a substantial portion of the total vehicle mass. A small mass savings of even 5-10% can greatly improve vehicle performance. The objective of this paper is to present the development of detailed tools for the analysis and design of in-space radiators using evolutionary computation techniques. The optimality criterion is defined as a two-dimensional radiator with a shape demonstrating the smallest mass for the greatest overall heat transfer, thus the end result is a set of highly functional radiator designs. This cross-disciplinary work combines topology optimization and thermal analysis design by means of a genetic algorithm The proposed design tool consists of the following steps; design parameterization based on the exterior boundary of the radiator, objective function definition (mass minimization and heat loss maximization), objective function evaluation via finite element analysis (thermal radiation analysis) and optimization based on evolutionary algorithms. The radiator design problem is defined as follows: the input force is a driving temperature and the output reaction is heat loss. Appropriate modeling of the space environment is added to capture its effect on the radiator. The design parameters chosen for this radiator shape optimization problem fall into two classes, variable height along the width of the radiator and a spline curve defining the -material boundary of the radiator. The implementation of multiple design parameter schemes allows the user to have more confidence in the radiator optimization tool upon demonstration of convergence between the two design parameter schemes. This tool easily allows the user to manipulate the driving temperature regions thus permitting detailed design of in

  17. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kleiman, Norman Jay [Columbia University

    2013-11-30

    The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9

  18. Neuro-genetic system for optimization of GMI samples sensitivity.

    Science.gov (United States)

    Pitta Botelho, A C O; Vellasco, M M B R; Hall Barbosa, C R; Costa Silva, E

    2016-03-01

    Magnetic sensors are largely used in several engineering areas. Among them, magnetic sensors based on the Giant Magnetoimpedance (GMI) effect are a new family of magnetic sensing devices that have a huge potential for applications involving measurements of ultra-weak magnetic fields. The sensitivity of magnetometers is directly associated with the sensitivity of their sensing elements. The GMI effect is characterized by a large variation of the impedance (magnitude and phase) of a ferromagnetic sample, when subjected to a magnetic field. Recent studies have shown that phase-based GMI magnetometers have the potential to increase the sensitivity by about 100 times. The sensitivity of GMI samples depends on several parameters, such as sample length, external magnetic field, DC level and frequency of the excitation current. However, this dependency is yet to be sufficiently well-modeled in quantitative terms. So, the search for the set of parameters that optimizes the samples sensitivity is usually empirical and very time consuming. This paper deals with this problem by proposing a new neuro-genetic system aimed at maximizing the impedance phase sensitivity of GMI samples. A Multi-Layer Perceptron (MLP) Neural Network is used to model the impedance phase and a Genetic Algorithm uses the information provided by the neural network to determine which set of parameters maximizes the impedance phase sensitivity. The results obtained with a data set composed of four different GMI sample lengths demonstrate that the neuro-genetic system is able to correctly and automatically determine the set of conditioning parameters responsible for maximizing their phase sensitivities.

  19. Semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia.

    Directory of Open Access Journals (Sweden)

    Ian S Miller

    Full Text Available Glioblastoma is the most malignant and lethal form of astrocytoma, with patients having a median survival time of approximately 15 months with current therapeutic modalities. It is therefore important to identify novel therapeutics. There is mounting evidence that microglia (specialized brain-resident macrophages play a significant role in the development and progression of glioblastoma tumors. In this paper we show that microglia, in addition to stimulating glioblastoma cell invasion, also promote glioblastoma cell proliferation and resistance to ionizing radiation in vitro. We found that semapimod, a drug that selectively interferes with the function of macrophages and microglia, potently inhibits microglia-stimulated GL261 invasion, without affecting serum-stimulated glioblastoma cell invasion. Semapimod also inhibits microglia-stimulated resistance of glioblastoma cells to radiation, but has no significant effect on microglia-stimulated glioblastoma cell proliferation. We also found that intracranially administered semapimod strongly increases the survival of GL261 tumor-bearing animals in combination with radiation, but has no significant benefit in the absence of radiation. In conclusion, our observations indicate that semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia and/or infiltrating macrophages.

  20. Semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia.

    Science.gov (United States)

    Miller, Ian S; Didier, Sebastien; Murray, David W; Turner, Tia H; Issaivanan, Magimairajan; Ruggieri, Rosamaria; Al-Abed, Yousef; Symons, Marc

    2014-01-01

    Glioblastoma is the most malignant and lethal form of astrocytoma, with patients having a median survival time of approximately 15 months with current therapeutic modalities. It is therefore important to identify novel therapeutics. There is mounting evidence that microglia (specialized brain-resident macrophages) play a significant role in the development and progression of glioblastoma tumors. In this paper we show that microglia, in addition to stimulating glioblastoma cell invasion, also promote glioblastoma cell proliferation and resistance to ionizing radiation in vitro. We found that semapimod, a drug that selectively interferes with the function of macrophages and microglia, potently inhibits microglia-stimulated GL261 invasion, without affecting serum-stimulated glioblastoma cell invasion. Semapimod also inhibits microglia-stimulated resistance of glioblastoma cells to radiation, but has no significant effect on microglia-stimulated glioblastoma cell proliferation. We also found that intracranially administered semapimod strongly increases the survival of GL261 tumor-bearing animals in combination with radiation, but has no significant benefit in the absence of radiation. In conclusion, our observations indicate that semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia and/or infiltrating macrophages.

  1. Genetic damage in subjects exposed to radiofrequency radiation.

    Science.gov (United States)

    Verschaeve, Luc

    2009-01-01

    Despite many research efforts and public debate there is still great concern about the possible adverse effects of radiofrequency (RF) radiation on human health. This is especially due to the enormous increase of wireless mobile telephones and other telecommunication devices throughout the world. The possible genetic effects of mobile phone radiation and other sources of radiofrequencies constitute one of the major points of concern. In the past several review papers were published on laboratory investigations that were devoted to in vitro and in vivo animal (cyto)genetic studies. However, it may be assumed that some of the most important observations are those obtained from studies with individuals that were exposed to relatively high levels of radiofrequency radiation, either as a result of their occupational activity or as frequent users of radiofrequency emitting tools. In this paper the cytogenetic biomonitoring studies of RF-exposed humans are reviewed. A majority of these studies do show that RF-exposed individuals have increased frequencies of genetic damage (e.g., chromosomal aberrations) in their lymphocytes or exfoliated buccal cells. However, most of the studies, if not all, have a number of shortcomings that actually prevents any firm conclusion. Radiation dosimetry was lacking in all papers, but some of the investigations were flawed by much more severe imperfections. Large well-coordinated multidisciplinary investigations are needed in order to reach any robust conclusion.

  2. [Factors of individual radiation sensitivity in caries prevalence in population of radiation polluted regions].

    Science.gov (United States)

    Sevbitov, A V; Skatova, E A

    2005-01-01

    Analysing dental diseases prevalence in population of radiation polluted regions after the Chernobyl accident, one should take into account not only the level of the soil contamination with radionuclides but also factors of individual sensitivity to radioactivity, main of which is the age of the exposed person.

  3. Targeting Nucleophosmin 1 Represents a Rational Strategy for Radiation Sensitization

    Energy Technology Data Exchange (ETDEWEB)

    Sekhar, Konjeti R. [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Benamar, Mouadh [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Venkateswaran, Amudhan; Sasi, Soumya [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Penthala, Narsimha R.; Crooks, Peter A. [Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hann, Stephen R. [Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Geng, Ling [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Balusu, Ramesh [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas (United States); Abbas, Tarek [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Freeman, Michael L., E-mail: michael.freeman@vanderbilt.edu [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States)

    2014-08-01

    Purpose: To test the hypothesis that small molecule targeting of nucleophosmin 1 (NPM1) represents a rational approach for radiosensitization. Methods and Materials: Wilde-type and NPM1-deficient mouse embryo fibroblasts (MEFs) were used to determine whether radiosensitization produced by the small molecule YTR107 was NPM1 dependent. The stress response to ionizing radiation was assessed by quantifying pNPM1, γH2AX, and Rad51 foci, neutral comet tail moment, and colony formation. NPM1 levels in a human-derived non-small-cell lung cancer (NSCLC) tissue microarray (TMA) were determined by immunohistochemistry. YTR107-mediated radiosensitization was assessed in NSCLC cell lines and xenografts. Results: Use of NPM1-null MEFs demonstrated that NPM1 is critical for DNA double- strand break (DSB) repair, that loss of NPM1 increases radiation sensitivity, and that YTR107-mediated radiosensitization is NPM1 dependent. YTR107 was shown to inhibit NPM1 oligomerization and impair formation of pNPM1 irradiation-induced foci that colocalized with γH2AX foci. Analysis of the TMA demonstrated that NPM1 is overexpressed in subsets of NSCLC. YTR107 inhibited DNA DSB repair and radiosensitized NSCLC lines and xenografts. Conclusions: These data demonstrate that YTR107-mediated targeting of NPM1 impairs DNA DSB repair, an event that increases radiation sensitivity.

  4. Genetic Loci Associated with Allergic Sensitization in Lithuanians.

    Directory of Open Access Journals (Sweden)

    Ingrida Šaulienė

    Full Text Available Allergic rhinitis (AR is a common and complex disease. It is associated with environmental as well as genetic factors. Three recent genome-wide association studies (GWAS reported altogether 47 single nucleotide polymorphisms (SNPs associated with AR or allergic sensitization (AS in Europeans and North Americans. Two follow up studies in Swedish and Chinese replicated 15 associations. In these studies individuals were selected based on the self-reported AR, or AR/AS diagnosed using blood IgE test or skin prick test (SPT, which were performed often without restriction to specific allergens. Here we performed third replication study in Lithuanians. We used SPT and carefully selected set of allergens prevalent in Lithuania, as well as Illumina Core Exome chip for SNP detection. We genotyped 270 SPT-positive individuals (137 Betulaceae -, 174 Poaceae-, 199 Artemisia-, 70 Helianthus-, 22 Alternaria-, 22 Cladosporium-, 140 mites-, 95 cat- and 97 dog dander-sensitive cases and 162 SPT-negative controls. We found altogether 13 known SNPs associated with AS (p ≤0.05. Three SNPs were found in Lithuanians sensitive to several allergens, and 10 SNPs were found in Lithuanians sensitive to a certain allergen. For the first time, SNP rs7775228:C was associated with patient sensitivity to dog allergens (F_A=0,269, F_U=0.180, P=0.008. Thus, careful assessment of AS allowed us to detect known genetic variants associated with AS/AR in relatively small cohort of Lithuanians.

  5. Genetic Loci Associated with Allergic Sensitization in Lithuanians.

    Science.gov (United States)

    Šaulienė, Ingrida; Greičiuvienė, Jūratė; Šukienė, Laura; Juškevičiūtė, Neringa; Benner, Christian; Zinkevičienė, Auksė; Ripatti, Samuli; Donner, Kati; Kainov, Denis

    2015-01-01

    Allergic rhinitis (AR) is a common and complex disease. It is associated with environmental as well as genetic factors. Three recent genome-wide association studies (GWAS) reported altogether 47 single nucleotide polymorphisms (SNPs) associated with AR or allergic sensitization (AS) in Europeans and North Americans. Two follow up studies in Swedish and Chinese replicated 15 associations. In these studies individuals were selected based on the self-reported AR, or AR/AS diagnosed using blood IgE test or skin prick test (SPT), which were performed often without restriction to specific allergens. Here we performed third replication study in Lithuanians. We used SPT and carefully selected set of allergens prevalent in Lithuania, as well as Illumina Core Exome chip for SNP detection. We genotyped 270 SPT-positive individuals (137 Betulaceae -, 174 Poaceae-, 199 Artemisia-, 70 Helianthus-, 22 Alternaria-, 22 Cladosporium-, 140 mites-, 95 cat- and 97 dog dander-sensitive cases) and 162 SPT-negative controls. We found altogether 13 known SNPs associated with AS (p ≤0.05). Three SNPs were found in Lithuanians sensitive to several allergens, and 10 SNPs were found in Lithuanians sensitive to a certain allergen. For the first time, SNP rs7775228:C was associated with patient sensitivity to dog allergens (F_A=0,269, F_U=0.180, P=0.008). Thus, careful assessment of AS allowed us to detect known genetic variants associated with AS/AR in relatively small cohort of Lithuanians.

  6. Advances in radiation biology: Relative radiation sensitivities of human organ systems. Volume 12

    Energy Technology Data Exchange (ETDEWEB)

    Lett, J.T.; Altman, K.I.; Ehmann, U.K.; Cox, A.B.

    1987-01-01

    This volume is a thematically focused issue of Advances in Radiation Biology. The topic surveyed is relative radiosensitivity of human organ systems. Topics considered include relative radiosensitivities of the thymus, spleen, and lymphohemopoietic systems; relative radiosensitivities of the small and large intestine; relative rediosensitivities of the oral cavity, larynx, pharynx, and esophagus; relative radiation sensitivity of the integumentary system; dose response of the epidermal; microvascular, and dermal populations; relative radiosensitivity of the human lung; relative radiosensitivity of fetal tissues; and tolerance of the central and peripheral nervous system to therapeutic irradiation.

  7. Genetic Variability in Susceptibility to Occupational Respiratory Sensitization

    Directory of Open Access Journals (Sweden)

    Berran Yucesoy

    2011-01-01

    Full Text Available Respiratory sensitization can be caused by a variety of substances at workplaces, and the health and economic burden linked to allergic respiratory diseases continues to increase. Although the main factors that affect the onset of the symptoms are the types and intensity of allergen exposure, there is a wide range of interindividual variation in susceptibility to occupational/environmental sensitizers. A number of gene variants have been reported to be associated with various occupational allergic respiratory diseases. Examples of genes include, but are not limited to, genes involved in immune/inflammatory regulation, antioxidant defenses, and fibrotic processes. Most of these variants act in combination with other genes and environmental factors to modify disease progression, severity, or resolution after exposure to allergens. Therefore, understanding the role of genetic variability and the interaction between genetic and environmental/occupational factors provides new insights into disease etiology and may lead to the development of novel preventive and therapeutic strategies. This paper will focus on the current state of knowledge regarding genetic influences on allergic respiratory diseases, with specific emphasis on diisocyanate-induced asthma and chronic beryllium disease.

  8. How plasticity, genetic assimilation and cryptic genetic variation may contribute to adaptive radiations.

    Science.gov (United States)

    Schneider, Ralf F; Meyer, Axel

    2017-01-01

    There is increasing evidence that phenotypic plasticity can promote population divergence by facilitating phenotypic diversification and, eventually, genetic divergence. When a 'plastic' population colonizes a new habitat, it has the possibility to occupy multiple niches by expressing several distinct phenotypes. These initially reflect the population's plastic range but may later become genetically fixed by selection via the process of 'genetic assimilation' (GA). Through this process multiple specialized sister lineages can arise that share a common plastic ancestor - the 'flexible stem'. Here, we review possible molecular mechanisms through which natural selection could fix an initially plastic trait during GA. These mechanisms could also explain how GA may contribute to cryptic genetic variation that can subsequently be coopted into other phenotypes or traits, but also lead to nonadaptive responses. We outline the predicted patterns of genetic and transcriptional divergence accompanying flexible stem radiations. The analysis of such patterns of (retained) adaptive and nonadaptive plastic responses within and across radiating lineages can inform on the state of ongoing GA. We conclude that, depending on the stability of the environment, the molecular architecture underlying plastic traits can facilitate diversification, followed by fixation and consolidation of an adaptive phenotype and degeneration of nonadaptive ones. Additionally, the process of GA may increase the cryptic genetic variation of populations, which on one hand may serve as substrate for evolution, but on another may be responsible for nonadaptive responses that consolidate local allopatry and thus reproductive isolation.

  9. Developing culturally sensitive cancer genetics communication aids for African Americans.

    Science.gov (United States)

    Baty, Bonnie Jeanne; Kinney, Anita Yeomans; Ellis, Sara Marie

    2003-04-15

    The goal of this project was to develop educational materials to communicate genetic health information in a culturally sensitive manner. These materials were designed to communicate information about cancer risk, genetic testing options, and health management options in an African American kindred with a known BRCA1 mutation. Educational materials were pilot-tested in four African American focus groups varying in socioeconomic status and gender. The audiotaped focus groups consisted of presentation of the educational materials, followed by a feedback session led by an African American facilitator. Qualitative analysis of the focus group transcripts identified important themes and the educational materials were revised in response to the participants' suggestions. The products included a booklet and a flip chart for use in educational sessions. Focus group participants recommended a substantial reduction in technical detail, and recommended that information be personalized and made relevant to the lives of the target population. Other critical themes included the importance of building trust in the medical system and avoiding words and images that have strong negative associations in the African American community. Strategies that were successful included nontechnical images to explain genetic concepts, clip art images to energize and personalize word slides, vibrant color, identifiably African American figures, and the development of themes relevant to many African Americans. The use of these materials in an ongoing study offering BRCA1 counseling and testing to a large, rural Louisiana-based kindred will provide additional feedback about the effectiveness of the culturally tailored genetic education and counseling materials.

  10. Genetic susceptibility: radiation effects relevant to space travel.

    Science.gov (United States)

    Peng, Yuanlin; Nagasawa, Hatsumi; Warner, Christy; Bedford, Joel S

    2012-11-01

    Genetic variation in the capacity to repair radiation damage is an important factor influencing both cellular and tissue radiosensitivity variation among individuals as well as dose rate effects associated with such damage. This paper consists of two parts. The first part reviews some of the available data relating to genetic components governing such variability among individuals in susceptibility to radiation damage relevant for radiation protection and discusses the possibility and extent to which these may also apply for space radiations. The second part focuses on the importance of dose rate effects and genetic-based variations that influence them. Very few dose rate effect studies have been carried out for the kinds of radiations encountered in space. The authors present here new data on the production of chromosomal aberrations in noncycling low passage human ATM+/+ or ATM+/- cells following irradiations with protons (50 MeV or 1 GeV), 1 GeV(-1) n iron ions and gamma rays, where doses were delivered at a high dose rate of 700 mGy(-1) min, or a lower dose rate of 5 mGy min(-1). Dose responses were essentially linear over the dose ranges tested and not significantly different for the two cell strains. Values of the dose rate effectiveness factor (DREF) were expressed as the ratio of the slopes of the dose-response curves for the high versus the lower (5 mGy min(-1)) dose rate exposures. The authors refer to this as the DREF5. For the gamma ray standard, DREF5 values of approximately two were observed. Similar dose rate effects were seen for both energies of protons (DREF5 ≈ 2.2 in both cases). For 1 GeV(-1) n iron ions [linear energy transfer (LET) ≈ 150 keV μ(-1)], the DREF5 was not 1 as might have been expected on the basis of LET alone but was approximately 1.3. From these results and conditions, the authors estimate that the relative biological effectiveness for 1 GeV(-1) n iron ions for high and low dose rates, respectively, were about 10 and 15

  11. Surprising Sensitivities in Simulations of Radiative Convective Equilibrium

    Science.gov (United States)

    Drotos, Gabor; Becker, Tobias; Mauritsen, Thorsten; Stevens, Bjorn

    2017-04-01

    The climate and climate-sensitivity of a global model run in radiative equilibrium is explored. Results from simulations with ECHAM6.3 coupled to a slab ocean and run in a wide range of configurations are presented. Simulations both with and without a parameterised representation of deep convection are conducted for CO2 concentrations ranging from one eighth of present day values to thirty-two times the present day, and for variations in the solar constant of more than a factor of two. Very long simulations, in some case more than a thousand years, are performed to adequately sample the attractor of the different climate states of the model, and provide robust estimates of the system's climate sensitivity parameter. For the standard configuration of the model the climate sensitivity progressively decreases from very large values (6-7K) for the coldest climates to well below 1 K for the warmest climates. For very high CO2 levels (16 and 32 times the present value) fluctuations of globally averaged temperature as large as 10 K arise on decadal time-scales. These fluctuations manifest as quasi-period coolings, driven by large and persistent global scale decks of stratiform low clouds, so that for a period of several years global temperatures drop to levels below the lowest temperatures of the climate with present day values of CO2. The same configuration of the model has more modest sensitivities when the insolation is reduced, but runaway warming results for small (10%) increases. Simulations without parameterised convection have colder (by roughly 10K) climates and smaller (1K) sensitivities, allowing a stable climate with earth-like temperatures even for insolation much (50%) larger than the present day. Such values of insolation are possible because over a large range of the insolation the climate sensitivity parameter is very near zero. The surprising sensitivities of the system, and the limit-cycle like behaviour of the very CO2 rich climates, can be traced to

  12. Sensitivity of blackbody effective emissivity to wavelength and temperature: By genetic algorithm

    Science.gov (United States)

    Ejigu, E. K.; Liedberg, H. G.

    2013-09-01

    A variable-temperature blackbody (VTBB) is used to calibrate an infrared radiation thermometer (pyrometer). The effective emissivity (ɛeff) of a VTBB is dependent on temperature and wavelength other than the geometry of the VTBB. In the calibration process the effective emissivity is often assumed to be constant within the wavelength and temperature range. There are practical situations where the sensitivity of the effective emissivity needs to be known and correction has to be applied. We present a method using a genetic algorithm to investigate the sensitivity of the effective emissivity to wavelength and temperature variation. Two matlab® programs are generated: the first to model the radiance temperature calculation and the second to connect the model to the genetic algorithm optimization toolbox. The effective emissivity parameter is taken as a chromosome and optimized at each wavelength and temperature point. The difference between the contact temperature (reading from a platinum resistance thermometer or liquid in glass thermometer) and radiance temperature (calculated from the ɛeff values) is used as an objective function where merit values are calculated and best fit ɛeff values selected. The best fit ɛeff values obtained as a solution show how sensitive they are to temperature and wavelength parameter variation. Uncertainty components that arise from wavelength and temperature variation are determined based on the sensitivity analysis. Numerical examples are considered for illustration.

  13. [Search problems of human radiation protection in the world of genetics of aging].

    Science.gov (United States)

    Koterov, A N

    2013-01-01

    Currently, the urgency for protection from negative effects of radiation in the range of low and medium dose where classic radioprotectors are ineffective is increased. In this respect it seems promising to study the molecular pathways that increase, on the one hand, the stability of the genome against radiation damage (inducers of carcinogenesis), and, on the other hand, elevate the radiation sensitivity of cell populations in order to eliminate potentially carcinogenic cells. This approach requires modification of cascade mechanisms of signal transduction to apoptosis and responses to DNA damage. Research plan is similar to the Genetics of Aging, where a number of hypotheses about the mechanism of aging have been proposed, including a decrease in the stability of the genome to external influences. Proceedings of the 2nd International Conference "The genetics of aging and longevity" (Moscow, April 2012) demonstrated, however, that patterns of aging mechanisms identified in model animals (nematodes, drosophila and mice) are far from the possibility of their practical application. Discovered genes that may be responsible for life expectancy (stress-inducible protein and other components of the signal transduction cascade, as well as suppressors and inducers) rarely find significance in the study of the genomes of centenarian cohorts. This may be due to the difficulty in transferring molecular genetic patterns from model objects to large mammals, including humans, with respect to systems of signal transduction. This point must be taken into account during the search for a new generation of radioprotective agents that promote anti-carcinogenic potential of human cells exposed to radiation at low and moderate doses. It may be necessary to search for such tools in large laboratory animals and in human tissue cultures obtained through genetic engineering or cloning.

  14. Genetics of childhood steroid-sensitive nephrotic syndrome.

    Science.gov (United States)

    Karp, Alana M; Gbadegesin, Rasheed A

    2016-07-29

    The pathogenesis of childhood-onset nephrotic syndrome (NS), disparity in incidence of NS among races, and variable responses to therapies in children with NS have defied explanation to date. In the last 20 years over 50 genetic causes of steroid-resistant nephrotic syndrome (SRNS) have been identified, and at least two disease loci for two pathologic variants of SRNS (focal segmental glomerulosclerosis and membranous nephropathy) have been defined. However, the genetic causes and risk loci for steroid-sensitive nephrotic syndrome (SSNS) remain elusive, partly because SSNS is relatively rare and also because cases of SSNS vary widely in phenotypic expression over time. A recent study of a well-defined modest cohort of children with SSNS identified variants in HLA-DQA1 as a risk factor for SSNS. Here we review what is currently known about the genetics of SSNS and also discuss how recent careful phenotypic and genomic studies reinforce the role of adaptive immunity in the molecular mechanisms of SSNS.

  15. Individual Differences in Scotopic Visual Acuity and Contrast Sensitivity: Genetic and Non-Genetic Influences.

    Directory of Open Access Journals (Sweden)

    Alex J Bartholomew

    Full Text Available Despite the large amount of variation found in the night (scotopic vision capabilities of healthy volunteers, little effort has been made to characterize this variation and factors, genetic and non-genetic, that influence it. In the largest population of healthy observers measured for scotopic visual acuity (VA and contrast sensitivity (CS to date, we quantified the effect of a range of variables on visual performance. We found that young volunteers with excellent photopic vision exhibit great variation in their scotopic VA and CS, and this variation is reliable from one testing session to the next. We additionally identified that factors such as Circadian preference, iris color, astigmatism, depression, sex and education have no significant impact on scotopic visual function. We confirmed previous work showing that the amount of time spent on the vision test influences performance and that laser eye surgery results in worse scotopic vision. We also showed a significant effect of intelligence and photopic visual performance on scotopic VA and CS, but all of these variables collectively explain <30% of the variation in scotopic vision. The wide variation seen in young healthy volunteers with excellent photopic vision, the high test-retest agreement, and the vast majority of the variation in scotopic vision remaining unexplained by obvious non-genetic factors suggests a strong genetic component. Our preliminary genome-wide association study (GWAS of 106 participants ruled out any common genetic variants of very large effect and paves the way for future, larger genetic studies of scotopic vision.

  16. Radiation sensitivity of Merkel cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Leonard, J.H.; Ramsay, J.R.; Birrell, G.W. [Queensland Institute of Medical Research (Australia)] [and others

    1995-07-30

    Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after {gamma} irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to {gamma} irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution. 25 refs., 3 figs., 1 tab.

  17. Radiation sensitivity of poliovirus, a model for norovirus, inoculated in oyster (Crassostrea gigas) and culture broth under different conditions

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Pil-Mun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Park, Jae Seok [Korea Food and Drug Administration, Seoul 122-704 (Korea, Republic of); Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Baek, Min [Atomic Energy Policy Division, Ministry of Education, Science and Technology, Gwacheon 427-715 (Korea, Republic of); Chung, Young-Jin [Department of Food and Nutrition, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Lee, Ju-Woon [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

    2009-07-15

    Poliovirus is a recognized surrogate for norovirus, pathogen in water and food, due to the structural and genetic similarity. Although radiation sensitivity of poliovirus in water or media had been reported, there has been no research in food model such as shellfish. In this study, oyster (Crassostrea gigas) was incubated in artificial seawater contaminated with poliovirus, and thus radiation sensitivity of poliovirus was determined in inoculated oyster. The effects of ionizing radiation on the sensitivity of poliovirus were also evaluated under different conditions such as pH (4-7) and salt concentration (1-15%) in culture broth, and temperature during irradiation. The D{sub 10} value of poliovirus in PBS buffer, virus culture broth and oyster was determined to 0.46, 2.84 and 2.94 kGy, respectively. The initial plaque forming unit (PFU) of poliovirus in culture broth was slightly decreased as the decrease of pH and the increase of salt concentration, but radiation sensitivity was not affected by pH and salt contents. However, radiation resistance of poliovirus was increased at frozen state. These results provide the basic information for the inactivation of pathogenic virus in foods by using irradiation.

  18. Radiation sensitivity of poliovirus, a model for norovirus, inoculated in oyster ( Crassostrea gigas) and culture broth under different conditions

    Science.gov (United States)

    Jung, Pil-Mun; Park, Jae Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Baek, Min; Chung, Young-Jin; Lee, Ju-Woon

    2009-07-01

    Poliovirus is a recognized surrogate for norovirus, pathogen in water and food, due to the structural and genetic similarity. Although radiation sensitivity of poliovirus in water or media had been reported, there has been no research in food model such as shellfish. In this study, oyster ( Crassostrea gigas) was incubated in artificial seawater contaminated with poliovirus, and thus radiation sensitivity of poliovirus was determined in inoculated oyster. The effects of ionizing radiation on the sensitivity of poliovirus were also evaluated under different conditions such as pH (4-7) and salt concentration (1-15%) in culture broth, and temperature during irradiation. The D10 value of poliovirus in PBS buffer, virus culture broth and oyster was determined to 0.46, 2.84 and 2.94 kGy, respectively. The initial plaque forming unit (PFU) of poliovirus in culture broth was slightly decreased as the decrease of pH and the increase of salt concentration, but radiation sensitivity was not affected by pH and salt contents. However, radiation resistance of poliovirus was increased at frozen state. These results provide the basic information for the inactivation of pathogenic virus in foods by using irradiation.

  19. Gadolinium nanoparticles and contrast agent as radiation sensitizers.

    Science.gov (United States)

    Taupin, Florence; Flaender, Mélanie; Delorme, Rachel; Brochard, Thierry; Mayol, Jean-François; Arnaud, Josiane; Perriat, Pascal; Sancey, Lucie; Lux, François; Barth, Rolf F; Carrière, Marie; Ravanat, Jean-Luc; Elleaume, Hélène

    2015-06-01

    The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist(®) in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL(-1)), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44   ±   0.33 and 1.50   ±   0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66   ±   0.17 and 1.01   ±   0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly 'energy dependent' for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs.

  20. Evaluation of γ-radiation-induced DNA damage in two species of bivalves and their relative sensitivity using comet assay.

    Science.gov (United States)

    Praveen Kumar, M K; Shyama, S K; Sonaye, B S; Naik, U Roshini; Kadam, S B; Bipin, P D; D'costa, A; Chaubey, R C

    2014-05-01

    Ionizing radiation is known to induce genetic damage in diverse groups of organisms. Under accidental situations, large quantities of radioactive elements get released into the environment and radiation emitted from these radionuclides may adversely affect both the man and the non-human biota. The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of 'Comet assay' for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz. Paphia malabarica and Meretrix casta to gamma radiation. The comet assays was optimized and validated using different concentrations (18, 32 and 56 mg/L) of ethyl methanesulfonate (EMS), a direct-acting reference genotoxic agent, to which the bivalves were exposed for various times (24, 48 and 72 h). Bivalves were irradiated (single acute exposure) with 5 different doses (viz. 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay. Haemolymph was collected from the adductor muscle at 24, 48 and 72 h of both EMS-exposed and irradiated bivalves and comet assay was carried out using standard protocol. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA damage at different concentrations of EMS and all the doses of gamma radiation as compared to controls in both bivalve species. This showed a dose-dependent increase of genetic damage induced in bivalves by EMS as well as gamma radiation. Further, the highest DNA damage was observed at 24h. The damage gradually decreased with time, i.e. was smaller at 48 and 72 h than at 24h post irradiation in both species of bivalves. This may indicate repair of the damaged DNA and/or loss of heavily damaged cells as the post irradiation time advanced. The present study

  1. Evaluation of γ-radiation-induced DNA damage in two species of bivalves and their relative sensitivity using comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Praveen Kumar, M.K., E-mail: here.praveen@gmail.com [Department of Zoology, Goa University, Goa 403206 (India); Shyama, S.K., E-mail: skshyama@gmail.com [Department of Zoology, Goa University, Goa 403206 (India); Sonaye, B.S. [Department of Radiation Oncology, Goa Medical College, Goa (India); Naik, U Roshini; Kadam, S.B.; Bipin, P.D.; D’costa, A. [Department of Zoology, Goa University, Goa 403206 (India); Chaubey, R.C. [Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai (India)

    2014-05-01

    Highlights: • Possible genotoxic effect of accidental exposure of aquatic fauna to γ radiation. • Relative sensitivity of bivalves to γ radiation is also analyzed using comet assay. • γ radiation induced significant genetic damage in both the species of bivalves. • P. malabarica and M. casta exhibited a similar level of sensitivity to γ radiation. • Comet assay may be used as a biomarker for the environmental biomonitoring. - Abstract: Ionizing radiation is known to induce genetic damage in diverse groups of organisms. Under accidental situations, large quantities of radioactive elements get released into the environment and radiation emitted from these radionuclides may adversely affect both the man and the non-human biota. The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of ‘Comet assay’ for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz. Paphia malabarica and Meretrix casta to gamma radiation. The comet assays was optimized and validated using different concentrations (18, 32 and 56 mg/L) of ethyl methanesulfonate (EMS), a direct-acting reference genotoxic agent, to which the bivalves were exposed for various times (24, 48 and 72 h). Bivalves were irradiated (single acute exposure) with 5 different doses (viz. 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay. Haemolymph was collected from the adductor muscle at 24, 48 and 72 h of both EMS-exposed and irradiated bivalves and comet assay was carried out using standard protocol. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA damage at different concentrations of EMS and all the doses of gamma radiation as compared to controls in

  2. Genetic basis for dosage sensitivity in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Isabelle M Henry

    2007-04-01

    Full Text Available Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI, exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and

  3. p53 activated by AND gate genetic circuit under radiation and hypoxia for targeted cancer gene therapy.

    Science.gov (United States)

    Ding, Miao; Li, Rong; He, Rong; Wang, Xingyong; Yi, Qijian; Wang, Weidong

    2015-09-01

    Radio-activated gene therapy has been developed as a novel therapeutic strategy against cancer; however, expression of therapeutic gene in peritumoral tissues will result in unacceptable toxicity to normal cells. To restrict gene expression in targeted tumor mass, we used hypoxia and radiation tolerance features of tumor cells to develop a synthetic AND gate genetic circuit through connecting radiation sensitivity promoter cArG6 , heat shock response elements SNF1, HSF1 and HSE4 with retroviral vector plxsn. Their construction and dynamic activity process were identified through downstream enhanced green fluorescent protein and wtp53 expression in non-small cell lung cancer A549 cells and in a nude mice model. The result showed that AND gate genetic circuit could be activated by lower required radiation dose (6 Gy) and after activated, AND gate could induce significant apoptosis effects and growth inhibition of cancer cells in vitro and in vivo. The radiation- and hypoxia-activated AND gate genetic circuit, which could lead to more powerful target tumoricidal activity represented a promising strategy for both targeted and effective gene therapy of human lung adenocarcinoma and low dose activation character of the AND gate genetic circuit implied that this model could be further exploited to decrease side-effects of clinical radiation therapy.

  4. Is there a genetic contribution to cultural differences? Collectivism, individualism and genetic markers of social sensitivity.

    Science.gov (United States)

    Way, Baldwin M; Lieberman, Matthew D

    2010-06-01

    Genes and culture are often thought of as opposite ends of the nature-nurture spectrum, but here we examine possible interactions. Genetic association studies suggest that variation within the genes of central neurotransmitter systems, particularly the serotonin (5-HTTLPR, MAOA-uVNTR) and opioid (OPRM1 A118G), are associated with individual differences in social sensitivity, which reflects the degree of emotional responsivity to social events and experiences. Here, we review recent work that has demonstrated a robust cross-national correlation between the relative frequency of variants in these genes and the relative degree of individualism-collectivism in each population, suggesting that collectivism may have developed and persisted in populations with a high proportion of putative social sensitivity alleles because it was more compatible with such groups. Consistent with this notion, there was a correlation between the relative proportion of these alleles and lifetime prevalence of major depression across nations. The relationship between allele frequency and depression was partially mediated by individualism-collectivism, suggesting that reduced levels of depression in populations with a high proportion of social sensitivity alleles is due to greater collectivism. These results indicate that genetic variation may interact with ecological and social factors to influence psychocultural differences.

  5. Sensitivity of aerosol radiative forcing calculations to spectral resolution

    Energy Technology Data Exchange (ETDEWEB)

    Grant, K.E.

    1996-10-01

    Potential impacts of aerosol radiative forcing on climate have generated considerable recent interest. An important consideration in estimating the forcing from various aerosol components is the spectral resolution used for the solar radiative transfer calculations. This paper examines the spectral resolution required from the viewpoint of overlapping spectrally varying aerosol properties with other cross sections. A diagnostic is developed for comparing different band choices, and the impact of these choices on the radiative forcing calculated for typical sulfate and biomass aerosols was investigated.

  6. Differential sensitivity of Chironomus and human hemoglobin to gamma radiation.

    Science.gov (United States)

    Gaikwad, Pallavi S; Panicker, Lata; Mohole, Madhura; Sawant, Sangeeta; Mukhopadhyaya, Rita; Nath, Bimalendu B

    2016-08-05

    Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study.

  7. Genetic radiation effects of Hiroshima and Nagasaki atomic bombs

    Energy Technology Data Exchange (ETDEWEB)

    Srsen, S. (Komenskeho Univ., Bratislava (Czechoslovakia). Lekarska Fakulta)

    1984-05-01

    A group of researchers examined persons who had survived the Hiroshima and Nagasaki bombs and were irradiated and their progeny with the aim of getting an idea of the genetic effects of these explosions. Teratogenic effects are not discussed. In the lymphocytes of the peripheral blood of persons who had been exposed to high dose irradiation the researchers found a significant increase in chromosomal aberrations by conventional and more recent methods of chromosomal analysis. In parents who had survived the atomic holocaust there were no significant deviations as against the rest of the population in still births, neonatal defects, infant mortality, and mortality of first generation progeny, in neonate weight, the sex ratio, increased occurence of leukosis and chromosomal aberrations in their children. These negative findings in the first generation do not signify that there is no danger from atomic bomb blasts for human kind. They only indicate that the effects of radiation were too small to be found by routine methods or that the methods used were not suitable.

  8. Losartan sensitizes selectively prostate cancer cell to ionizing radiation.

    Science.gov (United States)

    Yazdannejat, H; Hosseinimehr, S J; Ghasemi, A; Pourfallah, T A; Rafiei, A

    2016-01-11

    Losartan is an angiotensin II receptor (AT-II-R) blocker that is widely used by human for blood pressure regulation. Also, it has antitumor property. In this study, we investigated the radiosensitizing effect of losartan on cellular toxicity induced by ionizing radiation on prostate cancer and non-malignant fibroblast cells. Human prostate cancer (DU-145) and human non-malignant fibroblast cells (HFFF2) were treated with losartan at different concentrations (0.5, 1, 10, 50 and 100 µM) and then these cells were exposed to ionizing radiation. The cell proliferation was determined using MTT assay. Our results showed that losartan exhibited antitumor effect on prostate cancer cells; it was reduced cell survival to 66% at concentration 1 µM. Losartan showed an additive killing effect in combination with ionizing radiation on prostate cancer cell. The cell proliferation was reduced to 54% in the prostate cancer cells treated with losartan at concentration 1 µM in combination with ionizing radiation. Losartan did not exhibit any toxicity on HFFF2 cell. This result shows a promising effect of losartan on enhancement of therapeutic effect of ionizing radiation in patients during therapy.

  9. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair

    Science.gov (United States)

    Sterpone, Silvia; Cozzi, Renata

    2010-01-01

    It is well known that ionizing radiation (IR) can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to developing cancer; this variability is principally represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In particular we have focussed on single nucleotide polymorphisms (SNPs) of XRCC1, a gene that encodes for a scaffold protein involved basically in Base Excision Repair (BER). In this paper we have reported and presented recent studies that show an influence of XRCC1 variants on DNA repair capacity and susceptibility to breast cancer. PMID:20798883

  10. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair

    Directory of Open Access Journals (Sweden)

    Silvia Sterpone

    2010-01-01

    Full Text Available It is well known that ionizing radiation (IR can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to developing cancer; this variability is principally represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In particular we have focussed on single nucleotide polymorphisms (SNPs of XRCC1, a gene that encodes for a scaffold protein involved basically in Base Excision Repair (BER. In this paper we have reported and presented recent studies that show an influence of XRCC1 variants on DNA repair capacity and susceptibility to breast cancer.

  11. Simulated performance of a position sensitive radiation detecting system (COCAE)

    CERN Document Server

    Karafasoulis, K; Seferlis, S; Kaissas, I; Lambropoulos, C; Loukas, D; Poritiriadis, C

    2011-01-01

    Extensive simulations of a portable radiation detecting system have been performed in order to explore important performance parameters. The instrument consists of a stack of ten detecting layers made of pixelated Cadmium Telluride (CdTe) crystals. Its aim is to localize and identify radiation sources, by exploiting the Compton imaging technique. In this paper we present performance parameters based on simulation studies. Specifically the ratio of incompletely absorbed photons, the detector's absolute efficiency as well as its energy and angular resolution are evaluated in a wide range of incident photon energies.

  12. Optical imaging of radiation-induced metabolic changes in radiation-sensitive and resistant cancer cells

    Science.gov (United States)

    Alhallak, Kinan; Jenkins, Samir V.; Lee, David E.; Greene, Nicholas P.; Quinn, Kyle P.; Griffin, Robert J.; Dings, Ruud P. M.; Rajaram, Narasimhan

    2017-06-01

    Radiation resistance remains a significant problem for cancer patients, especially due to the time required to definitively determine treatment outcome. For fractionated radiation therapy, nearly 7 to 8 weeks can elapse before a tumor is deemed to be radiation-resistant. We used the optical redox ratio of FAD/(FAD+NADH) to identify early metabolic changes in radiation-resistant lung cancer cells. These radiation-resistant human A549 lung cancer cells were developed by exposing the parental A549 cells to repeated doses of radiation (2 Gy). Although there were no significant differences in the optical redox ratio between the parental and resistant cell lines prior to radiation, there was a significant decrease in the optical redox ratio of the radiation-resistant cells 24 h after a single radiation exposure (p=0.01). This change in the redox ratio was indicative of increased catabolism of glucose in the resistant cells after radiation and was associated with significantly greater protein content of hypoxia-inducible factor 1 (HIF-1α), a key promoter of glycolytic metabolism. Our results demonstrate that the optical redox ratio could provide a rapid method of determining radiation resistance status based on early metabolic changes in cancer cells.

  13. Optical imaging of radiation-induced metabolic changes in radiation-sensitive and resistant cancer cells.

    Science.gov (United States)

    Alhallak, Kinan; Jenkins, Samir V; Lee, David E; Greene, Nicholas P; Quinn, Kyle P; Griffin, Robert J; Dings, Ruud P M; Rajaram, Narasimhan

    2017-06-01

    Radiation resistance remains a significant problem for cancer patients, especially due to the time required to definitively determine treatment outcome. For fractionated radiation therapy, nearly 7 to 8 weeks can elapse before a tumor is deemed to be radiation-resistant. We used the optical redox ratio of FAD / ( FAD + NADH ) to identify early metabolic changes in radiation-resistant lung cancer cells. These radiation-resistant human A549 lung cancer cells were developed by exposing the parental A549 cells to repeated doses of radiation (2 Gy). Although there were no significant differences in the optical redox ratio between the parental and resistant cell lines prior to radiation, there was a significant decrease in the optical redox ratio of the radiation-resistant cells 24 h after a single radiation exposure ( p = 0.01 ). This change in the redox ratio was indicative of increased catabolism of glucose in the resistant cells after radiation and was associated with significantly greater protein content of hypoxia-inducible factor 1 ( HIF - 1 ? ), a key promoter of glycolytic metabolism. Our results demonstrate that the optical redox ratio could provide a rapid method of determining radiation resistance status based on early metabolic changes in cancer cells.

  14. Lay responses to health messages about the genetic risk factors for salt sensitivity: do mass media genetic health messages result in genetic determinism?

    Science.gov (United States)

    Smerecnik, Chris M R

    2010-08-01

    Media coverage of genetics may lead to overestimation of the impact of genetics on disease development. In this study, we presented one student sample and one general public sample from the Netherlands with a general or a genetic health message (HM) about salt sensitivity. After reading the genetic (but not the general) HM, participants reported higher perceived impact of genetic versus lifestyle factors and a higher attributable fraction of genetics on disease development. Nevertheless, participants were able to recognise the balance between lifestyle and genetic risk factors in disease development. They also contextualised and restricted the message's implications to the specific information provided, and did not extrapolate these implications to other diseases. These results illustrate the nuanced understanding the general public may have concerning genetic risk factors.

  15. Uncertainty and Sensitivity Analysis of Afterbody Radiative Heating Predictions for Earth Entry

    Science.gov (United States)

    West, Thomas K., IV; Johnston, Christopher O.; Hosder, Serhat

    2016-01-01

    The objective of this work was to perform sensitivity analysis and uncertainty quantification for afterbody radiative heating predictions of Stardust capsule during Earth entry at peak afterbody radiation conditions. The radiation environment in the afterbody region poses significant challenges for accurate uncertainty quantification and sensitivity analysis due to the complexity of the flow physics, computational cost, and large number of un-certain variables. In this study, first a sparse collocation non-intrusive polynomial chaos approach along with global non-linear sensitivity analysis was used to identify the most significant uncertain variables and reduce the dimensions of the stochastic problem. Then, a total order stochastic expansion was constructed over only the important parameters for an efficient and accurate estimate of the uncertainty in radiation. Based on previous work, 388 uncertain parameters were considered in the radiation model, which came from the thermodynamics, flow field chemistry, and radiation modeling. The sensitivity analysis showed that only four of these variables contributed significantly to afterbody radiation uncertainty, accounting for almost 95% of the uncertainty. These included the electronic- impact excitation rate for N between level 2 and level 5 and rates of three chemical reactions in uencing N, N(+), O, and O(+) number densities in the flow field.

  16. Epicatechin stimulates mitochondrial activity and selectively sensitizes cancer cells to radiation.

    Directory of Open Access Journals (Sweden)

    Hosam A Elbaz

    Full Text Available Radiotherapy is the treatment of choice for solid tumors including pancreatic cancer, but the effectiveness of treatment is limited by radiation resistance. Resistance to chemotherapy or radiotherapy is associated with reduced mitochondrial respiration and drugs that stimulate mitochondrial respiration may decrease radiation resistance. The objectives of this study were to evaluate the potential of (--epicatechin to stimulate mitochondrial respiration in cancer cells and to selectively sensitize cancer cells to radiation. We investigated the natural compound (--epicatechin for effects on mitochondrial respiration and radiation resistance of pancreatic and glioblastoma cancer cells using a Clark type oxygen electrode, clonogenic survival assays, and Western blot analyses. (--Epicatechin stimulated mitochondrial respiration and oxygen consumption in Panc-1 cells. Human normal fibroblasts were not affected. (--Epicatechin sensitized Panc-1, U87, and MIA PaCa-2 cells with an average radiation enhancement factor (REF of 1.7, 1.5, and 1.2, respectively. (--Epicatechin did not sensitize normal fibroblast cells to ionizing radiation with a REF of 0.9, suggesting cancer cell selectivity. (--Epicatechin enhanced Chk2 phosphorylation and p21 induction when combined with radiation in cancer, but not normal, cells. Taken together, (--epicatechin radiosensitized cancer cells, but not normal cells, and may be a promising candidate for pancreatic cancer treatment when combined with radiation.

  17. Silver nanoparticles: a novel radiation sensitizer for glioma?

    Science.gov (United States)

    Liu, Peidang; Huang, Zhihai; Chen, Zhongwen; Xu, Ruizhi; Wu, Hao; Zang, Fengchao; Wang, Cailian; Gu, Ning

    2013-11-01

    Malignant gliomas are the most common primary intracranial tumors with a dismal prognosis. Previous investigations by our group demonstrated the radiosensitizing effect of silver nanoparticles (AgNPs) on glioma cells in vitro. The goal of the present study was to evaluate the efficacy of intratumoral administration of AgNPs in combination with a single dose of ionizing radiation at clinically relevant MV energies for the treatment of C6 glioma-bearing rats. AgNPs (10 or 20 μg/10 μl) were stereotactically administered on day 8 after tumor implantation. One day after AgNP injection, rats bearing glioma received 10 Gy radiation. The mean survival times were 100.5 and 98 days, the corresponding percent increase in life spans was 513.2% and 497.7%, and the cure rates were 41.7 and 38.5% at 200 days for the 10 and 20 μg AgNPs and radiation combination groups, respectively. In contrast, the mean survival times for irradiated controls, 10 and 20 μg AgNPs alone, and untreated controls were 24.5, 16.1, 19.4, and 16.4 days, respectively. Furthermore, a cooperative antiproliferative and proapoptotic effect was obtained when gliomas were treated with AgNPs followed by radiotherapy. Our results showed the therapeutic efficacy of AgNPs in combination with radiotherapy without apparent systemic toxicity, suggesting the clinical potential of AgNPs in improving the outcome of malignant glioma radiotherapy.Malignant gliomas are the most common primary intracranial tumors with a dismal prognosis. Previous investigations by our group demonstrated the radiosensitizing effect of silver nanoparticles (AgNPs) on glioma cells in vitro. The goal of the present study was to evaluate the efficacy of intratumoral administration of AgNPs in combination with a single dose of ionizing radiation at clinically relevant MV energies for the treatment of C6 glioma-bearing rats. AgNPs (10 or 20 μg/10 μl) were stereotactically administered on day 8 after tumor implantation. One day after Ag

  18. ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation.

    Science.gov (United States)

    Biddlestone-Thorpe, Laura; Sajjad, Muhammad; Rosenberg, Elizabeth; Beckta, Jason M; Valerie, Nicholas C K; Tokarz, Mary; Adams, Bret R; Wagner, Alison F; Khalil, Ashraf; Gilfor, Donna; Golding, Sarah E; Deb, Sumitra; Temesi, David G; Lau, Alan; O'Connor, Mark J; Choe, Kevin S; Parada, Luis F; Lim, Sang Kyun; Mukhopadhyay, Nitai D; Valerie, Kristoffer

    2013-06-15

    Glioblastoma multiforme (GBM) is the most lethal form of brain cancer with a median survival of only 12 to 15 months. Current standard treatment consists of surgery followed by chemoradiation. The poor survival of patients with GBM is due to aggressive tumor invasiveness, an inability to remove all tumor tissue, and an innate tumor chemo- and radioresistance. Ataxia-telangiectasia mutated (ATM) is an excellent target for radiosensitizing GBM because of its critical role in regulating the DNA damage response and p53, among other cellular processes. As a first step toward this goal, we recently showed that the novel ATM kinase inhibitor KU-60019 reduced migration, invasion, and growth, and potently radiosensitized human glioma cells in vitro. Using orthotopic xenograft models of GBM, we now show that KU-60019 is also an effective radiosensitizer in vivo. Human glioma cells expressing reporter genes for monitoring tumor growth and dispersal were grown intracranially, and KU-60019 was administered intratumorally by convection-enhanced delivery or osmotic pump. Our results show that the combined effect of KU-60019 and radiation significantly increased survival of mice 2- to 3-fold over controls. Importantly, we show that glioma with mutant p53 is much more sensitive to KU-60019 radiosensitization than genetically matched wild-type glioma. Taken together, our results suggest that an ATM kinase inhibitor may be an effective radiosensitizer and adjuvant therapy for patients with mutant p53 brain cancers.

  19. Oyster radiation sensitivity; Sensibilidade de ostras a radiacao

    Energy Technology Data Exchange (ETDEWEB)

    Marchese, Sandra R.M. [Centro Tecnologico da Marinha em Sao Paulo (CTMSP), SP (Brazil); Mastro, Nelida L. del [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)

    1996-07-01

    Various food products like oysters, crabs and shrimps have been described as possible Vibrio spp. transmitting agents. Seafood irradiation is been presented as an alternative among the different public health intervention measures to control food borne diseases. The objective of this work was to establish, firstly, the radioresistance of Crassostrea brasiliana oysters. The oysters were irradiated with Co-60 radiation with doses of 0, 1.5,3 and 6 kGy. Survival curves a function of time showed that 100% of samples irradiated with 3 kGy survived at least 6 days; among those irradiated with 6 kGy, 100% survived 3 days. These results are encouraging since a dose of 2 kGy is already effective in diminishing oyster bioburden. (author)

  20. Telomerase antagonist imetelstat increases radiation sensitivity in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wu, Xuping; Zhang, Jing; Yang, Sijun; Kuang, Zhihui; Tan, Guolei; Yang, Gang; Wei, Qichun; Guo, Zhigang

    2017-01-13

    The morbidity and mortality of esophageal cancer is one of the highest around the world and the principal therapeutic method is radiation. Thus, searching for sensitizers with lower toxicity and higher efficiency to improve the efficacy of radiation therapy is critical essential. Our research group has previously reported that imetelstat, the thio-phosphoramidate oligonucleotide inhibitor of telomerase, can decrease cell proliferation and colony formation ability as well as increase DNA breaks induced by radiation in esophageal cancer cells. Further study in this project showed that imetelstat significantly sensitized esophageal cancer cells to radiation in vitro. Later study showed that imetelstat leads to increased cell apoptosis. We also measured the expression level of several DNA repair and apoptosis signaling proteins. pS345 CHK1, γ-H2AX, p53 and caspase3 expression were up-regulated in imetelstat treated cells, identifying these factors as molecular markers. Mouse in vivo model using imetelstat at clinically achievable concentrations and fractionated irradiation scheme yielded results demonstrating radiosensitization effect. Finally, TUNEL assay, caspase 3 and Ki67 staining in tumor tissue proved that imetelstat sensitized esophageal cancer to radiation in vivo through promoting cell apoptosis and inhibiting cell proliferation. Our study supported imetelstat increase radiation sensitivity of esophageal squamous cell carcinoma through inducing cell apoptosis and the specific inhibitor of telomerase might serve as a potential novel therapeutic tool for esophageal squamous cell carcinoma therapy.

  1. Radiation sensitivity and EPR dosimetric potential of gallic acid and its esters

    Science.gov (United States)

    Tuner, Hasan; Oktay Bal, M.; Polat, Mustafa

    2015-02-01

    In the preset work the radiation sensitivities of Gallic Acid anhydrous and monohydrate, Octyl, Lauryl, and Ethyl Gallate (GA, GAm, OG, LG, and EG) were investigated in the intermediate (0.5-20 kGy) and low radiation (<10 Gy) dose range using Electron Paramagnetic Resonance (EPR) spectroscopy. While OG, LG, and EG are presented a singlet EPR spectra, their radiation sensitivity found to be very different in the intermediate dose range. At low radiation dose range (<10 Gy) only LG is found to be present a signal that easily distinguished from the noise signals. The intermediate and low dose range radiation sensitivities are compared using well known EPR dosimeter alanine. The radiation yields (G) of the interested material were found to be 1.34×10-2, 1.48×10-2, 4.14×10-2, and 6.03×10-2, 9.44×10-2 for EG, GA, GAm, OG, and LG, respectively at the intermediate dose range. It is found that the simple EPR spectra and the noticeable EPR signal of LG make it a promising dosimetric material to be used below 10 Gy of radiation dose.

  2. Exponential sensitivity of noise-driven switching in genetic networks

    Science.gov (United States)

    Mehta, Pankaj; Mukhopadhyay, Ranjan; Wingreen, Ned S.

    2008-06-01

    There is increasing experimental evidence that cells can utilize biochemical noise to switch probabilistically between distinct gene-expression states. In this paper, we demonstrate that such noise-driven switching is dominated by tails of probability distributions and is therefore exponentially sensitive to changes in physiological parameters such as transcription and translation rates. Exponential sensitivity limits the robustness of noise-driven switching, suggesting cells may use other mechanisms in order to switch reliably. We discuss our results in the context of competence in the bacterium Bacillus subtilis.

  3. Radiation mutagenesis from molecular and genetic points of view

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.J.C.; Park, M.S.; Okinaka, R.T.; Jaberaboansari, A.

    1993-01-01

    An important biological effect of ionizing radiation on living organisms is mutation induction. Mutation is also a primary event in the etiology of cancer. The chain events, from induction of DNA damage by ionizing radiation to processing of these damages by the cellular repair/replication machinery, that lead to mutation are not well understood. The development of quantitative methods for measuring mutation-induction, such as the HPRT system, in cultured mammalian cells has provided an estimate of the mutagenic effects of x- and [gamma]-rays as wen as of high LET radiation in both rodent and human cells. A major conclusion from these mutagenesis data is that high LET radiation induces mutations more efficiently than g-rays. Molecular analysis of mutations induced by sparsely ionizing radiation have detected major structural alterations at the gene level. Our molecular results based on analysis of human HPRT deficient mutants induced by [gamma]-rays, [alpha]-particles and high energy charged particles indicate that higher LET radiation induce more total and large deletion mutations than [gamma]-rays. Utilizing molecular techniques including polymerase chain reaction (PCR), Single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE) and Direct DNA sequencing, mutational spectra induced by ionizing radiation have been compared in different cell systems. Attempts have also been made to determine the mutagenic potential and the nature of mutation induced by low dose rate [gamma]-rays. Defective repair, in the form of either a diminished capability for repair or inaccurate repair, can lead to increased risk of heritable mutations from radiation exposure. Therefore, the effects of DNA repair deficiency on the mutation induction in mammalian cells is reviewed.

  4. Radiation mutagenesis from molecular and genetic points of view

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.J.C.; Park, M.S.; Okinaka, R.T.; Jaberaboansari, A.

    1993-02-01

    An important biological effect of ionizing radiation on living organisms is mutation induction. Mutation is also a primary event in the etiology of cancer. The chain events, from induction of DNA damage by ionizing radiation to processing of these damages by the cellular repair/replication machinery, that lead to mutation are not well understood. The development of quantitative methods for measuring mutation-induction, such as the HPRT system, in cultured mammalian cells has provided an estimate of the mutagenic effects of x- and {gamma}-rays as wen as of high LET radiation in both rodent and human cells. A major conclusion from these mutagenesis data is that high LET radiation induces mutations more efficiently than g-rays. Molecular analysis of mutations induced by sparsely ionizing radiation have detected major structural alterations at the gene level. Our molecular results based on analysis of human HPRT deficient mutants induced by {gamma}-rays, {alpha}-particles and high energy charged particles indicate that higher LET radiation induce more total and large deletion mutations than {gamma}-rays. Utilizing molecular techniques including polymerase chain reaction (PCR), Single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE) and Direct DNA sequencing, mutational spectra induced by ionizing radiation have been compared in different cell systems. Attempts have also been made to determine the mutagenic potential and the nature of mutation induced by low dose rate {gamma}-rays. Defective repair, in the form of either a diminished capability for repair or inaccurate repair, can lead to increased risk of heritable mutations from radiation exposure. Therefore, the effects of DNA repair deficiency on the mutation induction in mammalian cells is reviewed.

  5. The sensitivity of genetic connectivity measures to unsampled and under-sampled sites.

    Directory of Open Access Journals (Sweden)

    Erin L Koen

    Full Text Available Landscape genetic analyses assess the influence of landscape structure on genetic differentiation. It is rarely possible to collect genetic samples from all individuals on the landscape and thus it is important to assess the sensitivity of landscape genetic analyses to the effects of unsampled and under-sampled sites. Network-based measures of genetic distance, such as conditional genetic distance (cGD, might be particularly sensitive to sampling intensity because pairwise estimates are relative to the entire network. We addressed this question by subsampling microsatellite data from two empirical datasets. We found that pairwise estimates of cGD were sensitive to both unsampled and under-sampled sites, and F(ST, D(est, and d(eucl were more sensitive to under-sampled than unsampled sites. We found that the rank order of cGD was also sensitive to unsampled and under-sampled sites, but not enough to affect the outcome of Mantel tests for isolation by distance. We simulated isolation by resistance and found that although cGD estimates were sensitive to unsampled sites, by increasing the number of sites sampled the accuracy of conclusions drawn from landscape genetic analyses increased, a feature that is not possible with pairwise estimates of genetic differentiation such as F(ST, D(est, and d(eucl. We suggest that users of cGD assess the sensitivity of this measure by subsampling within their own network and use caution when making extrapolations beyond their sampled network.

  6. High-sensitivity observations of solar flare decimeter radiation

    CERN Document Server

    Benz, Arnold O; Monstein, C; Benz, Arnold O.; Messmer, Peter; Monstein, Christian

    2000-01-01

    A new acousto-optic radio spectrometer has observed the 1 - 2 GHz radio emission of solar flares with unprecedented sensitivity. The number of detected decimeter type III bursts is greatly enhanced compared to observations by conventional spectrometers observing only one frequency at the time. The observations indicate a large number of electron beams propagating in dense plasmas. For the first time, we report weak, reversed drifting type III bursts at frequencies above simultaneous narrowband decimeter spikes. The type III bursts are reliable signatures of electron beams propagating downward in the corona, apparently away from the source of the spikes. The observations contradict the most popular spike model that places the spike sources at the footpoints of loops. Conspicuous also was an apparent bidirectional type U burst forming a fish-like pattern. It occurs simultaneously with an intense U-burst at 600-370 MHz observed in Tremsdorf. We suggest that it intermodulated with strong terrestrial interference ...

  7. A genetic variant near the PMAIP1/Noxa gene is associated with increased bleomycin sensitivity

    NARCIS (Netherlands)

    Gu, J.; Ye, Y.; Spitz, M.R.; Lin, J.; Kiemeney, L.A.L.M.; Xing, J.; Hildebrandt, M.A.T.; Ki Hong, W.; Amos, C.I.; Wu, X.

    2011-01-01

    Mutagen sensitivity, a measurement of chromatid breaks induced by various mutagens in short-term cultures of peripheral blood lymphocytes, is an established risk factor for a number of cancers and is highly heritable. The purpose of this study is to identify genetic predictors of mutagen sensitivity

  8. High-sensitivity observations of solar flare decimeter radiation

    Science.gov (United States)

    Benz, A. O.; Messmer, P.; Monstein, C.

    2001-01-01

    A new acousto-optic radio spectrometer has observed the 1-2 GHz radio emission of solar flares with unprecedented sensitivity. The number of detected decimeter type III bursts is greatly enhanced compared to observations by conventional spectrometers observing only one frequency at the time. The observations indicate a large number of electron beams propagating in dense plasmas. For the first time, we report weak, reversed drifting type III bursts at frequencies above simultaneous narrowband decimeter spikes. The type III bursts are reliable signatures of electron beams propagating downward in the corona, apparently away from the source of the spikes. The observations contradict the most popular spike model that places the spike sources at the footpoints of loops. Conspicuous also was an apparent bidirectional type U burst forming a fish-like pattern. It occurs simultaneously with an intense U-burst at 600-370 MHz observed in Tremsdorf. We suggest that it intermodulated with strong terrestrial interference(cellular phones) causing a spurious symmetric pattern in the spectrogram at 1.4 GHz. Symmetric features in the 1-2 GHz range, some already reported in the literature, therefore must be considered with utmost caution.

  9. Strategizing the clone wars: pharmacological control of cellular sensitivity to radiation.

    Science.gov (United States)

    Kimple, Randall J

    2010-12-01

    The combined administration of ionizing radiation and systemic chemotherapy is an accepted standard of care for numerous cancers. Improved efficacy through the combination of therapies reflects several interrelated processes, including DNA damage, inhibition of DNA synthesis, alteration of cell cycle distribution, and impaired DNA repair. Insights into cellular responses to radiation have led to the use of drugs that target specific intracellular signaling pathways to sensitize cells to radiation. Combinations of chemotherapy and radiation continue to be optimized, based on preclinical and early-phase clinical data that indicate the ideal sequencing of therapies, the best combinations of agents (including radiosensitizers), and the most reliable biological markers for predicting patient responsiveness. This review summarizes our current understanding of radiosensitization as it relates to preclinical drug development and discusses the potential benefits of judiciously incorporating both traditional and targeted chemotherapy into radiation regimens.

  10. Sensitive Detection: Photoacoustics, Thermography, and Optical Radiation Pressure

    Energy Technology Data Exchange (ETDEWEB)

    Diebold, Gerald J. [Brown Univ., Providence, RI (United States)

    2017-04-21

    Research during the granting period has been carried out in several areas concerned with sensitive detection. An infrared pyrometer based on the photoacoustic effect has been developed. The sensitivity of this instrument to temperature differentials has been shown to be 50 mK. An investigation of transients that accompany photoacoustic waves generated by pulsed lasers has been carried out. Experiments have shown the existence of the transients, and a theory based on rapid heat diffusion has been developed. The photoacoustic effect in one dimension is known to increase without bound (in the linear acoustics regime) when an optical beam moves in a fluid at the sound speed. A solution to the wave equation for pressure has been found that describes the photoacoustic effect in a cell where an infrared optical grating moves at the sound speed. It was shown that the amplification effect exists along with a cavity resonance that can be used to great advantage in trace gas detection. The theory of the photoacoustic effect in a structure where the acoustic properties periodically vary in a one-dimensional based has been formulated based on solutions to a Mathieu equation. It was found that it is possible to excite photoacoustic waves within the band gaps to produce large amplitude acoustic waves. The idea of self-oscillation in a photoacoustic cell using a continuous laser has been investigated. A theory has been completed showing that in a compressive wave, the absorption increases as a result of the density increase leading to further absorption and hence an increased amplitude photoacoustic effect with the result that in a resonator, self-oscillation can place. Experiments have been carried out where irradiation of a suspension of absorbing carbon particles with a high power laser has been shown to result in cavitation luminescence. That is, following generation of CO and H2 from the carbon particles through the carbon-steam reaction, an expanding gas bubble is

  11. Human Genetic Marker for Resistance to Radiation and Chemicals

    Energy Technology Data Exchange (ETDEWEB)

    DR. Howard B. Lieberman

    2001-05-11

    TO characterize the human HRDAD9 gene and evaluate its potential as a biomarker to predict susceptibility to the deleterious health effects potentially caused by exposure to radiations or chemicals present at DOE hazardous waste cleanup sites. HRAD9 is a human gene that is highly conserved throughout evolution. Related genes have been isolated from yeasts and mice, underscoring its biological significance. Most of our previous work involved characterization of the yeast gene cognate, wherein it was determined that the corresponding protein plays a significant role in promoting resistance of cells to radiations and chemicals, and in particular, controlling cell growth in response to DNA damage.

  12. Electroretinogram analysis of relative spectral sensitivity in genetically identified dichromatic macaques.

    Science.gov (United States)

    Hanazawa, A; Mikami, A; Sulistyo Angelika, P; Takenaka, O; Goto, S; Onishi, A; Koike, S; Yamamori, T; Kato, K; Kondo, A; Suryobroto, B; Farajallah, A; Komatsu, H

    2001-07-03

    The retinas of macaque monkeys usually contain three types of photopigment, providing them with trichromatic color vision homologous to that of humans. However, we recently used molecular genetic analysis to identify several macaques with a dichromatic genotype. The affected X chromosome of these animals contains a hybrid gene of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) photopigments instead of separate genes encoding L and M photopigments. The product of the hybrid gene exhibits a spectral sensitivity close to that of M photopigment; consequently, male monkeys carrying the hybrid gene are genetic protanopes, effectively lacking L photopigment. In the present study, we assessed retinal expression of L photopigment in monkeys carrying the hybrid gene. The relative sensitivities to middle-wavelength (green) and long-wavelength (red) light were measured by electroretinogram flicker photometry. We found the sensitivity to red light to be extremely low in protanopic male monkeys compared with monkeys with the normal genotype. In female heterozygotes, sensitivity to red light was intermediate between the genetic protanopes and normal monkeys. Decreased sensitivity to long wavelengths was thus consistent with genetic loss of L photopigment.

  13. Novel Combined Immune Deficiency and Radiation Sensitivity Blended Phenotype in an Adult with Biallelic Variations in ZAP70 and RNF168

    Science.gov (United States)

    Chinn, Ivan K.; Sanders, Robert P.; Stray-Pedersen, Asbjørg; Coban-Akdemir, Zeynep H.; Kim, Vy Hong-Diep; Dadi, Harjit; Roifman, Chaim M.; Quigg, Troy; Lupski, James R.; Orange, Jordan S.; Hanson, I. Celine

    2017-01-01

    With the advent of high-throughput genomic sequencing techniques, novel genetic etiologies are being uncovered for previously unexplained Mendelian phenotypes, and the underlying genetic architecture of disease is being unraveled. Although most of these “mendelizing” disease traits represent phenotypes caused by single-gene defects, a percentage of patients have blended phenotypes caused by pathogenic variants in multiple genes. We describe an adult patient with susceptibility to bacterial, herpesviral, and fungal infections. Immunologic defects included CD8+ T cell lymphopenia, decreased T cell proliferative responses to mitogens, hypogammaglobulinemia, and radiation sensitivity. Whole-exome sequencing revealed compound heterozygous variants in ZAP70. Biallelic mutations in ZAP70 are known to produce a spectrum of immune deficiency that includes the T cell abnormalities observed in this patient. Analyses for variants in genes associated with radiation sensitivity identified the presence of a homozygous RNF168 variant of unknown significance. RNF168 deficiency causes radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties syndrome and may account for the radiation sensitivity. Thus, the patient was found to have a novel blended phenotype associated with multilocus genomic variation: i.e., separate and distinct genetic defects. These findings further illustrate the clinical utility of applying genomic testing in patients with primary immunodeficiency diseases. PMID:28603521

  14. Genetic requirements for sensitivity of bacteriophage t7 to dideoxythymidine.

    Science.gov (United States)

    Tran, Ngoc Q; Tabor, Stanley; Richardson, Charles C

    2014-08-01

    We previously reported that the presence of dideoxythymidine (ddT) in the growth medium selectively inhibits the ability of bacteriophage T7 to infect Escherichia coli by inhibiting phage DNA synthese (N. Q. Tran, L. F. Rezende, U. Qimron, C. C. Richardson, and S. Tabor, Proc. Natl. Acad. Sci. U. S. A. 105:9373-9378, 2008, doi:10.1073/pnas.0804164105). In the presence of T7 gene 1.7 protein, ddT is taken up into the E. coli cell and converted to ddTTP. ddTTP is incorporated into DNA as ddTMP by the T7 DNA polymerase, resulting in chain termination. We have identified the pathway by which exogenous ddT is converted to ddTTP. The pathway consists of ddT transport by host nucleoside permeases and phosphorylation to ddTMP by the host thymidine kinase. T7 gene 1.7 protein phosphorylates ddTMP and ddTDP, resulting in ddTTP. A 74-residue peptide of the gene 1.7 protein confers ddT sensitivity to the same extent as the 196-residue wild-type gene 1.7 protein. We also show that cleavage of thymidine to thymine and deoxyribose-1-phosphate by the host thymidine phosphorylase greatly increases the sensitivity of phage T7 to ddT. Finally, a mutation in T7 DNA polymerase that leads to discrimination against the incorporation of ddTMP eliminates ddT sensitivity.

  15. Genetic determinants of sensitivity to beryllium in mice.

    Science.gov (United States)

    Tarantino-Hutchison, Lauren M; Sorrentino, Claudio; Nadas, Arthur; Zhu, Yiwen; Rubin, Edward M; Tinkle, Sally S; Weston, Ainsley; Gordon, Terry

    2009-06-01

    Chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung disease is caused by exposure to beryllium. This occupational hazard occurs in primary production and machining of Be-metal, BeO, beryllium - containing alloys, and other beryllium products. CBD begins as an MHC Class II-restricted, T(H)1 hypersensitivity, and the Human Leukocyte Antigen, HLA-DPB1E(69), is associated with risk of developing CBD. Because inbred strains of mice have not provided good models of CBD to date, three strains of HLA-DPB1 transgenic mice in an FVB/N background were developed; each contains a single allele of HLA-DPB1 that confers a different magnitude of risk for chronic beryllium disease: HLA-DPB1*0401 (OR approximately 0.2), HLA-DPB1*0201 (OR approximately 3), and HLA-DPB1*1701 (OR approximately 46). The mouse ear swelling test (MEST) was employed to determine if these different alleles would support a hypersensitivity response to beryllium. Mice were first sensitized on the back and subsequently challenged on the ear. In separate experiments, mice were placed into one of three groups (sensitization/challenge): C/C, C/Be, and Be/Be. In the HLA-DPB1*1701 mice, the strain with the highest risk transgene, the Be/Be group was the only group that displayed significant maximum increased ear thickness of 19.6% +/- 3.0% over the baseline measurement (p beryllium in seven inbred strains were investigated through use of the MEST, these included: FVB/N, AKR, Balb/c, C3H/HeJ, C57/BL6, DBA/2, and SJL/J. The FVB/N strain was least responsive, while the SJL/J and C57/BL6 strains were the highest responders. Our results suggest that the HLA-DPB1*1701 transgene product is an important risk factor for induction of the beryllium-sensitive phenotype. This model should be a useful tool for investigating beryllium sensitization.

  16. Sensitivity of Escherichia coli acrA Mutants to Psoralen plus Near-Ultraviolet Radiation

    DEFF Research Database (Denmark)

    Hansen, M. Trier

    1982-01-01

    The sensitivity to psoralen plus near-ultraviolet radiation (PUVA) was compared in a pair of E. coli strains differing at the acrA locus. Survival was determined for both bacteria and phage λ. AcrA mutant cells were 40 times more sensitive than wild type to the lethal effect of PUVA. Free λ phage...... specifically in the environment of the cellular DNA so as to allow increased intercalation and photobinding of psoralens....

  17. Proximate and ultimate causes of variable visual sensitivities: insights from cichlid fish radiations

    Science.gov (United States)

    Carleton, Karen L.; Dalton, Brian E.; Escobar-Camacho, Daniel; Nandamuri, Sri Pratima

    2016-01-01

    Animals vary in their sensitivities to different wavelengths of light. Sensitivity differences can have fitness implications in terms of animals’ ability to forage, find mates and avoid predators. As a result, visual systems are likely selected to operate in particular lighting environments and for specific visual tasks. This review focuses on cichlid vision, as cichlids have diverse visual sensitivities, and considerable progress has been made in determining the genetic basis for this variation. We describe both the proximate and ultimate mechanisms shaping cichlid visual diversity using the structure of Tinbergen’s four questions. We describe 1) the molecular mechanisms that tune visual sensitivities including changes in opsin sequence and expression; 2) the evolutionary history of visual sensitivity across the African cichlid flocks; 3) the ontological changes in visual sensitivity and how modifying this developmental program alters sensitivities among species; and 4) the fitness benefits of spectral tuning mechanisms with respect to survival and mating success. We further discuss progress to unravel the gene regulatory networks controlling opsin expression and suggest that a simple genetic architecture contributes to the lability of opsin gene expression. Finally, we identify unanswered questions including whether visual sensitivities are experiencing selection, and whether similar spectral tuning mechanisms shape visual sensitivities of other fishes. PMID:27061347

  18. Optimization of meander line radiators for frequency selective surfaces by using genetic algorithm

    Science.gov (United States)

    Bucuci, Stefania C.; Dumitrascu, Ana; Danisor, Alin; Berescu, Serban; Tamas, Razvan D.

    2015-02-01

    In this paper we propose the use of frequency selective surfaces based on meander line radiators, as targets for monitoring slow displacements with synthetic aperture radars. The optimization of the radiators is performed by using genetic algorithms on only two parameters i.e., gain and size. As an example, we have optimized a single meander antenna, resonating in the X-band, at 9.65 GHz.

  19. Sensitivity to plant modelling uncertainties in optimal feedback control of sound radiation from a panel

    DEFF Research Database (Denmark)

    Mørkholt, Jakob

    1997-01-01

    Optimal feedback control of broadband sound radiation from a rectangular baffled panel has been investigated through computer simulations. Special emphasis has been put on the sensitivity of the optimal feedback control to uncertainties in the modelling of the system under control.A model of a re...

  20. INHIBITION AND RADIATION SENSITIZING EFFECT OF INDOLEACETIC ACID COMBINED WITH HORSERADISH PEROXIDASE ON HELA CELLS

    Institute of Scientific and Technical Information of China (English)

    宋丽萍; 黄辰; 邱曙东; 王月英; 张健; 陈顺昌; 马军; 王全丽

    2004-01-01

    Objective To observe the inhibition and radiation-sensitizing effect of Indoleacetic acid (IAA) combined with horseradish peroxidase(HRP)on Hela cells. Methods Hela cells were cultured in vitro and classified into control group, drug group incubated with different doses of IAA(30, 60, 90μmol·L-1) plus 1.2μg·mL-1 HRP, radiation group (6MV-X, 4Gy ) and group of radiation plus IAA plus HRP(same dose as above). All the above were treated for 24-96 hours.The growth inhibition, radiation-sensitizing effect were observed with methyl thiazolyl tetrazolium (MTT) photocolorimetric assay and trypan blue dye assay. The-effect on cell proliferation cycle was determined by flow cytometry. Results The antiproliferation activities showed a significant time-effect and dose-effect relationship to some extent after Hela cells were treated with IAA combined with HRP. The group of radiation plus 60μmol·L-1 IAA plus 1.2μg·mL-1 HRP and radiation plus 90μmol·L-1 IAA plus 1.2μg·mL-1 HRP showed an obvious radiation sensitizing effect. After treatment with 90μmol·L-1 IAA plus 1.2μg·mL-1 HRP for 72 hours, the determination of cell cycle showed that the percentages of the cells on stages G2-M and S were all higher than those of the control group. For the group of radiation plus IAA combined with HRP, the percentages of the cells on stages G2-M were higher than those of the radiation group. Conclusion The above findings suggest that IAA combined with HRP has an inhibitive and killing effect on Hela cells. The effect was stronger during the cell cycles of G2-M and S. It also has a radiation sensitizing effect. Its mechanism might be that Hela cells were blocked on stages G2-M, and it presents a collaborative killing effect during miototic time.

  1. Sensitivity analysis of numerical weather prediction radiative schemes to forecast direct solar radiation over Australia

    Science.gov (United States)

    Mukkavilli, S. K.; Kay, M. J.; Taylor, R.; Prasad, A. A.; Troccoli, A.

    2014-12-01

    The Australian Solar Energy Forecasting System (ASEFS) project requires forecasting timeframes which range from nowcasting to long-term forecasts (minutes to two years). As concentrating solar power (CSP) plant operators are one of the key stakeholders in the national energy market, research and development enhancements for direct normal irradiance (DNI) forecasts is a major subtask. This project involves comparing different radiative scheme codes to improve day ahead DNI forecasts on the national supercomputing infrastructure running mesoscale simulations on NOAA's Weather Research & Forecast (WRF) model. ASEFS also requires aerosol data fusion for improving accurate representation of spatio-temporally variable atmospheric aerosols to reduce DNI bias error in clear sky conditions over southern Queensland & New South Wales where solar power is vulnerable to uncertainities from frequent aerosol radiative events such as bush fires and desert dust. Initial results from thirteen years of Bureau of Meteorology's (BOM) deseasonalised DNI and MODIS NASA-Terra aerosol optical depth (AOD) anomalies demonstrated strong negative correlations in north and southeast Australia along with strong variability in AOD (~0.03-0.05). Radiative transfer schemes, DNI and AOD anomaly correlations will be discussed for the population and transmission grid centric regions where current and planned CSP plants dispatch electricity to capture peak prices in the market. Aerosol and solar irradiance datasets include satellite and ground based assimilations from the national BOM, regional aerosol researchers and agencies. The presentation will provide an overview of this ASEFS project task on WRF and results to date. The overall goal of this ASEFS subtask is to develop a hybrid numerical weather prediction (NWP) and statistical/machine learning multi-model ensemble strategy that meets future operational requirements of CSP plant operators.

  2. Effects of anesthesia-induced modest hypothermia on cellular radiation sensitivity

    Institute of Scientific and Technical Information of China (English)

    XIANG; Yingsong(项莺松); TANG; Gusheng(唐古生); XU; Xiongfei(许熊飞); YANG; Rujun(杨如俊); CAI; Jianming(蔡建明); ZHANG; Minghui(张明辉); CAO; Xuetao(曹雪涛)

    2002-01-01

    To assess the mechanisms of modest hypothermia(MH) and its effects on cellular radiation response, a model of anesthesia-induced modest hypothermia(AIMH) in the adult mice and a model of pure MH in the newborn mice were established. The survival rate of lethally irradiated mice was increased to 72% through AIMH before irradiation. Both apoptosis and necrosis of human fetal bone marrow CD34+ hematopoietic stem cells cultured under MH were significantly decreased as detected by MTT and flow cytometry, with three-color labeled by PE-CD34+/ FITC-AnnexinV /7AAD. The survival and proliferation of mouse bone marrow MNC treated with MH after irradiation were also increased. The MH exerted similar protective effects on the leukemia cell lines A20, HL60, K562 to the normal bone marrow cells, but it enhanced the radiation sensitivity of leukemia cell line FBL3 and mouse melanoma B16F10. No effects have been found on the radiation sensitivity of those cells treated with MH before irradiation. The results also showed that MH mediated the effects on radiation sensitivity, in addition to increasing the oxygen tension. These results show different effects of MH on different cells:(i) AIMH exerts a protective effect on the normal hematopoietic stem cells, some leukemia cell lines A20, HL60, K562, and some neoplasma 3LL, LOVO. And MH exhibits a synthetic effect with anesthetic.(ii) MH enhances the radiation sensitivity of another leukemia and neoplasma cell lines FBL3, B16F10 and CT26. Therefore, AIMH has a potential to enhance the effects of radiation-therapy and decrease side effects on some tumors.

  3. Formates and dithionates: sensitive EPR-dosimeter materials for radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lund, E. [Department of Medicine and Care, Radiation Physics, Faculty of Health Sciences, University of Linkoeping, S-581 85 Linkoeping (Sweden)]. E-mail: eva.lund@imv.liu.se; Gustafsson, H. [Department of Medicine and Care, Radiation Physics, Faculty of Health Sciences, University of Linkoeping, S-581 85 Linkoeping (Sweden); Danilczuk, M. [Chemical Physics Laboratory, IFM, University of Linkoeping, S-581 83 Linkoeping (Sweden); Sastry, M.D. [Chemical Physics Laboratory, IFM, University of Linkoeping, S-581 83 Linkoeping (Sweden); Lund, A. [Chemical Physics Laboratory, IFM, University of Linkoeping, S-581 83 Linkoeping (Sweden); Vestad, T.A. [Department of Physics, University of Oslo, P.O. Box 1048 Blindern, N-0316 Oslo (Norway); Malinen, E. [Department of Physics, University of Oslo, P.O. Box 1048 Blindern, N-0316 Oslo (Norway); Hole, E.O. [Department of Physics, University of Oslo, P.O. Box 1048 Blindern, N-0316 Oslo (Norway); Sagstuen, E. [Department of Physics, University of Oslo, P.O. Box 1048 Blindern, N-0316 Oslo (Norway)

    2005-02-01

    Polycrystalline formates and dithionates are promising materials for EPR dosimetry, as large yields of radiation induced stable radicals are formed with a linear dose response. Rapid spin relaxation rates were detected in many of the substances, indicating that a high microwave power can be applied during EPR acquisition in order to improve sensitivity. Different techniques used to further improve the sensitivity, such as the replacement of {sup 7}Li with {sup 6}Li or exchange of protons with deuterons in the corresponding crystalline matrices and metal ion doping are discussed. It is concluded that formates and dithionates may be up to 10 times as sensitive as L-{alpha}-alanine.

  4. Inactivation of gadd45a sensitizes epithelial cancer cells to ionizing radiation in vivo resulting in prolonged survival.

    Science.gov (United States)

    Lu, Xiangdong; Yang, Chunyu; Hill, Reginald; Yin, Chaoyin; Hollander, M Christine; Fornace, Albert J; Van Dyke, Terry

    2008-05-15

    Ionizing radiation (IR) therapy is one of the most commonly used treatments for cancer patients. The responses of tumor cells to IR are often tissue specific and depend on pathway aberrations present in the tumor. Identifying molecules and mechanisms that sensitize tumor cells to IR provides new potential therapeutic strategies for cancer treatment. In this study, we used two genetically engineered mouse carcinoma models, brain choroid plexus carcinoma (CPC) and prostate, to test the effect of inactivating gadd45a, a DNA damage response p53 target gene, on tumor responses to IR. We show that gadd45a deficiency significantly increases tumor cell death after radiation. Effect on survival was assessed in the CPC model and was extended in IR-treated mice with gadd45a deficiency compared with those expressing wild-type gadd45a. These studies show a significant effect of gadd45a inactivation in sensitizing tumor cells to IR, implicating gadd45a as a potential drug target in radiotherapy management.

  5. Effects of sensitizer length on radiation crosslinked shape-memory polymers

    Energy Technology Data Exchange (ETDEWEB)

    Ware, Taylor, E-mail: tware@gatech.ed [School of Materials Science and Engineering, Georgia Institute of Technology, 771 Ferst Drive, Atlanta, GA 30332 (United States); Voit, Walter [School of Materials Science and Engineering, Georgia Institute of Technology, 771 Ferst Drive, Atlanta, GA 30332 (United States); Gall, Ken [School of Materials Science and Engineering, Georgia Institute of Technology, 771 Ferst Drive, Atlanta, GA 30332 (United States); Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 771 Ferst Drive, Atlanta, GA 30332 (United States)

    2010-04-15

    Shape-memory polymers (SMPs) are smart materials that can be designed to retain a metastable state and upon activation, recover a preprogrammed shape. In this study, poly(methyl acrylate) (PMA) is blended with poly(ethylene glycol) diacrylate (PEGDA) of various molecular weights in various concentrations and subsequently exposed to ionizing radiation. PEGDA sensitizes the radiation crosslinking of PMA, lowering the minimum absorbed dose for gelation and increasing the rubbery modulus, after crosslinking. Minimum dose for gelation, as determined by the Charlesby-Pinner equation, decreases from 25.57 kGy for unblended PMA to 2.06 kGy for PMA blended with 10.00 mole% PEGDA. Moreover, increase in the blend concentration of PEGDA increases the crosslinking density of the resulting networks. Sensitizer length, namely M{sub n} of PEGDA, also affects crosslinking and final mechanical properties. Increase in the length of the PEGDA molecule at a constant molar ratio increases the efficacy of the molecule as a radiation sensitizer as determined by the increase in gel fraction and rubbery modulus across doses. However, at a constant weight ratio of PEGDA to PMA, shorter PEGDA chains sensitize more crosslinking because they have more reactive ends per weight fraction. Sensitized samples of PMA with PEGDA were tested for shape-memory properties and showed shape fixity of greater than 99%. Samples had a glass transition temperature near 28 deg. C and recovered between 97% and 99% of the induced strain when strained to 50%.

  6. Effects of sensitizer length on radiation crosslinked shape-memory polymers

    Science.gov (United States)

    Ware, Taylor; Voit, Walter; Gall, Ken

    2010-04-01

    Shape-memory polymers (SMPs) are smart materials that can be designed to retain a metastable state and upon activation, recover a preprogrammed shape. In this study, poly(methyl acrylate) (PMA) is blended with poly(ethylene glycol) diacrylate (PEGDA) of various molecular weights in various concentrations and subsequently exposed to ionizing radiation. PEGDA sensitizes the radiation crosslinking of PMA, lowering the minimum absorbed dose for gelation and increasing the rubbery modulus, after crosslinking. Minimum dose for gelation, as determined by the Charlesby-Pinner equation, decreases from 25.57 kGy for unblended PMA to 2.06 kGy for PMA blended with 10.00 mole% PEGDA. Moreover, increase in the blend concentration of PEGDA increases the crosslinking density of the resulting networks. Sensitizer length, namely Mn of PEGDA, also affects crosslinking and final mechanical properties. Increase in the length of the PEGDA molecule at a constant molar ratio increases the efficacy of the molecule as a radiation sensitizer as determined by the increase in gel fraction and rubbery modulus across doses. However, at a constant weight ratio of PEGDA to PMA, shorter PEGDA chains sensitize more crosslinking because they have more reactive ends per weight fraction. Sensitized samples of PMA with PEGDA were tested for shape-memory properties and showed shape fixity of greater than 99%. Samples had a glass transition temperature near 28 °C and recovered between 97% and 99% of the induced strain when strained to 50%.

  7. Solar Radiation-Associated Adaptive SNP Genetic Differentiation in Wild Emmer Wheat, Triticum dicoccoides

    Science.gov (United States)

    Ren, Jing; Chen, Liang; Jin, Xiaoli; Zhang, Miaomiao; You, Frank M.; Wang, Jirui; Frenkel, Vladimir; Yin, Xuegui; Nevo, Eviatar; Sun, Dongfa; Luo, Ming-Cheng; Peng, Junhua

    2017-01-01

    Whole-genome scans with large number of genetic markers provide the opportunity to investigate local adaptation in natural populations and identify candidate genes under positive selection. In the present study, adaptation genetic differentiation associated with solar radiation was investigated using 695 polymorphic SNP markers in wild emmer wheat originated in a micro-site at Yehudiyya, Israel. The test involved two solar radiation niches: (1) sun, in-between trees; and (2) shade, under tree canopy, separated apart by a distance of 2–4 m. Analysis of molecular variance showed a small (0.53%) but significant portion of overall variation between the sun and shade micro-niches, indicating a non-ignorable genetic differentiation between sun and shade habitats. Fifty SNP markers showed a medium (0.05 ≤ FST ≤ 0.15) or high genetic differentiation (FST > 0.15). A total of 21 outlier loci under positive selection were identified by using four different FST-outlier testing algorithms. The markers and genome locations under positive selection are consistent with the known patterns of selection. These results suggested that genetic differentiation between sun and shade habitats is substantial, radiation-associated, and therefore ecologically determined. Hence, the results of this study reflected effects of natural selection through solar radiation on EST-related SNP genetic diversity, resulting presumably in different adaptive complexes at a micro-scale divergence. The present work highlights the evolutionary theory and application significance of solar radiation-driven natural selection in wheat improvement. PMID:28352272

  8. Radiation damage and sensitization effects on thermoluminescence of LiF:Mg,Ti (TLD-700)

    Science.gov (United States)

    Farag, M. A.; Sadek, A. M.; Shousha, Hany. A.; El-Hagg, A. A.; Atta, M. R.; Kitis, G.

    2017-09-01

    The radiation damage effects and enhancement the thermoluminescence (TL) efficiency of LiF:Mg,Ti (TLD-700)dosimeters via sensitization method were discussed. Attempts to eliminate the effects of damage and sensitization were made using different types of annealing processes. The results showed that after irradiating the dosimeters with dose > 250 Gy of 60Co gamma source, damage effects were observed. The sensitivity of the total area under the curve was decreased by a factor of ∼0.5 after irradiation at a pre-test dose of 2 kGy. However, the effects of radiation damage on each glow-peak are different. The glow-peak 2 was the only peak that was not affected by the high-dose irradiation. It has been shown that the degree of the radiation damage effect is related to the maximum dose-response function, f(D)max of the glow-peak. In general, significant radiation damage effects were observed for the glow-peaks of high f(D)max . Post-irradiation anneal at 280 °C for 30 min causes dramatic effects on the shape of the glow-curve and as well as on the sensitivity of the dosimeters. An increasing by a factor of ∼35 in the sensitivity of the total area under the curve was observed at a pre-test dose of 2 kGy. Improving the sensitivity of peak 7 by a factor of∼22 was the dominant factor in increasing the sensitivity of the dosimeters. On the other hand, an increasing by factors of ∼2.5 and ∼4 was found for peaks 2 and 5 respectively. On the other hand, a decreasing by a factor ∼0.5 was observed for peaks 3 and 4. At pre-test dose levels >250 Gy, a very strange and high intensity tail was observed in the high-temperature region of the glow-curves. The readout anneal was not enough to remove this tail. While, the furnace anneal could eliminate the sensitization effects but not the radiation damage effects on the sensitivity of the dosimeters.

  9. Bone sarcoma as a second malignant neoplasm in children: influence of radiation and genetic predisposition

    Energy Technology Data Exchange (ETDEWEB)

    Meadows, A.T.; Strong, L.C.; Li, F.P.; D' angio, G.J.; Schweisguth, O.; Freeman, A.I.; Jenkin, R.D.T.; Morris-Jones, P.; Nesbit, M.E.

    1980-12-15

    Osteosarcoma or chondrosarcoma developed as a second malignant neoplasm (SMN) in 40 of 188 individuals with SMN whose first neoplasm occurred in childhood. A genetic susceptibility to cancer was found in 23; the SMN developed in an irradiated field in 32; both factors were present in 16; neither in one. When a genetic predisposition was present, radiation shortened the interval to SMN. The intervals between tumors and the age at which the bone sarcomas developed in relation to genetic disease and therapy were analyzed by a two-mutation hypothesis.

  10. Genetic control of lithium sensitivity and regulation of inositol biosynthetic genes.

    Directory of Open Access Journals (Sweden)

    Jason King

    Full Text Available Lithium (Li(+ is a common treatment for bipolar mood disorder, a major psychiatric illness with a lifetime prevalence of more than 1%. Risk of bipolar disorder is heavily influenced by genetic predisposition, but is a complex genetic trait and, to date, genetic studies have provided little insight into its molecular origins. An alternative approach is to investigate the genetics of Li(+ sensitivity. Using the social amoeba Dictyostelium, we previously identified prolyl oligopeptidase (PO as a modulator of Li(+ sensitivity. In a link to the clinic, PO enzyme activity is altered in bipolar disorder patients. Further studies demonstrated that PO is a negative regulator of inositol(1,4,5trisphosphate (IP(3 synthesis, a Li(+ sensitive intracellular signal. However, it was unclear how PO could influence either Li(+ sensitivity or risk of bipolar disorder. Here we show that in both Dictyostelium and cultured human cells PO acts via Multiple Inositol Polyphosphate Phosphatase (Mipp1 to control gene expression. This reveals a novel, gene regulatory network that modulates inositol metabolism and Li(+ sensitivity. Among its targets is the inositol monophosphatase gene IMPA2, which has also been associated with risk of bipolar disorder in some family studies, and our observations offer a cellular signalling pathway in which PO activity and IMPA2 gene expression converge.

  11. Estimation of genetic variance for macro- and micro-environmental sensitivity using double hierarchical generalized linear models

    NARCIS (Netherlands)

    Mulder, H.A.; Ronnegard, L.; Veerkamp, R.F.; Strandberg, E.

    2013-01-01

    Background Genetic variation for environmental sensitivity indicates that animals are genetically different in their response to environmental factors. Environmental factors are either identifiable (e.g. temperature) and called macro-environmental or unknown and called micro-environmental. The

  12. A novel high-throughput irradiator for in vitro radiation sensitivity bioassays

    Science.gov (United States)

    Fowler, Tyler L.

    Given the emphasis on more personalized radiation therapy there is an ongoing and compelling need to develop high-throughput screening tools to further examine the biological effects of ionizing radiation on cells, tissues and organ systems in either the research or clinical setting. Conventional x-ray irradiators are designed to provide maximum versatility to radiobiology researchers, typically accommodating small animals, tissue or blood samples, and cellular applications. This added versatility often impedes the overall sensitivity and specificity of an experiment resulting in a trade-off between the number of absorbed doses (or dose rates) and biological endpoints that can be investigated in vitro in a reasonable amount of time. Therefore, modern irradiator designs are incompatible with current high-throughput bioassay technologies. Furthermore, important dosimetry and calibration characteristics (i.e. dose build-up region, beam attenuation, and beam scatter) of these irradiators are typically unknown to the end user, which can lead to significant deviation between delivered dose and intended dose to cells that adversely impact experimental results. Therefore, the overarching goal of this research is to design and develop a robust and fully automated high-throughput irradiator for in vitro radiation sensitivity investigations. Additionally, in vitro biological validation of this system was performed by assessing intracellular reactive oxygen species production, physical DNA double strand breaks, and activation of cellular DNA repair mechanisms. Finally, the high-throughput irradiator was used to investigate autophagic flux, a cellular adaptive response, as a potential biomarker of radiation sensitivity.

  13. The Sensitivity of Diagnostic Radiative Properties to Cloud Microphysics among Cloud-Resolving Model Simulations.

    Science.gov (United States)

    Xu, Kuan-Man

    2005-04-01

    This study examines the sensitivity of diagnosed radiative fluxes and heating rates to different treatments of cloud microphysics among cloud-resolving models (CRMs). The domain-averaged CRM outputs are used in this calculation. The impacts of the cloud overlap and uniform hydrometeor assumptions are examined using outputs having spatially varying cloud fields from a single CRM. It is found that the cloud overlap assumption impacts the diagnosis more significantly than the uniform hydrometeor assumption for all radiative fluxes. This is also the case for the longwave radiative cooling rate except for a layer above 7 km where it is more significantly impacted by the uniform hydrometeor assumption. The radiative cooling above upper-tropospheric anvils and the warming below these clouds are overestimated by about 0.5 K day-1 using the domain-averaged outputs. These results are used to further quantify intermodel differences in radiative properties due to different treatments of cloud microphysics among 10 CRMs. The magnitudes of the intermodel differences, as measured by the deviations from the consensus of 10 CRMs, are found to be smaller than those due to the cloud overlap assumption and comparable to those due to the uniform hydrometeor assumption for most shortwave radiative fluxes and the net radiative fluxes at the top of the atmosphere (TOA) and at the surface. For all longwave radiative fluxes, they are smaller than those due to cloud overlap and uniform hydrometeor assumptions. The consensus of all diagnosed radiative fluxes except for the surface downward shortwave flux agrees with observations to a degree that is close to the uncertainties of satellite- and ground-based measurements.

  14. Evolutionary concepts in ecotoxicology: tracing the genetic background of differential cadmium sensitivities in invertebrate lineages.

    Science.gov (United States)

    Dallinger, Reinhard; Höckner, Martina

    2013-07-01

    In many toxicological and ecotoxicological studies and experimental setups, the investigator is mainly interested in traditional parameters such as toxicity data and effects of toxicants on molecular, cellular or physiological functions of individuals, species or statistical populations. It is clear, however, that such approaches focus on the phenotype level of animal species, whilst the genetic and evolutionary background of reactions to environmental toxicants may remain untold. In ecotoxicological risk assessment, moreover, species sensitivities towards pollutants are often regarded as random variables in a statistical approach. Beyond statistics, however, toxicant sensitivity of every species assumes a biological significance, especially if we consider that sensitivity traits have developed in lineages of species with common evolutionary roots. In this article, the genetic and evolutionary background of differential Cd sensitivities among invertebrate populations and species and their potential of adaptation to environmental Cd exposure will be highlighted. Important evolutionary and population genetic concepts such as genome structure and their importance for evolutionary adaptation, population structure of affected individuals, as well as micro and macroevolutionary mechanisms of Cd resistance in invertebrate lineages will be stressed by discussing examples of work from our own laboratory along with a review of relevant literature data and a brief discussion of open questions along with some perspectives for further research. Both, differences and similarities in Cd sensitivity traits of related invertebrate species can only be understood if we consider the underlying evolutionary processes and genetic (or epigenetic) mechanisms. Keeping in mind this perception can help us to better understand and interpret more precisely why the sensitivity of some species or species groups towards a certain toxicant (or metal) may be ranked in the lower or higher range of

  15. Studies on the radiation application for development genetic resources

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Il; Song, Hi Sup; Kim, Jae Sung; Shin, In Chul; Lee, Sang Jae; Lee, Ki Woon; Lim, Young Tack; Lee, In Suk; Kang, Kwan Kyu

    1997-07-01

    For the development of nuclear application technique on the induction and selection of radiation mutation in in vitro and in vivo mutagenesis, several crops plants such as rice, soybean, perilla potato and sweet potato were irradiated with gamma rays of various dose to the seeds. Variants of sweet potato plantlets were obtained from embryogenic callus irradiated with gamma rays and variants were analyzed by using DNA, RNA and protein band patterns. Various mutants were selected from rice, soybean and perilla for short plant, earliness, high yield, large seed size and disease resistance in the advanced mutant generations. Several promising mutants of rice, soybean and perilla will be released to farmers. (author). 198 refs., 26 tabs.,15 figs.

  16. Identification of sensitive serum microRNA biomarkers for radiation biodosimetry.

    Directory of Open Access Journals (Sweden)

    Naduparambil Korah Jacob

    Full Text Available Exposure to ionizing radiation through environmental, occupational or a nuclear reactor accident such as the recent Fukushima Daiichi incident often results in major consequences to human health. The injury caused by radiation can manifest as acute radiation syndromes within weeks in organs with proliferating cells such as hematopoietic and gastrointestinal systems. Cancers, fibrosis and degenerative diseases are also reported in organs with differentiated cells, months or years later. Studies conducted on atom bomb survivors, nuclear reactor workers and animal models have shown a direct correlation of these effects with the absorbed dose. Physical dosimeters and the available radio-responsive biologics in body fluids, whose responses are rather indirect, have limitations to accurately evaluate the extent of post exposure damage. We have used an amplification-free, hybridization based quantitative assay utilizing the nCounter multiplex platform developed by nanoString Technologies to compare the levels of over 600 miRNAs in serum from mice irradiated at a range of 1 to 12 Gy at 24 and 48 hr time points. Development of a novel normalization strategy using multiple spike-in oligonucleotides allowed accurate measurement of radiation dose and time dependent changes in serum miRNAs. The response of several evolutionarily conserved miRNAs abundant in serum, were found to be robust and sensitive in the dose range relevant for medical triage and in patients who receive total body radiation as preparative regimen for bone marrow transplantation. Notably, miRNA-150, abundant in lymphocytes, exhibited a dose and time dependent decrease in serum, which we propose as a sensitive marker indicative of lymphocyte depletion and bone marrow damage. Our study has identified several markers useful for evaluation of an individual's response by minimally invasive methods, relevant to triage in case of a radiation accident and evaluation of toxicity and response

  17. Effect of test duration and feeding on relative sensitivity of genetically distinct clades of Hyalella azteca.

    Science.gov (United States)

    Soucek, David J; Dickinson, Amy; Major, Kaley M; McEwen, Abigail R

    2013-11-01

    The amphipod Hyalella azteca is widely used in ecotoxicology laboratories for the assessment of chemical risks to aquatic environments, and it is a cryptic species complex with a number of genetically distinct strains found in wild populations. While it would be valuable to note differences in contaminant sensitivity among different strains collected from various field sites, those findings would be influenced by acclimation of the populations to local conditions. In addition, potential differences in metabolism or lipid storage among different strains may confound assessment of sensitivity in unfed acute toxicity tests. In the present study, our aim was to assess whether there are genetic differences in contaminant sensitivity among three cryptic provisional species of H. azteca. Therefore, we used organisms cultured under the same conditions, assessed their ability to survive for extended periods without food, and conducted fed and unfed acute toxicity tests with two anions (nitrate and chloride) whose toxicities are not expected to be altered by the addition of food. We found that the three genetically distinct clades of H. azteca had substantially different responses to starvation, and the presence/absence of food during acute toxicity tests had a strong role in determining the relative sensitivity of the three clades. In fed tests, where starvation was no longer a potential stressor, significant differences in sensitivity were still observed among the three clades. In light of these differences in sensitivity, we suggest that ecotoxicology laboratories consider using a provisional species in toxicity tests that is a regionally appropriate surrogate.

  18. James V. Neel and Yuri E. Dubrova: Cold War debates and the genetic effects of low-dose radiation.

    Science.gov (United States)

    Goldstein, Donna M; Stawkowski, Magdalena E

    2015-01-01

    This article traces disagreements about the genetic effects of low-dose radiation exposure as waged by James Neel (1915-2000), a central figure in radiation studies of Japanese populations after World War II, and Yuri Dubrova (1955-), who analyzed the 1986 Chernobyl nuclear power plant accident. In a 1996 article in Nature, Dubrova reported a statistically significant increase in the minisatellite (junk) DNA mutation rate in the children of parents who received a high dose of radiation from the Chernobyl accident, contradicting studies that found no significant inherited genetic effects among offspring of Japanese A-bomb survivors. Neel's subsequent defense of his large-scale longitudinal studies of the genetic effects of ionizing radiation consolidated current scientific understandings of low-dose ionizing radiation. The article seeks to explain how the Hiroshima/Nagasaki data remain hegemonic in radiation studies, contextualizing the debate with attention to the perceived inferiority of Soviet genetic science during the Cold War.

  19. Preliminary Study of Position-Sensitive Large-Area Radiation Portal Monitor

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Chang Hwy; Kim, Hyunok; Moon, Myung Kook [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Jongyul [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Park, Jong Won; Lim, Yong Kon [Korea Institute of Ocean Science and Technology, Daejeon (Korea, Republic of)

    2013-10-15

    An RPM, which is a passive inspection method, is a system for monitoring the movement of radioactive materials at an airport, seaport, border, etc. To detect a γ-ray, an RPM using the plastic scintillator is generally used. The method of γ-ray detection using an RPM with a plastic scintillator is to measure lights generated by an incident γ-ray in the scintillator. Generally, a large-area RPM uses one or two photomultiplier tubes (PMT) for light collection. However, in this study, we developed a 4-ch RPM that can measure the radiation signal using 4 PMTs. The reason for using 4 PMTs is to calculate the position of the radiation source. In addition, we developed an electric device for acquisition of a 4-ch output signal at the same time. To estimate the performance of the developed RPM, we performed an RPM test using a {sup 60}Co γ-ray check source. In this study, we performed the development of a 4-ch RPM. The major function of the typical RPM is to measure the radiation. However, we developed a position-sensitive 4-ch RPM, which can be used to measure the location of the radiation source, as well as the radiation measurement, at the same time. In the future, we plan to develop an algorithm for a position detection of the radiation. In addition, an algorithm will be applied to an RPM.

  20. Rapamycin-mediated mTOR inhibition attenuates survivin and sensitizes glioblastoma cells to radiation therapy

    Institute of Scientific and Technical Information of China (English)

    Arunkumar Anandharaj; Senthilkumar Cinghu; Woo-Yoon Park

    2011-01-01

    Survivin, an antiapoptotic protein, is elevated in most malignancies and attributes to radiation resistance in tumors including glioblastoma multiforme. The downregulation of survivin could sensitize glioblastoma ceils to radiation therapy. In this study, we investigated the effect of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), in attenuating survivin and enhancing the therapeutic efficacy for glioblastoma cells, and elucidated the underlying mechanisms. Here we tested various concentrations of rapamycin (1-8 nM) in combination with radiation dose 4 Gy. Rapamycin effectively modulated the protein kinase B (Akt)/mTOR pathway by inhibiting the phosphorylation of Akt and mTOR proteins, and this inhibition was further enhanced by radiation. The expression level of survivin was decreased in rapamycin pre-treatment glioblastoma ceils followed by radiation; meanwhile, the phosphorylation of H2A histone family member X (H2AX) at serine-139 (γ-H2AX) was increased, p21 protein was also induce on radiation with rapamycin pre-treatment, which enhanced G1 arrest and the accumulation of cells at G0/subG1 phase. Furthermore, the clonogenic cell survival assay revealed a significant dose-dependent decrease in the surviving fraction for all three cell lines pre-treated with rapamycin. Our studies demonstrated that targeting survivin may be an effective approach for radiosensitization of malignant glioblastoma.

  1. Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants

    Science.gov (United States)

    Bowden, Jack; Fall, Tove; Ingelsson, Erik; Thompson, Simon G.

    2017-01-01

    Mendelian randomization investigations are becoming more powerful and simpler to perform, due to the increasing size and coverage of genome-wide association studies and the increasing availability of summarized data on genetic associations with risk factors and disease outcomes. However, when using multiple genetic variants from different gene regions in a Mendelian randomization analysis, it is highly implausible that all the genetic variants satisfy the instrumental variable assumptions. This means that a simple instrumental variable analysis alone should not be relied on to give a causal conclusion. In this article, we discuss a range of sensitivity analyses that will either support or question the validity of causal inference from a Mendelian randomization analysis with multiple genetic variants. We focus on sensitivity analyses of greatest practical relevance for ensuring robust causal inferences, and those that can be undertaken using summarized data. Aside from cases in which the justification of the instrumental variable assumptions is supported by strong biological understanding, a Mendelian randomization analysis in which no assessment of the robustness of the findings to violations of the instrumental variable assumptions has been made should be viewed as speculative and incomplete. In particular, Mendelian randomization investigations with large numbers of genetic variants without such sensitivity analyses should be treated with skepticism. PMID:27749700

  2. Radiation-sensitive indicator based on radiation-chemical formation of acids in polyvinyl butyral films containing chloral hydrate

    Science.gov (United States)

    Abdel-Fattah, Atef A.; El-Kelany, M.

    1998-03-01

    Radiation-sensitive indicators based on dyed polyvinyl butyral (PVB) containing acid-sensitive dye (bromophenol blue, BPB) and chloral hydrate (CCl 3CH(OH) 2, 2,2,2-trichloroethane-1, 1-diol) have been developed. These plastic film dosimeters undergo colour change from blue (the alkaline form of BPB) to yellow (the acidic form of BPB), indicating acid formation. The concentration of radiation-formed acids in the films containing different concentrations of chloral hydrate was calculated at different doses. The kinetics of the acid-formation reaction is discussed, indicating a half-order reaction with respect to chloral hydrate concentration. These films can be used as dosimeters for food irradiation applications where the maxima of the useful dose ranges are between 1 and 4 kGy depending on chloral hydrate concentration in the film. The response of these films depends on temperature during irradiation; therefore a correction should be applied. These films have the advantage of negligible humidity effects on response in the intermediate range of relative humidity from 10 to 70% as well as good post-irradiation stability when stored in the dark at room temperature.

  3. Aggressive Behavior between Siblings and the Development of Externalizing Problems: Evidence from a Genetically Sensitive Study

    Science.gov (United States)

    Natsuaki, Misaki N.; Ge, Xiaojia; Reiss, David; Neiderhiser, Jenae M.

    2009-01-01

    This study investigated the prospective links between sibling aggression and the development of externalizing problems using a multilevel modeling approach with a genetically sensitive design. The sample consisted of 780 adolescents (390 sibling pairs) who participated in 2 waves of the Nonshared Environment in Adolescent Development project.…

  4. Genetic variants associated with thermal pain sensitivity in a paediatric population

    NARCIS (Netherlands)

    Matic, M.; Bosch, G.E. van den; Wildt, S.N. de; Tibboel, D.; Schaik, R.H. van

    2016-01-01

    Pain sensitivity is an inherited factor that varies strongly between individuals. We investigated whether genetic polymorphisms in the candidate genes COMT, OPRM1, OPRD1, TAOK3, TRPA1, TRPV1, and SCN9A are contributing to experimental pain variability between children. Our study included 136

  5. Genetic variance in micro-environmental sensitivity for milk and milk quality in Walloon Holstein cattle

    NARCIS (Netherlands)

    Vandenplas, J.; Bastin, C.; Gengler, N.; Mulder, H.A.

    2013-01-01

    Animals that are robust to environmental changes are desirable in the current dairy industry. Genetic differences in micro-environmental sensitivity can be studied through heterogeneity of residual variance between animals. However, residual variance between animals is usually assumed to be homogene

  6. GENETIC BACKGROUND BUT NOT METALLOTHIONEIN PHENOTYPE DICTATES SENSITIVITY TO CADMIUM-INDUCED TESTICULAR INJURY IN MICE

    Science.gov (United States)

    Genetic Background but not Metallothionein Phenotype Dictates Sensitivity to Cadmium-Induced Testicular Injury in MiceJie Liu1,2, Chris Corton3, David J. Dix4, Yaping Liu1, Michael P. Waalkes2 and Curtis D. Klaassen1 ABSTRACTParenteral administrati...

  7. MOESHA: A genetic algorithm for automatic calibration and estimation of parameter uncertainty and sensitivity of hydrologic models

    Science.gov (United States)

    Characterization of uncertainty and sensitivity of model parameters is an essential and often overlooked facet of hydrological modeling. This paper introduces an algorithm called MOESHA that combines input parameter sensitivity analyses with a genetic algorithm calibration routin...

  8. Numerical Simulation of Sensitivities of Snow Melting to Spectral Composition of the Incoming Solar Radiation

    Institute of Scientific and Technical Information of China (English)

    LI Weiping; SUN Shufen; WANG Siao; LIU Xin

    2009-01-01

    Snow albedo is an important factor influencing the snow surface energy budget and snow melting,yet uncertainties remain in the calculation of spectrally resolved snow surface albedo because the spectral composition (visible versus near infrared) of the incident solar radiation is seldom available. The influence of the spectral composition of the incoming solar radiation on the snow surface albedo, snow surface energy budget, and final snow ablation is investigated through sensitivity experiments of four snow seasons at two open sites in the Alps by using a multi-layer Snow-Atmosphere-Soil-Transfer scheme (SAST). Since the snow albedo in the near infrared (NIR) spectral band is significantly lower than that in the visible (VIS) band, and almost the entire NIR part of the solar radiation is absorbed in the top layer of the snow pack, given a fixed amount of incoming solar radiation, a lower VIS/NIR ratio implies that more NIR radiation is reaching the ground surface and more is absorbed by the top layer of the snow pack, therefore, speeding up the snow melting and increasing the surface runoff, although a lesser part of the solar radiation in the visible band is transmitted into and trapped by the sub-layer of the snow pack. The above VIS/NIR ratio effect of the incoming solar radiation can result in a couple of days difference in the timing of snow ablation and it becomes more significant in late spring when the total solar radiation is intensified with seasonal evolution. Snow aging also slightly intensifies this VIS/NIR ratio effect.

  9. Temporal Dependence of Chromosomal Aberration on Radiation Quality and Cellular Genetic Background

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2017-01-01

    Radiation induced cancer risks are driven by genetic instability. It is not well understood how different radiation sources induce genetic instability in cells with different genetic background. Here we report our studies on genetic instability, particularly chromosome instability using fluorescence in situ hybridization (FISH), in human primary lymphocytes, normal human fibroblasts, and transformed human mammary epithelial cells in a temporal manner after exposure to high energy protons and Fe ions. The chromosome spread was prepared 48 hours, 1 week, 2 week, and 1 month after radiation exposure. Chromosome aberrations were analyzed with whole chromosome specific probes (chr. 3 and chr. 6). After exposure to protons and Fe ions of similar cumulative energy (??), Fe ions induced more chromosomal aberrations at early time point (48 hours) in all three types of cells. Over time (after 1 month), more chromosome aberrations were observed in cells exposed to Fe ions than in the same type of cells exposed to protons. While the mammary epithelial cells have higher intrinsic genetic instability and higher rate of initial chromosome aberrations than the fibroblasts, the fibroblasts retained more chromosomal aberration after long term cell culture (1 month) in comparison to their initial frequency of chromosome aberration. In lymphocytes, the chromosome aberration frequency at 1 month after exposure to Fe ions was close to unexposed background, and the chromosome aberration frequency at 1 month after exposure to proton was much higher. In addition to human cells, mouse bone marrow cells isolated from strains CBA/CaH and C57BL/6 were irradiated with proton or Fe ions and were analyzed for chromosome aberration at different time points. Cells from CBA mice showed similar frequency of chromosome aberration at early and late time points, while cells from C57 mice showed very different chromosome aberration rate at early and late time points. Our results suggest that relative

  10. Experimental study of variations in background radiation and the effect on Nuclear Car Wash sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Church, J; Slaughter, D; Norman, E; Asztalos, S; Biltoft, P

    2007-02-07

    Error rates in a cargo screening system such as the Nuclear Car Wash [1-7] depend on the standard deviation of the background radiation count rate. Because the Nuclear Car Wash is an active interrogation technique, the radiation signal for fissile material must be detected above a background count rate consisting of cosmic, ambient, and neutron-activated radiations. It was suggested previously [1,6] that the Corresponding negative repercussions for the sensitivity of the system were shown. Therefore, to assure the most accurate estimation of the variation, experiments have been performed to quantify components of the actual variance in the background count rate, including variations in generator power, irradiation time, and container contents. The background variance is determined by these experiments to be a factor of 2 smaller than values assumed in previous analyses, resulting in substantially improved projections of system performance for the Nuclear Car Wash.

  11. Sensitivity coefficients for the stochastic estimation of the radiation damage to the reactor pressure vessel

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, C.M.; Hernandez Valle, S. [Centro de Investigaciones Tecnologicas, Nucleares y Ambientales, La Habana (Cuba). E-mail: calvarez@ctn.isctn.edu.cu; svalle@ctn.isctn.edu.cu

    2000-07-01

    The construction of the sensitivity matrix in the case of the vessel radiation damage estimation by Monte Carlo techniques poses new problems related to the uncertainties of the obtained responses. In the case of deterministic calculations, the sensitivity coefficient obtention is a straightforward procedure based on the perturbation formalism through the calculation of the adjoint fluxes. In the paper an alternative procedure implementation based on the differential operator method is described with the modifications needed to the used HEXANN-EVALU code for the response estimations in the VVER-440 pressure vessel. (author)

  12. Crustaceous lichens sensitive monitor of caesium-137 radiation level in terrestrial environment

    Institute of Scientific and Technical Information of China (English)

    Du Chunguang; Zhao Ye; Zhang Jing; Xu Cuihua

    2005-01-01

    The activity of caesium-137 (Bq/kg) in the crustaceous lichens and other samples was determined to prove the feasibility that crustaceous lichens work as a sensitive biology monitor to record the caesium-137 (Bq/kg) radiation levels of terrestrial environment. The measurements were performed with GEM series HPGe (high-purity Germanium) coaxial detector system (ADCAM -100) made by EC & GORTEC Company in USA. It was found that the activity of caesium-137 (Bq/kg) in the crustaceous lichens was one order of magnitude higher than that found in surface soil,and was over three orders of magnitude higher than those found in the familiar biological samples. These results proved that crustaceous lichens may be one of the most sensitive biological monitors about the remote transmission and environmental radiation levels of caesium-137.

  13. Nonlinear quantitative radiation sensitivity prediction model based on NCI-60 cancer cell lines.

    Science.gov (United States)

    Zhang, Chunying; Girard, Luc; Das, Amit; Chen, Sun; Zheng, Guangqiang; Song, Kai

    2014-01-01

    We proposed a nonlinear model to perform a novel quantitative radiation sensitivity prediction. We used the NCI-60 panel, which consists of nine different cancer types, as the platform to train our model. Important radiation therapy (RT) related genes were selected by significance analysis of microarrays (SAM). Orthogonal latent variables (LVs) were then extracted by the partial least squares (PLS) method as the new compressive input variables. Finally, support vector machine (SVM) regression model was trained with these LVs to predict the SF2 (the surviving fraction of cells after a radiation dose of 2 Gy γ-ray) values of the cell lines. Comparison with the published results showed significant improvement of the new method in various ways: (a) reducing the root mean square error (RMSE) of the radiation sensitivity prediction model from 0.20 to 0.011; and (b) improving prediction accuracy from 62% to 91%. To test the predictive performance of the gene signature, three different types of cancer patient datasets were used. Survival analysis across these different types of cancer patients strongly confirmed the clinical potential utility of the signature genes as a general prognosis platform. The gene regulatory network analysis identified six hub genes that are involved in canonical cancer pathways.

  14. Nonlinear Quantitative Radiation Sensitivity Prediction Model Based on NCI-60 Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Chunying Zhang

    2014-01-01

    Full Text Available We proposed a nonlinear model to perform a novel quantitative radiation sensitivity prediction. We used the NCI-60 panel, which consists of nine different cancer types, as the platform to train our model. Important radiation therapy (RT related genes were selected by significance analysis of microarrays (SAM. Orthogonal latent variables (LVs were then extracted by the partial least squares (PLS method as the new compressive input variables. Finally, support vector machine (SVM regression model was trained with these LVs to predict the SF2 (the surviving fraction of cells after a radiation dose of 2 Gy γ-ray values of the cell lines. Comparison with the published results showed significant improvement of the new method in various ways: (a reducing the root mean square error (RMSE of the radiation sensitivity prediction model from 0.20 to 0.011; and (b improving prediction accuracy from 62% to 91%. To test the predictive performance of the gene signature, three different types of cancer patient datasets were used. Survival analysis across these different types of cancer patients strongly confirmed the clinical potential utility of the signature genes as a general prognosis platform. The gene regulatory network analysis identified six hub genes that are involved in canonical cancer pathways.

  15. Effect of free radicals and cultivation media on radiation sensitivities of escherichia coli and related bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Hitoshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2000-09-01

    Effects of gamma-irradiation on some strains of Escherichia coli, Salmonella enteritidis and Staphylococcus aureus were investigated in the presence of N{sub 2}, N{sub 2}O and O{sub 2} and with the hydroxyl radical (OH) scavengers glycerol, polyethylene glycerol and formate. Injured cell membrane of bacteria was detected using with MacConkey agar for E. coli and S. enteritidis and 7% NaCl Triptic soy agar for St. aureus instead of Tryptic soy agar for recovery medium. From this study, addition of glycerol significantly reduced the sensitivity in all of strains, and cell membrane was not injured significantly except in radiation sensitive strain E. coli A4-1. When superoxide radicals (O{sub 2}) were generated during irradiation in the presence of formate, injured cell membrane increased significantly in all of strains. However, molecular oxygen (O{sub 2}) and OH radicals also had some effects on the damage of cell membrane. These results suggest that most radiation induced cell lethality was responsible to the cooperative effects of intracellular OH radicals and O{sub 2} on DNA with lessor effect of damage on cell membrane by O{sub 2} radicals, O{sub 2} and OH radicals. On the radiation sensitive strain of E. coli, cell lethality occurred significantly by the injury of cell membrane compared with other strains. (author)

  16. Interaction of Ionizing Radiation, Genetically Active Chemicals, and Radiofrequency Radiation in Human and Rodent Cells

    Science.gov (United States)

    1990-12-01

    Martin L. Meltz, Ph.D. Patricia K. Holahan , Ph.D. Steven T. Smith, Ph.D. James J. Kerbacher, Ph.D. Victor Ciaravino, Ph.D. Department of Radiology PO...Chemicals, and Radiofrequency Radiation in Human and Rodent Cells 12 PERSONAL AUTHOR(S) Meltz. Martin L.; Holahan Patricia K.; Smith Steven Kerbacher...Potentiation of SCE Induction and Cell Killing by Adriamycin in CHO Cells (Ciaravino and Holahan , in preparation), showed that Adriamycin exposure at 410C

  17. Soft x rays as a tool to investigate radiation-sensitive sites in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, D.J.; Zaider, M.

    1983-01-01

    It is now clear that the initial geometrical distribution of primary radiation products in irradiated biological matter is fundamental to the observed end point (cell killing, mutation induction, chromosome aberrations, etc.). In recent years much evidence has accumulated indicating that for all radiations, physical quantities averaged over cellular dimensions (micrometers) are not good predictors of biological effect, and that energy-deposition processes at the nanometer level are critical. Thus irradiation of cells with soft x rays whose secondary electrons have ranges of the order of nanometers is a unique tool for investigating different models for predicting the biological effects of radiation. We demonstrate techniques whereby the biological response of the cell and the physical details of the energy deposition processes may be separated or factorized, so that given the response of a cellular system to, say, soft x rays, the response of the cell to any other radiation may be predicted. The special advantages of soft x rays for eliciting this information and also information concerning the geometry of the radiation sensitive structures within the cell are discussed.

  18. Genetic effects in somatic and germ cells, induced by ionizing radiations

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, B.; Benova, D.; Bajrakova, A.; Bulanova, M.; Vyglenov, A.; Rupova, I.; Georgieva, I. (Meditsinska Akademiya, Sofia (Bulgaria). Nauchen Inst. po Rentgenologiya i Radiobiologiya)

    1983-01-01

    Quantitative data are reported on injuries to hereditary structures in somatic and sex cells, induced by different types of ionizing radiation. The model systems used were human peripheral blood lymphocytes, in vitro irradiated with different doses: bone-marrow cells of mice and rats irradiated in vivo: mouse, rat, rabbit and hamster sex cells. To evaluate the dose-effect dependency after acute and chronic irradiation, the authors used mathematical models, describing the amount of chromosomal injuries. Attempt was made to estimate the somatic and genetic risk, following acute and chronic irradiation with different doses of ionizing radiations.

  19. Toxic variability and radiation sensitization by Pt(II) analogs in Salmonella typhimurium cells

    Energy Technology Data Exchange (ETDEWEB)

    Richmond, R.C.; Khokhar, A.R.; Teicher, B.A.; Douple, E.B.

    1984-09-01

    A rationale is presented for the development of toxic, i.e., cytocidal, antitumor drugs as clinical hypoxic cell radiation sensitizers. Pt(II) complex-induced hypoxic cell radiation sensitization may occur from Pt(II) complex in free solution and Pt(II) bound to DNA. Although both the free solution and the bound compartments may operate, the free solution compartment is more likely amenable to experimental and clinical control in the case of systemically active Pt drugs. Assuming equivalent cell uptake of different Pt(II) complexes, the free solution compartment of Pt(II) sensitization can be increased by utilizing less toxic analogs of the antitumor drug cis-dichlorodiammineplatinum(II). One such less toxic Pt(II) sensitizer currently in clinical use is found to be cis-(1,1-cyclobutanedicarboxylato)diammineplatinum(II). A new finding of both clinical and mechanistic usefulness is described: irradiation of hypoxic solutions of four cis-Pt(II) complexes, but not two trans-Pt(II) complexes, creates products that cause toxicity in excees of the unirradiated solutions.

  20. Possibility to sound the atmospheric ozone by a radiosonde equipped with two temperature sensors, sensitive and non-sensitive to the long wave radiation

    Science.gov (United States)

    Kitaoka, T.; Sumi, T.

    1994-01-01

    The sensitiveness of white coated thermistor sensors and non-sensitiveness of the gold coated over white thermistor sensors (which have been manufactured by a vacuum evaporation process) to long wave radiation were ascertained by some simple experiments in-room and also by analyses of some results of experimental soundings. From results of analyses on the temperature discrepancies caused by long wave radiation, the possibility to sound the atmospheric ozone partial pressure by a radiosonde equipped with two kinds of sensors, sensitive and non-sensitive to the long wave radiation was suggested, and the test results of the newly developed software for the deduction of ozone partial pressure in upper layers was also shown. However, it was found that the following is the necessary condition to realize the purpose. The sounding should be made by a radiosonde equipped with three sensors, instead of two, one being non-sensitive to the long wave radiation perfectly, and the other two also non-sensitive partially to the downward one, with two different angles of exposure upward. It is essential for the realization of the purpose to get two different values of temperature discrepancies simultaneously observed by the three sensors mentioned above and to avoid the troublesome effects of the upward long wave radiation.

  1. Lignocellulolytic mutants of Pleurotus ostreatus induced by gamma-ray radiation and their genetic similarities

    Science.gov (United States)

    Lee, Y.-K.; Chang, H.-H.; Kim, J.-S.; Kim, J. K.; Lee, K.-S.

    2000-02-01

    To induce the lignocellulolytic mutants of Pleurotus ostreatus, the mycelia were irradiated by gamma-ray radiation to doses of 1-2 kGy. Five strains were isolated by the criteria of clamp connection, fruiting body formation, growth rate and activities of extracellular enzymes. All isolated strains were able to form the fruiting bodies and grew similarly to the control. The extracellular enzymes activities in liquid media of isolated strains were up to 10 times higher than the control. Genetic similarities of the isolated strains ranged from 64.4% to 93.3% of the control. From these results, it seems that the genetic diversity of P. ostreatus could be changed and useful strains be induced by gamma-ray radiation to recycle or reuse biowastes.

  2. Lignocellulolytic mutants of Pleurotus ostreatus induced by gamma-ray radiation and their genetic similarities

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y-K. E-mail: yklee@nanum.kaeri.re.kr; Chang, H-H.; Kim, J-S.; Kim, J.K.; Lee, K-S

    2000-02-01

    To induce the lignocellulolytic mutants of Pleurotus ostreatus, the mycelia were irradiated by gamma-ray radiation to doses of 1-2 kGy. Five strains were isolated by the criteria of clamp connection, fruiting body formation, growth rate and activities of extracellular enzymes. All isolated strains were able to form the fruiting bodies and grew similarly to the control. The extracellular enzymes activities in liquid media of isolated strains were up to 10 times higher than the control. Genetic similarities of the isolated strains ranged from 64.4% to 93.3% of the control. From these results, it seems that the genetic diversity of P. ostreatus could be changed and useful strains be induced by gamma-ray radiation to recycle or reuse biowastes. (author)

  3. Sensitivity and Acclimation of Three Canopy-Forming Seaweeds to UVB Radiation and Warming

    KAUST Repository

    Xiao, Xi

    2015-12-02

    Canopy-forming seaweeds, as primary producers and foundation species, provide key ecological services. Their responses to multiple stressors associated with climate change could therefore have important knock-on effects on the functioning of coastal ecosystems. We examined interactive effects of UVB radiation and warming on juveniles of three habitat-forming subtidal seaweeds from Western Australia–Ecklonia radiata, Scytothalia dorycarpa and Sargassum sp. Fronds were incubated for 14 days at 16–30°C with or without UVB radiation and growth, health status, photosynthetic performance, and light absorbance measured. Furthermore, we used empirical models from the metabolic theory of ecology to evaluate the sensitivity of these important seaweeds to ocean warming. Results indicated that responses to UVB and warming were species specific, with Sargassum showing highest tolerance to a broad range of temperatures. Scytothalia was most sensitive to elevated temperature based on the reduced maximum quantum yields of PSII; however, Ecklonia was most sensitive, according to the comparison of activation energy calculated from Arrhenius’ model. UVB radiation caused reduction in the growth, physiological responses and thallus health in all three species. Our findings indicate that Scytothalia was capable of acclimating in response to UVB and increasing its light absorption efficiency in the UV bands, probably by up-regulating synthesis of photoprotective compounds. The other two species did not acclimate over the two weeks of exposure to UVB. Overall, UVB and warming would severely inhibit the growth and photosynthesis of these canopy-forming seaweeds and decrease their coverage. Differences in the sensitivity and acclimation of major seaweed species to temperature and UVB may alter the balance between species in future seaweed communities under climate change.

  4. Sensitivity and Acclimation of Three Canopy-Forming Seaweeds to UVB Radiation and Warming.

    Directory of Open Access Journals (Sweden)

    Xi Xiao

    Full Text Available Canopy-forming seaweeds, as primary producers and foundation species, provide key ecological services. Their responses to multiple stressors associated with climate change could therefore have important knock-on effects on the functioning of coastal ecosystems. We examined interactive effects of UVB radiation and warming on juveniles of three habitat-forming subtidal seaweeds from Western Australia-Ecklonia radiata, Scytothalia dorycarpa and Sargassum sp. Fronds were incubated for 14 days at 16-30°C with or without UVB radiation and growth, health status, photosynthetic performance, and light absorbance measured. Furthermore, we used empirical models from the metabolic theory of ecology to evaluate the sensitivity of these important seaweeds to ocean warming. Results indicated that responses to UVB and warming were species specific, with Sargassum showing highest tolerance to a broad range of temperatures. Scytothalia was most sensitive to elevated temperature based on the reduced maximum quantum yields of PSII; however, Ecklonia was most sensitive, according to the comparison of activation energy calculated from Arrhenius' model. UVB radiation caused reduction in the growth, physiological responses and thallus health in all three species. Our findings indicate that Scytothalia was capable of acclimating in response to UVB and increasing its light absorption efficiency in the UV bands, probably by up-regulating synthesis of photoprotective compounds. The other two species did not acclimate over the two weeks of exposure to UVB. Overall, UVB and warming would severely inhibit the growth and photosynthesis of these canopy-forming seaweeds and decrease their coverage. Differences in the sensitivity and acclimation of major seaweed species to temperature and UVB may alter the balance between species in future seaweed communities under climate change.

  5. Estimations of climate sensitivity based on top-of-atmosphere radiation imbalance

    Directory of Open Access Journals (Sweden)

    G. Schuster

    2009-11-01

    Full Text Available Large climate feedback uncertainties limit the accuracy in predicting the response of the Earth's climate to the increase of CO2 concentration within the atmosphere. This study explores a potential to reduce uncertainties in climate sensitivity estimations using energy balance analysis, especially top-of-atmosphere (TOA radiation imbalance. The time-scales studied generally cover from decade to century, that is, middle-range climate sensitivity is considered, which is directly related to the climate issue caused by atmospheric CO2 change. The significant difference between current analysis and previous energy balance models is that the current study targets at the boundary condition problem instead of solving the initial condition problem. Additionally, climate system memory and deep ocean heat transport are considered. The climate feedbacks are obtained based on the constraints of the TOA radiation imbalance and surface temperature measurements of the present climate.

    Currently, there is a lack of high accuracy measurements of TOA radiation imbalance. Available estimations indicate that TOA net radiative heating to the climate system is about 0.85 W/m2. Based on this value, a positive climate feedback with a feedback coefficient ranging from −1.3 to −1.0 W/m2/K is found. The range of feedback coefficient is determined by climate system memory. The longer the memory, the stronger the positive feedback. The estimated time constant of the climate is large (70~120 years mainly owing to the deep ocean heat transport, implying that the system may be not in an equilibrium state under the external forcing during the industrial era. For the doubled-CO2 climate (or 3.7 W/m2 forcing, the estimated global warming would be 3.1 K if the current estimate of 0.85 W/m2 TOA net radiative heating could be confirmed. With accurate long-term measurements of TOA radiation, the

  6. Modification of the cellular heat sensitivity of cucumber by growth under supplemental ultraviolet-B radiation

    Energy Technology Data Exchange (ETDEWEB)

    Caldwell, C.R. [Department of Agriculture, Beltsville, MD (United States)

    1994-02-01

    The effect of ultraviolet B (UV-B) radiation on the thermal sensitivity of cucumber (Cucumis sativus L.) was studied using UV-B-sensitive cv Poinsett 76 and UV-B-resistant cv Ashley grown under control and elevated (300 mW m{sup -2}) UV-B radiation levels. Using both cotyledon and leaf discs, the ability of the tissue to reduce triphenyl tetrazolium chloride (TTC) was determined after treatment at 50{degrees}C for various times. Semilogarithmic plots of TTC reduction as a function of time at 50{degrees}were curvilinear. They were monophasic for the control cucumber and biphasic for cucumber grown in the presence of elevated UV-B. Treatment of cucumber plants at 37{degrees}C for 24 h or of tissue discs at acute UV-B levels for 1 h further modified their response to elevated temperature. These results suggest that growth of cucumber under enhanced UV-B radiation levels increased its ability to withstand elevated temperatures. 19 refs., 2 figs., 2 tabs.

  7. Radiation sensitivity of graphene field effect transistors and other thin film architectures

    Science.gov (United States)

    Cazalas, Edward

    An important contemporary motivation for advancing radiation detection science and technology is the need for interdiction of nuclear and radiological materials, which may be used to fabricate weapons of mass destruction. The detection of such materials by nuclear techniques relies on achieving high sensitivity and selectivity to X-rays, gamma-rays, and neutrons. To be attractive in field deployable instruments, it is desirable for detectors to be lightweight, inexpensive, operate at low voltage, and consume low power. To address the relatively low particle flux in most passive measurements for nuclear security applications, detectors scalable to large areas that can meet the high absolute detection efficiency requirements are needed. Graphene-based and thin-film-based radiation detectors represent attractive technologies that could meet the need for inexpensive, low-power, size-scalable detection architectures, which are sensitive to X-rays, gamma-rays, and neutrons. The utilization of graphene to detect ionizing radiation relies on the modulation of graphene charge carrier density by changes in local electric field, i.e. the field effect in graphene. Built on the principle of a conventional field effect transistor, the graphene-based field effect transistor (GFET) utilizes graphene as a channel and a semiconducting substrate as an absorber medium with which the ionizing radiation interacts. A radiation interaction event that deposits energy within the substrate creates electron-hole pairs, which modify the electric field and modulate graphene charge carrier density. A detection event in a GFET is therefore measured as a change in graphene resistance or current. Thin (micron-scale) films can also be utilized for radiation detection of thermal neutrons provided nuclides with high neutron absorption cross section are present with appreciable density. Detection in thin-film detectors could be realized through the collection of charge carriers generated within the

  8. Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes

    DEFF Research Database (Denmark)

    Xie, W. J.; Wood, A. R.; Lyssenko, V.;

    2013-01-01

    . The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we...... performed a genome-wide association study (GWAS) of 14 insulin sensitivity-related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2...... for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits....

  9. [Useage of genetic markers to determine the impact of radiation on the human body].

    Science.gov (United States)

    Zedgenidze, A G; Namchevadze, E N; Nikuradze, T D; Zalinian, G G; Parsadanian, G G

    2015-02-01

    The timely determination of the fact of radiation impact on the organism is extremely important for preventive and curative interventions. Despite the fact that so far cytogenetic violations are considered to be the best biomarkers to determine the impact of ionizing radiation on the organism, actual problem is to find the optimal combination of different biomarkers. The aim of the work was investigation of the extended set of biomarkers in distant periods of exposure in people previously assigned to the radiation risk group, as well as the identification of genetic disorders in the process of radiotherapy. The object of the study were 37 residents of districts, where at the beginning of this century radioactive sources were discovered, and 6 oncology patients in the course of radiotherapy. Chromosome disorders, the overall level of DNA cells single-stranded damage by comet-assay method and a method of level detection of buccal micronuclei in were investigated. The results showed heterogeneity of different organism response to irradiation. Determination of absorbed dose, identification of various genetic disorders in individuals exposed to identical doses of radiation, offers the opportunity to judge the individual biological effect and is very important for individual preventive activities.

  10. Predicting Modeling Method of Ship Radiated Noise Based on Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Guohui Li

    2016-01-01

    Full Text Available Because the forming mechanism of underwater acoustic signal is complex, it is difficult to establish the accurate predicting model. In this paper, we propose a nonlinear predicting modeling method of ship radiated noise based on genetic algorithm. Three types of ship radiated noise are taken as real underwater acoustic signal. First of all, a basic model framework is chosen. Secondly, each possible model is done with genetic coding. Thirdly, model evaluation standard is established. Fourthly, the operation of genetic algorithm such as crossover, reproduction, and mutation is designed. Finally, a prediction model of real underwater acoustic signal is established by genetic algorithm. By calculating the root mean square error and signal error ratio of underwater acoustic signal predicting model, the satisfactory results are obtained. The results show that the proposed method can establish the accurate predicting model with high prediction accuracy and may play an important role in the further processing of underwater acoustic signal such as noise reduction and feature extraction and classification.

  11. Cyanobacteria: photosynthetic factories combining biodiversity, radiation resistance, and genetics to facilitate drug discovery.

    Science.gov (United States)

    Cassier-Chauvat, Corinne; Dive, Vincent; Chauvat, Franck

    2017-02-01

    Cyanobacteria are ancient, abundant, and widely diverse photosynthetic prokaryotes, which are viewed as promising cell factories for the ecologically responsible production of chemicals. Natural cyanobacteria synthesize a vast array of biologically active (secondary) metabolites with great potential for human health, while a few genetic models can be engineered for the (low level) production of biofuels. Recently, genome sequencing and mining has revealed that natural cyanobacteria have the capacity to produce many more secondary metabolites than have been characterized. The corresponding panoply of enzymes (polyketide synthases and non-ribosomal peptide synthases) of interest for synthetic biology can still be increased through gene manipulations with the tools available for the few genetically manipulable strains. In this review, we propose to exploit the metabolic diversity and radiation resistance of cyanobacteria, and when required the genetics of model strains, for the production and radioactive ((14)C) labeling of bioactive products, in order to facilitate the screening for new drugs.

  12. Annexin A2 Modulates Radiation-Sensitive Transcriptional Programming and Cell Fate

    Energy Technology Data Exchange (ETDEWEB)

    Waters, Katrina M.; Stenoien, David L.; Sowa, Marianne B.; von Neubeck, Claere; Chrisler, William B.; Tan, Ruimin; Sontag, Ryan L.; Weber, Thomas J.

    2013-01-01

    There is considerable public interest in the health effects of low doses of radiation (LDR) that fall below the doses that can be plausibly investigated in epidemiological studies. At these low doses, experimental models can detect perturbations in signaling pathways and use this information to define functional consequences of LDR exposures prospectively. In this study, we show increased nuclear annexin A2 (AnxA2) levels in human skin organotypic culture and murine progenitor cell model systems following exposure to X-radiation (10-200 cGy). LDR (2-20 cGy) inhibits cell transformation responses following epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA) exposures, indicating LDR may have a protective component mediated in part by nuclear localization of AnxA2. Oncogenic protein kinase C epsilon (PKC) levels are increased in nuclear extracts from AnxA2 silenced [shRNA] cells, suggesting that AnxA2 may contribute to PKC nuclear export, perhaps reducing oncogenic potential. Coordinately, silencing AnxA2 results in a sensitive phenotype and cells grow constitutively in soft agar. Using global microarray analysis, we show that silencing AnxA2 fundamentally alters transcriptional programming, changing the radioresponsive transcriptome and revealing biological processes that are induced in the absence of AnxA2. These observations suggest that AnxA2 plays a fundamental role in the sensitivity of cellular and tissue response to ionizing radiation, and deficiency of AnxA2 could result in a permissive environment for radiation-induced health effects.

  13. Development of a model system to study leukotriene-induced modification of radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Walden, T.L. Jr.; Holahan, E.V. Jr.; Catravas, G.N.

    1986-01-01

    Leukotrienes (LT) are an important class of biological mediators for which no information exists concerning their synthesis following a radiation insult or on their ability to modify cellular response to a subsequent radiation exposure. Results are presented which illustrate that the Chinese hamster lung fibroblast cell line, V79A03, is useful as a model system to study the metabolic fate of leukotrienes and the effect of LT on radiation sensitivity of mammalian cells in vitro. (U.K.).

  14. Potential sensitivity of photosynthesis and isoprene emission to direct radiative effects of atmospheric aerosol pollution

    Science.gov (United States)

    Strada, Susanna; Unger, Nadine

    2016-04-01

    A global Earth system model is applied to quantify the impacts of direct anthropogenic aerosol effective radiative forcing on gross primary productivity (GPP) and isoprene emission. The impacts of different pollution aerosol sources (anthropogenic, biomass burning, and non-biomass burning) are investigated by performing sensitivity experiments. The model framework includes all known light and meteorological responses of photosynthesis, but uses fixed canopy structures and phenology. On a global scale, our results show that global land carbon fluxes (GPP and isoprene emission) are not sensitive to pollution aerosols, even under a global decline in surface solar radiation (direct + diffuse) by ˜ 9 %. At a regional scale, GPP and isoprene emission show a robust but opposite sensitivity to pollution aerosols in regions where forested canopies dominate. In eastern North America and Eurasia, anthropogenic pollution aerosols (mainly from non-biomass burning sources) enhance GPP by +5-8 % on an annual average. In the northwestern Amazon Basin and central Africa, biomass burning aerosols increase GPP by +2-5 % on an annual average, with a peak in the northwestern Amazon Basin during the dry-fire season (+5-8 %). The prevailing mechanism varies across regions: light scattering dominates in eastern North America, while a reduction in direct radiation dominates in Europe and China. Aerosol-induced GPP productivity increases in the Amazon and central Africa include an additional positive feedback from reduced canopy temperatures in response to increases in canopy conductance. In Eurasia and northeastern China, anthropogenic pollution aerosols drive a decrease in isoprene emission of -2 to -12 % on an annual average. Future research needs to incorporate the indirect effects of aerosols and possible feedbacks from dynamic carbon allocation and phenology.

  15. MiR-224 expression increases radiation sensitivity of glioblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Upraity, Shailendra; Kazi, Sadaf; Padul, Vijay; Shirsat, Neelam Vishwanath, E-mail: nshirsat@actrec.gov.in

    2014-05-30

    Highlights: • MiR-224 expression in established glioblastoma cell lines and sporadic tumor tissues is low. • Exogenous miR-224 expression was found to increase radiation sensitivity of glioblastoma cells. • MiR-224 expression brought about 55–60% reduction in API5 expression levels. • Transfection with API5 siRNA increased radiation sensitivity of glioblastoma cells. • Low miR-224 and high API5 expression correlated with worse survival of GBM patients. - Abstract: Glioblastoma (GBM) is the most common and highly aggressive primary malignant brain tumor. The intrinsic resistance of this brain tumor limits the efficacy of administered treatment like radiation therapy. In the present study, effect of miR-224 expression on growth characteristics of established GBM cell lines was analyzed. MiR-224 expression in the cell lines as well as in primary GBM tumor tissues was found to be low. Exogenous transient expression of miR-224 using either synthetic mimics or stable inducible expression using doxycycline inducible lentiviral vector carrying miR-224 gene, was found to bring about 30–55% reduction in clonogenic potential of U87 MG cells. MiR-224 expression reduced clonogenic potential of U87 MG cells by 85–90% on irradiation at a dose of 6 Gy, a dose that brought about 50% reduction in clonogenic potential in the absence of miR-224 expression. MiR-224 expression in glioblastoma cells resulted in 55–65% reduction in the expression levels of API5 gene, a known target of miR-224. Further, siRNA mediated down-regulation of API5 was also found to have radiation sensitizing effect on glioblastoma cell lines. Analysis of the Cancer Genome Atlas data showed lower miR-224 expression levels in male GBM patients to correlate with poorer survival. Higher expression levels of miR-224 target API5 also showed significant correlation with poorer survival of GBM patients. Up-regulation of miR-224 or down-regulation of its target API5 in combination with radiation therapy

  16. Extraordinary radiation super-sensitivity accompanying with sorafenib combination therapy: what lies beneath?

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ja Young; Lee, Ju Hye; Yoon, Han Bin; Lee, Ho Jeong; Jeon, Ho Sang; Nam, Ji Ho [Dept. of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2017-06-15

    Primary liver tumor, especially hepatocellular carcinoma (HCC), is a common cause of cancer death worldwide. The incidence is generally higher in Asian countries than in western countries. Carcinogenesis of HCC is often associated with hepatitis viral infections. Current standard treatment of HCC is surgical resection or transplantation in patients with early stage disease. However, the patient with advanced stage disease, surgical resection is often limited. Sorafenib or other treatment modalities are not so effective as well. We report a case of unusual radiation super-sensitivity in advanced stage HCC, and review the literature.

  17. How does the sensitivity of climate affect stratospheric solar radiation management?

    Science.gov (United States)

    Ricke, K.; Rowlands, D. J.; Ingram, W.; Keith, D.; Morgan, M. G.

    2011-12-01

    If implementation of proposals to engineer the climate through solar radiation management (SRM) ever occurs, it is likely to be contingent upon climate sensitivity. Despite this, no modeling studies have examined how the effectiveness of SRM forcings differs between the typical Atmosphere-Ocean General Circulation Models (AOGCMs) with climate sensitivities close to the Coupled Model Intercomparison Project (CMIP) mean and ones with high climate sensitivities. Here, we use a perturbed physics ensemble modeling experiment to examine variations in the response of climate to SRM under different climate sensitivities. When SRM is used as a substitute for mitigation its ability to maintain the current climate state gets worse with increased climate sensitivity and with increased concentrations of greenhouse gases. However, our results also demonstrate that the potential of SRM to slow climate change, even at the regional level, grows with climate sensitivity. On average, SRM reduces regional rates of temperature change by more than 90 percent and rates of precipitation change by more than 50 percent in these higher sensitivity model configurations. To investigate how SRM might behave in models with high climate sensitivity that are also consistent with recent observed climate change we perform a "perturbed physics" ensemble (PPE) modelling experiment with the climateprediction.net (cpdn) version of the HadCM3L AOGCM. Like other perturbed physics climate modelling experiments, we simulate past and future climate scenarios using a wide range of model parameter combinations that both reproduce past climate within a specified level of accuracy and simulate future climates with a wide range of climate sensitivities. We chose 43 members ("model versions") from a subset of the 1,550 from the British Broadcasting Corporation (BBC) climateprediction.net project that have data that allow restarts. We use our results to explore how much assessments of SRM that use best

  18. A new era of semiconductor genetics using ion-sensitive field-effect transistors: the gene-sensitive integrated cell.

    Science.gov (United States)

    Toumazou, Christofer; Thay, Tan Sri Lim Kok; Georgiou, Pantelis

    2014-03-28

    Semiconductor genetics is now disrupting the field of healthcare owing to the rapid parallelization and scaling of DNA sensing using ion-sensitive field-effect transistors (ISFETs) fabricated using commercial complementary metal -oxide semiconductor technology. The enabling concept of DNA reaction monitoring introduced by Toumazou has made this a reality and we are now seeing relentless scaling with Moore's law ultimately achieving the $100 genome. In this paper, we present the next evolution of this technology through the creation of the gene-sensitive integrated cell (GSIC) for label-free real-time analysis based on ISFETs. This device is derived from the traditional metal-oxide semiconductor field-effect transistor (MOSFET) and has electrical performance identical to that of a MOSFET in a standard semiconductor process, yet is capable of incorporating DNA reaction chemistries for applications in single nucleotide polymorphism microarrays and DNA sequencing. Just as application-specific integrated circuits, which are developed in much the same way, have shaped our consumer electronics industry and modern communications and memory technology, so, too, do GSICs based on a single underlying technology principle have the capacity to transform the life science and healthcare industries.

  19. Genetic variance in micro-environmental sensitivity for milk and milk quality in Walloon Holstein cattle.

    Science.gov (United States)

    Vandenplas, J; Bastin, C; Gengler, N; Mulder, H A

    2013-09-01

    Animals that are robust to environmental changes are desirable in the current dairy industry. Genetic differences in micro-environmental sensitivity can be studied through heterogeneity of residual variance between animals. However, residual variance between animals is usually assumed to be homogeneous in traditional genetic evaluations. The aim of this study was to investigate genetic heterogeneity of residual variance by estimating variance components in residual variance for milk yield, somatic cell score, contents in milk (g/dL) of 2 groups of milk fatty acids (i.e., saturated and unsaturated fatty acids), and the content in milk of one individual fatty acid (i.e., oleic acid, C18:1 cis-9), for first-parity Holstein cows in the Walloon Region of Belgium. A total of 146,027 test-day records from 26,887 cows in 747 herds were available. All cows had at least 3 records and a known sire. These sires had at least 10 cows with records and each herd × test-day had at least 5 cows. The 5 traits were analyzed separately based on fixed lactation curve and random regression test-day models for the mean. Estimation of variance components was performed by running iteratively expectation maximization-REML algorithm by the implementation of double hierarchical generalized linear models. Based on fixed lactation curve test-day mean models, heritability for residual variances ranged between 1.01×10(-3) and 4.17×10(-3) for all traits. The genetic standard deviation in residual variance (i.e., approximately the genetic coefficient of variation of residual variance) ranged between 0.12 and 0.17. Therefore, some genetic variance in micro-environmental sensitivity existed in the Walloon Holstein dairy cattle for the 5 studied traits. The standard deviations due to herd × test-day and permanent environment in residual variance ranged between 0.36 and 0.45 for herd × test-day effect and between 0.55 and 0.97 for permanent environmental effect. Therefore, nongenetic effects also

  20. Radiative Effect of Clouds on Tropospheric Chemistry: Sensitivity to Cloud Vertical Distributions and Optical Properties

    Science.gov (United States)

    Liu, H.; Crawford, J. H.; Pierce, R. B.; Considine, D. B.; Logan, J. A.; Duncan, B. N.; Norris, P.; Platnick, S. E.; Chen, G.; Yantosca, R. M.; Evans, M. J.

    2005-12-01

    Representation of clouds in global models poses a significant challenge since most cloud processes occur on sub-grid scales and must be parameterized. Uncertainties in cloud distributions and optical properties are therefore a limiting factor in model assessments of the radiative effect of clouds on global tropospheric chemistry. We present an analysis of the sensitivity of the radiative effect of clouds to cloud vertical distributions and optical properties with the use of the GEOS-CHEM global 3-D chemistry transport model coupled with the Fast-J radiative transfer algorithm. GEOS-CHEM was driven with a series of meteorological archives (GEOS1-STRAT, GEOS-3, and GEOS-4) generated by the Goddard Earth Observing System data assimilation system (GEOS DAS) at the NASA global Modeling and Assimilation Office (GMAO), which have significantly different cloud optical depths and vertical distributions. The column cloud optical depths in GEOS-3 generally agree with the satellite retrieval products from the Moderate Resolution Imaging Spectroradiometer (MODIS) and the International Satellite Cloud Climatology Project (ISCCP) within ±10%, while those in GEOS1-STRAT and GEOS-4 are too low by factors of about 5 and 2, respectively. With respect to vertical distribution, clouds in GEOS-4 are optically much thinner in the tropical upper troposphere compared to those in GEOS1-STRAT and GEOS-3. Assuming linear scaling of cloud optical depth with cloud fraction in a grid-box, our model calculations indicate that the changes in global mean hydroxyl radical (OH) due to the radiative effect of clouds in June are about -1% (GEOS1-STRAT), 1% (GEOS-3), and 14% (GEOS-4), respectively. The effects on global mean OH are similar for GEOS1-STRAT and GEOS-3 due to similar vertical distributions of clouds, even though the column cloud optical depths in the two archives differ by a factor of about 5. Clouds in GEOS-4 have a much larger impact on global mean OH because more solar radiation is

  1. Enhanced radiation sensitivity and radiation recall dermatitis (RRD after hypericin therapy – case report and review of literature

    Directory of Open Access Journals (Sweden)

    Schäfer Christof

    2006-09-01

    Full Text Available Abstract Background Modern radiotherapy (RT reduces the side effects at organ at risk. However, skin toxicity is still a major problem in many entities, especially head and neck cancer. Some substances like chemotherapy provide a risk of increased side effects or can induce a "recall phenomenon" imitating acute RT-reactions months after RT. Moreover, some phototoxic drugs seem to enhance side effects of radiotherapy while others do not. We report a case of "radiation recall dermatitis" (RRD one year after RT as a result of taking hypericin (St. John's wort. Case report A 65 year old man with completely resected squamous cell carcinoma of the epiglottis received an adjuvant locoregional RT up to a dose of 64.8 Gy. The patient took hypericin during and months after RT without informing the physician. During radiotherapy the patient developed unusual intensive skin reactions. Five months after RT the skin was completely bland at the first follow up. However, half a year later the patient presented erythema, but only within the area of previously irradiated skin. After local application of a steroid cream the symptoms diminished but returned after the end of steroid therapy. The anamnesis disclosed that the patient took hypericin because of depressive mood. We recommended to discontinue hypericin and the symptoms disappeared afterward. Conclusion Several drugs are able to enhance skin toxicity of RT. Furthermore, the effect of RRD is well known especially for chemotherapy agents such as taxans. However, the underlying mechanisms are not known in detail so far. Moreover, it is unknown whether photosensitising drugs can also be considered to increase radiation sensitivity and whether a recall phenomenon is possible. The first report of a hypericin induced RRD and review of the literature are presented. In clinical practise many interactions between drugs and radiotherapy were not noticed and if registered not published. We recommend to ask especially

  2. Detecting a stochastic background of gravitational radiation Signal processing strategies and sensitivities

    CERN Document Server

    Allen, B; Allen, Bruce; Romano, Joseph D.

    1999-01-01

    We analyze the signal processing required for the optimal detection of a stochastic background of gravitational radiation using laser interferometric detectors. Starting with basic assumptions about the statistical properties of a stochastic gravity-wave background, we derive expressions for the optimal filter function and signal-to-noise ratio for the cross-correlation of the outputs of two gravity-wave detectors. Sensitivity levels required for detection are then calculated. Issues related to: (i) calculating the signal-to-noise ratio for arbitrarily large stochastic backgrounds, (ii) performing the data analysis in the presence of nonstationary detector noise, (iii) combining data from multiple detector pairs to increase the sensitivity of a stochastic background search, (iv) correlating the outputs of 4 or more detectors, and (v) allowing for the possibility of correlated noise in the outputs of two detectors are discussed. We briefly describe a computer simulation which mimics the generation and detectio...

  3. Luminescence, radiative recombination, and current voltage characteristics in sensitized TiO2 solar cells

    Science.gov (United States)

    Smestad, Greg P.

    1992-12-01

    A connection is made between the luminescence or radiative recombination in an absorber material and the current voltage characteristics of a quantum converter of light. A relationship between luminescence and voltage is derived, using detailed balance and the chemical potential of the excitation, which is similar to that obtained using the techniques of Shockley and Queisser or R. T. Ross. This model relates the absorptivity and photoluminescence efficiency of the light absorber to the I V curve. In this way both thermodynamic properties, or voltage, and the kinetics, or charge transfer and current, can be combined in order to optimize materials and configurations. The model is applied to dye sensitized Ti02 solar cells, and compared with preliminary experimental data for Ru based charge transfer dyes and inorganic compounds. The luminescence model is found to be applicable to dye sensitized converters, as well as to standard silicon solar cells, light detectors, and LEDs.

  4. The effect of free radical inhibitor on the sensitized radiation crosslinking and thermal processing stabilization of polyurethane shape memory polymers

    Science.gov (United States)

    Hearon, Keith; Smith, Sarah E.; Maher, Cameron A.; Wilson, Thomas S.; Maitland, Duncan J.

    2013-02-01

    The effects of free radical inhibitor on the electron beam crosslinking and thermal processing stabilization of novel radiation crosslinkable polyurethane shape memory polymers (SMPs) blended with acrylic radiation sensitizers have been determined. The SMPs in this study possess novel processing capabilities—that is, the ability to be melt processed into complex geometries as thermoplastics and crosslinked in a secondary step using electron beam irradiation. To increase susceptibility to radiation crosslinking, the radiation sensitizer pentaerythritol triacrylate (PETA) was solution blended with thermoplastic polyurethane SMPs made from 2-butene-1,4-diol and trimethylhexamethylene diisocyanate (TMHDI). Because the thermoplastic melt processing methods such as injection molding are often carried out at elevated temperatures, sensitizer thermal instability is a major processing concern. Free radical inhibitor can be added to provide thermal stabilization; however, inhibitor can also undesirably inhibit radiation crosslinking. In this study, we quantified both the thermal stabilization and radiation crosslinking inhibition effects of the inhibitor 1,4-benzoquinone (BQ) on polyurethane SMPs blended with PETA. Sol/gel analysis of irradiated samples showed that the inhibitor had little to no inverse effects on gel fraction at concentrations of 0-10,000 ppm, and dynamic mechanical analysis showed only a slight negative correlation between BQ composition and rubbery modulus. The 1,4-benzoquinone was also highly effective in thermally stabilizing the acrylic sensitizers. The polymer blends could be heated to 150 °C for up to 5 h or to 125 °C for up to 24 h if stabilized with 10,000 ppm BQ and could also be heated to 125 °C for up to 5 h if stabilized with 1000 ppm BQ without sensitizer reaction occurring. We believe this study provides significant insight into methods for manipulation of the competing mechanisms of radiation crosslinking and thermal stabilization of

  5. Genetic diversity in Scots pine populations along a radiation exposure gradient

    Energy Technology Data Exchange (ETDEWEB)

    Geras' kin, Stanislav A., E-mail: stgeraskin@gmail.com; Volkova, Polina Yu.

    2014-10-15

    Polymorphisms of antioxidant enzymes were studied in the endosperm and embryos of seeds from Scots pine populations inhabiting sites in the Bryansk region of Russia radioactively contaminated as a result of the Chernobyl accident. Chronic radiation exposure at dose rates from 0.8 μGy/h led to a significant increase in the rate of enzymatic loci mutations. The main parameters of genetic variability of the affected Scots pine populations had considerably higher values than those from the reference site. Changes in the genetic makeup of Scots pine populations were observed at dose rates greater than 10.4 μGy/h. However, the higher mutation rate had no effect on the activities of antioxidant enzymes. - Highlights: • Polymorphism of antioxidant enzymes was studied in affected Scots pine populations. • Genetic processes in affected Scots pine populations increase genetic diversity. • Chronic exposure at dose rates from 0.8 μGy/h lead to increasing of mutation rates. • Changes in population genetic structure were observed at dose rates from 10.4 μGy/h. • The higher rate of mutations had no effect on antioxidant enzymes activities.

  6. A Sensitivity Study on Radiation Dose of 500W RTPV having Different Source Shapes

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Seong Jae; Hong, Ser Gi [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    Radioisotope Thermoelectric Generators (RTG) has been considered as a power supply system for long-lived operation in space. RTG is an essentially nuclear battery that converts the heat resulted from the radioactive decay into electricity. RTG has the advantage of high energy density and long life operation because of the very long half-life of the radioisotopes. However, RTG systems have relatively low thermoelectric energy conversion efficiency of 3-7%. In this work, a sensitivity study on the total radiation dose was performed for 500W RTPVs having different source configurations. In particular, comparative shielding analysis using two different types of source design (a cubic source type and cylindrical sources type) were performed to show their relative performances. The results show that the RTPV(the cubic homogeneous source type and the cylindrical heterogeneous source type) device using the cylindrical sources type has lower dose values by 6-11% depending on the packing factor at the measurement cell than the RTPV device using the cubic source type. Also, we investigated the effect of the compactness of four cylindrical sources on the radiation dose. The results showed that the loosely packed sources give lower total radiation dose than the closely packed sources.

  7. Etoposide sensitizes CT26 colorectal adenocarcinoma to radiation therapy in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    Chia-Yuan Liu; Hui-Fen Liao; Tsang-En Wang; Shee-Chan Lin; Shou-Chuan Shih; Wen-Hsuing Chang; Yuh-Cheng Yang; Ching-Chung Lin; Yu-Jen Chen

    2005-01-01

    AIM: To investigate the combined effect of etoposide and radiation on CT26 colorectal adenocarcinoma implanted into BALB/c mice.METHODS: We evaluated the radiosensitizing effect of etoposide on CT26 colorectal adenocarcinoma in a syngeneic animal model. BALB/c mice were subcutaneously implanted with CT26 cells and divided into four groups:control (intra-peritoneal salinex2) group, etoposide (5 mg/kgintra-peritoneallyx2) group, radiation therapy (RT 5 Gyx2fractions) group, and combination therapy with etoposide (5 mg/kg intra-peritoneally 1 h before radiation) group.RESULTS: Tumor growth was significantly inhibited by RT and combination therapy. The effect of combination therapy was better than that of RT. No significant changes were noted in body weight, plasma alanine aminotransferase,or creatinine in any group. The leukocyte count significantly but transiently decreased in the RT and combination therapy groups, but not in the etoposide and control groups. There was no skin change or hair loss in the RT and combination therapy groups.CONCLUSION: Etoposide can sensitize CT26 colorectal adenocarcinoma in BALB/c mice to RT without significant toxicity.

  8. Are Freshwater Mixotrophic Ciliates Less Sensitive to Solar Ultraviolet Radiation than Heterotrophic Ones?1

    Science.gov (United States)

    SONNTAG, BETTINA; SUMMERER, MONIKA; SOMMARUGA, RUBEN

    2011-01-01

    We tested whether mixotrophic ciliates are more resistant to solar ultraviolet radiation (UVR) than heterotrophic ones because symbiotic algae can provide self-shading by cell matter absorption and eventually by direct UV screening from mycosporine-like amino acids (MAAs). Sensitivity of a natural assemblage to solar radiation was tested in experiments in the original lake and in a more UV transparent alpine lake after transplantation of the ciliates. In both lakes, the assemblage was exposed either to full sunlight, to photosynthetically active radiation only, or kept in the dark. In each lake, exposure was for 5 h at the surface and at the depth corresponding to the 10% attenuation depth at 320 nm. Overall, when the assemblage was exposed to surface UVR, only one out of four dominant mixotrophic ciliates, Vorticella chlorellata, was more resistant than heterotrophic species. The higher UV resistance in V. chlorellata was related to the presence of MAAs and the high percentage of ciliate volume occupied by algal symbionts. Our results indicate that effects of UVR were species-specific and depended on efficient screening of these wavelengths, but also on the depth preference of the ciliates and thus, on their previous exposure history to UVR. PMID:21414057

  9. Are freshwater mixotrophic ciliates less sensitive to solar ultraviolet radiation than heterotrophic ones?

    Science.gov (United States)

    Sonntag, Bettina; Summerer, Monika; Sommaruga, Ruben

    2011-01-01

    We tested whether mixotrophic ciliates are more resistant to solar ultraviolet radiation (UVR) than heterotrophic ones because symbiotic algae can provide self-shading by cell matter absorption and eventually by direct UV screening from mycosporine-like amino acids (MAAs). Sensitivity of a natural assemblage to solar radiation was tested in experiments in the original lake and in a more UV transparent alpine lake after transplantation of the ciliates. In both lakes, the assemblage was exposed either to full sunlight, to photosynthetically active radiation only, or kept in the dark. In each lake, exposure was for 5 h at the surface and at the depth corresponding to the 10% attenuation depth at 320 nm. Overall, when the assemblage was exposed to surface UVR, only one out of four dominant mixotrophic ciliates, Vorticella chlorellata, was more resistant than heterotrophic species. The higher UV resistance in V. chlorellata was related to the presence of MAAs and the high percentage of ciliate volume occupied by algal symbionts. Our results indicate that effects of UVR were species-specific and depended on efficient screening of these wavelengths, but also on the depth preference of the ciliates and thus, on their previous exposure history to UVR.

  10. Position-sensitive radiation monitoring (surface contamination monitor). Innovative technology summary report

    Energy Technology Data Exchange (ETDEWEB)

    1999-06-01

    The Shonka Research Associates, Inc. Position-Sensitive Radiation Monitor both detects surface radiation and prepares electronic survey map/survey report of surveyed area automatically. The electronically recorded map can be downloaded to a personal computer for review and a map/report can be generated for inclusion in work packages. Switching from beta-gamma detection to alpha detection is relatively simple and entails moving a switch position to alpha and adjusting the voltage level to an alpha detection level. No field calibration is required when switching from beta-gamma to alpha detection. The system can be used for free-release surveys because it meets the federal detection level sensitivity limits requires for surface survey instrumentation. This technology is superior to traditionally-used floor contamination monitor (FCM) and hand-held survey instrumentation because it can precisely register locations of radioactivity and accurately correlate contamination levels to specific locations. Additionally, it can collect and store continuous radiological data in database format, which can be used to produce real-time imagery as well as automated graphics of survey data. Its flexible design can accommodate a variety of detectors. The cost of the innovative technology is 13% to 57% lower than traditional methods. This technology is suited for radiological surveys of flat surfaces at US Department of Energy (DOE) nuclear facility decontamination and decommissioning (D and D) sites or similar public or commercial sites.

  11. Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy

    Science.gov (United States)

    Tamarov, Konstantin P.; Osminkina, Liubov A.; Zinovyev, Sergey V.; Maximova, Ksenia A.; Kargina, Julia V.; Gongalsky, Maxim B.; Ryabchikov, Yury; Al-Kattan, Ahmed; Sviridov, Andrey P.; Sentis, Marc; Ivanov, Andrey V.; Nikiforov, Vladimir N.; Kabashin, Andrei V.; Timoshenko, Victor Yu

    2014-01-01

    Offering mild, non-invasive and deep cancer therapy modality, radio frequency (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF sensitizers to selectively target cancer cells and thus avoid side effects. Here, we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF-induced therapy. Using nanoparticles produced by mechanical grinding of porous silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced heating of aqueous suspensions of the nanoparticles to temperatures above 45-50°C under relatively low nanoparticle concentrations (<1 mg/mL) and RF radiation intensities (1–5 W/cm2). For both types of nanoparticles the heating rate was linearly dependent on nanoparticle concentration, while laser-ablated nanoparticles demonstrated a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations from 0.01 to 0.4 mg/mL. The observed effect is explained by the Joule heating due to the generation of electrical currents at the nanoparticle/water interface. Profiting from the nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis lung carcinoma in vivo. Combined with the possibility of involvement of parallel imaging and treatment channels based on unique optical properties of Si-based nanomaterials, the proposed method promises a new landmark in the development of new modalities for mild cancer therapy. PMID:25391603

  12. Estimations of climate sensitivity based on top-of-atmosphere radiation imbalance

    Directory of Open Access Journals (Sweden)

    B. Lin

    2010-02-01

    Full Text Available Large climate feedback uncertainties limit the accuracy in predicting the response of the Earth's climate to the increase of CO2 concentration within the atmosphere. This study explores a potential to reduce uncertainties in climate sensitivity estimations using energy balance analysis, especially top-of-atmosphere (TOA radiation imbalance. The time-scales studied generally cover from decade to century, that is, middle-range climate sensitivity is considered, which is directly related to the climate issue caused by atmospheric CO2 change. The significant difference between current analysis and previous energy balance models is that the current study targets at the boundary condition problem instead of solving the initial condition problem. Additionally, climate system memory and deep ocean heat transport are considered. The climate feedbacks are obtained based on the constraints of the TOA radiation imbalance and surface temperature measurements of the present climate. In this study, the TOA imbalance value of 0.85 W/m2 is used. Note that this imbalance value has large uncertainties. Based on this value, a positive climate feedback with a feedback coefficient ranging from −1.3 to −1.0 W/m2/K is found. The range of feedback coefficient is determined by climate system memory. The longer the memory, the stronger the positive feedback. The estimated time constant of the climate is large (70~120 years mainly owing to the deep ocean heat transport, implying that the system may be not in an equilibrium state under the external forcing during the industrial era. For the doubled-CO2 climate (or 3.7 W/m2 forcing, the estimated global warming would be 3.1 K if the current estimate of 0.85 W/m2 TOA net radiative heating could be confirmed. With accurate long-term measurements of TOA radiation, the analysis method suggested by this study provides a great potential in the

  13. Induction of genetic instability by ionizing radiation; Instabilite genetique et rayonnements ionisants

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B. [Harvard School of Public Health, Boston, MA (United States). Dept. of Cancer Cell Biology

    1999-03-01

    Evidence is presented to support the hypothesis that radiation may induce a heritable, genome-wide process of instability that leads to an enhanced frequency of genetic changes occurring among the progeny of the original irradiated cell. This instability is transmissible over many generations of cell replication. Mutational instability is induced in a relatively large fraction (approximately 10 %) of the cell population, and may be modulated by factors acting in vivo. Thus, it cannot be a targeted event involving a specific gene or set of genes. There is no dose-response relationship in the range 2-12 Gy, suggesting that the instability phenotype may be induced by quite low radiation doses. The molecular mechanisms associated with the genesis of mutations in unstable populations differ from those for direct X-ray-induced mutations. These results suggest that it may not be possible to predict the nature of the dose-response relationship for the ultimate genetic effects of radiation based on a qualitative or quantitative analysis of the original DNA lesions. (author)

  14. Role of AKT and ERK pathways in controlling sensitivity to ionizing radiation and adaptive response induced by low-dose radiation in human immune cells.

    Science.gov (United States)

    Park, Hyung Sun; You, Ga Eun; Yang, Kwang Hee; Kim, Ji Young; An, Sungkwan; Song, Jie-Young; Lee, Su-Jae; Lim, Young-Khi; Nam, Seon Young

    2015-12-01

    Despite many studies of the effect of ionizing radiation, biological mechanisms of action might differ greatly depend on dose, dose rate, and cell type. This study was performed to explore the effects of low- and high-dose radiation in human immune cell lines. We examined cell sensitivity after irradiation with 0.05, 0.1, or 2Gy in two normal cell lines and three tumor cell lines. Low-dose radiation of 0.05 and 0.1Gy had no effect on cell survival in any tested cell line, with the exception of IM-9 cells, whose viability was transiently increased. However, IM-9 and C1R-sB7 cells were very sensitive to high-dose radiation-induced cell death, whereas Jurkat and JM1 cells showed moderate sensitivity, and THP-1 cells were completely resistant. This radiosensitivity was correlated with basal AKT activation, which is induced by phosphorylation. In radiosensitive IM-9 cells, priming with chronic low-dose irradiation blocked cell death induced by high-dose radiation challenge via inhibition of caspase activation and PARP cleavage. AKT phosphorylation was not altered in IM-9 cells, but ERK phosphorylation was greatly elevated immediately after chronic low-dose irradiation. Taken together, our results suggest that the different responses of normal and tumor cells to low-dose and high-dose radiation depend on AKT activation, which is regulated by protein phosphatase 2 (PP2A). In radiosensitive normal cells lacking basal AKT activity, chronic low-dose radiation increases activation of the ERK pathway, which plays an important role in the adaptive response to radiation, providing a very important insight into understanding the effects of ionizing radiation on health. Copyright © 2015 Elsevier GmbH. All rights reserved.

  15. Impact of Stromal Sensitivity on Radiation Response of Tumors Implanted in SCID Hosts Revisited

    Science.gov (United States)

    García-Barros, Mónica; Thin, Tin Htwe; Maj, Jerzy; Cordon-Cardo, Carlos; Haimovitz-Friedman, Adriana; Fuks, Zvi; Kolesnick, Richard

    2010-01-01

    Severe combined immunodeficient (SCID) mice carry a germ-line mutation in DNA-PK, associated with deficiency in recognition and repair DNA double strand breaks. Thus, SCID cells and tissues display increased sensitivity to radiation-induced post-mitotic (clonogenic) cell death. Nonetheless, the single radiation doses required for 50% permanent local control (TCD50) of tumors implanted in SCID mice are not significantly different from the TCD50 values of the same tumors in wild-type hosts. Whereas the tumor stroma is derived from the host, the observation that tumors implanted in SCID mice do not exhibit hypersensitivity to radiation might imply that stromal endothelial elements do not contribute substantially to tumor cure by ionizing radiation. Here we challenge this notion, testing the hypothesis that acid sphingomyelinase (ASMase)-mediated endothelial apoptosis, which results from plasma membrane alterations, not DNA damage, is a crucial element in the cure of tumors in SCID mice by single dose radiotherapy (SDRT). We show that endothelium in MCA/129 fibrosarcomas and B16 melanomas exhibit a wild-type apoptotic phenotype in SCID hosts, abrogated in tumors in SCIDasmase−/− littermates, which also acquire resistance to SDRT. Conversion into a radioresistant tumor phenotype when implanted in SCIDasmase−/− hosts provides compelling evidence that cell membrane ASMase-mediated microvascular dysfunction, rather than DNA damage-mediated endothelial clonogenic lethality, plays a mandatory role in the complex pathophysiologic mechanism of tumor cure by SDRT, and provides an explanation for the wild-type SDRT responses reported in tumors implanted in SCID mice. PMID:20924105

  16. Differential Sensitivity of Cells to Radiation Mediated by p53 Pulses

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Kang, Mi Young; Kawala, Remigius A.; Ryu, Tae Ho; Kim, Jin-Hong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    Exposure of cells to ionizing radiation activates protein genes related cell cycle arrest and cell death (apoptosis or autophagy). The tumor suppressor p53 participates not only in regulation of apoptosis, but also in autophagy mechanism. Apoptosis (type I cell death) is characterized by the activation of caspases and the formation of apoptotic bodies, and plays essential roles in all multicellular organisms. On the other hand, autophagy (type II cell death) is characterized by the presence of cytoplasmic engulfing vesicles, alias autophagosomes, and is a major intracellular pathway for degradation and recycling of proteins, ribosomes and entire organelles. The purpose of this study was to determine whether ionizing radiation treatment induces autophagy depending on the p53 expression levels. RKO (wild-type p53) and RKO E6 (null-type p53) cells were used to evaluate the effects of p53 on the sensitivity of cells to ionizing radiation. In the RKO E6 cells, the function of p53 was disabled with human papillomavirus E6 oncoprotein. These results indicated that p53 and p21 were required to block apoptosis and induce autophagy in RKO cells. The expression of p21 by a p53-dependent mechanism is required to develop autophagic properties after DNA damage. Results in this study suggest that the radioresistance of the RKO cells was associated with the increased p21 expression, resulting in autophagy induction. The tumor suppressor p53 could regulate radiosensitivity by inhibiting autophagy and activating apoptosis; the ionizing radiation-induced expression of p53 in the RKO cells regulated autophagy, suggesting the significance of the level of p53 in determining the radiosensitivity by regulating autophagy and apoptosis.

  17. Genetic variation and combining ability analysis of bruising sensitivity in Agaricus bisporus.

    Directory of Open Access Journals (Sweden)

    Wei Gao

    Full Text Available Advanced button mushroom cultivars that are less sensitive to mechanical bruising are required by the mushroom industry, where automated harvesting still cannot be used for the fresh mushroom market. The genetic variation in bruising sensitivity (BS of Agaricus bisporus was studied through an incomplete set of diallel crosses to get insight in the heritability of BS and the combining ability of the parental lines used and, in this way, to estimate their breeding value. To this end nineteen homokaryotic lines recovered from wild strains and cultivars were inter-crossed in a diallel scheme. Fifty-one successful hybrids were grown under controlled conditions, and the BS of these hybrids was assessed. BS was shown to be a trait with a very high heritability. The results also showed that brown hybrids were generally less sensitive to bruising than white hybrids. The diallel scheme allowed to estimate the general combining ability (GCA for each homokaryotic parental line and to estimate the specific combining ability (SCA of each hybrid. The line with the lowest GCA is seen as the most attractive donor for improving resistance to bruising. The line gave rise to hybrids sensitive to bruising having the highest GCA value. The highest negative SCA possibly indicates heterosis effects for resistance to bruising. This study provides a foundation for estimating breeding value of parental lines to further study the genetic factors underlying bruising sensitivity and other quality-related traits, and to select potential parental lines for further heterosis breeding. The approach of studying combining ability in a diallel scheme was used for the first time in button mushroom breeding.

  18. Genetics, Synergists, and Age Affect Insecticide Sensitivity of the Honey Bee, Apis mellifera

    Science.gov (United States)

    Rinkevich, Frank D.; Margotta, Joseph W.; Pittman, Jean M.; Danka, Robert G.; Tarver, Matthew R.; Ottea, James A.; Healy, Kristen B.

    2015-01-01

    The number of honey bee colonies in the United States has declined to half of its peak level in the 1940s, and colonies lost over the winter have reached levels that are becoming economically unstable. While the causes of these losses are numerous and the interaction between them is very complex, the role of insecticides has garnered much attention. As a result, there is a need to better understand the risk of insecticides to bees, leading to more studies on both toxicity and exposure. While much research has been conducted on insecticides and bees, there have been very limited studies to elucidate the role that bee genotype and age has on the toxicity of these insecticides. The goal of this study was to determine if there are differences in insecticide sensitivity between honey bees of different genetic backgrounds (Carniolan, Italian, and Russian stocks) and assess if insecticide sensitivity varies with age. We found that Italian bees were the most sensitive of these stocks to insecticides, but variation was largely dependent on the class of insecticide tested. There were almost no differences in organophosphate bioassays between honey bee stocks (bees aged, the sensitivity to phenothrin significantly decreased, but the sensitivity to naled significantly increased. These results demonstrate the variation arising from the genetic background and physiological transitions in honey bees as they age. This information can be used to determine risk assessment, as well as establishing baseline data for future comparisons to explain the variation in toxicity differences for honey bees reported in the literature. PMID:26431171

  19. Genetic Analysis and Molecular Mapping of Light-Sensitive Red-Root Mutant in Rice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jun-zhi; LIU Xiao; LI Chao; XIAO Ke; DONG Yan-jun

    2009-01-01

    The light-sensitive red-root mutant, designated as HG1, was newly observed from an indica rice variety, Nankinkodo, when seedlings were grown with roots exposed to natural light. The root color of the mutant began to turn slight-red when the roots were exposed to the light at the intensity of 29 μmol/(m2·s), then turned dark-red at the light intensity of 180 μmol/(m2·s), suggesting that the root color of the mutant was evidently sensitive to light. Furthermore, genetic analysis showed that the character of light-sensitive red-root of the HG1 mutant was controlled by a single dominant gene, tentatively designated as Lsr. With simple sequence repeat markers, Lsr gene was located between the markers RM252 and RM303 on chromosome 4 with the genetic distances of 9.8 cM and 6.4 cM, respectively. These results could be useful for fine mapping and cloning of Lsr gene in rice.

  20. Analysis of Fungicide Sensitivity and Genetic Diversity among Colletotrichum Species in Sweet Persimmon.

    Science.gov (United States)

    Gang, Geun-Hye; Cho, Hyun Ji; Kim, Hye Sun; Kwack, Yong-Bum; Kwak, Youn-Sig

    2015-06-01

    Anthracnose, caused by Colletotrichum gloeosporioides (C. gloeosporioides; Teleomorph: Glomerella cingulata), is the most destructive disease that affects sweet persimmon production worldwide. However, the biology, ecology, and genetic variations of C. gloeosporioides remain largely unknown. Therefore, in this study, the development of fungicide resistance and genetic diversity among an anthracnose pathogen population with different geographical origins and the exposure of this population to different cultivation strategies were investigated. A total of 150 pathogen isolates were tested in fungicide sensitivity assays. Five of the tested fungicides suppressed mycelial pathogen growth effectively. However, there were significant differences in the sensitivities exhibited by the pathogen isolates examined. Interestingly, the isolates obtained from practical management orchards versus organic cultivation orchards showed no differences in sensitivity to the same fungicide. PCR-restriction fragment length polymorphism (RFLP) analyses were performed to detect internal transcribed spacer regions and the β-tubulin and glutamine synthetase genes of the pathogens examined. Both the glutamine synthetase and β-tubulin genes contained a complex set of polymorphisms. Based on these results, the pathogens isolated from organic cultivation orchards were found to have more diversity than the isolates obtained from the practical management orchards.

  1. Analysis of Fungicide Sensitivity and Genetic Diversity among Colletotrichum Species in Sweet Persimmon

    Directory of Open Access Journals (Sweden)

    Geun-Hye Gang

    2015-06-01

    Full Text Available Anthracnose, caused by Colletotrichum gloeosporioides (C. gloeosporioides; Teleomorph: Glomerella cingulata, is the most destructive disease that affects sweet persimmon production worldwide. However, the biology, ecology, and genetic variations of C. gloeosporioides remain largely unknown. Therefore, in this study, the development of fungicide resistance and genetic diversity among an anthracnose pathogen population with different geographical origins and the exposure of this population to different cultivation strategies were investigated. A total of 150 pathogen isolates were tested in fungicide sensitivity assays. Five of the tested fungicides suppressed mycelial pathogen growth effectively. However, there were significant differences in the sensitivities exhibited by the pathogen isolates examined. Interestingly, the isolates obtained from practical management orchards versus organic cultivation orchards showed no differences in sensitivity to the same fungicide. PCR-restriction fragment length polymorphism (RFLP analyses were performed to detect internal transcribed spacer regions and the β-tubulin and glutamine synthetase genes of the pathogens examined. Both the glutamine synthetase and β-tubulin genes contained a complex set of polymorphisms. Based on these results, the pathogens isolated from organic cultivation orchards were found to have more diversity than the isolates obtained from the practical management orchards.

  2. Common genetic variation in the human CTF1 locus, encoding cardiotrophin-1, determines insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Stefan Z Lutz

    Full Text Available AIMS/HYPOTHESIS: Recently, cardiotrophin-1, a member of the interleukin-6 family of cytokines was described to protect beta-cells from apoptosis, to improve glucose-stimulated insulin secretion and insulin resistance, and to prevent streptozotocin-induced diabetes in mice. Here, we studied whether common single nucleotide polymorphisms (SNPs in the CTF1 locus, encoding cardiotrophin-1, influence insulin secretion and insulin sensitivity in humans. METHODS: We genotyped 1,771 German subjects for three CTF1 tagging SNPs (rs1046276, rs1458201, and rs8046707. The subjects were metabolically characterized by an oral glucose tolerance test. Subgroups underwent magnetic resonance (MR imaging/spectroscopy and hyperinsulinaemic-euglycaemic clamps. RESULTS: After appropriate adjustment, the minor allele of CTF1 SNP rs8046707 was significantly associated with decreased in vivo measures of insulin sensitivity. The other tested SNPs were not associated with OGTT-derived sensitivity parameters, nor did the three tested SNPs show any association with OGTT-derived parameters of insulin release. In the MR subgroup, SNP rs8046707 was nominally associated with lower visceral adipose tissue. Furthermore, the SNP rs1458201 showed a nominal association with increased VLDL levels. CONCLUSIONS: In conclusion, this study, even though preliminary and awaiting further confirmation by independent replication, provides first evidence that common genetic variation in CTF1 could contribute to insulin sensitivity in humans. Our SNP data indicate an insulin-desensitizing effect of cardiotrophin-1 and underline that cardiotrophin-1 represents an interesting target to influence insulin sensitivity.

  3. Multidisciplinary approach to assess the sensitivity of dwarf tomato plants to low-LET ionising radiation

    Science.gov (United States)

    De Micco, Veronica; De Pascale, Stefania; Aronne, Giovanna; Paradiso, Roberta; Vitaglione, Paola; Turano, Mimmo; Arena, Carmen

    Ionising radiation, acting alone or in interaction with microgravity and other environmental constraints, may affect plant at molecular, morpho-structural and physiological level. The intensity of the plant’s response depends on the properties of radiation and on the features of the plant itself. Indeed, different species are characterised by different susceptibility to radiation which may change during the life course. The aim of this research was to study the radiosensitivity to low-LET ionising radiation of plants of dwarf tomato (Solanum lycopersicum L. ‘Microtom’) at two phenological phases (vegetative and reproductive), within the purpose of analysing plants for consideration as candidates for Bioregenerative Life Support Systems (BLSS) in Space. To pursue this objective, plants of the cultivar Microtom were irradiated with different doses of X-rays either at the stage of the second true leaf (VP - vegetative phase) or when at least one flower was blossomed (RP - reproductive phase). Plant’s response to ionising radiation was assessed through a multidisciplinary approach combining genetic analyses, ecophysiological measurements, morpho-anatomical characterisation of leaves and fruits, nutritional analyses of fruits. Growth, molecular and morpho-functional traits were measured during plant development up to fruiting in both VP and RP plant groups, and compared with non-irradiated control plants. Plant growth was monitored weekly recording parameters such as plant height, number of leaves, leaf area, flowering and fruiting rate. Potential DNA alterations were explored through Random Amplified Polymorphic DNA (RAPD) technique. The efficiency of the photosynthetic apparatus was evaluated by determining photosynthetic pigment composition, photochemistry and leaf gas exchanges. Leaf and fruit structure were analysed through light and epi-fluorescence microscopy. Leaf anatomical traits related to photosynthetic efficiency, and to structural radioprotection

  4. Cost-sensitive case-based reasoning using a genetic algorithm: application to medical diagnosis.

    Science.gov (United States)

    Park, Yoon-Joo; Chun, Se-Hak; Kim, Byung-Chun

    2011-02-01

    The paper studies the new learning technique called cost-sensitive case-based reasoning (CSCBR) incorporating unequal misclassification cost into CBR model. Conventional CBR is now considered as a suitable technique for diagnosis, prognosis and prescription in medicine. However it lacks the ability to reflect asymmetric misclassification and often assumes that the cost of a positive diagnosis (an illness) as a negative one (no illness) is the same with that of the opposite situation. Thus, the objective of this research is to overcome the limitation of conventional CBR and encourage applying CBR to many real world medical cases associated with costs of asymmetric misclassification errors. The main idea involves adjusting the optimal cut-off classification point for classifying the absence or presence of diseases and the cut-off distance point for selecting optimal neighbors within search spaces based on similarity distribution. These steps are dynamically adapted to new target cases using a genetic algorithm. We apply this proposed method to five real medical datasets and compare the results with two other cost-sensitive learning methods-C5.0 and CART. Our finding shows that the total misclassification cost of CSCBR is lower than other cost-sensitive methods in many cases. Even though the genetic algorithm has limitations in terms of unstable results and over-fitting training data, CSCBR results with GA are better overall than those of other methods. Also the paired t-test results indicate that the total misclassification cost of CSCBR is significantly less than C5.0 and CART for several datasets. We have proposed a new CBR method called cost-sensitive case-based reasoning (CSCBR) that can incorporate unequal misclassification costs into CBR and optimize the number of neighbors dynamically using a genetic algorithm. It is meaningful not only for introducing the concept of cost-sensitive learning to CBR, but also for encouraging the use of CBR in the medical area

  5. Effect of ice-albedo feedback on global sensitivity in a one-dimensional radiative-convective climate model

    Science.gov (United States)

    Wang, W.-C.; Stone, P. H.

    1980-01-01

    The feedback between the ice albedo and temperature is included in a one-dimensional radiative-convective climate model. The effect of this feedback on global sensitivity to changes in solar constant is studied for the current climate conditions. This ice-albedo feedback amplifies global sensitivity by 26 and 39%, respectively, for assumptions of fixed cloud altitude and fixed cloud temperature. The global sensitivity is not affected significantly if the latitudinal variations of mean solar zenith angle and cloud cover are included in the global model. The differences in global sensitivity between one-dimensional radiative-convective models and energy balance models are examined. It is shown that the models are in close agreement when the same feedback mechanisms are included. The one-dimensional radiative-convective model with ice-albedo feedback included is used to compute the equilibrium ice line as a function of solar constant.

  6. Estimating option values of solar radiation management assuming that climate sensitivity is uncertain.

    Science.gov (United States)

    Arino, Yosuke; Akimoto, Keigo; Sano, Fuminori; Homma, Takashi; Oda, Junichiro; Tomoda, Toshimasa

    2016-05-24

    Although solar radiation management (SRM) might play a role as an emergency geoengineering measure, its potential risks remain uncertain, and hence there are ethical and governance issues in the face of SRM's actual deployment. By using an integrated assessment model, we first present one possible methodology for evaluating the value arising from retaining an SRM option given the uncertainty of climate sensitivity, and also examine sensitivities of the option value to SRM's side effects (damages). Reflecting the governance challenges on immediate SRM deployment, we assume scenarios in which SRM could only be deployed with a limited degree of cooling (0.5 °C) only after 2050, when climate sensitivity uncertainty is assumed to be resolved and only when the sensitivity is found to be high (T2x = 4 °C). We conduct a cost-effectiveness analysis with constraining temperature rise as the objective. The SRM option value is originated from its rapid cooling capability that would alleviate the mitigation requirement under climate sensitivity uncertainty and thereby reduce mitigation costs. According to our estimates, the option value during 1990-2049 for a +2.4 °C target (the lowest temperature target level for which there were feasible solutions in this model study) relative to preindustrial levels were in the range between $2.5 and $5.9 trillion, taking into account the maximum level of side effects shown in the existing literature. The result indicates that lower limits of the option values for temperature targets below +2.4 °C would be greater than $2.5 trillion.

  7. A Systems Genetic Approach to Identify Low Dose Radiation-Induced Lymphoma Susceptibility/DOE2013FinalReport

    Energy Technology Data Exchange (ETDEWEB)

    Balmain, Allan [University of California, San Francisco; Song, Ihn Young [University of California, San Francisco

    2013-05-15

    The ultimate goal of this project is to identify the combinations of genetic variants that confer an individual's susceptibility to the effects of low dose (0.1 Gy) gamma-radiation, in particular with regard to tumor development. In contrast to the known effects of high dose radiation in cancer induction, the responses to low dose radiation (defined as 0.1 Gy or less) are much less well understood, and have been proposed to involve a protective anti-tumor effect in some in vivo scientific models. These conflicting results confound attempts to develop predictive models of the risk of exposure to low dose radiation, particularly when combined with the strong effects of inherited genetic variants on both radiation effects and cancer susceptibility. We have used a Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

  8. Sensitivity Analysis on Fu-Liou-Gu Radiative Transfer Model for different lidar aerosol and cloud profiles

    Science.gov (United States)

    Lolli, Simone; Madonna, Fabio; Rosoldi, Marco; Pappalardo, Gelsomina; Welton, Ellsworth J.

    2016-04-01

    The aerosol and cloud impact on climate change is evaluated in terms of enhancement or reduction of the radiative energy, or heat, available in the atmosphere and at the Earth's surface, from the surface (SFC) to the Top Of the Atmosphere (TOA) covering a spectral range from the UV (extraterrestrial shortwave solar radiation) to the far-IR (outgoing terrestrial longwave radiation). Systematic Lidar network measurements from permanent observational sites across the globe are available from the beginning of this current millennium. From the retrieved lidar atmospheric extinction profiles, inputted in the Fu-Liou-Gu (FLG) Radiative Transfer code, it is possible to evaluate the net radiative effect and heating rate of the different aerosol species and clouds. Nevertheless, the lidar instruments may use different techniques (elastic lidar, Raman lidar, multi-wavelength lidar, etc) that translate into uncertainty of the lidar extinction retrieval. The goal of this study is to assess, applying a MonteCarlo technique and the FLG Radiative Transfer model, the sensitivity in calculating the net radiative effect and heating rate of aerosols and clouds for the different lidar techniques, using both synthetic and real lidar data. This sensitivity study is the first step to implement an automatic algorithm to retrieve the net radiative forcing effect of aerosols and clouds from the long records of aerosol measurements available in the frame of EARLINET and MPLNET lidar networks.

  9. Using satellites to investigate the sensitivity of longwave downward radiation to water vapor at high elevations

    Science.gov (United States)

    Naud, Catherine M.; Miller, James R.; Landry, Chris

    2012-03-01

    Many studies suggest that high-elevation regions may be among the most sensitive to future climate change. However, in situ observations in these often remote locations are too sparse to determine the feedbacks responsible for enhanced warming rates. One of these feedbacks is associated with the sensitivity of longwave downward radiation (LDR) to changes in water vapor, with the sensitivity being particularly large in many high-elevation regions where the average water vapor is often low. We show that satellite retrievals from the Moderate Resolution Imaging Spectroradiometer (MODIS) and Clouds and the Earth's Radiant Energy System (CERES) can be used to expand the current ground-based observational database and that the monthly averaged clear-sky satellite estimates of humidity and LDR are in good agreement with the well-instrumented Center for Snow and Avalanche Studies ground-based site in the southwestern Colorado Rocky Mountains. The relationship between MODIS-retrieved precipitable water vapor and surface specific humidity across the contiguous United States was found to be similar to that previously found for the Alps. More important, we show that satellites capture the nonlinear relationship between LDR and water vapor and confirm that LDR is especially sensitive to changes in water vapor at high elevations in several midlatitude mountain ranges. Because the global population depends on adequate fresh water, much of which has its source in high mountains, it is critically important to understand how climate will change there. We demonstrate that satellites can be used to investigate these feedbacks in high-elevation regions where the coverage of surface-based observations is insufficient to do so.

  10. Radiation sensitivity of foodborne pathogens in meat byproducts with different packaging

    Science.gov (United States)

    Yong, Hae In; Kim, Hyun-Joo; Nam, Ki Chang; Kwon, Joong Ho; Jo, Cheorun

    2015-10-01

    The aim of this study was to determine radiation sensitivity of Escherichia coli O157:H7 and Listeria monocytogenes in edible meat byproducts. Seven beef byproducts (heart, liver, lung, lumen, omasum, large intestine, and small intestine) and four pork byproducts (heart, large intestine, liver, and small intestine) were used. Electron beam irradiation significantly reduced the numbers of pathogenic microorganisms in meat byproducts and no viable cells were detected in both aerobically- and vacuum-packaged samples irradiated at 4 kGy. Meat byproducts packed under vacuum had higher D10 value than the ones packed aerobically. No significant difference was observed between the D10 values of E. coli O157:H7 and L. monocytogenes inoculated in either aerobically or vacuum packaged samples. These results suggest that low-dose electron beam irradiation can significantly decrease microbial numbers and reduce the risk of meat byproduct contamination by the foodborne pathogens.

  11. Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair.

    Science.gov (United States)

    Gustafsson, Ann-Sofie; Abramenkovs, Andris; Stenerlöw, Bo

    2014-11-01

    Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present study, by using siRNA against DNA-PKcs in four human cell lines, we examined how low levels of DNA-PKcs affected cellular response to ionizing radiation. Decrease of DNA-PKcs levels by 80-95%, induced by siRNA treatment, lead to extreme radiosensitivity, similar to that seen in cells completely lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M phase after irradiation and blocked progression of mitosis. Surprisingly, low levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or γ-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs inhibitor NU7441, in which DSB repair were severely compromised. This suggests that there are different mechanisms by which loss of DNA-PKcs functions can sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs (T2609 and S2056) co-localized with DSB and this was independent of the amount of DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study emphasizes on the critical role of DNA-PKcs for maintaining survival after radiation exposure which is uncoupled from its essential function in DSB repair. This could have implications for the development of therapeutic strategies aiming to radiosensitize tumors by affecting the DNA-PKcs function.

  12. Yes-associated protein (YAP modulates oncogenic features and radiation sensitivity in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Masahiro Tsujiura

    Full Text Available Yes-associated protein (YAP is a transcriptional co-activator and regulates cell proliferation and apoptosis. We investigated the clinical and biological significance of YAP in endometrial cancer (EMCA.YAP expression in 150 primary tumor tissues from patients with EMCA was evaluated by immunohistochemistry and its association with clinicopathological data was assessed. The biological functions of YAP were determined in EMCA cell lines through knockdown/overexpression of YAP. The role of YAP in modulating radiation sensitivity was also investigated in EMCA cells.Increased nuclear YAP expression was significantly associated with higher grade, stage, lympho-vascular space invasion, postoperative recurrence/metastasis and overall survival in estrogen mediated EMCA, called type 1 cancer (p = 0.019,  = 0.028,  = 0.0008,  = 0.046 and  = 0.015, respectively. In multivariate analysis, nuclear YAP expression was confirmed as an independent prognostic factor for overall survival in type 1 EMCA. YAP knockdown by siRNA resulted in a significant decrease in cell proliferation (p<0.05, anchorage-dependent growth (p = 0.015 and migration/invasion (p<0.05, and a significant increase in the number of cells in G0/G1 phase (p = 0.002. Conversely, YAP overexpression promoted cell proliferation. Clonogenic assay demonstrated enhanced radiosensitivity by approximately 36% in YAP inhibited cells.Since YAP functions as a transcriptional co-activator, its differential localization in the nucleus of cancer cells and subsequent impact on cell proliferation could have important consequences with respect to its role as an oncogene in EMCA. Nuclear YAP expression could be useful as a prognostic indicator or therapeutic target and predict radiation sensitivity in patients with EMCA.

  13. A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids

    Energy Technology Data Exchange (ETDEWEB)

    Kaufman, N.; Bicher, H.I.; Hetzel, F.W.; Brown, M.

    1981-01-01

    We have characterized some of the physiology of multicellular spheroids of different sizes grown from Chinese hamster lung fibroblast (V79) cells. Among the parameters studied were oxygen tension distributions within the spheroid. This was achieved using ultramicroelectrodes with tip diameters of 1-5 mu and a perfusion system whereby environmental conditions such as flow, temperature, and chemical makeup of the milieu could be measured and controlled. Plateau pO/sup 2/ values of less than 10 mm Hg were consistently obtained from spheroids under various conditions. We were able to modify these distributions by use of indirect radiation sensitizer drugs such as mechlorethamine HCl (mustargen) at nontoxic doses. We have also made determinations of the inhibitory capacities of several other drugs on the respiration rate of constituent cells of multicellular spheroids in single-cell suspensions. We have concluded that there are indeed hypoxic cells in spheroids whose radioresistance may be modified by essentially nontoxic levels of indirect radiosensitizer drugs and that the system described shows great promise for screening agents which may modify radiation response.

  14. Genetic effects of radiation in atomic-bomb survivors and their children: past, present and future.

    Science.gov (United States)

    Nakamura, Nori

    2006-01-01

    Genetic studies in the offspring of atomic bomb survivors have been conducted since 1948 at the Atomic Bomb Casualty Commission and its successor, the Radiation Effects Research Foundation, in Hiroshima and Nagasaki. Past studies include analysis of birth defects (untoward pregnancy outcome; namely, malformation, stillbirth, and perinatal death), chromosome aberrations, alterations of plasma and erythrocyte proteins as well as epidemiologic study on mortality (any cause) and cancer incidence (the latter study is still ongoing). There is, thus far, no indication of genetic effects in the offspring of survivors. Recently, the development of molecular biological techniques and human genome sequence databases made it possible to analyze DNA from parents and their offspring (trio-analysis). In addition, a clinical program is underway to establish the frequency of adult-onset multi-factorial diseases (diabetes mellitus, high blood pressure, and cardiovascular disease etc) in the offspring. The complementary kinds of data that will emerge from this three-pronged approach (clinical, epidemiologic, and molecular aspects) promise to shed light on health effects in the offspring of radiation-exposed people.

  15. Genetic risk score and acute skin toxicity after breast radiation therapy.

    Science.gov (United States)

    Borghini, Andrea; Vecoli, Cecilia; Mercuri, Antonella; Petruzzelli, Maria Fonte; D'Errico, Maria Patrizia; Portaluri, Maurizio; Andreassi, Maria Grazia

    2014-09-01

    Genetic predisposition has been shown to affect the severity of skin complications in breast cancer patients after radiotherapy. Limited data exist regarding the use of a genetic risk score (GRS) for predicting risk of tissue radiosensitivity. We evaluated the impact of different single-nucleotide polymorphisms (SNPs) in genes related to DNA repair mechanisms and oxidative stress response combined in a GRS on acute adverse effects induced by breast radiation therapy (RT). Skin toxicity was scored according to the Radiation Therapy Oncology Group (RTOG) criteria in 59 breast cancer patients who received RT. After genotyping, a multilocus GRS was constructed by summing the number of risk alleles. The hazard ratio (HR) for GSTM1 was 2.4 (95% confidence intervals [CI]=1.1-5.3, p=0.04). The other polymorphisms were associated to an increased adverse radiosensitivity, although they did not reach statistical significance. GRS predicted roughly 40% risk for acute skin toxicity per risk allele (HR 1.37, 95% CI=1.1-1.76, pskin reaction (HR 5.1, 95% CI=1.2-22.8, p=0.03). Our findings demonstrate that the joint effect of SNPs from oxidative stress and DNA damage repair genes may be a promising approach to identify patients with a high risk of skin reaction after breast RT.

  16. Genetic contribution to variation in DNA methylation at maternal smoking-sensitive loci in exposed neonates.

    Science.gov (United States)

    Gonseth, Semira; de Smith, Adam J; Roy, Ritu; Zhou, Mi; Lee, Seung-Tae; Shao, Xiaorong; Ohja, Juhi; Wrensch, Margaret R; Walsh, Kyle M; Metayer, Catherine; Wiemels, Joseph L

    2016-09-01

    Epigenome-wide DNA methylation association studies have identified highly replicable genomic loci sensitive to maternal smoking during gestation. The role of inter-individual genetic variation in influencing DNA methylation, leading to the possibility of confounding or bias of such associations, has not been assessed. We investigated whether the DNA methylation levels at the top 10 CpG sites previously associated with exposure to maternal smoking during gestation were associated with individual genetic variation at the genome-wide level. Genome-wide association tests between DNA methylation at the top 10 candidate CpG and genome-wide SNPs were performed in 736 case and control participants of the California Childhood Leukemia Study. Three of the strongest maternal-smoking sensitive CpG sites in newborns were significantly associated with SNPs located proximal to each gene: cg18146737 in the GFI1 gene with rs141819830 (P = 8.2×10(-44)), cg05575921 in the AHRR gene with rs148405299 (P = 5.3×10(-10)), and cg12803068 in the MYO1G gene with rs61087368 (P = 1.3×10(-18)). For the GFI1 CpG cg18146737, the underlying genetic variation at rs141819830 confounded the association between maternal smoking and DNA methylation in our data (the regression coefficient changed from -0.02 [P = 0.139] to -0.03 [P = 0.015] after including the genotype). Our results suggest that further studies using DNA methylation at cg18146737, cg05575921, or cg12803068 that aim to assess exposure to maternal smoking during gestation should include genotype at the corresponding SNP. New methods are required for adequate and routine inclusion of genotypic influence on DNA methylation in epigenome-wide association studies to control for potential confounding.

  17. Genetic Modifiers Predisposing to Congenital Heart Disease in the Sensitized Down Syndrome Population

    Science.gov (United States)

    Li, Huiqing; Cherry, Sheila; Klinedinst, Donna; DeLeon, Valerie; Redig, Jennifer; Reshey, Benjamin; Chin, Michael T.; Sherman, Stephanie L.; Maslen, Cheryl L.; Reeves, Roger H.

    2012-01-01

    Background About half of people with Down syndrome (DS) exhibit some form of congenital heart disease (CHD). However, trisomy for human chromosome 21 (Hsa21) alone is insufficient to cause CHD as half of all people with DS have a normal heart, suggesting that genetic modifiers interact with dosage sensitive gene(s) on Hsa21 to result in CHD. We hypothesize that a threshold exists in both Down syndrome and euploid populations for the number of genetic perturbations that can be tolerated before CHD results. Methods and Results We ascertained a group of individuals with DS and complete atrioventricular septal defect (AVSD) and sequenced two candidate genes for CHD, CRELD1, which is associated with AVSD in people with or without DS, and HEY2, whose mouse ortholog produces septal defects when mutated. Several deleterious variants were identified but the frequency of these potential modifiers was low. We crossed mice with mutant forms of these potential modifiers to the Ts65Dn mouse model of Down syndrome. Crossing loss-of-function alleles of either Creld1 or Hey2 onto the trisomic background caused a significant increase in the frequency of CHD, demonstrating an interaction between the modifiers and trisomic genes. We showed further that although either of these mutant modifiers is benign by itself, they interact to affect heart development when inherited together. Conclusions Using mouse models of Down syndrome and of genes associated with congenital heart disease we demonstrate a biological basis for an interaction that supports a threshold hypothesis for additive effects of genetic modifiers in the sensitized trisomic population. PMID:22523272

  18. A ΔdinB mutation that sensitizes Escherichia coli to the lethal effects of UV- and X-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mei-Chong W.; Franco, Magdalena; Vargas, Doris M. [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Hudman, Deborah A. [Department of Microbiology and Immunology, A.T. Still University, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501 (United States); White, Steven J. [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Fowler, Robert G., E-mail: rfowler@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Sargentini, Neil J. [Department of Microbiology and Immunology, A.T. Still University, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501 (United States)

    2014-05-15

    Highlights: • We describe Δ(dinB-yafN)883(::kan), a novel dinB allele, referred to as ΔdinB883, a deletion that sensitizes E. coli cells to UV irradiation. • This UV radiation sensitivity is most acute in the early logarithmic phase of culture growth. • This UV radiation sensitivity is completely dependent upon a functional umuDC operon. • Sequencing reveals ΔdinB883 retains the proximal 161 nucleotides, i.e., 54 amino acids, of the wild-type sequence. • The ΔdinB883 mutant is hypothesized to produce a peptide of 83 amino acids, DinB883, that compromises UmuDC function. - Abstract: The DinB (PolIV) protein of Escherichia coli participates in several cellular functions. We investigated a dinB mutation, Δ(dinB-yafN)883(::kan) [referred to as ΔdinB883], which strongly sensitized E. coli cells to both UV- and X-radiation killing. Earlier reports indicated dinB mutations had no obvious effect on UV radiation sensitivity which we confirmed by showing that normal UV radiation sensitivity is conferred by the ΔdinB749 allele. Compared to a wild-type strain, the ΔdinB883 mutant was most sensitive (160-fold) in early to mid-logarithmic growth phase and much less sensitive (twofold) in late log or stationary phases, thus showing a growth phase-dependence for UV radiation sensitivity. This sensitizing effect of ΔdinB883 is assumed to be completely dependent upon the presence of UmuDC protein; since the ΔdinB883 mutation did not sensitize the ΔumuDC strain to UV radiation killing throughout log phase and early stationary phase growth. The DNA damage checkpoint activity of UmuDC was clearly affected by ΔdinB883 as shown by testing a umuC104 ΔdinB883 double-mutant. The sensitivities of the ΔumuDC strain and the ΔdinB883 ΔumuDC double-mutant strain were significantly greater than for the ΔdinB883 strain, suggesting that the ΔdinB883 allele only partially suppresses UmuDC activity. The ΔdinB883 mutation partially sensitized (fivefold) uvrA and uvr

  19. Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair

    Energy Technology Data Exchange (ETDEWEB)

    Gustafsson, Ann-Sofie, E-mail: ann-sofie.gustafsson@bms.uu.se; Abramenkovs, Andris; Stenerlöw, Bo

    2014-11-15

    Highlights: • We reduced the level of DNA-PKcs with siRNA and examined cells after γ-irradiation. • Low DNA-PKcs levels lead to radiosensitivity but did not affect repair of DSB. • Low DNA-PKcs levels may block progression of mitosis. • DNA-PKcs role in mitotic progression is independent of its role in DSB repair. • We suggest different mechanisms by which loss of DNA-PKcs function sensitize cells. - Abstract: Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present study, by using siRNA against DNA-PKcs in four human cell lines, we examined how low levels of DNA-PKcs affected cellular response to ionizing radiation. Decrease of DNA-PKcs levels by 80–95%, induced by siRNA treatment, lead to extreme radiosensitivity, similar to that seen in cells completely lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M phase after irradiation and blocked progression of mitosis. Surprisingly, low levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or γ-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs inhibitor NU7441, in which DSB repair were severely compromised. This suggests that there are different mechanisms by which loss of DNA-PKcs functions can sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs (T2609 and S2056) co-localized with DSB and this was independent of the amount of DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study emphasizes on the critical role of DNA-PKcs for maintaining survival after radiation exposure

  20. Low-dose radiation employed in diagnostic imaging causes genetic effects in cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Ponzinibbio, Maria V.; Peral-Garcia, Pilar; Seoane, Analia (Inst. de Genetica Veterinaria, Univ. Nacional de La Plata CONICET, La Plata (Argentina)), e-mail: aseoane@fcv.unlp.edu.ar; Crudeli, Cintia (Agencia Nacional de Promocion Cientifica y Tecnologica, La Plata (Argentina))

    2010-11-15

    Background: Exposure to environmental, diagnostic, and occupational sources of radiation frequently involves low doses. Although these doses have no immediately noticeable impact on human health there is great interest in their long-term biological effects. Purpose: To assess immediate and time-delayed DNA damage in two cell lines exposed to low doses of ionizing radiation by using the comet assay and micronucleus test, and to compare these two techniques in the analysis of low-dose induced genotoxicity. Material and Methods: CHO and MRC-5 cells were exposed to 50 milliSievert (mSv) of ionizing radiation and assayed immediately after irradiation and at 16 or 12 passages post-irradiation, respectively. Comet assay and micronucleus test were employed. Results: The comet assay values observed in 50 mSv-treated cells were significantly higher than in the control group for both sample times and cell lines (P < 0.001). Micronuclei frequencies were higher in treated cells than in the control group (P < 0.01, CHO cells passage 16; P < 0.05, MRC-5 cells immediately after exposure; P < 0.01 MRC-5 cells passage 12). Correlation analysis between the two techniques was statistically significant (correlation coefficient 0.82, P < 0.05 and correlation coefficient 0.86, P < 0.05 for CHO and MRC-5 cells, respectively). Cells scored at passages 12 or 16 showed more damage than those scored immediately after exposure in both cell lines (no statistically significant differences). Conclusion: Cytomolecular and cytogenetic damage was observed in cells exposed to very low doses of X-rays and their progeny. A single low dose of ionizing radiation was sufficient to induce such response, indicating that mammalian cells are exquisitely sensitive to it. Comet and micronucleus assays are sensitive enough to assess this damage, although the former seems to be more efficient

  1. A robust hypothesis test for the sensitive detection of constant speed radiation moving sources

    Energy Technology Data Exchange (ETDEWEB)

    Dumazert, Jonathan, E-mail: jonathan.dumazert@cea.fr [CEA, LIST, Laboratoire Capteurs Architectures Electroniques, 91191 Gif-sur-Yvette (France); Coulon, Romain; Kondrasovs, Vladimir; Boudergui, Karim; Moline, Yoann; Sannié, Guillaume; Gameiro, Jordan; Normand, Stéphane [CEA, LIST, Laboratoire Capteurs Architectures Electroniques, 91191 Gif-sur-Yvette (France); Méchin, Laurence [CNRS, UCBN, Groupe de Recherche en Informatique, Image, Automatique et Instrumentation de Caen, 14050 Caen (France)

    2015-09-21

    Radiation Portal Monitors are deployed in linear networks to detect radiological material in motion. As a complement to single and multichannel detection algorithms, inefficient under too low signal-to-noise ratios, temporal correlation algorithms have been introduced. Test hypothesis methods based on empirically estimated mean and variance of the signals delivered by the different channels have shown significant gain in terms of a tradeoff between detection sensitivity and false alarm probability. This paper discloses the concept of a new hypothesis test for temporal correlation detection methods, taking advantage of the Poisson nature of the registered counting signals, and establishes a benchmark between this test and its empirical counterpart. The simulation study validates that in the four relevant configurations of a pedestrian source carrier under respectively high and low count rate radioactive backgrounds, and a vehicle source carrier under the same respectively high and low count rate radioactive backgrounds, the newly introduced hypothesis test ensures a significantly improved compromise between sensitivity and false alarm. It also guarantees that the optimal coverage factor for this compromise remains stable regardless of signal-to-noise ratio variations between 2 and 0.8, therefore allowing the final user to parametrize the test with the sole prior knowledge of background amplitude.

  2. Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy

    Science.gov (United States)

    Tamarov, Konstantin P.; Osminkina, Liubov A.; Zinovyev, Sergey V.; Maximova, Ksenia A.; Kargina, Julia V.; Gongalsky, Maxim B.; Ryabchikov, Yury; Al-Kattan, Ahmed; Sviridov, Andrey P.; Sentis, Marc; Ivanov, Andrey V.; Nikiforov, Vladimir N.; Kabashin, Andrei V.; Timoshenko, Victor Yu

    2014-11-01

    Offering mild, non-invasive and deep cancer therapy modality, radio frequency (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF sensitizers to selectively target cancer cells and thus avoid side effects. Here, we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF-induced therapy. Using nanoparticles produced by mechanical grinding of porous silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced heating of aqueous suspensions of the nanoparticles to temperatures above 45-50°C under relatively low nanoparticle concentrations (nanoparticles the heating rate was linearly dependent on nanoparticle concentration, while laser-ablated nanoparticles demonstrated a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations from 0.01 to 0.4 mg/mL. The observed effect is explained by the Joule heating due to the generation of electrical currents at the nanoparticle/water interface. Profiting from the nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis lung carcinoma in vivo. Combined with the possibility of involvement of parallel imaging and treatment channels based on unique optical properties of Si-based nanomaterials, the proposed method promises a new landmark in the development of new modalities for mild cancer therapy.

  3. Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy.

    Science.gov (United States)

    Tamarov, Konstantin P; Osminkina, Liubov A; Zinovyev, Sergey V; Maximova, Ksenia A; Kargina, Julia V; Gongalsky, Maxim B; Ryabchikov, Yury; Al-Kattan, Ahmed; Sviridov, Andrey P; Sentis, Marc; Ivanov, Andrey V; Nikiforov, Vladimir N; Kabashin, Andrei V; Timoshenko, Victor Yu

    2014-11-13

    Offering mild, non-invasive and deep cancer therapy modality, radio frequency (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF sensitizers to selectively target cancer cells and thus avoid side effects. Here, we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF-induced therapy. Using nanoparticles produced by mechanical grinding of porous silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced heating of aqueous suspensions of the nanoparticles to temperatures above 45-50 °C under relatively low nanoparticle concentrations (heating rate was linearly dependent on nanoparticle concentration, while laser-ablated nanoparticles demonstrated a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations from 0.01 to 0.4 mg/mL. The observed effect is explained by the Joule heating due to the generation of electrical currents at the nanoparticle/water interface. Profiting from the nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis lung carcinoma in vivo. Combined with the possibility of involvement of parallel imaging and treatment channels based on unique optical properties of Si-based nanomaterials, the proposed method promises a new landmark in the development of new modalities for mild cancer therapy.

  4. Radiation sensitivity of bacteria and virus in porcine xenoskin for dressing agent

    Science.gov (United States)

    Jo, Eu-Ri; Jung, Pil-Mun; Choi, Jong-il; Lee, Ju-Woon

    2012-08-01

    In this study, gamma irradiation sensitivities of bacteria and viruses in porcine skin were evaluated to establish the optimum sterilization condition for the dressing material and a xenoskin graft. Escherichia coli and Bacillus subtilis were used as model pathogens and inoculated at 106-107 log CFU/g. As model viruses, porcine parvovirus (PPV), bovine viral diarrhea virus (BVDV), and poliovirus were used and inoculated at 105-106 TCID50/g into porcine skin. The D10 value of E. coli was found to be 0.25±0.1 kGy. B. subtilis endospores produced under stressful environmental conditions showed lower radiation sensitivity as D10 was 3.88±0.3 kGy in porcine skin. The D10 values of PPV, BVDV, and poliovirus were found to be 1.73±0.2, 3.81±0.2, and 6.88±0.3 kGy, respectively. These results can offer the basic information required for inactivating pathogens by gamma irradiation and achieving dressing material and porcine skin grafts.

  5. Adjoint-based sensitivity analysis for high-energy density radiative transfer using flux-limited diffusion

    Science.gov (United States)

    Humbird, Kelli D.; McClarren, Ryan G.

    2017-03-01

    Uncertainty quantification and sensitivity analyses are a vital component for predictive modeling in the sciences and engineering. The adjoint approach to sensitivity analysis requires solving a primary system of equations and a mathematically related set of adjoint equations. The information contained in the equations can be combined to produce sensitivity information in a computationally efficient manner. In this work, sensitivity analyses are performed on systems described by flux-limited radiative diffusion using the adjoint approach. The sensitivities computed are shown to agree with standard perturbation theory and require significantly less computational time. The adjoint approach saves the computational cost of one forward solve per sensitivity, making the method attractive when multiple sensitivities are of interest.

  6. [Fluorescence used to investigate the sensitivity of spinach chloroplast membrane to low intensity electromagnetic radiation].

    Science.gov (United States)

    Xi, Gang; Yang, Yun-Jing; Lu, Hong

    2009-07-01

    A system for studying biological effect of radio frequency electromagnetic field was developed. The system can form an area where electromagnetic wave with large frequency range is well distributed. The strength of electromagnetic wave was measured easily. Electromagnetic wave in the system did not have effect on environment. The sensitivity of spinach chloroplast membrane to low intensity electromagnetic radiation of 300 MHz under power density of 5 mW x cm(-2) was studied by the spectral analysis method of fluorescence of 8-anilino-1-naphthalene-sulfonic acid (ANS) and the changes in chlorophyll a (Chla) fluorescence parameters of spinach chloroplast membrane. The result showed that the position of spectrum of ANS fluorescence of spinach chloroplast membrane did not change, but the intensity of ANS fluorescence was obviously increased under the action of electromagnetic radiation with power density of 1-5 mW x cm(-2). There was an increase in the intensity of ANS fluorescence with the increase in electromagnetic radiation. The increase of ANS fluorescence of spinach chloroplast membrane showed that low level electromagnetic field induced the decrease in fluidity of chloroplast membrane compared with control experiment. The cause of the change in the fluidity could be related to the polarization of chloroplast membrane under the electromagnetic field. The analysis of Chla fluorescence parameters of spinach chloroplast membrane indicated that low level electromagnetic field of 300 MHz made the fluorescence parameters F0 and F(VI/)F(V) decrease, and F(V)/Fo, Fv/F(m) and deltaF(V)/T increase. It was showed that low level electromagnetic field caused the change of non-active center of photosystem II of spinach chloroplast membrane to active center and the increase in potential active and photochemical efficiency of PSII, and promoted the transmit process of electron in photosynthesis of chloroplast membrane of photosynthesis cell in spinach leaf. The study confirmed

  7. Nimotuzumab enhances radiation sensitivity of NSCLC H292 cells in vitro by blocking epidermal growth factor receptor nuclear translocation and inhibiting radiation-induced DNA damage repair

    Directory of Open Access Journals (Sweden)

    Teng K

    2015-04-01

    Full Text Available Kai Teng,1,2,* Yong Zhang,1,* Xiaoyan Hu,1 Yihui Ding,1 Rui Gong,1 Li Liu1,* 1Department of Thoracic Oncology, Cancer Center of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Radiation Oncology, Hainan Cancer Hospital, Haikou, Hainan, People’s Republic of China *These authors contributed equally to this work Background: The epidermal growth factor receptor (EGFR signaling pathway plays a significant role in radiation resistance. There is evidence that EGFR nuclear translocation is associated with DNA double-strand breaks (DSB repair. Nimotuzumab has shown the effect of radiosensitization in various cancer cells, but little is known about the relationship between nimotuzumab and EGFR nuclear translocation in non-small cell lung cancer (NSCLC cell lines. In this study, we selected two NSCLC cell lines, namely, H292 (with high EGFR expression and H1975 (with low EGFR expression and explored the mechanisms underlying radiation sensitivity.Methods: MTT assay, clonogenic survival assay, and flow cytometry were performed separately to test cell viability, radiation sensitivity, cell cycle distribution, and apoptosis. Protein γ-H2AX, DNA-PK/p-DNA-PK, and EGFR/p-EGFR expression were further compared both in the cytoplasm and the nucleus with the western blot.Results: Nimotuzumab reduced the viability of H292 cells and sensitized H292 cells to ionizing radiation. The radiation sensitivity enhancement ratio (SER was 1.304 and 1.092 for H292 and H1975 cells, respectively. H292 cells after nimotuzumab administration were arrested at the G0/G1 phase in response to radiation. Apoptosis was without statistical significance in both cell lines. γ-H2AX formation in the combination group (nimotuzumab and radiation increased both in the cytoplasm and the nucleus along with the decreased expression of nuclear EGFR/p-EGFR and p-DNA-PK in H292 cells (P<0.05 that

  8. Effects of disclosing hypothetical genetic test results for salt sensitivity on salt restriction behavior

    Directory of Open Access Journals (Sweden)

    Takeshima T

    2013-05-01

    Full Text Available Taro Takeshima,1,2 Masanobu Okayama,1 Masanori Harada,3 Ryusuke Ae,4 Eiji Kajii1 1Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Tochigi, Japan; 2Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan; 3Department for Support of Rural Medicine, Yamaguchi Grand Medical Center, Yamaguchi, Japan; 4Department of General Internal Medicine, Hamasaka Public Hospital, Mikata, Japan Background: A few studies have explored the effects of disclosure of genetic testing results on chronic disease predisposition. However, these effects remain unclear in cases of hypertension. Reducing salt intake is an important nonpharmacological intervention for hypertension. We investigated the effects of genetic testing for salt sensitivity on salt restriction behavior using hypothetical genetic testing results. Methods: We conducted a cross-sectional study using a self-completed questionnaire. We enrolled consecutive outpatients who visited primary care clinics and small hospitals between September and December 2009 in Japan. We recorded the patients’ baseline characteristics and data regarding their salt restriction behavior, defined as reducing salt intake before and after disclosure of hypothetical salt sensitivity genetic test results. Behavioral stage was assessed according to the five-stage transtheoretical model. After dividing subjects into salt restriction and no salt restriction groups, we compared their behavioral changes following positive and negative test results and analyzed the association between the respondents’ characteristics and their behavioral changes. Results: We analyzed 1562 participants with a mean age of 58 years. In the no salt restriction group, which included patients at the precontemplation, contemplation, and preparation stages, 58.7% stated that their behavioral stage progressed after a positive test result, although 29

  9. S-phase cells are more sensitive to high-linear energy transfer radiation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H.; Naidu, M.; Liu, S.; Zhang, P.; Zhang, S.; Wang, H.; Wang, Y.

    2009-07-15

    S-phase cells are more resistant to low-linear energy transfer (LET) ionizing radiation (IR) than nonsynchronized and G{sub 1}-phase cells, because both nonhomologous end-joining (NHEJ) and homologous recombination repair can repair DNA double-strand breaks (DSBs) in the S phase. Although it was reported 3 decades ago that S-phase cells did not show more resistance to high-LET IR than cells in other phases, the mechanism remains unclear. We therefore attempted to study the phenotypes and elucidate the mechanism involved. Wild-type and NHEJ-deficient cell lines were synchronized using the double-thymidine approach. A clonogenic assay was used to detect the sensitivity of nonsynchronized, synchronized S-phase, and G{sub 2}-phase cells to high- and low-LET IR. The amounts of Ku bound to DSBs in the high- and low-LET-irradiated cells were also examined. S-phase wild-type cells (but not NHEJ-deficient cells) were more sensitive to high-LET IR than nonsynchronized and G{sub 2}-phase cells. In addition, S-phase wild-type cells showed less efficient Ku protein binding to DSBs than nonsynchronized and G{sub 2}-phase cells in response to high-LET IR, although all cells at all phases showed similarly efficient levels of Ku protein binding to DSBs in response to low-LET IR. S-phase cells are more sensitive to high-LET IR than nonsynchronized and G{sub 2}-phase cells, because of the following mechanism: it is more difficult for Ku protein to bind to high-LET IR-induced DNA DSBs in S-phase cells than in cells at other phases, which results in less efficient NHEJ.

  10. Genetic Algorithm Used for Load Shedding Based on Sensitivity to Enhance Voltage Stability

    Science.gov (United States)

    Titare, L. S.; Singh, P.; Arya, L. D.

    2014-12-01

    This paper presents an algorithm to calculate optimum load shedding with voltage stability consideration based on sensitivity of proximity indicator using genetic algorithm (GA). Schur's inequality based proximity indicator of load flow Jacobian has been selected, which indicates system state. Load flow Jacobian of the system is obtained using Continuation power flow method. If reactive power and active rescheduling are exhausted, load shedding is the last line of defense to maintain the operational security of the system. Load buses for load shedding have been selected on the basis of sensitivity of proximity indicator. The load bus having large sensitivity is selected for load shedding. Proposed algorithm predicts load bus rank and optimum load to be shed on load buses. The algorithm accounts inequality constraints not only in present operating conditions, but also for predicted next interval load (with load shedding). Developed algorithm has been implemented on IEEE 6-bus system. Results have been compared with those obtained using Teaching-Learning-Based Optimization (TLBO), particle swarm optimization (PSO) and its variant.

  11. Genetic radiation risks: a neglected topic in the low dose debate

    Science.gov (United States)

    2016-01-01

    Objectives To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (Abomb) survivors. Methods To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down’s syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about

  12. Curcumin Sensitizes Hepatocellular Carcinoma Cells to Radiation via Suppression of Radiation-Induced NF-κB Activity

    Directory of Open Access Journals (Sweden)

    Fei-Ting Hsu

    2015-01-01

    Full Text Available The effects and possible underlying mechanism of curcumin combined with radiation in human hepatocellular carcinoma (HCC cells in vitro were evaluated. The effects of curcumin, radiation, and combination of both on cell viability, apoptosis, NF-κB activation, and expressions of NF-κB downstream effector proteins were investigated with 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT, NF-κB reporter gene, mitochondrial membrane potential (MMP, electrophoretic mobility shift (EMSA, and Western blot assays in Huh7-NF-κB-luc2, Hep3B, and HepG2 cells. Effect of I kappa B alpha mutant (IκBαM vector, a specific inhibitor of NF-κB activation, on radiation-induced loss of MMP was also evaluated. Results show that curcumin not only significantly enhances radiation-induced cytotoxicity and depletion of MMP but inhibits radiation-induced NF-κB activity and expressions of NF-κB downstream proteins in HCC cells. IκBαM vector also shows similar effects. In conclusion, we suggest that curcumin augments anticancer effects of radiation via the suppression of NF-κB activation.

  13. Sensitivity simulations with direct shortwave radiative forcing by aeolian dust during glacial cycles

    Science.gov (United States)

    Bauer, E.; Ganopolski, A.

    2014-07-01

    Possible feedback effects between aeolian dust, climate and ice sheets are studied for the first time with an Earth system model of intermediate complexity over the late Pleistocene period. Correlations between climate and dust deposition records suggest that aeolian dust potentially plays an important role for the evolution of glacial cycles. Here climatic effects from the dust direct radiative forcing (DRF) caused by absorption and scattering of solar radiation are investigated. Key elements controlling the dust DRF are the atmospheric dust distribution and the absorption-scattering efficiency of dust aerosols. Effective physical parameters in the description of these elements are varied within uncertainty ranges known from available data and detailed model studies. Although the parameters can be reasonably constrained, the simulated dust DRF spans a~wide uncertainty range related to the strong nonlinearity of the Earth system. In our simulations, the dust DRF is highly localized. Medium-range parameters result in negative DRF of several watts per square metre in regions close to major dust sources and negligible values elsewhere. In the case of high absorption efficiency, the local dust DRF can reach positive values and the global mean DRF can be insignificantly small. In the case of low absorption efficiency, the dust DRF can produce a significant global cooling in glacial periods, which leads to a doubling of the maximum glacial ice volume relative to the case with small dust DRF. DRF-induced temperature and precipitation changes can either be attenuated or amplified through a feedback loop involving the dust cycle. The sensitivity experiments suggest that depending on dust optical parameters, dust DRF has the potential to either damp or reinforce glacial-interglacial climate changes.

  14. Sensitivity simulations with direct radiative forcing by aeolian dust during glacial cycles

    Science.gov (United States)

    Bauer, E.; Ganopolski, A.

    2014-01-01

    Possible feedback effects between aeolian dust, climate and ice sheets are studied for the first time with an Earth system model of intermediate complexity over the late Pleistocene period. Correlations between climate variables and dust deposits suggest that aeolian dust potentially plays an important role for the evolution of glacial cycles. Here climatic effects from the dust direct radiative forcing (DRF) caused by absorption and scattering of solar radiation are investigated. Key factors controlling the dust DRF are the atmospheric dust distribution and the absorption-scattering efficiency of dust aerosols. Effective physical parameters in the description of these factors are varied within uncertainty ranges known from available data and detailed model studies. Although the parameters are reasonably constrained by use of these studies, the simulated dust DRF spans a wide uncertainty range related to nonlinear dependencies. In our simulations, the dust DRF is highly localized. Medium-range parameters result in negative DRF of several W m-2 in regions close to major dust sources and negligible values elsewhere. In case of high absorption efficiency, the local dust DRF can reach positive values and the global mean DRF can be insignificantly small. In case of low absorption efficiency, the dust DRF can produce a significant global cooling in glacial periods which leads to a doubling of the maximum glacial ice volume relative to the case with small dust DRF. DRF-induced temperature and precipitation changes can either be attenuated or amplified through a feedback loop involving the dust cycle. The sensitivity experiments suggest that depending on dust optical parameters the DRF has the potential to either damp or reinforce glacial-interglacial climate changes.

  15. Rearrangement of RAG-1 recombinase gene in radiation-sensitive ``wasted`` mice

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E. [Argonne National Lab., IL (United States)]|[Loyola Univ., Maywood, IL (United States); Libertin, C.R.; Weaver, P. [Loyola Univ., Maywood, IL (United States); Churchill, M.; Chang-Liu, C.M. [Argonne National Lab., IL (United States)

    1993-09-01

    Mice recessive for the autosomal gene ``wasted`` (wst) display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (RAG-1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed expression of RAG-1 mRNA in spinal cord (but not brain) of control mice; no expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/{center_dot} mice). In thymus tissue, a small RAG-1 transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/{center_dot} mice, a two-fold increase in RAG-1 MRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/{center_dot} and not from wst/wst or parental control BCF{sub 1} mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage.

  16. Sensitive dependencies and separation distances for genetically modified herbicide-tolerant crops.

    Science.gov (United States)

    Perry, Joe N

    2002-06-07

    The amount of land available for the coexistent growing of both organic and genetically modified herbicide-tolerant (GMHT) crops depends on the separation distance between the two types of crop. The form of the decline in the proportion of land available for growing one of these crop types due to increasing separation distance is linear on a suitable scale, but with a slope and intercept that are sensitively dependent on the proportion of the other crop already present. Spatially explicit simulations from realistic scenarios indicate that a major increase in separation distances, currently under review by the UK government, may have serious implications for the future coexistence of organic and GMHT crops in the UK.

  17. The optimal condition of performing MTT assay for the determination of radiation sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Semie; Kim, Il Han [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2001-06-01

    The measurement of radiation survival using a clonogenic assay, the established standard, can be difficult and time consuming. In this study, We have used the MTT assay, based on the reduction of a tetrazolium salt to a purple formazan precipitate by living cells, as a substitution for clonogenic assay and have examined the optimal condition for performing this assay in determination of radiation sensitivity. Four human cancer cell lines - PCI-1, SNU-1066, NCI-H63O and RKO cells have been used. For each cell line, a clonogenic assay and a MTT assay using Premix WST-1 solution, which is one of the tetrazolium salts and does not require washing or solubilization of the precipitate were carried out after irradiation of 0, 2, 4, 6, 8, 10 Gy, For clonogenic assay, cells in 25 cm{sup 2} flasks were irradiated after overnight incubation and the resultant colonies containing more than 50 cells were scored after culturing the cells for 10-14 days, For MTT assay, the relationship between absorbance and cell number, optimal seeding cell number, and optimal timing of assay was determined. Then, MTT assay was performed when the irradiated cells had regained exponential growth or when the non-irradiated cells had undergone four or more doubling times. There was minimal variation in the values gained from these two methods with the standard deviation generally less than 5%, and there were no statistically significant differences between two methods according to t-test in low radiation dose (below 6 Gy). The regression analyses showed high linear correlation with the R{sup 2} value of 0.975-0.992 between data from the two different methods. The optimal cell numbers for MTT assay were found to be dependent on plating efficiency of used cell line. Less than 300 cells/well were appropriate for cells with high plating efficiency (more than 30%). For cells with low plating efficiency (less than 30%), 500 cells/well or more were appropriate for assay. The optimal time for MTT assay was

  18. Impact of Ice Nucleation Parameterization on CAM5 Simulated Arctic Clouds and Radiation: A Sensitivity Study

    Science.gov (United States)

    Xie, S.; Liu, X.; Zhao, C.; Zhang, Y.

    2012-12-01

    Sensitivity of Arctic clouds and radiation in the Community Atmospheric Model version 5 (CAM5) to ice nucleation parameterization is examined by testing a new and more physically based ice nucleation scheme that links the variation of ice nuclei (IN) number concentration to aerosol properties. The CAM5 default scheme parameterizes the IN number concentration simply as a function of ice supersaturation. The new scheme has led to a significant reduction in simulated IN number concentrations at all latitudes while changes in cloud and cloud properties are mainly seen in high latitudes and middle latitude storm tracks. In the Arctic region, there is a noticeable increase in mid- and high-level clouds and a decrease in low-level clouds. The smaller IN concentrations results in a considerable increase of cloud liquid water path and decrease of ice water path, which are likely related to the increase of optically intermediate and thick low- and middle-top clouds and the decrease of optically thin and intermediate high clouds, respectively. Overall, there is an increase of cloud optical depth of Arctic clouds, which leads to a stronger shortwave, longwave, and net cloud radiative forcing (cooling) at the top of the atmosphere. The comparison with satellite data indicates that the new scheme has slightly improved optically thin low cloud simulation, but produced too many optically thick middle and high clouds. A further comparison with Arctic ground-based measurements shows that the new scheme has led to a clearly better simulation of clouds and their properties, which helps reduce model errors in surface radiation. Uncertainties in these observations are discussed. Work at LLNL was performed under the auspices of the U. S. Department of Energy (DOE), Office of Science, Office of Biological and Environmental Research by Lawrence Livermore National Laboratory under contract No. DE-AC52-07NA27344. The Pacific Northwest National Laboratory (PNNL) is operated for the DOE by

  19. Genetic Determinism of Sensitivity to Corynespora cassiicola Exudates in Rubber Tree (Hevea brasiliensis).

    Science.gov (United States)

    Tran, Dinh Minh; Clément-Demange, André; Déon, Marine; Garcia, Dominique; Le Guen, Vincent; Clément-Vidal, Anne; Soumahoro, Mouman; Masson, Aurélien; Label, Philippe; Le, Mau Tuy; Pujade-Renaud, Valérie

    2016-01-01

    An indirect phenotyping method was developed in order to estimate the susceptibility of rubber tree clonal varieties to Corynespora Leaf Fall (CLF) disease caused by the ascomycete Corynespora cassiicola. This method consists in quantifying the impact of fungal exudates on detached leaves by measuring the induced electrolyte leakage (EL%). The tested exudates were either crude culture filtrates from diverse C. cassiicola isolates or the purified cassiicolin (Cas1), a small secreted effector protein produced by the aggressive isolate CCP. The test was found to be quantitative, with the EL% response proportional to toxin concentration. For eight clones tested with two aggressive isolates, the EL% response to the filtrates positively correlated to the response induced by conidial inoculation. The toxicity test applied to 18 clones using 13 toxinic treatments evidenced an important variability among clones and treatments, with a significant additional clone x treatment interaction effect. A genetic linkage map was built using 306 microsatellite markers, from the F1 population of the PB260 x RRIM600 family. Phenotyping of the population for sensitivity to the purified Cas1 effector and to culture filtrates from seven C. cassiicola isolates revealed a polygenic determinism, with six QTL detected on five chromosomes and percentages of explained phenotypic variance varying from 11 to 17%. Two common QTL were identified for the CCP filtrate and the purified cassiicolin, suggesting that Cas1 may be the main effector of CCP filtrate toxicity. The CCP filtrate clearly contrasted with all other filtrates. The toxicity test based on Electrolyte Leakage Measurement offers the opportunity to assess the sensitivity of rubber genotypes to C. cassiicola exudates or purified effectors for genetic investigations and early selection, without risk of spreading the fungus in plantations. However, the power of this test for predicting field susceptibility of rubber clones to CLF will have

  20. Alcohol induces sensitization to gluten in genetically susceptible individuals: a case control study.

    Directory of Open Access Journals (Sweden)

    Stuart Currie

    Full Text Available BACKGROUND: The mechanisms of cerebellar degeneration attributed to prolonged and excessive alcohol intake remain unclear. Additional or even alternative causes of cerebellar degeneration are often overlooked in suspected cases of alcohol-related ataxia. The objectives of this study were two fold: (1 to investigate the prevalence of gluten-related serological markers in patients with alcohol-related ataxia and; (2 to compare the pattern of brain involvement on magnetic resonance imaging between patients with alcohol and gluten ataxias. MATERIALS & METHODS: Patients diagnosed with alcohol and gluten ataxias were identified from a retrospective review of patients attending a tertiary clinic. HLA genotype and serological markers of gluten-related disorders were recorded. Cerebellar volumetry, MR spectroscopy and voxel-based morphometric analyses were performed on patients and compared with matched control data. RESULTS: Of 904 registered patients, 104 had alcohol ataxia and 159 had gluten ataxia. 61% of the alcohol ataxia group and 70% of the gluten ataxia group had HLA DQ2/DQ8 genotype compared to 30% in healthy local blood donors. 44% of patients with alcohol ataxia had antigliadin antibodies compared to 12% in the healthy local population and 10% in patients with genetically confirmed ataxias. None of the patients with alcohol ataxia and antigliadin antibodies had celiac disease compared to 40% in patients with gluten ataxia. The pattern of structural brain abnormality in patients with alcohol ataxia who had antigliadin antibodies differed from gluten ataxia and was identical to that of alcohol ataxia. CONCLUSIONS: Alcohol related cerebellar degeneration may, in genetically susceptible individuals, induce sensitization to gluten. Such sensitization may result from a primary cerebellar insult, but a more systemic effect is also possible. The duration and amount of exposure to alcohol may not be the only factors responsible for the cerebellar

  1. Genetic Determinism of Sensitivity to Corynespora cassiicola Exudates in Rubber Tree (Hevea brasiliensis)

    Science.gov (United States)

    Tran, Dinh Minh; Clément-Demange, André; Déon, Marine; Garcia, Dominique; Le Guen, Vincent; Clément-Vidal, Anne; Soumahoro, Mouman; Masson, Aurélien; Label, Philippe; Le, Mau Tuy; Pujade-Renaud, Valérie

    2016-01-01

    An indirect phenotyping method was developed in order to estimate the susceptibility of rubber tree clonal varieties to Corynespora Leaf Fall (CLF) disease caused by the ascomycete Corynespora cassiicola. This method consists in quantifying the impact of fungal exudates on detached leaves by measuring the induced electrolyte leakage (EL%). The tested exudates were either crude culture filtrates from diverse C. cassiicola isolates or the purified cassiicolin (Cas1), a small secreted effector protein produced by the aggressive isolate CCP. The test was found to be quantitative, with the EL% response proportional to toxin concentration. For eight clones tested with two aggressive isolates, the EL% response to the filtrates positively correlated to the response induced by conidial inoculation. The toxicity test applied to 18 clones using 13 toxinic treatments evidenced an important variability among clones and treatments, with a significant additional clone x treatment interaction effect. A genetic linkage map was built using 306 microsatellite markers, from the F1 population of the PB260 x RRIM600 family. Phenotyping of the population for sensitivity to the purified Cas1 effector and to culture filtrates from seven C. cassiicola isolates revealed a polygenic determinism, with six QTL detected on five chromosomes and percentages of explained phenotypic variance varying from 11 to 17%. Two common QTL were identified for the CCP filtrate and the purified cassiicolin, suggesting that Cas1 may be the main effector of CCP filtrate toxicity. The CCP filtrate clearly contrasted with all other filtrates. The toxicity test based on Electrolyte Leakage Measurement offers the opportunity to assess the sensitivity of rubber genotypes to C. cassiicola exudates or purified effectors for genetic investigations and early selection, without risk of spreading the fungus in plantations. However, the power of this test for predicting field susceptibility of rubber clones to CLF will have

  2. Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

    Science.gov (United States)

    Worgul, Basil V.; Smilenov, Lubomir; Brenner, David J.; Junk, Anna; Zhou, Wei; Hall, Eric J.

    2002-01-01

    It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.

  3. Context-sensitive network-based disease genetics prediction and its implications in drug discovery.

    Science.gov (United States)

    Chen, Yang; Xu, Rong

    2017-04-01

    Disease phenotype networks play an important role in computational approaches to identifying new disease-gene associations. Current disease phenotype networks often model disease relationships based on pairwise similarities, therefore ignore the specific context on how two diseases are connected. In this study, we propose a new strategy to model disease associations using context-sensitive networks (CSNs). We developed a CSN-based phenome-driven approach for disease genetics prediction, and investigated the translational potential of the predicted genes in drug discovery. We constructed CSNs by directly connecting diseases with associated phenotypes. Here, we constructed two CSNs using different data sources; the two networks contain 26 790 and 13 822 nodes respectively. We integrated the CSNs with a genetic functional relationship network and predicted disease genes using a network-based ranking algorithm. For comparison, we built Similarity-Based disease Networks (SBN) using the same disease phenotype data. In a de novo cross validation for 3324 diseases, the CSN-based approach significantly increased the average rank from top 12.6 to top 8.8% for all tested genes comparing with the SBN-based approach ( pdisease using CSNs, and demonstrated that the top-ranked genes are highly relevant to PD pathologenesis. We pin-pointed a top-ranked drug target gene for PD, and found its association with neurodegeneration supported by literature. In summary, CSNs lead to significantly improve the disease genetics prediction comparing with SBNs and provide leads for potential drug targets. nlp.case.edu/public/data/. rxx@case.edu.

  4. Genetic Sensitivity to Phenylthiocarbamide – Effect on Body Mass Indices and DNA damage

    Directory of Open Access Journals (Sweden)

    Gursatej Gandhi

    2012-06-01

    Full Text Available As sensitivity to bitter taste (phenylthiocarbamide [PTC] perception has been maintained at high frequency worldwide, its use as a potential genetic marker for food preferences and dietary choices and its influence on body weight/adiposity which in turn maybe a contributor to various co-morbidities including malignancy needs to be explored in the Punjabi context where there is higher per capita income, an adapted ‘western’ dietary pattern with traditional culinary habits and reduced physical activity. Since studies linking PTC tasting status, indices of obesity and DNA damage have not come to attention, the present study, using the alkaline Single Cell Gel Electrophoresis assay was carried out to assess genomic damage in peripheral blood leukocytes (PBL of 144 individuals, both obese (n=96, as determined by body mass index [BMI] and waist-hip ratio [WHR] and normal weight healthy (n=46 subjects. Their PTC status revealed 73 tasters and 69 non-tasters. The odds ratio revealed a 2.51 times increased risk in non-tasters (OR=2.51; 95%CI 1.20-5.25 for having BMI≥ 25.0 kg/m2 in comparison to risk in tasters while the risk ratio revealed a 1.32 times increased probability of non-tasters for having BMI≥ 25.0 kg/m2 in comparison to tasters (RR=1.32; 95%CI 1.05-1.66. The genetic damage in the obese group (characterized on the bases of their gender and PTC tasting ability was very highly significant (p<0.001 compared to the values in the matched control group (healthy, normal weight subjects. In both the taster and non-taster groups, BMI and WC (waist circumference significantly correlated to genetic damage indices though PTC tasting ability did not appear to influence BMI, WHR and WC.

  5. The Genetic Structure, Virulence, and Fungicide Sensitivity of Fusarium fujikuroi in Taiwan.

    Science.gov (United States)

    Chen, Yu-Chia; Lai, Ming-Hsin; Wu, Chia-Yi; Lin, Tsung-Chun; Cheng, An-Hsiu; Yang, Chin-Cheng; Wu, Hsin-Yuh; Chu, Sheng-Chi; Kuo, Chien-Chih; Wu, Yea-Fang; Lin, Guo-Cih; Tseng, Min-Nan; Tsai, Yi-Chen; Lin, Chun-Chi; Chen, Chi-Yu; Huang, Jenn-Wen; Lin, Heng-An; Chung, Chia-Lin

    2016-06-01

    The rice disease bakanae, caused by Fusarium fujikuroi Nirenberg, has been present in Taiwan for over a century. To better understand the genetic diversity and structure of F. fujikuroi, a set of 16 polymorphic simple sequence repeat (SSR) markers were newly developed and used to analyze 637 F. fujikuroi isolates collected in 14 cities or counties around Taiwan from 1996 to 2013. On the basis of Bayesian clustering, the isolates were classified into four highly differentiated clusters: cluster B likely derived from the more widespread and genetically diversified clusters A or C, and cluster D was restricted to four cities or counties and may have been introduced from unknown sources genetically distinct from clusters A, B, and C. The coexistence of both mating types (MAT1-1:MAT1-2 = 1:1.88) and the highly diversified vegetative compatibility groups (VCG) (16 VCG among the 21 assessed isolates) suggest the likelihood of sexual reproduction in the field. However, the biased mating type ratios and linkage disequilibrium in the population suggest nonrandom mating between individuals. A significant pattern of isolation by distance was also detected, which implies a geographical restricted gene flow and low dissemination ability of F. fujikuroi. Evaluation of 24 representative isolates on eight rice varieties revealed differential levels of virulence, however no clear pattern of specific variety x isolate interaction was observed. Investigations of the differences in virulence and fungicide sensitivity between 8 early isolates (1998 and 2002) and 52 recent isolates (2012) indicate the evolution of increased resistance to the fungicide prochloraz in F. fujikuroi in Taiwan.

  6. Genetic factors modulate the impact of pubertal androgen excess on insulin sensitivity and fertility.

    Directory of Open Access Journals (Sweden)

    Abigail R Dowling

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrine disorder of reproductive age women. The syndrome is caused by a combination of environmental influences and genetic predisposition. Despite extensive efforts, the heritable factors contributing to PCOS development are not fully understood. The objective of this study was to test the hypothesis that genetic background contributes to the development of a PCOS-like reproductive and metabolic phenotype in mice exposed to excess DHEA during the pubertal transition. We tested whether the PCOS phenotype would be more pronounced on the diabetes-prone C57BL/6 background than the previously used strain, BALB/cByJ. In addition, we examined strain-dependent upregulation of the expression of ovarian and extra-ovarian candidate genes implicated in human PCOS, genes containing known strain variants, and genes involved with steroidogenesis or insulin sensitivity. These studies show that there are significant strain-related differences in metabolic response to excess androgen exposure during puberty. Additionally, our results suggest the C57BL/6J strain provides a more robust and uniform experimental platform for PCOS research than the BALB/cByJ strain.

  7. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Nakadate, Yusuke [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Kodera, Yasuo; Kitamura, Yuka [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Tachibana, Taro [Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Tamura, Tomohide [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Koizumi, Fumiaki, E-mail: fkoizumi@ncc.go.jp [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2013-11-29

    Highlights: •Radiosensitization by PARG silencing was observed in multiple lung cancer cells. •PAR accumulation was enhanced by PARG silencing after DNA damage. •Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  8. Sensitivity analysis of radiative transfer for atmospheric remote sensing in thermal IR: atmospheric weighting functions and surface partials

    Science.gov (United States)

    Ustinov, E. A.

    2003-01-01

    In this presentation, we apply the adjoint sensitivity analysis of radiative transfer in thermal IR to the general case of the analytic evaluation of the weighting functions of atmospheric parameters together with the partial derivatives for the surface parameters. Applications to remote sensing of atmospheres of Mars and Venus are discussed.

  9. Punishment sensitivity and tension reduction: Exploring the potential influence of genetics on South Korean alcohol consumption

    Directory of Open Access Journals (Sweden)

    Benjamin J. Mahoney

    2016-12-01

    Full Text Available Aldehyde dehydrogenase 2*2 (ALDH2*2 is a genetically mutated enzyme that affects the liver’s ability to break down acetaldehyde, resulting in immediate negative physical effects following alcohol consumption. This usually leads to reduced lifetime alcohol dependence rates among those with ALDH2*2. Paradoxically, while around 30% of South Koreans have ALDH2*2, they still maintain both high levels of alcohol consumption and dependence. Therefore, how the negative reactions to alcohol experienced by those with ALDH2*2 interact with the expected effects of alcohol and sensitivity to punishment is of interest. Four hundred and sixty South Korean university students were tested for the ALDH2 gene type and completed alcohol expectancy and sensitivity to reward/punishment measures. The results indicated that there are different predictors of alcohol consumption depending on gene type, with ALDH2*2 heavy drinkers exhibiting lower levels of SP and higher levels of tension reduction expectancy. These findings suggest that ALDH2*2 plays a central role in differences in motivation for alcohol consumption among South Koreans.

  10. An Efficient Cost-Sensitive Feature Selection Using Chaos Genetic Algorithm for Class Imbalance Problem

    Directory of Open Access Journals (Sweden)

    Jing Bian

    2016-01-01

    Full Text Available In the era of big data, feature selection is an essential process in machine learning. Although the class imbalance problem has recently attracted a great deal of attention, little effort has been undertaken to develop feature selection techniques. In addition, most applications involving feature selection focus on classification accuracy but not cost, although costs are important. To cope with imbalance problems, we developed a cost-sensitive feature selection algorithm that adds the cost-based evaluation function of a filter feature selection using a chaos genetic algorithm, referred to as CSFSG. The evaluation function considers both feature-acquiring costs (test costs and misclassification costs in the field of network security, thereby weakening the influence of many instances from the majority of classes in large-scale datasets. The CSFSG algorithm reduces the total cost of feature selection and trades off both factors. The behavior of the CSFSG algorithm is tested on a large-scale dataset of network security, using two kinds of classifiers: C4.5 and k-nearest neighbor (KNN. The results of the experimental research show that the approach is efficient and able to effectively improve classification accuracy and to decrease classification time. In addition, the results of our method are more promising than the results of other cost-sensitive feature selection algorithms.

  11. Genetic variation in resistance to ionizing radiation. Final report, January 1, 1990--December 31, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Ayala, F.J.

    1992-12-31

    Results of an investigation of the gene coding for Cu, Zn superoxide dismutase (Sod) in Drosophila melanogaster seeking to understand the enzyme`s role in cell protection against ionizing radiation are reported. Components of the investigation include molecular characterization of the gene; measuring the response of different genotypes to increasing levels of radiation; and investigation of the processes that maintain the Sod polymorphism in populations. While two alleles, S and F, are commonly found at the Sod locus in natural populations of D. melanogaster we have isolated from a natural population a null (CA1) mutant that yields only 3.5% of normal SOD activity. The S, F, and CA1 alleles provide a model system to investigate SOD-dependent radioresistance, because each allele yields different levels of SOD, so that S > F >> CAl. The radioprotective effects of SOD can be established by showing protective effects for the various genotypes that correspond to those inequalities. Because the allele variants studied are derived from natural populations, the proposed investigation avoids problems that arise when mutants obtained my mutagenesis are used. Moreover, each allele is studied in multiple genetic backgrounds, so that we correct for effects attributable to other loci by randomizing these effects.

  12. Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Hui-Wen Chiu

    Full Text Available Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells and PC-3 cells (androgen-independent human prostate cancer cells were used to investigate the anti-cancer effects of ionizing radiation (IR combined with arsenic trioxide (ATO and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer.

  13. Sensitivity of aerosol optical thickness and aerosol direct radiative effect to relative humidity

    Directory of Open Access Journals (Sweden)

    H. Bian

    2008-07-01

    Full Text Available We present a sensitivity study on the effects of spatial and temporal resolution of atmospheric relative humidity (RH on calculated aerosol optical thickness (AOT and the aerosol direct radiative effects (DRE in a global model. Using the same aerosol fields simulated in the Global Modeling Initiative (GMI model, we find that, on a global average, the calculated AOT from RH in 1° latitude by 1.25° longitude spatial resolution is 11% higher than that in 2° by 2.5° resolution, and the corresponding DRE at the top of the atmosphere is 8–9% higher for total aerosols and 15% higher for only anthropogenic aerosols in the finer spatial resolution case. The difference is largest over surface escarpment regions (e.g. >200% over the Andes Mountains where RH varies substantially with surface terrain. The largest zonal mean AOT difference occurs at 50–60°N (16–21%, where AOT is also relatively larger. A similar increase is also found when the time resolution of RH is increased. This increase of AOT and DRE with the increase of model resolution is due to the highly non-linear relationship between RH and the aerosol mass extinction efficiency (MEE at high RH (>80%. Our study suggests that caution should be taken in a multi-model comparison (e.g. AeroCom since the comparison usually deals with results coming from different spatial/temporal resolutions.

  14. Sensitization of radiation (UV and gamma) induced DNA damage by halogenated bi-benzimidazole derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Petronella, N. [The University of Melbourne, Parkville, VIC (Australia). Department of Chemistry]|[Peter McCallum Cancer Institute, Melbourne, VIC (Australia); Cooper, R. [The University of Melbourne, Parkville, VIC (Australia). Department of Chemistry; Martin, R.F. [Peter McCallum Cancer Institute, Melbourne, VIC (Australia)

    1998-12-31

    Full text: In this study, an investigation was made into the photochemistry and radiation chemistry of ortho-Iodo Hoechst and meta-Iodo Hoechst. These compounds are related to the commercially available dye Hoechst 33258 and are being developed for potential use as radiosensitizers. An efficiency estimate of the number of dehalogenation events required to generate a DNA strand break was determined by quantitating relative yields of DNA strand breakage and ligand dehalogenation. DNA damage was assayed by agarose gel electrophoresis. A method was developed to separate reaction products from DNA after irradiation so that reaction products could be identified and dehalogenation quantitated by HPLC. From steady state photolysis investigations under aqueous conditions it was determined that there is a ten fold difference in quantum efficiency for the DNA strand breakage process. This is due to ortho-Iodo Hoechst having a ten times greater quantum yield of dehalogenation than meta-Iodo Hoechst. Thus it is interesting to note that both compounds require the same number of radical species to generate a DNA strand break. The addition of ethanol (a radical scavenger) to the solvent system, reduces: (1) yields of dehalogenation, (2) yields of DNA strand breakage and (3) the DNA strand breakage efficiencies of both analogues. However unlike the aqueous situation, in the presence of a radical scavenger the radical generated from ortho-Iodo Hoechst is more efficient than the meta-Iodo Hoechst generated radical at attacking and damaging DNA. Thus the radical generated from meta-Iodo Hoechst is more susceptible to interference from a radical scavenger than the ortho-Iodo Hoechst based radical. Steady state gamma radiolysis investigations have found that sensitization is only observed for ortho-Iodo Hoechst in a solvent system where hydroxyl radicals are scavenged by ethanol. The addition of e{sup -}{sub (aq)} scavengers (nitrate and oxygen) have demonstrated that sensitization is

  15. Effect of radiation-sensitive mutations and mutagens/carcinogens on bacterial recombination and mutagenesis. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Matney, T.S.

    1978-01-01

    Progress is reported on effects of temperature sensitive DNA-initiation mutation in E. coli K-12 mutants; the use of Bacillus subtilis transforming system as an in vitro mutagenesis system; characteristics of the E. coli lysogen used to test the permeability to polycyclic aromatic hydrocarbons; and the genetic toxicology of gentian violet. (PCS)

  16. Genetic sex determination in Astatotilapia calliptera, a prototype species for the Lake Malawi cichlid radiation

    Science.gov (United States)

    Peterson, Erin N.; Cline, Maggie E.; Moore, Emily C.; Roberts, Natalie B.; Roberts, Reade B.

    2017-06-01

    East African cichlids display extensive variation in sex determination systems. The species Astatotilapia calliptera is one of the few cichlids that reside both in Lake Malawi and in surrounding waterways. A. calliptera is of interest in evolutionary studies as a putative immediate outgroup species for the Lake Malawi species flock and possibly as a prototype ancestor-like species for the radiation. Here, we use linkage mapping to test association of sex in A. calliptera with loci that have been previously associated with genetic sex determination in East African cichlid species. We identify a male heterogametic XY system segregating at linkage group (LG) 7 in an A. calliptera line that originated from Lake Malawi, at a locus previously shown to act as an XY sex determination system in multiple species of Lake Malawi cichlids. Significant association of genetic markers and sex produce a broad genetic interval of approximately 26 megabases (Mb) using the Nile tilapia genome to orient markers; however, we note that the marker with the strongest association with sex is near a gene that acts as a master sex determiner in other fish species. We demonstrate that alleles of the marker are perfectly associated with sex in Metriaclima mbenjii, a species from the rock-dwelling clade of Lake Malawi. While we do not rule out the possibility of other sex determination loci in A. calliptera, this study provides a foundation for fine mapping of the cichlid sex determination gene on LG7 and evolutionary context regarding the origin and persistence of the LG7 XY across diverse, rapidly evolving lineages.

  17. Photosynthesis of two Arctic macroalgae under different ambient radiation levels and their sensitivity to enhanced UV radiation

    NARCIS (Netherlands)

    Brouwer, P.E.M.; Bischof, K.; Hanelt, D.; Kromkamp, J.C.

    2000-01-01

    The change in optimal quantum efficiency (F-v/F-m) of the Arctic species Laminaria saccharina and Palmaria palmata was investigated in a long-term experiment in situ under different radiation levels during the summer of 1997 in the Kongsfjord (Ny-Alesund, Spitsbergen, Norway, 78 degrees 55.5'N, 11

  18. Photosynthesis of two Arctic macroalgae under different ambient radiation levels and their sensitivity to enhanced UV radiation

    NARCIS (Netherlands)

    Brouwer, P.E.M.; Bischof, K.; Hanelt, D.; Kromkamp, J.C.

    2000-01-01

    The change in optimal quantum efficiency (F-v/F-m) of the Arctic species Laminaria saccharina and Palmaria palmata was investigated in a long-term experiment in situ under different radiation levels during the summer of 1997 in the Kongsfjord (Ny-Alesund, Spitsbergen, Norway, 78 degrees 55.5'N, 11 d

  19. Genetic and somatic radiation doses in radiotherapy of inflammatory and degenerative diseases of bones, joints and soft parts

    Energy Technology Data Exchange (ETDEWEB)

    Kirsch, M.; Keinert, K.; Schumann, E. (Medizinische Akademie, Erfurt (German Democratic Republic). Radiologische Klinik)

    1983-01-01

    Dose measurements were performed in several body regions of patients suffering from inflammatory degenerative diseases (humeral epicondylitis, humeroscapular periarthritis, gonarthrosis, axillary hidradenitis, rheumatoid arthritis, coxarthrosis, parotitis). The problem of the radiation induction of neoplasms is predominant concerning somatic as well as genetic risk, discussed by example of the most frequently occurring organ cancer. Compared to the rate of breast cancer in the highly developed industrial states (5,000 to 6,000 cancers/100,000 women) the 'radiation induction' calculated according to a mathematical model of ICRP 26 (1.25 cases of death for breast cancers/100,000 women following for example irradiation of epicondylitis) is behind several powers of ten and not demonstrable. The genetic radiation exposure is also low. Derived from the measurements it is wrong to give up reliable and approved indications of radiotherapy of non-malignant diseases because of unfounded radiophobia.

  20. Radiation exposure in the remote period after the Chernobyl accident caused oxidative stress and genetic effects in Scots pine populations

    Science.gov (United States)

    Volkova, Polina Yu.; Geras'Kin, Stanislav A.; Kazakova, Elizaveta A.

    2017-02-01

    Even 30 years after the Chernobyl accident, biological effects of irradiation are observed in the chronically exposed Scots pine populations. Chronic radiation exposure at dose rates above 50 mGy•yr-1 caused oxidative stress and led to the increase of antioxidants concentrations in these populations. Genetic variability was examined for 6 enzymes and 14 enzymatic loci of 6 Scots pine populations. Dose rates over 10 mGy•yr-1 caused the increased frequency of mutations and changes in genetic structure of Scots pine populations. However, the same dose rates had no effect on enzymatic activities. The results indicate that even relatively low dose rates of radiation can be considered as an ecological factor which should be taken into account for ecological management and radiation protection of biota species.

  1. Locally Targeted Delivery of a Micron-Size Radiation Therapy Source Using Temperature-Sensitive Hydrogel

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yusung, E-mail: yusung-kim@uiowa.edu [Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa (United States); Seol, Dong Rim [Department of Orthopaedic Surgery, The University of Iowa, Iowa City, Iowa (United States); Mohapatra, Sucheta [Department of Biomedical Engineering, The University of Iowa, Iowa City, Iowa (United States); Sunderland, John J. [Department of Radiology, The University of Iowa, Iowa City, Iowa (United States); Schultz, Michael K. [Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa (United States); Department of Radiology, The University of Iowa, Iowa City, Iowa (United States); Domann, Frederick E. [Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa (United States); Department of Surgery, The University of Iowa, Iowa City, Iowa (United States); Lim, Tae-Hong [Department of Biomedical Engineering, The University of Iowa, Iowa City, Iowa (United States)

    2014-04-01

    Purpose: To propose a novel radiation therapy (RT) delivery modality: locally targeted delivery of micron-size RT sources by using temperature-sensitive hydrogel (RT-GEL) as an injectable vehicle. Methods and Materials: Hydrogel is a water-like liquid at room temperature but gels at body temperature. Two US Food and Drug Administration-approved polymers were synthesized. Indium-111 (In-111) was used as the radioactive RT-GEL source. The release characteristics of In-111 from polymerized RT-GEL were evaluated. The injectability and efficacy of RT-GEL delivery to human breast tumor were tested using animal models with control datasets of RT-saline injection. As proof-of-concept studies, a total of 6 nude mice were tested by injecting 4 million tumor cells into their upper backs after a week of acclimatization. Three mice were injected with RT-GEL and 3 with RT-saline. Single-photon emission computed tomography (SPECT) and CT scans were performed on each mouse at 0, 24, and 48 h after injection. The efficacy of RT-GEL was determined by comparison with that of the control datasets by measuring kidney In-111 accumulation (mean nCi/cc), representing the distant diffusion of In-111. Results: RT-GEL was successfully injected into the tumor by using a 30-gauge needle. No difficulties due to polymerization of hydrogel during injection and intratumoral pressure were observed during RT-GEL injection. No back flow occurred for either RT-GEL or RT-saline. The residual tumor activities of In-111 were 49% at 24 h (44% at 48 h, respectively) for RT-GEL and 29% (22%, respectively) for RT-saline. Fused SPECT-CT images of RT-saline showed considerable kidney accumulation of In-111 (2886%, 261%, and 262% of RT-GEL at 0, 24, and 48 h, respectively). Conclusions: RT-GEL was successfully injected and showed much higher residual tumor activity: 170% (200%, respectively), than that of RT-saline at 24 h (48 h, respectively) after injection with a minimal accumulation of In-111 to the

  2. Radiation induced chemotherapy sensitization in trimodality therapy of stage 3 non small cell lung cancer. A preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Takita, H. [Millard Fillmore Hospital, Buffalo (United States); Shin, K. H. [CCS Oncology Center, Kenmore, NY, (United States)

    2000-12-01

    The overall cure rate of locally advanced non-small cell lung carcinoma (NSCLC) remains poor. Although there have been encouraging reports of preoperative use of chemotherapy, more recent trend is the trimodal approach of radiation, chemo, and surgical-therapies. With the trimodal therapy, increased tumor response and resectability are reported, however, there are increased treatment related side effects. It was observed that a relatively small dose of radiation given prior to induction chemotherapy greatly enhanced the tumor response to the chemotherapy without increased toxicity. A total of 18 patients (8 3. A and 10 3.B) were initially given 20 Gy of radiation therapy in 10 fractions and then received 2 courses of Taxol combination chemotherapy. The overall response rate was 83% (15/18) and 13 out of 18 patients underwent surgery. There was one postoperative death (not therapy related). It is speculated that the small dose of radiation therapy may have sensitized the tumor to subsequent chemotherapy, and it was suggested a new hypothesis of radiation therapy induced chemotherapy sensitization.

  3. The ESA IBER-3 Project- Gene Expression and Cytokine Monitoring for Biodosimetry and Radiation Sensitivity Screening (GYMBRASS)

    Science.gov (United States)

    Quintens, Roel; Moreels, Marjan; Tabury, Kevin; Macaeva, Ellina; Michaux, Arlette; Averbeck, Nicole; Chouker, Alexander; Baatout, Sarah

    2013-02-01

    In order to better understand and define the biological risks of cosmic radiation, it is important to identify biomarkers for exposure and for predicting individual sensitivity to radiation-induced biological damage. Our study aims at identifying new biomarkers for radiation exposure to low and high linear energy transfer (LET) radiation. We will focus on the use of gene, exon and/or cytokine expression signatures in human peripheral blood mononuclear cells (PBMCs) as biomarkers. These data will be integrated with those from DNA double strand break (DSB) repair kinetics in order to identify biomarkers of individual radiosensitivity. Our preliminary data indicate that gene/exon expression signatures can be used to accurately predict radiation doses of below 0.1 Gy (X-rays). Additionally, specific exon signatures may further enhance the sensitivity of prediction. Also, we found that there is a very strong overlap between gene expression changes in response to high doses (1 Gy) of low (X-ray) and high-LET (C-ions; 50-75 keV/μm) irradiation. However, we also identified genes that only responded to either X-rays or C-ions, suggesting that LET-specific gene signatures may also be identified.

  4. Estimating the risks of cancer mortality and genetic defects resulting from exposures to low levels of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Buhl, T.E.; Hansen, W.R.

    1984-05-01

    Estimators for calculating the risk of cancer and genetic disorders induced by exposure to ionizing radiation have been recommended by the US National Academy of Sciences Committee on the Biological Effects of Ionizing Radiations, the UN Scientific Committee on the Effects of Atomic Radiation, and the International Committee on Radiological Protection. These groups have also considered the risks of somatic effects other than cancer. The US National Council on Radiation Protection and Measurements has discussed risk estimate procedures for radiation-induced health effects. The recommendations of these national and international advisory committees are summarized and compared in this report. Based on this review, two procedures for risk estimation are presented for use in radiological assessments performed by the US Department of Energy under the National Environmental Policy Act of 1969 (NEPA). In the first procedure, age- and sex-averaged risk estimators calculated with US average demographic statistics would be used with estimates of radiation dose to calculate the projected risk of cancer and genetic disorders that would result from the operation being reviewed under NEPA. If more site-specific risk estimators are needed, and the demographic information is available, a second procedure is described that would involve direct calculation of the risk estimators using recommended risk-rate factors. The computer program REPCAL has been written to perform this calculation and is described in this report. 25 references, 16 tables.

  5. Mesenchymal stem cells are sensitive to treatment with kinase inhibitors and ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nicolay, Nils H.; Debus, Juergen; Huber, Peter E. [Heidelberg University Hospital, Department of Radiation Oncology, Heidelberg (Germany); German Cancer Research Center (dkfz), Department of Molecular and Radiation Oncology, Heidelberg (Germany); Sommer, Eva; Lopez Perez, Ramon; Wirkner, Ute [German Cancer Research Center (dkfz), Department of Molecular and Radiation Oncology, Heidelberg (Germany); Bostel, Tilman [Heidelberg University Hospital, Department of Radiation Oncology, Heidelberg (Germany); Ho, Anthony D.; Saffrich, Rainer [Heidelberg University Hospital, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Lahn, Michael [Lilly Research Laboratories, Oncology Early Clinical Investigation, Indianapolis, IN (United States)

    2014-11-15

    Mesenchymal stem cells (MSCs) can regenerate damaged tissues and may therefore be of importance for normal tissue repair after cancer treatment. Small molecule receptor kinase inhibitors (RKIs) have recently been introduced into cancer treatment. However, the influence of these drugs - particularly in combination with radiotherapy - on the survival of MSCs is largely unknown. The sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells to small molecule kinase inhibitors of the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and transforming growth factor β (TGFβ) receptors, as well to inhibitors of c-Kit, was examined in combination with ionizing radiation (IR); cell survival and proliferation were assessed. Expression patterns of different kinase receptors and ligands were investigated using gene arrays. MSCs were highly sensitive to the tyrosine kinase inhibitors SU14816 (imatinib) and SU11657 (sunitinib), but showed only moderate sensitivity to the selective TGFβ receptor 1 inhibitor LY2109761. Primary adult human fibroblasts were comparably resistant to all three inhibitors. The addition of IR had an additive or supra-additive effect in the MSCs, but this was not the case for differentiated fibroblasts. Proliferation was markedly reduced in MSCs following kinase inhibition, both with and without IR. Gene expression analysis revealed high levels of the PDGF α and β receptors, and lower levels of the TGFβ receptor 2 and Abl kinase. IR did not alter the expression of kinase receptors or their respective ligands in either MSCs or adult fibroblasts. These data show that MSCs are highly sensitive to RKIs and combination treatments incorporating IR. Expression analyses suggest that high levels of PDGF receptors may contribute to this effect. (orig.) [German] Mesenchymale Stammzellen (MSCs) koennen die Geweberegeneration unterstuetzen und haben daher moeglicherweise eine Rolle bei der Reparatur

  6. Radiation-induced bystander effects enhanced by elevated sodium chloride through sensitizing cells to bystander factors

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Lingyan; Han Wei; Chen Shaopeng; Zhao Ye; Jiang Erkang; Bao Lingzhi; Pei Bei; Yang Gen; Zhao Guoping; Wang Jun; Xu An [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031, Anhui (China); Wu Lijun [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031, Anhui (China)], E-mail: ljw@ipp.ac.cn

    2008-09-26

    Radiation-induced bystander effects (RIBE) have been demonstrated to occur widely in various cell lines. However, very little data is available on the genotoxic effects of RIBE combined with other factor(s). We reported previously that with a low dose of {alpha}-particle irradiation, the fraction of {gamma}-H2AX foci-positive cells in non-irradiated bystander cells was significantly increased under elevated NaCl culture conditions. In this study, we further investigated the functional role of NaCl in the enhancement of RIBE using a specially designed co-culture system and micronucleus (MN) test. It was shown that the MN frequency was not increased significantly by elevated NaCl (9.0 g/L) alone or by medium exposure. However, with 1.0 cGy {alpha}-particle irradiation, the induced MN frequency increased significantly in both irradiated and non-irradiated bystander regions. Additional studies showed that elevated NaCl made the non-irradiated bystander cells more vulnerable to bystander factors. Furthermore, it was found that the induced MN frequency in cells both in irradiated and non-irradiated bystander regions was weakened when the hypertonic medium was changed to normotonic medium for 2 h before irradiation. Such observations were quite similar to the co-effect of NaCl and hydrogen peroxide (H{sub 2}O{sub 2}), indicating that elevated NaCl might sensitize non-irradiated cells to bystander factors-induced oxidative stress.

  7. Sensitivity of aerosol optical thickness and aerosol direct radiative effect to relative humidity

    Directory of Open Access Journals (Sweden)

    H. Bian

    2009-04-01

    Full Text Available We present a sensitivity study of the effects of spatial and temporal resolution of atmospheric relative humidity (RH on calculated aerosol optical thickness (AOT and the aerosol direct radiative effects (DRE in a global model. We carry out different modeling experiments using the same aerosol fields simulated in the Global Modeling Initiative (GMI model at a resolution of 2° latitude by 2.5° longitude, using time-averaged fields archived every three hours by the Goddard Earth Observation System Version 4 (GEOS-4, but we change the horizontal and temporal resolution of the relative humidity fields. We find that, on a global average, the AOT calculated using RH at a 1°×1.25° horizontal resolution is 11% higher than that using RH at a 2°×2.5° resolution, and the corresponding DRE at the top of the atmosphere is 8–9% and 15% more negative (i.e., more cooling for total aerosols and anthropogenic aerosol alone, respectively, in the finer spatial resolution case. The difference is largest over surface escarpment regions (e.g. >200% over the Andes Mountains where RH varies substantially with surface terrain. The largest zonal mean AOT difference occurs at 50–60° N (16–21%, where AOT is also relatively larger. A similar impact is also found when the time resolution of RH is increased. This increase of AOT and aerosol cooling with the increase of model resolution is due to the highly non-linear relationship between RH and the aerosol mass extinction efficiency (MEE at high RH (>80%. Our study is a specific example of the uncertainty in model results highlighted by multi-model comparisons such as AeroCom, and points out one of the many inter-model differences that can contribute to the overall spread among models.

  8. Downregulation of MicroRNA-330 Correlates with the Radiation Sensitivity and Prognosis of Patients with Brain Metastasis from Lung Cancer.

    Science.gov (United States)

    Jiang, Li-Peng; Zhu, Zhi-Tu; Zhang, Yue; He, Chun-Yan

    2017-08-16

    The present study sought to explore the role of microRNA-330 (miR-330) in predicting the radiation response and prognosis of patients with brain metastasis (BM) from lung cancer (LC). Patients with BM from LC were identified and classified into radiation-sensitive and radiation-resistant groups according to the overall survival rate, local and distant recurrence rate after conventional whole-brain radiation therapy. Quantitative realtime polymerase chain reaction (qRT-PCR) was used to detect miR-330 expression in serum. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic value of miR-330 for the radiation sensitivity of brain metastasis from LC. Related clinical factors for radiation sensitivity were assessed by logistic regression analysis, and a survival analysis was conducted using COX regression and the Kaplan-Meier method. MiR-330 exhibited lower expression in the radiation-sensitive group than in the radiation-resistant group. The area under the ROC curve of miR-330 for predicting radiation sensitivity was 0.898 (optimal cut-off value, 0.815), with a sensitivity of 71.7% and a specificity of 90.1%. After radiation therapy, patients with low miR-330 expression, compared to patients with high miR-330 expression, displayed a lower survival rate and a median survival time. MiR-330 expression was correlated with extracranial metastasis, maximum BM diameter, tumor-node-metastasis (TNM) stage and node (N) stage. Logistic regression and COX regression analyses revealed that extracranial metastasis, TNM stage, N stage and miR-330 expression were factors that influenced both radiation sensitivity and individual prognostic factors in patients with BM from LC. These findings indicate that the downregulation of miR-330 correlates with radiation sensitivity and poor prognosis in patients with BM from LC. © 2017 The Author(s). Published by S. Karger AG, Basel.

  9. A new measurement for the revised reinforcement sensitivity theory: psychometric criteria and genetic validation

    Directory of Open Access Journals (Sweden)

    Martin eReuter

    2015-03-01

    Full Text Available Jeffrey Gray’s Reinforcement Sensitivity Theory (RST represents one of the most influential biologically-based personality theories describing individual differences in approach and avoidance tendencies. The most prominent self-report inventory to measure individual differences in approach and avoidance behavior to date is the BIS/BAS scale by Carver & White (1994. As Gray & McNaughton (2000 revised the RST after its initial formulation in the 1970/80s, and given the Carver & White measure is based on the initial conceptualization of RST, there is a growing need for self-report inventories measuring individual differences in the revised behavioral inhibition system (BIS, behavioral activation system (BAS and the fight, flight, freezing system (FFFS. Therefore, in this paper we present a new questionnaire measuring individual differences in the revised constructs of the BIS, BAS and FFFS in N = 1814 participants (German sample. An English translated version of the new measure is also presented and tested in N = 299 English language participants. A large number of German participants (N = 1090 also filled in the BIS/BAS scales by Carver & White (1994 and the correlations between these measures are presented. Finally, this same subgroup of participants provided buccal swaps for the investigation of the arginine vasopressin receptor 1a (AVPR1a gene. Here, a functional genetic polymorphism (rs11174811 on the AVPR1a gene was shown to be associated with individual differences in both the revised BIS and classic BIS dimensions.

  10. Mass Rearing of Temperature Sensitive Genetic Sexing Strains in the Mediterranean Fruit Fly (Ceratitis Capitata)

    Energy Technology Data Exchange (ETDEWEB)

    Caceres, C. [FAO/IAEA Agriculture and Biotechnology Laboratory, Entomology Unit, A-2444 Seibersdorf (Austria)]. E-mail: c.caceres@iaea.org

    2002-09-15

    Genetic sexing strains (GSS) based on the temperature sensitive lethal(tsl) mutation are being used to produce sterile male medflies for large scale sterile insect technique (SIT) programmes for this pest. The use of male-only strains increases the overall efficiency of the technique. Currently more than 1.4 billion sterile male-only pupae are produced per week in different facilities around the world. Due to the mutations used to construct these strains, that is, translocations and selectable markers, they require different and more careful mass rearing procedures than do bisexual strains (BSS). The basic rearing technology has been developed and can be used to produce only males on a predictable basis to a level of 99.9% accuracy. If specific rearing procedures are followed, then tsl-based GSS has a rearing efficiency that is equal to that of a BSS and it is already know that males produced by the tsl-based GSS are of equal quality to males produced by BSS. Based on current rearing technology the cost of production of male pupae is about the same for both types of strain. This is due to the large colony that is required for the tsl-based GSS. This paper discusses the considerations that need to be taken into account during mass rearing of GSS and identifies the most efficient production processes that are currently available. (author)

  11. A new measure for the revised reinforcement sensitivity theory: psychometric criteria and genetic validation.

    Science.gov (United States)

    Reuter, Martin; Cooper, Andrew J; Smillie, Luke D; Markett, Sebastian; Montag, Christian

    2015-01-01

    Jeffrey Gray's Reinforcement Sensitivity Theory (RST) represents one of the most influential biologically-based personality theories describing individual differences in approach and avoidance tendencies. The most prominent self-report inventory to measure individual differences in approach and avoidance behavior to date is the BIS/BAS scale by Carver and White (1994). As Gray and McNaughton (2000) revised the RST after its initial formulation in the 1970/80s, and given the Carver and White measure is based on the initial conceptualization of RST, there is a growing need for self-report inventories measuring individual differences in the revised behavioral inhibition system (BIS), behavioral activation system (BAS) and the fight, flight, freezing system (FFFS). Therefore, in this paper we present a new questionnaire measuring individual differences in the revised constructs of the BIS, BAS and FFFS in N = 1814 participants (German sample). An English translated version of the new measure is also presented and tested in N = 299 English language participants. A large number of German participants (N = 1090) also filled in the BIS/BAS scales by Carver and White (1994) and the correlations between these measures are presented. Finally, this same subgroup of participants provided buccal swaps for the investigation of the arginine vasopressin receptor 1a (AVPR1a) gene. Here, a functional genetic polymorphism (rs11174811) on the AVPR1a gene was shown to be associated with individual differences in both the revised BIS and classic BIS dimensions.

  12. EVALUATION OF THE CLINICAL USE OF HYPOXIC CELL SENSITIZERS IN RADIATION THERAPY OF MALIGNANT EPITHELIAL SKIN TUMORS

    Directory of Open Access Journals (Sweden)

    P. Yu. Polyakov

    2015-01-01

    Full Text Available Aim: To increase the efficacy of radiation therapy of malignant epithelial cell skin neoplasms with the use of radiation sensitizers of hypoxic tumor cells.Materials and methods: The study was performed in 517 patients with basal cell (n = 361 and squamous cell (n = 156 skin cancer, 274 (53% of whom had T2 and 243 (47%, T3 tumors. Patients with locally advanced and metastatic tumors were excluded from the study. The following treatment modalities were used: distant gamma-therapy, short-distance radiation therapy and combined radiation therapy with the use of non-conventional dose fractioning at total local doses equal to 72–73 Gr. The sensibilization of hypoxic tumor cells to radiation therapy with metronidazole was done by targeted delivery of the drug to the tumor by means of topical application of Coletex-M drapes impregnated with metronidazole in a high concentration (up to 20 mcg/cm². The second method of radiosensibilization of hypoxic tumor cells was based on a preliminary use of low intensity laser radiation onto the tumor. As a source this radiation, a helium neon laser was used with the power of up to 12 mVt and the wave length of 0.63 to 0.89 mcm, duration of sessions from 3 to 15 minutes. The control group comprised 192 skin cancer patients who underwent radiation therapy without the use of radiation sensitizers. Results: The use of metronidazole and low intensity laser radiation within the radiation therapy of T3 skin cancer patients, compared to the treatment without the radiation modifiers, significantly improved the immediate cure rates (full tumor regression at 1 to 1.5 months after completion of radiation from 75.5 ± 3.1% to 89.2 ± 1.9% (р < 0.05. In the group with basal cell skin cancer that underwent radiation therapy combined with metronidazole, there was an association of its radio-modifying effect and tumor size. Short-distance roentgenotherapy of patients with T2 basal cell skin cancer and tumor size of < 4 cm was

  13. Development of a model system to study leukotriene-induced modification of radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Walden, T.L.; Holahan, E.V.; Catravas, G.N.

    1986-01-01

    Leukotrienes (LT) are an important class of biological mediators, for which no information exists concerning their synthesis following a radiation insult, or on their ability to modify cellular response to a subsequent radiation exposure. LT are derived from arachidonic acid, as are prostaglandins, although by a separate enzyme system. Prostaglandins are able to modify radiosensitivity of mammalian cells in vivo and in vitro. In addition, the cytoprotective effect induced by prostaglandins may have significance in cancer therapy since certain breast cancers which secrete elevated levels of prostaglandins are more resistant to therapy than similar tumors without the prostaglandin elevation. The objective of this study was to define a model system in which the metabolic fate of the LT could be monitored, and the effort of LT on the ionizing radiation sensitivity of mammalian cells in vitro could also be characterized.

  14. Using synchrotron radiation angiography with a highly sensitive detector to identify impaired peripheral perfusion in rat pulmonary emphysema

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Hiromichi [University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Matsushita, Shonosuke, E-mail: shomatsu@md.tsukuba.ac.jp [University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Tsukuba University of Technology, Tsukuba, Ibaraki 305-8521 (Japan); Hyodo, Kazuyuki [High Energy Accelerator Research Organization, KEK, Tsukuba, Ibaraki 305-0801 (Japan); Sato, Yukio; Sakakibara, Yuzuru [University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)

    2013-03-01

    Synchrotron radiation angiography with a HARP detector made it possible to evaluate impaired pulmonary microcirculation in pulmonary emphysema by means of high sensitivity. Owing to limitations in spatial resolution and sensitivity, it is difficult for conventional angiography to detect minute changes of perfusion in diffuse lung diseases, including pulmonary emphysema (PE). However, a high-gain avalanche rushing amorphous photoconductor (HARP) detector can give high sensitivity to synchrotron radiation (SR) angiography. SR angiography with a HARP detector provides high spatial resolution and sensitivity in addition to time resolution owing to its angiographic nature. The purpose of this study was to investigate whether this SR angiography with a HARP detector could evaluate altered microcirculation in PE. Two groups of rats were used: group PE and group C (control). Transvenous SR angiography with a HARP detector was performed and histopathological findings were compared. Peak density of contrast material in peripheral lung was lower in group PE than group C (p < 0.01). The slope of the linear regression line in scattering diagrams was also lower in group PE than C (p < 0.05). The correlation between the slope and extent of PE in histopathology showed significant negative correlation (p < 0.05, r = 0.61). SR angiography with a HARP detector made it possible to identify impaired microcirculation in PE by means of its high spatial resolution and sensitivity.

  15. In Vitro Studies on Space Radiation-Induced Delayed Genetic Responses: Shielding Effects

    Science.gov (United States)

    Kadhim, Munira A.; Green, Lora M.; Gridley, Daila S.; Murray, Deborah K.; Tran, Da Thao; Andres, Melba; Pocock, Debbie; Macdonald, Denise; Goodhead, Dudley T.; Moyers, Michael F.

    2003-01-01

    Understanding the radiation risks involved in spaceflight is of considerable importance, especially with the long-term occupation of ISS and the planned crewed exploration missions. Several independent causes may contribute to the overall risk to astronauts exposed to the complex space environment, such as exposure to GCR as well as SPES. Protons and high-Z energetic particles comprise the GCR spectrum and may exert considerable biological effects even at low fluence. There are also considerable uncertainties associated with secondary particle effects (e.g. HZE fragments, neutrons etc.). The interaction of protons and high-LET particles with biological materials at all levels of biological organization needs to be investigated fully in order to establish a scientific basis for risk assessment. The results of these types of investigation will foster the development of appropriately directed countermeasures. In this study, we compared the biological responses to proton irradiation presented to the target cells as a monoenergetic beam of particles of complex composition delivered to cells outside or inside a tissue phantom head placed in the United States EVA space suit helmet. Measurements of chromosome aberrations, apoptosis, and the induction of key proteins were made in bone marrow from CBA/CaJ and C57BL/6 mice at early and late times post exposure to radiation at 0, 0.5, 1 and 2 Gy while inside or outside of the helmet. The data showed that proton irradiation induced transmissible chromosomal/genomic instability in haematopoietic stem cells in both strains of mice under both irradiation conditions and especially at low doses. Although differences were noted between the mouse strains in the degree and kinetics of transforming growth factor-beta 1 and tumor necrosis factor-alpha secretion, there were no significant differences observed in the level of the induced instability under either radiation condition, or for both strains of mice. Consequently, when

  16. Highly sensitive detection of ionizing radiations by a photoluminescent uranyl organic framework

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Jian; Wang, Yaxing; Liu, Wei; Yin, Xuemiao; Chen, Lanhua; Diwu, Juan; Chai, Zhifang; Wang, Shuao [School for Radiological and interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Zou, Youming [High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui (China); Albrecht-Schmitt, Thomas E. [Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL (United States); Liu, Guokui [Chemical Sciences and Engineering Division, Argonne National Laboratory, Argonne, IL (United States)

    2017-06-19

    Precise detection of low-dose X- and γ-radiations remains a challenge and is particularly important for studying biological effects under low-dose ionizing radiation, safety control in medical radiation treatment, survey of environmental radiation background, and monitoring cosmic radiations. We report here a photoluminescent uranium organic framework, whose photoluminescence intensity can be accurately correlated with the exposure dose of X- or γ-radiations. This allows for precise and instant detection of ionizing radiations down to the level of 10{sup -4} Gy, representing a significant improvement on the detection limit of approximately two orders of magnitude, compared to other chemical dosimeters reported up to now. The electron paramagnetic resonance analysis suggests that with the exposure to radiations, the carbonyl double bonds break affording oxo-radicals that can be stabilized within the conjugated uranium oxalate-carboxylate sheet. This gives rise to a substantially enhanced equatorial bonding of the uranyl(VI) ions as elucidated by the single-crystal structure of the γ-ray irradiated material, and subsequently leads to a very effective photoluminescence quenching through phonon-assisted relaxation. The quenched sample can be easily recovered by heating, enabling recycled detection for multiple runs. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  17. Radiation sensitivity of silicon imaging sensors on missions to the outer planets.

    Science.gov (United States)

    Brucker, G. J.; Cope, A. D.

    1972-01-01

    Review of the results of an investigation of the magnitude of the degradation effects of radiation on the operating characteristics of camera tubes using silicon diode arrays in the space environment, and discussion of the radiation damage mechanisms concerned. The effects produced by bombardment of bare-silicon-diode arrays or vidicon tubes with 85-kV X rays, Cobalt 60 gamma rays, 1 MeV and 11 MeV electrons, 3 MeV and 142 MeV protons, and reactor neutrons are presented. Interference effects produced by radiation bombardment during operation of television tubes are investigated, and limiting fluxes of electrons and protons are given.

  18. Severe mitochondrial damage associated with low-dose radiation sensitivity in ATM- and NBS1-deficient cells.

    Science.gov (United States)

    Shimura, Tsutomu; Kobayashi, Junya; Komatsu, Kenshi; Kunugita, Naoki

    2016-01-01

    Low-dose radiation risks remain unclear owing to a lack of sufficient studies. We previously reported that low-dose, long-term fractionated radiation (FR) with 0.01 or 0.05 Gy/fraction for 31 d inflicts oxidative stress in human fibroblasts due to excess levels of mitochondrial reactive oxygen species (ROS). To identify the small effects of low-dose radiation, we investigated how mitochondria respond to low-dose radiation in radiosensitive human ataxia telangiectasia mutated (ATM)- and Nijmegen breakage syndrome (NBS)1-deficient cell lines compared with corresponding cell lines expressing ATM and NBS1. Consistent with previous results in normal fibroblasts, low-dose, long-term FR increased mitochondrial mass and caused accumulation of mitochondrial ROS in ATM- and NBS1-complemented cell lines. Excess mitochondrial ROS resulted in mitochondrial damage that was in turn recognized by Parkin, leading to mitochondrial autophagy (mitophagy). In contrast, ATM- and NBS1-deficient cells showed defective induction of mitophagy after low-dose, long-term FR, leading to accumulation of abnormal mitochondria; this was determined by mitochondrial fragmentation and decreased mitochondrial membrane potential. Consequently, apoptosis was induced in ATM- and NBS1-deficient cells after low-dose, long-term FR. Antioxidant N-acetyl-L-cysteine was effective as a radioprotective agent against mitochondrial damage induced by low-dose, long-term FR among all cell lines, including radiosensitive cell lines. In conclusion, we demonstrated that mitochondria are target organelles of low-dose radiation. Mitochondrial response influences radiation sensitivity in human cells. Our findings provide new insights into cancer risk estimation associated with low-dose radiation exposure.

  19. Relationship between chromatin structure and sensitivity to molecularly targeted auger electron radiation therapy.

    NARCIS (Netherlands)

    Terry, S.Y.A.; Vallis, K.A.

    2012-01-01

    PURPOSE: The open structure of euchromatin renders it susceptible to DNA damage by ionizing radiation (IR) compared with compact heterochromatin. The effect of chromatin configuration on the efficacy of Auger electron radiotherapy was investigated. METHODS AND MATERIALS: Chromatin structure was

  20. Relationships between vegetation indices, radiation absorption, and net photosynthesis evaluated by a sensitivity analysis

    Science.gov (United States)

    Choudhury, Bhaskar J.

    1987-01-01

    A two-stream approximation to the radiative-transfer equation is used to calculate the vegetation indices (simple ratio and normalized difference), the fraction of incident photosynthetically active radiation (PAR) absorbed by the canopy, and the daily mean canopy net photosynthesis under clear-sky conditions. The model calculations are tested against field observations over wheat, cotton, corn, and soybean. The relationships between the vegetation indices and radiation absorption or net photosynthesis are generally found to be curvilinear, and changes in the soil reflectance affected these relationships. The curvilinearity of the relationship between normalized differences and PAR absorption decreases as the magnitude of soil reflectance increases. The vegetation indices might provide the fractional radiation absorption with some a priori knowledge about soil reflectance. The relationship between the vegetation indices and net photosynthesis must be distinguished for C3 and C4 crops. Effects of spatial heterogeneity are discussed.

  1. Relationships between vegetation indices, radiation absorption, and net photosynthesis evaluated by a sensitivity analysis

    Science.gov (United States)

    Choudhury, Bhaskar J.

    1987-01-01

    A two-stream approximation to the radiative-transfer equation is used to calculate the vegetation indices (simple ratio and normalized difference), the fraction of incident photosynthetically active radiation (PAR) absorbed by the canopy, and the daily mean canopy net photosynthesis under clear-sky conditions. The model calculations are tested against field observations over wheat, cotton, corn, and soybean. The relationships between the vegetation indices and radiation absorption or net photosynthesis are generally found to be curvilinear, and changes in the soil reflectance affected these relationships. The curvilinearity of the relationship between normalized differences and PAR absorption decreases as the magnitude of soil reflectance increases. The vegetation indices might provide the fractional radiation absorption with some a priori knowledge about soil reflectance. The relationship between the vegetation indices and net photosynthesis must be distinguished for C3 and C4 crops. Effects of spatial heterogeneity are discussed.

  2. Use of a Combined Duplex PCR/Dot Blot Assay for more sensitive genetic characterization

    Directory of Open Access Journals (Sweden)

    Erin Curry

    2008-01-01

    Full Text Available A reliable and sensitive method of genetic analysis is necessary to detect multiple specific nucleic acid sequences from samples containing limited template. The most widely utilized method of specific gene detection, polymerase chain reaction (PCR, imparts inconsistent results when assessing samples with restricted template, especially in a multiplex reaction when copies of target genes are unequal. This study aimed to compare two methods of PCR product analysis, fluorescent detection following agarose gel electrophoresis or dot blot hybridization with chemiluminescent evaluation, in the detection of a single copy gene (SRY and a multicopy gene (β-actin. Bovine embryo sex determination was employed to exploit the limited DNA template available and the target genes of unequal copies. Primers were used either independently or together in a duplex reaction with purified bovine genomic DNA or DNA isolated from embryos. When used independently, SRY and β-actin products were detected on a gel at the equivalent of 4-cell or 1-cell of DNA, respectively; however, the duplex reaction produced visible SRY bands at the 256 cell DNA equivalent and β-actin products at the 64 cell DNA equivalent. Upon blotting and hybridization of the duplex PCR reaction, product was visible at the 1–4 cell DNA equivalent. Duplex PCR was also conducted on 186 bovine embryos and product was subjected to gel electrophoresis or dot-blot hybridization in duplicate. Using PCR alone, sex determination was not possible for 22.6% of the samples. Using PCR combined with dot blot hybridization, 100.0% of the samples exhibited either both the male specific and β-actin products or the β-actin signal alone, indicating that the reaction worked in all samples. This study demonstrated that PCR amplification followed by dot blot hybridization provided more conclusive results in the evaluation of samples with low DNA concentrations and target genes of unequal copies.

  3. Sensitivity of surface radiation budget to clouds over the Asian monsoon region

    Indian Academy of Sciences (India)

    S Balachandran; M Rajeevan

    2007-04-01

    Using the ISCCP–FD surface radiative flux data for the summer season (June to September) of the period 1992 to 1995, an analysis was done to understand the role of clouds on the surface radiation budget over the Asian monsoon region. At the top of atmosphere (TOA) of convective regions of the Asian monsoon region, the short wave radiative forcing (SWCRF) and long wave radiative forcing (LWCRF) do not cancel each other resulting in occurrence of the net cloud radiative forcing values exceeding −30W/m2. This type of imbalance between SWCRF and LWCRF at TOA is reflected down on the earth surface–atmosphere system also as an imbalance between surface netcloud radiative forcing (NETCRF) and atmospheric NETCRF. Based on the regression analysis of the cloud effects on the surface radiation budget quantities, it has been observed that generally, the variance explained by multiple type cloud data is 50% more than that of total cloud cover alone. In case of SWCRF, the total cloud cover can explain about 3% (7%) of the variance whereas the three cloud type descriptions of clouds can explain about 44% (42%) of the variance over oceanic (land) regions. This highlights the importance of cloud type information in explaining the variations of surface radiation budget. It has been observed that the clouds produce more cooling effect in short-wave band than the warming effect in long-wave band resulting in a net cooling at the surface. Over the oceanic region, variations in high cloud amount contribute more to variations in SWCRF while over land regions both middle and high cloud variations make substantial contributions to the variations in both SWCRF and NETCRF.

  4. Differential response of a sensitive and tolerant sugarbeet line to Cercospora beticola infection and UV-B radiation

    Energy Technology Data Exchange (ETDEWEB)

    Leval, M.W. [Novartis Seeds, landskrona (Sweden); Bornman, J.F. [Lund Univ., Dept. of Plant Physiology, Lund (Sweden)

    2000-07-01

    Increased ultraviolet-B (UV-B, 280-320 nm) radiation, due to depletion of stratospheric ozone, is an increasing threat to living organisms. Furthermore, increased ground level temperatures as a consequence of global warming may favour development of pathogens, such as Cercospora beticola, that thrive at high temperatures. This study evaluates the effect of combined UV stress and Cercospora leaf-spot disease on young sugarbeet plants (Beta vulgaris L.). An inoculum consisting of twelve European isolates of C. beticola Sacc. was used in the experiments. One Cercospora-sensitive and one Cercospora-tolerant sugarbeet line were analysed from growth regimes where plants were grown either under visible radiation alone or with supplemental UV-B. Photosynthetic pigments and partial reactions of photosynthesis, including potential yield and quantum yield under illumination, non-photochemical quenching (q{sub NPQ}) and photochemical quenching (q{sub P}), were measured to assess plant response. The combination of Cercospora a and supplemental UV-B radiation in the sensitive line resulted in a decreased photosynthetic efficiency, shown by q{sub NPQ}) and quantum yield under illumination as compared with that for either stress applied alone. The F{sub v}/F{sub m} was unchanged for plants subjected to UV-B radiation without infection, although the q{sub NPQ} decreased, The Cercospora-tolerant line showed no significant differences under the different treatments. Thus, the line tolerant to Cercospora infection also proved to be tolerant to UV-B radiation alone and in combination with the infection. (au)

  5. Sensitivity of the distribution of mutational fitness effects to environment, genetic background, and adaptedness: a case study with Drosophila.

    Science.gov (United States)

    Wang, Alethea D; Sharp, Nathaniel P; Agrawal, Aneil F

    2014-03-01

    Heterogeneity in the fitness effects of individual mutations has been found across different environmental and genetic contexts. Going beyond effects on individual mutations, how is the distribution of selective effects, f(s), altered by changes in genetic and environmental context? In this study, we examined changes in the major features of f(s) by estimating viability selection on 36 individual mutations in Drosophila melanogaster across two different environments in two different genetic backgrounds that were either adapted or nonadapted to the two test environments. Both environment and genetic background affected selection on individual mutations. However, the overall distribution f(s) appeared robust to changes in genetic background but both the mean, E(s), and the variance, V(s) were dependent on the environment. Between these two properties, V(s) was more sensitive to environmental change. Contrary to predictions of fitness landscape theory, the match between genetic background and assay environment (i.e., adaptedness) had little effect on f(s).

  6. Genetics

    Science.gov (United States)

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  7. Predicting Radiative Heat Transfer in Oxy-Methane Flame Simulations: An Examination of Its Sensitivities to Chemistry and Radiative Property Models

    Directory of Open Access Journals (Sweden)

    Hassan Abdul-Sater

    2015-01-01

    Full Text Available Measurements from confined, laminar oxy-methane flames at different O2/CO2 dilution ratios in the oxidizer are first reported with measurements from methane-air flames included for comparison. Simulations of these flames employing appropriate chemistry and radiative property modeling options were performed to garner insights into the experimental trends and assess prediction sensitivities to the choice of modeling options. The chemistry was modeled employing a mixture-fraction based approach, Eddy dissipation concept (EDC, and refined global finite rate (FR models. Radiative properties were estimated employing four weighted-sum-of-gray-gases (WSGG models formulated from different spectroscopic/model databases. The mixture fraction and EDC models correctly predicted the trends in flame length and OH concentration variations, and the O2, CO2, and temperature measurements outside the flames. The refined FR chemistry model predictions of CO2 and O2 deviated from their measured values in the flame with 50% O2 in the oxidizer. Flame radiant power estimates varied by less than 10% between the mixture fraction and EDC models but more than 60% between the different WSGG models. The largest variations were attributed to the postcombustion gases in the temperature range 500 K–800 K in the upper sections of the furnace which also contributed significantly to the overall radiative transfer.

  8. FitSKIRT: genetic algorithms to automatically fit dusty galaxies with a Monte Carlo radiative transfer code

    CERN Document Server

    De Geyter, Gert; Fritz, Jacopo; Camps, Peter

    2012-01-01

    We present FitSKIRT, a method to efficiently fit radiative transfer models to UV/optical images of dusty galaxies. These images have the advantage that they have better spatial resolution compared to FIR/submm data. FitSKIRT uses the GAlib genetic algorithm library to optimize the output of the SKIRT Monte Carlo radiative transfer code. Genetic algorithms prove to be a valuable tool in handling the multi- dimensional search space as well as the noise induced by the random nature of the Monte Carlo radiative transfer code. FitSKIRT is tested on artificial images of a simulated edge-on spiral galaxy, where we gradually increase the number of fitted parameters. We find that we can recover all model parameters, even if all 11 model parameters are left unconstrained. Finally, we apply the FitSKIRT code to a V-band image of the edge-on spiral galaxy NGC4013. This galaxy has been modeled previously by other authors using different combinations of radiative transfer codes and optimization methods. Given the different...

  9. High-throughput identification of ionizing radiation-sensitive plant genes and development of radiation indicator plant and radiation sensing Genechip

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Sub; Kim, Jinbaek; Ha, Bokeun; Kim, Sang Hoon; Kim, Sunhee

    2013-05-15

    Physiological analysis of monocot model plant (rice) in response to ionizing radiation (cosmic-ray, gamma-ray, Ion beam). - Identification of antioxidant characters through cytochemical analysis. - Comparison of antioxidant activities in response to ionizing irradiation. - Evaluation of anthocyanin quantity in response to ionizing irradiation. Ionization energy response gene family analysis via bioinformatic validation. - Expression analysis of monocot and dicot gene families. - In silico and bioinformatic approach to elucidate gene function. Characterization and functional analysis of genes specifically expressed in response to ionizing irradiation (cosmic-ray, gamma-ray, Ion beam). - High throughput trancriptomic analysis of plants under ionizing radiation using microarray. - Promotor and cis-element analysis of genes specifically expressed in response to ionizing radiation. - Validation and function analysis of candidate genes. - Elucidation of plant mechanism of sensing and response to ionization energy. Development of bioindicator plants detecting ionization energy. - Cloning and identification of 'Radio marker genes (RMG)'. - Development of Over-expression (O/E) or Knock-out (K/O) plant using RMG. Development of Genechip as an ionization energy detector. - Expression profiling analysis of genes specifically expression in response to ionization energy. - Prepare high-conserved gene specific oligomer. - Development of ionization energy monitoring Genechip and application.

  10. [Measuring intraoperative radiation exposure of the trauma surgeon. Measuring eye, thyroid gland and hand with highly sensitive thermoluminescent detectors].

    Science.gov (United States)

    Fuchs, M; Modler, H; Schmid, A; Dumont, C; Stürmer, K M

    1999-05-01

    A prospective study of 24 operative procedures involving minimal invasive techniques and fluoroscopic guidance was undertaken in order to measure the radiation exposure to the primary surgeon. Radiation was monitored with the use of high sensitive thermoluminescent dosimeters. At the spots of dosimetry (eyes, thyroid gland, hand and genitals under lead apron) the dose was uniformly low and ranged from 0.6 muSv at the eyes to 259.3 muSv at the hand. The dose is determined by the duration of fluoroscopy and the amount of scattered rays, which in turn depends on the volume being x-rayed. On the basis of our results there is no likelihood of exceeding the limits of safety regulations even in a very busy operative environment, although a statistically increased incidence of thyroid cancer or a radiation-induced glaucoma is present. In vitro measurements with irradiation of a phantom resulted in the following recommendations: 1) fluoroscopy should be performed using the magnification-mechanism of the x-ray apparatus, 2) during lateral fluoroscopy the primary surgeon should be positioned close to the image intensifier. At least the surgeon should be familiar with the technique of closed reduction and instrumentation to reduce the duration of fluoroscopy which proved to be the most important factor for the amount of the radiation exposure.

  11. Afatinib increases sensitivity to radiation in non-small cell lung cancer cells with acquired EGFR T790M mutation.

    Science.gov (United States)

    Zhang, Shirong; Zheng, Xiaoliang; Huang, Haixiu; Wu, Kan; Wang, Bing; Chen, Xufeng; Ma, Shenglin

    2015-03-20

    Afatinib is a second-generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and has shown a significant clinical benefit in non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, the potential therapeutic effects of afatinib combining with other modalities, including ionizing radiation (IR), are not well understood. In this study, we developed a gefitinib-resistant cell subline (PC-9-GR) with a secondary EGFR mutation (T790M) from NSCLC PC-9 cells after chronic exposures to increasing doses of gefitinib. The presence of afatinib significantly increases the cell killing effect of radiation in PC-9-GR cells harboring acquired T790M, but not in H1975 cells with de novo T790M or in H460 cells that express wild-type EGFR. In PC-9-GR cells, afatinib remarkable blocks baseline of EGFR and ERK phosphorylations, and causes delay of IR-induced AKT phosphorylation. Afatinib treatment also leads to increased apoptosis and suppressed DNA damage repair in irradiated PC-9-GR cells, and enhanced tumor growth inhibition when combined with IR in PC-9-GR xenografts. Our findings suggest a potential therapeutic impact of afatinib as a radiation sensitizer in lung cancer cells harboring acquired T790M mutation, providing a rationale for a clinical trial with combination of afatinib and radiation in NSCLCs with EGFR T790M mutation.

  12. Deficient expression of aldehyde dehydrogenase 1A1 is consistent with increased sensitivity of Gorlin syndrome patients to radiation carcinogenesis.

    Science.gov (United States)

    Wright, Aaron T; Magnaldo, Thierry; Sontag, Ryan L; Anderson, Lindsey N; Sadler, Natalie C; Piehowski, Paul D; Gache, Yannick; Weber, Thomas J

    2015-06-01

    Human phenotypes that are highly susceptible to radiation carcinogenesis have been identified. Sensitive phenotypes often display robust regulation of molecular features that modify biological response, which can facilitate identification of the pathways/networks that contribute to pathophysiological outcomes. Here we interrogate primary dermal fibroblasts isolated from Gorlin syndrome patients (GDFs), who display a pronounced inducible tumorigenic response to radiation, in comparison to normal human dermal fibroblasts (NHDFs). Our approach exploits newly developed thiol reactive probes to define changes in protein thiol profiles in live cell studies, which minimizes artifacts associated with cell lysis. Redox probes revealed deficient expression of an apparent 55 kDa protein thiol in GDFs from independent Gorlin syndrome patients, compared with NHDFs. Proteomics tentatively identified this protein as aldehyde dehydrogenase 1A1 (ALDH1A1), a key enzyme regulating retinoic acid synthesis, and ALDH1A1 protein deficiency in GDFs was confirmed by Western blot. A number of additional protein thiol differences in GDFs were identified, including radiation responsive annexin family members and lamin A/C. Collectively, candidates identified in our study have plausible implications for radiation health effects and cancer susceptibility.

  13. Oscillation photography of radiation-sensitive crystals using a synchrotron source

    Energy Technology Data Exchange (ETDEWEB)

    Rossmann, M.G.; Erickson, J.W. (Purdue Univ., Lafayette, IN (USA). Dept. of Biological Sciences)

    1983-12-01

    A method is described to determine the accurate setting of a crystal placed in an unknown orientation on an oscillation camera. This avoids time-consuming setting operations during which the crystal is subject to continuous radiation damage initiated by the first setting photograph. It also ensures maximal use of synchrotron radiation time as there is no need for any prior setting and developing periods. The method is dependent on measuring the lengths and orientations of the major axes of the ellipses on two, preferably approximately orthogonal, 'still' photographs. The method is applied to five different rhinovirus (common cold) crystals.

  14. Quasi-analytical solutions of hybrid platform and the optimization of highly sensitive thin-film sensors for terahertz radiation

    CERN Document Server

    Tapsanit, Piyawath; Ishihara, Teruya; Otani, Chiko

    2016-01-01

    We present quasi-analytical solutions (QANS) of hybrid platform (HP) comprising metallic grating (MG) and stacked-dielectric layers for terahertz (THz) radiation. The QANS are validated by finite difference time domain simulation. It is found that the Wood anomalies induce the high-order spoof surface plasmon resonances in the HP. The QANS are applied to optimize new perfect absorber for THz sensing of large-area thin film with ultrahigh figure of merit reaching fifth order of magnitude for the film thickness 0.0001p (p: MG period). The first-order Wood's anomaly of the insulator layer and the Fabry-Perot in the slit's cavity account for the resonance of the perfect absorber. The QANS and the new perfect absorber may lead to highly sensitive and practical nano-film refractive index sensor for THz radiation.

  15. Adjoint Sensitivity Analysis of Radiative Transfer Equation: Temperature and Gas Mixing Ratio Weighting Functions for Remote Sensing of Scattering Atmospheres in Thermal IR

    Science.gov (United States)

    Ustinov, E.

    1999-01-01

    Sensitivity analysis based on using of the adjoint equation of radiative transfer is applied to the case of atmospheric remote sensing in the thermal spectral region with non-negligeable atmospheric scattering.

  16. SiRNA-mediated IGF-1R inhibition sensitizes human colon cancer SW480 cells to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yavari, Kamal; Taghikhani, Mohammad; Mesbah-Namin, Seyed A. (Dept. of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares Univ., Tehran (Iran)); Maragheh, Mohammad Ghannadi (Nuclear Fuel Cycle Research Center, Nuclear Sciences and Technology Research Inst., Tehran (Iran)); Babaei, Mohammad Hosein (Radioisotope Quality Control Center, Nuclear Sciences and Technology Research Inst., Tehran (Iran)); Arfaee, Ali Jabbary; Madani, Hossein; Mirzaei, Hamid Reza (Radiation Oncology Dept., Shohada Hospital, Shahid Beheshti Medical Sciences Univ., Tehran (Iran))

    2010-01-15

    Purpose. Insulin like growth factor receptor 1 (IGF-1R) is well-documented to play a key role in radiation response and tumor radiosensitivity, thus offering an attractive clinic drug target to enhance tumor sensitivity to anti-cancer radiotherapy. Material and methods. Human colon carcinoma SW480 cells were transfected with the specific small interference RNA (siRNA) expression vector (pkD-shRNA-IGF-1R-V2) designed to target IGF-1R mRNA. The expression of IGF-1R mRNA and its protein among the transfected and untransfected cells were detected by semi-quantitative RT-PCR and ELISA assay. The changes in cell radiosensitivity were examined by MTT assay. Results. Transfection of mammalian expression vector pkD containing IGF-1R siRNA was shown to reduce IGF-1R mRNA levels by up to 95%. ELISA assay detected a similar inhibition of IGF-1R protein levels in cells transfected with IGF-1R siRNA. SW480 cells transfected with the expression vector for siRNA significantly rendered cells more sensitive to radiation and the highest radiation enhancement ratio was 2.02 +- 0.08. Conclusion. These data provide the first evidence that specific siRNA fragment (pkD-shRNA-IGF-1R-V2) targeting human IGF-1R mRNA is able to enhance colon cancer radiosensitivity. Also results indicated that, combining IGF-1R siRNA and radiation significantly enhances antitumor efficacy compared with either modality alone

  17. Patterns in ultraviolet radiation sensitivity of tropical, temperate and Arctic marine macroalgae

    NARCIS (Netherlands)

    van de Poll, Willem Hendrik

    2003-01-01

    Marine macroalgae on rocky substrates are an important component of the coastal ecosystem in terms of biomass and diversity. Because macroalgae depend on sunlight to drive photosynthesis they also face exposure to harmful ultraviolet-B radiation (UVBR: 280-315 nm). UVBR induces DNA damage (mainly cy

  18. Advanced data readout technique for Multianode Position Sensitive Photomultiplier Tube applicable in radiation imaging detectors

    Science.gov (United States)

    Popov, V.

    2011-01-01

    Most of the best performing PSPMT tubes from Hamamatsu and Burle are designed with a pad-matrix anode layout. However, for obtaining a high resolution, a small-sized anode photomultiplier tubes are preferable; these tubes may have 64, 256 or 1024 anodes per tube. If the tubes are used in array to get a larger area detector, the number of analog channels may range from hundreds to thousands. Multichannel analog readout requires special electronics ICs, ASICs etc., which are attached to multichannel DAQ system. As a result, the data file and data processing time will be increased. Therefore, this readout could not be performed in a small project. Usually, most of radiation imaging applications allow the use of analog data processing in front-end electronics, significantly reducing the number of the detector's output lines to data acquisition without reducing the image quality. The idea of pad-matrix decoupling circuit with gain correction was invented and intensively tested in JLab. Several versions of PSPMT readout electronics were produced and studied. All developments were done and optimized specifically for radiation imaging projects. They covered high resolution SPECT, high speed PET, fast neutron imaging, and single tube and multi tube array systems. This paper presents and discusses the summary of the observed results in readout electronics evaluation with different PSPMTs and radiation imaging systems, as well as the advantages and limitations of the developed approach to radiation imaging detectors readout.

  19. Patterns in ultraviolet radiation sensitivity of tropical, temperate and Arctic marine macroalgae

    NARCIS (Netherlands)

    van de Poll, Willem Hendrik

    2003-01-01

    Marine macroalgae on rocky substrates are an important component of the coastal ecosystem in terms of biomass and diversity. Because macroalgae depend on sunlight to drive photosynthesis they also face exposure to harmful ultraviolet-B radiation (UVBR: 280-315 nm). UVBR induces DNA damage (mainly cy

  20. Sensitivity of APSIM/ORYZA model due to estimation errors in solar radiation

    NARCIS (Netherlands)

    Heinemann, A.B.; Oort, van P.A.J.; Simoes Fernandes, D.; Maia, A.H.N.

    2012-01-01

    Crop models are ideally suited to quantify existing climatic risks. However, they require historic climate data as input. While daily temperature and rainfall data are often available, the lack of observed solar radiation (Rs) data severely limits site-specific crop modelling. The objective of this

  1. Aminopeptidase N (APN/CD13 inhibitor, Ubenimex, enhances radiation sensitivity in human cervical cancer

    Directory of Open Access Journals (Sweden)

    Nawa Akihiro

    2008-03-01

    Full Text Available Abstract Background Radiotherapy can be used to treat all stages of cervical cancer. For improving local control via radiotherapy, it is important to use additional antitumor agents. Aminopeptidase N (APN/CD13, a 150-kDa metalloproteinase, is a multifunctional cell surface aminopeptidase with ubiquitous expression. Recent studies have suggested that APN/CD13 plays an important role in tumor progression in several human malignancies. Methods We investigated whether the suppression of APN/CD13 using Ubenimex, an inhibitor of APN/CD13 activity, may affect tumor radiosensitivity in cervical cancer cells both in vitro and in vivo. Cell surface APN/CD13 activity in HeLa cells was calculated using alanine-p-nitroanilido as a substrate. For colony formation assays, single-dose radiation and/or Ubenimex were administered to each dish of HeLa cells, and these dishes were cultured for 14 days. Molecular changes of apoptosis were determined by Western blot. Apoptosis was evaluated by Annexin-V PI staining (flow cytometry analysis and the Tunel method. Moreover, we investigated the effect of combining Ubenimex and low-dose radiation on tumor growth using nude mice. Results We demonstrated that Ubenimex enhanced the effectiveness of radiotherapy, acting as a radiosensitizer both in vitro and in vivo. In colony formation assays, a significant decline in clonogenic survival was observed in Ubenimex-treated cells. Mice treated with a combination of radiation and Ubenimex showed a significant prolongation of the tumor-doubling time compared with the control, Ubenimex, or radiation-alone groups. We also showed that ubenimex enhanced radiation-induced apoptosis in vitro and in vivo. Conclusion Although further studies are needed, this report suggests that Ubeniemx acts as a radiosensitizer in cervical cancer treatment, and that the inhibition of APN/CD13 activity may represent a new approach for improving the therapeutic efficacy of radiotherapy for uterine

  2. The role of autophagy in sensitizing malignant glioma cells to radiation therapy

    Institute of Scientific and Technical Information of China (English)

    Wenzhuo Zhuang; Zhenghong Qin; Zhongqin Liang

    2009-01-01

    Malignant gliomas representthe majority of primary brain tumors.The current standard treatments for malignant gliomas include surgical resection,radiation therapy,and chemotherapy.Radiotherapy,a standard adjuvant therapy,confers some survival advantages,but resistance of the glioma cells to the efficacy of radiation limits the success of the treatment.The mechanisms underlying glioma cell radioresistance have remained elusive.Autophagy is a protein degradation system characterized by a prominent formation of double-membrane vesicles in the cytoplasm.Recent studies suggest that autophagy may be important in the regulation of cancer development and progression and in determining the response of tumor cells to anticancer therapy.Also,autophagy is a novel response of glioma cells to ionizing radiation.Autophagic cell death is considered programmed cell death type Ⅱ,whereas apoptosis is programmed cell death type Ⅰ.These two types of cell death are predominantly distinctive,but many studies demonstrate a cross-talk between them.Whether autophagy in cancer cells causes death or protects cells is controversial.The regulatory pathways of autophagy share several molecules.P13K/Akt/Mtor,DNA-PK,tumor suppressor genes, mitochondrial damage,and lysosome may play important roles in radiation-induced autophagy in glioma cells.Recently,a highly tumorigenic glioma tumor subpopulation,termed cancer stem cell or tumor-initiating cell,has been shown to promote therapeutic resistance.This review summarizes the main mediators associated with radiation-induced autophagy in malignant glioma cells and discusses the implications of the cancer stem cell hypothesis for the development of future therapies for brain tumors.

  3. The Genetic Architecture of Flowering Time and Photoperiod Sensitivity in Maize as Revealed by QTL Review and Meta Analysis

    Institute of Scientific and Technical Information of China (English)

    Jie Xu; Tingzhao Rong; Yaxi Liu; Jian Liu; Moju Cao; Jing Wang; Hai Lan; Yunbi Xu; Yanli Lu; Guangtang Pan

    2012-01-01

    The control of flowering is not only important for reproduction,but also plays a key role in the processes of domestication and adaptation.To reveal the genetic architecture for flowering time and photoperiod sensitivity,a comprehensive evaluation of the relevant literature was performed and followed by meta analysis.A total of 25 synthetic consensus quantitative trait loci (QTL) and four hot-spot genomic regions were identified for photoperiod sensitivity including 11 genes related to photoperiod response or flower morphogenesis and development.Besides,a comparative analysis of the QTL for flowering time and photoperiod sensitivity highlighted the regions containing shared and unique QTL for the two traits.Candidate genes associated with maize flowering were identified through integrated analysis of the homologous genes for flowering time in plants and the consensus QTL regions for photoperiod sensitivity in maize (Zea mays L.).Our results suggest that the combination of literature review,meta-analysis and homologous blast is an efficient approach to identify new candidate genes and create a global view of the genetic architecture for maize photoperiodic flowering.Sequences of candidate genes can be used to develop molecular markers for various models of marker-assisted selection,such as marker-assisted recurrent selection and genomic selection that can contribute significantly to crop environmental adaptation.

  4. Preparation of PbSeO3 as a new material, sensitive to the electromagnetic radiation in UV range

    Science.gov (United States)

    Tomaev, V. V.; Smolyaninov, V. D.; Stoyanova, T. V.; Egorov, S. V.

    2016-08-01

    The new technology of the formation of photoresistive structures sensitive in ultraviolet range of electromagnetic spectrum based on lead selenide and lead selenite composite is discussed. Studies of photosensitivity were carried out using a set of LEDs in the visible and ultraviolet spectral range. Obtained structures show considerable sensitivity in ultraviolet and blue range of radiation, meanwhile that in red and yellow region of light turned to be small. The structures were formed by oxidation of PbSe crystals. Diffusion of the oxygen through the surface layer of PbSe was suggested to be a key mechanism of oxidation. Oxidation kinetics were studied by means of roentgen lines chemical shift and roentgen diffraction.

  5. Enhancement in dose sensitivity of polymer gel dosimeters composed of radiation-crosslinked gel matrix and less toxic monomers

    Science.gov (United States)

    Hiroki, A.; Yamashita, S.; Taguchi, M.

    2015-01-01

    Polymer gel dosimeters based on radiation-crosslinked hydroxypropyl cellulose gel were prepared, which comprised 2-hydroxyethyl methacrylate (HEMA) and polyethylene glycol #400 dimethacrylate (9G) as less toxic monomers and tetrakis (hydroxymethyl) phosphonium chloride (THPC) as an antioxidant. The dosimeters exposed to 60Co γ-rays became cloudy at only 1 Gy. The irradiated dosimeters were optically analyzed by using a UV- vis spectrophotometer to evaluate dose response. Absorbance of the dosimeters linearly increased in the dose range from 0 to 10 Gy, in which dose sensitivity increased with increasing 9G concentration. The dose sensitivity of the dosimeters with 2 wt% HEMA and 3 wt% 9G was also enhanced by increment in THPC.

  6. Characterization of pH-sensitive Poly (acrylic acid-co-N-vinyl-2-pyrrolidone) Hydrogels Prepared by Gamma Radiation

    Institute of Scientific and Technical Information of China (English)

    YANG Ming-cheng; HE Su-qin; LIU Wen-tao; SONG Hong-yan; ZHU Cheng-shen

    2007-01-01

    The pH-sensitive copolymer hydrogels were prepared with the monomers of acrylic acid and N-vinyl-2-pyrrolidone based on gamma radiation technique. The morphology of the hydrogels was monitored by using scanning electron microscope. The influence of absorbed dose, monomer compasition and concentration on the swelling ratio (SR) of the hydrogels were investigated in detail. The effect of pH and temperature of the swelling medium on the swelling behavior of the hydrogels were also examined. The results show that the SR of the copolymer hydrogels decreases with the monomer concentration and absorbed dose increasing. The copolymer hydrogels show a better pH-sensitive behavior. In alkaline solution, the SR of the hydrogels is much higher than in acid solution.

  7. Chemogenomic landscape of RUNX1-mutated AML reveals importance of RUNX1 allele dosage in genetics and glucocorticoid sensitivity.

    Science.gov (United States)

    Simon, Laura; Lavallée, Vincent-Philippe; Bordeleau, Marie-Eve; Krosl, Jana; Baccelli, Irene; Boucher, Geneviève; Lehnertz, Bernhard; Chagraoui, Jalila; MacRae, Tara; Ruel, Réjean; Chantigny, Yves A; Lemieux, Sébastien; Marinier, Anne; Hébert, Josée; Sauvageau, Guy

    2017-08-30

    RUNX1-mutated (RUNX1mut) Acute Myeloid Leukemia (AML) is associated with adverse outcome, highlighting the urgent need for a better genetic characterization of this AML subgroup and for the design of efficient therapeutic strategies for this disease. Towards this goal, we further dissected the mutational spectrum and gene expression profile of RUNX1mut AML and correlated these results to drug sensitivity to identify novel compounds targeting this AML subgroup. RNA-sequencing of 47 RUNX1mut primary AML specimens was performed and sequencing results were compared to those of RUNX1 wild-type samples. Chemical screens were also conducted using RUNX1mut specimens to identify compounds selectively affecting the viability of RUNX1mut AML. We show that samples with no remaining RUNX1 wild-type allele are clinically and genetically distinct and display a more homogeneous gene expression profile. Chemical screening revealed that most RUNX1mut specimens are sensitive to glucocorticoids (GCs) and we confirmed that GCs inhibit AML cell proliferation through their interaction with the Glucocorticoid Receptor (GR). We observed that specimens harboring RUNX1 mutations expected to result in low residual RUNX1 activity are most sensitive to GCs, and that co-associating mutations as well as that GR levels contribute to GC sensitivity. Accordingly, acquired glucocorticoid sensitivity was achieved by negatively regulating RUNX1 expression in human AML cells. Our findings show the profound impact of RUNX1 allele dosage on gene expression profile and glucocorticoid sensitivity in AML, thereby opening opportunities for preclinical testing which may lead to drug repurposing and improved disease characterization. Copyright ©2017, American Association for Cancer Research.

  8. Studies on the radiation application for the development of genetic resources -Studies on application of radiation and radioisotopes-

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Il; Song, Hi Sup; Kim, Jae Sung; Shin, In Chul; Lee, Sang Jae; Lee, Ki Woon; Lim, Yong Tack [Korea Atomic Energy Res. Inst., Taejon (Korea, Republic of)

    1994-07-01

    Present research carried out on the development of techniques of plant tissue culture, on the induction and selection of radiation mutation and on the evaluation of mutant germplasm of several important crops. Optimum dosage of radiation were investigated for induction of mutation and selection of mutant in field or in vitro culture. The optimum dosage of potato nodal stem was revealed the range of 30-50 Gy in in vitro cultured plants. Variation of such agronomic traits was observed as earliness, short culm, high yield and other promising characters derived from irradiated rice, soybean, perilla, potato and some other crops in field and in vitro culture. The rice mutants of 18 lines were selected from irradiated rice cultivars and 48 soybean mutants were selected for earliness, large seed size and 2,000 line of soybean and rice, perilla were evaluated for the preservation of germplasm. Influence of plant growth regulators on P-32 uptake was observed in Broccoli callus in vitro culture. (Author).

  9. Genetic Factors Affecting Susceptibility to Low Dose & Low Dose-Rate Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bedford, Joel

    2014-04-18

    Our laboratory has, among other things, developed and used the gamma H2AX focus assay and other chromosomal and cell killing assays to show that differences in this DNA double strand break (dsb) related response can be clearly and distinctly demonstrated for cells which are mildly hyper-radiosensitive such as those associated with A-T heterozygosity. We have found this level of mild hypersensitivity for cells from some 20 to 30 % of apparently normal individuals and from apparently normal parents of Retinoblastoma patients. We found significant differences in gene expression in somatic cells from unaffected parents of Rb patients as compared with normal controls, suggesting that these parents may harbor some as yet unidentified genetic abnormality. In other experiments we sought to determine the extent of differences in normal human cellular reaponses to radiation depending on their irradiation in 2D monolayer vs 3D organized acinar growth conditions. We exmined cell reproductive death, chromosomal aberration induction, and the levels of γ-H2AX foci in cells after single acute gamma-ray doses and immediately after 20 hours of irradiation at a dose rate of 0.0017 Gy/min. We found no significant differences in the dose-responses of these cells under the 2D or 3D growth conditions. While this does not mean such differences cannot occur in other situations, it does mean that they do not generally or necessarily occur. In another series of studies in collaboration with Dr Chuan Li, with supprt from this current grant. We reported a role for apoptotic cell death in promoting wound healing and tissue regeneration in mice. Apoptotic cells released growth signals that stimulated the proliferation of progenitor or stem cells. In yet another collaboration with Dr, B. Chen with funds from this grant, the relative radiosensitivity to cell killing as well as chromosomal instability of 13 DNA-PKcs site-directed mutant cell lines (defective at phosphorylation sites or kinase

  10. Optimized absorption of solar radiations in nano-structured thin films of crystalline silicon via a genetic algorithm

    Science.gov (United States)

    Mayer, Alexandre; Muller, Jérôme; Herman, Aline; Deparis, Olivier

    2015-08-01

    We developed a genetic algorithm to achieve optimal absorption of solar radiation in nano-structured thin films of crystalline silicon (c-Si) for applications in photovoltaics. The device includes on the front side a periodic array of inverted pyramids, with conformal passivation layer (a-Si:H or AlOx) and anti-reflection coating (SiNx). The device also includes on the back side a passivation layer (a-Si:H) and a flat reflector (ITO and Ag). The geometrical parameters of the inverted pyramids as well as the thickness of the different layers must be adjusted in order to maximize the absorption of solar radiations in the c-Si. The genetic algorithm enables the determination of optimal solutions that lead to high performances by evaluating only a reduced number of parameter combinations. The results achieved by the genetic algorithm for a 40μm thick c-Si lead to short-circuit currents of 37 mA/cm2 when a-Si:H is used for the front-side passivation and 39.1 mA/cm2 when transparent AlOx is used instead.

  11. Radiation sensitivity of the gastrula-stage embryo: Chromosome aberrations and mutation induction in lacZ transgenic mice: The roles of DNA double-strand break repair systems.

    Science.gov (United States)

    Jacquet, Paul; van Buul, Paul; van Duijn-Goedhart, Annemarie; Reynaud, Karine; Buset, Jasmine; Neefs, Mieke; Michaux, Arlette; Monsieurs, Pieter; de Boer, Peter; Baatout, Sarah

    2015-10-01

    At the gastrula phase of development, just after the onset of implantation, the embryo proper is characterized by extremely rapid cell proliferation. The importance of DNA repair is illustrated by embryonic lethality at this stage after ablation of the genes involved. Insight into mutation induction is called for by the fact that women often do not realize they are pregnant, shortly after implantation, a circumstance which may have important consequences when women are subjected to medical imaging using ionizing radiation. We screened gastrula embryos for DNA synthesis, nuclear morphology, growth, and chromosome aberrations (CA) shortly after irradiation with doses up to 2.5Gy. In order to obtain an insight into the importance of DNA repair for CA induction, we included mutants for the non-homologous end joining (NHEJ) and homologous recombination repair (HRR) pathways, as well as Parp1-/- and p53+/- embryos. With the pUR288 shuttle vector assay, we determined the radiation sensitivity for point mutations and small deletions detected in young adults. We found increased numbers of abnormal nuclei 5h after irradiation; an indication of disturbed development was also observed around this time. Chromosome aberrations 7h after irradiation arose in all genotypes and were mainly of the chromatid type, in agreement with a cell cycle dominated by S-phase. Increased frequencies of CA were found for NHEJ and HR mutants. Gastrula embryos are unusual in that they are low in exchange induction, even after compromised HR. Gastrula embryos were radiation sensitive in the pUR288 shuttle vector assay, giving the highest mutation induction ever reported for this genetic toxicology model. On theoretical grounds, a delayed radiation response must be involved. The compromised developmental profile after doses up to 2.5Gy likely is caused by both apoptosis and later cell death due to large deletions. Our data indicate a distinct radiation-sensitive profile of gastrula embryos, including

  12. Modeling radiative transfer in tropical rainforest canopies: sensitivity of simulated albedo to canopy architectural and optical parameters.

    Science.gov (United States)

    Yanagi, Sílvia N M; Costa, Marcos H

    2011-12-01

    This study evaluates the sensitivity of the surface albedo simulated by the Integrated Biosphere Simulator (IBIS) to a set of Amazonian tropical rainforest canopy architectural and optical parameters. The parameters tested in this study are the orientation and reflectance of the leaves of upper and lower canopies in the visible (VIS) and near-infrared (NIR) spectral bands. The results are evaluated against albedo measurements taken above the K34 site at the INPA (Instituto Nacional de Pesquisas da Amazônia) Cuieiras Biological Reserve. The sensitivity analysis indicates a strong response to the upper canopy leaves orientation (χup) and to the reflectivity in the near-infrared spectral band (ρNIR,up), a smaller sensitivity to the reflectivity in the visible spectral band (ρVIS,up) and no sensitivity at all to the lower canopy parameters, which is consistent with the canopy structure. The combination of parameters that minimized the Root Mean Square Error and mean relative error are χup = 0.86, ρVIS,up = 0.062 and ρNIR,up = 0.275. The parameterizations performed resulted in successful simulations of tropical rainforest albedo by IBIS, indicating its potential to simulate the canopy radiative transfer for narrow spectral bands and permitting close comparison with remote sensing products.

  13. Monsoon sensitivity to aerosol direct radiative forcing in the community atmosphere model

    Science.gov (United States)

    Sajani, S.; Krishna Moorthy, K.; Rajendran, K.; Nanjundiah, Ravi S.

    2012-08-01

    Aerosol forcing remains a dominant uncertainty in climate studies. The impact of aerosol direct radiative forcing on Indian monsoon is extremely complex and is strongly dependent on the model, aerosol distribution and characteristics specified in the model, modelling strategy employed as well as on spatial and temporal scales. The present study investigates (i) the aerosol direct radiative forcing impact on mean Indian summer monsoon when a combination of quasi-realistic mean annual cycles of scattering and absorbing aerosols derived from an aerosol transport model constrained with satellite observed Aerosol Optical Depth (AOD) is prescribed, (ii) the dominant feedback mechanism behind the simulated impact of all-aerosol direct radiative forcing on monsoon and (iii) the relative impacts of absorbing and scattering aerosols on mean Indian summer monsoon. We have used CAM3, an atmospheric GCM (AGCM) that has a comprehensive treatment of the aerosol-radiation interaction. This AGCM has been used to perform climate simulations with three different representations of aerosol direct radiative forcing due to the total, scattering aerosols and black carbon aerosols. We have also conducted experiments without any aerosol forcing. Aerosol direct impact due to scattering aerosols causes significant reduction in summer monsoon precipitation over India with a tendency for southward shift of Tropical Convergence Zones (TCZs) over the Indian region. Aerosol forcing reduces surface solar absorption over the primary rainbelt region of India and reduces the surface and lower tropospheric temperatures. Concurrent warming of the lower atmosphere over the warm oceanic region in the south reduces the land-ocean temperature contrast and weakens the monsoon overturning circulation and the advection of moisture into the landmass. This increases atmospheric convective stability, and decreases convection, clouds, precipitation and associated latent heat release. Our analysis reveals a

  14. Genetic Analysis and Primary Mapping of pms4,a Photoperiod-Sensitive Genic Male Sterility Gene in Rice (Oryza sativa)

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    To understand the genetic characteristics of a new photoperiod-sensitive genic male sterile line Mian 9S,some reciprocal crosses were made between Mian 9S and six indica rice materials,Yangdao 6,Luhui 602,Shuihui 527,Mianhui 725,Fuhui 838 and Yixiang 1B.Genetic analysis results suggested that the photoperiod-sensitive genic male sterility (PGMS) of Mian 9S was controlled by a single recessive nuclear gene.Thus,the F2 population derived from the cross of Yangdao 6/Mian 9S was used to map the PGMS gene in Mian 9S.By using SSR markers,the PGMS gene of Mian 9S was mapped on one side of the markers,RM6659 and RM1305,on rice chromosome 4,with the genetic distances of 3.0 cM and 3.5 cM,respectively.The gene was a novel PGMS gene and designated tentatively as pros4.In addition,the application of the pros4 gene was discussed.

  15. Mitotic arrest deficient protein MAD2B is overexpressed in human glioma, with depletion enhancing sensitivity to ionizing radiation.

    Science.gov (United States)

    Zhao, Jun; Liu, Shuizhong; Wang, Hongwei; Zhang, Xiaomei; Kang, Tiejiang; Li, Zhanyi; Deng, Hemin; Yue, Wu; Cao, Shujie

    2011-06-01

    Mitotic arrest deficient protein MAD2B, an enzyme involved in translesion DNA synthesis, has been implicated in several cancers. However, its role in human glioma has not been defined. In the present study, we investigated the expression levels of MAD2B in human gliomas and normal brain tissues, and determined whether depletion of MAD2B enhanced the sensitivity of glioma cells to ionizing radiation. Using reverse transcription-polymerase chain reaction and immunohistochemical analysis, MAD2B was found to be overexpressed in glioma specimens compared with normal brain tissue. Silencing of MAD2B markedly reduced clonogenic survival of glioma cells and significantly enhanced apoptosis in response to ionizing radiation. This effect was associated with caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, disruption of MAD2B potentiated radiation-induced genomic damage, as evidenced by increased phosphorylation of gamma histone H2AX (γ-H2AX). Our findings reveal that expression of MAD2B is deregulated in glioma, and targeting MAD2B may be a potential strategy for improving the efficacy of radiotherapy. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. TERRA Expression Levels Do Not Correlate With Telomere Length and Radiation Sensitivity in Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Alexandra eSmirnova

    2013-05-01

    Full Text Available Mammalian telomeres are transcribed into long non-coding telomeric RNA molecules (TERRA that seem to play a role in the maintenance of telomere stability. In human cells, CpG island promoters drive TERRA transcription and are regulated by methylation. It was suggested that the amount of TERRA may be related to telomere length. To test this hypothesis we measured telomere length and TERRA levels in single clones isolated from five human cell lines: HeLa (cervical carcinoma, BRC-230 (breast cancer, AKG and GK2 (gastric cancers and GM847 (SV40 immortalized skin fibroblasts. We observed great clonal heterogeneity both in TRF (Terminal Restriction Fragment length and in TERRA levels. However, these two parameters did not correlate with each other. Moreover, cell survival to γ-rays did not show a significant variation among the clones, suggesting that, in this cellular system, the intra-population variability in telomere length and TERRA levels does not influence sensitivity to ionizing radiation. This conclusion was supported by the observation that in a cell line in which telomeres were greatly elongated by the ectopic expression of telomerase, TERRA expression levels and radiation sensitivity were similar to the parental HeLa cell line.

  17. AN ESCHERICHIA-COLI STRAIN DEFICIENT FOR BOTH EXONUCLEASE-V AND DEOXYCYTIDINE TRIPHOSPHATE DEAMINASE SHOWS ENHANCED SENSITIVITY TO IONIZING-RADIATION

    NARCIS (Netherlands)

    ESTEVENON, AM; KOOISTRA, J; SICARD, N

    1995-01-01

    An Escherichia coli mutant lacking deoxycytidine triphosphate deaminase (Dcd) activity and an unknown function encoded by a gene designated ior exhibits sensitivity to ionizing radiation whereas dcd mutants themselves are not sensitive. A DNA fragment from an E. coli genomic library that restores th

  18. Sensitivity of the Upper Ocean Temperature and Circulation in the Equatorial Pacific to Solar Radiation Penetration Due to Phytoplankton

    Institute of Scientific and Technical Information of China (English)

    LIN Pengfei; LIU Hailong; ZHANG Xuehong

    2007-01-01

    Solar radiation penetration in the upper ocean is strongly modulated by phytoplankton, which impacts the upper ocean temperature structure, especially in the regions abundant with phytoplankton. In the paper,a new solar radiation penetration scheme, based on the concentration of chlorophyll-a, was introduced into the LASG/IAP (State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics/Institute of Atmospheric Physics) Climate system Ocean Model (LICOM). By comparing the simulations using this new scheme with those using the old scheme that included the constant e-folding attenuation depths in LICOM, it was found that the sea surface temperature (SST) and circulation in the central and eastern equatorial Pacific were both sensitive to the amount of phytoplankton present. Distinct from other regions, the increase of chlorophyll-a concentration would lead to SST decrease in the central and eastern equatorial Pacific. The higher chlorophyll-a concentration at the equator in comparison to the off-equator regions can enlarge the subsurface temperature gradient, which in turn strengthens the upper current near the equator and induces an enhancing upwelling. The enhancing upwelling can then lead to a decrease in the SST in the central and eastern equatorial Pacific. The results of these two sensitive experiments testify to the fact that the meridional gradient in the chlorophyll-a concentration can result in an enhancement in the upper current and a decrease in the SST, along with the observation that a high chlorophyll-a concentration at the equator is one of the predominant reasons leading to a decrease in the SST. This study points out that these results can be qualitatively different simply because of the choice of the solar radiation penetration schemes for comparison. This can help explain previously reported contradictory conclusions.

  19. Chromatin status of apoptosis genes correlates with sensitivity to chemo-, immune- and radiation therapy in colorectal cancer cell lines.

    Science.gov (United States)

    Benard, Anne; Janssen, Connie M; van den Elsen, Peter J; van Eggermond, Marja C J A; Hoon, Dave S B; van de Velde, Cornelis J H; Kuppen, Peter J K

    2014-12-01

    The apoptosis pathway of programmed cell death is frequently deregulated in cancer. An intact apoptosis pathway is required for proper response to anti-cancer treatment. We investigated the chromatin status of key apoptosis genes in the apoptosis pathway in colorectal cancer cell lines in relation to apoptosis induced by chemo-, immune- or radiation therapy. Using chromatin immunoprecipitation (ChIP), we measured the presence of transcription-activating histone modifications H3Ac and H3K4me3 and silencing modifications H3K9me3 and H3K27me3 at the gene promoter regions of key apoptosis genes Bax, Bcl2, Caspase-9, Fas (CD95) and p53. Cell lines DLD1, SW620, Colo320, Caco2, Lovo and HT29 were treated with cisplatin, anti-Fas or radiation. The apoptotic response was measured by flow cytometry using propidium iodide and annexin V-FITC. The chromatin status of the apoptosis genes reflected the activation status of the intrinsic (Bax, Bcl2, Caspase-9 and p53) and extrinsic (Fas) pathways. An active intrinsic apoptotic pathway corresponded to sensitivity to cisplatin and radiation treatment of cell lines DLD1, SW620 and Colo320. An active Fas promoter corresponded to an active extrinsic apoptotic pathway in cell line DLD1. mRNA expression data correlated with the chromatin status of the apoptosis genes as measured by ChIP. In conclusion, the results presented in this study indicate that the balance between activating and silencing histone modifications, reflecting the chromatin status of apoptosis genes, can be used to predict the response of tumor cells to different anti-cancer therapies and could provide a novel target to sensitize tumors to obtain adequate treatment responses.

  20. Radiation-sensitive severe combined immunodeficiency: The arguments for and against conditioning before hematopoietic cell transplantation--what to do?

    Science.gov (United States)

    Cowan, Morton J; Gennery, Andrew R

    2015-11-01

    Defects in DNA cross-link repair 1C (DCLRE1C), protein kinase DNA activated catalytic polypeptide (PRKDC), ligase 4 (LIG4), NHEJ1, and NBS1 involving the nonhomologous end-joining (NHEJ) DNA repair pathway result in radiation-sensitive severe combined immunodeficiency (SCID). Results of hematopoietic cell transplantation for radiation-sensitive SCID suggest that minimizing exposure to alkylating agents and ionizing radiation is important for optimizing survival and minimizing late effects. However, use of preconditioning with alkylating agents is associated with a greater likelihood of full T- and B-cell reconstitution compared with no conditioning or immunosuppression alone. A reduced-intensity regimen using fludarabine and low-dose cyclophosphamide might be effective for patients with LIG4, NHEJ1, and NBS1 defects, although more data are needed to confirm these findings and characterize late effects. For patients with mutations in DCLRE1C (Artemis-deficient SCID), there is no optimal approach that uses standard dose-alkylating agents without significant late effects. Until nonchemotherapy agents, such as anti-CD45 or anti-CD117, become available, options include minimizing exposure to alkylators, such as single-agent low-dose targeted busulfan, or achieving T-cell reconstitution, followed several years later with a conditioning regimen to restore B-cell immunity. Gene therapy for these disorders will eventually remove the issues of rejection and graft-versus-host disease. Prospective multicenter studies are needed to evaluate these approaches in this rare but highly vulnerable patient population.

  1. Sensitivity of radiative properties of persistent contrails to the ice water path

    Directory of Open Access Journals (Sweden)

    R. Rodríguez De León

    2011-07-01

    Full Text Available The dependence of the radiative properties of persistent linear contrails on the variability of their ice water path is assessed in a two-stream radiative transfer model. It is assumed that the ice water content and the effective size of ice crystals in aged contrails do not differ from those observed in natural cirrus; the parameterization of these two variables, based on in situ observations, allows a more realistic representation than the common assumption of fixed values for the contrail optical depth and ice crystal effective radius.

    The results show that the large variability in ice water content that aged contrails may share with natural cirrus, together with an assumed contrail vertical thickness between 220 and 1000 m, translate into a wider range of radiative forcings from linear contrails (0.3 to 51.6 mW m−2 than that reported in previous studies, including IPCC's (3 to 30 mW m−2. The derivation of a best estimate within this range is complicated by the fact that the ice water contents measured in situ imply mean optical depths between 0.08 and 0.32, coinciding with the range commonly assumed in contrail studies, while optical depths derived from satellite ice water content retrievals are significantly larger (0.51–2.02. Further field and modelling studies of the temporal evolution of contrail properties will thus be needed to reduce the uncertainties associated with the values assumed in large scale contrail studies.

  2. Studies on the radiation sensitivity of food microorganism by high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Han Joon; Lee, Eun Jung; Yu, Hyun Hee; Lee, Jae Ho [Korea University, Seoul (Korea, Republic of)

    2010-04-15

    We investigated the radio resistance of pathogenic microorganisms (Bacillus cereus, Staphylococcus aureus, Methicillin resistant Staphylococcus aureus(MRSA) and Escherichia coli O157) in irradiating environments. Their radiation conditions of pathogenic microorganisms varied with pH(3-10), salt concentration(1-15%), temperature(-20, 4 and 25 .deg. C) and atmospheric condition. In addition, the effect of {gamma}-irradiation on the inactivation of pathogenic microorganisms inoculated into food (saengsik, sliced ham, chopped beef) was investigated. The radiation dose ranged from 0 to 3 kGy. The {gamma}--irradiated B.cereus({gamma}--BC) St.aureus({gamma}--SA), MRSA({gamma}--MRSA) and E.coli O157({gamma}--EC) were then cultured and the viable cell count on plate count agar and D10-values(dose required to inactivate 90% of a microbial population) were calculated. The number of pathogenic microorganisms at pH(3-10) and salt concentration(1-15%), temperature(-20, 4 and 25 .deg. C) and atmospheric condition decreased by 1 log CFU/ml after irradiation. The D{sub 10}-value of {gamma}--SA in the optimum condition was 0.152 kGy, and these of {gamma}--MRSA and {gamma}--EC were 0.346 and 0.240 kGy, respectively. The initial cell counts of pathogenic microorganisms in culture broth were slightly decreased as the decrease of pH and the increase of salt concentration. However, radiation resistance of pathogenic microorganisms was increased at frozen state. Moreover, D{sub 10}-values of these is test strains in saengsik, sliced ham and chopped beef were 0.597, 0.226 , 0.398 and 0.416 kGy, respectively. These results provide the basic information for the in activation of pathogenic microorganisms in foods by irradiation

  3. X-ray sensitivity of fifty-three human diploid fibroblast cell strains from patients with characterized genetic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Weichselbaum, R.R.; Nove, J.; Little, J.B.

    1980-03-01

    The in vitro response of 53 human diploid fibroblast strains to x-irradiation was studied using a clonogenic survival assay. The strains, derived from patients with a variety of characterized clinical conditions, most with a genetic component, ranged in Do (a measure of the slope of the survival curve) from 43 to 168 rads. The mean Do's of six strains from normal individuals was 140 to 152 rads, with an overall range, based on the extremes of their standard errors, of 128 to 164 rads. Three-quarters of the strains studied fell within this range. Strains identified as sensitive came from patients with ataxia telangiectasia, progeria, the two genetic forms of retinoblastoma, and partial trisomy of chromosome 13. No marked radiosensitivity was found among strains derived from patients with a number of other conditions associated with a predisposition to malignancy.

  4. Application of a One-Dimensional Position Sensitive Chamber on Synchrotron Radiation

    Science.gov (United States)

    Qi, Huirong; Liu, Mei

    2014-02-01

    In the last few years, wire chambers have been frequently used for X-ray detection because of their low cost, large area and reliability. X-ray diffraction is an irreplaceable method for powder crystal lattice measurements. A one-dimensional single-wire chamber has been developed in our lab to provide high position resolution for powder diffraction experiments using synchrotron radiation. There are 200 readout strips of 0.5 mm width with a pitch of 1.0 mm in the X direction, and the working gas is a mixture of Ar and CO2 (90/10). The one-dimensional position of the original ionization point is determined by the adjacent strip's distribution information using the center of gravity method. Recently, a study of the detector's performance and diffraction image was completed at the 1W1B laboratory of the Beijing Synchrotron Radiation Facility (BSRF) using a sample of SiO2. Most of the relative errors between the measured values of diffraction angles and existing data were less than 1%. The best position resolution achieved for the detector in the test was 71 μm (σ value) with a 20 μm slit collimator. Finally, by changing the detector height in incremental distances from the center of the sample, the one-dimensional detector achieved a two-dimensional diffraction imaging function, and the results are in good agreement with standard data.

  5. Beam test of a one-dimensional position sensitive chamber on synchrotron radiation

    CERN Document Server

    Mei, Liu; Hui-Rong, Qi; Bao-An, Zhuang; Jian, Zhang; Rong-Guang, Liu; Qi-Ming, Zhu; Qun, Ouyang; Yuan-Bo, Chen; Xiao-Shan, Jiang; Ya-Jie, Wang; Peng, Liu; Guang-Cai, Chang

    2013-01-01

    One-dimensional single-wire chamber was developed to provide high position resolution for powder diffraction experiments with synchrotron radiation. A diffraction test using the sample of SiO2 has been accomplished at 1W2B laboratory of Beijing Synchrotron Radiation Source. The data of beam test were analyzed and some diffraction angles were obtained. The experimental results were in good agreement with standard data from ICDD powder diffraction file. The precision of diffraction angles was 1% to 4.7%. Most of relative errors between measured values of diffraction angles and existing data were less than 1%. As for the detector, the best position resolution in the test was 138 um (sigma value) with an X-ray tube. Finally, discussions of the results were given. The major factor that affected the precision of measurement was deviation from the flat structure of detector. The effect was analyzed and it came to a conclusion that it would be the optimal measurement scheme when the distance between the powder sample...

  6. Shortwave radiative heating rate profiles in hazy and clear atmosphere: a sensitivity study

    Science.gov (United States)

    Doppler, Lionel; Fischer, Jürgen; Ravetta, François; Pelon, Jacques; Preusker, René

    2010-05-01

    Aerosols have an impact on shortwave heating rate profiles (additional heating or cooling). In this survey, we quantify the impact of several key-parameters on the heating rate profiles of the atmosphere with and without aerosols. These key-parameters are: (1) the atmospheric model (tropical, midlatitude summer or winter, US Standard), (2) the integrated water vapor amount (IWV ), (3) the ground surface (flat and rough ocean, isotropic surface albedo for land), (4) the aerosol composition (dusts, soots or maritimes mixtures with respect to the OPAC-database classification), (5) the aerosol optical depth and (6) vertical postion, and (7) the single-scattering albedo (?o) of the aerosol mixture. This study enables us to evaluate which parameters are most important to take into account in a radiative energy budget of the atmosphere and will be useful for a future study: the retrieval of heating rates profiles from satellite data (CALIPSO, MODIS, MERIS) over the Mediterranean Sea. All the heating rates are computed by using the vector irradiances computed at each pressure level in the spectral interval 0.2 - 3.6μm (shortwave) by the 1D radiative transfer model for atmosphere and ocean: MOMO (Matrix-Operator MOdel) of the Institute for Space Science, FU Berlin 1

  7. BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xin-Tong; Bao, Ci-Hang; Jia, Yi-Bin; Wang, Nana [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China); Ma, Wei [Department of Radiation Oncology, Cancer Hospital, General Hospital of Ningxia Medical University, Yinchuan 750000 (China); Liu, Fang [Medical Imaging, Shandong Medical College, Jinan 250002 (China); Wang, Cong; Wang, Jian-Bo; Song, Qing-Xu [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China); Cheng, Yu-Feng, E-mail: qlcyf1965@126.com [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China)

    2014-10-03

    Highlights: • BIIB021 downregulated radioresistant proteins in ESCC cell lines. • BIIB021 increased radiation-induced apoptotic cells. • BIIB021 enhanced G{sub 2} arrest in ESCC cell lines. • BIIB021 is a good candidate for radiosensitizer in radiotherapy of ESCC patients. - Abstract: BIIB021 is a novel, orally available inhibitor of heat shock protein 90 (Hsp90) that is currently in phase I/II clinical trials. BIIB021 induces the apoptosis of various types of tumor cells in vitro and in vivo. The aim of this study is to investigate the effect of BIIB021 on the radiosensitivity of esophageal squamous cell carcinoma (ESCC). The results indicated that BIIB021 exhibited strong antitumor activity in ESCC cell lines, either as a single agent or in combination with radiation. BIIB021 significantly downregulated radioresistant proteins including EGFR, Akt, Raf-1 of ESCC cell lines, increased apoptotic cells and enhanced G{sub 2} arrest that is more radiosensitive cell cycle phase. These results suggest that this synthetic Hsp90 inhibitor simultaneously affects multiple pathways involved in tumor development and progression in the ESCC setting and may represent a better strategy for the treatment of ESCC patients, either as a monotherapy or a radiosensitizer.

  8. Sensitivity to ultraviolet radiation of Lassa, vaccinia, and Ebola viruses dried on surfaces.

    Science.gov (United States)

    Sagripanti, Jose-Luis; Lytle, C David

    2011-03-01

    Germicidal UV (also known as UVC) provides a means to decontaminate infected environments as well as a measure of viral sensitivity to sunlight. The present study determined UVC inactivation slopes (and derived D(37) values) of viruses dried onto nonporous (glass) surfaces. The data obtained indicate that the UV resistance of Lassa virus is higher than that of Ebola virus. The UV sensitivity of vaccinia virus (a surrogate for variola virus) appeared intermediate between that of the two virulent viruses studied. In addition, the three viruses dried on surfaces showed a relatively small but significant population of virions (from 3 to 10 % of virus in the inoculum) that appeared substantially more protected by their environment from the effect of UV than the majority of virions tested. The findings reported in this study should assist in estimating the threat posed by the persistence of virus in environments contaminated during epidemics or after an accidental or intentional release.

  9. Rapid sensitive analysis of IDH1 mutation in lower-grade gliomas by automated genetic typing involving a quenching probe.

    Science.gov (United States)

    Kurimoto, Michihiro; Suzuki, Hiromichi; Aoki, Kosuke; Ohka, Fumiharu; Kondo, Goro; Motomura, Kazuya; Iijima, Kentaro; Yamamichi, Akane; Ranjit, Melissa; Wakabayashi, Toshihiko; Kimura, Shinya; Natsume, Atsushi

    2016-01-01

    The authors recently found that 80% of lower-grade gliomas (LGGs) harbored a mutation in IDH1. Intraoperative detection of the mutated IDH1 helps not only differentiate LGGs from other type of brain tumors, but determine the resection border. In the current study, the authors have applied an automated genetic typing involving a quenching probe to detect the mutated IDH1. If tumor cells with the mutated IDH1 contained 10% or more in the mixture of normal and tumor cells, the device could detect it sensitively. The intraoperative assessment of IDH1 mutation is useful in brain tumor surgeries.

  10. Genetic Modeling of Radiation Injury in Prostate Cancer Patients Treated with Radiotherapy

    Science.gov (United States)

    2016-10-01

    nucleotide polymorphisms, prostate cancer, radiation therapy, adverse effects, urinary morbidity, rectal injury, sexual dysfunction 16. SECURITY ...TANC1 paper and the ATM paper]. Literature Cited 1. Viswanathan AN, Yorke ED, Marks LB et al.Radiation dose-volume effects of the urinary bladder... machines , for the other split of the data. The base predictors will be combined into heterogeneous ensemble predictors in a supervised manner so as to

  11. A common genetic determinism for sensitivities to soil water deficit and evaporative demand: meta-analysis of quantitative trait Loci and introgression lines of maize.

    Science.gov (United States)

    Welcker, Claude; Sadok, Walid; Dignat, Grégoire; Renault, Morgan; Salvi, Silvio; Charcosset, Alain; Tardieu, François

    2011-10-01

    Evaporative demand and soil water deficit equally contribute to water stress and to its effect on plant growth. We have compared the genetic architectures of the sensitivities of maize (Zea mays) leaf elongation rate with evaporative demand and soil water deficit. The former was measured via the response to leaf-to-air vapor pressure deficit in well-watered plants, the latter via the response to soil water potential in the absence of evaporative demand. Genetic analyses of each sensitivity were performed over 21 independent experiments with (1) three mapping populations, with temperate or tropical materials, (2) one population resulting from the introgression of a tropical drought-tolerant line in a temperate line, and (3) two introgression libraries genetically independent from mapping populations. A very large genetic variability was observed for both sensitivities. Some lines maintained leaf elongation at very high evaporative demand or water deficit, while others stopped elongation in mild conditions. A complex architecture arose from analyses of mapping populations, with 19 major meta-quantitative trait loci involving strong effects and/or more than one mapping population. A total of 68% of those quantitative trait loci affected sensitivities to both evaporative demand and soil water deficit. In introgressed lines, 73% of the tested genomic regions affected both sensitivities. To our knowledge, this study is the first genetic demonstration that hydraulic processes, which drive the response to evaporative demand, also have a large contribution to the genetic variability of plant growth under water deficit in a large range of genetic material.

  12. Polymorphism of FGFR4 in cancer development and sensitivity to cisplatin and radiation in head and neck cancer.

    Science.gov (United States)

    Ansell, Anna; Farnebo, Lovisa; Grénman, Reidar; Roberg, Karin; Thunell, Lena K

    2009-01-01

    The aim of this study was to investigate the predisposition of the FGFR4 Gly/Arg polymorphism for development of head and neck squamous cell carcinoma (HNSCC) and, furthermore, to examine if the FGFR4 Arg(388) allele can be associated with resistance to chemo- and radiotherapy. When analysing 110 tumour biopsies a significant 1.7-fold increased risk to develop HNSCC in individuals carrying the Gly(388) allele (p=0.026) was found. Moreover a 2-fold increased risk for males harbouring the Gly(388) allele (p=0.031) to develop HNSCC was detected. In 39 HNSCC cell lines the role of the Arg(388) allele for radiation and cisplatin sensitivity was investigated. Our results show no role of the Arg(388) allele for the radiosensitivity (p=0.996) but indicate a tendency to increased cisplatin sensitivity (p=0.141). When screening the transmembrane and kinase domains in the FGFR4 gene a novel mutation, probably generating a truncated protein lacking exons 14-18, was found in six of eight selected cell lines. Taken together, we have here identified a marker that predicts the risk to develop HNSCC and possibly the sensitivity to cisplatin as well as a novel mutation in the FGFR4 gene.

  13. Control of the sensitivity of CRLH interdigital microstrip balanced structures using a co-design genetic algorithm approach

    Science.gov (United States)

    Siragusa, R.; Perret, E.; Nguyen, H. V.; Lemaître-Auger, P.; Tedjini, S.; Caloz, C.

    2011-06-01

    A fully automated tool for designing CRLH interdigital microstrip structures using a co-design synthesis computational approach is proposed and demonstrated experimentally. This approach uses an electromagnetic simulator in conjunction with a genetic algorithm to synthesize and optimize a balanced CRLH interdigital microstrip transmission line. The high sensitivity of a long balanced transmission line to fabrication tolerances is controlled by the use of a high precision 3D simulator. The 2.5D simulator used was found insufficient for a large number of unit cells. A 13 UC CRLH transmission line is designed with the proposed approach. The response sensitivity of the balanced transmission lines to the over/under-etching factor is highlighted by comparing the measurements of four lines with different factors. The effect of over/under-etching is significant for values larger than 10 μm.

  14. Illumination of the Spatial Order of Intracellular pH by Genetically Encoded pH-Sensitive Sensors

    Directory of Open Access Journals (Sweden)

    Mojca Benčina

    2013-12-01

    Full Text Available Fluorescent proteins have been extensively used for engineering genetically encoded sensors that can monitor levels of ions, enzyme activities, redox potential, and metabolites. Certain fluorescent proteins possess specific pH-dependent spectroscopic features, and thus can be used as indicators of intracellular pH. Moreover, concatenated pH-sensitive proteins with target proteins pin the pH sensors to a definite location within the cell, compartment, or tissue. This study provides an overview of the continually expanding family of pH-sensitive fluorescent proteins that have become essential tools for studies of pH homeostasis and cell physiology. We describe and discuss the design of intensity-based and ratiometric pH sensors, their spectral properties and pH-dependency, as well as their performance. Finally, we illustrate some examples of the applications of pH sensors targeted at different subcellular compartments.

  15. Identification and Expression Profiling of Radiation-sensitive Genes Using Plant Model System, Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong-Sub; Kang, Si-Yong; Lee, Geung-Joo; Kim, Jin-Baek

    2008-06-15

    The purpose of this study is to characterize genes specifically expressed in response to ionizing energy (gamma-rays) of acute irradiation and elucidate signalling mechanisms via functional analysis of isolated genes in Arabidopsis thaliana. Recent improvements in DNA microarray technologies and bioinformatics have made it possible to look for common features of ionizing radiation-responsive genes and their regulatory regions. It has produced massive quantities of gene expression and other functional genomics data, and its application will increase in plant genomics. In this study, we used oligonucleotide microarrays to detect the Arabidopsis genes expressed differentially by a gamma-irradiation during the vegetative (VT, 21 DAG) and reproductive (RT, 28 DAG) stages. Wild-type (Ler) Arabidopsis was irradiated with gamma-rays with 100 and 800 Gy doses. Among the 21,500 genes represented in the Agilent chip, approximately 13,500 ({sup {approx}}61.4 %) responsive genes to {nu} -irradiation were expressed with signal intensity greater than 192 when compared to the combined control (non-irradiated vegetative and reproductive pool). Expression patterns of several radiation inducible genes were confirmed by RT-PCR and Northern blotting. Our microarray results may contribute to an overall understanding of the type and quantities of genes that are expressed by an acute gamma-irradiation. In addition, to investigate the oxidative damage caused by irradiation, RT-PCR analysis for the expression of antioxidant isoenzyme genes, and a Transmission Electron Microscope (TEM) observation for visualizing the H{sub 2}O{sub 2} scavenging activity in leaves were applied.

  16. Radiative forcing and feedback by forests in warm climates - a sensitivity study

    Science.gov (United States)

    Port, Ulrike; Claussen, Martin; Brovkin, Victor

    2016-07-01

    We evaluate the radiative forcing of forests and the feedbacks triggered by forests in a warm, basically ice-free climate and in a cool climate with permanent high-latitude ice cover using the Max Planck Institute for Meteorology Earth System Model. As a paradigm for a warm climate, we choose the early Eocene, some 54 to 52 million years ago, and for the cool climate, the pre-industrial climate, respectively. To isolate first-order effects, we compare idealised simulations in which all continents are covered either by dense forests or by deserts with either bright or dark soil. In comparison with desert continents covered by bright soil, forested continents warm the planet for the early Eocene climate and for pre-industrial conditions. The warming can be attributed to different feedback processes, though. The lapse-rate and water-vapour feedback is stronger for the early Eocene climate than for the pre-industrial climate, but strong and negative cloud-related feedbacks nearly outweigh the positive lapse-rate and water-vapour feedback for the early Eocene climate. Subsequently, global mean warming by forests is weaker for the early Eocene climate than for pre-industrial conditions. Sea-ice related feedbacks are weak for the almost ice-free climate of the early Eocene, thereby leading to a weaker high-latitude warming by forests than for pre-industrial conditions. When the land is covered with dark soils, and hence, albedo differences between forests and soil are small, forests cool the early Eocene climate more than the pre-industrial climate because the lapse-rate and water-vapour feedbacks are stronger for the early Eocene climate. Cloud-related feedbacks are equally strong in both climates. We conclude that radiative forcing by forests varies little with the climate state, while most subsequent feedbacks depend on the climate state.

  17. Genetic variation during persistent reovirus infection: isolation of cold-sensitive and temperature-sensitive mutants from persistently infected L cells.

    Science.gov (United States)

    Ahmed, R; Kauffman, R S; Fields, B N

    1983-11-01

    We have examined the evolution of reovirus in two independently established persistently infected (p.i.) cell lines. We found that reovirus undergoes extensive mutation during persistent infection in L cells. However, there was no consistent pattern of virus evolution; in one p.i. cell line temperature-sensitive (ts) mutants were selected, whereas cold-sensitive (cs) mutants were isolated from the second p.i. culture. Neither the cs nor the ts mutants isolated from the carrier cultures expressed their defect at 37 degrees, the temperature at which the p.i. cells were maintained, indicating that the cs and ts phenotypes were nonselected markers. These results emphasize the point that emergence of the ts or cs mutants during persistent infection only signifies that the virus has changed; it does not necessarily imply that the particular mutant is essential for the maintenance of the persistent infection. Given the high mutation rate of viruses, and the wide spectrum of viral mutants present in carrier cultures, it is essential to distinguish the relevant changes from those which may simply represent an epiphenomenon. In the accompanying paper (R. S. Kauffman, R. Ahmed, and B. N. Fields Virology, 130, 79-87, 1983), we show that by using a genetic approach, it is possible to identify the viral gene(s) which are critical for the maintenance of persistent reovirus infection.

  18. Genetic and Environmental Risk Factors for Childhood Eczema Development and Allergic Sensitization in the CCAAPS Cohort

    OpenAIRE

    Myers, Jocelyn M. Biagini; Wang, Ning; LeMasters, Grace; Bernstein, David I; Epstein, Tolly; Lindsey, Mark; Ericksen, Mark; Chakraborty, Ranajit; Ryan, Patrick; Villareal, Manuel; Burkle, Jeff; Lockey, James; Reponen, Tiina; Hershey, Gurjit K Khurana

    2009-01-01

    Eczema is very common and increasing in prevalence. Prospective studies investigating environmental and genetic risk factors for eczema in a birth cohort are lacking. We evaluated risk factors that may promote development of childhood eczema in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort (n = 762) of infants with at least one atopic parent. Objective environmental exposure data were available for each participant. At annual physical examinations, children un...

  19. Angular dependence of dose sensitivity of nanoDot optically stimulated luminescent dosimeters in different radiation geometries

    Energy Technology Data Exchange (ETDEWEB)

    Jursinic, Paul A., E-mail: pjursinic@wmcc.org [West Michigan Cancer Center, 200 North Park Street, Kalamazoo, Michigan 49007 (United States)

    2015-10-15

    Purpose: A type of in vivo dosimeter, an optically stimulated luminescent dosimeter, OSLD, may have dose sensitivity that depends on the angle of incidence of radiation. This work measures how angular dependence of a nanoDot changes with the geometry of the phantom in which irradiation occurs and with the intrinsic structure of the nanoDot. Methods: The OSLDs used in this work were nanoDot dosimeters (Landauer, Inc., Glenwood, IL), which were read with a MicroStar reader (Landauer, Inc., Glenwood, IL). Dose to the OSLDs was delivered by 6 MV x-rays. NanoDots with various intrinsic sensitivities were irradiated in numerous phantoms that had geometric shapes of cylinders, rectangles, and a cube. Results: No angular dependence was seen in cylindrical phantoms, cubic phantoms, or rectangular phantoms with a thickness to width ratio of 0.3 or 1.5. An angular dependence of 1% was observed in rectangular phantoms with a thickness to width of 0.433–0.633. A group of nanoDots had sensitive layers with mass density of 2.42–2.58 g/cm{sup 3} and relative sensitivity of 0.92–1.09 and no difference in their angular dependence. Within experimental uncertainty, nanoDot measurements agree with a parallel-plate ion chamber at a depth of maximum dose. Conclusions: When irradiated in cylindrical, rectangular, and cubic phantoms, nanoDots show a maximum angular dependence of 1% or less at an incidence angle of 90°. For a sample of 78 new nanoDots, the range of their relative intrinsic sensitivity is 0.92–1.09. For a sample of ten nanoDots, on average, the mass in the sensitive layer is 73.1% Al{sub 2}O{sub 3}:C and 26.9% polyester. The mass density of the sensitive layer of a nanoDot disc is between 2.42 and 2.58 g/cm{sup 3}. The angular dependence is not related to Al{sub 2}O{sub 3}:C loading of the nanoDot disc. The nanoDot at the depth of maximum dose has no more angular dependence than a parallel-plate ion chamber.

  20. Ultraviolet sensitivity of the addition, deletion and replacement of long nonhomologous DNA segments by genetic transformation of Haemophilus influenzae

    Energy Technology Data Exchange (ETDEWEB)

    Walter, R.B.; Stuy, J.H. (Florida State Univ., Tallahassee (USA). Dept. of Biological Science)

    1982-03-01

    The construction and some properties of Haemophilus influenzae Rd strains with long and different R plasmid-derived DNA segments (nonhomologous inserts) at the same site in the HP1 prophage have previously been described. These inserts can be added to a recipient's genome by genetic transformation, they can be deleted from the recipient genome, or they can be replaced by another insert. It is reported that the UV inactivation of all three phenomena followed single hit kinetics. Deletion was roughly 10 times more resistant; its UV-sensitivity equalled that of a high-efficiency point mutation. There was an inverse correlation between UV-sensitivity and additive transformation efficiency of the various inserts; sensitivity may thus be a measure of insert size. This correlation was not seen for deletion. All three phenomena were more sensitive when they were measured on excision repair-deficient uvr/sup -/ recipients. The dose-reduction factor for addition was about 1.5 while it was about 2.6 for deletion.

  1. Evaluating the effects of genetic variants of DNA repair genes using cytogenetic mutagen sensitivity approaches.

    Science.gov (United States)

    Abdel-Rahman, Sherif Z; El-Zein, Randa A

    2011-08-01

    Mutagen sensitivity, measured in short-term cultures of peripheral blood lymphocytes by cytogenetic endpoints, is an indirect measure for DNA repair capacity and has been used for many years as a biomarker for intrinsic susceptibility for cancer. In this article, we briefly give an overview of the different cytogenetic mutagen sensitivity approaches that have been used successfully to evaluate the biological effects of polymorphisms in DNA repair genes based on a current review of the literature and based on the need for biomarkers that would allow the characterization of the biological and functional significance of such polymorphisms. We also address some of the future challenges facing this emerging area of research.

  2. Genetic variants in PI3K/AKT pathway are associated with severe radiation pneumonitis in lung cancer patients treated with radiation therapy.

    Science.gov (United States)

    Tang, Yang; Liu, Bo; Li, Jing; Wu, Huanlei; Yang, Ju; Zhou, Xiao; Yi, Mingxiao; Li, Qianxia; Yu, Shiying; Yuan, Xianglin

    2016-01-01

    PI3K/AKT pathway plays important roles in inflammatory and fibrotic diseases while its connection to radiation pneumonitis (RP) is unclear. In this study, we explored the associations of genetic variants in PI3K/AKT pathway with RP in lung cancer patients with radiotherapy. Two hundred and sixty one lung cancer patients with radiotherapy were included in this prospective study (NCT02490319) and genotyped by MassArray and Sanger Sequence methods. By multivariate Cox hazard analysis and multiple testing, GA/GG genotype of AKT2: rs33933140 (HR = 0.272, 95% CI: 0.140-0.530, P = 1.3E-4, Pc = 9.1E-4), and the GT/GG genotype of PI3CA: rs9838117 (HR = 0.132, 95% CI: 0.042-0.416, P = 0.001, Pc = 0.006) were found to be strongly associated with a decreased occurrence of RP ≥ grade 3. And patients with the CT/TT genotype of AKT2: rs11880261 had a notably higher incidence of RP ≥ grade 3 (HR = 2.950, 95% CI: 1.380-6.305, P = 0.005, Pc = 0.025). We concluded that the genetic variants of PI3K/AKT pathway were significantly related to RP of grade ≥ 3 and may thus be predictors of severe RP before radiotherapy, if further validated in larger population.

  3. Genetic Sensitivity to Peer Behaviors: "5HTTLPR", Smoking, and Alcohol Consumption

    Science.gov (United States)

    Daw, Jonathan; Shanahan, Michael; Harris, Kathleen Mullan; Smolen, Andrew; Haberstick, Brett; Boardman, Jason D.

    2013-01-01

    We investigate whether the serotonin transporter-linked polymorphic region ("5HTTLPR"), a gene associated with environmental sensitivity, moderates the association between smoking and drinking patterns at adolescents' schools and their corresponding risk for smoking and drinking themselves. Drawing on the school-based design of the National…

  4. Genetic Sensitivity to Peer Behaviors: "5HTTLPR", Smoking, and Alcohol Consumption

    Science.gov (United States)

    Daw, Jonathan; Shanahan, Michael; Harris, Kathleen Mullan; Smolen, Andrew; Haberstick, Brett; Boardman, Jason D.

    2013-01-01

    We investigate whether the serotonin transporter-linked polymorphic region ("5HTTLPR"), a gene associated with environmental sensitivity, moderates the association between smoking and drinking patterns at adolescents' schools and their corresponding risk for smoking and drinking themselves. Drawing on the school-based design of the National…

  5. Chemical Genetics Approach to Engineer Kinesins with Sensitivity towards a Small-Molecule Inhibitor of Eg5.

    Science.gov (United States)

    Möckel, Martin M; Hund, Corinna; Mayer, Thomas U

    2016-11-03

    Due to their fast and often reversible mode of action, small molecules are ideally suited to dissect biological processes. Yet, the validity of small-molecule studies is intimately tied to the specificity of the applied compounds, thus imposing a great challenge to screens for novel inhibitors. Here, we applied a chemical-genetics approach to render kinesin motor proteins sensitive to inhibition by the well-characterized small molecule S-Trityl-l-cysteine (STLC). STLC specifically inhibits the kinesin Eg5 through binding to a known allosteric site within the motor domain. Transfer of this allosteric binding site into the motor domain of the human kinesins Kif3A and Kif4A sensitizes them towards STLC. Single-molecule microscopy analyses confirmed that STLC inhibits the movement of chimeric but not wild-type Kif4A along microtubules. Thus, our proof-of-concept study revealed that this chemical-genetic approach provides a powerful strategy to specifically inhibit kinesins in vitro for which small-molecule inhibitors are not yet available. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. The R527H mutation in LMNA gene causes an increased sensitivity to ionizing radiation.

    Science.gov (United States)

    di Masi, Alessandra; D'Apice, Maria Rosaria; Ricordy, Ruggero; Tanzarella, Caterina; Novelli, Giuseppe

    2008-07-01

    Mandibuloacral dysplasia type A (MADA; OMIM # 248370) is a premature ageing disease caused by the homozygous R527H mutation in the LMNA gene. At the cellular level, MADA is characterized by unprocessed prelamin A accumulation, nuclear architecture alterations, chromatin defects and increased incidence of apoptosis. In some progeroid laminopathies (e.g., HGPS) it has been demonstrated that such biochemical and morphological alterations are strongly linked with genomic instability. To test this also in MADA fibroblasts, their response to the ionising radiation-induced damage was analysed. We observed that their ability to repair the damage was significantly impaired, as demonstrated by the increased chromosome damage and the higher percentage of residual gamma-H2AX foci, corresponding to unrepaired DNA-damage sites. Moreover, MADA fibroblasts showed a markedly reduced phosphorylation of p53 at Ser15(S15) and a lower induction of p53 and CDKN1A proteins after irradiation, compared to the control cell line. Upon irradiation, we also detected differences in the expression of some p53 downstream target genes. In addition, MADA cells showed partial defects in the checkpoint response, particularly in G(1)/S transition. Our results indicate that accumulation of the lamin A precursor protein determines a defect in DNA damage response after X-ray exposure, supporting a crucial role of lamin A in regulating DNA repair process and cell cycle control.

  7. Cloud sensitivity studies for stratospheric and lower mesospheric ozone profile retrievals from measurements of limb scattered solar radiation

    Directory of Open Access Journals (Sweden)

    T. Sonkaew

    2009-02-01

    Full Text Available Clouds in the atmosphere play an important role in reflection, absorption and transmission of solar radiation affecting trace gas retrievals. The main goal of this paper is to examine the sensitivity of stratospheric and lower mesospheric ozone retrievals from limb-scattered radiance measurements to clouds using the SCIATRAN radiative transfer model and retrieval package. Assuming an aerosol-free atmosphere and Mie phase functions for cloud particles, we compute the relative error of ozone profile retrievals in a cloudy atmosphere if clouds are neglected in the retrieval. To access altitudes from the lower stratosphere up to lower mesosphere, we combine the retrievals in the Chappuis and Hartley ozone absorption bands. We find significant cloud sensitivity of the limb ozone retrievals in the Chappuis bands at lower stratospheric altitudes. The relative error in the retrieved ozone concentrations gradually decreases with increasing altitude and becomes negligible above about 40 km. The parameters with the largest impact on the ozone retrievals are cloud optical thickness, ground albedo and solar zenith angle. Clouds with different geometrical thicknesses or different cloud altitudes have a similar impact on the ozone retrievals for a given cloud optical thickness value, if the clouds are outside the field of view of the instrument. The effective radius of water droplets has a small influence on the error, i.e., less than 0.5% at altitudes above the cloud top height. Furthermore, the impact of clouds on the ozone profile retrievals was found to have a rather small dependence on the solar azimuth angle (less than 1% for all possible azimuth angles. For the most frequent cloud types the total error is below 6% above 15 km altitude, if clouds are completely neglected in the retrieval. Neglecting clouds in the ozone profile retrievals generally leads to a low bias for a low ground albedo and to a high bias for a high ground albedo, assuming that the

  8. Radiobiological studies with the nematode Caenorhabditis elegans. Genetic and developmental effects of high LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, G.A.; Schubert, W.W.; Marshall, T.M. (Jet Propulsion Lab., Pasadena, CA (United States))

    1992-01-01

    The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long-duration space flights where exposure levels represents a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets. There are many consequences of this feature to biological endpoints when compared with effects of ionizing photons. Dose vs response and dose-rate kinetics may be modified, DNA and cellular repair systems may be altered in their abilities to cope with damage, and the qualitative features of damage may be unique for different ions. The nematode Caenorhabditis elegans is being used to address these and related questions associated with exposure to radiation. HZE-induced mutation, chromosome aberration, cell inactivation and altered organogenesis are discussed along with plans for radiobiological experiments in space. (author).

  9. Radiobiological studies with the nematode Caenorhabditis elegans. Genetic and developmental effects of high LET radiation

    Science.gov (United States)

    Nelson, G. A.; Schubert, W. W.; Marshall, T. M.

    1992-01-01

    The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long-duration space flights where exposure levels represent a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets. There are many consequences of this feature to biological endpoints when compared with effects of ionizing photons. Dose vs response and dose-rate kinetics may be modified, DNA and cellular repair systems may be altered in their abilities to cope with damage, and the qualitative features of damage may be unique for different ions. The nematode Caenorhabditis elegans is being used to address these and related questions associated with exposure to radiation. HZE-induced mutation, chromosome aberration, cell inactivation and altered organogenesis are discussed along with plans for radiobiological experiments in space.

  10. Trefoil factor 3 (TFF3) enhances the oncogenic characteristics of prostate carcinoma cells and reduces sensitivity to ionising radiation.

    Science.gov (United States)

    Perera, Omesha; Evans, Angharad; Pertziger, Mikhail; MacDonald, Christa; Chen, Helen; Liu, Dong-Xu; Lobie, Peter E; Perry, Jo K

    2015-05-28

    Trefoil factor 3 (TFF3) is a secreted protein which functions in mucosal repair of the gastrointestinal tract. This is achieved through the combined stimulation of cell migration and prevention of apoptosis and anoikis, thus facilitating repair. Deregulated TFF3 expression at the gene and protein level is implicated in numerous cancers. In prostate cancer TFF3 has previously been reported as a potential biomarker, overexpressed in a subset of primary and metastatic cases. Here we investigated the effect of increased TFF3 expression on prostate cancer cell behaviour. Oncomine analysis demonstrated that TFF3 mRNA expression was upregulated in prostate cancer compared to normal tissue. Forced-expression models were established in the prostate cancer cell lines, DU145 and PC3, by stable transfection of an expression vector containing the TFF3 cDNA. Forced expression of TFF3 significantly increased total cell number and cell viability, cell proliferation and cell survival. In addition, TFF3 enhanced anchorage independent growth, 3-dimensional colony formation, wound healing and cell migration compared to control transfected cell lines. We also observed reduced sensitivity to ionising radiation in stably transfected cell lines. In dose response experiments, forced expression of TFF3 significantly enhanced the regrowth of PC3 cells following ionising radiation compared with control transfected cells. In addition, TFF3 enhanced clonogenic survival of DU145 and PC3 cells. These studies indicate that targeting TFF3 for the treatment of prostate cancer warrants further investigation.

  11. Plasma Taurine, Diabetes Genetic Predisposition, and Changes of Insulin Sensitivity in Response to Weight-Loss Diets.

    Science.gov (United States)

    Zheng, Yan; Ceglarek, Uta; Huang, Tao; Wang, Tiange; Heianza, Yoriko; Ma, Wenjie; Bray, George A; Thiery, Joachim; Sacks, Frank M; Qi, Lu

    2016-10-01

    Taurine metabolism disturbance is closely linked to obesity, insulin resistance, and diabetes. Previous evidence suggested that the preventative effects of taurine on diabetes might be through regulating the expression levels of diabetes-related genes. We estimated whether blood taurine levels modified the overall genetic susceptibility to diabetes on improvement of insulin sensitivity in a randomized dietary trial. We genotyped 31 diabetes-associated variants to calculate a genetic risk score (GRS) and measured plasma taurine levels and glycemic traits among participants from the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial. Seven-hundred eleven overweight or obese participants (age 30-70 y; 60% females) had genetic variants genotyped and blood taurine levels measured. Participants went on 2-year weight-loss diets, which were different in macronutrient composition. Improvements in glycemic traits were measured. We found that baseline taurine levels significantly modified the effects of diabetes GRS on changes in fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) during the 2-year diet intervention (P-interaction = .04, .01, .002, respectively), regardless of weight loss. High baseline taurine levels were associated with a less reduction in both glucose and HOMA-IR among the participants with the lowest tertile of diabetes GRS (both P = .02), and with a greater reduction in both insulin and HOMA-IR among those with the highest tertile of diabetes GRS (both P = .04). Our data suggest that blood taurine levels might differentially modulate the effects of diabetes-related genes on improvement of insulin sensitivity among overweight/obese patients on weight-loss diets.

  12. mTOR inhibition reduces cellular proliferation and sensitizes pituitary adenoma cells to ionizing radiation.

    Science.gov (United States)

    Sukumari-Ramesh, Sangeetha; Singh, Nagendra; Dhandapani, Krishnan M; Vender, John R

    2011-02-23

    Pituitary adenomas are the most frequent brain tumor in adults. Although histologically benign, pituitary tumors cause significant morbidity and mortality. Neurosurgery and medical therapeutics may lessen the morbidity and mortality associated with pituitary tumors; however, these treatments are associated with significant adverse side effects. Thus, an improved understanding of pituitary adenomas at the molecular and cellular level is needed to design novel therapeutic compounds. To assess the effect of mammalian target of rapamycin (mTOR) inhibition on pituitary adenoma cells, rat GH3 or MMQ cells were treated with the clinically useful mTOR inhibitors, rapamycin or RAD001. Cellular proliferation and growth following exposure to mTOR inhibitors or radiation were assessed using biochemical methods. In the present study, we observed basal activation of mTOR, downstream of constitutive Akt signaling, in rat GH3 adenoma cells. Functionally, the mTOR inhibitors, rapamycin and RAD001 (500 pM-5 nM), induced G1 growth arrest within 24 hours, an effect associated with reduced cellular proliferation. Both rapamycin and RAD001 decreased the phosphorylation of mTOR at the serine 2448, a key determinant of mTOR activity. Inhibition of mTOR also radiosensitized GH3 cells such that 2.5 Gy in combination with 500 pM rapamycin or RAD001 reduced cellular viability more effectively than 2.5 or 10 Gy alone. These data may support a possible therapeutic role for mTOR inhibitors in limiting the cellular proliferation and radioresistance of pituitary adenoma cells.

  13. Sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation will increase in lipopolysaccharide-induced inflammation in vitro model

    OpenAIRE

    Zuo, Wen-Qi; Hu, Yu-Juan; Yang, Yang; Zhao, Xue-Yan; Zhang,Yuan-Yuan; Kong, Wen; Kong, Wei-Jia

    2015-01-01

    Background With the increasing popularity of mobile phones, the potential hazards of radiofrequency electromagnetic radiation (RF-EMR) on the auditory system remain unclear. Apart from RF-EMR, humans are also exposed to various physical and chemical factors. We established a lipopolysaccharide (LPS)-induced inflammation in vitro model to investigate whether the possible sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation (at specific absorption ra...

  14. Label-free and high-sensitive detection for genetic point mutation based on hyperspectral interferometry

    Science.gov (United States)

    Fu, Rongxin; Li, Qi; Zhang, Junqi; Wang, Ruliang; Lin, Xue; Xue, Ning; Su, Ya; Jiang, Kai; Huang, Guoliang

    2016-10-01

    Label free point mutation detection is particularly momentous in the area of biomedical research and clinical diagnosis since gene mutations naturally occur and bring about highly fatal diseases. In this paper, a label free and high sensitive approach is proposed for point mutation detection based on hyperspectral interferometry. A hybridization strategy is designed to discriminate a single-base substitution with sequence-specific DNA ligase. Double-strand structures will take place only if added oligonucleotides are perfectly paired to the probe sequence. The proposed approach takes full use of the inherent conformation of double-strand DNA molecules on the substrate and a spectrum analysis method is established to point out the sub-nanoscale thickness variation, which benefits to high sensitive mutation detection. The limit of detection reach 4pg/mm2 according to the experimental result. A lung cancer gene point mutation was demonstrated, proving the high selectivity and multiplex analysis capability of the proposed biosensor.

  15. STUDY OF SENSITIVITY OF THE PARAMETERS OF A GENETIC ALGORITHM FOR DESIGN OF WATER DISTRIBUTION NETWORKS

    Directory of Open Access Journals (Sweden)

    Pedro L. Iglesias

    2007-01-01

    Full Text Available The Genetic Algorithms (GAs are a technique of optimization used for water distribution networks design. This work has been made with a modified pseudo genetic algorithm (PGA, whose main variation with a classical GA is a change in the codification of the chromosomes, which is made of numerical form instead of the binary codification. This variation entails a series of special characteristics in the codification and in the definition of the operations of mutation and crossover. Initially, the work displays the results of the PGA on a water network studied in the literature. The results show the kindness of the method. Also is made a statistical analysis of the obtained solutions. This analysis allows verifying the values of mutation and crossing probability more suitable for the proposed method. Finally, in the study of the analyzed water supply networks the concept of reliability in introduced. This concept is essential to understand the validity of the obtained results. The second part, starting with values optimized for the probability of crossing and mutation, the influence of the population size is analyzed in the final solutions on the network of Hanoi, widely studied in the bibliography. The aim is to find the most suitable configuration of the problem, so that good solutions are obtained in the less time.

  16. STUDY OF SENSITIVITY OF THE PARAMETERS OF A GENETIC ALGORITHM FOR DESIGN OF WATER DISTRIBUTION NETWORKS

    Directory of Open Access Journals (Sweden)

    Pedro L. Iglesias

    2007-12-01

    Full Text Available The Genetic Algorithms (GAs are a technique of optimization used for water distribution networks design. This work has been made with a modified pseudo genetic algorithm (PGA, whose main variation with a classical GA is a change in the codification of the chromosomes, which is made of numerical form instead of the binary codification. This variation entails a series of special characteristics in the codification and in the definition of the operations of mutation and crossover. Initially, the work displays the results of the PGA on a water network studied in the literature. The results show the kindness of the method. Also is made a statistical analysis of the obtained solutions. This analysis allows verifying the values of mutation and crossing probability more suitable for the proposed method. Finally, in the study of the analyzed water supply networks the concept of reliability in introduced. This concept is essential to understand the validity of the obtained results. The second part, starting with values optimized for the probability of crossing and mutation, the influence of the population size is analyzed in the final solutions on the network of Hanoi, widely studied in the bibliography. The aim is to find the most suitable configuration of the problem, so that good solutions are obtained in the less time.

  17. Efficiently Hiding Sensitive Itemsets with Transaction Deletion Based on Genetic Algorithms

    Directory of Open Access Journals (Sweden)

    Chun-Wei Lin

    2014-01-01

    Full Text Available Data mining is used to mine meaningful and useful information or knowledge from a very large database. Some secure or private information can be discovered by data mining techniques, thus resulting in an inherent risk of threats to privacy. Privacy-preserving data mining (PPDM has thus arisen in recent years to sanitize the original database for hiding sensitive information, which can be concerned as an NP-hard problem in sanitization process. In this paper, a compact prelarge GA-based (cpGA2DT algorithm to delete transactions for hiding sensitive itemsets is thus proposed. It solves the limitations of the evolutionary process by adopting both the compact GA-based (cGA mechanism and the prelarge concept. A flexible fitness function with three adjustable weights is thus designed to find the appropriate transactions to be deleted in order to hide sensitive itemsets with minimal side effects of hiding failure, missing cost, and artificial cost. Experiments are conducted to show the performance of the proposed cpGA2DT algorithm compared to the simple GA-based (sGA2DT algorithm and the greedy approach in terms of execution time and three side effects.

  18. 辐射敏感器件辐射设计裕量指标的计算%An Algorithm of Radiation Design Margins Index for Radiation Sensitive Devices

    Institute of Scientific and Technical Information of China (English)

    刘燕芳

    2015-01-01

    为了降低辐射对操作设备所产生的危害,在寿命周期内满足规定的连续性和可用性等可靠性指标要求。综合考虑设备所处位置的辐射特性,建立了总剂量效应敏感器件和位移损伤效应敏感器件RDM的一种计算方法。建设性地提出了辐射敏感器件施加不同RDM值所对应的风险等级,为在辐射环境下操作设备的设计工作寿命提供了保证。%In order to reduce the harmful effects of the operation equipment which works in the radiation environ-ment, meet the requirements of continuity and availability within the life cycle, considering the position envi-ronmental characteristics of the operation equipment, an algorithm of radiation design margins for total dose effect sensitive devices and displacement damage effect sensitive devices was given, which can control the radia-tion damage risk.Four risk levels basic on different radiation design margin of the radiation-sensitive devices were described, which can provide a guarantee for the design life of the equipment used in the radiation environment.

  19. Genetic background of enhanced radioresistance in an anhydrobiotic insect: transcriptional response to ionizing radiations and desiccation.

    Science.gov (United States)

    Ryabova, Alina; Mukae, Kyosuke; Cherkasov, Alexander; Cornette, Richard; Shagimardanova, Elena; Sakashita, Tetsuya; Okuda, Takashi; Kikawada, Takahiro; Gusev, Oleg

    2017-01-01

    It is assumed that resistance to ionizing radiation, as well as cross-resistance to other abiotic stresses, is a side effect of the evolutionary-based adaptation of anhydrobiotic animals to dehydration stress. Larvae of Polypedilum vanderplanki can withstand prolonged desiccation as well as high doses of ionizing radiation exposure. For a further understanding of the mechanisms of cross-tolerance to both types of stress exposure, we profiled genome-wide mRNA expression patterns using microarray techniques on the chironomid larvae collected at different stages of desiccation and after exposure to two types of ionizing radiation-70 Gy of high-linear energy transfer (LET) ions ((4)He) and the same dose of low-LET radiation (gamma rays). In expression profiles, a wide transcriptional response to desiccation stress that much exceeded the amount of up-regulated transcripts to irradiation exposure was observed. An extensive group of coincidently up-regulated overlapped transcripts in response to desiccation and ionizing radiation was found. Among this, overlapped set of transcripts was indicated anhydrobiosis-related genes: antioxidants, late embryogenesis abundant (LEA) proteins, and heat-shock proteins. The most overexpressed group was that of protein-L-isoaspartate/D-aspartate O-methyltransferase (PIMT), while probes, corresponding to LEA proteins, were the most represented. Performed functional analysis showed strongly enriched gene ontology terms associated with protein methylation. In addition, active processes of DNA repair were detected. We assume that the cross-tolerance of the sleeping chironomid to both desiccation and irradiation exposure comes from a complex mechanism of adaptation to anhydrobiosis.

  20. Reduction of Radioactive Backgrounds in Electroformed Copper for Ultra-Sensitive Radiation Detectors

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, Eric W. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Aalseth, Craig E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Farmer, Orville T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hossbach, Todd W. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Liezers, Martin [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Miley, Harry S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Overman, Nicole R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Reeves, James H. [Reeves and Son LLC., Richland, WA (United States)

    2014-07-07

    Abstract Ultra-pure construction materials are required for the next generation of neutrino physics, dark matter and environmental science applications. These new efforts require materials with purity levels at or below 1 uBq/kg 232Th and 238U. Yet radiometric analysis lacks sensitivity below ~10 uBq/kg for the U and Th decay chains. This limits both the selection of clean materials and the validation of purification processes. Copper is an important high-purity material for low-background experiments due to the ease with which it can be purified by electrochemical methods. Electroplating for purification into near-final shapes, known as electroforming, is one such method. Continued refinement of the copper electroforming process is underway, for the first time guided by an ICP-MS based assay method that can measure 232Th and 238U near the desired purity levels. An assay of electroformed copper at 10 uBq/kg for 232Th has been achieved and is described. The implications of electroformed copper at or better than this purity on next-generation low-background experiments are discussed.

  1. Reduction of radioactive backgrounds in electroformed copper for ultra-sensitive radiation detectors

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, E.W., E-mail: eric.hoppe@pnnl.gov [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Aalseth, C.E.; Farmer, O.T.; Hossbach, T.W.; Liezers, M.; Miley, H.S.; Overman, N.R. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Reeves, J.H. [Reeves and Son LLC, 10 Albert Ave., Richland, WA 99352 (United States)

    2014-11-11

    Ultra-pure construction materials are required for the next generation of neutrino physics, dark matter and environmental science applications. These materials are also important for use in high-purity germanium spectrometers used in screening materials for radiopurity. The next-generation science applications require materials with radiopurity levels at or below 1 μBq/kg {sup 232}Th and {sup 238}U. Yet radiometric analysis lacks sensitivity below ∼10 μBq/kg for the U and Th decay chains. This limits both the selection of clean materials and the validation of purification processes. Copper is an important high-purity material for low-background experiments due to the ease with which it can be purified by electrochemical methods. Electroplating for purification into near-final shapes, known as electroforming, is one such method. Continued refinement of the copper electroforming process is underway, for the first time guided by an ICP-MS based assay method that can measure {sup 232}Th and {sup 238}U near the desired purity levels. An assay of electroformed copper at a μBq/kg level has been achieved and is described. The implications of electroformed copper at or better than this purity on next-generation low-background experiments are discussed.

  2. [Justifying genetic and immune markers of efficiency and sensitivity under combined exposure to risk factors in mining industry workers].

    Science.gov (United States)

    Dolgikh, O V; Zaitseva, N V; Krivtsov, A V; Gorshkova, K G; Lanin, D V; Bubnova, O A; Dianova, D G; Lykhina, T S; Vdovina, N A

    2014-01-01

    The authors evaluated and justified immunologic and genetic markers under combined exposure to risk factors in mining industry workers. Analysis covered polymorphism features of 29 genes with variant alleles possibly participating in occupationally conditioned diseases formation and serving as sensitivity markers of these diseases risk. The genes association selected demonstrates reliably changed polymorphism vs. the reference group (SOD2 superoxidedismutase gene, ANKK1 dophamine receptor gene, SULT1A1 sulphtransaminase gene, MTHFR methylene tetrahydrofolate reductase gene, VEGF endothelial growth factor gene, TNF-alpha tumor necrosis factor gene). Under combined exposure to occupational hazards (sylvinite dust, noise) in mining industry, this association can serve as adequate marking complex of sensitivity to development of occupationally conditioned diseases. Increased-production of immune cytokine regulation markers: tumor necrosis factor and vascular endothelial growth factor. Genes SOD2, ANKK1, SULT1A1, VEGF, TNFalpha are recommended as sensitivity markers, and the coded cytokines (tumor necrosis factor and endothelial growth factor) are proposed as effect markers in evaluation of health risk for workers in mining industry.

  3. Identification of the common radiation-sensitive and glucose metabolism-related expressed genes in the thymus of ICR and AKR/J mice

    Energy Technology Data Exchange (ETDEWEB)

    Bong, Jin Jong; Kang, Yumi; Choi, Suk Cjul; Choi, Moo Hyun; Choi, Seung Jin; Kim, Hee Sun [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd, Seoul (Korea, Republic of)

    2011-11-15

    Our goal was to identify the common radiation-sensitive expressed genes in the thymus of ICR and AKR/J mice on 100 days after irradiation. Thus, we performed microarray analysis for thymus of ICR and AKR/J mice, respectively. We categorized differential expressed genes by the analysis of DAVID Bioinformatics Resources v 6.7 and GeneSpring GX 11.5.1 and validated gene expression patterns by QPCR analysis. Our result demonstrated that radiation-sensitive expressed genes and signaling pathways in the thymus of irradiated ICR and AKR/J mice.

  4. The sensitivity of tropical convective precipitation to the direct radiative forcings of black carbon aerosols emitted from major regions

    Directory of Open Access Journals (Sweden)

    C. Wang

    2009-10-01

    Full Text Available Previous works have suggested that the direct radiative forcing (DRF of black carbon (BC aerosols are able to force a significant change in tropical convective precipitation ranging from the Pacific and Indian Ocean to the Atlantic Ocean. In this in-depth analysis, the sensitivity of this modeled effect of BC on tropical convective precipitation to the emissions of BC from 5 major regions of the world has been examined. In a zonal mean base, the effect of BC on tropical convective precipitation is a result of a displacement of ITCZ toward the forcing (warming hemisphere. However, a substantial difference exists in this effect associated with BC over different continents. The BC effect on convective precipitation over the tropical Pacific Ocean is found to be most sensitive to the emissions from Central and North America due to a persistent presence of BC aerosols from these two regions in the lowermost troposphere over the Eastern Pacific. The BC effect over the tropical Indian and Atlantic Ocean is most sensitive to the emissions from South as well as East Asia and Africa, respectively. Interestingly, the summation of these individual effects associated with emissions from various regions mostly exceeds their actual combined effect as shown in the model run driven by the global BC emissions, so that they must offset each other in certain locations and a nonlinearity of this type of effect is thus defined. It is known that anthropogenic aerosols contain many scattering-dominant constituents that might exert an effect opposite to that of absorbing BC. The combined aerosol forcing is thus likely differing from the BC-only one. Nevertheless, this study along with others of its kind that isolates the DRF of BC from other forcings provides an insight of the potentially important climate response to anthropogenic forcings particularly related to the unique particulate solar absorption.

  5. Differential sensitivity of coral larvae to natural levels of ultraviolet radiation during the onset of larval competence.

    KAUST Repository

    Aranda, Manuel

    2011-07-01

    Scleractinian corals are the major builders of the complex structural framework of coral reefs. They live in tropical waters around the globe where they are frequently exposed to potentially harmful ultraviolet radiation (UVR). The eggs and early embryonic stages of some coral species are highly buoyant and remain near the sea surface for prolonged periods of time and may therefore be the most sensitive life stages with respect to UVR. Here, we analysed gene expression changes in five developmental stages of the Caribbean coral Montastraea faveolata to natural levels of UVR using high-density cDNA microarrays (10 930 clones). We found that larvae exhibit low sensitivity to natural levels of UVR during early development as reflected by comparatively few transcriptomic changes in response to UVR. However, we identified a time window of high UVR sensitivity that coincides with the motile planula stage and the onset of larval competence. These processes have been shown to be affected by UVR exposure, and the transcriptional changes we identified explain these observations well. Our analysis of differentially expressed genes indicates that UVR alters the expression of genes associated with stress response, the endoplasmic reticulum, Ca(2+) homoeostasis, development and apoptosis during the motile planula stage and affects the expression of neurogenesis-related genes that are linked to swimming and settlement behaviour at later stages. Taken together, our study provides further data on the impact of natural levels of UVR on coral larvae. Furthermore, our results might allow a better prediction of settlement and recruitment rates after coral spawning events if UVR climate data are taken into account.

  6. Artificial semi-rigid tissue sensitized with natural pigments: Effect of photon radiations

    Directory of Open Access Journals (Sweden)

    Adnan Jaradat

    2011-01-01

    Full Text Available Background: A new approach for evaluating the optical penetration depth and testing its validity with Monte Carlo simulations and Kubelka-Munk theory is used for artificial semi-rigid tissue sensitized with natural pigments. Photodynamic therapy is a promising cancer treatment in which a photosensitizing drug concentrates in malignant cells and is activated by visible light at certain wavelength. Materials and Methods: Cheap artificial semi-rigid tissue incorporated with scattering and absorbing materials along with some other composites comparable to normal human tissue has been performed. The optical parameters as measured with different conditions and calculated with various techniques are investigated. Results: The probability of interaction of light with tissue is very high when exposed to light in presence of Cichorium pumilum and RBCs followed by photohemolysis or/and photodegradation. The optical penetration depth calculated by linear absorption coefficient ranges from 0.63 to 2.85 mm is found to be comparable to those calculated using Kubelka-Munk theory or Monte Carlo simulation (range from 0.78 to 2.42 mm. The ratio of absorption to the scattering is independent of thickness and decreases with increasing irradiation time. Moreover, the optical parameters as well as their ratios are in very good agreement in the two approaches of calculation. The values of absorption and scattering coefficients are independent of thickness. Furthermore, the average photon ranges in the samples containing no scattering and absorbing materials are about three times greater than those samples containing scattering materials. Conclusion: Our results suggest that light propagation with optical properties presented in this work could be applicable in diagnostic and therapeutic of the human biological tissue for photodynamic therapy.

  7. Induction of interferon by temperature-sensitive mutants of Newcastle disease virus. [Uv radiation, chick embryos

    Energy Technology Data Exchange (ETDEWEB)

    Kowal, K.J.; Youngner, J.S.

    1978-10-01

    Spontaneously selected and mutagen-induced temperature-sensitive (ts) mutants of Newcastle disease virus (NDV) were used to study interferon induction in chick embryo (CE) cells at temperatures permissive (37/sup 0/) and nonpermissive (42/sup 0/) for virus replication. Both infectious and uv-irradiated virus were tested for interferon-inducing ability in cells pretreated or not pretreated with homologous interferon. At 37/sup 0/, only uv-irradiated NDV was capable of inducing interferon in cells not treated with interferon before infection. In cells pretreated with interferon, on the other hand, both unirradiated and uv-irradiated virus stimulated the production of interferon. At 42/sup 0/, the interferon-inducing phenotype for some uv-irradiated ts mutants was dependent on whether or not cells were pretreated with interferon. For example, out of 10 mutants examined, one uv-irradiated ts mutant induced interferon in both untreated and interferon pretreated cells; 7 mutants failed to induce in untreated cells but induced from 25 to 100 percent of the wild-type level of interferon in cells pretreated with interferon; and two mutants failed to induce interferon in both types of cells. In addition, one mutant (NDV/sub 0/ ts-100) induced low or undetectable levels of interferon at both 37 and 42/sup 0/, conditions under which wild-type virus (NDV/sub 0/) produced significant levels of interferon. Co-infection of cells with uv-irradiated ts-100 and a preparation of NDV/sub 0/ exposed to prolonged irradiation resulted in considerable production of interferon. These results suggest the possibility that more than one virus function may be involved in interferon induction by NDV in CE cells.

  8. The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity.

    Directory of Open Access Journals (Sweden)

    Slavé Petrovski

    2015-09-01

    Full Text Available Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at recognizing the sequence stretches in the human genome that are most important in regulating the expression of genes. For this reason, it is difficult to apply to the regulatory regions the same kinds of analytical paradigms that are being successfully applied to identify mutations among protein-coding regions that influence risk. To determine whether dosage sensitive genes have distinct patterns among their noncoding sequence, we present two primary approaches that focus solely on a gene's proximal noncoding regulatory sequence. The first approach is a regulatory sequence analogue of the recently introduced residual variation intolerance score (RVIS, termed noncoding RVIS, or ncRVIS. The ncRVIS compares observed and predicted levels of standing variation in the regulatory sequence of human genes. The second approach, termed ncGERP, reflects the phylogenetic conservation of a gene's regulatory sequence using GERP++. We assess how well these two approaches correlate with four gene lists that use different ways to identify genes known or likely to cause disease through changes in expression: 1 genes that are known to cause disease through haploinsufficiency, 2 genes curated as dosage sensitive in ClinGen's Genome Dosage Map, 3 genes judged likely to be under purifying selection for mutations that change expression levels because they are statistically depleted of loss-of-function variants in the general population, and 4 genes judged unlikely to cause disease based on the presence of copy number variants in the general population. We find that both noncoding scores are highly predictive of dosage sensitivity using any of these criteria. In a similar way to ncGERP, we assess two ensemble-based predictors of regional noncoding

  9. The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity.

    Science.gov (United States)

    Petrovski, Slavé; Gussow, Ayal B; Wang, Quanli; Halvorsen, Matt; Han, Yujun; Weir, William H; Allen, Andrew S; Goldstein, David B

    2015-09-01

    Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at recognizing the sequence stretches in the human genome that are most important in regulating the expression of genes. For this reason, it is difficult to apply to the regulatory regions the same kinds of analytical paradigms that are being successfully applied to identify mutations among protein-coding regions that influence risk. To determine whether dosage sensitive genes have distinct patterns among their noncoding sequence, we present two primary approaches that focus solely on a gene's proximal noncoding regulatory sequence. The first approach is a regulatory sequence analogue of the recently introduced residual variation intolerance score (RVIS), termed noncoding RVIS, or ncRVIS. The ncRVIS compares observed and predicted levels of standing variation in the regulatory sequence of human genes. The second approach, termed ncGERP, reflects the phylogenetic conservation of a gene's regulatory sequence using GERP++. We assess how well these two approaches correlate with four gene lists that use different ways to identify genes known or likely to cause disease through changes in expression: 1) genes that are known to cause disease through haploinsufficiency, 2) genes curated as dosage sensitive in ClinGen's Genome Dosage Map, 3) genes judged likely to be under purifying selection for mutations that change expression levels because they are statistically depleted of loss-of-function variants in the general population, and 4) genes judged unlikely to cause disease based on the presence of copy number variants in the general population. We find that both noncoding scores are highly predictive of dosage sensitivity using any of these criteria. In a similar way to ncGERP, we assess two ensemble-based predictors of regional noncoding importance, nc

  10. Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.

    Science.gov (United States)

    Wen, Juyi; Liu, Hongliang; Wang, Qiming; Liu, Zhensheng; Li, Yangkai; Xiong, Huihua; Xu, Ting; Li, Peng; Wang, Li-E; Gomez, Daniel R; Mohan, Radhe; Komaki, Ritsuko; Liao, Zhongxing; Wei, Qingyi

    2014-07-01

    LIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumourigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A) and LIN28B (rs314280 G>A, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio(chemo)therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders. Multivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ⩾3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR=2.97 and 2.23, 95% confidence interval (CI)=1.32-6.72 and 1.01-4.94, P=0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR=2.30 and 2.00, 95% CI=1.24-4.28 and 1.11-3.62, and P=0.008 and 0.022, respectively). Further stratified analyses showed a more consistent and profound risk in the subgroups of age LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings. Copyright © 2014. Published by Elsevier Ltd.

  11. Ethics, genetics and dynamics: an emerging systematic approach to radiation protection of the environment.

    Science.gov (United States)

    Pentreath, R J

    2004-01-01

    There is now a general consensus of opinion that an explicit approach is necessary to demonstrate radiation protection of the environment, and that this approach needs to be developed in a systematic way. The framework that is emerging links ethical and moral issues (anthropocentric, biocentric, and ecocentric) to broad-based principles and objectives of environmental protection (sustainable development, maintaining biological diversity, and habitat protection) and then links these, in turn, to the needs of current environmental management practices, such as environmental exploitation, pollution control, and nature conservation. The relevance of this to radiation is that its effects (such as causing early mortality, morbidity, reduced reproductive success, as well as resulting in observable (scorable) cytogenetic damage) are those that may have a bearing on these same environmental management practices. The devise that would appear to be most useful to bridge the gap between our disparate data on radiation effects and the needs of environmental management, is that of adding to the concept of Reference Man in the shape of a small set of Reference Animals and Plants. This approach has now been adopted by the ICRP, adding new dynamics-the motive forces, both moral and physical-to the subject. The way is now clear for rapid progress to be made on a number of fronts.

  12. Ethics, genetics and dynamics: an emerging systematic approach to radiation protection of the environment

    Energy Technology Data Exchange (ETDEWEB)

    Pentreath, R.J

    2004-07-01

    There is now a general consensus of opinion that an explicit approach is necessary to demonstrate radiation protection of the environment, and that this approach needs to be developed in a systematic way. The framework that is emerging links ethical and moral issues (anthropocentric, biocentric, and ecocentric) to broad-based principles and objectives of environmental protection (sustainable development, maintaining biological diversity, and habitat protection) and then links these, in turn, to the needs of current environmental management practices, such as environmental exploitation, pollution control, and nature conservation. The relevance of this to radiation is that its effects (such as causing early mortality, morbidity, reduced reproductive success, as well as resulting in observable (scorable) cytogenetic damage) are those that may have a bearing on these same environmental management practices. The devise that would appear to be most useful to bridge the gap between our disparate data on radiation effects and the needs of environmental management, is that of adding to the concept of Reference Man in the shape of a small set of Reference Animals and Plants. This approach has now been adopted by the ICRP, adding new dynamics--the motive forces, both moral and physical--to the subject. The way is now clear for rapid progress to be made on a number of fronts.

  13. Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination.

    Science.gov (United States)

    Refetoff, Samuel; Dumitrescu, Alexandra M

    2007-06-01

    At least six major steps are required for secreted thyroid hormone (TH) to exert its action on target tissues. Mutations interfering with three of these steps have been so far identified. The first recognized defect, which causes resistance to TH, involves the TH receptor beta gene and has been given the acronym RTH. Occurring in approximately 1 per 40,000 newborns, more than 1000 affected subjects, from 339 families, have been identified. The gene defect remains unknown in 15% of subjects with RTH. Two novel syndromes causing reduced sensitivity to TH were recently identified. One, producing severe psychomotor defects in > 100 males from 26 families, is caused by mutations in the cell-membrane transporter of TH, MCT8; the second, affecting the intracellular metabolism of TH in four individuals from two families, is caused by mutations in the SECISBP2 gene, which is required for the synthesis of selenoproteins, including TH deiodinases.

  14. Sharing privacy-sensitive access to neuroimaging and genetics data: a review and preliminary validation

    Science.gov (United States)

    Sarwate, Anand D.; Plis, Sergey M.; Turner, Jessica A.; Arbabshirani, Mohammad R.; Calhoun, Vince D.

    2014-01-01

    The growth of data sharing initiatives for neuroimaging and genomics represents an exciting opportunity to confront the “small N” problem that plagues contemporary neuroimaging studies while further understanding the role genetic markers play in the function of the brain. When it is possible, open data sharing provides the most benefits. However, some data cannot be shared at all due to privacy concerns and/or risk of re-identification. Sharing other data sets is hampered by the proliferation of complex data use agreements (DUAs) which preclude truly automated data mining. These DUAs arise because of concerns about the privacy and confidentiality for subjects; though many do permit direct access to data, they often require a cumbersome approval process that can take months. An alternative approach is to only share data derivatives such as statistical summaries—the challenges here are to reformulate computational methods to quantify the privacy risks associated with sharing the results of those computations. For example, a derived map of gray matter is often as identifiable as a fingerprint. Thus alternative approaches to accessing data are needed. This paper reviews the relevant literature on differential privacy, a framework for measuring and tracking privacy loss in these settings, and demonstrates the feasibility of using this framework to calculate statistics on data distributed at many sites while still providing privacy. PMID:24778614

  15. A drug-sensitive genetic network masks fungi from the immune system.

    Directory of Open Access Journals (Sweden)

    Robert T Wheeler

    2006-04-01

    Full Text Available Fungal pathogens can be recognized by the immune system via their beta-glucan, a potent proinflammatory molecule that is present at high levels but is predominantly buried beneath a mannoprotein coat and invisible to the host. To investigate the nature and significance of "masking" this molecule, we characterized the mechanism of masking and consequences of unmasking for immune recognition. We found that the underlying beta-glucan in the cell wall of Candida albicans is unmasked by subinhibitory doses of the antifungal drug caspofungin, causing the exposed fungi to elicit a stronger immune response. Using a library of bakers' yeast (Saccharomyces cerevisiae mutants, we uncovered a conserved genetic network that is required for concealing beta-glucan from the immune system and limiting the host response. Perturbation of parts of this network in the pathogen C. albicans caused unmasking of its beta-glucan, leading to increased beta-glucan receptor-dependent elicitation of key proinflammatory cytokines from primary mouse macrophages. By creating an anti-inflammatory barrier to mask beta-glucan, opportunistic fungi may promote commensal colonization and have an increased propensity for causing disease. Targeting the widely conserved gene network required for creating and maintaining this barrier may lead to novel broad-spectrum antimycotics.

  16. Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis.

    Science.gov (United States)

    Mou, Haiwei; Moore, Jill; Malonia, Sunil K; Li, Yingxiang; Ozata, Deniz M; Hough, Soren; Song, Chun-Qing; Smith, Jordan L; Fischer, Andrew; Weng, Zhiping; Green, Michael R; Xue, Wen

    2017-04-04

    Genetic lesions that activate KRAS account for ∼30% of the 1.6 million annual cases of lung cancer. Despite clinical need, KRAS is still undruggable using traditional small-molecule drugs/inhibitors. When oncogenic Kras is suppressed by RNA interference, tumors initially regress but eventually recur and proliferate despite suppression of Kras Here, we show that tumor cells can survive knockout of oncogenic Kras, indicating the existence of Kras-independent survival pathways. Thus, even if clinical KRAS inhibitors were available, resistance would remain an obstacle to treatment. Kras-independent cancer cells exhibit decreased colony formation in vitro but retain the ability to form tumors in mice. Comparing the transcriptomes of oncogenic Kras cells and Kras knockout cells, we identified 603 genes that were specifically up-regulated in Kras knockout cells, including the Fas gene, which encodes a cell surface death receptor involved in physiological regulation of apoptosis. Antibodies recognizing Fas receptor efficiently induced apoptosis of Kras knockout cells but not oncogenic Kras-expressing cells. Increased Fas expression in Kras knockout cells was attributed to decreased association of repressive epigenetic marks at the Fas promoter. Concordant with this observation, treating oncogenic Kras cells with histone deacetylase inhibitor and Fas-activating antibody efficiently induced apoptosis, thus bypassing the need to inhibit Kras. Our results suggest that activation of Fas could be exploited as an Achilles' heel in tumors initiated by oncogenic Kras.

  17. Capillary electrophoresis with electrochemiluminescent detection for highly sensitive assay of genetically modified organisms.

    Science.gov (United States)

    Guo, Longhua; Yang, Huanghao; Qiu, Bin; Xiao, Xueyang; Xue, Linlin; Kim, Donghwan; Chen, Guonan

    2009-12-01

    A capillary electrophoresis coupled with electrochemiluminescent detection system (CE-ECL) was developed for the detection of polymerase chain reaction (PCR) amplicons. The ECL luminophore, tris(1,10-phenanthroline) ruthenium(II) (Ru(phen)(3)(2+)), was labeled to the PCR primers before amplification. Ru(phen)(3)(2+) was then introduced to PCR amplicons by PCR amplification. Eventually, the PCR amplicons were separated and detected by the homemade CE-ECL system. The detection of a typical genetically modified organism (GMO), Roundup Ready Soy (RRS), was shown as an example to demonstrate the reliability of the proposed approach. Four pairs of primers were amplified by multiple PCR (MPCR) simultaneously, three of which were targeted on the specific sequence of exogenous genes of RRS, and another was targeted on the endogenous reference gene of soybean. Both the conditions for PCR amplification and CE-ECL separation and detection were investigated in detail. Results showed that, under the optimal conditions, the proposed method can accurately identifying RRS. The corresponding limit of detection (LOD) was below 0.01% with 35 PCR cycles.

  18. Integrative approach to pain genetics identifies pain sensitivity loci across diseases.

    Science.gov (United States)

    Ruau, David; Dudley, Joel T; Chen, Rong; Phillips, Nicholas G; Swan, Gary E; Lazzeroni, Laura C; Clark, J David; Butte, Atul J; Angst, Martin S

    2012-01-01

    Identifying human genes relevant for the processing of pain requires difficult-to-conduct and expensive large-scale clinical trials. Here, we examine a novel integrative paradigm for data-driven discovery of pain gene candidates, taking advantage of the vast amount of existing disease-related clinical literature and gene expression microarray data stored in large international repositories. First, thousands of diseases were ranked according to a disease-specific pain index (DSPI), derived from Medical Subject Heading (MESH) annotations in MEDLINE. Second, gene expression profiles of 121 of these human diseases were obtained from public sources. Third, genes with expression variation significantly correlated with DSPI across diseases were selected as candidate pain genes. Finally, selected candidate pain genes were genotyped in an independent human cohort and prospectively evaluated for significant association between variants and measures of pain sensitivity. The strongest signal was with rs4512126 (5q32, ABLIM3, P = 1.3×10⁻¹⁰) for the sensitivity to cold pressor pain in males, but not in females. Significant associations were also observed with rs12548828, rs7826700 and rs1075791 on 8q22.2 within NCALD (P = 1.7×10⁻⁴, 1.8×10⁻⁴, and 2.2×10⁻⁴ respectively). Our results demonstrate the utility of a novel paradigm that integrates publicly available disease-specific gene expression data with clinical data curated from MEDLINE to facilitate the discovery of pain-relevant genes. This data-derived list of pain gene candidates enables additional focused and efficient biological studies validating additional candidates.

  19. Integrative approach to pain genetics identifies pain sensitivity loci across diseases.

    Directory of Open Access Journals (Sweden)

    David Ruau

    Full Text Available Identifying human genes relevant for the processing of pain requires difficult-to-conduct and expensive large-scale clinical trials. Here, we examine a novel integrative paradigm for data-driven discovery of pain gene candidates, taking advantage of the vast amount of existing disease-related clinical literature and gene expression microarray data stored in large international repositories. First, thousands of diseases were ranked according to a disease-specific pain index (DSPI, derived from Medical Subject Heading (MESH annotations in MEDLINE. Second, gene expression profiles of 121 of these human diseases were obtained from public sources. Third, genes with expression variation significantly correlated with DSPI across diseases were selected as candidate pain genes. Finally, selected candidate pain genes were genotyped in an independent human cohort and prospectively evaluated for significant association between variants and measures of pain sensitivity. The strongest signal was with rs4512126 (5q32, ABLIM3, P = 1.3×10⁻¹⁰ for the sensitivity to cold pressor pain in males, but not in females. Significant associations were also observed with rs12548828, rs7826700 and rs1075791 on 8q22.2 within NCALD (P = 1.7×10⁻⁴, 1.8×10⁻⁴, and 2.2×10⁻⁴ respectively. Our results demonstrate the utility of a novel paradigm that integrates publicly available disease-specific gene expression data with clinical data curated from MEDLINE to facilitate the discovery of pain-relevant genes. This data-derived list of pain gene candidates enables additional focused and efficient biological studies validating additional candidates.

  20. Polo-like kinase 1 (PLK1 inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells

    Directory of Open Access Journals (Sweden)

    Harris Peter S

    2012-03-01

    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (PLK1 is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy. Methods We examined the expression of PLK1 mRNA in medulloblastoma tumor samples using microarray analysis. The impact of PLK1 on cell proliferation was evaluated by depleting expression with RNA interference (RNAi or by inhibiting function with the small molecule inhibitor BI 2536. Colony formation studies were performed to examine the impact of BI 2536 on medulloblastoma cell radiosensitivity. In addition, the impact of depleting PLK1 mRNA on tumor-initiating cells was evaluated using tumor sphere assays. Results Analysis of gene expression in two independent cohorts revealed that PLK1 mRNA is overexpressed in some, but not all, medulloblastoma patient samples when compared to normal cerebellum. Inhibition of PLK1 by RNAi significantly decreased medulloblastoma cell proliferation and clonogenic potential and increased cell apoptosis. Similarly, a low nanomolar concentration of BI 2536, a small molecule inhibitor of PLK1, potently inhibited cell growth, strongly suppressed the colony-forming ability, and increased cellular apoptosis of medulloblastoma cells. Furthermore, BI 2536 pretreatment sensitized medulloblastoma cells to ionizing radiation. Inhibition of PLK1 impaired tumor sphere formation of medulloblastoma cells and decreased the expression of SRY (sex determining region Y-box 2 (SOX2 mRNA in tumor spheres indicating a possible role in targeting tumor inititiating cells. Conclusions Our data suggest that targeting PLK1 with small molecule inhibitors, in combination with radiation therapy, is a novel strategy in the treatment of

  1. Strain Dependent Genetic Networks for Antibiotic-Sensitivity in a Bacterial Pathogen with a Large Pan-Genome.

    Directory of Open Access Journals (Sweden)

    Tim van Opijnen

    2016-09-01

    Full Text Available The interaction between an antibiotic and bacterium is not merely restricted to the drug and its direct target, rather antibiotic induced stress seems to resonate through the bacterium, creating selective pressures that drive the emergence of adaptive mutations not only in the direct target, but in genes involved in many different fundamental processes as well. Surprisingly, it has been shown that adaptive mutations do not necessarily have the same effect in all species, indicating that the genetic background influences how phenotypes are manifested. However, to what extent the genetic background affects the manner in which a bacterium experiences antibiotic stress, and how this stress is processed is unclear. Here we employ the genome-wide tool Tn-Seq to construct daptomycin-sensitivity profiles for two strains of the bacterial pathogen Streptococcus pneumoniae. Remarkably, over half of the genes that are important for dealing with antibiotic-induced stress in one strain are dispensable in another. By confirming over 100 genotype-phenotype relationships, probing potassium-loss, employing genetic interaction mapping as well as temporal gene-expression experiments we reveal genome-wide conditionally important/essential genes, we discover roles for genes with unknown function, and uncover parts of the antibiotic's mode-of-action. Moreover, by mapping the underlying genomic network for two query genes we encounter little conservation in network connectivity between strains as well as profound differences in regulatory relationships. Our approach uniquely enables genome-wide fitness comparisons across strains, facilitating the discovery that antibiotic responses are complex events that can vary widely between strains, which suggests that in some cases the emergence of resistance could be strain specific and at least for species with a large pan-genome less predictable.

  2. Strain Dependent Genetic Networks for Antibiotic-Sensitivity in a Bacterial Pathogen with a Large Pan-Genome.

    Science.gov (United States)

    van Opijnen, Tim; Dedrick, Sandra; Bento, José

    2016-09-01

    The interaction between an antibiotic and bacterium is not merely restricted to the drug and its direct target, rather antibiotic induced stress seems to resonate through the bacterium, creating selective pressures that drive the emergence of adaptive mutations not only in the direct target, but in genes involved in many different fundamental processes as well. Surprisingly, it has been shown that adaptive mutations do not necessarily have the same effect in all species, indicating that the genetic background influences how phenotypes are manifested. However, to what extent the genetic background affects the manner in which a bacterium experiences antibiotic stress, and how this stress is processed is unclear. Here we employ the genome-wide tool Tn-Seq to construct daptomycin-sensitivity profiles for two strains of the bacterial pathogen Streptococcus pneumoniae. Remarkably, over half of the genes that are important for dealing with antibiotic-induced stress in one strain are dispensable in another. By confirming over 100 genotype-phenotype relationships, probing potassium-loss, employing genetic interaction mapping as well as temporal gene-expression experiments we reveal genome-wide conditionally important/essential genes, we discover roles for genes with unknown function, and uncover parts of the antibiotic's mode-of-action. Moreover, by mapping the underlying genomic network for two query genes we encounter little conservation in network connectivity between strains as well as profound differences in regulatory relationships. Our approach uniquely enables genome-wide fitness comparisons across strains, facilitating the discovery that antibiotic responses are complex events that can vary widely between strains, which suggests that in some cases the emergence of resistance could be strain specific and at least for species with a large pan-genome less predictable.

  3. Construction and Genetic Analysis of Murine Hepatitis Virus Strain A59 Nsp16 Temperature Sensitive Mutant and the Revertant Virus

    Institute of Scientific and Technical Information of China (English)

    Guo-hui Chang; Bao-jun Luo; Pin Lu; Lei Lin; Xiao-yan Wu; Jing Li; Yi Hu; Qing-yu Zhu

    2011-01-01

    Coronaviruses (CoVs) are generally associated with respiratory and enteric infections and have long been recognized as important pathogens of livestock and companion animals. Mouse hepatitis virus (MHV) is a widely studied model system for Coronavirus replication and pathogenesis. In this study, we created a MHV-A59 temperature sensitive (ts) mutant Wu"-ts18(cd) using the recombinant vaccinia reverse genetics system. Virus replication assay in 17C1-1 cells showed the plaque phenotype and replication characterization of constructed Wu"-ts18(cd) were indistinguishable from the reported ts mutant Wu"-ts 18. Then we cultured the ts mutant Wu"-ts 18(cd) at non-permissive temperature 39.5℃, which "forced" the ts recombinant virus to use second-site mutation to revert from a ts to a non-ts phenotype. Sequence analysis showed most of the revertants had the same single amino acid mutation at Nsp16 position 43. The single amino acid mutation at Nsp16 position 76 or position 130 could also revert the ts mutant Wu"-ts 18 (cd) to non-ts phenotype, an additional independent mutation in Nsp13 position 115 played an important role on plaque size. The results provided us with genetic information on the functional determinants of Nsp16. This allowed us to build up a more reasonable model of CoVs replication-transcription complex.

  4. Surface solar radiation and hydrological cycle in 20th century China: sensitivity studies with ECHAM5-HAM

    Science.gov (United States)

    Folini, D.; Wild, M.

    2012-04-01

    The world, and China in particular, has seen a tremendous population growth and industrialization in the 20th century. These changes were accompanied, among others, by a substantial increase in aerosol emission. To learn more about associated consequences for the climate system we have carried out a comparatively large set of transient sensitivity studies with the global atmosphere only climate model ECHAM5-HAM, using aerosol emission data from NIES (National Institute of Environmental Studies, Japan) and prescribed, observation based sea surface temperatures (SSTs) from the Hadley Center. The sensitivity studies cover the period from 1870 to 2005 and comprise ensembles of simulations (up to 13 members per ensemble), which allow to address the role of different aerosol species, greenhouse gases, and prescribed sea surface temperatures. Here we analyze these simulation data with particular focus on surface solar radiation, temperature, and the hydrological cycle in China. Physical mechanisms able to explain the results will be discussed. We generally find the strongest effects in the east of the country, where urbanization and industrialization is strongest and emissions increased most. The decrease of surface solar radiation (SSR) under clear sky conditions reaches up to around -8 W / m2 per decade from 1950 to 1990. Comparable values are found for all sky conditions. Dimming ceases in the second half of the 1990s, when we even see a renewed increase in SSR in some regions. Overall, these findings are in line with observation based estimates. Modeled surface temperatures reflect the decrease in SSR but carry also a substantial SST signature. After remaining roughly constant from 1870 to 1900, we find modeled surface temperatures to increase by about 1 degree Celsius till 1950, then decrease again by -0.2 to -1.2 degree Celsius till 1990, before a renewed increase sets in. Precipitation decreases in our model results from 1950 to 2000 by up to 10% or 150 mm per year

  5. Genetic and environmental risk factors for childhood eczema development and allergic sensitization in the CCAAPS cohort.

    Science.gov (United States)

    Biagini Myers, Jocelyn M; Wang, Ning; LeMasters, Grace K; Bernstein, David I; Epstein, Tolly G; Lindsey, Mark A; Ericksen, Mark B; Chakraborty, Ranajit; Ryan, Patrick H; Villareal, Manuel S; Burkle, Jeff W; Lockey, James E; Reponen, Tiina; Khurana Hershey, Gurjit K

    2010-02-01

    Eczema is very common and increasing in prevalence. Prospective studies investigating environmental and genetic risk factors for eczema in a birth cohort are lacking. We evaluated risk factors that may promote development of childhood eczema in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort (n=762) of infants with at least one atopic parent. Objective environmental exposure data were available for each participant. At annual physical examinations, children underwent skin prick tests (SPTs), eczema was diagnosed by a clinician, and DNA was collected. Among Caucasian children, 39% developed eczema by age 3. Children with a pet dog were significantly less likely to have eczema at age one (odds ratio (OR)=0.62, 95% confidence interval (CI): 0.40-0.97) or at both ages 2 and 3 (OR=0.54, 95% CI: 0.30-0.97). This finding was most significant among children carrying the CD14-159C/T CC genotype. Carriers of the CD14-159C/T and IL4Ralpha I75V single-nucleotide polymorphisms (SNPs) had an increased risk of eczema at both ages 2 and 3 (OR=3.44, 95% CI: 1.56-7.57), especially among children who were SPT+. These results provide new insights into the pathogenesis of eczema in high-risk children and support a protective role for early exposure to dog, especially among those carrying the CD14-159C/T SNP. The results also demonstrate a susceptibility effect of the combination of CD14 and IL4Ralpha SNPs with eczema.

  6. Childhood Trauma and Children’s Emerging Psychotic Symptoms: A Genetically Sensitive Longitudinal Cohort Study

    Science.gov (United States)

    Arseneault, Louise; Cannon, Mary; Fisher, Helen L.; Polanczyk, Guilherme; Moffitt, Terrie E.; Caspi, Avshalom

    2012-01-01

    Objective Using longitudinal and prospective measures of trauma during childhood, the authors assessed the risk of developing psychotic symptoms associated with maltreatment, bullying, and accidents in a nationally representative U.K. cohort of young twins. Method Data were from the Environmental Risk Longitudinal Twin Study, which follows 2,232 twin children and their families. Mothers were interviewed during home visits when children were ages 5, 7, 10, and 12 on whether the children had experienced maltreatment by an adult, bullying by peers, or involvement in an accident. At age 12, children were asked about bullying experiences and psychotic symptoms. Children’s reports of psychotic symptoms were verified by clinicians. Results Children who experienced maltreatment by an adult (relative risk=3.16, 95% CI=1.92–5.19) or bullying by peers (relative risk=2.47, 95% CI=1.74–3.52) were more likely to report psychotic symptoms at age 12 than were children who did not experience such traumatic events. The higher risk for psychotic symptoms was observed whether these events occurred early in life or later in childhood. The risk associated with childhood trauma remained significant in analyses controlling for children’s gender, socioeconomic deprivation, and IQ; for children’s early symptoms of internalizing or externalizing problems; and for children’s genetic liability to developing psychosis. In contrast, the risk associated with accidents was small (relative risk=1.47, 95% CI=1.02–2.13) and inconsistent across ages. Conclusions Trauma characterized by intention to harm is associated with children’s reports of psychotic symptoms. Clinicians working with children who report early symptoms of psychosis should inquire about traumatic events such as maltreatment and bullying. PMID:20952460

  7. Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Hawes Alicia C

    2007-11-01

    Full Text Available Abstract Background Community acquired (CA methicillin-resistant Staphylococcus aureus (MRSA increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear. Results We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA, isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from S. epidermidis. The USA300 sequence was aligned with other sequenced S. aureus genomes and regions unique to USA300 MRSA were identified. Conclusion USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens.

  8. Study of genetic effects of high energy radiations with different ionizing capacities on extracellular phages.

    Science.gov (United States)

    Bresler, S E; Kalinin, V L; Kopylova, Y U; Krivisky, A S; Rybchin, V N; Shelegedin, V N

    1975-07-01

    The inactivating and mutagenic action of high-energy radiations with different ionizing capacities (gamma-rays, protons, alpha-particles and accelerated ions of 12C and 20Ne) was studied by using coliphages lambda11 and SD as subjects. In particular the role of irradiation conditions (broth suspension, pure buffer, dry samples) and of the host functions recA, exrA and polA was investigated. The dose-response curve of induced mutagenesis was studied by measuring the yield of vir mutants in lambda11 and plaque mutants in SD. The following results were obtained. (1) The inactivation kinetics of phages under the action of gamma-rays and protons was first order to a survival of 10(-7). Heavy ions also showed exponential inactivation kinetics to a survival of 10(-4). At higher doses of 20Ne ion bombardment some deviation from one-hit kinetics was observed. For dry samples of phages the dimensions of targets for all types of radiation were approximately proportional to the molecular weights of phage DNA's. For densely ionizing radiation (heavy ions) the inactivating action was 3-5 times weaker than for gamma-rays and protons. (2) Mutagenesis was observed for all types of radiation, but heavy ions were 1-5-2 times less efficient than gamma-rays. For both phages studied the dose-response curve of mutagenesis was non-linear. The dependence on the dose was near to parabolic for lambda11. For SD a plateau or maximum of mutagenesis was observed for the relative number of mutants at a survival of about 10(-4). (3) Host-cell functions recA and exrA were practically indifferent for survival of gamma-irradiated phage lambda11, but indispensable for mutagenesis. Mutation recAI3 abolished induced vir mutations totally and exrA- reduced them significantly. The absence of the function polA had a considerable influence on phage survival, but no effect on vir mutation yield (if compared at the same survival level). (4) In conditions of indirect action of gamma-rays no vir mutations were

  9. Radiation-induced intestinal neoplasia in a genetically-predisposed mouse (Min)

    Energy Technology Data Exchange (ETDEWEB)

    Ellender, M.; Larder, S.M.; Harrison, J.D.; Cox, R.; Silver, A.R.J. [National Radiological Protection Board, Chilton (United Kingdom)

    1997-03-01

    A mouse lineage with inherited predisposition to multiple intestinal neoplasia (min) has been proposed as a model to study human colorectal cancer. Min mice are heterozygous for the adenomatous polyposis coli (Apc) gene implicated in human familial adenomatous polyposis (FAP). There is an increased risk of intestinal cancer in humans following radiation exposure and the min mouse model may be used to further our understanding of the molecular mechanisms involved. The present study showed a 2 Gy dose of x-rays doubles the tumour numbers in the murine gastrointestinal tract of F1 min heterozygotes. The distribution of tumours through the gut was also recorded. (authors)

  10. Genetic and molecular analyses of UV radiation-induced mutations in the fem-3 gene of Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, P.S.; De Wilde, D.; Dwarakanath, V.N. [Texas Christian Univ., Fort Worth, TX (United States). Dept. of Biology

    1995-06-01

    The utility of a new target gene (fem-3) is described for investigating the molecular nature of mutagenesis in the nematode Caenorhabditis elegans. As a principal attribute, this system allows for the selection, maintenance and molecular analysis of any type of mutation that disrupts the gene, including deletions. In this study, 86 mutant strains were isolated, of which 79 proved to have mutations in fem-3. Twenty of these originally tested as homozygous inviable. Homozygous inviability was expected, as Stewart and coworkers had previously observed that, unlike in other organisms, most UV radiation-induced mutations in C. elegans are chromosomal rearrangements of deficiencies (Mutat. Res 249, 37-54, 1991). However, additional data, including Southern blot analyses on 49 of the strains, indicated that most of the UV radiation-induced fem-3 mutations were not deficiencies, as originally inferred from their homozygous inviability. Instead, the lethals were most likely ``coincident mutations`` in linked, essential genes that were concomitantly induced. As such, they were lost owing to genetic recombination during stock maintenance. As in mammalian cells, yeast and bacteria, the frequency of coincident mutations was much higher than would be predicted by chance. (Author).

  11. White Paper of the Society of Computed Body Tomography and Magnetic Resonance on Dual-Energy CT, Part 2: Radiation Dose and Iodine Sensitivity.

    Science.gov (United States)

    Foley, W Dennis; Shuman, William P; Siegel, Marilyn J; Sahani, Dushyant V; Boll, Daniel T; Bolus, David N; De Cecco, Carlo N; Kaza, Ravi K; Morgan, Desiree E; Schoepf, U Joseph; Vrtiska, Terri J; Yeh, Benjamin M; Berland, Lincoln L

    This is the second of a series of 4 white papers that represent Expert Consensus Documents developed by the Society of Computed Body Tomography and Magnetic Resonance through its task force on dual-energy computed tomography. This paper, part 2, addresses radiation dose and iodine sensitivity in dual-energy computed tomography.

  12. G-quadruplex DNA biosensor for sensitive visible detection of genetically modified food.

    Science.gov (United States)

    Jiang, Xiaohua; Zhang, Huimin; Wu, Jun; Yang, Xiang; Shao, Jingwei; Lu, Yujing; Qiu, Bin; Lin, Zhenyu; Chen, Guonan

    2014-10-01

    In this paper, a novel label-free G-quadruplex DNAzyme sensor has been proposed for colorimetric identification of GMO using CaMV 35S promoter sequence as the target. The binary probes can fold into G-quadruplex structure in the presence of DNA-T (Target DNA) and then combine with hemin to form a DNAzyme resembling horseradish peroxidase. The detection system consists of two G-rich probes with 2:2 split mode by using the absorbance and color of ABTS(2-) as signal reporter. Upon the addition of a target sequence, two probes both hybridize with target and then their G-rich sequences combine to form a G-quadruplex DNAzyme, and the DNAzyme can catalyze the reaction of ABTS(2-) with H2O2. Then the linear range is from 0.05 to 0.5 μM while detection limit is 5nM. These results demonstrate that the proposed G-quadruplex DNAzyme method could be used as a simple, sensitive and cost-effective approach for assays of GMO.

  13. A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment.

    Science.gov (United States)

    Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang

    2015-08-04

    Digital PCR has developed rapidly since it was first reported in the 1990 s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products.

  14. Meningioma 40 years after radiation therapy for retinoblastoma: genetic and phenotypic analysis, and minireview of literature.

    Science.gov (United States)

    Balik, V; Sarissky, M; Lohmann, D; Sulla, I

    2008-11-01

    The authors present a case of 44-year-old Caucasian female diagnosed with meningothelial meningioma 40 years after radiotherapy for sporadic unilateral retinoblastoma. The genetic analysis of DNA from the meningioma revealed no oncogenic mutation in the RB1 gene. The analysis of meningioma cells by flow cytometry revealed the following immunophenotype: vimentin++ CD56+ GFAP- EGFR-. Intermediate intensities of Her-2/neu and Pgp expression were detected in a small percentage of tumour cells. Data suggest that the tumour was most likely induced by radiotherapy and did not arise as a second tumour as there was no hereditary predisposition to retinoblastoma.

  15. Genetic Engineering of a Radiation-Resistant Bacterium for Biodegradation of Mixed Wastes--Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Mary E. Lidstrom

    2003-12-26

    Aqueous mixed low level wastes (MLLW) containing radionuclides, solvents, and/or heavy metals represent a serious current and future problem for DOE environmental management and cleanup. In order to provide low-cost treatment alternatives under mild conditions for such contained wastes, we have proposed to use the radiation-resistant bacterium, Deinococcus radiodurans. This project has focused on developing D. radiodurans strains for dual purpose processes: cometabolic treatment of haloorganics and other solvents and removal of heavy metals from waste streams in an above-ground reactor system. The characteristics of effective treatment strains that must be attained are: (a) high biodegradative and metal binding activity; (b) stable treatment characteristics in the absence of selection and in the presence of physiological stress; (c) survival and activity under harsh chemical conditions, including radiation. The result of this project has been a suite of strains with high biodegradative capabilities that are candidates for pilot stage treatment systems. In addition, we have determined how to create conditions to precipitate heavy metals on the surface of the bacterium, as the first step towards creating dual-use treatment strains for contained mixed wastes of importance to the DOE. Finally, we have analyzed stress response in this bacterium, to create the foundation for developing treatment processes that maximize degradation while optimizing survival under high stress conditions.

  16. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  17. Response of Lymphocytes to Radiation in Untreated Breast Cancer Patients as Detected with Three Different Genetic Assays

    Institute of Scientific and Technical Information of China (English)

    JIAN-LIN LOU; ZHI-JIAN CHEN; JIANG WEI; JI-LIANG HE; LI-FEN JIN; SHI-JIE CHEN; WEI ZHENG; SHI-JIE XU

    2008-01-01

    To detect the response of lymphocytes to radiation in untreated breast cancer patients with three different genetic assays.Methods Blood samples were collected from 25 untreated patients and 25 controls.Each blood sample was divided into two parts:one was irradiated by 3-Gy X-ray (irradiated sample),the other was not irradiated (non-irradiated sample).The radiosensitivity of lymphocytes was assessed by comet assay,cytokinesis-block micronucleus (CBMN) assay and 6-TG-resistant cells scored (TG) assay.Results The baseline values of micronucleated cell frequency (MCF) and micronucleus frequency (MNF) in the patients were significantly higher than those in the controls (P<0.01),and 3-Gy X-ray induced genetic damage to lymphocytes in the patients increased significantly as compared with that in the controls as detected with the three genetic assays (P<0.01).The proportion of radiosensitive cases in the patient group was 48% for the mean tail length (MTL),40% for the mean tail moment (MTM),40% for MCE 44% for MNE and 48% for mutation frequencies of the hprt gene (Mfs-hprt),respectively,whereas the proportion of radiosensitive cases in the control group was only 8% for all the parameters.Conclusion The difference in the lymphocyte radiosensitivity between the breast cancer patients and the controls is significant.Moreover,there are wide individual variations in lymphocyte radiosensitivity of patients with breast cancer.In some cases,the radiosensitivity of the same patient may be different as detected with the different assays.It is suggested that multiple assays should be used to assess the radiosensitivity of patients with breast cancer before therapy.

  18. The fibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor {alpha}-mediated superoxide dismutase induction in HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xianguang; An, Zhengzhe; Song, Hye Jin; Kim, Won Dong; Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of); Jang, Seong Soon [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Yu, Jae Ran [Konkuk University College of Medicine, Chungju (Korea, Republic of)

    2012-06-15

    The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) {alpha} and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofi brate (FF). Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. In HeLa cells total SOD activity was increased with increasing FF doses up to 30 {mu}M. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, PPAR{alpha} and PPAR{gamma} were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and PPAR{alpha} were not increased with FF. However, the mRNA of PPAR{gamma} was increased with FF. FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with PPAR{alpha}.

  19. Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition : a meta-analysis

    NARCIS (Netherlands)

    Jansen-van der Weide, Marijke C.; Greuter, Marcel J. W.; Jansen, Liesbeth; Oosterwijk, Jan C.; Pijnappel, Ruud M.; de Bock, Geertruida H.

    2010-01-01

    Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the

  20. DMS atmospheric concentrations and sulphate aerosol indirect radiative forcing: a sensitivity study to the DMS source representation and oxidation

    Directory of Open Access Journals (Sweden)

    O. Boucher

    2003-01-01

    Full Text Available The global sulphur cycle has been simulated using a general circulation model with a focus on the source and oxidation of atmospheric dimethylsulphide (DMS. The sensitivity of atmospheric DMS to the oceanic DMS climatology, the parameterisation of the sea-air transfer and to the oxidant fields have been studied. The importance of additional oxidation pathways (by O3 in the gas- and aqueous-phases and by BrO in the gas phase not incorporated in global models has also been evaluated. While three different climatologies of the oceanic DMS concentration produce rather similar global DMS fluxes to the atmosphere at 24-27 Tg S yr -1, there are large differences in the spatial and seasonal distribution. The relative contributions of OH and NO3 radicals to DMS oxidation depends critically on which oxidant fields are prescribed in the model. Oxidation by O3 appears to be significant at high latitudes in both hemispheres. Oxidation by BrO could be significant even for BrO concentrations at sub-pptv levels in the marine boundary layer. The impact of such refinements on the DMS chemistry onto the indirect radiative forcing by anthropogenic sulphate aerosols is also discussed.

  1. A sensitization effect of hematoporphyrin oligomer (HpO) and caffeine for X-ray radiation of skin cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ishiguro, Kazumori; Ueda, Keiichi; Miyoshi, Norio; Nakanishi, Kazuo; Fukuda, Masaru (Fukui Medical School, Matsuoka (Japan))

    1990-05-01

    Human malignant melanoma cells (G-361) were irradiated with X-ray for different irradiation times. The amount of DNA damage was much increased by the treatment of the cells with hematoporphyrin oligomer (HpO) before X-ray irradiation. Furthermore, it was found that the caffeine inhibited effectively the repair of the damaged DNA. Furthermore, HpO was administered before X-ray irradiation of transplantable skin tumor in C3H mice and/or caffeine was to be given the mouse after X-ray irradiation. The growth of the irradiated tumor combined with HpO and/or caffeine was more inhibited, and the necrotic area was more expanded than that of the tumor irradiated with X-ray only. Labeling Index utilizing bromodeoxyuridine (BrdU) in the viable area of the treated tumor decreased when HpO and/or caffeine were administered. The amount of DNA damage more increased in the irradiated tumor cells given HpO than the only irradiated cells. And, the repair of the damaged DNA was more delayed in the irradiated tumor cells combined with HpO and caffeine than those with other treatments. In conclusion, it was considered that HpO might be a radioactive sensitizer and caffeine enhanced the inhibition of the repair of DNA damaged. We hope that the treatment of X-ray radiation combined with HpO and caffeine is useful for clinical treatment of human malignant tumor. (author) 54 refs.

  2. A sensitivity function-based conjugate gradient method for optical tomography with the frequency-domain equation of radiative transfer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Keol [Departement des Sciences Appliquees, Universite du Quebec a Chicoutimi, Chicoutimi, Que., G7H 2B1 (Canada); Charette, Andre [Departement des Sciences Appliquees, Universite du Quebec a Chicoutimi, Chicoutimi, Que., G7H 2B1 (Canada)]. E-mail: andre_charette@uqac.ca

    2007-03-15

    The Sensitivity Function-based Conjugate Gradient Method (SFCGM) is described. This method is used to solve the inverse problems of function estimation, such as the local maps of absorption and scattering coefficients, as applied to optical tomography for biomedical imaging. A highly scattering, absorbing, non-reflecting, non-emitting medium is considered here and simultaneous reconstructions of absorption and scattering coefficients inside the test medium are achieved with the proposed optimization technique, by using the exit intensity measured at boundary surfaces. The forward problem is solved with a discrete-ordinates finite-difference method on the framework of the frequency-domain full equation of radiative transfer. The modulation frequency is set to 600 MHz and the frequency data, obtained with the source modulation, is used as the input data. The inversion results demonstrate that the SFCGM can retrieve simultaneously the spatial distributions of optical properties inside the medium within a reasonable accuracy, by significantly reducing a cross-talk between inter-parameters. It is also observed that the closer-to-detector objects are better retrieved.

  3. Interparental conflict, parent psychopathology, hostile parenting, and child antisocial behavior: examining the role of maternal versus paternal influences using a novel genetically sensitive research design.

    Science.gov (United States)

    Harold, Gordon T; Elam, Kit K; Lewis, Gemma; Rice, Frances; Thapar, Anita

    2012-11-01

    Past research has linked interparental conflict, parent psychopathology, hostile parenting, and externalizing behavior problems in childhood. However, few studies have examined these relationships while simultaneously allowing the contribution of common genetic factors underlying associations between family- and parent-level variables on child psychopathology to be controlled. Using the attributes of a genetically sensitive in vitro fertilization research design, the present study examined associations among interparental conflict, parents' antisocial behavior problems, parents' anxiety symptoms, and hostile parenting on children's antisocial behavior problems among genetically related and genetically unrelated mother-child and father-child groupings. Path analyses revealed that for genetically related mothers, interparental conflict and maternal antisocial behavior indirectly influenced child antisocial behavior through mother-to-child hostility. For genetically unrelated mothers, effects were apparent only for maternal antisocial behavior on child antisocial behavior through mother-to-child hostility. For both genetically related and genetically unrelated fathers and children, interparental conflict and paternal antisocial behavior influenced child antisocial behavior through father-to-child hostility. Effects of parental anxiety symptoms on child antisocial behavior were apparent only for genetically related mothers and children. Results are discussed with respect to the relative role of passive genotype-environment correlation as a possible confounding factor underlying family process influences on childhood psychopathology.

  4. Effects of age and liquid holding on the UV-radiation sensitivities of wild-type and mutant Caenorhabditis elegans dauer larvae

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, P.S.

    1984-01-01

    The dauer larva is a facultative developmental stage in the life cycle of the nematode Caenorhabditis elegans. Dauer larvae, which can survive under starvation for over 60 days, resume normal development when feeding is resumed. Wild-type (N2) and 4 radiation-sensitive (rad) mutant dauer larvae were tested for their abilities to develop into adults after UV-irradiation. The rad-3 mutant was over 30 times as sensitive as N2; rad-1, rad-2 and rad-7 mutants were not hypersensitive. Irradiation also delayed development in survivors. Wild-type dauer larvae did not differ in radiation sensitivity from 0 through 50 days of age. There was no liquid holding recovery (LHR); that is, survival did not increase when wild-type dauer larvae were held in buffer after irradiation. (orig.). 28 refs.; 4 figs.

  5. An investigation on the radiation sensitivity of DNA conformations to {sup 60}Co gamma rays by using Geant4 toolkit

    Energy Technology Data Exchange (ETDEWEB)

    Semsarha, F. [Institute of Biochemistry and Biophysics (IBB), University of Tehran, P.O. Box 13145-1384, Tehran (Iran, Islamic Republic of); Goliaei, B., E-mail: goliaei@ibb.ut.ac.ir [Institute of Biochemistry and Biophysics (IBB), University of Tehran, P.O. Box 13145-1384, Tehran (Iran, Islamic Republic of); Raisali, G.; Khalafi, H. [Radiation Applications Research School, Nuclear Science and Technology Research Institute, P.O. Box 11365-3486, Tehran (Iran, Islamic Republic of); Mirzakhanian, L. [Medical Physics Unit, McGill University, 1650 Cedar Avenue, Montreal, Quebec (Canada)

    2014-03-15

    To investigate the impact of conformational properties of genetic material of living cells on radiation-induced DNA damage, single strand breaks (SSB), double strand breaks (DSB) and some microdosimetric quantities of A, B and Z-DNA conformations caused by {sup 60}Co gamma rays, have been calculated. Based on a previous B-DNA geometrical model, models of A and Z forms have been developed. Simple 34 base pairs segments of each model repeated in high number and secondary electron spectrum of {sup 60}Co gamma rays have been simulated in a volume of a typical animal cell nucleus. All simulations in this study have been performed by using the Geant4 (GEometry ANd Tracking 4)-DNA extension of the Geant4 toolkit. The results showed that, B-DNA has the lowest yield of simple strand breaks with 2.23 × 10{sup −10} Gy{sup −1} Da{sup −1} and 1.0 × 10{sup −11} Gy{sup −1} Da{sup −1} for the SSB and DSB damage yield, respectively. The A-DNA has the highest SSB yield with 3.59 × 10{sup −10} Gy{sup −1} Da{sup −1} and the Z-DNA has the highest DSB yields with 1.8 × 10{sup −11} Gy{sup −1} Da{sup −1}. It has been concluded that there is a direct correlation between the hit probability, mean specific imparted energy and SSB yield in each model of DNA. Moreover, there is a direct correlation between the DSB yield and both the mean lineal energy and topological characteristics of each model.

  6. Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jansen-van der Weide, Marijke C. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands); Greuter, Marcel J.W.; Pijnappel, Ruud M. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); Jansen, Liesbeth [University Medical Center Groningen, University of Groningen, Department of Surgery, Groningen (Netherlands); Oosterwijk, Jan C. [University Medical Center Groningen, University of Groningen, Department of Clinical Genetics, Groningen (Netherlands); Bock, Geertruida H. de [University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands)

    2010-11-15

    Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the question of how low-dose radiation exposure affects breast cancer risk among high-risk women. A systematic search was conducted for articles addressing breast cancer, mammography screening, radiation and high-risk women. Effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR). Of 127 articles found, 7 were selected for the meta-analysis. Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8). Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1) or a mean of {>=}5 exposures (OR = 1.8, 95% CI: 1.1-3.0) was significantly associated with a higher radiation-induced breast cancer risk. Low-dose radiation increases breast cancer risk among high-risk women. When using low-dose radiation among high-risk women, a careful approach is needed, by means of reducing repeated exposure, avoidance of exposure at a younger age and using non-ionising screening techniques. (orig.)

  7. SU-E-T-146: Effects of Uncertainties of Radiation Sensitivity of Biological Modelling for Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Oita, M [Department of Radiological Technology, Graduate School of Health Sciences, Okayama University (Japan); Department of Life System, Institute of Technology and Science, Graduate School, The Tokushima University (Japan); Uto, Y; Hori, H [Department of Life System, Institute of Technology and Science, Graduate School, The Tokushima University (Japan); Tominaga, M [Department of Radiological Technology, Institute of Health Biosciences, Graduate School, The Tokushima University (Japan); Sasaki, M [Department of Radiology, Tokushima University Hospital (Japan)

    2014-06-01

    Purpose: The aim of this study was to evaluate the distribution of uncertainty of cell survival by radiation, and assesses the usefulness of stochastic biological model applying for gaussian distribution. Methods: For single cell experiments, exponentially growing cells were harvested from the standard cell culture dishes by trypsinization, and suspended in test tubes containing 1 ml of MEM(2x10{sup 6} cells/ml). The hypoxic cultures were treated with 95% N{sub 2}−5% CO{sub 2} gas for 30 minutes. In vitro radiosensitization was also measured in EMT6/KU single cells to add radiosensitizer under hypoxic conditions. X-ray irradiation was carried out by using an Xray unit (Hitachi X-ray unit, model MBR-1505R3) with 0.5 mm Al/1.0 mm Cu filter, 150 kV, 4 Gy/min). In vitro assay, cells on the dish were irradiated with 1 Gy to 24 Gy, respectively. After irradiation, colony formation assays were performed. Variations of biological parameters were investigated at standard cell culture(n=16), hypoxic cell culture(n=45) and hypoxic cell culture(n=21) with radiosensitizers, respectively. The data were obtained by separate schedule to take account for the variation of radiation sensitivity of cell cycle. Results: At standard cell culture, hypoxic cell culture and hypoxic cell culture with radiosensitizers, median and standard deviation of alpha/beta ratio were 37.1±73.4 Gy, 9.8±23.7 Gy, 20.7±21.9 Gy, respectively. Average and standard deviation of D{sub 50} were 2.5±2.5 Gy, 6.1±2.2 Gy, 3.6±1.3 Gy, respectively. Conclusion: In this study, we have challenged to apply these uncertainties of parameters for the biological model. The variation of alpha values, beta values, D{sub 50} as well as cell culture might have highly affected by probability of cell death. Further research is in progress for precise prediction of the cell death as well as tumor control probability for treatment planning.

  8. A Polymorphism Within the Promoter of the TGF{beta}1 Gene Is Associated With Radiation Sensitivity Using an Objective Radiologic Endpoint

    Energy Technology Data Exchange (ETDEWEB)

    Kelsey, Chris R., E-mail: kelse003@mc.duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Jackson, Lauren [Department of Pathology, Duke University Medical Center, Durham, NC (United States); Langdon, Scott [Department of Immunology, Duke University Medical Center, Durham, NC (United States); Owzar, Kouros [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC (United States); Hubbs, Jessica [Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC (United States); Vujaskovic, Zeljko; Das, Shiva [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC (United States)

    2012-02-01

    Purpose: To evaluate whether single nucleotide polymorphisms (SNPs) in the transforming growth factor-{beta}1 (TGF{beta}1) gene are associated with radiation sensitivity using an objective radiologic endpoint. Methods and Materials: Preradiation therapy and serial postradiation therapy single photon emission computed tomography (SPECT) lung perfusion scans were obtained in patients undergoing treatment for lung cancer. Serial blood samples were obtained to measure circulating levels of TGF{beta}1. Changes in regional perfusion were related to regional radiation dose yielding a patient-specific dose-response curve, reflecting the patient's inherent sensitivity to radiation therapy. Six TGF{beta}1 SNPs (-988, -800, -509, 869, 941, and 1655) were assessed using high-resolution melting assays and DNA sequencing. The association between genotype and slope of the dose-response curve, and genotype and TGF{beta}1 ratio (4-week/preradiation therapy), was analyzed using the Kruskal-Wallis test. Results: 39 white patients with preradiation therapy and {>=}6-month postradiation therapy SPECT scans and blood samples were identified. Increasing slope of the dose-response curve was associated with the C(-509)T SNP (p = 0.035), but not the other analyzed SNPs. This SNP was also associated with higher TGF{beta}1 ratios. Conclusions: This study suggests that a polymorphism within the promoter of the TGF{beta}1 gene is associated with increased radiation sensitivity (defined objectively by dose-dependent changes in SPECT lung perfusion).

  9. Sanazole as a sensitizer of hypoxic cells with radical radiation in the treatment of advanced cancer of cervix an Indian experience.

    Science.gov (United States)

    Huilgol, Nagraj G; Dobrowsky, Werner; Tatsuzaki, Hideo; Chatterjee, Neela A; Kagiya, V T; Das, Kaushik

    2002-06-01

    AK-2123, is a nitrotriazole with a potential to sensitize hypoxic tissue to radiation. Cancer of cervix in advanced stages are predominantly treated with radiation. These are the tumours which harbour a large hypoxic core. This is an Indian experience of the multicentric trial. Patients were randomized to control and AK-2123 arm. 49 patients were randomized to each group. Patients received external radiation with telecobalt to a dose of 50 Gy in five weeks. Those in the study arm received 600 mg/m2, on alternate days. The patients were further treated with intracavitory radiation a dose of 20 Gy. The total dose of 70 Gy was achieved. Patients in the study arm had a complete response of 71.43% (35 of 49) while only 21 of 49 (42.86%) responded in the control group. The overall survival at two years was 72.2% for the study group and 32.43% for control. Neuropathy, a drug related toxicity was transient except, in one patient, which has persisted. AK-2123, has shown significant radiation sensitizing potential.

  10. Phenotypic and Genetic Analyses of the Varroa Sensitive Hygienic Trait in Russian Honey Bee (Hymenoptera: Apidae) Colonies

    Science.gov (United States)

    Kirrane, Maria J.; de Guzman, Lilia I.; Holloway, Beth; Frake, Amanda M.; Rinderer, Thomas E.; Whelan, Pádraig M.

    2015-01-01

    Varroa destructor continues to threaten colonies of European honey bees. General hygiene, and more specific Varroa Sensitive Hygiene (VSH), provide resistance towards the Varroa mite in a number of stocks. In this study, 32 Russian (RHB) and 14 Italian honey bee colonies were assessed for the VSH trait using two different assays. Firstly, colonies were assessed using the standard VSH behavioural assay of the change in infestation of a highly infested donor comb after a one-week exposure. Secondly, the same colonies were assessed using an “actual brood removal assay” that measured the removal of brood in a section created within the donor combs as a potential alternative measure of hygiene towards Varroa-infested brood. All colonies were then analysed for the recently discovered VSH quantitative trait locus (QTL) to determine whether the genetic mechanisms were similar across different stocks. Based on the two assays, RHB colonies were consistently more hygienic toward Varroa-infested brood than Italian honey bee colonies. The actual number of brood cells removed in the defined section was negatively correlated with the Varroa infestations of the colonies (r2 = 0.25). Only two (percentages of brood removed and reproductive foundress Varroa) out of nine phenotypic parameters showed significant associations with genotype distributions. However, the allele associated with each parameter was the opposite of that determined by VSH mapping. In this study, RHB colonies showed high levels of hygienic behaviour towards Varroa -infested brood. The genetic mechanisms are similar to those of the VSH stock, though the opposite allele associates in RHB, indicating a stable recombination event before the selection of the VSH stock. The measurement of brood removal is a simple, reliable alternative method of measuring hygienic behaviour towards Varroa mites, at least in RHB stock. PMID:25909856

  11. Phenotypic and genetic analyses of the varroa sensitive hygienic trait in Russian honey bee (hymenoptera: apidae colonies.

    Directory of Open Access Journals (Sweden)

    Maria J Kirrane

    Full Text Available Varroa destructor continues to threaten colonies of European honey bees. General hygiene, and more specific Varroa Sensitive Hygiene (VSH, provide resistance towards the Varroa mite in a number of stocks. In this study, 32 Russian (RHB and 14 Italian honey bee colonies were assessed for the VSH trait using two different assays. Firstly, colonies were assessed using the standard VSH behavioural assay of the change in infestation of a highly infested donor comb after a one-week exposure. Secondly, the same colonies were assessed using an "actual brood removal assay" that measured the removal of brood in a section created within the donor combs as a potential alternative measure of hygiene towards Varroa-infested brood. All colonies were then analysed for the recently discovered VSH quantitative trait locus (QTL to determine whether the genetic mechanisms were similar across different stocks. Based on the two assays, RHB colonies were consistently more hygienic toward Varroa-infested brood than Italian honey bee colonies. The actual number of brood cells removed in the defined section was negatively correlated with the Varroa infestations of the colonies (r2 = 0.25. Only two (percentages of brood removed and reproductive foundress Varroa out of nine phenotypic parameters showed significant associations with genotype distributions. However, the allele associated with each parameter was the opposite of that determined by VSH mapping. In this study, RHB colonies showed high levels of hygienic behaviour towards Varroa -infested brood. The genetic mechanisms are similar to those of the VSH stock, though the opposite allele associates in RHB, indicating a stable recombination event before the selection of the VSH stock. The measurement of brood removal is a simple, reliable alternative method of measuring hygienic behaviour towards Varroa mites, at least in RHB stock.

  12. Soft-electron beam and gamma-radiation sensitivity and DNA damage in phosphine-resistant and -susceptible strains of Rhyzopertha dominica.

    Science.gov (United States)

    Hasan, Md Mahbub; Todoriki, Setsuko; Miyanoshita, Akihiro; Imamura, Taro; Hayashi, Toru

    2006-10-01

    The soft-electron beam (low-energy electrons) and gamma-radiation sensitivities of phosphine-resistant (PHR) and -susceptible (PHS) strains of adults lesser grain borer Rhyzopertha dominica (F.) were studied, with particular reference to DNA damage assessed using single-cell electrophoresis (comet assay). Results showed that mortality in adult R. dominica varied significantly between both PHR and PHS strains. Adults of the PHR strain were found to be more tolerant toward soft-electron and gamma radiation than adults of the PHS strain. Studies on the longevity of strains showed that mean survival time and dose rate were highly correlated with both strains and treatments. Results also showed that adults of the PHR strain lived longer than adults of PHS strain for both treatments. Radiation sensitivity indices, however, decreased as radiation dose increased in both strains. Analysis of DNA damage, after 40- and 160-Gy gamma radiation, was carried out using cells obtained from both strains. Gamma-irradiated adults of both strains showed typical DNA fragmentation, compared with cells from nonirradiated adults, which showed more intact DNA. Investigations using the comet assay showed that tail length, moment, olive-tail moment, percentage of tail DNA, and percentage of DNA damage were all greater in the PHS strain compared with the PHR strain and the control insects. Results also showed that DNA damage remained at a constant level for up to 24 h after irradiation. The results have been discussed in relation to the observed strain differences in radiation sensitivity and resistance to phosphine.

  13. Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model

    OpenAIRE

    Inoue Takeshi; Anai Satoshi; Onishi Sayuri; Miyake Makito; Tanaka Nobumichi; Hirayama Akihide; Fujimoto Kiyohide; Hirao Yoshihiko

    2013-01-01

    Abstract Background COX-2 inhibitors have an antitumor potential and have been verified by many researchers. Treatment of cancer cells with external stressors such as irradiation can stimulate the over-expression of COX-2 and possibly confer radiation resistance. In this study, we tested if topical diclofenac, which inhibits both COX-1 and COX-2, administration rendered prostate tumor cells sensitize to the effects of radiation. Methods LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 1...

  14. Modeling radiative transfer in tropical rainforest canopies: sensitivity of simulated albedo to canopy architectural and optical parameters

    Directory of Open Access Journals (Sweden)

    Sílvia N. M. Yanagi

    2011-12-01

    Full Text Available This study evaluates the sensitivity of the surface albedo simulated by the Integrated Biosphere Simulator (IBIS to a set of Amazonian tropical rainforest canopy architectural and optical parameters. The parameters tested in this study are the orientation and reflectance of the leaves of upper and lower canopies in the visible (VIS and near-infrared (NIR spectral bands. The results are evaluated against albedo measurements taken above the K34 site at the INPA (Instituto Nacional de Pesquisas da Amazônia Cuieiras Biological Reserve. The sensitivity analysis indicates a strong response to the upper canopy leaves orientation (x up and to the reflectivity in the near-infrared spectral band (rNIR,up, a smaller sensitivity to the reflectivity in the visible spectral band (rVIS,up and no sensitivity at all to the lower canopy parameters, which is consistent with the canopy structure. The combination of parameters that minimized the Root Mean Square Error and mean relative error are Xup = 0.86, rVIS,up = 0.062 and rNIR,up = 0.275. The parameterizations performed resulted in successful simulations of tropical rainforest albedo by IBIS, indicating its potential to simulate the canopy radiative transfer for narrow spectral bands and permitting close comparison with remote sensing products.Este estudo avalia a sensibilidade do albedo da superfície pelo Simulador Integrado da Biosfera (IBIS a um conjunto de parâmetros que representam algumas propriedades arquitetônicas e óticas do dossel da floresta tropical Amazônica. Os parâmetros testados neste estudo são a orientação e refletância das folhas do dossel superior e inferior nas bandas espectrais do visível (VIS e infravermelho próximo (NIR. Os resultados são avaliados contra observações feitas no sítio K34 pertencente ao Instituto Nacional de Pesquisas da Amazônia (INPA na Reserva Biológica de Cuieiras. A análise de sensibilidade indica uma forte resposta aos parâmetros de orienta

  15. miR-15a/16 Enhances Radiation Sensitivity of Non-Small Cell Lung Cancer Cells by Targeting the TLR1/NF-κB Signaling Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lan, Fengming [Radiation Oncology Department, PLA Airforce General Hospital, Beijing (China); Radiation Oncology Department, Tianjin Hospital, Tianjin (China); Yue, Xiao [Tianjin Huanhu Hospital, Tianjin Neurosurgery Institute, Tianjin (China); Ren, Gang; Li, Hongqi; Ping, Li; Wang, Yingjie [Radiation Oncology Department, PLA Airforce General Hospital, Beijing (China); Xia, Tingyi, E-mail: xiatingyi1959@163.com [Radiation Oncology Department, PLA Airforce General Hospital, Beijing (China)

    2015-01-01

    Purpose: Many miRNAs have been identified as essential issues and core determining factors in tumor radiation. Recent reports have demonstrated that miRNAs and Toll-like receptors could exert reciprocal effects to control cancer development in various ways. However, a novel role of miR-15a/16 in enhancing radiation sensitivity by directly targeting TLR1 has not been reported, to our knowledge. Methods and Materials: Bioinformatic analyses, luciferase reporter assay, biochemical assays, and subcutaneous tumor establishment were used to characterize the signaling pathways of miRNA-15a/16 in response to radiation treatment. Results: First, an inverse correlation between the expression of miR-15a/16 and TLR1 protein was revealed in non-small cell lung cancer (NSCLC) and normal lung tissues. Next, we corroborated that miR-15a/16 specifically bound to TLR1 3′UTR and inhibited the expression of TLR1 in H358 and A549 cells. Furthermore, miR-15a/16 downregulated the activity of the NF-κB signaling pathway through TLR1. In addition, overexpression of miR-15a/16 inhibited survival capability and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in H358 and A549 cells. Finally, subcutaneous tumor bearing NSCLC cells in a nude mice model was established, and the results showed that combined groups (miR-15a/16 + radiation) inhibited tumor growth more significantly than did radiation alone. Conclusions: We mainly elucidate that miRNA-15a/16 can enhance radiation sensitivity by regulating the TLR1/NF-κB signaling pathway and act as a potential therapeutic approach to overcome radioresistance for lung cancer treatment.

  16. Cost-Risk Trade-off of Solar Radiation Management and Mitigation under Probabilistic Information on Climate Sensitivity

    Science.gov (United States)

    Khabbazan, Mohammad Mohammadi; Roshan, Elnaz; Held, Hermann

    2017-04-01

    In principle solar radiation management (SRM) offers an option to ameliorate anthropogenic temperature rise. However we cannot expect it to simultaneously compensate for anthropogenic changes in further climate variables in a perfect manner. Here, we ask to what extent a proponent of the 2°C-temperature target would apply SRM in conjunction with mitigation in view of global or regional disparities in precipitation changes. We apply cost-risk analysis (CRA), which is a decision analytic framework that makes a trade-off between the expected welfare-loss from climate policy costs and the climate risks from transgressing a climate target. Here, in both global-scale and 'Giorgi'-regional-scale analyses, we evaluate the optimal mixture of SRM and mitigation under probabilistic information about climate sensitivity. To do so, we generalize CRA for the sake of including not only temperature risk, but also globally aggregated and regionally disaggregated precipitation risks. Social welfare is maximized for the following three valuation scenarios: temperature-risk-only, precipitation-risk-only, and equally weighted both-risks. For now, the Giorgi regions are treated by equal weight. We find that for regionally differentiated precipitation targets, the usage of SRM will be comparably more restricted. In the course of time, a cooling of up to 1.3°C can be attributed to SRM for the latter scenario and for a median climate sensitivity of 3°C (for a global target only, this number reduces by 0.5°C). Our results indicate that although SRM would almost completely substitute for mitigation in the globally aggregated analysis, it only saves 70% to 75% of the welfare-loss compared to a purely mitigation-based analysis (from economic costs and climate risks, approximately 4% in terms of BGE) when considering regional precipitation risks in precipitation-risk-only and both-risks scenarios. It remains to be shown how the inclusion of further risks or different regional weights would

  17. Fast-forward genetics by radiation hybrids to saturate the locus regulating nuclear-cytoplasmic compatibility in Triticum.

    Science.gov (United States)

    Bassi, Filippo M; Ghavami, Farhad; Hayden, Matthew J; Wang, Yi; Forrest, Kerrie L; Kong, Stephan; Dizon, Rhoderissa; Michalak de Jimenez, Monika K; Meinhardt, Steven W; Mergoum, Mohamed; Gu, Yong Q; Kianian, Shahryar F

    2016-08-01

    The nuclear-encoded species cytoplasm specific (scs) genes control nuclear-cytoplasmic compatibility in wheat (genus Triticum). Alloplasmic cells, which have nucleus and cytoplasm derived from different species, produce vigorous and vital organisms only when the correct version of scs is present in their nucleus. In this study, bulks of in vivo radiation hybrids segregating for the scs phenotype have been genotyped by sequencing with over 1.9 million markers. The high marker saturation obtained for a critical region of chromosome 1D allowed identification of 3318 reads that mapped in close proximity of the scs. A novel in silico approach was deployed to extend these short reads to sequences of up to 70 Kb in length and identify candidate open reading frames (ORFs). Markers were developed to anchor the short contigs containing ORFs to a radiation hybrid map of 650 individuals with resolution of 288 Kb. The region containing the scs locus was narrowed to a single Bacterial Artificial Chromosome (BAC) contig of Aegilops tauschii. Its sequencing and assembly by nano-mapping allowed rapid identification of a rhomboid gene as the only ORF existing within the refined scs locus. Resequencing of this gene from multiple germplasm sources identified a single nucleotide mutation, which gives rise to a functional amino acid change. Gene expression characterization revealed that an active copy of this rhomboid exists on all homoeologous chromosomes of wheat, and depending on the specific cytoplasm each copy is preferentially expressed. Therefore, a new methodology was applied to unique genetic stocks to rapidly identify a strong candidate gene for the control of nuclear-cytoplasmic compatibility in wheat.

  18. ALTERED SENSITIVITY OF THE MOUSE FETUS TO IMPAIRED PROSTATIC BUD FORMATION BY DIOXIN: INFLUENCE OF GENETIC BACKGROUND AND NULL EXPRESSION OF TGF-ALFA AND EGF

    Science.gov (United States)

    Altered sensitivity of the mouse fetus to impaired prostatic bud formation by dioxin: Influence of genetic background and null expression of TGF and EGF. Rasmussen, N.T., Lin T-M., Fenton, S.E., Abbott, B.D. and R.E. Peterson. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)...

  19. Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC Applied in Optimization of Radiation Pattern Control of Phased-Array Radars for Rocket Tracking Systems

    Directory of Open Access Journals (Sweden)

    Leonardo W. T. Silva

    2014-08-01

    Full Text Available In launching operations, Rocket Tracking Systems (RTS process the trajectory data obtained by radar sensors. In order to improve functionality and maintenance, radars can be upgraded by replacing antennas with parabolic reflectors (PRs with phased arrays (PAs. These arrays enable the electronic control of the radiation pattern by adjusting the signal supplied to each radiating element. However, in projects of phased array radars (PARs, the modeling of the problem is subject to various combinations of excitation signals producing a complex optimization problem. In this case, it is possible to calculate the problem solutions with optimization methods such as genetic algorithms (GAs. For this, the Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC method was developed to control the radiation pattern of PAs. The GA-MMC uses a reconfigurable algorithm with multiple objectives, differentiated coding and a new crossover genetic operator. This operator has a different approach from the conventional one, because it performs the crossover of the fittest individuals with the least fit individuals in order to enhance the genetic diversity. Thus, GA-MMC was successful in more than 90% of the tests for each application, increased the fitness of the final population by more than 20% and reduced the premature convergence.

  20. Highly Sensitive Detection of Organophosphate Insecticides Using Biosensors Based on Genetically Engineered Acetylcholinesterase and Poly(3,4-Ethylenedioxythiophene

    Directory of Open Access Journals (Sweden)

    Tomasz Sikora

    2011-01-01

    Full Text Available A poly(3,4-ethylenedioxythiophene (PEDOT conducting ink is presented as a new electroactive material to be incorporated in acetylcholinesterase-(AChE- based screen printed biosensors, acting not only as a conducting template but also as an electrochemical mediator for thiocholine oxidation. Two different strategies have been studied for the chemical synthesis of PEDOT: (a a classical oxidative polymerisation and (b a more innovative enzymatic polymerisation, giving a water-soluble PEDOT. The use of this water-soluble conducting polymer as mediator in screen-printed biosensors enables its deposition by printing like the rest of the layers. Highly sensitive acetylcholinesterase-(AChE- based screen-printed biosensors have been constructed using both classical and enzymatic PEDOT, in combination with genetically modified AChE. These electrodes allow the measurement of thiocholine oxidation at potentials of 100 mV versus Ag/AgCl reference electrode through the mediation of PEDOT. Inhibition of thiocholine production in presence of CPO allow for detection of this pesticide in concentrations as low as 1·10−10 M.

  1. Evaluation of a reverse-hybridization StripAssay for the detection of genetic polymorphisms leading to acenocoumarol sensitivity.

    Science.gov (United States)

    Gialeraki, Argyri; Markatos, Christos; Grouzi, Elisabeth; Merkouri, Efrosyni; Travlou, Anthi; Politou, Marianna

    2010-04-01

    Acenocoumarol is mainly catabolized by CYP2C9 isoform of cytochrome P450 (CYP) liver complex and exerts its anticoagulant effect through the inhibition of Vitamin K Epoxide Reductase (VKOR). The most important genetic polymorphisms which lead to an impaired enzymatic activity and therefore predispose to acenocoumarol sensitivity, are considered to be CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A, respectively. In this study we compared the results of the PGXThrombo StripAssay kit (ViennaLab Diagnostics,Vienna, Austria) with direct DNA sequencing and in house Restriction Fragment Length Polymorphisms (RFLP) for the detection of the aforementioned Single Nucleotide Polymorphisms (SNPs). The reverse hybridization StripAssay was found to be equally effective with RFLP and direct DNA sequencing for the detection of CYP2C9*2 and CYP2C9*3 polymorphisms, respectively. The comparison of the RFLP reference method with the reverse hybridization StripAssay for the detection of VKORC1-1639 G>A polymorphism showed that the reverse hybridization StripAsssay might misclassify some A/A homozygotes as heterozygotes. Optimization of the hybridization procedures may eliminate the extra low signal band observed in some samples at the reverse hybridization StripAssay and improve its diagnostic value.

  2. A sensitive method to extract DNA from biological traces present on ammunition for the purpose of genetic profiling.

    Science.gov (United States)

    Dieltjes, Patrick; Mieremet, René; Zuniga, Sofia; Kraaijenbrink, Thirsa; Pijpe, Jeroen; de Knijff, Peter

    2011-07-01

    Exploring technological limits is a common practice in forensic DNA research. Reliable genetic profiling based on only a few cells isolated from trace material retrieved from a crime scene is nowadays more and more the rule rather than the exception. On many crime scenes, cartridges, bullets, and casings (jointly abbreviated as CBCs) are regularly found, and even after firing, these potentially carry trace amounts of biological material. Since 2003, the Forensic Laboratory for DNA Research is routinely involved in the forensic investigation of CBCs in the Netherlands. Reliable DNA profiles were frequently obtained from CBCs and used to match suspects, victims, or other crime scene-related DNA traces. In this paper, we describe the sensitive method developed by us to extract DNA from CBCs. Using PCR-based genotyping of autosomal short tandem repeats, we were able to obtain reliable and reproducible DNA profiles in 163 out of 616 criminal cases (26.5%) and in 283 out of 4,085 individual CBC items (6.9%) during the period January 2003-December 2009. We discuss practical aspects of the method and the sometimes unexpected effects of using cell lysis buffer on the subsequent investigation of striation patterns on CBCs.

  3. Comprehensive tool for calculation of radiative fluxes: illustration of shortwave aerosol radiative effect sensitivities to the details in aerosol and underlying surface characteristics

    Science.gov (United States)

    Derimian, Yevgeny; Dubovik, Oleg; Huang, Xin; Lapyonok, Tatyana; Litvinov, Pavel; Kostinski, Alex B.; Dubuisson, Philippe; Ducos, Fabrice

    2016-05-01

    The evaluation of aerosol radiative effect on broadband hemispherical solar flux is often performed using simplified spectral and directional scattering characteristics of atmospheric aerosol and underlying surface reflectance. In this study we present a rigorous yet fast computational tool that accurately accounts for detailed variability of both spectral and angular scattering properties of aerosol and surface reflectance in calculation of direct aerosol radiative effect. The tool is developed as part of the GRASP (Generalized Retrieval of Aerosol and Surface Properties) project. We use the tool to evaluate instantaneous and daily average radiative efficiencies (radiative effect per unit aerosol optical thickness) of several key atmospheric aerosol models over different surface types. We then examine the differences due to neglect of surface reflectance anisotropy, nonsphericity of aerosol particle shape and accounting only for aerosol angular scattering asymmetry instead of using full phase function. For example, it is shown that neglecting aerosol particle nonsphericity causes mainly overestimation of the aerosol cooling effect and that magnitude of this overestimate changes significantly as a function of solar zenith angle (SZA) if the asymmetry parameter is used instead of detailed phase function. It was also found that the nonspherical-spherical differences in the calculated aerosol radiative effect are not modified significantly if detailed BRDF (bidirectional reflectance distribution function) is used instead of Lambertian approximation of surface reflectance. Additionally, calculations show that usage of only angular scattering asymmetry, even for the case of spherical aerosols, modifies the dependence of instantaneous aerosol radiative effect on SZA. This effect can be canceled for daily average values, but only if sun reaches the zenith; otherwise a systematic bias remains. Since the daily average radiative effect is obtained by integration over a range

  4. A-bomb radiation effects digest

    Energy Technology Data Exchange (ETDEWEB)

    Shigematsu, Itsuzo; Akiyama, Mitoshi; Sasaki, Hideo (Radiation Effects Research Foundation, Hiroshima (Japan)); Ito, Chikako; Kamada, Nanao.

    1993-01-01

    This publication is the digest of the book 'Genbaku Hoshasen no Jintai Eikyo (Effects of A-bomb Radiation on the Human Body)' (365p.), published in Japanese by Hiroshima International Council for Medical Care of the Radiation-Exposed. Following a brief description on the damage of the atomic bomb, the subjects of malignant tumors, endocrine and metabolic deseases, ocular lesions, dermatologic effects, prenatal exposure, chromosoal aberrations, mutations, sensitivity to radiation, immune function, genetic effects and other effects of radiation are summarized. (J.P.N.).

  5. Lauriston S. Taylor Lecture: The evolution of radiation protection--from erythema to genetic risks to risks of cancer to...?

    Science.gov (United States)

    Meinhold, Charles B

    2004-09-01

    Radiation Protection has evolved and will continue to evolve as new information becomes available, as the result of changes in public perception and concern and, perhaps in the future, as a result of enormous expenditures on reducing small risks. In the early part of the last century it was a sense of real danger among medical Practitioners that prompted the first set of exposure limiting suggestions. Addressing medical concerns continued to be the basis of guidance until after the Second World War. An array of new sources and applications led to new approaches, which modified many of the technical issues but didn't result in substantial changes in the dose limits. Fallout from the first generation of thermonuclear weapons in the 1950's resulted in focusing attention on genetic effects, which continued until the middle 1970's. Data from the Japanese Survivor Studies provided the information for risk based recommendations beginning in 1977 and continue to do so today. Both the ICRP and the NCRP are heavily criticized by both those groups of individuals which believe the risk estimates are underestimated and by those which believe the risks are greatly overestimated. Perhaps both organizations can take some comfort in Saint Thomas Aquinas' suggestion, "In medio virtus."

  6. Ionizing radiation and genetic risks. VIII. The concept of mutation component and its use in risk estimation for multifactorial diseases.

    Science.gov (United States)

    Denniston, C; Chakraborty, R; Sankaranarayanan, K

    1998-08-31

    Multifactorial diseases, which include the common congenital abnormalities (incidence: 6%) and chronic diseases with onset predominantly in adults (population prevalence: 65%), contribute substantially to human morbidity and mortality. Their transmission patterns do not conform to Mendelian expectations. The model most frequently used to explain their inheritance and to estimate risks to relatives is a Multifactorial Threshold Model (MTM) of disease liability. The MTM assumes that: (i) the disease is due to the joint action of a large number of genetic and environmental factors, each of which contributing a small amount of liability, (ii) the distribution of liability in the population is Gaussian and (iii) individuals whose liability exceeds a certain threshold value are affected by the disease. For most of these diseases, the number of genes involved or the environmental factors are not fully known. In the context of radiation exposures of the population, the question of the extent to which induced mutations will cause an increase in the frequencies of these diseases has remained unanswered. In this paper, we address this problem by using a modified version of MTM which incorporates mutation and selection as two additional parameters. The model assumes a finite number of gene loci and threshold of liability (hence, the designation, Finite-Locus Threshold Model or FLTM). The FLTM permits one to examine the relationship between broad-sense heritability of disease liability and mutation component (MC), the responsiveness of the disease to a change in mutation rate. Through the use of a computer program (in which mutation rate, selection, threshold, recombination rate and environmental variance are input parameters and MC and heritability of liability are output estimates), we studied the MC-heritability relationship for (i) a permanent increase in mutation rate (e.g., when the population sustains radiation exposure in every generation) and (ii) a one-time increase

  7. Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Kamran A. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Fulp, William J.; Berglund, Anders E. [Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Hoffe, Sarah E.; Dilling, Thomas J. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Eschrich, Steven A. [Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Shridhar, Ravi [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States)

    2015-07-15

    Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger

  8. Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway.

    Science.gov (United States)

    Wang, Lei; Li, Xiankui; Song, Yi-Min; Wang, Bin; Zhang, Fu-Rui; Yang, Rui; Wang, Hua-Qi; Zhang, Guo-Jun

    2015-07-01

    At present, it is elusive how non-small cell lung cancer (NSCLC) develops resistance to γ-radiation; however, the transcription factor nuclear factor-κB (NF-κB) and NF-κB-regulated gene products have been proposed as mediators. Ginsenoside Rg3 is a steroidal saponin, which was isolated from Panax ginseng. Ginsenoside Rg3 possesses high pharmacological activity and has previously been shown to suppress NF-κB activation in various types of tumor cell. Therefore, the present study aimed to determine whether Rg3 could suppress NF-κB activation in NSCLC cells and sensitize NSCLC to γ-radiation, using an NSCLC cell line and NSCLC xenograft. A clone formation assay and lung tumor xenograft experiment were used to assess the radiosensitizing effects of ginsenoside Rg3. NF-κB/inhibitor of NF-κB (IκB) modulation was ascertained using an electrophoretic mobility shift assay and western blot analysis. NF-κB-regulated gene products were monitored by western blot analysis. The present study demonstrated that ginsenoside Rg3 was able to sensitize A549 and H1299 lung carcinoma cells to γ-radiation and significantly enhance the efficacy of radiation therapy in C57BL/6 mice bearing a Lewis lung carcinoma cell xenograft tumor. Furthermore, ginsenoside Rg3 suppressed NF-κB activation, phosphorylation of IκB protein and expression of NF-κB-regulated gene products (cyclin D1, c-myc, B-cell lymphoma 2, cyclooxygenase-2, matrix metalloproteinase-9 and vascular endothelial growth factor), a number of which were induced by radiation therapy and mediate radioresistance. In conclusion, the results of the present study suggested that ginsenoside Rg3 may potentiate the antitumor effects of radiation therapy in NSCLC by suppressing NF-κB activity and NF-κB-regulated gene products, leading to the inhibition of tumor progression.

  9. Acute Radiation-Induced Nocturia in Prostate Cancer Patients Is Associated With Pretreatment Symptoms, Radical Prostatectomy, and Genetic Markers in the TGF{beta}1 Gene

    Energy Technology Data Exchange (ETDEWEB)

    De Langhe, Sofie, E-mail: Sofie.DeLanghe@UGent.be [Department of Basic Medical Sciences, Ghent University, Gent (Belgium); De Ruyck, Kim [Department of Basic Medical Sciences, Ghent University, Gent (Belgium); Ost, Piet; Fonteyne, Valerie [Department of Radiation Oncology, Ghent University Hospital, Gent (Belgium); Werbrouck, Joke [Department of Basic Medical Sciences, Ghent University, Gent (Belgium); De Meerleer, Gert; De Neve, Wilfried [Department of Radiation Oncology, Ghent University Hospital, Gent (Belgium); Thierens, Hubert [Department of Basic Medical Sciences, Ghent University, Gent (Belgium)

    2013-02-01

    Purpose: After radiation therapy for prostate cancer, approximately 50% of the patients experience acute genitourinary symptoms, mostly nocturia. This may be highly bothersome with a major impact on the patient's quality of life. In the past, nocturia is seldom reported as a single, physiologically distinct endpoint, and little is known about its etiology. It is assumed that in addition to dose-volume parameters and patient- and therapy-related factors, a genetic component contributes to the development of radiation-induced damage. In this study, we investigated the association among dosimetric, clinical, and TGF{beta}1 polymorphisms and the development of acute radiation-induced nocturia in prostate cancer patients. Methods and Materials: Data were available for 322 prostate cancer patients treated with primary or postoperative intensity modulated radiation therapy (IMRT). Five genetic markers in the TGF{beta}1 gene (-800 G>A, -509 C>T, codon 10 T>C, codon 25 G>C, g.10780 T>G), and a high number of clinical and dosimetric parameters were considered. Toxicity was scored using an symptom scale developed in-house. Results: Radical prostatectomy (P<.001) and the presence of pretreatment nocturia (P<.001) are significantly associated with the occurrence of radiation-induced acute toxicity. The -509 CT/TT (P=.010) and codon 10 TC/CC (P=.005) genotypes are significantly associated with an increased risk for radiation-induced acute nocturia. Conclusions: Radical prostatectomy, the presence of pretreatment nocturia symptoms, and the variant alleles of TGF{beta}1 -509 C>T and codon 10 T>C are identified as factors involved in the development of acute radiation-induced nocturia. These findings may contribute to the research on prediction of late nocturia after IMRT for prostate cancer.

  10. HSV-1 amplicon-mediated post-transcriptional inhibition of Rad51 sensitizes human glioma cells to ionizing radiation.

    Science.gov (United States)

    Saydam, O; Saydam, N; Glauser, D L; Pruschy, M; Dinh-Van, V; Hilbe, M; Jacobs, A H; Ackermann, M; Fraefel, C

    2007-08-01

    Standard treatment for glioblastoma multiforme and other brain tumors consists of surgical resection followed by combined radio-/chemotherapy. However, radiation resistance of tumor cells limits the success of this treatment, and the tumors invariably recur. Therefore, the selective inhibition of molecular mediators of radiation resistance may provide therapeutic benefit to the patient. One of these targets is the Rad51 protein, which is a key component of the homologous recombinational repair of DNA double-strand breaks. Here, we investigated whether post-transcriptional silencing of Rad51 by herpes simplex virus-type 1 (HSV-1) amplicon vector-mediated short interfering RNA expression can enhance the antitumor effect of radiation therapy. We demonstrate that these vectors specifically and efficiently inhibited the radiation-induced recruitment of Rad51 into nuclear foci in human glioma cells. The combination of vector-mediated silencing of Rad51 expression and treatment with ionizing radiation resulted in a pronounced reduction of the survival of human glioma cells in culture. In athymyc mice, a single intratumoral injection of Rad51-specific HSV-1 amplicon vector followed by a single radiation treatment resulted in a significant decrease in tumor size. In control animals, including mice that received an intratumoral injection of Rad51-specific amplicon vector but no radiation treatment, the tumor sizes increased.

  11. High-Density and Very-Low-Density Lipoprotein Have Opposing Roles in Regulating Tumor-Initiating Cells and Sensitivity to Radiation in Inflammatory Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, Adam R. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Atkinson, Rachel L. [Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reddy, Jay P. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Debeb, Bisrat G.; Larson, Richard; Li, Li [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Masuda, Hiroko; Brewer, Takae [Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Atkinson, Bradley J. [Department of Clinical Pharmacy Services, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Brewster, Abeena [Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ueno, Naoto T. [Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A., E-mail: wwoodward@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-04-01

    Purpose: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. Methods and Materials: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. Results: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). Conclusions: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients

  12. Analysis of DNA methylation variation in wheat genetic background after alien chromatin introduction based on methylation-sensitive amplification polymorphism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    During the process of alien germplasm introduced into wheat genome by chromosome engineering,extensive genetic variations of genome structure and gene expression in recipient could be induced.In this study,we performed GISH(genome in situ hybridization)and AFLP(amplified fragment length polymorphism) on wheat-rye chromosome transIocation lines and their parents to detect the identity in genomic structure of different translocation lines.The results showed that the genome primary structure variations were not obviously detected in different translocation lines except the same 1RS chromosome translocation.Methylation sensitive amplification polymorphism(MSAP)analyses on genomic DNA showed that the ratios of fully-methylated sites were significantly increased in translocation lines(CN12,20.15%;CN17,20.91%;CN18,22.42%),but the ratios of hemimethylated sites were significantly lowered(CN12,21.41%;CN17,23.43%;CN18,22.42%),whereas 16.37%were fully-methylated and 25.44%were hemimethylated in case of their wheat parent.Twenty-nine classes of methylation patterns were identified in a comparative assay of cytosine methylation patterns between wheat-rye translocation lines and their wheat parent,including 13 hypermethylation patterns(33.74%),9 demethylation patterns(22.76%)and 7 uncertain patterns(4.07%).In further sequence analysis,the alterations of methylation pattern affected both repetitive DNA sequences,such as retrotransposons and tandem repetitive sequences,and low-copy DNA.

  13. Targeting helicase-dependent amplification products with an electrochemical genosensor for reliable and sensitive screening of genetically modified organisms.

    Science.gov (United States)

    Moura-Melo, Suely; Miranda-Castro, Rebeca; de-Los-Santos-Álvarez, Noemí; Miranda-Ordieres, Arturo J; Dos Santos Junior, J Ribeiro; da Silva Fonseca, Rosana A; Lobo-Castañón, Maria Jesús

    2015-08-18

    Cultivation of genetically modified organisms (GMOs) and their use in food and feed is constantly expanding; thus, the question of informing consumers about their presence in food has proven of significant interest. The development of sensitive, rapid, robust, and reliable methods for the detection of GMOs is crucial for proper food labeling. In response, we have experimentally characterized the helicase-dependent isothermal amplification (HDA) and sequence-specific detection of a transgene from the Cauliflower Mosaic Virus 35S Promoter (CaMV35S), inserted into most transgenic plants. HDA is one of the simplest approaches for DNA amplification, emulating the bacterial replication machinery, and resembling PCR but under isothermal conditions. However, it usually suffers from a lack of selectivity, which is due to the accumulation of spurious amplification products. To improve the selectivity of HDA, which makes the detection of amplification products more reliable, we have developed an electrochemical platform targeting the central sequence of HDA copies of the transgene. A binary monolayer architecture is built onto a thin gold film where, upon the formation of perfect nucleic acid duplexes with the amplification products, these are enzyme-labeled and electrochemically transduced. The resulting combined system increases genosensor detectability up to 10(6)-fold, allowing Yes/No detection of GMOs with a limit of detection of ∼30 copies of the CaMV35S genomic DNA. A set of general utility rules in the design of genosensors for detection of HDA amplicons, which may assist in the development of point-of-care tests, is also included. The method provides a versatile tool for detecting nucleic acids with extremely low abundance not only for food safety control but also in the diagnostics and environmental control areas.

  14. Genetic damage in mammalian somatic cells exposed to radiofrequency radiation: a meta-analysis of data from 63 publications (1990-2005).

    Science.gov (United States)

    VIjayalaxmi; Prihoda, Thomas J

    2008-05-01

    During the last several decades, numerous researchers have examined the potential of in vitro and /or in vivo exposure of radiofrequency( RF) radiation to damage the genetic material in mammalian somatic cells. A meta-analysis of reported data was conducted to obtain a quantitative estimate ( with 95% confidence intervals) of genotoxicity in RF-radiation-exposed cells compared with sham-exposed/unexposed control cells. The extent of genotoxicity was assessed for various end points, including single- and double-strand breaks in the DNA, incidence of chromosomal aberrations, micronuclei and sister chromatid exchanges. Among the several variables in the experimental protocols used in individual investigations, the influence of three specific variables related to RF-radiation exposure characteristics was examined in the meta-analysis: frequency, specific absorption rate, and exposure as continuous-wave, pulsed-wave and occupationally exposed/cell phone users. The overall data indicated that (1) the difference between RF-radiation exposure was small with few exceptions; (2) at certain RF radiation exposure conditions, there were statistically significant increases in genotoxicity for some end points; and (3) the mean indices for chromosomal aberrations and micronuclei in RF-radiation -exposed and sham-/unexposed controls were within the spontaneous levels reported in the historical database. Considerable evidence for publication bias was found in the meta-analysis.

  15. Sensitivity to Antibiotics of Bacteria Exposed to Gamma Radiation Emitted from Hot Soils of the High Background Radiation Areas of Ramsar, Northern Iran.

    Science.gov (United States)

    Mortazavi, Seyed Mohammad Javad; Zarei, Samira; Taheri, Mohammad; Tajbakhsh, Saeed; Mortazavi, Seyed Alireza; Ranjbar, Sahar; Momeni, Fatemeh; Masoomi, Samaneh; Ansari, Leila; Movahedi, Mohammad Mehdi; Taeb, Shahram; Zarei, Sina; Haghani, Masood

    2017-04-01

    Over the past several years our laboratories have investigated different aspects of the challenging issue of the alterations in bacterial susceptibility to antibiotics induced by physical stresses. To explore the bacterial susceptibility to antibiotics in samples of Salmonella enterica subsp. enterica serovar Typhimurium (S. typhimurium), Staphylococcus aureus, and Klebsiella pneumoniae after exposure to gamma radiation emitted from the soil samples taken from the high background radiation areas of Ramsar, northern Iran. Standard Kirby-Bauer test, which evaluates the size of the zone of inhibition as an indicator of the susceptibility of different bacteria to antibiotics, was used in this study. The maximum alteration of the diameter of inhibition zone was found for K. pneumoniae when tested for ciprofloxacin. In this case, the mean diameter of no growth zone in non-irradiated control samples of K. pneumoniae was 20.3 (SD 0.6) mm; it was 14.7 (SD 0.6) mm in irradiated samples. On the other hand, the minimum changes in the diameter of inhibition zone were found for S. typhimurium and S. aureus when these bacteria were tested for nitrofurantoin and cephalexin, respectively. Gamma rays were capable of making significant alterations in bacterial susceptibility to antibiotics. It can be hypothesized that high levels of natural background radiation can induce adaptive phenomena that help microorganisms better cope with lethal effects of antibiotics.

  16. Progress Towards High-Sensitivity Arrays of Detectors of Sub-mm Radiation Using Superconducting Tunnel Junctions with Integrated Radio Frequency Single-Electron Transistors

    Science.gov (United States)

    Stevenson, T. R.; Hsieh, W.-T.; Li, M. J.; Prober, D. E.; Rhee, K. W.; Schoelkopf, R. J.; Stahle, C. M.; Teufel, J.; Wollack, E. J.

    2004-01-01

    For high resolution imaging and spectroscopy in the FIR and submillimeter, space observatories will demand sensitive, fast, compact, low-power detector arrays with 104 pixels and sensitivity less than 10(exp -20) W/Hz(sup 0.5). Antenna-coupled superconducting tunnel junctions with integrated rf single-electron transistor readout amplifiers have the potential for achieving this high level of sensitivity, and can take advantage of an rf multiplexing technique. The device consists of an antenna to couple radiation into a small superconducting volume and cause quasiparticle excitations, and a single-electron transistor to measure current through junctions contacting the absorber. We describe optimization of device parameters, and results on fabrication techniques for producing devices with high yield for detector arrays. We also present modeling of expected saturation power levels, antenna coupling, and rf multiplexing schemes.

  17. Optimization of beam angles for intensity modulated radiation therapy treatment planning using genetic algorithm on a distributed computing platform.

    Science.gov (United States)

    Nazareth, Daryl P; Brunner, Stephen; Jones, Matthew D; Malhotra, Harish K; Bakhtiari, Mohammad

    2009-07-01

    Planning intensity modulated radiation therapy (IMRT) treatment involves selection of several angle parameters as well as specification of structures and constraints employed in the optimization process. Including these parameters in the combinatorial search space vastly increases the computational burden, and therefore the parameter selection is normally performed manually by a clinician, based on clinical experience. We have investigated the use of a genetic algorithm (GA) and distributed-computing platform to optimize the gantry angle parameters and provide insight into additional structures, which may be necessary, in the dose optimization process to produce optimal IMRT treatment plans. For an IMRT prostate patient, we produced the first generation of 40 samples, each of five gantry angles, by selecting from a uniform random distribution, subject to certain adjacency and opposition constraints. Dose optimization was performed by distributing the 40-plan workload over several machines running a commercial treatment planning system. A score was assigned to each resulting plan, based on how well it satisfied clinically-relevant constraints. The second generation of 40 samples was produced by combining the highest-scoring samples using techniques of crossover and mutation. The process was repeated until the sixth generation, and the results compared with a clinical (equally-spaced) gantry angle configuration. In the sixth generation, 34 of the 40 GA samples achieved better scores than the clinical plan, with the best plan showing an improvement of 84%. Moreover, the resulting configuration of beam angles tended to cluster toward the patient's sides, indicating where the inclusion of additional structures in the dose optimization process may avoid dose hot spots. Additional parameter selection in IMRT leads to a large-scale computational problem. We have demonstrated that the GA combined with a distributed-computing platform can be applied to optimize gantry angle

  18. Genetic sensitivity to bitter taste of 6-n Propylthiouracil: A useful diagnostic aid to detect early childhood caries in pre-school children

    Directory of Open Access Journals (Sweden)

    Raghavendra Pidamale

    2012-01-01

    Full Text Available Purpose: Genetic factor to bitter taste perception appears to be largely mediated by the TAS2R38 gene. The insensitivity to bitter compounds like 6-n-propylthiouracil (PROP is mediated by this gene. PROP, a pharmacological drug used in treatment of Graves′ disease, proved to be useful tool in determining the genetic sensitivity levels to bitter and sweet taste. The purpose of this study is to show much simpler PROP sensitivity technique for the clinical examiner and its application as a diagnostic aid in Early Childhood Caries (ECC detection among preschool children. Materials and Methods: A total of 119 children belonging to the age group of 36 to 71 months of both sexes, were recruited from A. J. Institute of Dental Sciences, Mangalore (Karnataka. PROP sensitivity test was carried out to determine the inherent genetic ability to taste a bitter or sweet substance. This study used simpler scaling method to find out genetic sensitivity to bitter taste; one who tasted bitter as taster and one who was not able to differentiate/tasted like paper as non-taster. A questionnaire was provided to evaluate their dietary habits and caries experience was recorded. Collected data were tabulated and subjected to statistical analysis. Results: In the total of 119 children the mean dmfs was definitely higher in non-taster children compared to tasters. The tasters had a mean dmfs value of 9.5120 (S.D. 7.0543 and non-tasters had a value of 7.7250 (S.D. 8.33147, which was statistically significant. The results suggested that there was increase in caries experience among the group of non-tasters as compared to tasters. Tasters tended to be sweet dislikers and non-tasters tended to be sweet likers. On the whole, tasters had a bad dentition as compared to non tasters. Conclusion: The PROP sensitivity test (filter paper test proved to be a useful diagnostic tool in determining the genetic sensitivity levels of bitter taste. The knowledge of a child′s taste

  19. CpG-ODN 7909 increases radiation sensitivity of radiation-resistant human lung adenocarcinoma cell line by overexpression of Toll-like receptor 9.

    Science.gov (United States)

    Yan, Li; Xu, Guoxiong; Qiao, Tiankui; Chen, Wei; Yuan, Sujuan; Li, Xuan

    2013-09-01

    Radioresistance is one of the main reasons for the failure of radiotherapy in lung cancer. The aim of this study was to establish a radiation-resistant lung cancer cell line, to evaluate whether CpG oligodeoxyribonucleotide (CpG-ODN) 7909 could increase its radiosensitivity and to explore the relevant mechanisms. The radioresistant cell line, referred to as R-A549, was generated by reduplicative fractionated irradiation from the human lung adenocarcinoma cell line A549. The radioresistance of R-A549 cells were confirmed by the Cell Counting Kit-8 (CCK-8), cell viability assay, and clonogenic assay. Cell growth kinetics, morphological feature, and radiosensitivity were compared between the original A549 cells and R-A549 cells treated with or without CpG-ODN 7909 or radiation. To further explore the potential mechanisms of radiosensitivity, the cell cycle distributions and the expression of Toll-like receptor 9 (TLR-9) were examined by Western blot and flow cytometry. The R-A549 cell line was generated and its radioresistance was further confirmed. CpG-ODN 7909 was found to increase much more radiosensitivity of R-A549 cells under combined treatments with CpG-ODN 7909 and radiation compared with its control group without any treatments. They presented their respective D0 1.33 ± 0.20 Gy versus 1.76 ± 0.25 Gy with N 3.44 ± 1.01 versus 4.96 ± 0.32. Further, there was a larger cell population of R-A549 cells under combined treatment in the G2/M phase compared with the control group after treatment with CpG-ODN7909 or radiation alone at 24 and 48 hour. The expression level of TLR-9 in R-A549 cells was found higher than in A549 cells. These results suggested that CpG-ODN 7909 increased the radiosensitivity of R-A549 cells, which might be mediated via the upregulated TLR-9 and prolonged cell cycle arrest in the G2/M phase compared with A549 cells.

  20. 薄板结构辐射声功率及其灵敏度分析%Study of Radiated Sound Power and Its Sensitivity Analysis of Plate

    Institute of Scientific and Technical Information of China (English)

    刘聪; 姜哲

    2012-01-01

    Joint using the finite element method and acoustic radiation modal method to solve the sound power structure sheet radiation, the structure radiation sound power about the design variable sensitivity was analyzed. In the structure vibration link, surface vibration velocity was obtained using the finite element method; in the sound radiation link, the sound field information about radiation of surface vibration can be obtained by expansions of the acoustic radiation modes. For the radiation of a stiffened panel, sound power sensitivity with respect to design variable was analyzed, and the results showed that the sound power was reduced by using stiffeners when the excitation frequency was far from the natural frequency of the body, but it had negative influence and was useless by using stiffeners when the natural frequency was close to the excitation frequency.%联合利用有限元方法和声辐射模态方法求解薄板结构辐射的声功率,并分析结构辐射声功率关于设计变量的灵敏度.在结构振动环节,利用有限元方法对结构进行动力响应分析得到表面振速;在声辐射环节,采用声辐射模态展开获得振动表面辐射的声场信息.以加筋板结构为例,计算结构振动辐射的声功率及其关于设计变量的灵敏度.结果表明,当激励频率远离结构振动固有频率时,加筋可以降低结构辐射的声功率;而当加筋使结构固有频率接近激励频率时,加筋甚至产生负面影响,此时通过加筋降低结构辐射声功率是没有意义的.

  1. Effect of Genetic Information Regarding Salt-Sensitive Hypertension on the Intent to Maintain a Reduced Salt Diet: Implications for Health Communication in Japan.

    Science.gov (United States)

    Miyamoto, Keiko; Iwakuma, Miho; Nakayama, Takeo

    2017-03-01

    The authors investigated the relationship between the awareness of dietary salt and genetics and the intent to maintain a low-salt diet. In particular, they assessed whether hypothetical genetic information regarding salt-sensitive hypertension motivates the intent to reduce dietary salt for communicating the health benefits of lower salt consumption to citizens. A self-administered questionnaire survey was conducted with 2500 randomly sampled residents aged 30 to 69 years living in Nagahama, Japan. Genetic information regarding higher salt sensitivity increased motivation to reduce salt intake for both those who agreed that genes cause hypertension and those who did not. Less than 50% of those who agreed that genes cause hypertension lost their intention to lower their salt consumption when they found they did not possess the susceptibility gene. Communicating genetic information positively affected motivation to reduce salt intake. The present study clarifies the difficulty in changing the behavioral intent of those who have significantly less incentive to reduce salt intake. Therefore, a multidimensional approach is crucial to reduce salt consumption. ©2016 Wiley Periodicals, Inc.

  2. Solar radiation absorption in the atmosphere due to water and ice clouds: Sensitivity experiments with plane-parallel clouds

    Energy Technology Data Exchange (ETDEWEB)

    Gautier, C. [Univ. of California, Santa Barbara, CA (United States)

    1995-09-01

    One cloud radiation issue that has been troublesome for several decades is the absorption of solar radiation by clouds. Many hypotheses have been proposed to explain the discrepancies between observations and modeling results. A good review of these often-competing hypotheses has been provided by Stephens and Tsay. They characterize the available hypotheses as failing into three categories: (1) those linked to cloud microphysical and consequent optical properties; (2) those linked to the geometry and heterogeneity of clouds; and (3) those linked to atmospheric absorption.Current modeling practice is seriously inconsistent with new observational inferences concerning absorption of solar radiation in the atmosphere. The author and her colleagues contend that an emphasis on R may, therefore, not be the optimal way of addressing the cloud solar absorption issue. 4 refs., 1 fig.

  3. Donor-specific cell-based assays in studying sensitivity to low-dose radiation: a population-based perspective

    Directory of Open Access Journals (Sweden)

    Dora eIl'yasova

    2014-11-01

    Full Text Available Currently, a linear no-threshold model is used to estimate health risks associated with exposure to low-dose radiation, a prevalent exposure in the general population, because the direct estimation from epidemiological studies suffers from uncertainty. This model has been criticized based on unique biology of low-dose radiation. Whether the departure from linearity is toward increased or decreased risk is intensely debated. We present an approach based on individual radiosensitivity testing and discuss how individual radiosensitivity can be assessed with the goal to develop a quantifiable measure of cellular response that can be conducted via high-throughput population testing.

  4. Genetic Sensitivity to the Environment: The Case of the Serotonin Transporter Gene and Its Implications for Studying Complex Diseases and Traits

    Science.gov (United States)

    Caspi, Avshalom; Hariri, Ahmad R.; Holmes, Andrew; Uher, Rudolf; Moffitt, Terrie E.

    2010-01-01

    Evidence of marked variability in response among people exposed to the same environmental risk implies that individual differences in genetic susceptibility might be at work. The study of such Gene-by-Environment (G×E) interactions has gained momentum. In this article, the authors review research about one of the most extensive areas of inquiry: variation in the promoter region of the serotonin transporter gene (SLC6A4; also known as 5-HTT) and its contribution to stress sensitivity. Research in this area has both advanced basic science and generated broader lessons for studying complex diseases and traits. The authors evaluate four lines of evidence about the 5-HTT stress-sensitivity hypothesis: 1) observational studies about the serotonin transporter linked polymorphic region (5-HTTLPR), stress sensitivity, and depression in humans; 2) experimental neuroscience studies about the 5-HTTLPR and biological phenotypes relevant to the human stress response; 3) studies of 5-HTT variation and stress sensitivity in nonhuman primates; and 4) studies of stress sensitivity and genetically engineered 5-HTT mutations in rodents. The authors then dispel some misconceptions and offer recommendations for G×E research. The authors discuss how G×E interaction hypotheses can be tested with large and small samples, how G×E research can be carried out before as well as after replicated gene discovery, the uses of G×E research as a tool for gene discovery, the importance of construct validation in evaluating G×E research, and the contribution of G×E research to the public understanding of genetic science. PMID:20231323

  5. Differences of UV-B radiation sensitivity of rice%水稻对UV-B辐射响应的敏感性差异

    Institute of Scientific and Technical Information of China (English)

    何永美; 湛方栋; 高召华; 祖艳群; 李元

    2012-01-01

    综述了UV-B辐射对水稻(Oryza sativa L.)的影响和水稻对UV-B辐射的抗性机制.UV-B辐射对水稻生长、叶片形态、生物量、产量、光合系统、病害等产生一定的影响.水稻对UV-B辐射的敏感性因子主要有CPD光解酶、UV-B吸收物质、抗氧化酶等.UV-B辐射使