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Sample records for mechanisms radiation resistance

  1. Biological improvement of radiation resistance

    Energy Technology Data Exchange (ETDEWEB)

    Chun, K. J.; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J

    2000-08-01

    To investigate the mechanisms of gene action related to the radiation resistance in microorganisms could be essentially helpful for the development of radiation protectants and hormeric effects of low dose radiation. This book described isolation of radiation-resistant microorganisms, induction of radiation-resistant and functionally improved mutants by gamma-ray radiation, cloning and analysis of the radiation resistance related genes and analysis of the expressed proteins of the radiation resistant related genes.

  2. Some resistance mechanisms to ultraviolet radiation; Algunos mecanismos de resistencia a radiacion ultravioleta

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    Alcantara D, D. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2002-12-15

    The cyclical exposure of bacterial cells to the ultraviolet light (UV) it has as consequence an increment in the resistance to the lethal effects of this type of radiation, increment that happens as a result of a selection process of favorable genetic mutations induced by the same UV light. With object to study the reproducibility of the genetic changes and the associate mechanisms to the resistance to UV in the bacteria Escherichia coli, was irradiated cyclically with UV light five different derived cultures of a single clone, being obtained five stumps with different resistance grades. The genetic mapping Hfr revealed that so much the mutation events like of selection that took place during the adaptation to the UV irradiation, happened of random manner, that is to say, each one of the resistant stumps it is the result of the unspecified selection of mutations arisen at random in different genes related with the repair and duplication of the DNA. (Author)

  3. Induction of radiation resistance and radio-protective mechanism. On the reactive oxygen and free radical

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    Yukawa, Osami [National Inst. of Radiological Sciences, Chiba (Japan). Research Center for Radiation Safety

    2003-03-01

    Radical scavenging system for reactive oxygen species (ROS) leading to radio-protection is reviewed on findings in animals, tissues and cells. Protection against oxygen toxicity in evolution can be seen in anaerobes' superoxide dismutase (SOD) over 3500 million years ago. ROS is generated endogenously and also by radiation. However, the intracellular sites of the generated ROS are different depending on its cause. The protection is done through enzymes like SOD, peroxidase, catalase, glutathione-related enzymes and through substances like GSH, {alpha}-tocopherol, ascorbic acid etc. Induction of ROS scavenging substances related with radio-resistance includes the responses to the low dose radiation (5-50 cGy) in those enzymes described above; to middle to high dose radiation (1-30 Gy) in a similar and in other unknown mechanisms; to exposure of ROS like H{sub 2}O{sub 2} at low concentration; and to antioxidant treatment. The cross-resistance between radiation and drugs suggests necessity of this induction. (N.I.)

  4. A preliminary study on the radiation-resistance mechanism in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Qi Liao

    2013-01-01

    Full Text Available Aim: The present study was designed to explore the radiation-resistance mechanism by interfering in checkpoints kinase 1 (CHK1 and DNA-activated protein kinase (DNA-PK genes with short hairpin RNA (shRNA transfection into Skov3 cells derived from ovarian cancer and HeLa cells derived from cervical cancer. Materials and Methods: The cultured Skov3 and HeLa cells were transfected with plasmid vectors containing CHK1 shRNA and DNA-PK shRNA, respectively, through Lipofectimine™ 2000 mediation, and cultured for 20 hours before exposure to 2 Gy X-radiation. The cells were harvested 4 and 28 after X-irradiation respectively then washed 3 times with PBS. These cells were stained with Annexin V/PI and applied by flow cytometer to analyze alteration of apoptosis with software CellQuest. Results: The apoptotic response in Skov3 cells to X-radiation was significantly lower than that in HeLa cells at 4 hour (t = 15.22, P < 0.001 and 28 hours (t = 15.78, P < 0.001 of post-irradiation. The shRNA might not affect the apoptosis of Skov3 and HeLa cells, while shRNA-transfection significantly enhanced the apoptotic response in Skov3 cells to X-radiation as compared with that in HeLa cells. Conclusions: The present work suggests that the CHK1 and DNA-PK genes are very likely to play a role in developing a radiation resistance in ovarian cancer.

  5. Gravitational radiation resistance, radiation damping and field fluctuations

    Science.gov (United States)

    Schaefer, G.

    1981-03-01

    Application is made of two different generalized fluctuation-dissipation theorems and their derivations to the calculation of the gravitational quadrupole radiation resistance using the radiation-reaction force given by Misner, Thorne and Wheeler and the usual tidal force on one hand and the tidal force and the free gravitational radiation field on the other hand. The quantum-mechanical version (including thermal generalizations) of the well known classical quadrupole radiation damping formula is obtained as a function of the radiation resistance.

  6. Radiation resistance of acinetobacter spp.

    Science.gov (United States)

    Whitby, James L.

    1995-02-01

    The radiation resistance of 78 different strains of Acinetobacter sp. 42 from clinical isolates and 36 from other sources were compared with 15 clinical isolates and 12 other strains from Denmark. None of the Canadian strains was as resistant as resistant-enhanced Danish strains. Four strains had D 10 values of 3.1-3.6 kGy. Irradiated and unirradiated cells from all strains grew well, when cultured in Trypticase-Soy Broth at 30°C. Most cultures grew after overnight incubation. It was concluded that there would be no difficulty in detecting these strains, using ISO methodology for establishing the radiation sterilization dose for devices.

  7. Radiation Bystander Effects Mechanism

    Directory of Open Access Journals (Sweden)

    Shokohzaman Soleymanifard

    2009-06-01

    Full Text Available Introduction: Radiation Induced Bystander Effect (RIBE which cause radiation effects in non-irradiated cells, has challenged the principle according to which radiation traversal through the nucleus of a cell is necessary for producing biological responses. What is the mechanism of this phenomenon? To have a better understanding of this rather ambiguous concept substantial number of original and reviewed article were carefully examined. Results: Irradiated cells release molecules which can propagate in cell environment and/or transmit through gap junction intercellular communication. These molecules can reach to non-irradiated cells and transmit bystander signals. In many investigations, it has been confirmed that these molecules are growth factors, cytokines, nitric oxide and free radicals like reactive oxygen species (ROS. Transmission of by stander signal to neighboring cells persuades them to produce secondary growth factors which in their turn cause further cell injuries. Some investigators suggest, organelles other than nucleus (mitochondria and cell membrane are the origin of these signals.  There is another opinion which suggests double strand breaks (DSB are not directly generated in bystander cells, rather they are due to smaller damage like single strand breaks which accumulate and end up to DSB. Although bystander mechanisms have not been exactly known, it can be confirmed that multiple mechanisms and various pathways are responsible for this effect. Cell type, radiation type, experimental conditions and end points identify the dominant mechanism. Conclusion: Molecules and pathways which are responsible for RIBE, also cause systemic responses to other non-irradiation stresses. So RIBE is a kind of systemic stress or innate immune responses, which are performed by cell microenvironment. Irradiated cells and their signals are components of microenvironment for creating bystander effects.

  8. Research of radiation-resistant microbial organisms

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    Kim, Dongho; Lim, Sangyong; Joe, Minho; Park, Haejoon; Song, Hyunpa; Im, Seunghun; Kim, Haram; Kim, Whajung; Choi, Jinsu; Park, Jongchun

    2012-01-15

    Many extremophiles including radiation-resistant bacteria Deinococcus radiodurans have special characteristics such as novel enzymes and physiological active substances different from known biological materials and are being in the spotlight of biotechnology science. In this research, basic technologies for the production of new genetic resources and microbial strains by a series of studies in radiation-resistant microbial organisms were investigated and developed. Mechanisms required for radiation-resistant in Deinococcus radiodurans were partly defined by analyzing the function of dinB, pprI, recG, DRA{sub 0}279, pprM, and two-component signal transduction systems. To apply genetic resource and functional materials from Deinococcus species, omics analysis in response to cadmium, construction of macroscopic biosensor, and characterization of carotenoids and chaperon protein were performed. Additionally, potential use of D. geothermalis in monosaccharide production from non-biodegradable plant materials was evaluated. Novel radiation resistant yeasts and bacteria were isolated and identified from environmental samples to obtain microbial and genomic resources. An optimal radiation mutant breeding method was set up for efficient and rapid isolation of target microbial mutants. Furthermore, an efficient ethanol producing mutant strain with high production yield and productivity was constructed using the breeding method in collaboration with Korea Research Institute of Bioscience and Biotechnology. Three Deinococcal bioindicators for radiation dosage confirmation after radiation sterilization process were developed. These results provide a comprehensive information for novel functional genetic elements, enzymes, and physiological active substances production or application. Eventually, industrial microbial cell factories based on radiation resistant microbial genomes can be developed and the technologies can be diffused to bioindustry continuously by this project.

  9. Bacterial and archaeal resistance to ionizing radiation

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    Confalonieri, F; Sommer, S, E-mail: fabrice.confalonieri@u-psud.fr, E-mail: suzanne.sommer@u-psud.fr [University Paris-Sud, CNRS UMR8621, Institut de Genetique et Microbiologie, Batiments 400-409, Universite Paris-Sud, 91405 Orsay (France)

    2011-01-01

    Organisms living in extreme environments must cope with large fluctuations of temperature, high levels of radiation and/or desiccation, conditions that can induce DNA damage ranging from base modifications to DNA double-strand breaks. The bacterium Deinococcus radiodurans is known for its resistance to extremely high doses of ionizing radiation and for its ability to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Recently, extreme ionizing radiation resistance was also generated by directed evolution of an apparently radiation-sensitive bacterial species, Escherichia coli. Radioresistant organisms are not only found among the Eubacteria but also among the Archaea that represent the third kingdom of life. They present a set of particular features that differentiate them from the Eubacteria and eukaryotes. Moreover, Archaea are often isolated from extreme environments where they live under severe conditions of temperature, pressure, pH, salts or toxic compounds that are lethal for the large majority of living organisms. Thus, Archaea offer the opportunity to understand how cells are able to cope with such harsh conditions. Among them, the halophilic archaeon Halobacterium sp and several Pyrococcus or Thermococcus species, such as Thermococcus gammatolerans, were also shown to display high level of radiation resistance. The dispersion, in the phylogenetic tree, of radioresistant prokaryotes suggests that they have independently acquired radioresistance. Different strategies were selected during evolution including several mechanisms of radiation byproduct detoxification and subtle cellular metabolism modifications to help cells recover from radiation-induced injuries, protection of proteins against oxidation, an efficient DNA repair tool box, an original pathway of DNA double-strand break repair, a condensed nucleoid that may prevent the dispersion of the DNA fragments and specific radiation-induced proteins involved in

  10. Bacterial and archaeal resistance to ionizing radiation

    Science.gov (United States)

    Confalonieri, F.; Sommer, S.

    2011-01-01

    Organisms living in extreme environments must cope with large fluctuations of temperature, high levels of radiation and/or desiccation, conditions that can induce DNA damage ranging from base modifications to DNA double-strand breaks. The bacterium Deinococcus radiodurans is known for its resistance to extremely high doses of ionizing radiation and for its ability to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Recently, extreme ionizing radiation resistance was also generated by directed evolution of an apparently radiation-sensitive bacterial species, Escherichia coli. Radioresistant organisms are not only found among the Eubacteria but also among the Archaea that represent the third kingdom of life. They present a set of particular features that differentiate them from the Eubacteria and eukaryotes. Moreover, Archaea are often isolated from extreme environments where they live under severe conditions of temperature, pressure, pH, salts or toxic compounds that are lethal for the large majority of living organisms. Thus, Archaea offer the opportunity to understand how cells are able to cope with such harsh conditions. Among them, the halophilic archaeon Halobacterium sp and several Pyrococcus or Thermococcus species, such as Thermococcus gammatolerans, were also shown to display high level of radiation resistance. The dispersion, in the phylogenetic tree, of radioresistant prokaryotes suggests that they have independently acquired radioresistance. Different strategies were selected during evolution including several mechanisms of radiation byproduct detoxification and subtle cellular metabolism modifications to help cells recover from radiation-induced injuries, protection of proteins against oxidation, an efficient DNA repair tool box, an original pathway of DNA double-strand break repair, a condensed nucleoid that may prevent the dispersion of the DNA fragments and specific radiation-induced proteins involved in

  11. Radiation resistance of Acinetobacter spp.

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    Whitby, J.L. [University of Western Ontario, London, ON (Canada)

    1995-10-01

    The radiation resistance of 78 different strains of Acinetobacter sp. 42 from clinical isolates and 36 from other sources were compared with 15 clinical isolates and 12 other strains from Denmark. None of the Canadian strains was as resistant as resistant-enhanced Danish strains. Four strains had D{sub 10} values of 3.1-3.6 kGy. Irradiated and unirradiated cells from all strains grew well, when cultured in Trypticase-Soy Broth at 30{sup o}C. Most cultures grew after overnight incubation. It was concluded that there would be no difficulty in detecting these strains, using ISO methodology for establishing the radiation sterilization dose for devices. (Author).

  12. Radiation resistant modified polypropylene; Polipropylen modyfikowany odporny radiacyjnie

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    Bojarski, J.; Zimek, Z. [Institute of Nuclear Chemistry and Technology, Warsaw (Poland)

    1997-10-01

    Radiation technology for production of radiation resistant polypropylene for medical use has been presented. The method consists in radiation induced copolymerization of polypropylene with ethylene and addition of small amount of copolymer of polyethylene and vinyl acetate. The material of proposed composition has a very good mechanical properties and elevated radiation resistivity decided on possibility of radiosterilization of products made of this material and designed for medical use. 3 figs, 3 tabs.

  13. Effects of electron beam radiation on mechanical properties and on the resistance to punctures caused by Plodia interpunctella in cereal bar packaging

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    Alves, Juliana N.; Moura, Esperidiana A.B.; Oliveira, Vitor M., E-mail: julianaabc@usp.b, E-mail: eabmoura@ipen.b, E-mail: volmiranda@gmail.co [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Potenza, Marcos R., E-mail: potenza@biologico.sp.gov.b [Instituto Biologico de Sao Paulo/APTA, Sao Paulo, SP (Brazil); Arthur, Valter, E-mail: varthur@cena.usp.b [Centro de Energia Nuclear na Agricultura (CENA/USP), Piracicaba, SP (Brazil)

    2009-07-01

    Plodia interpunctella is an important pest in stored products in the tropical and subtropical regions, infesting grains and flours. The adult of P. interpunctella is a small butterfly with about 15 - 20mm of spread and the female places separately of 100 the 400 eggs in groups on the grains whose hard incubation some days. This insect infesting diverse types of food packaging, depreciating the products and causing economic losses. It is therefore critical for these products a packaging that presents, in addition to good mechanical, barrier and machinability properties, a good resistance to puncture by insects, in order to prevent the contact and spread of pests in the packaged food. This study evaluates the changes on mechanical properties and puncture resistance by P. interpunctella in BOPPmet/BOPP structure, used commercially as cereal bar packaging, after electron beam irradiation. The material samples were irradiated up to 120 kGy using a 1.5 MeV electrostatic accelerator, at room temperature, in air, dose rate 11.22 kGy/s. Irradiation doses were measured using cellulose triacetate film dosimeters 'CTA-FTR-125' from Fuji Photo Film Co. Ltd. After irradiation the BOPPmet/BOPP samples were subjected to tests of puncture resistance by P. interpunctella, tensile tests and penetration resistance. The results showed significant decreases (p<0.05) in the original mechanical properties of the structures according to the radiation doses applied and effective resistance against punctures by P. interpunctella for irradiated and nonirradiated BOPPmet/BOPP samples. These results indicate that non-irradiated and irradiated BOPPmet/BOPP structure presents puncture resistance against P. interpunctella and that electron-beam irradiation, in conditions studied in this work, may turn the structure inappropriate for cereal bar packaging, due to high reduction its mechanical properties after irradiation. (author)

  14. Sustainably Sourced, Thermally Resistant, Radiation Hard Biopolymer

    Science.gov (United States)

    Pugel, Diane

    2011-01-01

    This material represents a breakthrough in the production, manufacturing, and application of thermal protection system (TPS) materials and radiation shielding, as this represents the first effort to develop a non-metallic, non-ceramic, biomaterial-based, sustainable TPS with the capability to also act as radiation shielding. Until now, the standing philosophy for radiation shielding involved carrying the shielding at liftoff or utilizing onboard water sources. This shielding material could be grown onboard and applied as needed prior to different radiation landscapes (commonly seen during missions involving gravitational assists). The material is a bioplastic material. Bioplastics are any combination of a biopolymer and a plasticizer. In this case, the biopolymer is a starch-based material and a commonly accessible plasticizer. Starch molecules are composed of two major polymers: amylase and amylopectin. The biopolymer phenolic compounds are common to the ablative thermal protection system family of materials. With similar constituents come similar chemical ablation processes, with the potential to have comparable, if not better, ablation characteristics. It can also be used as a flame-resistant barrier for commercial applications in buildings, homes, cars, and heater firewall material. The biopolymer is observed to undergo chemical transformations (oxidative and structural degradation) at radiation doses that are 1,000 times the maximum dose of an unmanned mission (10-25 Mrad), indicating that it would be a viable candidate for robust radiation shielding. As a comparison, the total integrated radiation dose for a three-year manned mission to Mars is 0.1 krad, far below the radiation limit at which starch molecules degrade. For electron radiation, the biopolymer starches show minimal deterioration when exposed to energies greater than 180 keV. This flame-resistant, thermal-insulating material is non-hazardous and may be sustainably sourced. It poses no hazardous

  15. Potential mechanisms involved in resistant phenotype of MCF-7 breast carcinoma cells to ionizing radiation induced apoptosis

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    Wang Yanling [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China); Zhang Hong [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China)], E-mail: zhangh@impcas.ac.cn; Li Ning [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China); Wang Xiaohu [Department of Radiotherapy, Gansu Tumor Hospital, Lanzhou 730050 (China); Hao Jifang [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Zhao Weiping [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China)

    2009-03-15

    In the present study, we investigated the mechanisms of apoptosis resistance and the roles of the phosphorylation of BRCA1, p21, the Bax/Bcl-2 protein ratio and cell cycle arrest in IR-induced apoptosis in MCF-7 cells. X-irradiation, in particular at low dose (1 Gy), but not carbon ion irradiation, had a significant antiproliferative effect on the growth of MCF-7 cells. 1 Gy X-irradiation resulted in G1 and G2 phase arrest, but 4 Gy induced a significant G1 block. In contrast, carbon ion irradiation resulted in a significant accumulation in the G2 phase. Concomitant with the phosphorylation of H2AX induced by DNA damage, carbon ion irradiation resulted in an approximately 1.9-2.8-fold increase in the phosphorylation of BRCA1 on serine residue 1524, significantly greater than that detected for X-irradiation. Carbon ion irradiation caused a dramatic increase in p21 expression and drastic decrease in Bax expression compared with X-irradiation. The data implicated that phosphorylation of BRCA1 on serine residue 1524 might, at least partially, induce p21 expression but repress Bax expression. Together, our results suggested that the phosphorylation of BRCA1 at Ser-1524 might contribute to the G2 phase arrest and might be an upstream signal involved in preventing apoptosis signal via upregulation of p21 and downregulation of the Bax/Bcl-2 ratio.

  16. Mechanisms of drug resistance: quinolone resistance.

    Science.gov (United States)

    Hooper, David C; Jacoby, George A

    2015-09-01

    Quinolone antimicrobials are synthetic and widely used in clinical medicine. Resistance emerged with clinical use and became common in some bacterial pathogens. Mechanisms of resistance include two categories of mutation and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes, DNA gyrase and DNA topoisomerase IV, are commonly in a localized domain of the GyrA and ParE subunits of the respective enzymes and reduce drug binding to the enzyme-DNA complex. Other resistance mutations occur in regulatory genes that control the expression of native efflux pumps localized in the bacterial membrane(s). These pumps have broad substrate profiles that include quinolones as well as other antimicrobials, disinfectants, and dyes. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids can confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is due to Qnr proteins that protect the target enzymes from quinolone action, one mutant aminoglycoside-modifying enzyme that also modifies certain quinolones, and mobile efflux pumps. Plasmids with these mechanisms often encode additional antimicrobial resistances and can transfer multidrug resistance that includes quinolones. Thus, the bacterial quinolone resistance armamentarium is large.

  17. Molecular mechanisms of antibiotic resistance.

    Science.gov (United States)

    Blair, Jessica M A; Webber, Mark A; Baylay, Alison J; Ogbolu, David O; Piddock, Laura J V

    2015-01-01

    Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.

  18. Mechanisms of Herbicide-resistance

    Institute of Scientific and Technical Information of China (English)

    MA Hong; CHEN Yibing; TAO Bo

    2006-01-01

    This paper discussed mechanisms of herbicide-resistance. There are at least four mechanisms identified by which weeds become resistant to a herbicide. The two most common mechanisms are those involving metabolic reactions and changes in the deoxyribonucleic acid sequence (mutations) that alter the structure and features of the target proteins. The other two mechanisms involve either an alteration in the penetration or translocation of the herbicides to the target site or the depolarization of membrane within the weed.

  19. CERN selects Fujikura's radiation resistant fiber

    CERN Multimedia

    2007-01-01

    "Fujikura Europe Ltd. (search for Fujikura Europe) today announced that its radiation resistant singlemode optical fiber has been selected by CERN to provide communicaton links within the world's largest particle accelerator..."(2/3 page)

  20. A Novel Radiation-Resistant Yeast, Filobasidium elegans RRY1

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    Singh, Harinder; Kim, Ha Ram; Song, Hyun Pa; Lim, Sang Yong; Kim, Dong Ho [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2012-05-15

    The tolerance to ionizing radiation stress is present among different classes and species of organisms. As listed by Rainey et al., ionizing radiation resistant organisms were isolated from a variety of different sources like processed/canned food items, paper industry, soil and water samples. Apart from extensively reported bacteria and Archea group, many fungal species like Aspergillus, Curvularia, Alternaria, Cryptococcus, and Ustilago maydis have been found to be resistant to ionizing radiation. However, different environmental sources are constantly been explored for novel radioresistant organisms, which can help in understanding the molecular mechanism behind these extreme stress responses. On the basis of this, present study was initiated to find novel radiation resistant yeast from sea water source

  1. Towards understanding the extreme radiation resistance of Ustilago maydis.

    Science.gov (United States)

    Holloman, William K; Schirawski, Jan; Holliday, Robin

    2007-12-01

    Ustilago maydis is a phytopathogenic fungus exhibiting extreme resistance to UV and ionizing radiation. The molecular mechanisms underlying this resistance are as yet unknown. The recently determined genome sequence was examined for clues to the radiation resistance, focusing on proteins in homologous recombination, but there was little that was unusual about them. Furthermore, by comparison, its recombinational repair system seems to be only minimally related to the extended synthesis-dependent DNA strand-annealing system of Deinococcus radiodurans. Thus, consideration should be given to the possibility that incremental structural changes in repair proteins or their elevated expression are the basis for the extreme radiation resistance in U. maydis. Evolution of a system enabling the survival of U. maydis under such conditions could be a secondary consequence of adaptation to an environment of continual genotoxic stress encountered in its habitat.

  2. Mechanisms of drug resistance: daptomycin resistance.

    Science.gov (United States)

    Tran, Truc T; Munita, Jose M; Arias, Cesar A

    2015-09-01

    Daptomycin (DAP) is a cyclic lipopeptide with in vitro activity against a variety of Gram-positive pathogens, including multidrug-resistant organisms. Since its introduction into clinical practice in 2003, DAP has become an important key frontline antibiotic for severe or deep-seated infections caused by Gram-positive organisms. Unfortunately, DAP resistance (DAP-R) has been extensively documented in clinically important organisms such as Staphylococcus aureus, Enterococcus spp., and Streptococcus spp. Studies on the mechanisms of DAP-R in Bacillus subtilis and other Gram-positive bacteria indicate that the genetic pathways of DAP-R are diverse and complex. However, a common phenomenon emerging from these mechanistic studies is that DAP-R is associated with important adaptive changes in cell wall and cell membrane homeostasis with critical changes in cell physiology. Findings related to these adaptive changes have provided novel insights into the genetics and molecular mechanisms of bacterial cell envelope stress response and the manner in which Gram-positive bacteria cope with the antimicrobial peptide attack and protect vital structures of the cell envelope, such as the cell membrane. In this review, we will examine the most recent findings related to the molecular mechanisms of resistance to DAP in relevant Gram-positive pathogens and discuss the clinical implications for therapy against these important bacteria.

  3. Radiation resistence of microorganisms from radiation sterilization processing environments

    Science.gov (United States)

    Sabovljev, Svetlana A.; Žunić, Zora S.

    The radiation resistance of microorganisms was examined on the samples of dust collected from the radiation sterilization processing environments including assembly, storage, and sterilization plant areas. The isolation of radiation resistant strains was performed by irradiation with screening doses ranging from 10 to 35 kGy and test pieces containing 10 6 to 10 8 CFU in dried serum-broth, representing 100 to 5000 colonies of primary cultures of microorganisms from 7 different sites. In an examination of 16900 colonies of aerobic microorganisms from 3 hygienically controlled production sites and 4 uncontrolled ones, 30 strains of bacteria were isolated. Of those 15 were classified as genus Bacillus, 9 as Micrococcus and 6 as Sarcina. All of the 15 strains of Gram positive sporeforming aerobic rods exhibited an exponential decrease in the surviving fraction as a function of dose, indicating that the inactivation of spores of aerobic rods is a consequence of a single energy deposition into the target. All strains were found to be moderately resistant to radiation with D-6 values (dose required to reduce survival to 6 log cycles) between 18 and 26 kGy. All of the isolated Gram positive cocci showed inactivation curves having a shoulder, indicating that different processes are involved in the inactivation of these cells, e.g. accumulation of sublethal lesions, or final repair capacity of potential lethal lesions. Moderate radiation resistance was observed in 13 strains with D-6 values between 16 to 30 kGy. Two slow-growing, red pigmented strains tentatively classified as genus Micrococcus isolated from uncontrolled sites (human dwellings) were exceptionally resistant with D-6 more than 45 kGy. For hygienically controlled sites, Gram positive spereforming rods composed two thirds of the resistant microflora, while Gram positive cocci comprised one third. For hygienically uncontrolled sites this ratio was reversed. An assumption is made that one isolated strain has grown

  4. Mechanisms of Resistance to Cabazitaxel

    Science.gov (United States)

    Duran, George E.; Wang, Yan C.; Francisco, E. Brian; Rose, John C.; Martinez, Francisco J.; Coller, John; Brassard, Diana; Vrignaud, Patricia; Sikic, Branimir I.

    2015-01-01

    We studied mechanisms of resistance to the novel taxane cabazitaxel in established cellular models of taxane resistance. We also developed cabazitaxel-resistant variants from MCF-7 breast cancer cells by stepwise selection in drug alone (MCF-7/CTAX) or drug plus the transport inhibitor PSC-833 (MCF-7/CTAX-P). Among multidrug resistant (MDR) variants, cabazitaxel was relatively less cross-resistant than paclitaxel and docetaxel (15 vs. 200-fold in MES-SA/Dx5 and 9 vs. 60-fold in MCF-7/TxT50, respectively). MCF-7/TxTP50 cells that were negative for MDR but had 9-fold resistance to paclitaxel were also 9-fold resistant to cabazitaxel. Selection with cabazitaxel alone (MCF-7/CTAX) yielded 33-fold resistance to cabazitaxel, 52-fold resistance to paclitaxel, activation of ABCB1, and 3-fold residual resistance to cabazitaxel with MDR inhibition. The MCF-7/CTAX-P variant did not express ABCB1, nor did it efflux rhodamine-123, BODIPY-labeled paclitaxel, and [3H]-docetaxel. These cells are hypersensitive to depolymerizing agents (vinca alkaloids and colchicine), have reduced baseline levels of stabilized microtubules, and impaired tubulin polymerization in response to taxanes (cabazitaxel or docetaxel) relative to MCF-7 parental cells. Class III β-tubulin (TUBB3) RNA and protein were elevated in both MCF-7/CTAX and MCF-7/CTAX-P. Decreased BRCA1 and altered epithelial-mesenchymal transition (EMT) markers are also associated with cabazitaxel resistance in these MCF-7 variants, and may serve as predictive biomarkers for its activity in the clinical setting. In summary, cabazitaxel resistance mechanisms include MDR (although at a lower level than paclitaxel and docetaxel), and alterations in microtubule dynamicity, as manifested by higher expression of TUBB3, decreased BRCA1, and by the induction of EMT. PMID:25416788

  5. Modulating Radiation Resistance: Novel Protection Paradigms Based on Defenses against Ionizing Radiation in the Extremophile Deinococcus radiodurans

    Science.gov (United States)

    2010-05-10

    cellular damge caused by ionizing radiation and ultraviolet light. Deinococcus radiodurans; Lactobacillus plantarurn; cyanobacteria ; radiation...6 3. K. S. Makarova and MICHAEL J. DALY (2010) Comparative genomics of stress response systems in Deinococcus bacteria. Bacterial Stress Responses...In Press) Abstract | The prospect of comparative genomics resolving the seemingly paradoxical mechanism of extreme radiation resistance in

  6. Research of radiation resistant Er doped fiber for space detection

    Science.gov (United States)

    Huang, Jian-ping; Zhang, Ge; Wang, Pu-pu; Li, Run-dong; Jiang, Cong; Xiao, Chun

    2016-11-01

    In this paper, erbium doped fibers for space detection are researched for feature of radiation resistance. Fibers with different coated carbon are hydrogen loaded and radiated, and too thick of carbon layer around fiber would not bring best radiation-resistant performance, since thick carbon layer would make the entering of hydrogen difficult. We also research the duration of saturated hydrogen loading under the high and low temperature respectively, and it's found that the fibers' photo sensitivities tend to be flat after some days. Hydrogen is reloaded into the fibers which have been loaded once, this help us to deep understand the mechanism of hydrogen loading for the fiber gratings. Loss and wave width changes are also researched under different radiation dose.

  7. Radiation therapy for resistant sternal hydatid disease

    Energy Technology Data Exchange (ETDEWEB)

    Ulger, S.; Barut, H.; Tunc, M.; Aydinkarahaliloglu, E. [Ataturk Chest Disease and Thorasic Surgery Training and Research Hospital, Ankara (Turkey). Dept. of Radiation Oncology; Aydin, E.; Karaoglanoglu, N. [Ataturk Chest Disease and Thorasic Surgery Training and Research Hospital, Ankara (Turkey). Dept. of Thorasic Surgery; Gokcek, A. [Ataturk Chest Disease and Thorasic Surgery Training and Research Hospital, Ankara (Turkey). Dept. of Radiology

    2013-06-15

    Hydatid disease is a zoonotic infectious disease for which there are known treatment procedures and effective antibiotics; however, there are resistant cases that do not respond to medication or surgery. We report a case diagnosed as hydatid disease of the chest wall and treated with radiation therapy (RT) after medical and surgical therapy had failed. In conclusion, RT represents an alternative treatment modality in resistant cases. (orig.)

  8. Mechanisms of antidepressant resistance

    Directory of Open Access Journals (Sweden)

    Wissam eEl Hage

    2013-11-01

    Full Text Available Depression is one of the most frequent and severe mental disorder. Since the discovery of antidepressant properties of the imipramine and then after of other tricyclic compounds, several classes of psychotropic drugs have shown be effective in treating major depressive disorder. However, there is a wide range of variability in response to antidepressants that might lead to non response or partial response or in increased rate of relapse or recurrence. The mechanisms of response to antidepressant therapy are poorly understood, and few biomarkers are available than can predict response to pharmacotherapy. Here, we will first review markers that can be used to predict response to pharmacotherapy, such as markers of drug metabolism or blood-brain barrier function, the activity of specific brain areas or neurotransmitter systems, hormonal dysregulations or plasticity, and related molecular targets. We will describe both clinical and preclinical studies and describe factors that might affect the expression of these markers, including environmental or genetic factors and comorbidities. This information will permit us to suggest practical recommendations and innovative treatment strategies to improve therapeutic outcomes.

  9. Mechanisms of antidepressant resistance

    Science.gov (United States)

    El-Hage, Wissam; Leman, Samuel; Camus, Vincent; Belzung, Catherine

    2013-01-01

    Depression is one of the most frequent and severe mental disorder. Since the discovery of antidepressant (AD) properties of the imipramine and then after of other tricyclic compounds, several classes of psychotropic drugs have shown be effective in treating major depressive disorder (MDD). However, there is a wide range of variability in response to ADs that might lead to non response or partial response or in increased rate of relapse or recurrence. The mechanisms of response to AD therapy are poorly understood, and few biomarkers are available than can predict response to pharmacotherapy. Here, we will first review markers that can be used to predict response to pharmacotherapy, such as markers of drug metabolism or blood-brain barrier (BBB) function, the activity of specific brain areas or neurotransmitter systems, hormonal dysregulations or plasticity, and related molecular targets. We will describe both clinical and preclinical studies and describe factors that might affect the expression of these markers, including environmental or genetic factors and comorbidities. This information will permit us to suggest practical recommendations and innovative treatment strategies to improve therapeutic outcomes. PMID:24319431

  10. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Samir Bhattacharya; Debleena Dey; Sib Sankar Roy

    2007-03-01

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, leading to a reduced amount of IR protein in insulin target cells. PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of this important area, emphasizing the current status.

  11. CERN selects Fujikura's radiation resistant fiber

    CERN Multimedia

    2007-01-01

    "Fujikura recently announced that its radiation resistant single mode optical fiber has been selected by CERN, the European Laboratory for Particle Physics, to provide communication links within the world's largest particle accelerator - the Large Hadron Collider (LHC) - near Geneva, Switzerland." (1/2 page)

  12. CERN selects Fujikura's radiation resistant fibre

    CERN Multimedia

    2007-01-01

    "Fujikura today announced that its radiation resistant single mode optical fibre has been selected by CERN, the European Laboratory for Particle Physics, to provide communication links within the world's largest particle accelerator - the Large hadron Collider (LHC) - near Genevan, Switzerland. (1/2 page)

  13. Glioblastoma Multiforme Therapy and Mechanisms of Resistance

    Directory of Open Access Journals (Sweden)

    Yulian P. Ramirez

    2013-11-01

    Full Text Available Glioblastoma multiforme (GBM is a grade IV brain tumor characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy. The current standard of care, comprised of surgical resection followed by radiation and the chemotherapeutic agent temozolomide, only provides patients with a 12–14 month survival period post-diagnosis. Long-term survival for GBM patients remains uncommon as cells with intrinsic or acquired resistance to treatment repopulate the tumor. In this review we will describe the mechanisms of resistance, and how they may be overcome to improve the survival of GBM patients by implementing novel chemotherapy drugs, new drug combinations and new approaches relating to DNA damage, angiogenesis and autophagy.

  14. Pathophysiological mechanisms of insulin resistance

    NARCIS (Netherlands)

    Brands, M.

    2013-01-01

    In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the pathophy

  15. Pathophysiological mechanisms of insulin resistance

    NARCIS (Netherlands)

    Brands, M.

    2013-01-01

    In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the pathophy

  16. Pathophysiological mechanisms of insulin resistance

    NARCIS (Netherlands)

    Brands, M.

    2013-01-01

    In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the

  17. Antimicrobial Resistance Mechanisms among Campylobacter

    Science.gov (United States)

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed. PMID:23865047

  18. Antimicrobial resistance mechanisms among Campylobacter.

    Science.gov (United States)

    Wieczorek, Kinga; Osek, Jacek

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed.

  19. Development of application technology of radiation-resistant microorganism

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Ho; Lim, Sang Yong; Joe, Min Ho; Jung, Jin Woo; Jung, Sun Wook; Song, Du Sup; Choi, Young Ji [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-02-15

    The scope of the project is divided into of three parts; (i) to define the survival strategy of radiation-resistant microbes, especially Deinococcus (ii) acquisition of gene resources encoding the novel protein and related with the production of functional materials (iii) development of control technology against radiation-resistant microbes. To this aim, first, the whole transcriptional response of the D. radiodurans strain haboring pprI mutation, which plays an important role in radiation resistance, was analyzed by cDNA microarray. The anti-oxidant activity of the major carotenoid of D. radiodurans, deinoxanthin, was analyzed and the strain was constructed, in which the gene necessary for bio- synthesis of deinoxanthin is deleted. The response to cadmium of D. radiodurans was also investigated through cDNA microarray analysis. Radiogenic therapy, one of the cancer treatments, is designed to use radiation-inducible gene for the treatment. To develop the gene-transfer vehicle for radiogenic therapy, we have investigated the virulence mechanism of Salmonella, which is tumor-targeting bacteria and studied the synergistic effect of some anti-cancer agents on radiation treatment for cancer. Finally, we confirmed that irradiation could decompose a fungus toxin, patulin, into various harmless by-products.

  20. Modeling of secondary radiation damage in LIGA PMMA resist exposure

    Science.gov (United States)

    Ting, Aili

    2003-01-01

    Secondary radiation during LIGA PMMA resist exposure adversely affects feature definition, sidewall taper and overall sidewall offset. Additionally, it can degrade the resist adjacent to the substrate, leading to the loss of free-standing features through undercutting during resist development or through mechanical failure of the degraded material. The source of this radiation includes photoelectrons, Auger electrons, fluorescence photons, etc. Sandia"s Integrated Tiger Series (ITS), a coupled electron/photon Monte Carlo transport code, was used to compute dose profiles within 1 to 2 microns of the absorber edge and near the interface of the resist with a metallized substrate. The difficulty of sub-micron resolution requirement was overcome by solving a few local problems having carefully designed micron-scale geometries. The results indicate a 2-μm dose transition region near the absorber edge resulting from PMMA"s photoelectrons. This region leads to sidewall offset and to tapered sidewalls following resist development. The results also show a dose boundary layer of around 1 μm near the substrate interface due to electrons emitted from the substrate metallization layer. The maximum dose at the resist bottom under the absorber can be very high and can lead to feature loss during development. This model was also used to investigate those resist doses resulting from multi-layer substrate.

  1. High Radiation Resistance IMM Solar Cell

    Science.gov (United States)

    Pan, Noren

    2015-01-01

    Due to high launch costs, weight reduction is a key driver for the development of new solar cell technologies suitable for space applications. This project is developing a unique triple-junction inverted metamorphic multijunction (IMM) technology that enables the manufacture of very lightweight, low-cost InGaAsP-based multijunction solar cells. This IMM technology consists of indium (In) and phosphorous (P) solar cell active materials, which are designed to improve the radiation-resistant properties of the triple-junction solar cell while maintaining high efficiency. The intrinsic radiation hardness of InP materials makes them of great interest for building solar cells suitable for deployment in harsh radiation environments, such as medium Earth orbit and missions to the outer planets. NASA Glenn's recently developed epitaxial lift-off (ELO) process also will be applied to this new structure, which will enable the fabrication of the IMM structure without the substrate.

  2. Mechanisms of buffer therapy resistance.

    Science.gov (United States)

    Bailey, Kate M; Wojtkowiak, Jonathan W; Cornnell, Heather H; Ribeiro, Maria C; Balagurunathan, Yoganand; Hashim, Arig Ibrahim; Gillies, Robert J

    2014-04-01

    Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, we confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  3. Negative differential resistance devices for generation of terahertz radiation

    OpenAIRE

    H. Eisele

    2015-01-01

    This paper discusses the principles of operation, state of the art, and future potential of active two-terminal devices for generation of low-noise, continuous-wave terahertz radiation. These devices use transit-time, transferred-electron, and quantum-mechanical effects (or a combination of them) to create a negative differential resistance (NDR) at the frequency of interest. Many different types of NDR devices have been proposed since the earliest days of semiconductor devices and studied in...

  4. EGFR相关的DNA修复及放射抗拒机制研究现状%Relativity of EGFR signal as a regulatory mechanism to DNA repair and radiation resistance

    Institute of Scientific and Technical Information of China (English)

    白静; 白晓平; 赵巧艳

    2012-01-01

    目的:总结国外关于表皮生长因子受体(EGFR)通过各种信号通路调节DNA修复导致辐射抗拒相关机制的研究进展.方法:应用PubMed数据库系统,以“表皮生长因子受体、信号通路、DNA损伤修复、放射抗拒”为关键词检索2005-01-2011-12的相关文献,共检索到英文文献198篇.纳入标准:1)EGFR的表达;2)辐射抗拒和DNA损伤修复机制;3)EGFR和辐射诱导的DNA损伤修复;4)EGFR信号通路调控DNA损伤修复导致放射抗拒的可能机制.根据纳入标准,纳入分析22篇文献.结果:EGFR过表达与放化疗抗拒相关.它可以通过联接DNA蛋白激酶催化亚单位(DNA-PKcs)来调节放疗诱导的DNA损伤的修复.EGFR及其对DNA修复能力之间的分子连接可能通过该受体的一个或多个下游信号通路介导.结论:EGFR作为调节DNA损伤修复机制的信号通路与放射抗拒之间存在相关性,靶向于其中激活的信号通路可以为改善放射抗拒提供新的治疗思路.%OBJECTIVE:To sum up the articles related to improvement that epidermal growth factor receptor (EGFR) modulate DNA repair after radiation-induced damage through many signal pathways. METHODS: Epidermal growth factor receptor,signal pathway ,DNA-damage repair and radiation resistance were searched as key words by Pubmed database system from 2005-01 to 2011-12, Altogether 198 English literatures were obtained. Enrolled criteria: 1, EGFR expression; 2. mechanism of DNA repair and radiation resistances 3, EGFR and radiation resistances 4, EGFR signal as a regulatory mechanism to DNA repair and radiation resistance. By extraction according to enrolled criteria, among roughing hundreds of relative articles,46 papers were selected, and 22 papers were finally analyzed. RESULTS: EGFR Overexpres-sion is associated with resistance to chemotherapy and radiotherapy. It modulates DNA repair after radiation-induced damage through association with the catalytic subunit of DNA protein

  5. Extreme Ionizing-Radiation-Resistant Bacterium

    Science.gov (United States)

    Vaishampayan, Parag A.; Venkateswaran, Kasthuri J.; Schwendner, Petra

    2013-01-01

    There is a growing concern that desiccation and extreme radiation-resistant, non-spore-forming microorganisms associated with spacecraft surfaces can withstand space environmental conditions and subsequent proliferation on another solar body. Such forward contamination would jeopardize future life detection or sample return technologies. The prime focus of NASA s planetary protection efforts is the development of strategies for inactivating resistance-bearing micro-organisms. Eradi cation techniques can be designed to target resistance-conferring microbial populations by first identifying and understanding their physiologic and biochemical capabilities that confers its elevated tolerance (as is being studied in Deinococcus phoenicis, as a result of this description). Furthermore, hospitals, food, and government agencies frequently use biological indicators to ensure the efficacy of a wide range of radiation-based sterilization processes. Due to their resistance to a variety of perturbations, the nonspore forming D. phoenicis may be a more appropriate biological indicator than those currently in use. The high flux of cosmic rays during space travel and onto the unshielded surface of Mars poses a significant hazard to the survival of microbial life. Thus, radiation-resistant microorganisms are of particular concern that can survive extreme radiation, desiccation, and low temperatures experienced during space travel. Spore-forming bacteria, a common inhabitant of spacecraft assembly facilities, are known to tolerate these extreme conditions. Since the Viking era, spores have been utilized to assess the degree and level of microbiological contamination on spacecraft and their associated spacecraft assembly facilities. Members of the non-sporeforming bacterial community such as Deinococcus radiodurans can survive acute exposures to ionizing radiation (5 kGy), ultraviolet light (1 kJ/m2), and desiccation (years). These resistive phenotypes of Deinococcus enhance the

  6. A novel radiation-induced p53 mutation is not implicated in radiation resistance via a dominant-negative effect.

    Directory of Open Access Journals (Sweden)

    Yunguang Sun

    Full Text Available Understanding the mutations that confer radiation resistance is crucial to developing mechanisms to subvert this resistance. Here we describe the creation of a radiation resistant cell line and characterization of a novel p53 mutation. Treatment with 20 Gy radiation was used to induce mutations in the H460 lung cancer cell line; radiation resistance was confirmed by clonogenic assay. Limited sequencing was performed on the resistant cells created and compared to the parent cell line, leading to the identification of a novel mutation (del at the end of the DNA binding domain of p53. Levels of p53, phospho-p53, p21, total caspase 3 and cleaved caspase 3 in radiation resistant cells and the radiation susceptible (parent line were compared, all of which were found to be similar. These patterns held true after analysis of p53 overexpression in H460 cells; however, H1299 cells transfected with mutant p53 did not express p21, whereas those given WT p53 produced a significant amount, as expected. A luciferase assay demonstrated the inability of mutant p53 to bind its consensus elements. An MTS assay using H460 and H1299 cells transfected with WT or mutant p53 showed that the novel mutation did not improve cell survival. In summary, functional characterization of a radiation-induced p53 mutation in the H460 lung cancer cell line does not implicate it in the development of radiation resistance.

  7. Thermal and radiation resistance of stabilized LDPE

    Energy Technology Data Exchange (ETDEWEB)

    Zaharescu, T., E-mail: traian_zaharescu@yahoo.co [INCDIE ICPE CA, Department of Radiation Processing, 313 Splaiul Unirii, P.O. Box 149, Bucharest 030138 (Romania); Jipa, S. [INCDIE ICPE CA, Department of Radiation Processing, 313 Splaiul Unirii, P.O. Box 149, Bucharest 030138 (Romania); ' Valahia' University of Targoviste, Faculty of Sciences, Targoviste 130024 (Romania); Henderson, D. [Trinity College, Hartford, CT 06106 (United States); Kappel, W. [INCDIE ICPE CA, Department of Radiation Processing, 313 Splaiul Unirii, P.O. Box 149, Bucharest 030138 (Romania); Maris, D.A.; Maris, M. [' Ovidius' University, 7 Ilarie Voronca St, P.O. Box 8700, Constanta (Romania)

    2010-03-15

    The effect of capsaicin on the radiation stability of low density polyethylene was accomplished by applying the chemiluminescence procedure. The neat and modified polymer with 0.25% and 0.50% (w/w) capsaicin were exposed to gamma-irradiation in air receiving 10, 20 and 30 kGy. The synergistic effect due to the presence of metallic selenium was demonstrated. The significant improvement in oxidation induction time was obtained demonstrating the efficient antioxidant activity of capsaicin in LDPE. The simultaneous protection action of metallic selenium in LDPE/capsaicin systems brought about a supplementary enhancement in the oxidation resistance of irradiated samples.

  8. [Mechanisms of electromagnetic radiation damaging male reproduction].

    Science.gov (United States)

    Xue, Lei; Chen, Hao-Yu; Wang, Shui-Ming

    2012-08-01

    More and more evidence from over 50 years of researches on the effects of electromagnetic radiation on male reproduction show that a certain dose of electromagnetic radiation obviously damages male reproduction, particularly the structure and function of spermatogenic cells. The mechanisms of the injury may be associated with energy dysmetabolism, lipid peroxidation, abnormal expressions of apoptosis-related genes and proteins, and DNA damage.

  9. Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy.

    Science.gov (United States)

    Kim, Byeong Mo; Hong, Yunkyung; Lee, Seunghoon; Liu, Pengda; Lim, Ji Hong; Lee, Yong Heon; Lee, Tae Ho; Chang, Kyu Tae; Hong, Yonggeun

    2015-11-10

    Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR.

  10. Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Byeong Mo Kim

    2015-11-01

    Full Text Available Ionizing radiation (IR, such as X-rays and gamma (γ-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR.

  11. Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy

    Science.gov (United States)

    Kim, Byeong Mo; Hong, Yunkyung; Lee, Seunghoon; Liu, Pengda; Lim, Ji Hong; Lee, Yong Heon; Lee, Tae Ho; Chang, Kyu Tae; Hong, Yonggeun

    2015-01-01

    Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR. PMID:26569225

  12. Targeting Notch to overcome radiation resistance.

    Science.gov (United States)

    Yahyanejad, Sanaz; Theys, Jan; Vooijs, Marc

    2016-02-16

    Radiotherapy represents an important therapeutic strategy in the treatment of cancer cells. However, it often fails to eliminate all tumor cells because of the intrinsic or acquired treatment resistance, which is the most common cause of tumor recurrence. Emerging evidences suggest that the Notch signaling pathway is an important pathway mediating radiation resistance in tumor cells. Successful targeting of Notch signaling requires a thorough understanding of Notch regulation and the context-dependent interactions between Notch and other therapeutically relevant pathways. Understanding these interactions will increase our ability to design rational combination regimens that are more likely to be safe and effective. Here we summarize the role of Notch in mediating resistance to radiotherapy, the different strategies to block Notch in cancer cells and how treatment scheduling can improve tumor response. Finally, we discuss a need for reliable Notch related biomarkers in specific tumors to measure pathway activity and to allow identification of a subset of patients who are likely to benefit from Notch targeted therapies.

  13. Radiation resistance of microorganisms on unsterilized infusion sets

    DEFF Research Database (Denmark)

    Christensen, E. Ahrensburg; Kristensen, H.; Hoborn, J.;

    1991-01-01

    Three different methods were used for detecting and isolating microorganisms with high radiation resistance from the microbial contamination on infusion sets prior to sterilization. By all three methods, microorganisms with a radiation resistance high enough to be a critical factor in a steriliza......Three different methods were used for detecting and isolating microorganisms with high radiation resistance from the microbial contamination on infusion sets prior to sterilization. By all three methods, microorganisms with a radiation resistance high enough to be a critical factor...

  14. Archway for Radiation and Micrometeorite Occurrence Resistance

    Science.gov (United States)

    Giersch, Louis R.

    2012-01-01

    The environmental conditions of the Moon require mitigation if a long-term human presence is to be achieved for extended periods of time. Radiation, micrometeoroid impacts, high-velocity debris, and thermal cycling represent threats to crew, equipment, and facilities. For decades, local regolith has been suggested as a candidate material to use in the construction of protective barriers. A thickness of roughly 3m is sufficient protection from both direct and secondary radiation from cosmic rays and solar protons; this thickness is sufficient to reduce radiation exposure even during solar flares. NASA has previously identified a need for innovations that will support lunar habitats using lightweight structures because the reduction of structural mass translates directly into additional up and down mass capability that would facilitate additional logistics capacity and increased science return for all mission phases. The development of non-pressurized primary structures that have synergy with the development of pressurized structures is also of interest. The use of indigenous or in situ materials is also a well-known and active area of research that could drastically improve the practicality of human exploration beyond low-Earth orbit. The Archway for Radiation and Micrometeorite Occurrence Resistance (ARMOR) concept is a new, multifunctional structure that acts as radiation shielding and micrometeorite impact shielding for long-duration lunar surface protection of humans and equipment. ARMOR uses a combination of native regolith and a deployed membrane jacket to yield a multifunctional structure. ARMOR is a robust and modular system that can be autonomously assembled on-site prior to the first human surface arrival. The system provides protection by holding a sufficiently thick (3 m) archshaped shell of local regolith around a central cavity. The regolith is held in shape by an arch-shaped jacket made of strong but deployable material. No regolith processing is

  15. Evaluation of the radiation resistance of electrical insulation materials

    Science.gov (United States)

    Perrin, Sh.; Schönbacher, H.; Tavlet, M.; Widler, R.

    2002-12-01

    The qualification of insulating materials for electrical cables is often accomplished according to the IEC 60544 standard of the International Electrotechnical Commission. The mechanical properties of the polymeric insulators are tested prior and after irradiation at relatively high dose rates. To assess the ageing of selected materials under realistic service conditions, usually at lower dose rate, an IEC Working Group has proposed extrapolation methods (IEC 61244-2), one of which is applied here for a cable sheathing material from Huber+Suhner. The method is found to be suitable to compare radiation resistance data of different materials irradiated under different conditions.

  16. Radiation-Resistant Micrococcus luteus SC1204 and Its Proteomics Change Upon Gamma Irradiation.

    Science.gov (United States)

    Deng, Wuyuan; Yang, Yang; Gao, Peng; Chen, Hao; Wen, Wenting; Sun, Qun

    2016-06-01

    To explore the radiation-resistance mechanisms in bacteria, a radiation-resistant strain SC1204 was isolated from the surrounding area of a (60)Co-γ radiation facility. SC1204 could survive up to 8 kGy dose of gamma irradiation and was identified as Micrococcus luteus by phylogenetic analysis of 16S rRNA gene sequences. Its proteomic changes under 2-kGy irradiation were examined by two-dimensional electrophoresis followed by MALDI-TOF-TOF/MS analysis. The results showed that at least 24 proteins displayed significant changes (p changing significantly (p resistance in M. luteus.

  17. 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.

  18. 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.

  19. Experiments on the resistance of airplane wheels and radiators

    Science.gov (United States)

    1924-01-01

    Experiments were made on the resistance of four airplane wheels of different sizes and coverings and two Lamblin radiators. The results show the important influence of the wheel coverings. The closing of a shutter, which was fitted to one of the radiators, considerably lessened the resistance.

  20. Molecular mechanism of cisplatin resistance

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Cisplatin is widely used in the treatment of many tumors,particularly in ovarian cancer.GST-π,metallothionein(MT), multidrug resistance associated proteins(MRPs), nucleotide excision repair(NER), mismatch repair(MMR) and oncogenes contribute to drug resistance of cisplatin.

  1. Radiation and Heat Resistance of Moraxella-Acinetobacter in Meats

    Science.gov (United States)

    1978-01-23

    growth 7 Vacuum packaging and impact on growth of resistant isolates .... 7 Effect of fat content of meat on radiation and heat resistance of...approximately 10 cells per ml. Storage for culture main- tenance after growth was at 3-5*C. Vacuum packaging and impact on growth of resistant isolates...sensitive to reduced oxygen occur- ring with vacuum packaging of foods (Maxcy et al., 1976). Furthermore, most of the radiation-resiscant M-A were

  2. Antioxidant mechanisms in radiation injury and radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, J.F.; Kumar, K.S.

    1988-01-01

    Oxygen is a very important factor in determining radiosensitivity because it enhances the damage to cellular components caused by ionizing radiation, although mechanisms involved in UV irradiation damage may overlap ionizing radiation effects. This paper emphasizes chemical protection against damage by ionizing radiation and predominantly against the effects of photons (and gamma radiation). It is possible that free radicals and their products induced by ionizing radiation can interact with reactive oxygen species formed during normal processes, such as superoxide and hydrogen peroxide produced by phagocytic cells or during enzymatic processes (xanthine oxidase activity; enzymes involved in eicosanoid metabolism). Metals such as iron can promote free radical damage, whereas some bound metals have radioprotectant potential, e.g., metallothionein and ceruloplasmin. There is increasing evidence that maintenance of the proper oxidation-reduction state of cells by the interconversion of the peptide sulfhydryl glutathione (GSH), and its disulfide form (GSSG) is a factor in the modulation of cellular radiosensitivity. Other protein and nonprotein sulfhydryls may also play a role both as targets of radiation damage and as protectors. Other physiological antioxidants (vitamin E) and antioxidant enzymes are interrelated in their function of controlling oxidative processes. This review concentrates on the role of oxygen, glutathione, and antioxidant enzymes in radiosensitivity and how exogenous chemicals interact with these endogenous factors.

  3. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens

    Directory of Open Access Journals (Sweden)

    Sirijan Santajit

    2016-01-01

    Full Text Available The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens.

  4. First resistance mechanisms characterization in glyphosate-resistant Leptochloa virgata.

    Directory of Open Access Journals (Sweden)

    Ricardo Alcántara-de la Cruz

    2016-11-01

    Full Text Available Leptochloa virgata (L. P. Beauv. is an annual weed common in citrus groves in the states of Puebla and Veracruz, Mexico limiting their production. Since 2010, several L. virgata populations were identified as being resistant to glyphosate, but studies of their resistance mechanisms developed by this species have been conducted. In this work, three glyphosate-resistant populations (R8, R14 and R15 collected in citrus orchards from Mexico, were used to study their resistance mechanisms comparing them to one susceptible population (S. Dose-response and shikimic acid accumulation assays confirmed the glyphosate resistance of the three resistant populations. Higher doses of up to 720 g ae ha-1 (field dose were needed to control by 50% plants of resistant populations. The S population absorbed between 7 and 13% more 14C-glyphosate than resistant ones, and translocated up to 32.2% of 14C-glyphosate to the roots at 96 h after treatment (HAT. The R8, R14 and R15 populations translocated only 24.5, 26.5 and 21.9%, respectively. The enzyme activity of 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS was not different in the S, R8 and R14 populations. The R15 Population exhibited 165.9 times greater EPSPS activity. Additionally, this population showed a higher EPSPS basal activity and a substitution in the codon 106 from Proline to Serine in the EPSPS protein sequence. EPSPS gene expression in the R15 population was similar to that of S population. In conclusion, the three resistant L. virgata populations show reduced absorption and translocation of 14C-glyphosate. Moreover, a mutation and an enhanced EPSPS basal activity at target-site level confers higher resistance to glyphosate. These results describe for the first time the glyphosate resistance mechanisms developed by resistant L. virgata populations of citrus orchards from Mexico.

  5. First Resistance Mechanisms Characterization in Glyphosate-Resistant Leptochloa virgata

    Science.gov (United States)

    Alcántara-de la Cruz, Ricardo; Rojano-Delgado, Antonia M.; Giménez, María J.; Cruz-Hipolito, Hugo E.; Domínguez-Valenzuela, José A.; Barro, Francisco; De Prado, Rafael

    2016-01-01

    Leptochloa virgata (L.) P. Beauv. is an annual weed common in citrus groves in the states of Puebla and Veracruz, Mexico limiting their production. Since 2010, several L. virgata populations were identified as being resistant to glyphosate, but studies of their resistance mechanisms developed by this species have been conducted. In this work, three glyphosate-resistant populations (R8, R14, and R15) collected in citrus orchards from Mexico, were used to study their resistance mechanisms comparing them to one susceptible population (S). Dose-response and shikimic acid accumulation assays confirmed the glyphosate resistance of the three resistant populations. Higher doses of up to 720 g ae ha-1 (field dose) were needed to control by 50% plants of resistant populations. The S population absorbed between 7 and 13% more 14C-glyphosate than resistant ones, and translocated up to 32.2% of 14C-glyphosate to the roots at 96 h after treatment (HAT). The R8, R14, and R15 populations translocated only 24.5, 26.5, and 21.9%, respectively. The enzyme activity of 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS) was not different in the S, R8 and R14 populations. The R15 Population exhibited 165.9 times greater EPSPS activity. Additionally, this population showed a higher EPSPS basal activity and a substitution in the codon 106 from Proline to Serine in the EPSPS protein sequence. EPSPS gene expression in the R15 population was similar to that of S population. In conclusion, the three resistant L. virgata populations show reduced absorption and translocation of 14C-glyphosate. Moreover, a mutation and an enhanced EPSPS basal activity at target-site level confers higher resistance to glyphosate. These results describe for the first time the glyphosate resistance mechanisms developed by resistant L. virgata populations of citrus orchards from Mexico. PMID:27917189

  6. Tumourigenicity and radiation resistance of mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Horsman, Michael Robert; Kassem, Moustapha

    2012-01-01

    Background. Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart. Material and methods....... Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under...... the intercellular matrix. These results also indicate that cancer stem cells are more radiation resistant than stem cells of the same origin....

  7. Antifungal Agents: Mode of Action, Mechanisms of Resistance, and Correlation of These Mechanisms with Bacterial Resistance

    OpenAIRE

    Ghannoum, Mahmoud A.; Rice, Louis B

    1999-01-01

    The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antimicrobial resistance from different angles. Areas addressed include mechanisms underlying this resistance, improved methods to detect resistance when it occurs, alternate options for the treatment of infections caused by resistant organisms, and strategies to ...

  8. The radiation resistance of the bioburden from medical devices

    Energy Technology Data Exchange (ETDEWEB)

    Takehisa, M.; Shintani, H.; Sekiguchi, M.; Koshikawa, T.; Oonishi, T.; Tsuge, M.; Sou, K.; Yamase, Y.; Kinoshita, S.; Tsukamoto, H.; Endo, T.; Yashima, K.; Nagai, M.; Ishigaki, K.; Sato, Y.; Whitby, J. L

    1998-06-01

    An extensive study of the radiation resistance of microbial species constituting the bioburden of a number of different medical devices obtained from Japanese medical device manufacturers has been carried out. A standard protocol for determining radiation resistance was used and validated at the fourteen centres involved in the study. Individual microbial isolates from the bioburden obtained from seven different devices manufactured in these centres were studied. A total of 3742 unselected isolates were obtained, of which 197 failed to survive long enough for subsequent radiation resistance studies. The remainder were subjected to an initial screen test to identify those organisms that were sensitive to the lethal effects of radiation with a D{sub 10} of < 1.5kGy. The 465 isolates that survived the screen doses were then tested for survival in an incremental series of radiation doses using methods similar to those of Whitby (1979) and Yan and Tallentire (1995). The isolates from 'dry' devices were more resistant than those obtained from the one water filled ('wet') device studied. The overall distribution of radiation resistance among the isolates was considered to be similar to that forming the 'Standard Distribution of Resistance' (SDR) included in the ISO International Standard 11137 'Sterilization of Health Care Products - Requirements for validation and routine control - Radiation sterilization'.

  9. Radiation resistivity of polyacenaphthylene-grafted polyethylene

    Science.gov (United States)

    Hayakawa, Kiyoshi; Kawase, Kaoru; Yamakita, Hiromi

    Thin poly (ethylene-g-acenaphthylene) films prepared by the vapor-phase grafting method were subjected to the γ-irradiation in air, and various changes in tensile and structural properties of the film were investigated by comparing with those of the untreated or crosslinked polyethylene film. Polyethylene got to lose its inherent necking property by oxidative degradation and to be brittle-fractured by the irradiation dose less than 100 Mrad in air. The polyacenaphthylene-grafted polyethylenes (extent of grafting, ˜ 54 by {100( P-P°) }/{P°}), however, kept their ductility up to 200 Mrad or more, and the rate of increase in elastic modulus as well as yield strength with the increasing irradiation dose was considerably lower than that of untreated or crosslinked polyethylene. The effect of the grafting extent, and that of the irradiation dose-rate on the fracture energy were also examined. The weight increase of polyethylene due to the oxygen consumption and the resulting formation of carbonyl group which proceeded proportionally with the irradiation dose were remarkably suppressed by the grafting, whereas the double bond formation seemed to be unaffected by it. The grafted film held the original content of gel fraction unchanged during the irradiation in air, but the average molecular weight of the sol fraction decreased gradually. Meanwhile, the gel fraction of the crosslinked polyethylene was degenerated by a small dose of irradiation. The analysis of gaseous products revealed the formation of water, methanol, acetaldehyde and so forth from the irradiated grafted film. The grafting procedure and the subsequent irradiation of the grafted film did not affect the degree of crystallinity of the backbone polyethylene. The role played by the grafted polyacenaphthylene for endowing the radiation resistivity to polyethylene and its inherent limitation in effect were discussed from the structural point of view of the grafted film.

  10. Radiation resistance and injury of Yersinia enterocolitica

    Energy Technology Data Exchange (ETDEWEB)

    El-Zawahry, Y.A.; Rowley, D.B.

    1979-01-01

    The D values of Yersinia enterocolitica strains IP134, IP107, and WA, irradiated at 25/sup 0/C in Trypticase soy broth, ranged from 9.7 to 11.8 krad. When irradiated in ground beef at 25 and -30/sup 0/C, the D value of strain IP107 and 19.5 and 38.8 krad, respectively. Cells suspended in Trypticase soy broth were more sensitive to storage at -20/sup 0/C than those mixed in ground beef. The percentages of inactivation and of injury (inability to form colonies in the presence of 3.0% NaCl) of cells stored in ground beef for 10 days at -20/sup 0/C were 70 and 23%, respectively. Prior irradiation did not alter the cell's sensitivity to storage at -20/sup 0/C, nor did storage at -20/sup 0/C alter the cell's resistance to irradiation at 25/sup 0/C. Added NaCl concentrations of up to 4.0% in Trypticase soy agar (TSA) (which contains 0.5% NaCl) had little effect on colony formation at 36/sup 0/C of unirradiated Y. enterocolitica. With added 4.0% NaCl, 79% of the cells formed colonies at 36/sup 0/C; with 5.0% NaCl added, no colonies were formed. Although 2.5% NaCl added to ground beef did not sensitize Y. enterocolitica cells to irradiation, when added to TSA it reduced the number of apparent radiation survivors. Cells uninjured by irradiation formed colonies on TSA when incubated at either 36 or 5/sup 0/C. More survivors of an exposure to 60 krad were capable of recovery and forming colonies on TSA when incubated at 36/sup 0/C for 1 day than at 5/sup 0/C for 14 days. This difference in count was considered a manifestation of injury to certain survivors of irradiation.

  11. Resistance mechanisms to arsenicals and antimonials.

    Science.gov (United States)

    Rosen, B P

    1995-01-01

    Salts and organic derivatives of arsenic and antimony are quite toxic. Living organisms have adapted to this toxicity by the evolution of resistance mechanisms. Both prokaryotic and eukaryotic cells develop resistance when exposed to arsenicals or antimonials. In the case of bacteria resistance is conferred by plasmid-encoded arsenical resistance (ars) operons. The genes and gene products of the ars operon of the clinically-isolated conjugative R-factor R773 have been identified and their mechanism of action elucidated. The operon encodes an ATP-driven pump that extrudes arsenite and antimonite from the cells. The lowering of their intracellular concentration results in resistance. Arsenate resistance results from the action of the plasmid-encoded arsenate reductase that reduces arsenate to arsenite, which is then pumped out of the cell.

  12. Mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis.

    Science.gov (United States)

    Yujiao, Zhang; Xiaojing, Li; Kaixia, Mi

    2016-10-20

    Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is one of the world's deadliest bacterial infectious disease. It is still a global-health threat, particularly because of the drug-resistant forms. Fluoroquinolones, with target of gyrase, are among the drugs used to treat tuberculosis. However, their widespread use has led to bacterial resistance. The molecular mechanisms of fluoroquinolone resistance in mycobacterium tuberculosis have been reported, such as DNA gyrase mutations, drug efflux pumps system, bacterial cell wall thickness and pentapeptide proteins (MfpA) mediated regulation of gyrase. Mutations in gyrase conferring quinolone resistance play important roles and have been extensively studied. Recent studies have shown that the regulation of DNA gyrase affects mycobacterial drug resistance, but the mechanisms, especially by post-translational modification and regulatory proteins, are poorly understood. In this review, we summarize the fluoroquinolone drug development, and the molecular genetics of fluoroquinolone resistance in mycobacteria. Comprehensive understanding of the mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis will open a new view on understanding drug resistance in mycobacteria and lead to novel strategies to develop new accurate diagnosis methods.

  13. Mechanisms of antibiotic resistance in enterococci

    Science.gov (United States)

    Miller, William R; Munita, Jose M; Arias, Cesar A

    2015-01-01

    Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches. PMID:25199988

  14. Mechanisms of antibiotic resistance in enterococci.

    Science.gov (United States)

    Miller, William R; Munita, Jose M; Arias, Cesar A

    2014-10-01

    Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches.

  15. Mechanisms of Candida biofilm drug resistance

    Science.gov (United States)

    Taff, Heather T; Mitchell, Kaitlin F; Edward, Jessica A; Andes, David R

    2013-01-01

    Candida commonly adheres to implanted medical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. As currently available antifungals have minimal activity against biofilms, new drugs to treat these recalcitrant infections are urgently needed. Recent investigations have begun to shed light on the mechanisms behind the profound resistance associated with the biofilm mode of growth. This resistance appears to be multifactorial, involving both mechanisms similar to conventional, planktonic antifungal resistance, such as increased efflux pump activity, as well as mechanisms specific to the biofilm lifestyle. A unique biofilm property is the production of an extracellular matrix. Two components of this material, β-glucan and extracellular DNA, promote biofilm resistance to multiple antifungals. Biofilm formation also engages several stress response pathways that impair the activity of azole drugs. Resistance within a biofilm is often heterogeneous, with the development of a subpopulation of resistant persister cells. In this article we review the molecular mechanisms underlying Candida biofilm antifungal resistance and their relative contributions during various growth phases. PMID:24059922

  16. Mechanisms of insulin resistance in obesity

    Science.gov (United States)

    Ye, Jianping

    2014-01-01

    Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

  17. Mechanisms of insulin resistance in obesity.

    Science.gov (United States)

    Ye, Jianping

    2013-03-01

    Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy.

  18. Mechanisms of Resistance to Photodynamic Therapy

    Science.gov (United States)

    Casas, Adriana; Di Venosa, Gabriela; Hasan, Tayyaba; Batlle, Alcira

    2013-01-01

    Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by illumination with visible light, leading to generation of reactive oxygen species. The mechanisms of resistance to PDT ascribed to the PS may be shared with the general mechanisms of drug resistance, and are related to altered drug uptake and efflux rates or altered intracellular trafficking. As a second step, an increased inactivation of oxygen reactive species is also associated to PDT resistance via antioxidant detoxifying enzymes and activation of heat shock proteins. Induction of stress response genes also occurs after PDT, resulting in modulation of proliferation, cell detachment and inducing survival pathways among other multiple extracellular signalling events. In addition, an increased repair of induced damage to proteins, membranes and occasionally to DNA may happen. PDT-induced tissue hypoxia as a result of vascular damage and photochemical oxygen consumption may also contribute to the appearance of resistant cells. The structure of the PS is believed to be a key point in the development of resistance, being probably related to its particular subcellular localization. Although most of the features have already been described for chemoresistance, in many cases, no cross-resistance between PDT and chemotherapy has been reported. These findings are in line with the enhancement of PDT efficacy by combination with chemotherapy. The study of cross resistance in cells with developed resistance against a particular PS challenged against other PS is also highly complex and comprises different mechanisms. In this review we will classify the different features observed in PDT resistance, leading to a comparison with the mechanisms most commonly found in chemo resistant cells. PMID:21568910

  19. Molecular mechanisms of insulin resistance

    African Journals Online (AJOL)

    insulin action from receptor to the alteration of blood glucose. Hence, in order to ... and regulation of the insulin receptor in our efforts to unravel the cause of this ... defined mechanisms of signal transduction. Structure ..... found in muscle and fat is the most important and mediates ..... glycogen metabolism in skeletal muscle.

  20. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria

    Directory of Open Access Journals (Sweden)

    Abiola Olumuyiwa Olaitan

    2014-11-01

    Full Text Available Polymyxins are polycationic antimicrobial peptides that are currently the last-resort antibiotics for the treatment of multidrug-resistant, Gram-negative bacterial infections. The reintroduction of polymyxins for antimicrobial therapy has been followed by an increase in reports of resistance among Gram-negative bacteria. Some bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, develop resistance to polymyxins in a process referred to as acquired resistance, whereas other bacteria, such as Proteus spp., Serratia spp. and Burkholderia spp., are naturally resistant to these drugs. Reports of polymyxin resistance in clinical isolates have recently increased, including acquired and intrinsically resistant pathogens. This increase is considered a serious issue, prompting concern due to the low number of currently available effective antibiotics. This review summarizes current knowledge concerning the different strategies bacteria employ to resist the activities of polymyxins.Gram-negative bacteria employ several strategies to protect themselves from polymyxin antibiotics (polymyxin B and colistin, including a variety of lipopolysaccharide (LPS modifications, such as modifications of lipid A with phosphoethanolamine and 4-amino-4-deoxy-L-arabinose, in addition to the use of efflux pumps, the formation of capsules and overexpression of the outer membrane protein OprH, which are all effectively regulated at the molecular level. The increased understanding of these mechanisms is extremely vital and timely to facilitate studies of antimicrobial peptides and find new potential drugs targeting clinically relevant Gram-negative bacteria.

  1. Radiation Effects of Commercial Resistive Random Access Memories

    Science.gov (United States)

    Chen, Dakai; LaBel, Kenneth A.; Berg, Melanie; Wilcox, Edward; Kim, Hak; Phan, Anthony; Figueiredo, Marco; Buchner, Stephen; Khachatrian, Ani; Roche, Nicolas

    2014-01-01

    We present results for the single-event effect response of commercial production-level resistive random access memories. We found that the resistive memory arrays are immune to heavy ion-induced upsets. However, the devices were susceptible to single-event functional interrupts, due to upsets from the control circuits. The intrinsic radiation tolerant nature of resistive memory makes the technology an attractive consideration for future space applications.

  2. Molecular mechanisms for tumour resistance to chemotherapy.

    Science.gov (United States)

    Pan, Shu-Ting; Li, Zhi-Ling; He, Zhi-Xu; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2016-08-01

    Chemotherapy is one of the prevailing methods used to treat malignant tumours, but the outcome and prognosis of tumour patients are not optimistic. Cancer cells gradually generate resistance to almost all chemotherapeutic drugs via a variety of distinct mechanisms and pathways. Chemotherapeutic resistance, either intrinsic or acquired, is caused and sustained by reduced drug accumulation and increased drug export, alterations in drug targets and signalling transduction molecules, increased repair of drug-induced DNA damage, and evasion of apoptosis. In order to better understand the mechanisms of chemoresistance, this review highlights our current knowledge of the role of altered drug metabolism and transport and deregulation of apoptosis and autophagy in the development of tumour chemoresistance. Reduced intracellular activation of prodrugs (e.g. thiotepa and tegafur) or enhanced drug inactivation by Phase I and II enzymes contributes to the development of chemoresistance. Both primary and acquired resistance can be caused by alterations in the transport of anticancer drugs which is mediated by a variety of drug transporters such as P-glycoprotein (P-gp), multidrug resistance associated proteins, and breast cancer resistance protein. Presently there is a line of evidence indicating that deregulation of programmed cell death including apoptosis and autophagy is also an important mechanism for tumour resistance to anticancer drugs. Reversal of chemoresistance is likely via pharmacological and biological approaches. Further studies are warranted to grasp the full picture of how each type of cancer cells develop resistance to anticancer drugs and to identify novel strategies to overcome it.

  3. Mechanisms of resistance to paraquat in plants.

    Science.gov (United States)

    Hawkes, Timothy R

    2014-09-01

    The aim of this brief review is to draw information from studies of the mechanism of evolved resistance in weeds, together with information from laboratory studies of paraquat tolerance in model plants. Plants having mutations that limit paraquat uptake into cytoplasm, that confer various stress tolerances or that have transgenes that co-express two or more of the chloroplast Halliwell-Asada cycle enzymes can all exhibit enhanced tolerance to paraquat. However, none of these mechanisms correspond to the high-level resistances that have evolved naturally in weeds. Most, but not all, of the evidence from studies of paraquat-resistant biotypes of weeds can reasonably be reconciled with the proposal of a single major gene mechanism that sequesters paraquat away from chloroplasts and into the vacuole. However, the molecular details of this putative mechanism remain ill-defined.

  4. Radiation resistivity of PbF sub 2 crystals

    CERN Document Server

    Kozma, P; Kozma, P

    2002-01-01

    Radiation hardness of a 4x4x24 cm sup 3 PbF sub 2 crystal has been studied for doses up to 10 sup 5 Gy. Radiation resistivity was examined by the measurement of optical transmission through the lead fluoride crystal before and after gamma-ray irradiations. The results have been compared with radiation hardness measurements for a 4x4x40 cm sup 3 Pb-glasses SF sub 5 and SF sub 6 and a 3x3x6 cm sup 3 CeF sub 3 scintillation crystal, as well. Complete recovery of radiation damage was observed a few day after the irradiations.

  5. Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance.

    Science.gov (United States)

    Ghannoum, M A; Rice, L B

    1999-10-01

    The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antimicrobial resistance from different angles. Areas addressed include mechanisms underlying this resistance, improved methods to detect resistance when it occurs, alternate options for the treatment of infections caused by resistant organisms, and strategies to prevent and control the emergence and spread of resistance. In this review, the mode of action of antifungals and their mechanisms of resistance are discussed. Additionally, an attempt is made to discuss the correlation between fungal and bacterial resistance. Antifungals can be grouped into three classes based on their site of action: azoles, which inhibit the synthesis of ergosterol (the main fungal sterol); polyenes, which interact with fungal membrane sterols physicochemically; and 5-fluorocytosine, which inhibits macromolecular synthesis. Many different types of mechanisms contribute to the development of resistance to antifungals. These mechanisms include alteration in drug target, alteration in sterol biosynthesis, reduction in the intercellular concentration of target enzyme, and overexpression of the antifungal drug target. Although the comparison between the mechanisms of resistance to antifungals and antibacterials is necessarily limited by several factors defined in the review, a correlation between the two exists. For example, modification of enzymes which serve as targets for antimicrobial action and the involvement of membrane pumps in the extrusion of drugs are well characterized in both the eukaryotic and prokaryotic cells.

  6. Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni

    Energy Technology Data Exchange (ETDEWEB)

    Aitken, R.; Coulson, P.S.; Dixon, B.; Wilson, R.A.

    1987-11-01

    Vaccination of mice with attenuated cercariae of Schistosoma mansoni induces specific acquired resistance to challenge infection. This resistance is immunologically-mediated, possibly via a delayed-type hypersensitivity. Studies of parasite migration have shown that the protective mechanism operates most effectively in the lungs of vaccinated mice. We have probed the mechanism by exposing mice to 500 rads of gamma radiation before challenge infection. Our results show that the effector mechanism operative against challenge larvae is resistant to radiation. In contrast, classical immune responses are markedly suppressed by the same treatment. While leukocyte populations in the blood fall dramatically after irradiation, numbers of cells recoverable by bronchoalveolar lavage are unaffected. We suggest that vaccination with attenuated cercariae establishes populations of sensitized cells in the lungs which trigger the mechanism of resistance when challenge schistosomula migrate through pulmonary capillary beds. Although the cells may be partially disabled by irradiation, they remain responsive to worm antigens and thereby capable of initiating the elimination mechanism. This hypothesis would explain the radiation resistance of vaccine-induced immunity to S. mansoni.

  7. Acute Cerebrovascular Radiation Syndrome: Radiation Neurotoxicity , mechanisms of CNS radiation injury, advanced countermeasures for Radiation Protection of Central Nervous System.

    Science.gov (United States)

    Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

    . Antiradiation Vaccine and Antiradiation IgG preparations - prospective effective antidote/countermeasure for ϒ-irradiation, heavy ions irradiation, neutron irradiation. Recommendations for treatment and immune-prophylaxis of CNS injury, induced by radiation, were proposed. Specific immune therapy and specific immune prophylaxis reduce symptoms of ACvRS. This manuscript summarizes the results of experiments and considering possibility for blocking toxicological mechanisms of action of Radiation and Radiation Neurotoxins and prevention or diminishing clinical signs of injury of CNS. Experimental data suggest that Antiradiation vaccine and Antiradiation IgG with specific antibodies to Radiation Neurotoxins, Cytotoxins protect CNS against high doses of radiation.

  8. Study of the resistance mechanisms to ultraviolet radiation in Escherichia Coli. II. General characteristics of the mutants resistant to ultraviolet radiation of Escherichia Coli PQ30; Estudio de los mecanismos de resistencia a UV en E. coli. II. Caracteristicas generales de los mutantes resistentes a UV de E. coli PQ30

    Energy Technology Data Exchange (ETDEWEB)

    Alcantara D, D. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    1995-12-15

    Inside this second work the results are shown on the preliminary characterization of the 5 populations of Escherichia coli that its were subjected to the light UV, by means of 80 irradiation- growth cycles, the dose of which it was duplicated each 10 cycles. The course that the resistance to UV to those 5 populations continued along the process, that covers some 165 generations, and the level reached at the end by each one of them suggests the presence of different resistance mechanisms to the UV light. (Author)

  9. Tumourigenicity and radiation resistance of mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Horsman, Michael Robert; Kassem, Moustapha

    2012-01-01

    . Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under......Background. Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart. Material and methods...... are involved in apoptosis evasion while the genes TIMP3, MMP1 and LOX are involved in regulation of the surrounding matrix. The first group may contribute to the difference in radiation resistance observed and the latter could be a major contributor to the tumourigenic capabilities by degrading...

  10. Effect of Ni content on thermal and radiation resistance of VVER RPV steel

    Science.gov (United States)

    Shtrombakh, Ya. I.; Gurovich, B. A.; Kuleshova, E. A.; Frolov, A. S.; Fedotova, S. V.; Zhurko, D. A.; Krikun, E. V.

    2015-06-01

    In this paper thermal stability and radiation resistance of VVER-type RPV steels for pressure vessels of advanced reactors with different nickel content were studied. A complex of microstructural studies and mechanical tests of the steels in different states (after long thermal exposures, provoking embrittling heat treatment and accelerated neutron irradiation) was carried out. It is shown that nickel content (other things being equal) determines the extent of materials degradation under influence of operational factors: steels with a lower nickel concentration demonstrate a higher thermal stability and radiation resistance.

  11. Metal-nanotube composites as radiation resistant materials

    Energy Technology Data Exchange (ETDEWEB)

    González, Rafael I.; Valencia, Felipe; Mella, José; Kiwi, Miguel, E-mail: m.kiwi.t@gmail.com [Departamento de Física, Facultad de Ciencias, CEDENNA, Universidad de Chile, Casilla 653, Santiago 7800024 (Chile); Duin, Adri C. T. van [Department of Mechanical and Nuclear Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802 (United States); So, Kang Pyo; Li, Ju [Department of Nuclear Science and Engineering and Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Bringa, Eduardo M. [CONICET and Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza 5500 (Argentina)

    2016-07-18

    The improvement of radiation resistance in nanocomposite materials is investigated by means of classical reactive molecular dynamics simulations. In particular, we study the influence of carbon nanotubes (CNTs) in an Ni matrix on the trapping and possible outgassing of He. When CNTs are defect-free, He atoms diffuse alongside CNT walls and, although there is He accumulation at the metal-CNT interface, no He trespassing of the CNT wall is observed, which is consistent with the lack of permeability of a perfect graphene sheet. However, when vacancies are introduced to mimic radiation-induced defects, He atoms penetrate CNTs, which play the role of nano-chimneys, allowing He atoms to escape the damaged zone and reduce bubble formation in the matrix. Consequently, composites made of CNTs inside metals are likely to display improved radiation resistance, particularly when radiation damage is related to swelling and He-induced embrittlement.

  12. Proteome studies of bacterial antibiotic resistance mechanisms.

    Science.gov (United States)

    Vranakis, Iosif; Goniotakis, Ioannis; Psaroulaki, Anna; Sandalakis, Vassilios; Tselentis, Yannis; Gevaert, Kris; Tsiotis, Georgios

    2014-01-31

    Ever since antibiotics were used to help humanity battle infectious diseases, microorganisms straight away fought back. Antibiotic resistance mechanisms indeed provide microbes with possibilities to by-pass and survive the action of antibiotic drugs. Several methods have been employed to identify these microbial resistance mechanisms in an ongoing effort to reduce the steadily increasing number of treatment failures due to multi-drug-resistant microbes. Proteomics has evolved to an important tool for this area of research. Following rapid advances in whole genome sequencing, proteomic technologies have been widely used to investigate microbial gene expression. This review highlights the contribution of proteomics in identifying microbial drug resistance mechanisms. It summarizes different proteomic studies on bacteria resistant to different antibiotic drugs. The review further includes an overview of the methodologies used, as well as lists key proteins identified, thus providing the reader not only a summary of research already done, but also directions for future research. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.

  13. Role of Mn2+ and Compatible Solutes in the Radiation Resistance of Thermophilic Bacteria and Archaea

    Directory of Open Access Journals (Sweden)

    Kimberly M. Webb

    2012-01-01

    Full Text Available Radiation-resistant bacteria have garnered a great deal of attention from scientists seeking to expose the mechanisms underlying their incredible survival abilities. Recent analyses showed that the resistance to ionizing radiation (IR in the archaeon Halobacterium salinarum is dependent upon Mn-antioxidant complexes responsible for the scavenging of reactive oxygen species (ROS generated by radiation. Here we examined the role of the compatible solutes trehalose, mannosylglycerate, and di-myo-inositol phosphate in the radiation resistance of aerobic and anaerobic thermophiles. We found that the IR resistance of the thermophilic bacteria Rubrobacter xylanophilus and Rubrobacter radiotolerans was highly correlated to the accumulation of high intracellular concentration of trehalose in association with Mn, supporting the model of Mn2+-dependent ROS scavenging in the aerobes. In contrast, the hyperthermophilic archaea Thermococcus gammatolerans and Pyrococcus furiosus did not contain significant amounts of intracellular Mn, and we found no significant antioxidant activity from mannosylglycerate and di-myo-inositol phosphate in vitro. We therefore propose that the low levels of IR-generated ROS under anaerobic conditions combined with highly constitutively expressed detoxification systems in these anaerobes are key to their radiation resistance and circumvent the need for the accumulation of Mn-antioxidant complexes in the cell.

  14. Ways of providing radiation resistance of magnetic field semiconductor sensors

    CERN Document Server

    Bolshakova, I A; Holyaka, R; Matkovskii, A; Moroz, A

    2001-01-01

    Hall magnetic field sensors resistant to hard ionizing irradiation are being developed for operation under the radiation conditions of space and in charged particle accelerators. Radiation resistance of the sensors is first determined by the properties of semiconductor materials of sensitive elements; we have used microcrystals and thin layers of III-V semiconductors. Applying complex doping by rare-earth elements and isovalent impurities in certain proportions, we have obtained magnetic field sensors resistant to irradiation by fast neutrons and gamma-quanta. Tests of their radiation resistance were carried out at IBR-2 at the Joint Institute for Nuclear Research (Dubna). When exposed to neutrons with E=0.1-13 MeV and intensity of 10 sup 1 sup 0 n cm sup - sup 2 s sup - sup 1 , the main parameter of the sensors - their sensitivity to magnetic fields - changes by no more than 0.1% up to fluences of 10 sup 1 sup 4 n cm sup - sup 2. Further improvement of radiation resistance of sensor materials is expected by ...

  15. Radiation-induced cisplatin resistance in two human cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Eichholtz-Wirth, H.; Stotzer, O. [GSF-Institute of Radiobiology and Cytometry, Neuherberg (Germany); Marx, K. [Medical Clin. III, University, Munich (Germany)

    1997-03-01

    Cisplatin resistance has been induced in human HT-29 and HeLa cells after low-dose fractionated {gamma}-irradiation. The drug resistance is modest and does not confer cross-resistance to irradiation. Alterations that were recently shown to correlate with radiation-induced cisplatin resistance in murine cells are not involved in the resistant HeLa-C3 cells. Scavengers, such as GSH or metallothioneins are unchanged and there is no alteration of the cGMP transduction pathway. Preliminary results in HeLa-C3 cells indicate that resistance is associated with differences of the apoptotic pathway, with enhancement of the p53 suppressor protein after cisplatin treatment but unchanged bcl-2 protein expression. (authors)

  16. Determination of radiation resistant of electronic components in robot system

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hee Dong [Kyungpook National University, Taegu (Korea); Kim, Do Sung [Taegu University, Taegu (Korea); Woo, Hong [Kyungsan University, Kyungsan (Korea)

    1998-04-01

    We investigated the characteristic change for the electronic components of the systems which were used in radiation area, when those were exposured by gamma rays. Bipolar transistor, FET, TTL, CMOS, operational amplifier, some capacitors, and several electronic components were selected for experiment. We applied irradiated gamma ray to the electronic components in the range of 10{sup 6} rad, by {sup 6}0Co(KAERI). We made up appropriate assessment circuit for each electronic component during the performance test, and assessed the reliability and radiation-resistance of them for the each radiation irradiation. (author). 59 refs., 35 figs., 8 tabs.

  17. Radiation resistance of clinical Acinetobacter spp. : A need for concern

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, E.A.; Gerner-Smidt, P.; Kristensen, H. (Control Department, Statens Seruminstitut, Copenhagen (Denmark))

    1991-06-01

    As part of an epidemiological investigation of hospital infections caused by Acinetobacter spp. the radiation resistance of 15 clinical isolates and four reference strains was assessed. The radiation resistance (in D-6 values, viz. the dose necessary for reducing the initial number of colony forming units by a factor of 10(6)) was, in general, higher in the isolates of A. radioresistens than in the isolates of the A. calcoaceticus-A. baumannii complex and of A. lwoffi. However, the least resistant isolates of A. radioresistens had a D-6 value equal to or lower than the most resistant isolates of the other groups. The lowest D-6 values found were for two of the reference strains. The highest D-6 value was 35 kGy. Three isolates of A. johnsonii could not survive long enough in a dried preparation to make an assessment of the D-6 values possible. The radiation resistance of the 15 clinical isolates in the present study was higher than the resistance found in a study of similar isolates in 1970.

  18. Mechanisms of multidrug resistance in cancer.

    Science.gov (United States)

    Gillet, Jean-Pierre; Gottesman, Michael M

    2010-01-01

    The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by numerous mechanisms including decreased drug uptake, increased drug efflux, activation of detoxifying systems, activation of DNA repair mechanisms, evasion of drug-induced apoptosis, etc. In the first part of this chapter, we briefly summarize the current knowledge on individual cellular mechanisms responsible for MDR, with a special emphasis on ATP-binding cassette transporters, perhaps the main theme of this textbook. Although extensive work has been done to characterize MDR mechanisms in vitro, the translation of this knowledge to the clinic has not been crowned with success. Therefore, identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing clinical samples could help to predict the development of resistance and lead to treatments designed to circumvent it. Our thoughts about translational research needed to achieve significant progress in the understanding of this complex phenomenon are therefore discussed in a third section. The pleotropic response of cancer cells to chemotherapy is summarized in a concluding diagram.

  19. 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.

  20. [Quinolones. Nowadays perspectives and mechanisms of resistance].

    Science.gov (United States)

    Álvarez-Hernández, Diego Abelardo; Garza-Mayén, Gilda Sofía; Vázquez-López, Rosalno

    2015-10-01

    Quinolones are a family of synthetic broad-spectrum antimicrobial drugs whose target is the synthesis of DNA. They directly inhibit DNA replication by interacting with two enzymes; DNA gyrase and topoisomerase IV. They have been widely used for the treatment of several community and hospital acquired infections, in the food processing industry and in the agricultural field, making the increasing incidence of quinolone resistance a frequent problem associated with constant exposition to diverse microorganisms. Resistance may be achieved by three non-exclusive mechanisms; through chromosomic mutations in the Quinolone Resistance-Determining Regions of DNA gyrase and topoisomerase IV, by reducing the intracytoplasmic concentrations of quinolones actively or passively and by Plasmid-Mediated Quinolones-Resistance genes, [Qnr determinant genes of resistance to quinolones, variant gene of the aminoglycoside acetyltransferase (AAC(6')-Ib-c)] and encoding genes of efflux pumps (qepA and oqxAB)]. The future of quinolones is uncertain, however, meanwhile they continue to be used in an irrational way, increasing resistance to quinolones should remain as an area of primary priority for research.

  1. Mechanism of quinolone action and resistance.

    Science.gov (United States)

    Aldred, Katie J; Kerns, Robert J; Osheroff, Neil

    2014-03-18

    Quinolones are one of the most commonly prescribed classes of antibacterials in the world and are used to treat a variety of bacterial infections in humans. Because of the wide use (and overuse) of these drugs, the number of quinolone-resistant bacterial strains has been growing steadily since the 1990s. As is the case with other antibacterial agents, the rise in quinolone resistance threatens the clinical utility of this important drug class. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome. This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quinolone action against their enzyme targets. It will then discuss the following three mechanisms that decrease the sensitivity of bacterial cells to quinolones. Target-mediated resistance is the most common and clinically significant form of resistance. It is caused by specific mutations in gyrase and topoisomerase IV that weaken interactions between quinolones and these enzymes. Plasmid-mediated resistance results from extrachromosomal elements that encode proteins that disrupt quinolone-enzyme interactions, alter drug metabolism, or increase quinolone efflux. Chromosome-mediated resistance results from the underexpression of porins or the overexpression of cellular efflux pumps, both of which decrease cellular concentrations of quinolones. Finally, this review will discuss recent advancements in our understanding of how quinolones interact with gyrase and topoisomerase IV and how mutations in these enzymes cause resistance. These last findings suggest approaches to designing new drugs that display improved activity against resistant strains.

  2. Negative differential resistance devices for generation of terahertz radiation

    Science.gov (United States)

    Eisele, H.

    2015-08-01

    This paper discusses the principles of operation, state of the art, and future potential of active two-terminal devices for generation of low-noise, continuous-wave terahertz radiation. These devices use transit-time, transferred-electron, and quantum-mechanical effects (or a combination of them) to create a negative differential resistance (NDR) at the frequency of interest. Many different types of NDR devices have been proposed since the earliest days of semiconductor devices and studied in detailed simulations for their power generation potential, but have yet to be demonstrated experimentally. The paper focuses on NDR devices that not only yielded significant output powers at millimeter waves frequencies and higher, but also have the strong potential of generating radiation at terahertz frequencies. Examples of such NDR devices are resonant tunneling diodes (RTDs), superlattice electronic devices (SLEDs), and InP Gunn devices. Examples of their state-of-the-art results are output powers of 0.2 mW at 443 GHz and 5 μW at 1.53 THz from InGaAs/AlAs double barrier RTDs on InP substrate; 5.0 mW at 123.3 GHz, 1.1 mW at 155.1 GHz, and 0.52 mW at 252.8 GHz from GaAs/AlAs superlattice electronic devices on GaAs substrate; and 330 μW at 412 GHz, 86 μW at 479 GHz, and 18 μW at 502 GHz from InP Gunn devices.

  3. [Shielding ability of lead loaded radiation resistant gloves].

    Science.gov (United States)

    Kawano, T; Ebihara, H

    1990-02-01

    The shielding ability of radiation resistant gloves was examined. The gloves are made of lead loaded (as PbO2) polyvinyl chloride resin and are about 0.4 mm in thickness (70 mg/cm2). Eleven test pieces were sampled from each of three gloves (total 33) and the transmission rates for radiations (X-ray or gamma-ray) through the test pieces were measured with radiation sources, 99mTc, 57Co, 133Ba, 133Xe and 241Am. The differences of the transmission rates for radiations by the positions of the gloves were smaller than 15%, and the differences by three gloves were smaller than 5% in the case of 60 keV and 141 keV radiations. The average transmission rates for radiations in the 33 test pieces were about 40% for 30 keV radiation, about 90% for 80 keV and 140 keV radiations. The shielding characteristic of the gloves is equivalent to about 0.026 mm thick lead plate.

  4. Deinococcus geothermalis: the pool of extreme radiation resistance genes shrinks.

    Directory of Open Access Journals (Sweden)

    Kira S Makarova

    Full Text Available Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR, ultraviolet light (UV and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and

  5. Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

    Energy Technology Data Exchange (ETDEWEB)

    Makarova, Kira S. [National Center for Biotechnology Information; Omelchenko, Marina [National Center for Biotechnology Information; Gaidamakova, Elena [Uniformed Services University of the Health Sciences (USUHS); Matrosova, Vera [Uniformed Services University of the Health Sciences (USUHS); Vasilenko, Alexander [Uniformed Services University of the Health Sciences (USUHS); Zhai, Min [Uniformed Services University of the Health Sciences (USUHS); Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute; Copeland, A [U.S. Department of Energy, Joint Genome Institute; Kim, Edwin [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Pitluck, Samual [U.S. Department of Energy, Joint Genome Institute; Richardson, P M [U.S. Department of Energy, Joint Genome Institute; Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Brettin, Tom [Los Alamos National Laboratory (LANL); Saunders, Elizabeth H [Los Alamos National Laboratory (LANL); Lai, Barry [Argonne National Laboratory (ANL); Ravel, Bruce [Argonne National Laboratory (ANL); Kemner, Kenneth M [Argonne National Laboratory (ANL); Wolf, Yuri [National Center for Biotechnology Information; Sorokin, Alexei [Genetique Microbienne; Gerasimova, Anna [Research Institute of Genetics and Selection of Industrial Microorganisms, Mosco; Gelfand, Mikhail [Moscow State University; Fredrickson, James K [Pacific Northwest National Laboratory (PNNL); Koonin, Eugene [National Center for Biotechnology Information; Daly, Michael [Uniformed Services University of the Health Sciences (USUHS)

    2007-01-01

    Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to

  6. Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

    Energy Technology Data Exchange (ETDEWEB)

    Makarova, Kira S.; Omelchenko, Marina V.; Gaidamakova, Elena K.; Matrosova, Vera Y.; Vasilenko, Alexander; Zhai, Min; Lapidus, Alla; Copeland, Alex; Kim, Edwin; Land, Miriam; Mavrommatis, Konstantinos; Pitluck, Samuel; Richardson, Paul M.; Detter, Chris; Brettin, Thomas; Saunders, Elizabeth; Lai, Barry; Ravel, Bruce; Kemner, Kenneth M.; Wolf, Yuri I.; Sorokin, Alexander; Gerasimova, Anna V.; Gelfand, Mikhail S.; Fredrickson, James K.; Koonin, Eugene V.; Daly, Michael J.

    2007-07-24

    Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at itsoptimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to

  7. Atomistic simulations of the radiation resistance of oxides

    Energy Technology Data Exchange (ETDEWEB)

    Chartier, A., E-mail: alain.chartier@cea.fr [CEA-Saclay, DEN/DANS/DPC/SCP, 91191 Gif-Sur-Yvette (France); Van Brutzel, L. [CEA-Saclay, DEN/DANS/DPC/SCP, 91191 Gif-Sur-Yvette (France); Crocombette, J.-P. [CEA-Saclay, DEN/DANS/DMN/SRMP, 91191 Gif-Sur-Yvette (France)

    2012-09-01

    Fluorite compounds such as urania and ceria, or related compounds such as pyrochlores and also spinels show different behaviors under irradiations, which ranges from perfect radiation resistance to crystalline phase change or even complete amorphization depending on their structure and/or their composition. Displacement cascades - dedicated to the understanding of the ballistic regime and performed by empirical potentials molecular dynamics simulations - have revealed that the remaining damages of the above mentioned oxides are reduced to point defects unlike what is observed in zircon and zirconolite, which directly amorphize during the cascade. The variable behavior of these point defects is the key of the various responses of these materials to irradiations. This behavior can be investigated by two specific molecular dynamics methodologies that will be reviewed here: (i) the method of point defects accumulation as a function of temperature that gives access to the dose effects and to the critical doses for amorphization; (ii) the study Frenkel pairs life-time - i.e. their time of recombination as function of temperature - that may be used as a tool to understand the results obtained in displacements cascades or to identify the microscopic mechanisms responsible for the amorphization/re-crystallization during the point defects accumulations.

  8. Mechanisms of Anticancer Drugs Resistance: An Overview

    Directory of Open Access Journals (Sweden)

    M. R. Chorawala

    2012-01-01

    Full Text Available The management of cancer involves surgery, radiotherapy and chemotherapy. Development of chemoresistance is a persistent problem during the chemotherapy treatment. Cytotoxic drugs that selectively, but not exclusively, target actively proliferating cells include such diverse groups as DNA-alkylating agents, anti-metabolites, intercalating agents and mitotic inhibitors. Resistance constitutes a lack of response to drug-induced tumour growth inhibition; it may be inherent in a subpopulation of heterogeneous cancer cells or be acquired as a cellular response to drug exposure. Principle mechanisms may include altered membrane transport involving the p-glycoprotein product of the multidrug resistance (MDR gene as well as other associated proteins, altered target enzyme, decreased drug activation, increased drug degradation due to altered expression of drug metabolising enzymes, drug inactivation due to conjugation with increased glutathione, subcellular redistribution, drug interaction, enhanced DNA repair and failure to apoptosis as a result of mutated cell cycle proteins such as p53. Attempts to overcome resistance involves the use of combination drug therapy using different classes of drugs with minimally overlapping toxicities to allow maximal dosages, necessary for bone marrow recovery. Adjuvant therapy with p-glycoprotein inhibitors and in specific instances, the use of growth factor and protein kinase C inhibitors are newer experimental approaches that may also prove effective in delaying onset of resistance. Gene knockout using antisense molecules may be effective way of blocking drug resistance.

  9. 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.

  10. Ionizing radiation resistant bacteria; Des bacteries resistantes aux rayonnements ionisants

    Energy Technology Data Exchange (ETDEWEB)

    Libert, M. [CEA/Cadarache, Dept. d' Entreposage et de Stockage des Dechets (DESD), 13 - Saint-Paul-lez-Durance (France)

    2000-07-01

    The living being are not equal face to ionizing radiations. The palm of resistance goes to some bacteria. The champion at any category, the Deinococcus radiodurans, tolerates radiations doses whom one thousandth would kill a man. Two reasons to this fact: after irradiation, the DNA replication is stopped in order that the bacteria can use a repair process called multiple recombination. It cuts intact pieces of a injured chromosome and recombines them with other intact pieces, reconstituting a functional chromosome. It has also an ability to endure the extended action of oxygen, large source of damages for DNA. (N.C.)

  11. Mechanisms of lichen resistance to metallic pollution

    Energy Technology Data Exchange (ETDEWEB)

    Sarret, C.; Manceau, A.; Eybert-Berard, L. [Univ. of Grenoble and CNRS (France). Environmental Geochemistry Group; Cuny, D.; Haluwyn, C. van [Lab. de Botanique et de Cryptogamie, Lille (France); Deruelle, S. [Institut d`Ecologie, Paris (France); Hazemann, J.L.; Menthonnex, J.J. [Univ. of Grenoble and CNRS (France). Environmental Geochemistry Group]|[CNRS, Grenoble (France). Lab. de Cristallographie; Soldo, Y. [CNRS, Grenoble (France). Lab. de Cristallographie

    1998-11-01

    Some lichens have a unique ability to grow in heavily contaminated areas due to the development of adaptative mechanisms allowing a high tolerance to metals. Here the authors report on the chemical forms of Pb and Zn in the metal hyperaccumulator Diploschistes muscorum and of Pb in the metal tolerant lichen Xanthoria parietina. The speciation of Zn and Pb has been investigated by powder X-ray diffraction (XRD) and extended X-ray absorption fine structure (EXAFS) spectroscopy using the advanced third-generation synchrotron radiation source of the European synchrotron radiation facility (ESRF in Grenoble). This study reveals that in both lichens cells are protected from toxicity by complexation of heavy metals, but the strategies differ: in D. muscorum, Pb and Zn are accumulated through an enhanced synthesis of oxalate, which precipitates toxic elements as insoluble salts, whereas in X. parietina, Pb is complexed to carboxylic groups of the fungal cell walls. The authors conclude that hyperaccumulation of metals results from a reactive mechanism of organic acid production, whereas metallo-tolerance is achieved by a passive complexation to existing functional groups.

  12. A New Perspective on Radiation Resistance Based on Deinococcus radiodurans

    Science.gov (United States)

    2009-03-01

    for resistant and sensi‑ tive bacteria exposed to ultraviolet C ( UVC ) radiation (265 nm) or γ‑rays were not nearly sufficient to account for the...differences in bacterial survival19,20. UVC causes substantial direct dam‑ age to both DNA and proteins in vivo19. For proteins, UVC disrupts certain...Highly localized extreme damage to proteins with exposed inorganic Fe–S prosthetic groups Release of Fe2+ from proteins leads to Fenton chemistry

  13. The relative effects of radiation crosslinking and type of counterface on the wear resistance of ultrahigh-molecular-weight polyethylene.

    Science.gov (United States)

    Bistolfi, Alessandro; Bellare, Anuj

    2011-09-01

    The lifetime of total joint replacement prostheses utilizing ultrahigh-molecular-weight polyethylene (UHMWPE) components has historically been determined by their wear resistance. It has been discovered that radiation crosslinking of UHMWPE can substantially increase its wear resistance. However, it is also well recognized that there is a radiation-dose-dependent decrease in several important mechanical properties of UHMWPE, such as fracture toughness and resistance to fatigue crack propagation. In this study, the effect of radiation crosslinking (followed by remelting) on the morphology, tensile properties and wear resistance of UHMWPE was investigated. Wear tests were conducted against both the commonly used cobalt-chromium counterface polished to implant grade smoothness as well as a smoother ceramic (alumina) counterface. The results showed that 50kGy dose radiation crosslinking increased the wear resistance of UHMWPE against the cobalt-chromium counterface 7-fold, but the coupling of remelted, crosslinked UHMWPE against the smoother alumina counterface led to a 20-fold increase in wear resistance. This study shows that the use of an alumina counterface would circumvent the need to use a high radiation dose in crosslinking UHMWPE, associated with poor mechanical properties, without compromising wear resistance.

  14. Designing Radiation Resistance in Materials for Fusion Energy

    Science.gov (United States)

    Zinkle, S. J.; Snead, L. L.

    2014-07-01

    Proposed fusion and advanced (Generation IV) fission energy systems require high-performance materials capable of satisfactory operation up to neutron damage levels approaching 200 atomic displacements per atom with large amounts of transmutant hydrogen and helium isotopes. After a brief overview of fusion reactor concepts and radiation effects phenomena in structural and functional (nonstructural) materials, three fundamental options for designing radiation resistance are outlined: Utilize matrix phases with inherent radiation tolerance, select materials in which vacancies are immobile at the design operating temperatures, or engineer materials with high sink densities for point defect recombination. Environmental and safety considerations impose several additional restrictions on potential materials systems, but reduced-activation ferritic/martensitic steels (including thermomechanically treated and oxide dispersion-strengthened options) and silicon carbide ceramic composites emerge as robust structural materials options. Materials modeling (including computational thermodynamics) and advanced manufacturing methods are poised to exert a major impact in the next ten years.

  15. Mechanisms of bacterial resistance to chromium compounds.

    Science.gov (United States)

    Ramírez-Díaz, Martha I; Díaz-Pérez, César; Vargas, Eréndira; Riveros-Rosas, Héctor; Campos-García, Jesús; Cervantes, Carlos

    2008-06-01

    Chromium is a non-essential and well-known toxic metal for microorganisms and plants. The widespread industrial use of this heavy metal has caused it to be considered as a serious environmental pollutant. Chromium exists in nature as two main species, the trivalent form, Cr(III), which is relatively innocuous, and the hexavalent form, Cr(VI), considered a more toxic species. At the intracellular level, however, Cr(III) seems to be responsible for most toxic effects of chromium. Cr(VI) is usually present as the oxyanion chromate. Inhibition of sulfate membrane transport and oxidative damage to biomolecules are associated with the toxic effects of chromate in bacteria. Several bacterial mechanisms of resistance to chromate have been reported. The best characterized mechanisms comprise efflux of chromate ions from the cell cytoplasm and reduction of Cr(VI) to Cr(III). Chromate efflux by the ChrA transporter has been established in Pseudomonas aeruginosa and Cupriavidus metallidurans (formerly Alcaligenes eutrophus) and consists of an energy-dependent process driven by the membrane potential. The CHR protein family, which includes putative ChrA orthologs, currently contains about 135 sequences from all three domains of life. Chromate reduction is carried out by chromate reductases from diverse bacterial species generating Cr(III) that may be detoxified by other mechanisms. Most characterized enzymes belong to the widespread NAD(P)H-dependent flavoprotein family of reductases. Several examples of bacterial systems protecting from the oxidative stress caused by chromate have been described. Other mechanisms of bacterial resistance to chromate involve the expression of components of the machinery for repair of DNA damage, and systems related to the homeostasis of iron and sulfur.

  16. Physiological Mechanisms of Acute Intestinal Radiation Death

    Science.gov (United States)

    1986-06-01

    Radiation Death 18 3 1 A eutron 19 ABSTRACT (Contfnuo on rlvorJ of re.•u•ldy ,d d..nfflfy by blo*,t ftmO,) e overall objective was to claikUTyhe role...neutron kerma rates. These changes are attributable to attenuation of neutrons and the production of gamma rays by thermal neutroncapture by hydrogen in...but also injuries from blast and thermal effects. These non-ionizing radiation traumas can result in sequestering large amounts of fluid and

  17. Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of Cryptococcus neoformans

    Directory of Open Access Journals (Sweden)

    Kwang-Woo Jung

    2016-11-01

    Full Text Available The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation. Particularly, deletion of recombinase RAD51 and two DNA-dependent ATPase genes, RAD54 and RDH54, increased cellular susceptibility to both gamma radiation and DNA-damaging agents. A variety of oxidative stress response genes were also upregulated. Among them, sulfiredoxin contributed to gamma radiation resistance in a peroxiredoxin/thioredoxin-independent manner. Furthermore, we found that genes involved in molecular chaperone expression, ubiquitination systems, and autophagy were induced, whereas genes involved in the biosynthesis of proteins and fatty acids/sterols were downregulated. Most importantly, we discovered a number of novel C. neoformans genes, the expression of which was modulated by gamma radiation exposure, and their deletion rendered cells susceptible to gamma radiation exposure, as well as DNA damage insults. Among these genes, we found that a unique transcription factor containing the basic leucine zipper domain, named Bdr1, served as a regulator of the gamma radiation resistance of C. neoformans by controlling expression of DNA repair genes, and its expression was regulated by the evolutionarily conserved DNA damage response protein kinase Rad53. Taken together, the current transcriptome and functional analyses contribute to the understanding of the unique molecular mechanism of the radiation-resistant fungus C. neoformans.

  18. Radiation-resistant extremophiles and their potential in biotechnology and therapeutics.

    Science.gov (United States)

    Gabani, Prashant; Singh, Om V

    2013-02-01

    Extremophiles are organisms able to thrive in extreme environmental conditions. Microorganisms with the ability to survive high doses of radiation are known as radioresistant or radiation-resistant extremophiles. Excessive or intense exposure to radiation (i.e., gamma rays, X-rays, and particularly UV radiation) can induce a variety of mutagenic and cytotoxic DNA lesions, which can lead to different forms of cancer. However, some populations of microorganisms thrive under different types of radiation due to defensive mechanisms provided by primary and secondary metabolic products, i.e., extremolytes and extremozymes. Extremolytes (including scytonemin, mycosporine-like amino acids, shinorine, porphyra-334, palythine, biopterin, and phlorotannin, among others) are able to absorb a wide spectrum of radiation while protecting the organism's DNA from being damaged. The possible commercial applications of extremolytes include anticancer drugs, antioxidants, cell-cycle-blocking agents, and sunscreens, among others. This article aims to review the strategies by which microorganisms thrive in extreme radiation environments and discuss their potential uses in biotechnology and the therapeutic industry. The major challenges that lie ahead are also discussed.

  19. Early mechanisms in radiation-induced biological damage

    Energy Technology Data Exchange (ETDEWEB)

    Powers, E.L.

    1983-01-01

    An introduction to the mechanisms of radiation action in biological systems is presented. Several questions about the nature of the radiation damage process are discussed, including recognition of the oxygen effects, dose-response relationships, and the importance of the hydroxyl radical. (ACR)

  20. Transcription and activity of antioxidant enzymes after ionizing irradiation in radiation-resistant and radiation-sensitive mice

    OpenAIRE

    Hardmeier, Rosmarie; Hoeger, Harald; Fang-Kircher, Susanne; Khoschsorur, Ali; Lubec, Gert

    1997-01-01

    The involvement of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase in radiobiological processes has been described at the enzyme activity level. We irradiated radiation-resistant (RR) and radiation-sensitive (RS) mice and studied antioxidant enzymes at the transcriptional and activity level. In addition, aromatic hydroxylation and lipid peroxidation parameters were determined to study radiation resistance at the oxidation level. RS BALB/c/J Him m...

  1. Bile resistance mechanisms in Lactobacillus and Bifidobacterium

    Directory of Open Access Journals (Sweden)

    Lorena eRuiz

    2013-12-01

    Full Text Available Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Most of the probiotic bacteria currently available in the market belong to the genera Lactobacillus and Bifidobacterium, and specific health-promoting activities, such as treatment of diarrhea or amelioration of gastrointestinal discomfort, have been attributed to them. In order to be able to survive the gastrointestinal transit and transiently colonise our gut, these bacteria must be able to counteract the deleterious action of bile salts, which are the main components of bile. Bile salts are detergent-like biological substances synthesised in the liver from cholesterol. Host enzymes conjugate the newly synthesised free bile acids in the liver with the amino acids glycine or taurine, generating conjugated bile salts. These compounds are stored in the gall bladder and they are released into the duodenum during digestion to perform their physiological function, which is the solubilisation of fat coming from diet. These bile salts possess strong antimicrobial activity, since they are able to disorganize the structure of the cell membrane, as well as trigger DNA damage. This means that bacteria inhabiting our intestinal tract must have intrinsic resistance mechanisms to cope with bile salts. To do that, Lactobacillus and Bifidobacterium display a variety of proteins devoted to the efflux of bile salts or protons, to modify sugar metabolism or to prevent protein misfolding. In this manuscript, we review and discuss specific bile resistance mechanisms, as well as the processes responsible for the adaptation of bifidobacteria and lactobacilli to bile.

  2. Emetic Mechanism in Acute Radiation Sickness

    Science.gov (United States)

    1987-08-20

    emetic effect of radiation in a single episode recorded from the thoracic cavity consists typically of two phases. Initial repetitive negative...three additional cats, all combined with vagotomy. Wang et al. (1958) found no effect at all of "abdominal sympathectomy " performed as the sole...Wang and Borison (1951) performed total sympathectomies in dogs. We therefore now find uninterpretable the results of "abdominal sympathectomy " in the

  3. Mechanisms of radiation-induced brain injury / Review

    Directory of Open Access Journals (Sweden)

    Nataša Šuštar

    2014-11-01

    Full Text Available Normal 0 21 false false false SL X-NONE X-NONE MicrosoftInternetExplorer4 Mechanisms of radiation-induced brain injury are not yet fully understood. Early failure occurs because of the effect of ionizing radiation on dividing endothelialcells and oligodendrocytes. Hypothetically, late radiation-induced brain injury is causedby chronic inflammation and oxidative stress. In the case of irradiation of thehippocampus, the failure of neurogenesis and cognitive decline could be consequencesof such pathological mechanisms. Due to lack of diagnostic tools, that could not more precisely define the brain injury after radiation, therapy, that may prevent such consequences in patients who require radiotherapy, is not currently known. This articlesummarizes research hypotheses regarding processes of the brain damage after radiation, prospects in the diagnosis and therapeutic approaches.

  4. Radiation-Induced Heart Disease: Pathologic Abnormalities and Putative Mechanisms

    Directory of Open Access Journals (Sweden)

    Neil K Taunk

    2015-02-01

    Full Text Available Breast cancer is a common diagnosis in women. Breast radiation has become a critical in managing patients who receive breast conserving surgery, or have certain high-risk features after mastectomy. Most patients have an excellent prognosis, therefore understanding the late effects of radiation to the chest is important. Radiation induced heart disease (RIHD comprises a spectrum of cardiac pathology including myocardial fibrosis and cardiomyopathy, coronary artery disease, valvular disease, pericardial disease, and arrhythmias. Tissue fibrosis is a common mediator in RIHD. Multiple pathways converge with both acute and chronic cellular, molecular, and genetic changes to result in fibrosis. In this article, we review the pathophysiology of cardiac disease related to radiation therapy to the chest. Our understanding of these mechanisms has improved substantially, but much work remains to further refine radiation delivery techniques and develop therapeutics to battle late effects of radiation.

  5. Mechanism of Burn Resistance of Alloy Ti40

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The Ti fire found in high performance engines promotes the development of burn resistant Ti alloys. The burn resistant mechanism of Ti40 alloy is investigated. Ti40 alloy reveals good burn resistance. Its interfacial products between burning products and the matrix are tenacious,which retard the diffusion of oxygen into the matrix. Two burn resistant mechanisms, that is, fast scatter dispersion of heat and suppression of oxygen diffusion, are proposed.

  6. Insecticide resistance and resistance mechanisms in bed bugs, Cimex spp. (Hemiptera: Cimicidae).

    Science.gov (United States)

    Dang, Kai; Doggett, Stephen L; Veera Singham, G; Lee, Chow-Yang

    2017-06-29

    The worldwide resurgence of bed bugs [both Cimex lectularius L. and Cimex hemipterus (F.)] over the past two decades is believed in large part to be due to the development of insecticide resistance. The transcriptomic and genomic studies since 2010, as well as morphological, biochemical and behavioral studies, have helped insecticide resistance research on bed bugs. Multiple resistance mechanisms, including penetration resistance through thickening or remodelling of the cuticle, metabolic resistance by increased activities of detoxification enzymes (e.g. cytochrome P450 monooxygenases and esterases), and knockdown resistance by kdr mutations, have been experimentally identified as conferring insecticide resistance in bed bugs. Other candidate resistance mechanisms, including behavioral resistance, some types of physiological resistance (e.g. increasing activities of esterases by point mutations, glutathione S-transferase, target site insensitivity including altered AChEs, GABA receptor insensitivity and altered nAChRs), symbiont-mediated resistance and other potential, yet undiscovered mechanisms may exist. This article reviews recent studies of resistance mechanisms and the genes governing insecticide resistance, potential candidate resistance mechanisms, and methods of monitoring insecticide resistance in bed bugs. This article provides an insight into the knowledge essential for the development of both insecticide resistance management (IRM) and integrated pest management (IPM) strategies for successful bed bug management.

  7. Microstructure and mechanics of human resistance arteries.

    Science.gov (United States)

    Bell, J S; Adio, A O; Pitt, A; Hayman, L; Thorn, C E; Shore, A C; Whatmore, J L; Winlove, C P

    2016-12-01

    Vascular diseases such as diabetes and hypertension cause changes to the vasculature that can lead to vessel stiffening and the loss of vasoactivity. The microstructural bases of these changes are not presently fully understood. We present a new methodology for stain-free visualization, at a microscopic scale, of the morphology of the main passive components of the walls of unfixed resistance arteries and their response to changes in transmural pressure. Human resistance arteries were dissected from subcutaneous fat biopsies, mounted on a perfusion myograph, and imaged at varying transmural pressures using a multimodal nonlinear microscope. High-resolution three-dimensional images of elastic fibers, collagen, and cell nuclei were constructed. The honeycomb structure of the elastic fibers comprising the internal elastic layer became visible at a transmural pressure of 30 mmHg. The adventitia, comprising wavy collagen fibers punctuated by straight elastic fibers, thinned under pressure as the collagen network straightened and pulled taut. Quantitative measurements of fiber orientation were made as a function of pressure. A multilayer analytical model was used to calculate the stiffness and stress in each layer. The adventitia was calculated to be up to 10 times as stiff as the media and experienced up to 8 times the stress, depending on lumen diameter. This work reveals that pressure-induced reorganization of fibrous proteins gives rise to very high local strain fields and highlights the unique mechanical roles of both fibrous networks. It thereby provides a basis for understanding the micromechanical significance of structural changes that occur with age and disease.

  8. Action and resistance mechanisms of antibiotics: A guide for clinicians

    Directory of Open Access Journals (Sweden)

    Garima Kapoor

    2017-01-01

    Full Text Available Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and “bypass” of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials.

  9. Mechanisms of radiation interaction with DNA: Potential implications for radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Sinclair, W.K.; Fry, R.J.M.

    1987-01-01

    An overview of presentations and discussions which took place at the US Department of Energy/Commission of European Communities (DOE/CEC) workshop on ''Mechanisms of Radiation Interaction with DNA: Potential Implications for Radiation Protection,'' held at San Diego, California, January 21-22, 1987, is provided. The Department has traditionally supported fundamental research on interactions of ionizing radiation with different biological systems and at all levels of biological organization. The aim of this workshop was to review the base of knowledge in the area of mechanisms of radiation action at the DNA level, and to explore ways in which this information can be applied to the development of scientifically sound concepts and procedures for use in the field of radiation protection.

  10. Radiation Resistant Hybrid Lotus Effect Photoelectrocatalytic Self-Cleaning Anti-Contamination Coatings Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This project will develop radiation resistant hybrid Lotus Effect photoelectrocatalytic self-cleaning anti-contamination coatings for application to Lunar...

  11. Mechanisms of radiation-induced gene responses

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E.; Paunesku, T.

    1996-10-01

    In the process of identifying genes differentially expressed in cells exposed ultraviolet radiation, we have identified a transcript having a 26-bp region that is highly conserved in a variety of species including Bacillus circulans, yeast, pumpkin, Drosophila, mouse, and man. When the 5` region (flanking region or UTR) of a gene, the sequence is predominantly in +/+ orientation with respect to the coding DNA strand; while in the coding region and the 3` region (UTR), the sequence is most frequently in the +/-orientation with respect to the coding DNA strand. In two genes, the element is split into two parts; however, in most cases, it is found only once but with a minimum of 11 consecutive nucleotides precisely depicting the original sequence. The element is found in a large number of different genes with diverse functions (from human ras p21 to B. circulans chitonase). Gel shift assays demonstrated the presence of a protein in HeLa cell extracts that binds to the sense and antisense single-stranded consensus oligomers, as well as to the double- stranded oligonucleotide. When double-stranded oligomer was used, the size shift demonstrated as additional protein-oligomer complex larger than the one bound to either sense or antisense single-stranded consensus oligomers alone. It is speculated either that this element binds to protein(s) important in maintaining DNA is a single-stranded orientation for transcription or, alternatively that this element is important in the transcription-coupled DNA repair process.

  12. Mechanisms of radiation-induced neoplastic cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table.

  13. Mechanisms of rhizobacteria-mediated induced systemic resistance

    NARCIS (Netherlands)

    Hase, S.; Pieterse, C.M.J.; Loon, L.C. van

    2001-01-01

    Some of non-pathogenic rhizosphere bacteria reduce disease by activating a resistance mechanism in the plant called rhizobacteria-mediated induced systemic resistance (ISR). Rhizobacteria-mediated ISR resembles classic pathogen-induced systemic acquired resistance (SAR) in that both types of induced

  14. Mechanisms of Antimicrobial Peptide Resistance in Gram-Negative Bacteria

    Directory of Open Access Journals (Sweden)

    Victor I. Band

    2014-12-01

    Full Text Available Cationic antimicrobial peptides (CAMPs are important innate immune defenses that inhibit colonization by pathogens and contribute to clearance of infections. Gram-negative bacterial pathogens are a major target, yet many of them have evolved mechanisms to resist these antimicrobials. These resistance mechanisms can be critical contributors to bacterial virulence and are often crucial for survival within the host. Here, we summarize methods used by Gram-negative bacteria to resist CAMPs. Understanding these mechanisms may lead to new therapeutic strategies against pathogens with extensive CAMP resistance.

  15. Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    Introduction: Cerebrovascular Acute Radiation Syndrome (CvARS) is an extremely severe in-jury of Central Nervous System (CNS) and Peripheral Nervous System (PNS). CvARS can be induced by the high doses of neutron, heavy ions, or gamma radiation. The Syndrome clinical picture depends on a type, timing, and the doses of radiation. Four grades of the CvARS were defined: mild, moderate, severe, and extremely severe. Also, four stages of CvARS were developed: prodromal, latent, manifest, outcome -death. Duration of stages depends on the types, doses, and time of radiation. The CvARS clinical symptoms are: respiratory distress, hypotension, cerebral edema, severe disorder of cerebral blood microcirculation, and acute motor weakness. The radiation toxins, Cerebro-Vascular Radiation Neurotoxins (SvARSn), determine development of the acute radiation syndrome. Mechanism of action of the toxins: Though pathogenesis of radiation injury of CNS remains unknown, our concept describes the Cv ARS as a result of Neurotoxicity and Excitotoxicity, cell death through apoptotic necrosis. Neurotoxicity occurs after the high doses radiation exposure, formation of radiation neuro-toxins, possible bioradicals, or group of specific enzymes. Intracerebral hemorrhage can be a consequence of the damage of endothelial cells caused by radiation and the radiation tox-ins. Disruption of blood-brain barrier (BBB)and blood-cerebrospinal fluid barrier (BCFB)is possibly the most significant effect of microcirculation disorder and metabolic insufficiency. NMDA-receptors excitotoxic injury mediated by cerebral ischemia and cerebral hypoxia. Dam-age of the pyramidal cells in layers 3 and 5 and Purkinje cell layer the cerebral cortex , damage of pyramidal cells in the hippocampus occur as a result of cerebral ischemia and intracerebral bleeding. Methods: Radiation Toxins of CV ARS are defined as glycoproteins with the molec-ular weight of RT toxins ranges from 200-250 kDa and with high enzymatic activity

  16. What have the mechanisms of resistance to glyphosate taught us?

    Science.gov (United States)

    Shaner, Dale L; Lindenmeyer, Richard Bradley; Ostlie, Michael H

    2012-01-01

    The intensive use of glyphosate alone to manage weeds has selected populations that are glyphosate resistant. The three mechanisms of glyphosate resistance that have been elucidated are (1) target-site mutations, (2) gene amplification and (3) altered translocation due to sequestration. What have we learned from the selection of these mechanisms, and how can we apply those lessons to future herbicide-resistant crops and new mechanisms of action? First, the diversity of glyphosate resistance mechanisms has helped further our understanding of the mechanism of action of glyphosate and advanced our knowledge of plant physiology. Second, the relatively rapid evolution of glyphosate-resistant weed populations provides further evidence that no herbicide is invulnerable to resistance. Third, as new herbicide-resistant crops are developed and new mechanisms of action are discovered, the weed science community needs to ensure that we apply the lessons we have learned on resistance management from the experience with glyphosate. Every new weed management system must be evaluated during development for its potential to select for resistance, and stewardship programs should be in place when the new program is introduced.

  17. Radiation-Induced Bystander Response: Mechanism and Clinical Implications

    Science.gov (United States)

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure. Recent advances: Recent advances in radiation biology and oncology have demonstrated that bystander effects, which are emerged in cells that have never been exposed, but neighboring irradiated cells, are also involved in radiation effects. Bystander effects are now recognized as an indispensable component of tissue response related to deleterious effects of IR. Critical issues: Evidence has indicated that nonapoptotic premature senescence is commonly observed in various tissues and organs. Senesced cells were found to secrete various proteins, including cytokines, chemokines, and growth factors, most of which are equivalent to those identified as bystander factors. Secreted factors could trigger cell proliferation, angiogenesis, cell migration, inflammatory response, etc., which provide a tissue microenvironment assisting tissue repair and remodeling. Future directions: Understandings of the mechanisms and physiological relevance of radiation-induced bystander effects are quite essential for the beneficial control of wound healing and care. Further studies should extend our knowledge of the mechanisms of bystander effects and mode of cell death in response to IR. PMID:24761341

  18. Analysis and modeling of resistive switching mechanisms oriented to resistive random-access memory

    Institute of Scientific and Technical Information of China (English)

    Huang Da; Wu Jun-Jie; Tang Yu-Hua

    2013-01-01

    With the progress of the semiconductor industry,the resistive random-access memory (RAM) has drawn increasing attention.The discovery of the memristor has brought much attention to this study.Research has focused on the resistive switching characteristics of different materials and the analysis of resistive switching mechanisms.We discuss the resistive switching mechanisms of different materials in this paper and analyze the differences of those mechanisms from the view point of circuitry to establish their respective circuit models.Finally,simulations are presented.We give the prospect of using different materials in resistive RAM on account of their resistive switching mechanisms,which are applied to explain their resistive switchings.

  19. Invasive oral cancer stem cells display resistance to ionising radiation.

    Science.gov (United States)

    Gemenetzidis, Emilios; Gammon, Luke; Biddle, Adrian; Emich, Helena; Mackenzie, Ian C

    2015-12-22

    There is a significant amount of evidence to suggest that human tumors are driven and maintained by a sub-population of cells, known as cancer stem cells (CSC). In the case of head and neck cancer, such cells have been characterised by high expression levels of CD44 cell surface glycoprotein, while we have previously shown the presence of two diverse oral CSC populations in vitro, with different capacities for cell migration and proliferation. Here, we examined the response of oral CSC populations to ionising radiation (IR), a front-line measure for the treatment of head and neck tumors. We show that oral CSC initially display resistance to IR-induced growth arrest as well as relative apoptotic resistance. We propose that this is a result of preferential activation of the DNA damagerepair pathway in oral CSC with increased activation of ATM and BRCA1, elevated levels of DNA repair proteins RAD52, XLF, and a significantly faster rate of DNA double-strand-breaks clearance 24 hours following IR. By visually identifying CSC sub-populations undergoing EMT, we show that EMT-CSC represent the majority of invasive cells, and are more radio-resistant than any other population in re-constructed 3D tissues. We provide evidence that IR is not sufficient to eliminate CSC in vitro, and that sensitization of CD44hi/ESAlow cells to IR, followed by secondary EMT blockade, could be critical in order to reduce primary tumor recurrence, but more importantly to be able to eradicate cells capable of invasion and distant metastasis.

  20. Molecular mechanisms of bortezomib resistant adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Erika Suzuki

    Full Text Available Bortezomib (Velcade™ is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM. Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ~30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response.

  1. Effect of Ionizing Beta Radiation on the Mechanical Properties of Poly(ethylene under Thermal Stress

    Directory of Open Access Journals (Sweden)

    Bednarik Martin

    2016-01-01

    Full Text Available It was found in this study, that ionizing beta radiation has a positive effect on the mechanical properties of poly(ethylene. In recent years, there have been increasing requirements for quality and cost effectiveness of manufactured products in all areas of industrial production. These requirements are best met with the polymeric materials, which have many advantages in comparison to traditional materials. The main advantages of polymer materials are especially in their ease of processability, availability, and price of the raw materials. Radiation crosslinking is one of the ways to give the conventional plastics mechanical, thermal, and chemical properties of expensive and highly resistant construction polymers. Several types of ionizing radiation are used for crosslinking of polymers. Each of them has special characteristics. Electron beta and photon gamma radiation are used the most frequently. The great advantage is that the crosslinking occurs after the manufacturing process at normal temperature and pressure. The main purpose of this paper has been to determine the effect of ionizing beta radiation on the tensile modulus, strength and elongation of low and high density polyethylene (LDPE and HDPE. These properties were examined in dependence on the dosage of the ionizing beta radiation (non-irradiated samples and those irradiated by dosage 99 kGy were compared and on the test temperature. Radiation cross-linking of LDPE and HDPE results in increased tensile strength and modulus, and decreased of elongation. The measured results indicate that ionizing beta radiation treatment is effective tool for improvement of mechanical properties of LDPE and HDPE under thermal stress.

  2. Molecular and biochemical mechanisms of drug resistance in fungi.

    Science.gov (United States)

    Yamaguchi, H

    1999-01-01

    This paper reviews the current status of our understanding of resistance mechanisms of three major classes of antifungal drugs for systemic use, amphotericin B (AMPH), flucytosine (5-FC) and several azole antifungals, in particular fluconazole (FLCZ), at the molecular and cellular levels. Although the number of reports of AMPH- or 5-FC-resistant fungal species and strains is limited, several mechanisms of resistance have been described. AMPH-resistant Candida have a marked decrease in ergosterol content compared with AMPH-susceptible control isolates. A lesion in the UMP-pyrophosphorylase is the most frequent determinant of 5-FC resistance in C. albicans. Recently resistance of C. albicans to azoles has become an increasing problem. Extensive biochemical studies have highlighted a significant diversity in mechanisms conferring resistance to FLCZ and other azoles, which include alterations in sterol biosynthesis, target site, uptake and efflux. Among them, the most important mechanism clinically is reduced access of the drug to the intracellular P450 14 DM target, probably because of the action of a multidrug resistance efflux pump, and overproduction of that target. However, other possible resistance mechanisms for azoles remain to be identified.

  3. Genetic Mechanisms of Antimicrobial Resistance of Acinetobacter baumannii.

    Science.gov (United States)

    Esterly, John S; Richardson, Chad L; Eltoukhy, Noha S; Qi, Chao; Scheetz, Marc H

    2011-02-01

    To summarize published data identifying known genetic mechanisms of antibiotic resistance in Acinetobacter baumannii and the correlating phenotypic expression of antibiotic resistance. MEDLINE databases (1966-July 15, 2010) were searched to identify original reports of genetic mechanisms of antibiotic resistance in A. baumannii. Numerous genetic mechanisms of resistance to multiple classes of antibiotics are known to exist in A. baumannii, a gram-negative bacterium increasingly implicated in nosocomial infections. Mechanisms may be constitutive or acquired via plasmids, integrons, and transposons. Methods of resistance include enzymatic modification of antibiotic molecules, modification of antibiotic target sites, expression of efflux pumps, and downregulation of cell membrane porin channel expression. Resistance to β-lactams appears to be primarily caused by β-lactamase production, including extended spectrum β-lactamases (b/aTEM, blaSHV, b/aTX-M,b/aKPC), metallo-β-lactamases (blaMP, blaVIM, bla, SIM), and most commonly, oxacillinases (blaOXA). Antibiotic target site alterations confer resistance to fluoroquinolones (gyrA, parC) and aminoglycosides (arm, rmt), and to a much lesser extent, β-lactams. Efflux pumps (tet, ade, abe) contribute to resistance against β-lactams, tetracyclines, fluoroquinolones, and aminoglycosides. Finally, porin channel deletion (carO, oprD) appears to contribute to β-lactam resistance and may contribute to rarely seen polymyxin resistance. Of note, efflux pumps and porin deletions as solitary mechanisms may not render clinical resistance to A. baumannii. A. baumannii possesses copious genetic resistance mechanisms. Knowledge of local genotypes and expressed phenotypes for A. baumannii may aid clinicians more than phenotypic susceptibilities reported in large epidemiologic studies. © 2011 SAGE Publications.

  4. A new mechanism for radiation damage processes in alkali halides

    NARCIS (Netherlands)

    Dubinko, V.I.; Turkin, A.A.; Vainshtein, D.I.; Hartog, H.W. den

    1999-01-01

    We present a theory of radiation damage formation in alkali halides based on a new mechanism of dislocation climb, which involves the production of VF centers (self-trapped hole neighboring a cation vacancy) as a result of the absorption of H centers of dislocation lines. We consider the evolution o

  5. Detecting mechanisms of acquired BRAF inhibitor resistance in melanoma.

    Science.gov (United States)

    Lo, Roger S; Shi, Hubing

    2014-01-01

    (V600)BRAF mutation was identified as an ideal target for clinical therapy due to its indispensable roles in supporting melanoma initiation and progression. Despite the fact that BRAF inhibitors (BRAFi) can elicit anti-tumor responses in the majority of treated patients and confer overall survival benefits, acquired drug resistance is a formidable obstacle to long-term management of the disease. Several aberrant events including RTK upregulation, NRAS mutation, mutant BRAF amplification or alternative splicing, and MEK mutation have been reported as acquired BRAFi resistance mechanisms. Clinially, detection of these resistance mechanisms help understand drug response patterns and help guide combinatorial therapeutic strategies. Therefore, quick and accurate diagnosis of the resistant mechanisms in tumor biopsies has become an important starting point for personalized therapy. In this chapter, we review the major acquired BRAFi resistance mechanisms, highlight their therapeutic implications, and provide the diagnostic methods from clinical samples.

  6. Radiation-resistant bacteria and their application to metal and radionuclides bioremediation

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-Long

    2004-01-01

    Microorganisms have a number of applications in the nuclear industry, which would benefit from the use of radiation-resistant microorganisms. Environmentally isolated bacteria have shown to be resistant to gamma irradiation up to a dose of 30,000 Gy. It has also been reported that the presence of ionizing radiation may induce radio-resistance in bacteria. Recent demonstrations of the removal and immobilization of inorganic contaminants by microbial transformations, sorption and mineralization show the potential of both natural and engineered microorganisms as bioremedial tools. This review is to provide an overview of the application of radiation-resistant bacteria to decontamination of metal and radionuclide.

  7. Mechanisms Linking Inflammation to Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Li Chen

    2015-01-01

    Full Text Available Obesity is now widespread around the world. Obesity-associated chronic low-grade inflammation is responsible for the decrease of insulin sensitivity, which makes obesity a major risk factor for insulin resistance and related diseases such as type 2 diabetes mellitus and metabolic syndromes. The state of low-grade inflammation is caused by overnutrition which leads to lipid accumulation in adipocytes. Obesity might increase the expression of some inflammatory cytokines and activate several signaling pathways, both of which are involved in the pathogenesis of insulin resistance by interfering with insulin signaling and action. It has been suggested that specific factors and signaling pathways are often correlated with each other; therefore, both of the fluctuation of cytokines and the status of relevant signaling pathways should be considered during studies analyzing inflammation-related insulin resistance. In this paper, we discuss how these factors and signaling pathways contribute to insulin resistance and the therapeutic promise targeting inflammation in insulin resistance based on the latest experimental studies.

  8. Drug-resistance mechanisms and prevalence of Enterobacter cloacae resistant to multi-antibiotics

    Institute of Scientific and Technical Information of China (English)

    张杰; 顾怡明; 俞云松; 周志慧; 杜小玲

    2004-01-01

    @@The main drug-resistance mechanism of gram-negative bacteria is producing β-lactamases. Two kinds of enzymes cause drug resistance by hydrolyzing oxyimino-cephalosporins and aztreonam: one is chromosomally encoded AmpC β-lactamases, the other is plasmid-mediated extended-spectrum β-lactamases (ESBLs). Enterobacter cloacae can produce both of them, so that these strains are seriously resistance to many antibiotics. In order to study the main drug-resistant mechanism in Enterobacter cloacae, PCR and nucleotide sequencing were performed on 58 multidrug resistant strains.

  9. Molecular mechanisms of methicillin resistance in Staphylococcus aureus.

    Science.gov (United States)

    Domínguez, M A; Liñares, J; Martín, R

    1997-09-01

    Methicillin-resistant Staphylococcus aureus (MRSA) strains are among the most common nosocomial pathogens. The most significant mechanism of resistance to methicillin in this-species is the acquisition of a genetic determinant (mecA gene). However, resistance seems to have a more complex molecular basis, since additional chromosomal material is involved in such resistance. Besides, overproduction of penicillinase and/or alterations in the PBPs can contribute to the formation of resistance phenotypes. Genetic and environmental factors leading to MRSA are reviewed.

  10. Radiation toxins: molecular mechanisms of action and radiomimetic properties .

    Science.gov (United States)

    Popov, Dmitri; Maliev, Vecheslav

    Introduction: Acute Radiation Disease (ARD) or Acute Radiation Syndromes (ARS) were defined as a toxic poisonous with development of the acute pathological processes in irradi-ated animals: systemic inflammatory response syndrome(SIRS), toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMOD), toxic multiple organ failure (TMOF). However, the nature of radiation toxins, their mechanisms of formation, molecular structure, and mechanism of actions remain uncertain. Moderate and high doses of radiation induce apoptotic necrosis of radiosensitive cells with formation of Radiation Toxins and in-flammation development. Mild doses of radiation induce apoptosis or controlled programmed death of radiosensitive cells without Radiation Toxins formation and development of inflam-mation processes. Only radiation induced apoptotic necrosis initiates formation of Radiation Toxins(RT). Radiation Toxins are playing an important role as the trigger mechanisms for in-flammation development and cell lysis. The systemic inflammatory response syndrome after radiation involves an influence of various endogenous agents and mediators of inflammation such as bradykinin, histamine, serotonin and phospholipases activation, prostaglandins biosyn-thesis. Although, formation of non-specific toxins such as Reactive Oxygen Species (ROS) is an important pathological process at mild or high doses of radiation. Reactive Oxygen Species play an important role in molecules damage and development of peroxidation of lipids and pro-teins which are the structural parts of cell and mitochondrial membranes. ROS and bio-radicals induce damage of DNA and RNA and peroxidation of their molecules. But high doses of radia-tion, severe and extremely severe physiological stress, result in cells death by apoptotic necrosis and could be defined as the neuroimmune acute disease. Excitotoxicity is an important patho-logical mechanism which damages the central nervous system. We postulate that

  11. Role of Chemotherapy and Mechanisms of Resistance to Chemotherapy in Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Lohiya, Vipin; Aragon-Ching, Jeanny B.; Sonpavde, Guru

    2016-01-01

    Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide. Here, we discuss the various mechanisms of resistance to chemotherapy in metastatic CRPC and the potential role of emerging regimens and agents in varying clinical phases of development.

  12. Tangent Resistance of Soil on Moldboard and the Mechanism of Resistance Reduction of Bionic Moldboard

    Institute of Scientific and Technical Information of China (English)

    Deng Shi-qiao; Ren Lu-quan; Liu Yan; Han Zhi-wu

    2005-01-01

    The tangent resistance on the interface of the soil-moldboard is an important component of the resistance to moving soil . We developed simplified mechanical models to analyze this resistance. We found that it is composed of two components, the frictional and adhesive resistances. These two components originate from the soil pore, which induced a capillary suction effect, and the soil-moldboard contact area produced tangent adhesive resistance. These two components varied differently with soil moisture. Thus we predicted that resistance reduction against soil exerted on the non-smooth bionic moldboard is mainly due to the elimination of capillary suction and the reduction of physical-chemical adsorption of soil.

  13. Drug resistance mechanisms and novel drug targets for tuberculosis therapy.

    Science.gov (United States)

    Islam, Md Mahmudul; Hameed, H M Adnan; Mugweru, Julius; Chhotaray, Chiranjibi; Wang, Changwei; Tan, Yaoju; Liu, Jianxiong; Li, Xinjie; Tan, Shouyong; Ojima, Iwao; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Zhang, Tianyu

    2017-01-20

    Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance.

  14. Basic mechanisms of radiation effects in the natural space radiation environment

    Energy Technology Data Exchange (ETDEWEB)

    Schwank, J.R.

    1994-06-01

    Four general topics are covered in respect to the natural space radiation environment: (1) particles trapped by the earth`s magnetic field, (2) cosmic rays, (3) radiation environment inside a spacecraft, (4) laboratory radiation sources. The interaction of radiation with materials is described by ionization effects and displacement effects. Total-dose effects on MOS devices is discussed with respect to: measurement techniques, electron-hole yield, hole transport, oxide traps, interface traps, border traps, device properties, case studies and special concerns for commercial devices. Other device types considered for total-dose effects are SOI devices and nitrided oxide devices. Lastly, single event phenomena are discussed with respect to charge collection mechanisms and hard errors. (GHH)

  15. Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids

    Directory of Open Access Journals (Sweden)

    Susu He

    2016-12-01

    Full Text Available The dissemination of resistance among bacteria has been facilitated by the fact that resistance genes are usually located on a diverse and evolving set of transmissible plasmids. However, the mechanisms generating diversity and enabling adaptation within highly successful resistance plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we have performed a detailed analysis of the mobilome (the entire mobile genetic element content of a set of previously sequenced carbapenemase-producing Enterobacteriaceae (CPE from the National Institutes of Health Clinical Center. This analysis revealed that plasmid reorganizations occurring in the natural context of colonization of human hosts were overwhelmingly driven by genetic rearrangements carried out by replicative transposons working in concert with the process of homologous recombination. A more complete understanding of the molecular mechanisms and evolutionary forces driving rearrangements in resistance plasmids may lead to fundamentally new strategies to address the problem of antibiotic resistance.

  16. Study on Drug Resistance and Relative Mechanisms of Chlamydia Trachomatis

    Institute of Scientific and Technical Information of China (English)

    侯淑萍; 刘全忠

    2004-01-01

    Abstract: Chlamydia Trachomatis (C.T.) is one of the most common pathogens of human sexually transmitted diseases. Treatment of C.T. infection primarily depends on Tetracyclines, Macrolides and Quinolones, but with the wide use of antibiotics an increasing number of drug-resistant Chlamydia trachomatis cases have been reported. This review summarizes the resistant conditions and the possible resistance mechanisms of C.T..

  17. Mechanism of resistance to benzalkonium chloride by Pseudomonas aeruginosa.

    OpenAIRE

    Sakagami, Y; Yokoyama, H; Nishimura, H.; Ose, Y; Tashima, T.

    1989-01-01

    The mechanisms of resistance of Pseudomonas aeruginosa to benzalkonium chloride (BC) were studied. The effluence of cell components was observed in susceptible P. aeruginosa by electron microscopy, but resistant P. aeruginosa seemed to be undamaged. No marked changes in cell surface potential between Escherichia coli NIHJC-2 and a spheroplast strain were found. The contents of phospholipids (PL) and fatty and neutral lipids (FNL) in the cell walls of resistant P. aeruginosa were higher than t...

  18. Lin28 mediates radiation resistance of breast cancer cells via regulation of caspase, H2A.X and Let-7 signaling.

    Science.gov (United States)

    Wang, Linbo; Yuan, Chao; Lv, Kezhen; Xie, Shuduo; Fu, Peifen; Liu, Xiaojiao; Chen, Yongxia; Qin, Chuan; Deng, Wuguo; Hu, Wenxian

    2013-01-01

    Resistance to radiation therapy is a major obstacle for the effective treatment of cancers. Lin28 has been shown to contribute to breast tumorigenesis; however, the relationship between Lin28 and radioresistance remains unknown. In this study, we investigated the association of Lin28 with radiation resistance and identified the underlying mechanisms of action of Lin28 in human breast cancer cell lines. The results showed that the expression level of Lin28 was closely associated with resistance to radiation treatment. The T47D cancer cell line, which highly expresses Lin28, is more resistant to radiation than MCF7, Bcap-37 or SK-BR-3 cancer cell lines, which have low-level Lin28 expression. Transfection with Lin28 siRNA significantly led to an increase of sensitivity to radiation. By contrast, stable expression of Lin28 in breast cancer cells effectively attenuated the sensitivity to radiation treatment. Stable expression of Lin28 also significantly inhibited radiation-induced apoptosis. Moreover, further studies have shown that caspases, H2A.X and Let-7 miRNA were the molecular targets of Lin28. Stable expression of Lin28 and treatment with radiation induced H2AX expression, while inhibited p21 and γ-H2A.X. Overexpression of Let-7 enhanced the sensitivities to radiation in breast cancer cells. Taken together, these results indicate that Lin28 might be one mechanism underlying radiation resistance, and Lin28 could be a potential target for overcoming radiation resistance in breast cancer.

  19. Lin28 mediates radiation resistance of breast cancer cells via regulation of caspase, H2A.X and Let-7 signaling.

    Directory of Open Access Journals (Sweden)

    Linbo Wang

    Full Text Available Resistance to radiation therapy is a major obstacle for the effective treatment of cancers. Lin28 has been shown to contribute to breast tumorigenesis; however, the relationship between Lin28 and radioresistance remains unknown. In this study, we investigated the association of Lin28 with radiation resistance and identified the underlying mechanisms of action of Lin28 in human breast cancer cell lines. The results showed that the expression level of Lin28 was closely associated with resistance to radiation treatment. The T47D cancer cell line, which highly expresses Lin28, is more resistant to radiation than MCF7, Bcap-37 or SK-BR-3 cancer cell lines, which have low-level Lin28 expression. Transfection with Lin28 siRNA significantly led to an increase of sensitivity to radiation. By contrast, stable expression of Lin28 in breast cancer cells effectively attenuated the sensitivity to radiation treatment. Stable expression of Lin28 also significantly inhibited radiation-induced apoptosis. Moreover, further studies have shown that caspases, H2A.X and Let-7 miRNA were the molecular targets of Lin28. Stable expression of Lin28 and treatment with radiation induced H2AX expression, while inhibited p21 and γ-H2A.X. Overexpression of Let-7 enhanced the sensitivities to radiation in breast cancer cells. Taken together, these results indicate that Lin28 might be one mechanism underlying radiation resistance, and Lin28 could be a potential target for overcoming radiation resistance in breast cancer.

  20. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    Science.gov (United States)

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

  1. New mechanisms of bacterial arsenic resistance

    Directory of Open Access Journals (Sweden)

    Hung-Chi Yang

    2016-02-01

    Full Text Available Arsenic is the most pervasive environmental substance and is classified by the International Agency for Research on Cancer as a Group 1 human carcinogen. Nearly every organism has resistance pathways for inorganic arsenic, and in bacteria, their genes are found in arsenic resistance (ars operons. Recently, a parallel pathway for organic arsenicals has been identified. The ars genes responsible for the organoarsenical detoxification includes arsM, which encodes an As(III S-adenosylmethionine methyltransferase, arsI, which encodes a C–As bond lyase, and arsH, which encodes a methylarsenite oxidase. The identification and properties of arsM, arsI and arsH are described in this review.

  2. Evolution of herbicide resistance mechanisms in grass weeds.

    Science.gov (United States)

    Matzrafi, Maor; Gadri, Yaron; Frenkel, Eyal; Rubin, Baruch; Peleg, Zvi

    2014-12-01

    Herbicide resistant weeds are becoming increasingly common, threatening global food security. Here, we present BrIFAR: a new model system for the functional study of mechanisms of herbicide resistance in grass weeds. We have developed a large collection of Brachypodium accessions, the BrI collection, representing a wide range of habitats. Wide screening of the responses of the accessions to four major herbicide groups (PSII, ACCase, ALS/AHAS and EPSPS inhibitors) identified 28 herbicide-resistance candidate accessions. Target-site resistance to PSII inhibitors was found in accessions collected from habitats with a known history of herbicide applications. An amino acid substitution in the psbA gene (serine264 to glycine) conferred resistance and also significantly affected the flowering and shoot dry weight of the resistant accession, as compared to the sensitive accession. Non-target site resistance to ACCase inhibitors was found in accessions collected from habitats with a history of herbicide application and from a nature reserve. In-vitro enzyme activity tests and responses following pre-treatment with malathion (a cytochrome-P450 inhibitor) indicated sensitivity at the enzyme level, and give strong support to diclofop-methyl and pinoxaden enhanced detoxification as NTS resistance mechanism. BrIFAR can promote better understanding of the evolution of mechanisms of herbicide resistance and aid the implementation of integrative management approaches for sustainable agriculture. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Mechanisms of Resistance to Antibody-Drug Conjugates.

    Science.gov (United States)

    Loganzo, Frank; Sung, Matthew; Gerber, Hans-Peter

    2016-12-01

    Drug resistance limits the effectiveness of cancer therapies. Despite attempts to develop curative anticancer treatments, tumors evolve evasive mechanisms limiting durable responses. Hence, diverse therapies are used to attack cancer, including cytotoxic and targeted agents. Antibody-drug conjugates (ADC) are biotherapeutics designed to deliver potent cytotoxins to cancer cells via tumor-specific antigens. Little is known about the clinical manifestations of drug resistance to this class of therapy; however, recent preclinical studies reveal potential mechanisms of resistance. Because ADCs are a combination of antibody and small molecule cytotoxin, multifactorial modes of resistance are emerging that are inherent to the structure and function of the ADC. Decreased cell-surface antigen reduces antibody binding, whereas elevated drug transporters such as MDR1 and MRP1 reduce effectiveness of the payload. Inherent to the uniqueness of the ADC, other novel resistance mechanisms are emerging, including altered antibody trafficking, ADC processing, and intracellular drug release. Most importantly, the modular nature of the ADC allows components to be switched and replaced, enabling development of second-generation ADCs that overcome acquired resistance. This review is intended to highlight recent progress in our understanding of ADC resistance, including approaches to create preclinical ADC-refractory models and to characterize their emerging mechanisms of resistance. Mol Cancer Ther; 15(12); 2825-34. ©2016 AACR.

  4. Biomarkers and mechanisms of natural disease resistance in dairy cows

    NARCIS (Netherlands)

    Altena, van S.E.C.

    2016-01-01

    The aim of this thesis was to define and test biomarkers for disease resistance in dairy cows and to determine the underlying mechanism in natural disease resistance. The health status of the cows is an important issue in dairy farming. Due to the mandatory reduction in the use of antibiotics, alter

  5. Herbicide resistance in weeds: Survey, characterization, and mechanisms

    Science.gov (United States)

    The goal of this paper is to present a systematic diagnostic approach towards the characterization of herbicide resistance in a given weed population with regards to profile (single, multiple, cross resistance), magnitude (fold level), mechanism, and related bio-physiological aspects. Diagnosing her...

  6. Mechanism of Resistance to Dietary Cholesterol

    Directory of Open Access Journals (Sweden)

    Lindsey R. Boone

    2011-01-01

    Full Text Available Background. Alterations in expression of hepatic genes that could contribute to resistance to dietary cholesterol were investigated in Sprague-Dawley rats, which are known to be resistant to the serum cholesterol raising action of dietary cholesterol. Methods. Microarray analysis was used to provide a comprehensive analysis of changes in hepatic gene expression in rats in response to dietary cholesterol. Changes were confirmed by RT-PCR analysis. Western blotting was employed to measure changes in hepatic cholesterol 7α hydroxylase protein. Results. Of the 28,000 genes examined using the Affymetrix rat microarray, relatively few were significantly altered. As expected, decreases were observed for several genes that encode enzymes of the cholesterol biosynthetic pathway. The largest decreases were seen for squalene epoxidase and lanosterol 14α demethylase (CYP 51A1. These changes were confirmed by quantitative RT-PCR. LDL receptor expression was not altered by dietary cholesterol. Critically, the expression of cholesterol 7α hydroxylase, which catalyzes the rate-limiting step in bile acid synthesis, was increased over 4-fold in livers of rats fed diets containing 1% cholesterol. In contrast, mice, which are not resistant to dietary cholesterol, exhibited lower hepatic cholesterol 7α hydroxylase (CYP7A1 protein levels, which were not increased in response to diets containing 2% cholesterol.

  7. Chemotherapy resistance mechanisms in advanced skin cancer

    Directory of Open Access Journals (Sweden)

    Bhuvanesh Sukhlal Kalal

    2017-03-01

    Full Text Available Melanoma is a most dangerous and deadly type of skin cancer, and considered intrinsically resistant to both radiotherapy and chemotherapy. It has become a major public health concern as the incidence of melanoma has been rising steadily over recent decades with a 5-year survival remaining less than 5%. Detection of the disease in early stage may be curable, but late stage metastatic disease that has spread to other organs has an extremely poor prognosis with a median survival of less than 10 months. Since metastatic melanoma is unresponsive to therapy that is currently available, research is now focused on different treatment strategies such as combinations of surgery, chemotherapy and radiotherapy. The molecular basis of resistance to chemotherapy seen in melanoma is multifactorial; defective drug transport system, altered apoptotic pathway, deregulation of apoptosis and/or changes in enzymatic systems that mediate cellular metabolic machinery. Understanding of alterations in molecular processes involved in drug resistance may help in developing new therapeutic approaches to treatment of malignant melanoma.

  8. Conduction Mechanism of Valence Change Resistive Switching Memory: A Survey

    Directory of Open Access Journals (Sweden)

    Ee Wah Lim

    2015-09-01

    Full Text Available Resistive switching effect in transition metal oxide (TMO based material is often associated with the valence change mechanism (VCM. Typical modeling of valence change resistive switching memory consists of three closely related phenomena, i.e., conductive filament (CF geometry evolution, conduction mechanism and temperature dynamic evolution. It is widely agreed that the electrochemical reduction-oxidation (redox process and oxygen vacancies migration plays an essential role in the CF forming and rupture process. However, the conduction mechanism of resistive switching memory varies considerably depending on the material used in the dielectric layer and selection of electrodes. Among the popular observations are the Poole-Frenkel emission, Schottky emission, space-charge-limited conduction (SCLC, trap-assisted tunneling (TAT and hopping conduction. In this article, we will conduct a survey on several published valence change resistive switching memories with a particular interest in the I-V characteristic and the corresponding conduction mechanism.

  9. Molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis clinical isolates

    Directory of Open Access Journals (Sweden)

    Meng Dong-Ya

    2014-01-01

    Full Text Available To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs of DNA gyrase (gyrA and gyrB and topoisomerase IV (parC and parE in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX, intermediate resistant to Levofloxacin (LVX and Sparfloxacin (SFX, and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.

  10. Molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis clinical isolates.

    Science.gov (United States)

    Meng, Dong-Ya; Sun, Chang-Jian; Yu, Jing-Bo; Ma, Jun; Xue, Wen-Cheng

    2014-01-01

    To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH) clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs) of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX), intermediate resistant to Levofloxacin (LVX) and Sparfloxacin (SFX), and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.

  11. Mechanisms linking brain insulin resistance to Alzheimer's disease

    OpenAIRE

    Maria Niures P.S. Matioli; Ricardo Nitrini

    2015-01-01

    Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dy...

  12. Mechanisms of radiation interaction with DNA: Potential implications for radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    1988-01-01

    The Office of Health and Environmental Research (OHER) of the US Department of Energy conducts a broad multidisciplinary research program which includes basic biophysics, biophysical chemistry, molecular and cellular biology as well as experimental animal studies and opportunistic human studies. This research is directed at understanding how low levels of radiation of various qualities produce the spectrum of biological effects that are seen for such exposures. This workshop was entitled ''Mechanisms of Radiation Interaction with DNA: Potential Implications for Radiation Protection.'' It ws jointly sponsored by the Department of Energy and the Commission of European Communities. The aim of the workshop was to review the base of knowledge in the area of mechanisms of radiation action at the DNA level, and to explore ways in which this information can be applied to the development of scientifically sound concepts and procedures for use in the field of radiation protection. The overview of research provided by this multidisciplinary group will be helpful to the Office in program planning. This report includes a summary of the presentations, extended abstracts, the meeting agenda, research recommendations, and a list of participants. Individual papers are processed separately for the data base.

  13. Cross-resistance and biochemical mechanisms of resistance to indoxacarb in the diamondback moth, Plutella xylostella.

    Science.gov (United States)

    Zhang, Shuzhen; Zhang, Xiaolei; Shen, Jun; Li, Dongyang; Wan, Hu; You, Hong; Li, Jianhong

    2017-08-01

    Indoxacarb belongs to a class of insecticides known as oxadiazines and is the first commercialized pyrazoline-type voltage-dependent sodium channel blocker. A moderate level of resistance to indoxacarb has evolved in field populations of Plutella xylostella from Central China. In the present study, cross-resistance, resistance stability and metabolic mechanisms of indoxacarb resistance were investigated in this moth species. A P. xylostella strain with a high level of resistance to indoxacarb was obtained through continuous selection in the laboratory. The strain showed cross-resistance to metaflumizone, beta-cypermethrin and chlorfenapyr, but no resistance to cyantraniliprole, chlorantraniliprole, abamectin, chlorfluazuron, spinosad and diafenthiuron compared with the susceptible strain. Synergism tests revealed that piperonyl butoxide (PBO) (synergistic ratio, SR=7.8) and diethyl maleate (DEF) (SR=3.5) had considerable synergistic effects on indoxacarb toxicity in the resistant strain (F58). Enzyme activity data showed there was an approximate 5.8-fold different in glutathione S-transferase (GST) and a 6.8-fold different in cytochrome P450 monooxygenase between the resistant strain (F58) and susceptible strain, suggesting that the increased activity of these two enzymes is likely the main detoxification mechanism responsible for the species' resistance to indoxacarb. These results will be helpful for insecticide resistance management strategies to delay the development of indoxacarb resistance in fields. Copyright © 2017. Published by Elsevier Inc.

  14. Physiological Defense Mechanism of Ligularia intermedia Against UV-B Radiation on Dongling Mountain

    Institute of Scientific and Technical Information of China (English)

    李鑫; 贾顺姬; 简嘉; 林孟仪; 李骑昂; 黄晓春; 张超; 张荣庆; 张贵友

    2003-01-01

    Ligularia intermedia growing at different altitudes were used to investigate the mechanism of ultraviolet (UV)-resistance on physiological aspects in the field.The tests compared the absorbance of the UV-absorbing compound, the content of chlorophyll a, chlorophyll b, and carotenoids, and the activities of peroxidase (POX) and superoxide dismutase (SOD) in Ligularia intermedia growing at three different altitudes on Dongling Mountain in northern China.There were no significant differences between the plants growing at 1160 m and 1820 m.However, all of these factors increased dramatically at 2190 m.The results indicate that the UV-resistance of the plants mainly depends on the mechanism of filtering the radiation and preventing the reactive oxygen species (ROS) damage produced by UV-B.

  15. Molecular mechanisms of polymyxin resistance: knowns and unknowns.

    Science.gov (United States)

    Baron, Sophie; Hadjadj, Linda; Rolain, Jean-Marc; Olaitan, Abiola Olumuyiwa

    2016-12-01

    Colistin, also referred to as polymyxin E, is an effective antibiotic against most multidrug-resistant Gram-negative bacteria and is currently used as a last-line drug for treating severe bacterial infections. Colistin resistance has increased gradually for the last few years, and knowledge of its multifaceted mechanisms is expanding. This includes the newly discovered plasmid-mediated colistin resistance gene mcr-1, which has been detected in over 20 countries within 3 months of its first report. We previously reported all of the known mechanisms of polymyxin resistance in our first review in 2014, but an update seems necessary in 2016, considering the significant recent discoveries that have been made in this domain. This review provides an update about what is already known, what is new, and some unresolved questions with respect to colistin resistance.

  16. Radiation damage in negative-differential resistance devices

    Energy Technology Data Exchange (ETDEWEB)

    Soliman, F.A.S. (Nuclear Materials Authority, Cairo (Egypt)); Kamh, S.A. (Ain-Shams Univ., Cairo (Egypt). Faculty of Women for Arts, Science and Education)

    1994-02-01

    Tunnel diodes made with silicon and gallium arsenide have been tested in both neutron- and gamma-radiation environments. Experimental data show that failure usually occurs in the range 10[sup 14]-10[sup 18] n cm[sup -2] or 50-270 Mrad range. The primary failure mechanism for neutron irradiated samples is an increase in the valley current (from 0.10 mA to 0.58 mA and from 1.5 [mu]A to 30 [mu]A for silicon and GaAs diodes, respectively). In the case of gamma-irradiated silicon samples, the valley current reaches a value of 0.48 mA, at 260.8 Mrad, although their initial values are 0.1 mA. As a result, the peak-to-valley current ratios of the irradiated devices were shown to decrease severely. Both the valley and forward peak voltage values were shown to decrease with radiation. Values of 0.18 and 0.25 V for silicon samples were measured after exposure to 5 x 10[sup 16] n cm[sup -2] although their initial values were 0.42 and 0.80 V, respectively. As a result, the devices' output power were shown to be affected seriously. Finally, silicon devices irradiated for 48 h in the ET-RR-1 research reactor, Egypt, for up to 1.872 x 10[sup 18] n cm[sup -2] or to gamma doses up to 2.6 x 10[sup 8] rad, were greatly influenced and they lost their main feature as PN-junctions. (Author).

  17. Targeting the Mechanisms of Resistance to Chemotherapy and Radiotherapy with the Cancer Stem Cell Hypothesis

    Directory of Open Access Journals (Sweden)

    Ryan Morrison

    2011-01-01

    Full Text Available Despite advances in treatment, cancer remains the 2nd most common cause of death in the United States. Poor cure rates may result from the ability of cancer to recur and spread after initial therapies have seemingly eliminated detectable signs of disease. A growing body of evidence supports a role for cancer stem cells (CSCs in tumor regrowth and spread after initial treatment. Thus, targeting CSCs in combination with traditional induction therapies may improve treatment outcomes and survival rates. Unfortunately, CSCs tend to be resistant to chemo- and radiation therapy, and a better understanding of the mechanisms underlying CSC resistance to treatment is necessary. This paper provides an update on evidence that supports a fundamental role for CSCs in cancer progression, summarizes potential mechanisms of CSC resistance to treatment, and discusses classes of drugs currently in preclinical or clinical testing that show promise at targeting CSCs.

  18. Molecular exploration of the highly radiation resistant cyanobacterium Arthrospira sp. PCC 8005

    Science.gov (United States)

    Badri, Hanène; Leys, Natalie; Wattiez, Ruddy

    Arthrospira (Spirulina) is a photosynthetic cyanobacterium able to use sunlight to release oxygen from water and remove carbon dioxide and nitrate from water. In addition, it is suited for human consumption (edible). For these traits, the cyanobacterium Arthrospira sp. PCC 8005 was selected by the European Space Agency (ESA) as part of the life support system MELiSSA for recycling oxygen, water, and food during future long-haul space missions. However, during such extended missions, Arthrospira sp. PCC 8005 will be exposed to continuous artificial illumination and harmful cosmic radiation. The aim of this study was to investigate how Arthrospira will react and behave when exposed to such stress environment. The cyanobacterium Arthrospira sp. PCC 8005 was exposed to high gamma rays doses in order to unravel in details the response of this bacterium following such stress. Test results showed that after acute exposure to high doses of 60Co gamma radiation upto 3200 Gy, Arthrospira filaments were still able to restart photosynthesis and proliferate normally. Doses above 3200 Gy, did have a detrimental effect on the cells, and delayed post-irradiation proliferation. The photosystem activity, measured as the PSII quantum yield immediately after irradiation, decreased significantly at radiation doses above 3200 Gy. Likewise through pigment content analysis a significant decrease in phycocyanin was observed following exposure to 3200 Gy. The high tolerance of this bacterium to 60Co gamma rays (i.e. ca. 1000x more resistant than human cells for example) raised our interest to investigate in details the cellular and molecular mechanisms behind this amazing resistance. Optimised DNA, RNA and protein extraction methods and a new microarray chip specific for Arthrospira sp. PCC 8005 were developed to identify the global cellular and molecular response following exposure to 3200 Gy and 5000 Gy A total of 15,29 % and 30,18 % genes were found differentially expressed in RNA

  19. Effects of Mechanical and Radiative Supernova Feedback on Subhalo Evolution

    Science.gov (United States)

    Quirk, Amanda; Choi, Ena; Ostriker, Jeremiah P.

    2017-01-01

    Using cosmological hydrodynamical simulations, we investigate the effects supernova feedback has on populations of subhalos at current redshift. A group of halos was run through two simulations, each with different feedback models. One had thermal feedback, and the other had mechanical and radiative feedback. We used a friend-of-friend halo finder on the output of these simulations to explore the stellar and dark matter subhalos created. The number of stellar subhalos created by the mechanical feedback simulation was significantly less than the number created by the thermal feedback model, especially at low mass. Thus, the mechanical feedback model created a number of stellar subhalos more consistent with observations. The mechanical feedback model also showed a presence of dark matter subhalos that lacked stellar particles, or dark subhalos. The results of this analysis can give insight to the Missing Satellite Problem.

  20. Ribosome-targeting antibiotics and mechanisms of bacterial resistance.

    Science.gov (United States)

    Wilson, Daniel N

    2014-01-01

    The ribosome is one of the main antibiotic targets in the bacterial cell. Crystal structures of naturally produced antibiotics and their semi-synthetic derivatives bound to ribosomal particles have provided unparalleled insight into their mechanisms of action, and they are also facilitating the design of more effective antibiotics for targeting multidrug-resistant bacteria. In this Review, I discuss the recent structural insights into the mechanism of action of ribosome-targeting antibiotics and the molecular mechanisms of bacterial resistance, in addition to the approaches that are being pursued for the production of improved drugs that inhibit bacterial protein synthesis.

  1. Resistance Mechanisms of Anopheles stephensi (Diptera: Culicidae to Temephos

    Directory of Open Access Journals (Sweden)

    Aboozar Soltani

    2015-10-01

    Full Text Available Background: Anopheles stephensi is a sub-tropical species and has been considered as one of the most important vector of human malaria throughout the Middle East and South Asian region including the malarious areas of southern Iran. Current reports confirmed An. stephensi resistance to temephos in Oman and India. However, there is no comprehensive research on mechanisms of temephos resistance in An. stephensi in the literature. This study was designed in order to clarify the enzymatic and molecular mechanisms of temephos resistance in this species.Methods: Profile activities of α- and ß-esterases, mixed function oxidase (MFO, glutathione-S-transferase (GST, insensitive acetylcholinesterase, and para-nitrophenyl acetate (PNPA-esterase enzymes were tested for An. stephensi strain with resistance ratio of 15.82 to temephos in comparison with susceptible strain.Results: Results showed that the mean activity of α-EST, GST and AChE enzymes were classified as altered indicating metabolic mechanisms have considerable role in resistance of An. stephensi to temephos. Molecular study using PCR-RFLP method to trace the G119S mutation in ACE-1 gene showed lack of the mutation responsible for organophosphate insecticide resistance in the temephos-selected strain of An. stephensi.Conclusion: This study showed that the altered enzymes but not targets site insensitivity of ACE-1 are responsible for temephos resistance in An. stephensi in south of Iran.

  2. Pseudomonas aeruginosa: arsenal of resistance mechanisms, decades of changing resistance profiles, and future antimicrobial therapies.

    Science.gov (United States)

    El Zowalaty, Mohamed E; Al Thani, Asmaa A; Webster, Thomas J; El Zowalaty, Ahmed E; Schweizer, Herbert P; Nasrallah, Gheyath K; Marei, Hany E; Ashour, Hossam M

    2015-01-01

    Antimicrobial resistance is one of the most serious public health issues facing humans since the discovery of antimicrobial agents. The frequent, prolonged, and uncontrolled use of antimicrobial agents are major factors in the emergence of antimicrobial-resistant bacterial strains, including multidrug-resistant variants. Pseudomonas aeruginosa is a leading cause of nosocomial infections. The abundant data on the increased resistance to antipseudomonal agents support the need for global action. There is a paucity of new classes of antibiotics active against P. aeruginosa. Here, we discuss recent antibacterial resistance profiles and mechanisms of resistance by P. aeruginosa. We also review future potential methods for controlling antibiotic-resistant bacteria, such as phage therapy, nanotechnology and antipseudomonal vaccines.

  3. Insecticide resistance in vector Chagas disease: evolution, mechanisms and management.

    Science.gov (United States)

    Mougabure-Cueto, Gastón; Picollo, María Inés

    2015-09-01

    Chagas disease is a chronic parasitic infection restricted to America. The disease is caused by the protozoa Trypanosoma cruzi, which is transmitted to human through the feces of infected triatomine insects. Because no treatment is available for the chronic forms of the disease, vector chemical control represents the best way to reduce the incidence of the disease. Chemical control has been based principally on spraying dwellings with insecticide formulations and led to the reduction of triatomine distribution and consequent interruption of disease transmission in several areas from endemic region. However, in the last decade it has been repeatedly reported the presence triatomnes, mainly Triatoma infestans, after spraying with pyrethroid insecticides, which was associated to evolution to insecticide resistance. In this paper the evolution of insecticide resistance in triatomines is reviewed. The insecticide resistance was detected in 1970s in Rhodnius prolixus and 1990s in R. prolixus and T. infestans, but not until the 2000s resistance to pyrthroids in T. infestans associated to control failures was described in Argentina and Bolivia. The main resistance mechanisms (i.e. enhanced metabolism, altered site of action and reduced penetration) were described in the T. infestans resistant to pyrethrods. Different resistant profiles were demonstrated suggesting independent origin of the different resistant foci of Argentina and Bolivia. The deltamethrin resistance in T. infestans was showed to be controlled by semi-dominant, autosomally inherited factors. Reproductive and developmental costs were also demonstrated for the resistant T. infestans. A discussion about resistance and tolerance concepts and the persistence of T. infestans in Gran Chaco region are presented. In addition, theoretical concepts related to toxicological, evolutionary and ecological aspects of insecticide resistance are discussed in order to understand the particular scenario of pyrethroid

  4. Optimization of a conical antenna for pulse radiation - An efficient design using resistive loading

    Science.gov (United States)

    Maloney, James G.; Smith, Glenn S.

    1993-07-01

    The conical monopole antenna with a section of continuous resistive loading is considered as a radiator for temporally short, broad-bandwidth pulses. The geometrical details of the coaxial feed and the resistive loading are varied to optimize this structure for pulse radiation. Compared with the perfectly conducting cone, the optimized resistive cone radiates a better reproduction of the pulse excitation with no loss in amplitude, and has internal reflections that are much smaller in amplitude. Graphical displays of the field surrounding the antenna are used to give insight into the physical processes for transient radiation from this antenna. Experimental models were constructed to verify the optimization and demonstrate the practicality of the design. Measurements of both the reflected voltage in the feed line and the time-varying radiated field are in excellent agreement with the theoretical calculations.

  5. RADIATION RESISTANT LED POWER SUPPLY RELEASED UNDER CERN OPEN HARDWARE LICENSE

    CERN Multimedia

    2016-01-01

    As part of the design of a new emergency lighting system for the CERN accelerator complex a new design for a radiation resistant power supply has been produced. The design is available from the Open Hardware Repository.

  6. Different mechanisms of resistance modulate sulfite tolerance in wine yeasts.

    Science.gov (United States)

    Nadai, Chiara; Treu, Laura; Campanaro, Stefano; Giacomini, Alessio; Corich, Viviana

    2016-01-01

    From a technological point of view, yeast resistance to sulfite is of great interest and represents an important technological character for winemaking. Several mechanisms are involved, and strain-dependent strategies to obtain SO2 resistance can deeply influence wine quality, although this choice is less relevant in determining the technological performance of the strain during fermentation. In this study, to better understand the strain-specific mechanisms of resistance, 11 Saccharomyces cerevisiae strains, whose genomes have been previously sequenced, were selected. Their attitude towards sulfites, in terms of resistance and production, was evaluated, and RNA-sequencing of four selected strains was performed during fermentation process in synthetic grape must in the presence of SO2. Results demonstrated that at molecular level, the physical effect of SO2 triggered multiple stress responses in the cell and high tolerance to general enological stressing condition increased SO2 resistance. Adaptation mechanism due to high basal gene expression level rather than specific gene induction in the presence of sulfite seemed to be responsible in modulating strain resistance. This mechanism involved higher basal gene expression level of specific cell wall proteins, enzymes for lipid biosynthesis, and enzymes directly involved in SO2 assimilation pathway and efflux.

  7. Complete genome sequence of Rufibacter tibetensis strain 1351, a radiation-resistant bacterium from Tibet plateau.

    Science.gov (United States)

    Zhang, Yi; Yu, Can; Zhou, Mengzhou; Tang, Jingfeng; Li, Xin; Wang, Zhi; Li, Zhijun; Yao, Juan; Li, Pei; Zheng, Guobin; Chen, Xiong; Dai, Jun

    2015-12-20

    Rufibacter tibetensis strain 1351, isolated from the soil of the Tibet plateau of China, belongs to the family of Cytophagaceae. It is a red-pigmented, gram-negative, strictly aerobic and rod-shaped bacterium and shows resistance to UV radiation. Here, we report its complete genome sequence, which can help us find the key genes of the carotenoid biosynthesis and resistance to UV radiation.

  8. Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment.

    Science.gov (United States)

    Arendrup, Maiken Cavling; Patterson, Thomas F

    2017-08-15

    Invasive Candida infections remain an important cause of morbidity and mortality, especially in hospitalized and immunocompromised or critically ill patients. A limited number of antifungal agents from only a few drug classes are available to treat patients with these serious infections. Resistance can be either intrinsic or acquired. Resistance mechanisms are not exchanged between Candida; thus, acquired resistance either emerges in response to an antifungal selection pressure in the individual patient or, more rarely, occur due to horizontal transmission of resistant strains between patients. Although multidrug resistance is uncommon, increasing reports of multidrug resistance to the azoles, echinocandins, and polyenes have occurred in several Candida species, most notably Candida glabrata and more recently Candida auris. Drivers are overall antifungal use, subtherapeutic drug levels at sites of infection/colonization, drug sequestration in the biofilm matrix, and, in the setting of outbreaks, suboptimal infection control. Moreover, recent research suggests that DNA mismatch repair gene mutations may facilitate acquisition of resistance mutations in C. glabrata specifically. Diagnosis of antifungal-resistant Candida infections is critical to the successful management of patients with these infections. Reduction of unnecessary use of antifungals via antifungal stewardship is critical to limit multidrug resistance emergence. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  9. Evanescent radiation, quantum mechanics and the Casimir effect

    Science.gov (United States)

    Schatten, Kenneth H.

    1989-01-01

    An attempt to bridge the gap between classical and quantum mechanics and to explain the Casimir effect is presented. The general nature of chaotic motion is discussed from two points of view: the first uses catastrophe theory and strange attractors to describe the deterministic view of this motion; the underlying framework for chaos in these classical dynamic systems is their extreme sensitivity to initial conditions. The second interpretation refers to randomness associated with probabilistic dynamics, as for Brownian motion. The present approach to understanding evanescent radiation and its relation to the Casimir effect corresponds to the first interpretation, whereas stochastic electrodynamics corresponds to the second viewpoint. The nonlinear behavior of the electromagnetic field is also studied. This well-understood behavior is utilized to examine the motions of two orbiting charges and shows a closeness between the classical behavior and the quantum uncertainty principle. The evanescent radiation is used to help explain the Casimir effect.

  10. Numerical Treatment of Anisotropic Radiation Field Coupling with the Relativistic Resistive Magnetofluids

    CERN Document Server

    Takahashi, Hiroyuki R

    2013-01-01

    We develop a numerical scheme for solving a fully special relativistic resistive radiation magnetohydrodynamics. Our code guarantees conservations of total mass, momentum and energy. Radiation energy density and radiation flux are consistently updated using the M-1 closure method, which can resolve an anisotropic radiation fields in contrast to the Eddington approximation as well as the flux-limited diffusion approximation. For the resistive part, we adopt a simple form of the Ohm's law. The advection terms are explicitly solved with an approximate Riemann solver, mainly HLL scheme, and HLLC and HLLD schemes for some tests. The source terms, which describe the gas-radiation interaction and the magnetic energy dissipation, are implicitly integrated, relaxing the Courant-Friedrichs-Lewy condition even in optically thick regime or a large magnetic Reynolds number regime. Although we need to invert $4\\times 4$ (for gas-radiation interaction) and $3\\times 3$ (for magnetic energy dissipation) matrices at each grid ...

  11. Acquired Tumor Cell Radiation Resistance at the Treatment Site Is Mediated Through Radiation-Orchestrated Intercellular Communication

    Energy Technology Data Exchange (ETDEWEB)

    Aravindan, Natarajan, E-mail: naravind@ouhsc.edu [Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Aravindan, Sheeja; Pandian, Vijayabaskar; Khan, Faizan H.; Ramraj, Satish Kumar; Natt, Praveen [Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Natarajan, Mohan [Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States)

    2014-03-01

    Purpose: Radiation resistance induced in cancer cells that survive after radiation therapy (RT) could be associated with increased radiation protection, limiting the therapeutic benefit of radiation. Herein we investigated the sequential mechanistic molecular orchestration involved in radiation-induced radiation protection in tumor cells. Results: Radiation, both in the low-dose irradiation (LDIR) range (10, 50, or 100 cGy) or at a higher, challenge dose IR (CDIR), 4 Gy, induced dose-dependent and sustained NFκB-DNA binding activity. However, a robust and consistent increase was seen in CDIR-induced NFκB activity, decreased DNA fragmentation, apoptosis, and cytotoxicity and attenuation of CDIR-inhibited clonal expansion when the cells were primed with LDIR prior to challenge dose. Furthermore, NFκB manipulation studies with small interfering RNA (siRNA) silencing or p50/p65 overexpression unveiled the influence of LDIR-activated NFκB in regulating CDIR-induced DNA fragmentation and apoptosis. LDIR significantly increased the transactivation/translation of the radiation-responsive factors tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), cMYC, and SOD2. Coculture experiments exhibit LDIR-influenced radiation protection and increases in cellular expression, secretion, and activation of radiation-responsive molecules in bystander cells. Individual gene-silencing approach with siRNAs coupled with coculture studies showed the influence of LDIR-modulated TNF-α, IL-1α, cMYC, and SOD2 in induced radiation protection in bystander cells. NFκB inhibition/overexpression studies coupled with coculture experiments demonstrated that TNF-α, IL-1α, cMYC, and SOD2 are selectively regulated by LDIR-induced NFκB. Conclusions: Together, these data strongly suggest that scattered LDIR-induced NFκB-dependent TNF-α, IL-1α, cMYC, and SOD2 mediate radiation protection to the subsequent challenge dose in tumor cells.

  12. Defense mechanisms against radiation induced teratogenic damage in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kato, F.; Ootsuyama, A.; Nomoto, S.; Norimura, T. [Univ. of Occupational and Environmental Health, Kitakyushu, (Japan)

    2002-07-01

    Experimental studies with mice have established that fetuses at midgestational stage are highly susceptible to malformation at high, but not low, doses of radiation. When DNA damage is produced by a small amount of radiation, it is efficiently eliminated by DNA repair. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. In order to elucidate the essential role of p53 gene in apoptotic tissue repair, we compared the incidence of radiation-induced malformations and deaths (deaths after day 10) in wild-type p53 (+/+) mice and null p53 (-/-) mice. For p53 (+/+) mice, an X-ray dose of 2 Gy given at a high dose-rate (450 mGy/min) to fetuses at 9.5 days of gestation was highly lethal and considerably teratogenic whereas it was only slightly lethal but highly teratogenic for p53 (-/-) fetuses. This reciprocal relationship of radiosensitivity to malformations and deaths supports the notion that fetal tissues have a p53 -dependent idguardianln of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. When an equal dose of 2 Gy given at a 400-fold lower dose-rate (1.2 mGy/min), this dose became not teratogenic for p53 (+/+) fetuses exhibiting p53 -dependent apoptosis, whereas this dose remained teratogenic for p53 (-/-) fetuses unable to carry out apoptosis. Furthermore, when the dose was divided into two equal dose fractions (1+1 Gy) at high dose rate, separated by 24 hours, the incidences of malformations were equal with control level for p53 (+/+), but higher for p53 (-/-) mice. Hence, complete elimination of teratogenic damage from irradiated tissues requires a concerted cooperation of two mechanisms; proficient DNA repair and p53-dependent apoptotic tissue repair.

  13. Heat and mechanical resistance of zinc coating

    Directory of Open Access Journals (Sweden)

    Karel Horák

    2010-01-01

    Full Text Available The article is aimed at studying the effect of temperature on structure of intermetallic phases of the protective zinc layer. The main objective of the article is a description of the structure and the changes that can occur during the heating process. The first part of the article deals with the description of the structure and mechanical properties of the interfacial phases and their arrangement. The main part of the article is aimed at study of brittle intermetallic phases, which arise due to increased temperature. For this reason, a set of samples of steel CSN 11 321 (DC01 was prepared. These samples were subjected to thermal heating in the tempering furnace. Subsequently metallographic cross sections were prepared, observed and assessed using SEM microscopy and EDS analysis. Also accelerated corrosion tests and pull off bend tests were performed. Conclusion of the article is trying to explain the influence of intermetallic phases on degradation of the protective layer.

  14. Biochemical mechanisms for metaflumizone resistance in beet armyworm, Spodoptera exigua.

    Science.gov (United States)

    Tian, Xiangrui; Sun, Xingxing; Su, Jianya

    2014-07-01

    The metaflumizone, which belongs to the class of voltage-dependent sodium channel blockers, was registered to control Spodoptera exigua on vegetables in China in 2009. The present study revealed S. exigua has developed high resistance to this novel chemistry insecticide shortly after 2-3 years application in Guangdong Province of China. The metabolic mechanisms for metaflumizone resistance in this insect were analysed. The inhibitor of esterases greatly potentiates the toxicity of this chemical against the field resistant populations. The synergism ratio is 5.7 and 3.4-fold for S. exigua collected from Huizhou, Guangdong Province in 2011 and 2012, respectively. The activity of esterases in field populations (HZ12) is also significantly greater than that in the susceptible strain, and further significantly increased by challenge with metaflumizone for 3 generations. However, the inhibitor of P450s or GSTs only has slight synergism on metaflumizone toxicity against resistant populations, and there are no obvious differences in activities of P450s or GSTs between resistant populations and the susceptible strain. These results suggest that esterases might take pivotal role in conferring metabolic resistance to metaflumizone in the field populations of S. exigua, and P450s or GSTs are not involved in this resistance. Moreover, flavin-dependent monooxygenases (FMOs) are discovered to involve in metaflumizone resistance in the field populations of S. exigua. The FMO inhibitor, methimazole, potentiates metaflumizone toxicity in resistant larva of this species substantially. The synergism ratios for methimazole in resistant populations HZ11 and HZ12 were 3.1 and 1.9, respectively. Enzymatic assays also revealed higher FMO activities in resistant populations than in the susceptible strain, and successive selection with metaflumizone further increased the FMO activity in the field resistant population, but not significantly. The higher FMO activities in the older larval

  15. ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-10-1-0582 TITLE: ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer PRINCIPAL...ETS gene fusion status associated with clinical outcomes following radiation therapy , by analyzing both the collected biomarker and clinical data...denotes absence of an ERG fusion). ETS gene fusions status did not predict outcomes following radiation therapy , as demonstrated by Kaplan Meier

  16. Mechanisms of antibiotic resistance of Enterobacteriaceae family representatives

    Directory of Open Access Journals (Sweden)

    K. R. Kotsyuba

    2014-04-01

    Full Text Available The paper deals with the basic medical scheme of antibiotics use for treatment of lesions caused by enterobacteria and mechanisms of resistance of Enterobacteriaceae to different classes of antibiotics. It is known that the main mechanisms of resistance to antibiotics are enzymatic inactivation, modification of the target, efflux, violation of conduct through the membrane and formation of metabolic shunt. The most common cases of resistance to beta-lactams among Enterobacteriaceae relate to production of plasmid and chromosomal beta-lactamases, violation of the permeability of the outer membrane, and modification of target penicillin binding proteins. Active release of antibiotics from the cell, or efflux, in Enterobacteriaceae is used for maintaining resistance to tetracyclines, macrolides, carbapenems. Genes of efflux system are localized on plasmids and contribute to rapid spreading among Enterobacteriaceae. Mutations are the basis of resistance to novobiocinum and rifampicinum. Enzymatic inactivation by modifying is typical for resistance to aminoglycosides. Three groups of enzymes are engaged in the process, by adding the molecule of acetic acid, phosphate or adenine. Joining of these groups is irreversible and leads to complete loss of biological activity of the antibiotic. Resistance to aminoglycosides appears also due to inhibition of drug penetration, that is associated with genetically determined mechanisms of electron transport through the membrane. Resistance to quinolones and fluoroquinolones is associated with the modification of topoisomerase II and IV which are targets of these groups of antibiotics. Resistance is possible as a result of changes in the structure of the target, breaching of penetration into the cell, and active release from the cell. The highest level of resistance is develope in the case of two- or three-stage mutations in one or the other, or both, subunits in different genes. At the same time, for breaching of

  17. Mechanisms of resistance to bacteriocins targeting the mannose phosphotransferase system.

    Science.gov (United States)

    Kjos, Morten; Nes, Ingolf F; Diep, Dzung B

    2011-05-01

    The membrane proteins IIC and IID of the mannose phosphotransferase system (Man-PTS) together form a membrane-located complex that serves as a receptor for several different bacteriocins, including the pediocin-like class IIa bacteriocins and the class IIc bacteriocin lactococcin A. Bacterial strains sensitive to class IIa bacteriocins readily give rise to resistant mutants upon bacteriocin exposure. In the present study, we have therefore investigated lactococcin A-resistant mutants of Lactococcus lactis as well as natural food isolates of Listeria monocytogenes with different susceptibilities to class IIa bacteriocins. We found two major mechanisms of resistance. The first involves downregulation of Man-PTS gene expression, which takes place both in spontaneous resistant mutants and in natural resistant isolates. The second involves normal expression of the Man-PTS system, but the underlying mechanism of resistance for these cells is unknown. In some cases, the resistant phenotype was linked to a shift in the metabolism; i.e., reduced growth on glucose due to reduction in Man-PTS expression was accompanied by enhanced growth on another sugar, such as galactose. The implications of these findings in terms of metabolic heterogeneity are discussed.

  18. Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: resistance mechanisms and implications for therapy.

    Science.gov (United States)

    Zavascki, Alexandre P; Carvalhaes, Cecília G; Picão, Renata C; Gales, Ana C

    2010-01-01

    Pseudomonas aeruginosa and Acinetobacter baumannii are major nosocomial pathogens worldwide. Both are intrinsically resistant to many drugs and are able to become resistant to virtually any antimicrobial agent. An increasing prevalence of infections caused by multidrug-resistant (MDR) isolates has been reported in many countries. The resistance mechanisms of P. aeruginosa and A. baumannii include the production of beta-lactamases, efflux pumps, and target-site or outer membrane modifications. Resistance to multiple drugs is usually the result of the combination of different mechanisms in a single isolate or the action of a single potent resistance mechanism. There are many challenges in the treatment of MDR P. aeruginosa and A. baumannii, especially considering the absence of new antimicrobials in the drug-development pipeline. In this review, we present the major resistance mechanisms of P. aeruginosa and A. baumannii, and discuss how they can affect antimicrobial therapy, considering recent clinical, microbiological, pharmacokinetic and pharmacodynamic findings of the main drugs used to treat MDR isolates.

  19. Lead resistant bacteria: lead resistance mechanisms, their applications in lead bioremediation and biomonitoring.

    Science.gov (United States)

    Naik, Milind Mohan; Dubey, Santosh Kumar

    2013-12-01

    Lead (Pb) is non-bioessential, persistent and hazardous heavy metal pollutant of environmental concern. Bioremediation has become a potential alternative to the existing technologies for the removal and/or recovery of toxic lead from waste waters before releasing it into natural water bodies for environmental safety. To our best knowledge, this is a first review presenting different mechanisms employed by lead resistant bacteria to resist high levels of lead and their applications in cost effective and eco-friendly ways of lead bioremediation and biomonitoring. Various lead resistant mechanisms employed by lead resistant bacteria includes efflux mechanism, extracellular sequestration, biosorption, precipitation, alteration in cell morphology, enhanced siderophore production and intracellular lead bioaccumulation.

  20. Role of graphene layers on the radiation resistance of copper-graphene nanocomposite: Inhibiting the expansion of thermal spike

    Science.gov (United States)

    Huang, Hai; Tang, Xiaobin; Chen, Feida; Liu, Jian; Chen, Da

    2017-09-01

    Metal-graphene nanocomposites are expected to have excellent radiation resistance. The intrinsic role of the graphene layers (GrLs) in their performance has not been fully understood. Five copper-graphene nanocomposite (CGNC) systems were used to investigate the detailed mechanisms underpinning this behaviour by atomistic simulation. Results showed that GrLs can reduce the formation, growth, and intensity of the thermal spike of CGNC; this effect became more evident with the increasing number of layers of graphene. The role of the GrLs can be explained by three mechanisms: first, the ultra-strength C-C bonds of graphene hindered the penetration of high-energy atoms, second, the number of recoiled atoms decreased with the increasing number of layers of graphene, and third, the energy dissipation along the graphene planes also indirectly weakened the damage caused to the entire system. These mechanisms may provide a pathway to prevent material degradation in extreme radiation environments.

  1. Molecular investigation of the radiation resistance of edible cyanobacterium Arthrospira sp. PCC 8005

    OpenAIRE

    2015-01-01

    The aim of this work was to characterize in detail the response of Arthrospira to ionizing radiation, to better understand its radiation resistance capacity. Live cells of Arthrospira sp. PCC 8005 were irradiated with 60Co gamma rays. This study is the first, showing that Arthrospira is highly tolerant to gamma rays, and can survive at least 6400 Gy (dose rate of 527 Gy h−1), which identified Arthrospira sp. PCC 8005 as a radiation resistant bacterium. Biochemical, including proteomic and tra...

  2. Metallic Photonic Bandgap Resonant Antennas with High Directivity and High Radiation Resistance

    Institute of Scientific and Technical Information of China (English)

    林青春; 符建; 何赛灵; 章坚武

    2002-01-01

    A metallic photonic bandgap (MPBG) resonant antenna is introduced, which has novel characteristics (such as high directivity and high radiation resistance for a certain range of frequencies) as compared to conventional MPBG antennas. The linear MPBG resonant antenna is formed by infinitely long metallic rods in vacuum. The numerical results for the radiation pattern and the radiation resistance are presented. By adjusting the struct ure of the MPBG resonant antenna and its working frequency, an optimal structure is achieved. The physical reasons for the novel characteristics of the MPBG resonant antenna are also explained.

  3. Testing and Modeling of Mechanical Characteristics of Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels;

    2003-01-01

    The dynamic mechanical response of resistance welding machine is very important to the weld quality in resistance welding especially in projection welding when collapse or deformation of work piece occurs. It is mainly governed by the mechanical parameters of machine. In this paper, a mathematical...... for both upper and lower electrode systems. This has laid a foundation for modeling the welding process and selecting the welding parameters considering the machine factors. The method is straightforward and easy to be applied in industry since the whole procedure is based on tests with no requirements...

  4. Macrolide resistance mechanisms in Enterobacteriaceae: Focus on azithromycin.

    Science.gov (United States)

    Gomes, Cláudia; Martínez-Puchol, Sandra; Palma, Noemí; Horna, Gertrudis; Ruiz-Roldán, Lidia; Pons, Maria J; Ruiz, Joaquim

    2017-02-01

    From its introduction in 1952 onwards, the clinical use of macrolides has been steadily increasing, both in human and veterinary medicine. Although initially designed to the treatment of Gram-positive microorganisms, this antimicrobial family has also been used to treat specific Gram-negative bacteria. Some of them, as azithromycin, are considered in the armamentarium against Enterobacteriaceae infections. However, the facility that this bacterial genus has to gain or develop mechanisms of antibiotic resistance may compromise the future usefulness of these antibiotics to fight against Enterobacteriaceae infections. The present review is focused on the mechanisms of macrolide resistance, currently described in Enterobacteriaceae.

  5. Mechanism of Interaction between Ionizing Radiation and Chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Lee, B. H.; Shin, H. S. (and others)

    2008-03-15

    This research project has been carried out jointly with INP (Poland) to develop technologies for 'Mechanism of Interaction between ionizing radiation and chemicals{sup .} Several biological end-points were assessed in experimental organisms such as higher plants, rats, cell lines and yeast cells to establish proper bioassay techniques. The Tradescantia somatic cell mutation assay was carried out, and immunohistochemistry and hormone assays were done in Fisher 344 rats and cell lines to analyse the combined effect of ionizing radiation with mercury chloride. Using the common regularities of combined actions of two factors, a theoretical model was established, and applied to the thermo radiation action and synergism between two chemicals, as well. The model approach made it possible to predict the condition under which the maximum synergism could be attained. The research results were published in high standard journals and presented in the scientific conferences to verify KAERI's current technology level. The experience of collaboration can be used as a fundamental tool for multinational collaboration, and make the role of improving relationship between Korea and Poland.

  6. Degradation mechanisms of cable insulation materials during radiation-thermal ageing in radiation environment

    Science.gov (United States)

    Seguchi, Tadao; Tamura, Kiyotoshi; Ohshima, Takeshi; Shimada, Akihiko; Kudoh, Hisaaki

    2011-02-01

    Radiation and thermal degradation of ethylene-propylene rubber (EPR) and crosslinked polyethylene (XLPE) as cable insulation materials were investigated by evaluating tensile properties, gel-fraction, and swelling ratio, as well as by the infrared (FTIR) analysis. The activation energy of thermal oxidative degradation changed over the range 100-120 °C for both EPR and XLPE. This may be attributed to the fact that the content of an antioxidant used as the stabilizer for polymers decreases by evaporation during thermal ageing at high temperatures. The analysis of antioxidant content and oxidative products in XLPE as a model sample showed that a small amount of antioxidant significantly reduced the extent of thermal oxidation, but was not effective for radiation induced oxidation. The changes in mechanical properties were well reflected by the degree of oxidation. A new model of polymer degradation mechanisms was proposed where the degradation does not take place by chain reaction via peroxy radical and hydro-peroxide. The role of the antioxidant in the polymer is the reduction of free radical formation in the initiation step in thermal oxidation, and it could not stop radical reactions for either radiation or thermal oxidation.

  7. Degradation mechanisms of cable insulation materials during radiation-thermal ageing in radiation environment

    Energy Technology Data Exchange (ETDEWEB)

    Seguchi, Tadao, E-mail: seguchi@aj.wakwak.co [Japan Atomic Energy Agency, Tokai 319-1195 (Japan); Tamura, Kiyotoshi; Ohshima, Takeshi; Shimada, Akihiko [Japan Atomic Energy Agency, Tokai 319-1195 (Japan); Kudoh, Hisaaki [University of Tokyo, Tokai 319-1195 (Japan)

    2011-02-15

    Radiation and thermal degradation of ethylene-propylene rubber (EPR) and crosslinked polyethylene (XLPE) as cable insulation materials were investigated by evaluating tensile properties, gel-fraction, and swelling ratio, as well as by the infrared (FTIR) analysis. The activation energy of thermal oxidative degradation changed over the range 100-120 {sup o}C for both EPR and XLPE. This may be attributed to the fact that the content of an antioxidant used as the stabilizer for polymers decreases by evaporation during thermal ageing at high temperatures. The analysis of antioxidant content and oxidative products in XLPE as a model sample showed that a small amount of antioxidant significantly reduced the extent of thermal oxidation, but was not effective for radiation induced oxidation. The changes in mechanical properties were well reflected by the degree of oxidation. A new model of polymer degradation mechanisms was proposed where the degradation does not take place by chain reaction via peroxy radical and hydro-peroxide. The role of the antioxidant in the polymer is the reduction of free radical formation in the initiation step in thermal oxidation, and it could not stop radical reactions for either radiation or thermal oxidation.

  8. Mechanisms of resistance to decitabine in the myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Taichun Qin

    Full Text Available PURPOSE: The DNA methylation inhibitor 5-aza-2'-deoxycytidine (DAC is approved for the treatment of myelodysplastic syndromes (MDS, but resistance to DAC develops during treatment and mechanisms of resistance remain unknown. Therefore, we investigated mechanisms of primary and secondary resistance to DAC in MDS. PATIENTS AND METHODS: We performed Quantitative Real-Time PCR to examine expression of genes related to DAC metabolism prior to therapy in 32 responders and non-responders with MDS as well as 14 patients who achieved a complete remission and subsequently relapsed while on therapy (secondary resistance. We then performed quantitative methylation analyses by bisulfite pyrosequencing of 10 genes as well as Methylated CpG Island Amplification Microarray (MCAM analysis of global methylation in secondary resistance. RESULTS: Most genes showed no differences by response, but the CDA/DCK ratio was 3 fold higher in non-responders than responders (P<.05, suggesting that this could be a mechanism of primary resistance. There were no significant differences at relapse in DAC metabolism genes, and no DCK mutations were detected. Global methylation measured by the LINE1 assay was lower at relapse than at diagnosis (P<.05. On average, the methylation of 10 genes was lower at relapse (16.1% compared to diagnosis (18.1% (P<.05. MCAM analysis showed decreased methylation of an average of 4.5% (range 0.6%-9.7% of the genes at relapse. By contrast, new cytogenetic changes were found in 20% of patients. CONCLUSION: Pharmacological mechanisms are involved in primary resistance to DAC, whereas hypomethylation does not prevent a relapse for patients with DAC treatment.

  9. Multiple-stress tolerance of ionizing radiation-resistant bacterial isolates obtained from various habitats: correlation between stresses.

    Science.gov (United States)

    Shukla, Manish; Chaturvedi, Ruchi; Tamhane, Dhruti; Vyas, Pranav; Archana, G; Apte, Shree; Bandekar, J; Desai, Anjana

    2007-02-01

    Isolation of five ionizing radiation (IR)-resistant bacteria by screening of isolates from various habitats classified as common and stressed is reported. IR-resistant isolates exhibited varying degrees of resistance to gamma-radiation and were classified as highly and moderately radiation resistant. Resistance to ultraviolet (UV) radiation correlated well with gamma-radiation resistance, whereas a comparable desiccation resistance for all the highly and moderately radiation-resistant isolates was observed. However, salt tolerance failed to correlate with IR resistance, indicating a divergent evolution of the salt tolerance and radiation resistance. Characterization of isolates by the amplified rDNA restriction analysis profiling attested to the clustering of these isolates with their stress phenotype. 16S rRNA gene-based analysis of the isolates showed that the bacteria with similar-resistance physiologies clustered together and belonged to related genera. Hydrogen peroxide resistance and mitomycin survival patterns of the isolates indicated the roles of oxidative-stress tolerance in desiccation survival and recombination repair in higher radiation resistance, respectively.

  10. Mechanisms of biotic resistance across complex life cycles.

    Science.gov (United States)

    Rius, Marc; Potter, Elaine E; Aguirre, J David; Stachowicz, John J

    2014-01-01

    Biotic resistance is the ability of communities to inhibit the establishment, spread or impact of novel species. However, the interactions that underlie biotic resistance depend heavily on the contexts in which species interact. Consequently, studies of biotic resistance that consider single processes, patches, species or life-history stages may provide an incomplete picture of the capacity for communities to resist invasion. Many organisms have multiphasic life cycles, where individuals can occupy distinct niches at different stages of the life history. Generally, studies of biotic resistance focus on interactions within a single life-history stage, and interactions at other life-history stages are overlooked. Here, we demonstrate that different mechanisms of biotic resistance occur across the life history and together limit the invasion success of an introduced marine invertebrate (Ciona intestinalis) in Northern California. We tested the role of interactions (competition and predation) with the resident community in limiting the abundance of Ciona through experiments conducted on fertilization, larval survival, settlement, early postsettlement survival, and the survival of juveniles and adults. Under some circumstances, Ciona became abundant in mid-successional stages and showed more rapid growth rates than a morphologically similar native species, Ascidia ceratodes. However, predators reduced Ciona abundance much more than that of Ascidia at several life stages. Furthermore, Ciona appeared to be a weaker competitor at the adult stage. Early life-history interactions with other sessile species at the fertilization, larval and recruit stages had modest to no effects on Ciona abundance. The presence of biotic resistance mechanisms acting at multiple life stages, and potentially under different conditions, suggests that different components of biotic resistance interact to enhance the resident community's resistance to invasion.

  11. Radiation induced oxidative degradation of polymers. 3. Effect of radiation on mechanical properties. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Seguchi, T.; Arakawa, K.; Ito, M.; Hayakawa, N.; Machi, S. (Japan Atomic Energy Research Inst., Takasaki, Gunma. Takasaki Radiation Chemistry Research Establishment)

    1983-01-01

    The changes of mechanical properties of various kinds of polyethylene (PE) and ethylene-propylene copolymer (EPR) with the irradiation in air, in oxygen of 10 atm, and under vacuum were investigated. The decrease in the elongation (Esub(b)) and the tensile strength (Tsub(b)) of PE by the irradiation in oxygen is larger than under vacuum. The changes of Esub(b) well reflect the degradation of PE. In case of EPR, the Tsub(b) decreases sharply with dose in any environments, and the Esub(b) decreases under vacuum to a larger extent than in oxygen. The modulus at 200% elongation of EPR increases with dose under vacuum, but decreases in oxygen. When the samples were irradiated in air, the changes of the mechanical properties were the intermediate between oxygen and vacuum and dependent on the ratio of oxidation and non-oxidation layers in the film. The antioxidant (Irganox 1010 or DPPD) mixed in polymers was found to retard effectively the polymer degradation by the irradiation in oxygen.

  12. Fenpyroximate resistance in Tetranychus urticae (Acari: Tetranychidae): cross-resistance and biochemical resistance mechanisms.

    Science.gov (United States)

    Kim, Young-Joon; Lee, Si-Hyeock; Lee, Si-Woo; Ahn, Young-Joon

    2004-10-01

    A field colony of the Two-spotted spider mite, Tetranychus urticae (Koch), resistant to fenpyroximate was further selected with fenpyroximate 5SC for 20 generations at a selection pressure of 30-50% mortality (designated as FR-20 strain). Resistance and cross-resistance levels of the FR-20 strain to 18 acaricides were determined using a spray method. The FR-20 strain was extremely resistant to fenpyroximate [resistance ratio (RR) 252]. The strain exhibited extremely strong positive cross-resistance to acrinathrin (RR 196), and high levels of resistance to benzoximate (RR 55) and propargite (RR 64). Moderate levels of cross-resistance (RR 11-40) to abamectin, fenbutatin oxide, fenpropathrin, pyridaben, pyridaben + bifenthrin and tebufenpyrad were observed. The FR-20 strain showed low levels of resistance (RR fenazaquin and milbemectin. Synergist experiments with different metabolic inhibitors revealed that piperonyl butoxide had the greatest effect on the efficacy of fenpyroximate, followed by iprobenfos and triphenyl phosphate. In a comparative assay with detoxifying enzymes, the FR-20 strain showed 2.5-fold higher activity in p-nitroanisole-O-demethylation, and 2.5- and 2.2-fold higher activities in alpha- and beta-naphthyl acetate hydrolysis, respectively. These results suggested that enhanced activities of both mixed-function oxidases and esterases likely contribute to the fenpyroximate resistance of the FR-20 strain of T urticae.

  13. Longevity, oxygen toxicity and radiation-enhanced resistance to oxygen in tribolium confusum

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y.J.

    1985-01-01

    Sublethal doses of ionizing radiation increase longevity in a variety of insects suggesting that irradiation may retard the age-dependent decline of physiological functions. There have been no systematic investigations of the response of irradiated populations to stress, however. The authors have demonstrated that resistance of adult flour beetles, Tribolium confusum, to oxygen poisoning declines progressively with age. They have examined oxygen resistance of irradiated populations of T. confusum as a function of age at irradiation, of time after irradiation, and of radiation dose and of dose-modifying factors. Shortly after gamma-irradiation, flour beetles exhibited a decline in resistance to oxygen toxicity. Then, about two weeks after irradiation, the LD/sub 50/ exposure time in pure oxygen was much greater than that of nonirradiated beetles, and this enhanced resistance persisted for about 6 months. The magnitude of the enhancement was a function of dose, decreased with increasing age at irradiation, and was modified by radiation factors. Sublethal irradiation under anoxia, at low dose rate, or with dose fractionation reduced the development of oxygen resistance to approximately the same degree that it reduced acute radiation lethality . Radiation-enhanced resistance to stress may be an important factor in the increased longevity of irradiated insects.

  14. Mechanism of resistance of evolved glyphosate-resistant Palmer amaranth (Amaranthus palmeri).

    Science.gov (United States)

    Gaines, Todd A; Shaner, Dale L; Ward, Sarah M; Leach, Jan E; Preston, Christopher; Westra, Philip

    2011-06-01

    Evolved glyphosate resistance in weedy species represents a challenge for the continued success and utility of glyphosate-resistant crops. Glyphosate functions by inhibiting the plant enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). The resistance mechanism was determined in a population of glyphosate-resistant Palmer amaranth from Georgia (U.S.). Within this population, glyphosate resistance correlates with increases in (a) genomic copy number of EPSPS, (b) expression of the EPSPS transcript, (c) EPSPS protein level, and (d) EPSPS enzymatic activity. Dose response results from the resistant and an F(2) population suggest that between 30 and 50 EPSPS genomic copies are necessary to survive glyphosate rates between 0.5 and 1.0 kg ha(-1). These results further confirm the role of EPSPS gene amplification in conferring glyphosate resistance in this population of Palmer amaranth. Questions remain related to how the EPSPS amplification initially occurred and the occurrence of this mechanism in other Palmer amaranth populations and other glyphosate-resistant species.

  15. Pathogen derived resistance to Potato virus Y: mechanisms and risks

    Directory of Open Access Journals (Sweden)

    T. MÄKI-VALKAMA

    2008-12-01

    Full Text Available Since the concept of pathogen derived resistance (PDR was proposed in 1985, genetic transformation of plants to express virus-derived sequences has been used to engineer resistance to many viruses. This paper reviews PDR approaches to Potato virus Y (PVY, type member of the genus Potyvirus. PDR to viruses operates often through RNA-mediated resistance mechanisms that do not require protein expression. Studies on the RNA-mediated resistance have led to the discovery of post-transcriptional gene silencing (PTGS, a mechanism that controls gene expression in eukaryotic cells and provides natural protection against virus infections. Viruses, in turn, can suppress the PTGS with some of their proteins, such as the helper component-proteinase protein of PVY. Expression of PVY proteins in transgenic plants entails a risk for heterologous encapsidation or synergism with viruses that infect the PVY-resistant transgenic plant. These risks are avoided using RNA-mediated resistance, but a risk still exists for recombination between the transgene transcript and the RNA genome of the infecting virus, which may create a virus with altered properties. The harmful consequences can be limited to some extent by removing functional motifs from the viral sequence used as a transgene.;

  16. Mechanisms of radiation-induced emesis. Technical report, 10 February 1984-1 March 1987

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, D.O.

    1988-08-31

    Nausea and vomiting following radiation exposure are factors which may seriously limit the ability of humans to perform in military situations and are side effects of such significance in radiation therapy that they may limit the patient's acceptance of treatment regimes (1). At doses of 1.5 Gy approximately 50% of humans experience nausea and vomiting, while at 3.0 Gy the figure approaches 100%. While irradiation almost anywhere may produce symptoms, the upper abdomen is the most-sensitive site. Dogs, cats, and monkeys also vomit on exposure to ionizing radiation, although cats and monkeys are considerably more resistant than dogs and man. These studies were designed to attempt to determine the roles of the area postrema and the vagus in radiation-induced emesis by ablation and electrophysiological studies, and to test the effects of some drugs on the emetic response. In addition, the authorrecorded from neurons in the dog area postrema, applying substances which may be emetic, in an attempt to determine which transmitters, peptides and hormones might function as chemical mediators of emesis. Finally, he have tested the emetic effects of some of these substances given intravenously in awake dogs, with particular emphasis on study of the mechanism of action of emetic agents on the area postrema neurons.

  17. Comments on the Japanese study of the radiation resistance of the bioburden of medical devices

    Energy Technology Data Exchange (ETDEWEB)

    Whitby, James L

    1998-06-01

    The findings obtained in an extensive study of the radiation resistance electrons, even with a broad energy sa number of medical devices has been carried out by Takehisa et al. and reported in this number of this Journal. The following paper reviews the expected behaviour of the reported populations under the conditions specified in ISO Standard 11137 Method 1, which is widely used in the determination of the radiation sterilization dose required for sterilization of medical devices. The populations reported for 'dry' devices contain a higher proportion of more radiation resistant microbes than that found in the standard distribution of resistance (SDR) that is used for setting the sterilization dose in Method 1. A possible alternative dose setting method for more resistant microbial populations is introduced and discussed.

  18. Resistive switching characteristics and mechanisms in silicon oxide memory devices

    Science.gov (United States)

    Chang, Yao-Feng; Fowler, Burt; Chen, Ying-Chen; Zhou, Fei; Wu, Xiaohan; Chen, Yen-Ting; Wang, Yanzhen; Xue, Fei; Lee, Jack C.

    2016-05-01

    Intrinsic unipolar SiOx-based resistance random access memories (ReRAM) characterization, switching mechanisms, and applications have been investigated. Device structures, material compositions, and electrical characteristics are identified that enable ReRAM cells with high ON/OFF ratio, low static power consumption, low switching power, and high readout-margin using complementary metal-oxide semiconductor transistor (CMOS)-compatible SiOx-based materials. These ideas are combined with the use of horizontal and vertical device structure designs, composition optimization, electrical control, and external factors to help understand resistive switching (RS) mechanisms. Measured temperature effects, pulse response, and carrier transport behaviors lead to compact models of RS mechanisms and energy band diagrams in order to aid the development of computer-aided design for ultralarge-v scale integration. This chapter presents a comprehensive investigation of SiOx-based RS characteristics and mechanisms for the post-CMOS device era.

  19. Cross-resistance of bisultap resistant strain of Nilaparvata lugens and its biochemical mechanism.

    Science.gov (United States)

    Ling, Shanfeng; Zhang, Runjie

    2011-02-01

    The resistant (R) strain of the planthopper Nilaparvata lugens (Stål) selected for bisultap resistance displayed 7.7-fold resistance to bisultap and also had cross-resistance to nereistoxin (monosultap, thiocyclam, and cartap), chlorpyrifos, dimethoate, and malathion but no cross-resistance to buprofezin, imidacloprid, and fipronil. To find out the biochemical mechanism of resistance to bisultap, biochemical assay was done. The results showed that cytochrome P450 monooxygenases (P450) activity in R strain was 2.71-fold that in susceptible strain (S strain), in which the changed activity for general esterase (EST) was 1.91 and for glutathione S-transferases only 1.32. Piperonyl butoxide (PBO) could significantly inhibit P450 activity (percentage of inhibition [PI]: 37.31%) in the R strain, with ESTs PI = 16.04% by triphenyl phosphate (TPP). The results also demonstrated that diethyl maleate had no synergism with bisultap. However, PBO displayed significant synergism in three different strains, and the synergism increased with resistance (S strain 1.42, Lab strain, 2.24 and R strain, 3.23). TPP also showed synergism for three strains, especially in R strain (synergistic ratio = 2.47). An in vitro biochemical study and in vivo synergistic study indicated that P450 might be play important role in the biochemical mechanism of bisultap resistance and that esterase might be the important factor of bisultap resistance. Acetylcholinesterase (AChE) insensitivity play important role in bisultap resistance. We suggest that buprofezin, imidacloprid, and fipronil could be used in resistance management programs for N. lugens via alternation and rotation with bisultap.

  20. Correlation of electromagnetic radiation emitted from coal or rock to supporting resistance

    Institute of Scientific and Technical Information of China (English)

    JIA Hui-lin; WANG En-yuan; SONG Xiao-yan; ZHANG Hong-jie; LI Zhong-hui

    2009-01-01

    More accurate forecasting of rock burst might be possible from observations of electromagnetic radiation emitted in the mine. We analyzed experimental observations and field data from the Muchengjian coal mine to study the relationship between electromagnetic radiation signal intensity and stress during the fracturing of coal, or rock, and samples under load. The results show that the signal intensity is positively correlated with stress. In addition, we investigated the change in the electromagnetic radiation intensity, the supporting resistance in a real coal mine environment, and the coal or rock stress in the mining area. The data analysis indicates that: 1) electromagnetic radiation intensity can accurately reflect the distribution of stress in the mining area; and, 2) there is a correlation between electromagnetic radiation intensity and supporting resistance. The research has some practical guiding significance for rock burst forecasting and for the prevention of accidents in coal mines.

  1. Mechanisms of Helicobacter pylori antibiotic resistance and molecular testing

    Directory of Open Access Journals (Sweden)

    Toshihiro eNishizawa

    2014-10-01

    Full Text Available Antibiotic resistance in Helicobacter pylori (H. pylori is the main factor affecting the efficacy of current treatment methods against infection caused by this organism. The traditional culture methods for testing bacterial susceptibility to antibiotics are expensive and require 10 to 14 days. Since resistance to clarithromycin, fluoroquinolone, and tetracycline seems to be exclusively caused by specific mutations in a small region of the responsible gene, molecular methods offer an attractive alternative to the above-mentioned techniques. The technique of polymerase chain reaction (PCR is an accurate and rapid method for the detection of mutations that confer antibiotic resistance. This review highlights the mechanisms of antibiotic resistance in H. pylori and the molecular methods for antibiotic susceptibility testing.

  2. Lipid-induced insulin resistance: unravelling the mechanism

    Science.gov (United States)

    Samuel, Varman T; Petersen, Kitt Falk; Shulman, Gerald I

    2010-01-01

    Insulin resistance has long been associated with obesity. More than 40 years ago, Randle and colleagues postulated that lipids impaired insulin-stimulated glucose use by muscles through inhibition of glycolysis at key points. However, work over the past two decades has shown that lipid-induced insulin resistance in skeletal muscle stems from defects in insulin-stimulated glucose transport activity. The steatotic liver is also resistant to insulin in terms of inhibition of hepatic glucose production and stimulation of glycogen synthesis. In muscle and liver, the intracellular accumulation of lipids—namely, diacylglycerol—triggers activation of novel protein kinases C with subsequent impairments in insulin signalling. This unifying hypothesis accounts for the mechanism of insulin resistance in obesity, type 2 diabetes, lipodystrophy, and ageing; and the insulin-sensitising effects of thiazolidinediones. PMID:20609972

  3. Pool of resistance mechanisms to glyphosate in Digitaria insularis.

    Science.gov (United States)

    de Carvalho, Leonardo Bianco; Alves, Pedro Luis da Costa Aguiar; González-Torralva, Fidel; Cruz-Hipolito, Hugo Enrique; Rojano-Delgado, Antonia María; De Prado, Rafael; Gil-Humanes, Javier; Barro, Francisco; de Castro, María Dolores Luque

    2012-01-18

    Digitaria insularis biotypes resistant to glyphosate have been detected in Brazil. Studies were carried out in controlled conditions to determine the role of absorption, translocation, metabolism, and gene mutation as mechanisms of glyphosate resistance in D. insularis. The susceptible biotype absorbed at least 12% more (14)C-glyphosate up to 48 h after treatment (HAT) than resistant biotypes. High differential (14)C-glyphosate translocation was observed at 12 HAT, so that >70% of the absorbed herbicide remained in the treated leaf in resistant biotypes, whereas 42% remained in the susceptible biotype at 96 HAT. Glyphosate was degraded to aminomethylphosphonic acid (AMPA), glyoxylate, and sarcosine by >90% in resistant biotypes, whereas a small amount of herbicide (up to 11%) was degraded by the susceptible biotype up to 168 HAT. Two amino acid changes were found at positions 182 and 310 in EPSPS, consisting of a proline to threonine and a tyrosine to cysteine substitution, respectively, in resistant biotypes. Therefore, absorption, translocation, metabolism, and gene mutation play an important role in the D. insularis glyphosate resistance.

  4. Mechanisms of resistance to HER2 target therapy.

    Science.gov (United States)

    Tortora, Giampaolo

    2011-01-01

    In the past years, several agents targeting signaling proteins critical for breast cancer growth and dissemination entered clinical evaluation. They include drugs directed against the HER/ErbB family of receptor tyrosine kinases, especially HER2; several downstream signal transducers; and proteins involved in tumor angiogenesis and dissemination. Unfortunately, resistance to targeted agents is a quite common feature, and understanding of the molecular mechanisms predicting response or failure has become a crucial issue to optimize treatment and select patients who are the best candidates to respond. The neoadjuvant setting offers unique opportunities allowing tumor sampling and search for molecular determinants of response. A variety of tumor and host factors may account for the onset of resistance. Major progress has been made in the understanding of the mechanisms involved in the primary and acquired resistance to targeted agents, especially the anti-HER2 drugs, which play a pivotal role in the weaponry against breast cancer.

  5. Mechanisms of Drug Resistance in Relapse and Refractory Multiple Myeloma

    Science.gov (United States)

    Yang, Wen-Chi; Lin, Sheng-Fung

    2015-01-01

    Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients eventually relapse or become refractory to current treatments. Although the treatments have improved, the major problem in MM is resistance to therapy. Clonal evolution of MM cells and bone marrow microenvironment changes contribute to drug resistance. Some mechanisms affect both MM cells and microenvironment, including the up- and downregulation of microRNAs and programmed death factor 1 (PD-1)/PD-L1 interaction. Here, we review the pathogenesis of MM cells and bone marrow microenvironment and highlight possible drug resistance mechanisms. We also review a potential molecular targeting treatment and immunotherapy for patients with refractory or relapse MM. PMID:26649299

  6. Molecular mechanisms of cisplatin resistance in cervical cancer

    Directory of Open Access Journals (Sweden)

    Zhu H

    2016-06-01

    Full Text Available Haiyan Zhu, Hui Luo, Wenwen Zhang, Zhaojun Shen, Xiaoli Hu, Xueqiong Zhu Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. Keywords: cisplatin, epithelial–mesenchymal transition, microRNA, molecular mechanism, resistance

  7. Mechanisms of resistance to carbapenems in meropenem- resistant Acinetobacter isolates from clinical samples

    Directory of Open Access Journals (Sweden)

    Sinha M

    2007-01-01

    Full Text Available Purpose: To analyze the resistance mechanisms in Acinetobacter species by phenotypic methods. Methods: Antibiotic susceptibility profile for 150 clinical isolates of Acinetobacte r was determined by the standard disk diffusion method. Isolates detected to be meropenem resistant were tested further by broth microdilution minimum inhibitory concentration (MIC for meropenem. The resistant isolates were also tested for metallo β -lactamase (MBL production by the double-disk approximation test, for AmpC beta-lactamase production and efflux pump detection by agar microdilution MIC with and without reserpine. Results: Twenty-one isolates were found resistant to meropenem by the standard disk diffusion method. Nine samples were from patients admitted in intensive care units (ICUs. Broth microdilution MICs of the isolates revealed low-level resistance to meropenem. MBL was not produced by any of these isolates. AmpC β -lactamases were produced by nine (43% isolates. ′Efflux pump′-mediated resistance to meropenem was detected in two out of nine random isolates tested for the same . Conclusions: Carbapenem resistance is not uncommon in Acinetobacter isolates. AmpC production may cause carbapenem resistance. MBL and efflux pump may not be important causes of carbapenem resistance.

  8. Prevalence and characterisation of quinolone resistance mechanisms in Salmonella spp.

    Science.gov (United States)

    Wasyl, Dariusz; Hoszowski, Andrzej; Zając, Magdalena

    2014-07-16

    The study was focused on characterisation of quinolone resistance mechanisms in Salmonella isolated from animals, food, and feed between 2008 and 2011. Testing of Minimal Inhibitory Concentrations revealed 6.4% of 2680 isolates conferring ciprofloxacin resistance. Simultaneously 37.7% and 40.8% were accounted for, respectively, nalidixic acid and ciprofloxacin Non Wild-Type populations. Amplification and sequencing of quinolone resistance determining region of topoisomerases genes in 44 isolates identified multiple amino-acid substitutions in gyrA at positions Ser83 (N=22; → Leu, → Phe, → Tyr), Asp87 (N=22; → Asn, → Gly, → Tyr) and parC (Thr57Ser, N=23; Ala141Ser, N=1). No relevant mutations were identified in gyrB and parE. Twelve patterns combining one or two substitutions were related to neither serovar nor ciprofloxacin MIC. In 92 isolates suspected for plasmid mediated quinolone resistance two qnr alleles were found: qnrS1 (or qnrS3; N=50) and qnrB19 (or qnrB10; N=24). Additionally, two isolates with chromosomally encoded mechanisms carried qnrS1 and qnrS2. All tested isolates were negative for qnrA, qnrC, qnrD, qepA, aac(6')-Ib-cr. Both chromosomal and plasmid mediated quinolone resistance determinants were found in several Salmonella serovars and Pulsed Field Gel Electrophoresis was used to assess phylogenetic similarity of selected isolates (N=82). Salmonella Newport was found to accumulate quinolone resistance determinants and the serovar was spreading clonally with either variable gyrA mutations, qnrS1/S3, or qnrB10/B19. Alternatively, various determinants are dispersed among related S. Enteritidis isolates. Antimicrobial selection pressure, multiple resistance determinants and scenarios for their acquisition and spread make extremely difficult to combat quinolone resistance.

  9. The operational mechanism of ferroelectric-driven organic resistive switches

    NARCIS (Netherlands)

    Kemerink, M.; Asadi, K.; Blom, P.W.M.; Leeuw, D.M. de

    2012-01-01

    The availability of a reliable memory element is crucial for the fabrication of 'plastic' logic circuits. We use numerical simulations to show that the switching mechanism of ferroelectric-driven organic resistive switches is the stray field of the polarized ferroelectric phase. The stray field modu

  10. Sphingolipids in neuroblastoma : Their role in drug resistance mechanisms

    NARCIS (Netherlands)

    Sietsma, H; Dijkhuis, AJ; Kamps, W; Kok, JW

    2002-01-01

    Disseminated neuroblastoma usually calls for chemotherapy as the primary approach for treatment. Treatment failure is often attributable to drug resistance. This involves a variety of cellular mechanisms, including increased drug efflux through expression of ATP-binding cassette transporters (e.g.,

  11. Mechanism of Action for Anti-Radiation Vaccine in Reducing the Biological Impact of High-Dose Irradiation

    Science.gov (United States)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    2006-01-01

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. We partially analyzed the biochemical characteristics of the SRDs. The SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  12. Mechanism of action for anti-radiation vaccine in reducing the biological impact of high-dose gamma irradiation

    Science.gov (United States)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after high-dose gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naïve animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which they mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  13. Radiation hormesis in plant - Analysis and utilization of plant antioxidative mechanism by radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Haeng Soon; Kwon, Seok Yoon; Shin, Seung Yung [Korea Research Institute of Bioscience and Biotechnology, Taejon (Korea)

    2000-04-01

    In the tobacco transgenic plants simultaneously expressing SOD and APX in chloroplast, the specific activities of SOD and APX (CA, AM, C/A, A/C) were much higher than in the transgenic plants expressing SOD (CuZnSOD, MnSOD) or APX alone, respectively. Plant growth was severely inhibited showing a well correlation with the dose of gamma-irradiation. In 70 Gy-irradiation, C/A plants showed a slight resistance to gamma radiation. The stAPX gene in tobacco was not as strongly affected by gamma irradiation. After irradiation, the stAPX transcript level decreased at 2 h, then slightly increased at 6 h and the level was maintained until 48 h. Catalase transcripts level decreased at the early time point but at the late time points the level slightly increased. The gamma radiation-induced changes of proteins in tobacco suspension cells were investigated by two-dimensional gel electrophoresis. In the gamma-irradiated cells, a few polypeptides of were newly synthesized, increased, and decreased by comparing total proteins from gamma-irradiated and non-irradiated tobacco suspension cells. With the isolation and analysis of these polypeptides, irradiation-induced proteins could be developed. 35 refs., 5 figs. (Author)

  14. Low-Viscosity, Radiation-Resistant Resin System with Increased Toughness

    Science.gov (United States)

    Reed, R. P.; Evans, D.

    2004-06-01

    Most radiation-resistant resin systems have relatively high viscosities and short working times (pot life) that do not permit their use for resin-transfer or vacuum pressure impregnation for the bonding of superconducting coils. Others are too expensive for practical use in either commercial coils or experimental projects that require large resin volumes. A new resin system has been developed that has low viscosities (100 mPaṡs to 250 mPaṡs) and long working times (8 h to 20 h) at 40 °C to 50 °C. The system consists of a DGEBF epoxy resin blended with PPGDGE with a DETD hardener. The ratio of DGEBF to PPGDGE can be varied to achieve desired viscosity and working time and increased resin toughness. The resin system was developed for use in the very large Atlas end-cap toroids and is also being used successfully to bond superconducting coils for commercial applications. Data on viscosity as a function of time, temperature, and DGEBF/PPGDGE blend are provided. Radiation effects (outgassing, swelling, moduli changes), low-temperature physical properties (density, elastic moduli, thermal conductivity, thermal contraction, dielectric breakdown, glass transition temperature), and low-temperature mechanical properties (shear/compression, flexure, short-beam shear) measurement results are presented.

  15. Fundamental Processes of Coupled Radiation Damage and Mechanical Behavior in Nuclear Fuel Materials for High Temperature Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Phillpot, Simon; Tulenko, James

    2011-09-08

    The objective of this work has been to elucidate the relationship among microstructure, radiation damage and mechanical properties for nuclear fuel materials. As representative nuclear materials, we have taken an hcp metal (Mg as a generic metal, and Ti alloys for fast reactors) and UO2 (representing fuel). The degradation of the thermo-mechanical behavior of nuclear fuels under irradiation, both the fissionable material itself and its cladding, is a longstanding issue of critical importance to the nuclear industry. There are experimental indications that nanocrystalline metals and ceramics may be more resistant to radiation damage than their coarse-grained counterparts. The objective of this project look at the effect of microstructure on radiation damage and mechanical behavior in these materials. The approach to be taken was state-of-the-art, large-scale atomic-level simulation. This systematic simulation program of the effects of irradiation on the structure and mechanical properties of polycrystalline Ti and UO2 identified radiation damage mechanisms. Moreover, it will provided important insights into behavior that can be expected in nanocrystalline microstructures and, by extension, nanocomposites. The fundamental insights from this work can be expected to help in the design microstructures that are less susceptible to radiation damage and thermomechanical degradation.

  16. Out of band radiation effects on resist patterning

    Energy Technology Data Exchange (ETDEWEB)

    George, Simi A .; Naulleau, Patrick P.

    2011-03-11

    Our previous work estimated the expected out-of-band (OOB) flare contribution at the wafer level assuming that there is a given amount of OOB at the collector focus. We found that the OOB effects are wavelength, resist, and pattern dependent. In this paper, results from rigorous patterning evaluation of multiple OOB-exposed resists using the SEMATECH Berkeley 0.3-NA MET are presented. A controlled amount of OOB is applied to the resist films before patterning is completed with the MET. LER and process performance above the resolution limit and at the resolution limits are evaluated and presented. The results typically show a negative impact on LER and process performance after the OOB exposures except in the case of single resist formulation, where resolution and performance improvement was observed.

  17. Mechanisms and consequences of bacterial resistance to antimicrobial peptides.

    Science.gov (United States)

    Andersson, D I; Hughes, D; Kubicek-Sutherland, J Z

    2016-05-01

    Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings.

  18. Down-regulation of PERK enhances resistance to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Oommen, Deepu, E-mail: oommen1978@gmail.com; Prise, Kevin M.

    2013-11-08

    Highlights: •PERK enhances the sensitivity of cancer cells to ionizing radiation. •Down-regulation of PERK results in enhanced DNA repair. •Ionizing radiation-induced apoptosis is inhibited in PERK-down regulated cancer cells. -- Abstract: Although, ionizing radiation (IR) has been implicated to cause stress in endoplasmic reticulum (ER), how ER stress signaling and major ER stress sensors modulate cellular response to IR is unclear. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) is an ER transmembrane protein which initiates unfolded protein response (UPR) or ER stress signaling when ER homeostasis is disturbed. Here, we report that down-regulation of PERK resulted in increased clonogenic survival, enhanced DNA repair and reduced apoptosis in irradiated cancer cells. Our study demonstrated that PERK has a role in sensitizing cancer cells to IR.

  19. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism.

    Directory of Open Access Journals (Sweden)

    Eveline Snelders

    2008-11-01

    Full Text Available BACKGROUND: Resistance to triazoles was recently reported in Aspergillus fumigatus isolates cultured from patients with invasive aspergillosis. The prevalence of azole resistance in A. fumigatus is unknown. We investigated the prevalence and spread of azole resistance using our culture collection that contained A. fumigatus isolates collected between 1994 and 2007. METHODS AND FINDINGS: We investigated the prevalence of itraconazole (ITZ resistance in 1,912 clinical A. fumigatus isolates collected from 1,219 patients in our University Medical Centre over a 14-y period. The spread of resistance was investigated by analyzing 147 A. fumigatus isolates from 101 patients, from 28 other medical centres in The Netherlands and 317 isolates from six other countries. The isolates were characterized using phenotypic and molecular methods. The electronic patient files were used to determine the underlying conditions of the patients and the presence of invasive aspergillosis. ITZ-resistant isolates were found in 32 of 1,219 patients. All cases were observed after 1999 with an annual prevalence of 1.7% to 6%. The ITZ-resistant isolates also showed elevated minimum inhibitory concentrations of voriconazole, ravuconazole, and posaconazole. A substitution of leucine 98 for histidine in the cyp51A gene, together with two copies of a 34-bp sequence in tandem in the gene promoter (TR/L98H, was found to be the dominant resistance mechanism. Microsatellite analysis indicated that the ITZ-resistant isolates were genetically distinct but clustered. The ITZ-sensitive isolates were not more likely to be responsible for invasive aspergillosis than the ITZ-resistant isolates. ITZ resistance was found in isolates from 13 patients (12.8% from nine other medical centres in The Netherlands, of which 69% harboured the TR/L98H substitution, and in six isolates originating from four other countries. CONCLUSIONS: Azole resistance has emerged in A. fumigatus and might be more

  20. Isolation and Characterization of Radiation-resistant Lung Cancer D6-R Cell Line

    Institute of Scientific and Technical Information of China (English)

    QI-CHUN WEI; LI SHEN; SHU ZHENG; YONG-LIANG ZHU

    2008-01-01

    To isolate an isogenic radioresistant cancer cell line after fractioned X-ray radiation and characterize the resistant cells. Methods D6 cells were exposed to repeated X-ray irradiation, and after a total dose of 5200 cGy in 8 fractions, a radioresistant monoclone D6-R was obtained. The radiosensitivity and drug sensitivity of the novel radioresistant D6-R cells, together with their parent D6 cells, were measured using clonogenic assay and MTT assay respectively. Cell cycle distribution was analyzed by flow cytometry. Fluorescence microscopy and flow cytometry were applied for apoptosis detection. Comet assay was used for the detection of DNA damage and repair. Results D6-R cells showed higher and broader initial shoulder (D=2.08 Gy, D=1.64 Gy, N=2.20) than the parent D6 ceils (D=1.84 Gy, D=0.34 Gy, N=1.20). They were 1.65-fold more radioresistant than D6 cells in terms of SF(63% vs 38%) and were more resistant to ADM (3.15-fold) and 5-FU (3.86-fold) as compared with the latter. It was found that D6-R cells had higher fractions of cells in S phase (53.4% vs 37.8%) and lower fractions of ceils in G(44.1% vs 57.2%) and G-M phase (2.5% vs 5%). There was no difference in radiation-induced apoptosis between D6-R and D6 cells. D6-R cells showed less initial DNA damage and increased capacity in DNA repair after irradiation, as compared with the parent cells. Conclusions D6-R cells have been isolated by exposing the parental D6 cells to repeated irradiation. The difference in cell cycle pattern together with the induction and repair of DNA damage might, at least partially, explain the mechanism of the radioresistance.

  1. Nosocomial infection and its molecular mechanisms of antibiotic resistance.

    Science.gov (United States)

    Xia, Jufeng; Gao, Jianjun; Tang, Wei

    2016-02-01

    Nosocomial infection is a kind of infection, which is spread in various hospital environments, and leads to many serious diseases (e.g. pneumonia, urinary tract infection, gastroenteritis, and puerperal fever), and causes higher mortality than community-acquired infection. Bacteria are predominant among all the nosocomial infection-associated pathogens, thus a large number of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and carbapenems, are adopted in clinical treatment. However, in recent years antibiotic resistance quickly spreads worldwide and causes a critical threat to public health. The predominant bacteria include Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. In these bacteria, resistance emerged from antibiotic resistant genes and many of those can be exchanged between bacteria. With technical advances, molecular mechanisms of resistance have been gradually unveiled. In this review, recent advances in knowledge about mechanisms by which (i) bacteria hydrolyze antibiotics (e.g. extended spectrum β-lactamases, (ii) AmpC β-lactamases, carbapenemases), (iii) avoid antibiotic targeting (e.g. mutated vanA and mecA genes), (iv) prevent antibiotic permeation (e.g. porin deficiency), or (v) excrete intracellular antibiotics (e.g. active efflux pump) are summarized.

  2. Insulin Resistance: Metabolic mechanisms and consequences in the heart

    Science.gov (United States)

    Abel, E. Dale; O'Shea, Karen M.; Ramasamy, Ravichandran

    2013-01-01

    Insulin resistance is a characteristic feature of obesity and Type 2 diabetes and impacts the heart in various ways. Impaired insulin-mediated glucose uptake is a uniformly observed characteristic of the heart in these states, although changes in upstream kinase signaling are variable and dependent on the severity and duration of the associated obesity or diabetes. The understanding of the physiological and pathophysiological role of insulin resistance in the heart is evolving. To maintain its high energy demands, the heart is capable of utilizing many metabolic substrates. Although, insulin signaling may directly regulate cardiac metabolism, its main role is likely the regulation of substrate delivery from the periphery to the heart. In addition to promoting glucose uptake, insulin regulates long chain fatty acid uptake, protein synthesis, and vascular function in the normal cardiovascular system. Recent advances in understanding the role of metabolic, signaling, and inflammatory pathways in obesity have provided opportunities to better understand the pathophysiology of insulin resistance in the heart. This review will summarize our current understanding of metabolic mechanisms for and consequences of insulin resistance in the heart and discuss potential new areas for investigating novel mechanisms that contribute to insulin resistance in the heart. PMID:22895668

  3. Mechanisms of antimicrobial resistance in finfish aquaculture environments

    Directory of Open Access Journals (Sweden)

    Claudio D. Miranda

    2013-08-01

    Full Text Available Consumer demand for affordable fish drives the ever-growing global aquaculture industry. The intensification and expansion of culture conditions in the production of several finfish species has been coupled with an increase in bacterial fish disease and the need for treatment with antimicrobials. Understanding the molecular mechanisms of antimicrobial resistance prevalent in aquaculture environments is important to design effective disease treatment strategies, to prioritize the use and registration of antimicrobials for aquaculture use, and to assess and minimize potential risks to public health. In this brief article we provide an overview of the molecular mechanisms of antimicrobial resistance mechanisms in finfish aquaculture environments and highlight specific research that should provide the basis of sound, science-based policies for the use of antimicrobials in aquaculture.

  4. Mechanisms of antifungal drug resistance in Candida dubliniensis.

    LENUS (Irish Health Repository)

    Coleman, David C

    2010-06-01

    Candida dubliniensis was first described in 1995 and is the most closely related species to the predominant human fungal pathogen Candida albicans. C. dubliniensis is significantly less prevalent and less pathogenic than C. albicans and is primarily associated with infections in HIV-infected individuals and other immunocompromised cohorts. The population structure of C. dubliniensis consists of three well-defined major clades and is significantly less diverse than C. albicans. The majority of C. dubliniensis isolates are susceptible to antifungal drugs commonly used to treat Candida infections. To date only two major patterns of antifungal drug resistance have been identified and the molecular mechanisms of these are very similar to the resistance mechanisms that have been described previously in C. albicans. However, significant differences are evident in the predominant antifungal drug mechanisms employed by C. dubliniensis, differences that reflect its more clonal nature, its lower prevalence and characteristics of its genome, the complete sequence of which has only recently been determined.

  5. Characterisation of Dynamic Mechanical Properties of Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2005-01-01

    The dynamic mechanical properties of a resistance welding machine have significant influence on weld quality, which must be considered when simulating the welding process numerically. However, due to the complexity of the machine structure and the mutual coupling of components of the machine system...... characterizing the dynamic mechanical characteristics of resistance welding machines is suggested, and a test set-up is designed determining the basic, independent machine parameters required in the model. The model is verified by performing a series of mechanical tests as well as real projection welds......., it is very difficult to measure or calculate the basic, independent machine parameters required in a mathematical model of the machine dynamics, and no test method has so far been presented in literature, which can be applied directly in an industrial environment. In this paper, a mathematical model...

  6. Characterisation of Dynamic Mechanical Properties of Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2005-01-01

    The dynamic mechanical properties of a resistance welding machine have significant influence on weld quality, which must be considered when simulating the welding process numerically. However, due to the complexity of the machine structure and the mutual coupling of components of the machine system......, it is very difficult to measure or calculate the basic, independent machine parameters required in a mathematical model of the machine dynamics, and no test method has so far been presented in literature, which can be applied directly in an industrial environment. In this paper, a mathematical model...... characterizing the dynamic mechanical characteristics of resistance welding machines is suggested, and a test set-up is designed determining the basic, independent machine parameters required in the model. The model is verified by performing a series of mechanical tests as well as real projection welds....

  7. Identification of Mechanical parameters for Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2003-01-01

    Mechanical dynamic responses of resistance welding machine have a significant influence on weld quality and electrode service life, it must be considered when the real welding production is carried out or the welding process is simulated. The mathematical models for characterizing the mechanical...... to the complexities and differences of machine constructions. In this paper, a method of identifying the machine mechanical parameters based on the measured data is presented no matter how the machine construction and what types of machine are. The computations are implemented in MATLAB....

  8. Identification of Mechanical parameters for Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2003-01-01

    Mechanical dynamic responses of resistance welding machine have a significant influence on weld quality and electrode service life, it must be considered when the real welding production is carried out or the welding process is simulated. The mathematical models for characterizing the mechanical...... to the complexities and differences of machine constructions. In this paper, a method of identifying the machine mechanical parameters based on the measured data is presented no matter how the machine construction and what types of machine are. The computations are implemented in MATLAB....

  9. Effects of low dose gamma radiation on the early growth of red pepper and the resistance to subsquent high dose of radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J. S.; Baek, M. H.; Kim, D. H.; Lee, Y. K. [KAERI, Taejon (Korea, Republic of); Lee, Y. B. [Chungnam National Univ., Taejon (Korea, Republic of)

    2001-05-01

    Red pepper (capsicum annuum L. cv. Jokwang and cv. Johong) seeds were irradiated with the dose of 0{approx}50 Gy to investigated the effect of the low dose gamma radiation on the early growth and resistance to subsequent high dose of radiation. The effect of the low dose gamma radiation on the early growth and resistance to subsequenct high dose of radiation were enhanced in Johong cultivar but not in Jokwang cultivar. Germination rate and early growth of Johong cultivar were noticeably increased at 4 Gy-, 8 Gy- and 20 Gy irradiation group. Resistance to subsequent high dose of radiation of Johong cultivar were increased at almost all of the low dose irradiation group. Especially it was highest at 4 Gy irradiation group. The carotenoid contents and enzyme activity on the resistance to subsequent high dose of radiation of Johong cultivar were increased at the 4 Gy and 8 Gy irradiation group.

  10. ESTABLISHMENT OF K562/ADM/VER CELL SUBLINE RESISTANT TO VERAPAMIL AND ITS RESISTANT MECHANISM

    Institute of Scientific and Technical Information of China (English)

    谢佐福; 周冬梅; 林贤东; 林声; 吴允昆

    2001-01-01

    Objective: To understand whether verapamil (VER) resistance development in the multidrug-resistant cell line and its mechanism. Methods: K562/ADM/VER cell subline resistant to verapamil was established through a gradual increase of VER concentration in the media. MTT method was used to assay resistance to VER, cross resistance to dipyriamole (DPM), cyclosporin A (CsA) in the cells, and HPLC and spectrofluorometer to detect intracellular accumulation of VER or ADM respectively, as well as S-P immunocytochemical technique for detection of genes expression. Results: It were observed that 7.9-fold increase in VER resistance, significantly reduced intracellular accumulation of VER or ADM and also develop across resistance to DPM and CsA in K562/ADM/VER cells, compared with its parent cell, K562/ADM. High-level of p-glycoprotein(pgp), middle-level of p53, p16, was present in two cell lines without expression of GSTPI, C-myc, C-myc, C-fos and C-erbB-2. Bc1-2 protein expression was found only in K562/ADM cells. Conclusion: K562/ADM cells were capable of being induced to develop resistance to VER.

  11. Mechanism of resistance to benzalkonium chloride by Pseudomonas aeruginosa.

    Science.gov (United States)

    Sakagami, Y; Yokoyama, H; Nishimura, H; Ose, Y; Tashima, T

    1989-01-01

    The mechanisms of resistance of Pseudomonas aeruginosa to benzalkonium chloride (BC) were studied. The effluence of cell components was observed in susceptible P. aeruginosa by electron microscopy, but resistant P. aeruginosa seemed to be undamaged. No marked changes in cell surface potential between Escherichia coli NIHJC-2 and a spheroplast strain were found. The contents of phospholipids (PL) and fatty and neutral lipids (FNL) in the cell walls of resistant P. aeruginosa were higher than those in the cell walls of susceptible P. aeruginosa. The amounts of BC adsorbed to PL and FNL of cell walls of BC-resistant P. aeruginosa were lower than those for BC-susceptible P. aeruginosa. Fifteen species of cellular fatty acids were identified by capillary gas chromatography and gas chromatography-mass spectrometry. The ability of BC to permeate the cell wall was reduced because of the increase in cellular fatty acids. These results suggested that the resistance of P. aeruginosa to BC is mainly a result of increased in the contents of PL and FNL. In resistant P. aeruginosa, the decrease in the amount of BC adsorbed is likely to be the result of increases in the contents of PL and FNL. Images PMID:2506813

  12. Molecular mechanism of resistance of Fusarium fujikuroi to benzimidazole fungicides.

    Science.gov (United States)

    Chen, Zihao; Gao, Tao; Liang, Shuping; Liu, Kexue; Zhou, Mingguo; Chen, Changjun

    2014-08-01

    Although carbendazim (MBC) and other benzimidazole fungicides have effectively controlled bakanae disease of rice (which is caused by Fusarium fujikuroi, F. proliferatum, and F. verticillioides) in the past, MBC resistance has become common. Previous research has shown that MBC resistance results from a mutation in the β1 -tubulin (β1 tub) gene in F. verticillioides. However, MBC resistance in F. fujikuroi, a predominant species in China, does not result from a mutation in the β1 tub. The molecular mechanism of F. fujikuroi resistance against benzimidazole fungicides is poorly understood. In this study, we determined that although β1 tub and β2 -tubulin (β2 tub) in F. fujikuroi have high homology with β1 tub and β2 tub in F. verticillioides, MBC resistance in F. fujikuroi results from mutations in β2 tub [GAG(Glu)→GTG(Val) at codon 198, TTC(Phe)→TAC(Tyr) at codon 200, and GGC(Gly)→GGT(Gly) at codon 235] but not in β1 tub. Δβ2 tub (β2 tub deletion) mutants were highly sensitive to MBC, produced fewer conidia and were less virulent than parental strains. Complementation of the Δβ2 tub mutants with a copy of the whole β2 tub locus from their parental strains restored the level of MBC resistance (or sensitivity) to that of the parental strain.

  13. The Landscape of Pancreatic Cancer Therapeutic Resistance Mechanisms.

    Science.gov (United States)

    Chand, Saswati; O'Hayer, Kevin; Blanco, Fernando F; Winter, Jordan M; Brody, Jonathan R

    2016-01-01

    Pancreatic cancer (pancreatic ductal adenocarcinoma, PDA) is infamously moving to the top of the list as one of the most lethal cancers with an overall 5 year survival rate of 7%. Multiple genomic-based and molecular characterization studies of PDA specimens and established animal models have provided the field with multiple targets and a progression model of this disease. Still, to date, the best therapeutic options are surgery and combination cytotoxic therapies. In general, even in the best case scenario (i.e., an early stage diagnosis and a response to a specific therapy), most of these fortunate patients' PDA cells acquire or exert resistance mechanisms and eventually kill the patient. Herein, we touch on a growing field of investigation that focuses on PDA cell therapeutic resistance mechanisms. We examine extrinsic elements (i.e., the tumor microenvironment, hypoxia) to the intrinsic processes within the cell (i.e., post-transcriptional gene regulation and somatic mutations) that are important for therapeutic efficacy and resistance. Even as better targeted and personalized approaches move through the clinical trial pipeline the discussed resistance mechanisms will most likely play a role in the management of this deadly disease.

  14. Radiobiological mechanisms of stereotactic body radiation therapy and stereotactic radiation surgery

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Sook; Kim, Won Woo; Park, In Hwan; Kim, Hee Jong; Lee, Eun Jin; Jung, Jae Hoon [Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Cho, Lawrence Chin Soo; Song, Chang W. [Dept. of Radiation Oncology, University of Minnesota Medical School, Minneapolis (United States)

    2015-12-15

    Despite the increasing use of stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS) in recent years, the biological base of these high-dose hypo-fractionated radiotherapy modalities has been elusive. Given that most human tumors contain radioresistant hypoxic tumor cells, the radiobiological principles for the conventional multiple-fractionated radiotherapy cannot account for the high efficacy of SBRT and SRS. Recent emerging evidence strongly indicates that SBRT and SRS not only directly kill tumor cells, but also destroy the tumor vascular beds, thereby deteriorating intratumor microenvironment leading to indirect tumor cell death. Furthermore, indications are that the massive release of tumor antigens from the tumor cells directly and indirectly killed by SBRT and SRS stimulate anti-tumor immunity, thereby suppressing recurrence and metastatic tumor growth. The reoxygenation, repair, repopulation, and redistribution, which are important components in the response of tumors to conventional fractionated radiotherapy, play relatively little role in SBRT and SRS. The linear-quadratic model, which accounts for only direct cell death has been suggested to overestimate the cell death by high dose per fraction irradiation. However, the model may in some clinical cases incidentally do not overestimate total cell death because high-dose irradiation causes additional cell death through indirect mechanisms. For the improvement of the efficacy of SBRT and SRS, further investigation is warranted to gain detailed insights into the mechanisms underlying the SBRT and SRS.

  15. Low-dose radiation reverses cisplatin resistance in ovarian cancer cells by changing Survivin and Caspase-3 expression

    Institute of Scientific and Technical Information of China (English)

    Qing Dong; Tao Jiang; Donghai Liang; Xiaoran Liu; Hongsheng Yu

    2016-01-01

    Objective Cisplatin (DDP) is the main chemotherapy drug for ovarian cancer. However, ovarian cancer cel s tend to develop cisplatin resistance in the clinical setting. Tumor cel s are sensitive to low-dose radia-tion (LDR). LDR therapy can improve the ef ects of chemotherapy drugs on ovarian cancer, but the underly-ing mechanisms are not clear. In this study, we explored the impact of low-dose radiation on Survivin and Caspase-3 levels in SKOV3/DDP ovarian cancer cel s that are resistant to cisplatin. Methods Cel viability was examined by cel counting kit-8 (CCK-8) assay, and quantitative PCR was used to detect Caspase-3 and Survivin transcript levels. Flow cytometry was used to detect and quantify apoptotic cel s. Results Cel viability was lower when cel s were treated with LDR and cisplatin than when cel s were treated with conventional radiation and cisplatin, or cisplatin alone (P Conclusion LDR reverses cisplatin resistance in SKOV3/DDP cel s, and may do so by suppressing Survivin expression and increasing Caspase-3 expression.

  16. Diversity of polymyxin resistance mechanisms among Acinetobacter baumannii clinical isolates.

    Science.gov (United States)

    Girardello, Raquel; Visconde, Marina; Cayô, Rodrigo; Figueiredo, Regina Célia Bressan Queiroz de; Mori, Marcelo Alves da Silva; Lincopan, Nilton; Gales, Ana Cristina

    2017-01-01

    Polymyxins have become drugs of last resort for treatment of multi-drug resistant (MDR) Gram-negative infections. However, the mechanisms of resistance to this compound have not been completely elucidated. In this study, we evaluated the mechanisms of resistance to this antimicrobial in two A. baumannii clinical isolates, respectively, susceptible (A027) and resistant (A009) to polymyxin B before and after polymyxin B exposure (A027(ind) and A009(ind)). The pmrAB and lpxACD were sequenced and their transcriptional levels were analyzed by qRT-PCR. The bacterial cell morphology was evaluated by transmission electronic microscopy (TEM) and the membrane potential was measured using Zeta-potential analyzer. The virulence of strains was studied using a Caenorhabditis elegans model. Both clinical isolates exhibited an elevation of the polymyxin B MIC after exposure to this compound. On the other hand, A027(ind) showed decreased values of MIC for β-lactams, aminoglycosides, vancomycin, teicoplanin, oxacillin and erythromycin. A027(ind) harbored two mutations in pmrB and the ISAba125 disrupting the lpxA. In contrast, A009(ind) strain exhibited increase of pmrB transcriptional level, after polymyxin B exposure, despite the absence of mutations in the pmrAB genes. The TEM images revealed a thicker and more electron-dense peptidoglycan layer for A009 than that of A027. The exposure to polymyxin B induced a strong condensation and darkening of intracellular material, mainly in A009(ind). In addition, the surface charge of A009 was significantly less negative than the one of A027. Using the C. elegans model, only A027(ind) strain showed a reduction on virulence. The diversity of polymyxin B resistance mechanisms among A. baumannii strains evaluated in this study confirms the complexity of these mechanisms, which may vary depending of the background of each strain.

  17. Deformation mechanism in swollen radiation-grafted polyethylene

    Science.gov (United States)

    Ungar, G.; Dlugosz, J.; Ranogajec, F.

    Stress-strain behaviour of anisotropic polyethylene (PE) film radiation-grafted with styrene was studied with the samples immersed in xylene. The glassy polystyrene (PS) phase (1) is softened by swelling. Whereas the tensile modulus of dry graft increases somewhat with increasing PS content, for the swollen graft it decreases sharply. However the yield stress and the elongation at break remain fairly large. For highly grafted films (PS/PE > 1) deformation is almost fully reversible and proceeds without necking up to draw ratios as high as 5:1. With the aid of additional X-ray diffraction and transmission electron microscopy results the deformation mechanism is interpreted in terms of the known morphology of the copolymer.

  18. Deformation mechanism in swollen radiation-grafted polyethylene

    Energy Technology Data Exchange (ETDEWEB)

    Ungar, G.; Ranogajec, F. (Institut Rudjer Boskovic, Zagreb (Yugoslavia)); Dlugosz, J. (Bristol Univ. (UK). H.H. Wills Physics Lab.)

    1981-01-01

    Stress-strain behaviour of anisotropic polyethylene (PE) film radiation-grafted with styrene was studied with the samples immersed in xylene. The glassy polystyrene (PS) phase is softened by swelling. Whereas the tensile modulus of dry graft increases somewhat with increasing PS content, for the swollen graft it decreases sharply. However the yield stress and the elongation at break remain fairly large. For highly grafted films (PS/PE > 1) deformation is almost fully reversible and proceeds without necking up to draw ratios as high as 5:1. With the aid of additional X-ray diffraction and transmission electron microscopy results the deformation mechanism is interpreted in terms of the known morphology of the copolymer.

  19. Mechanisms of resistance to sulfur dioxide in the Cucurbitaceae

    Energy Technology Data Exchange (ETDEWEB)

    Bressan, R.A.; Wilson, L.G.; Filner, P.

    1978-05-01

    The relative resistance of four cultivars of the Cucurbitaceae (Cucumis sativus L. cv. National Pickling, and inbred line SC 25; Cucurbita pepo L. cv. Prolific Straightneck Squash, and cv. Small Sugar Pumpkin) to SO/sub 2/ was determined. According to plots of the degree of exposure to SO/sub 2/ (which depends on the SO/sub 2/ concentration and the duration of the exposure), there is an 8-fold difference in resistance to this toxic gas among these cultivars. However, if the degree of injury is plotted as a function of the amount of SO/sub 2/ absorbed, all four cultivars appear similarly sensitive to the gas. We conclude that the principal reason for special and varietal differences in resistance among these cultivars is the relative rate of absorption of the gas. The densities of stomata on the upper and lower surfaces of leaves did not differ sufficiently between cultivars to account for the differences in absorption rates. It remains to be determined whether the differences in rate of SO/sub 2/ absorption reflect differences in stomatal activity. Resistance of individual leaves changes with position on the plant axis (age of the leaf). There exists a gradient of decreasing resistance from the apex downward. This resistance gradient cannot be accounted for by differences in rates of SO/sub 2/ absorption. We infer the existence of a biochemically based, developmentally controlled resistance mechanism which functions after SO/sub 2/ has entered the leaf. Biochemical comparisons of old and young leaves with such differences in resistance should be helpful in determining the biochemistry of SO/sub 2/ toxicity.

  20. A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria.

    Science.gov (United States)

    Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V; Rizk, Shahir S; Njimoh, Dieudonne L; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M; Wiest, Olaf; Haldar, Kasturi

    2015-04-30

    Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of resistance to them raises risk of wiping out recent gains achieved in reducing worldwide malaria burden and threatens future malaria control and elimination on a global level. Genome-wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination.

  1. A Study on the Interaction Mechanism between Thermal Radiation and Materials

    Institute of Scientific and Technical Information of China (English)

    Dehong XIA; Tao YU; Chuangu WU; Qingqing CHANG; Honglei JIAO

    2005-01-01

    From the viewpoint of field synergy principle and dipole radiation theory, the interaction between the incident thermal radiation wave and materials is analyzed to reveal the mechanism of selective absorption of incident thermal radiation. It is shown that the frequency of the incident thermal radiation and the damping constant of damping oscillators in materials are of vital importance for the thermal radiation properties (reflectivity, absorptivity, transmissivity, etc.) of materials.

  2. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

    OpenAIRE

    Kim, Jae Ho; Jenrow, Kenneth A; Brown, Stephen L.

    2014-01-01

    To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered ...

  3. [Trastuzumab (Herceptin) and breast cancer: mechanisms of resistance].

    Science.gov (United States)

    Dieras, Véronique; Vincent-Salomon, Anne; Degeorges, Armelle; Beuzeboc, Philippe; Mignot, Laurent; de Cremoux, Patricia

    2007-03-01

    The detection of overexpression of human epidermal growth factor receptor 2 (HER2) in some breast cancer tumors has led to the development of a targeted treatment that is tumor selective, effective at extending life expectancy in the patients with advanced or early breast cancers. Trastuzumab (Herceptin), a humanized monoclonal antibody to HER2 is indicated for patients whose tumor demonstrates an amplified copy number for the HER2 oncogene and/or overexpresses the HER2 oncoprotein. Despite a high level of efficacy in combination with chemotherapy, trastuzumab as single agent has limited effectiveness (up to 30% response rates) and patients who respond to trastuzumab will relapse despite continued treatment. The mechanism of trastuzumab action is not fully understood but has been related to cell cycle inhibition. As to mechanisms of resistance, little is known but many preclinical data raised different hypothesis. Thus, the co-expression of growth factor receptors (EGFR family, IGF-1 R), and the activation of PI3K-Akt pathway, mainly by loss of PTEN function may be responsible for the resistance phenotype. It would be interesting to identify the mechanisms of trastuzumab resistance in breast tumors in order to reverse or prevent it. The characterization of these mechanisms would also provide novel strategies for alternative treatments.

  4. Resistance of YAG:Nd sup 3+ laser frequency converters to ionizing radiation

    Science.gov (United States)

    Zakharkin, B. I.; Kulevskiy, L. A.; Nikolayev, V. N.; Toropkin, G. N.

    1986-02-01

    This study presents a review of published work on the radiation resistance of YAG:Nd sup 3+ laser frequency converters, and describes the results of experiments on the influence of gamma-irradiation of nonlinear crystals on the output characteristics of YAG:Nd sup 3+ lasers with second-harmonic generation inside or outside the cavity. The influence of radiation on the optical properties of nonlinear crystals is investigated. It is found that radiation degrades the generation of optical harmonics in YAG:ND sup 3+ lasers employing nonlinear elements made of SDA, DSDA, LiIO3 and DKDR crystals, starting at doses of 10 to the 5th power - 10 to the 6th power rad. Deuterized nonlinear crystals are found to be more resistant to ionizing radiation.

  5. Mechanism Study of Reversible Resistivity Change in Oxide Thin Film

    Energy Technology Data Exchange (ETDEWEB)

    Hong, S.; Chang, S. H.; Phatak, C.; Magyari-Kope, Blanka; Nishi, Y; Chattopadhyay, Soma; Kim, Jung Ho

    2015-01-01

    Here we present our findings related to the mechanism of reversible resistivity in Pt/TiO2/Pt cells and in Ta2O5 thin films. Our findings for Pt/TiO2/Pt cells indicate that there exists a photovoltaic-like effect, which modulates the resistance reversibly by a few orders of magnitude, depending on the intensity of impinging x-rays. We found that this effect, combined with the x-ray irradiation induced phase transition confirmed by transmission electron microscopy, triggers a non-volatile reversible resistance change. For Ta2O5 thin films, we found that there are strong correlations among oxygen vacancy number and positions and energy gaps. Ab initio band structure calculations explain the evolution of the electronic excitation spectrum as a function of oxygen vacancy number and positions and importantly provide a predictive description of the oxygen deficient Ta oxide that may improve the desired performance based on atomic level design.

  6. Materials That Enhance Efficiency and Radiation Resistance of Solar Cells

    Science.gov (United States)

    Sun, Xiadong; Wang, Haorong

    2012-01-01

    A thin layer (approximately 10 microns) of a novel "transparent" fluorescent material is applied to existing solar cells or modules to effectively block and convert UV light, or other lower solar response waveband of solar radiation, to visible or IR light that can be more efficiently used by solar cells for additional photocurrent. Meanwhile, the layer of fluorescent coating material remains fully "transparent" to the visible and IR waveband of solar radiation, resulting in a net gain of solar cell efficiency. This innovation alters the effective solar spectral power distribution to which an existing cell gets exposed, and matches the maximum photovoltaic (PV) response of existing cells. By shifting a low PV response waveband (e.g., UV) of solar radiation to a high PV response waveband (e.g. Vis-Near IR) with novel fluorescent materials that are transparent to other solar-cell sensitive wavebands, electrical output from solar cells will be enhanced. This approach enhances the efficiency of solar cells by converting UV and high-energy particles in space that would otherwise be wasted to visible/IR light. This innovation is a generic technique that can be readily implemented to significantly increase efficiencies of both space and terrestrial solar cells, without incurring much cost, thus bringing a broad base of economical, social, and environmental benefits. The key to this approach is that the "fluorescent" material must be very efficient, and cannot block or attenuate the "desirable" and unconverted" waveband of solar radiation (e.g. Vis-NIR) from reaching the cells. Some nano-phosphors and novel organometallic complex materials have been identified that enhance the energy efficiency on some state-of-the-art commercial silicon and thin-film-based solar cells by over 6%.

  7. Radiation resistance of copper alloys at high exposure levels

    Energy Technology Data Exchange (ETDEWEB)

    Garner, F.A. (Pacific Northwest Lab., Richland, WA (USA)); Zinkle, S.J. (Oak Ridge National Lab., TN (USA))

    1990-08-01

    Copper alloys are currently being considered for high heat flux applications in fusion power devices. A review is presented of the results of two separate series of experiments on the radiation response of copper and copper alloys. One of these involved pure copper and boron-doped copper in the ORR mixed spectrum reactor. The other series included pure copper and a wide array of copper alloys irradiated in the FFTF fast reactor 16 refs., 13 figs.

  8. [Determination of insecticide-resistance and resistance mechanisms of Blattella germanica (Dictyoptera: Blattellidae)].

    Science.gov (United States)

    Díaz, Pantoja Cristina; Alvarez Gavilán, Yudelmis; de Armas Rodríguez, Yaxsier; Bisset Lazcano, Juan A

    2007-01-01

    In this paper, the level of resistance to four insecticides of 3 Blatella germanica strains collected from various places in the City of Havana province was evaluated. These strains were resistant to two pyrethroids (cypermethrin and lambda-cyalothrine) and to organophosphorate malathion but susceptible to carbamate propoxur. The values of alpha and beta esterases, acetylcholinesterase and gluthatione-S-transferase were estimated in three strains involved in the study. The results of the study showed high esterase activity in all the strains, mainly beta esterases and two of the three strains presented with high gluthation-S-transferase enzyme. No changes in acetylcholinesterase were demonstrated in relation to the reference strain. The association of levels of resistance to insecticides, the possible resistance mechanisms in each strain and the results of the enzymatic activity were also analyzed.

  9. Heavy irradiation effects in radiation-resistant optical fibers

    Energy Technology Data Exchange (ETDEWEB)

    Shikama, Tatsuo [Tohoku Univ., Oarai, Ibaraki (Japan). Oarai Branch, Inst. for Materials Research

    1998-07-01

    Development of a system for optical measurements in a nuclear reactor has been progressing to investigate dynamic changes in a material caused by heavy irradiation. In such system, transfer of optical signals to out-pile measuring systems is being attempted by the use of optical fibers. In this report, the characteristics of optical fibers in the heavy irradiation field were summarized. It has been known that amorphous silica might produce radiolysis and structural defects by the exposure to ionizing radiation. The effects of heavy irradiation on molten silica were extremely complicated. A large intensity of visible light absorption occurred from an early time during start-up of the reactor. The absorption range was limited below 700 nm for the radiation associating fast neutron and the absorption was mostly attributed to non-bridging oxygen hole center. The depletion of optical transferring capacity under the radiation might be related to the internal stress. Therefore, it seems desirable to use optical fibers in the conditions without leading too much stress. (M.N.)

  10. Towards the Understanding of Resistance Mechanisms in Clinically Isolated Trimethoprim-resistant, Methicillin-resistant Staphylococcus aureus Dihydrofolate Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Frey, K.; Lombardo, M; Wright, D; Anderson, A

    2010-01-01

    Resistance to therapeutics such as trimethoprim-sulfamethoxazole has become an increasing problem in strains of methicillin-resistant Staphylococcus aureus (MRSA). Clinically isolated trimethoprim-resistant strains reveal a double mutation, H30N/F98Y, in dihydrofolate reductase (DHFR). In order to develop novel and effective therapeutics against these resistant strains, we evaluated a series of propargyl-linked antifolate lead compounds for inhibition of the mutant enzyme. For the propargyl-linked antifolates, the F98Y mutation generates minimal (between 1.2- and 6-fold) losses of affinity and the H30N mutation generates greater losses (between 2.4- and 48-fold). Conversely, trimethoprim affinity is largely diminished by the F98Y mutation (36-fold) and is not affected by the H30N mutation. In order to elucidate a mechanism of resistance, we determined a crystal structure of a complex of this double mutant with a lead propargyl-linked antifolate. This structure suggests a resistance mechanism consistent both for the propargyl-linked class of antifolates and for trimethoprim that is based on the loss of a conserved water-mediated hydrogen bond.

  11. Mechanisms of Resistance and Clinical Relevance of Resistance to β-Lactams, Glycopeptides, and Fluoroquinolones

    Science.gov (United States)

    Rice, Louis B.

    2012-01-01

    The widespread use of antibiotics has resulted in a growing problem of antimicrobial resistance in the community and hospital settings. Antimicrobial classes for which resistance has become a major problem include the β-lactams, the glycopeptides, and the fluoroquinolones. In gram-positive bacteria, β-lactam resistance most commonly results from expression of intrinsic low-affinity penicillin-binding proteins. In gram-negative bacteria, expression of acquired β-lactamases presents a particular challenge owing to some natural spectra that include virtually all β-lactam classes. Glycopeptide resistance has been largely restricted to nosocomial Enterococcus faecium strains, the spread of which is promoted by ineffective infection control mechanisms for fecal organisms and the widespread use of colonization-promoting antimicrobials (especially cephalosporins and antianaerobic antibiotics). Fluoroquinolone resistance in community-associated strains of Escherichia coli, many of which also express β-lactamases that confer cephalosporin resistance, is increasingly prevalent. Economic and regulatory forces have served to discourage large pharmaceutical companies from developing new antibiotics, suggesting that the antibiotics currently on the market may be all that will be available for the coming decade. As such, it is critical that we devise, test, and implement antimicrobial stewardship strategies that are effective at constraining and, ideally, reducing resistance in human pathogenic bacteria. PMID:22305032

  12. Flame-retardant EPDM compounds containing phenanthrene to enhance radiation resistance

    Science.gov (United States)

    Chen, Jian; Huang, Wei; Jiang, Shu-Bin; Li, Xiao-Yan; An, You; Li, Chuang; Gao, Xiao-Ling; Chen, Hong-Bing

    2017-01-01

    Ethylene propylene diene monomer (EPDM) compounds with good flame-retardant and γ-ray radiation resistant properties were prepared by adding complex flame retardants and phenathrene. The resultant EPDM formulations have a long time to ignition (TTI >46 s), a low peak heat release rate (PHRR 341 kW/m2) and a high limited oxygen index (LOI >30). Effects of γ-ray radiation on the resultant flame-retardant EPDM was investigated. The formulated EPDM is a crosslinking dominated polymer under γ-ray radiation. The γ-ray radiation resistant property of EPDM was enhanced by adding phenanthrene. Elongation at break of EPDM formulated with phenanthrene could retain 91% after being irradiated to 0.3 MGy and still retains 40% elongation even after being irradiated to 0.9 MGy, which is much better the control. It is expected that the formulated flame-retardant and radiation resistant EPDM materials could meet the requirements for use in radiation environments.

  13. Mechanism of Radiation Damage Reduction in Equiatomic Multicomponent Single Phase Alloys.

    Science.gov (United States)

    Granberg, F; Nordlund, K; Ullah, Mohammad W; Jin, K; Lu, C; Bei, H; Wang, L M; Djurabekova, F; Weber, W J; Zhang, Y

    2016-04-01

    Recently a new class of metal alloys, of single-phase multicomponent composition at roughly equal atomic concentrations ("equiatomic"), have been shown to exhibit promising mechanical, magnetic, and corrosion resistance properties, in particular, at high temperatures. These features make them potential candidates for components of next-generation nuclear reactors and other high-radiation environments that will involve high temperatures combined with corrosive environments and extreme radiation exposure. In spite of a wide range of recent studies of many important properties of these alloys, their radiation tolerance at high doses remains unexplored. In this work, a combination of experimental and modeling efforts reveals a substantial reduction of damage accumulation under prolonged irradiation in single-phase NiFe and NiCoCr alloys compared to elemental Ni. This effect is explained by reduced dislocation mobility, which leads to slower growth of large dislocation structures. Moreover, there is no observable phase separation, ordering, or amorphization, pointing to a high phase stability of this class of alloys.

  14. Mechanism of Radiation Damage Reduction in Equiatomic Multicomponent Single Phase Alloys

    Science.gov (United States)

    Granberg, F.; Nordlund, K.; Ullah, Mohammad W.; Jin, K.; Lu, C.; Bei, H.; Wang, L. M.; Djurabekova, F.; Weber, W. J.; Zhang, Y.

    2016-04-01

    Recently a new class of metal alloys, of single-phase multicomponent composition at roughly equal atomic concentrations ("equiatomic"), have been shown to exhibit promising mechanical, magnetic, and corrosion resistance properties, in particular, at high temperatures. These features make them potential candidates for components of next-generation nuclear reactors and other high-radiation environments that will involve high temperatures combined with corrosive environments and extreme radiation exposure. In spite of a wide range of recent studies of many important properties of these alloys, their radiation tolerance at high doses remains unexplored. In this work, a combination of experimental and modeling efforts reveals a substantial reduction of damage accumulation under prolonged irradiation in single-phase NiFe and NiCoCr alloys compared to elemental Ni. This effect is explained by reduced dislocation mobility, which leads to slower growth of large dislocation structures. Moreover, there is no observable phase separation, ordering, or amorphization, pointing to a high phase stability of this class of alloys.

  15. Mechanisms of alteration of the immune system by ionizing radiations: a basis for radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Bourguignon, M. [Direction Generale de la Surete Nucleaire et de la Radioprotection, 75 - Paris (France); Perez, M.; Dubner, D.; Michelin, S. [Autoridad Regulatoria Nuclear, Buenos Aires (Argentina); Carosella, E. [CEA, Service de Recherches en Hemato -Immunologie, 75 - Paris (France)

    2006-07-01

    Full text of publication follows: Alterations of the immune system appear in relationship with exposure to ionizing radiation (IR) in different situations, e.g., accidents, radiation therapy of cancer, prenatal irradiation, some human diseases with hypersensitivity to IR and aging. Thus, the comprehension of the mechanisms of the alterations of the immune system by IR is necessary to elaborate strategies of protection and to pave the way for future possible therapies. At least 9 mechanisms of alterations can be identified: 1- Apoptosis. Apoptosis is a key mechanism of the natural regulation of the immune system and plays also a key role in the response to IR: lymphocytes die rapidly by apoptosis after exposure. Different pathways of induction of apoptosis have been identified, and include p53 dependent and mitochondria mediated pathways, as well as CD95 and ROS initiation; 2- TCR mutations. The T cell antigen receptor is responsible to discriminate between self and non self. Mutations of the TCR may result from exposure to IR; 3- Modification of the Th1-Th2 balance. T helper cells may express 2 distinct secretion patterns: Th1 cytokines promote cell-mediated immunity while Th2 cytokines favor humoral immunity. Although the effects of IR on the Th1/Th2 balance remains controversial, an imbalance towards a Th2 profile is likely and patients with cancer and systemic auto-immune disease often present a switch from Th1 to Th2; 4- Bystander effects and genetic instability. Stimulatory effect or genomic instability have been observed in haematopoietic cells exposed to IR and related to a bystander mechanism. 5- Shift toward an inflammatory profile. Ionizing radiation may induce a persistent inflammatory profile as a result of dis-regulation of cytokine production; such a status of persistent inflammation has been observed in Hiroshima and Nagasaki survivors. 6- Modification of antigen presentation. Antigen presentation by dendritic cells is an essential function preceding

  16. Castration-Resistant Prostate Cancer: Mechanisms, Targets, and Treatment

    Directory of Open Access Journals (Sweden)

    Teresa Maria Santos Amaral

    2012-01-01

    Full Text Available Patients with castration-resistant prostate cancer (CRPC, who progress after docetaxel therapy, had until very recently, only a few therapeutic options. Recent advances in this field brought about new perspectives in the treatment of this disease. Molecular, basic, and translational research has given us a better understanding on the mechanisms of CRPC. This great investment has turned into a more rational approach to the development of new drugs. Some of the new treatments are already available to our patients outside clinical trials and may include inhibitors of androgen biosynthesis; new chemotherapy agents; bone-targeted therapy; and immunotherapy. This paper aims to review the mechanisms of prostate cancer resistance, possible therapeutic targets, as well as new options to treat CRPC.

  17. Mechanisms of acquired resistance to tyrosine kinase inhibitors

    Directory of Open Access Journals (Sweden)

    Yi-fan Chen

    2011-12-01

    Full Text Available In recent years, structural and functional studies reveal that tyrosine kinases (TKs act as the essential components of signal transduction pathways that regulate cancer cell proliferation, apoptosis and angiogenesis, and therefore become potential targets for anticancer therapy. Most of TK inhibitors (TKIs are small molecular and hydrophobic compounds, thus they can rapidly reach their specific intracellular targets and inhibit the activation of the related TKs. Unfortunately, accompanied with patients who gain great benefit of TKIs therapy, increasing evidences of acquired resistance to these agents have been documented. The unveiling point mutations within the kinase domain, gene amplification or overexpression, or modification of signaling pathway have been implicated in drug resistance. Additionally, overexpression of ABC transporters is likely to set stage for resistant development. In this review, we focus on the discussion of the molecular mechanisms of acquired resistance to TKIs therapy. The mechanistic understanding may help to put forward new hypotheses on drug development and design better therapies to overcome TKIs resistance.

  18. [MOLECULAR MECHANISMS OF DRUG RESISTANCE NEISSERIA GONORRHOEAE HISTORY AND PROSPECTS].

    Science.gov (United States)

    Bodoev, I N; Il'ina, E N

    2015-01-01

    Neisseria gonorrhoeae (gonococcus) is a strict human pathogen, which causes gonorrhea--an infectious disease, whose origin dates back to more than two thousand years. Due to the unique plasticity of the genetic material, these bacteria have acquired the capacity to adapt to the host immune system, cause repeated infections, as well as withstand antimicrobials. Since the introduction of antibiotics in 1930s, gonococcus has displayed its propensity to develop resistance to all clinically useful antibiotics. It is important to note that the known resistance determinants of N. gonorrhoeae were acquired through horizontal gene transfer, recombination and spontaneous mutagenesis, and may be located both in the chromosome and on the plasmid. After introduction of a new antimicrobial drug, gonococcus becomes resistant within two decades and replaces sensitive bacterial population. Currently Ceftriaxone is the last remaining antibiotic for first-line treatment of gonorrhea. However, the first gonococcus displaying high-level resistance to Ceftriaxone was isolated in Japan a few years ago. Therefore, in the near future, gonorrhea may become untreatable. In the present review, we discuss the chronology of the anti-gonorrhea drugs (antibiotics) replacement, the evolution of resistance mechanisms emergence and future perspectives of N. gonorrhoeae treatment.

  19. Mechanisms of resistance to HER family targeting antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Kruser, Tim J. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Wheeler, Deric L., E-mail: dlwheeler@wisc.edu [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States)

    2010-04-15

    The epidermal growth factor (EGF) family of receptor tyrosine kinases consists of four members: EGFR (HER1/ErbB1), HER2/neu (ErbB2), HER3 (ErbB3) and HER4 (ErbB4). Receptor activation via ligand binding leads to downstream signaling that influence cell proliferation, angiogenesis, invasion and metastasis. Aberrant expression or activity of EGFR and HER2 have been strongly linked to the etiology of several human epithelial cancers including but not limited to head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and breast cancer. With this, intense efforts have been made to inhibit the activity of the EGFR and HER2 by designing antibodies against the ligand binding domains (cetuximab, panitumumab and trastuzumab) or small molecules against the tyrosine kinase domains (erlotinib, gefitinib, and lapatinib). Both approaches have shown considerable clinical promise. However, increasing evidence suggests that the majority of patients do not respond to these therapies, and those who show initial response ultimately become refractory to treatment. While mechanisms of resistance to tyrosine kinase inhibitors have been extensively studied, resistance to monoclonal antibodies is less well understood, both in the laboratory and in the clinical setting. In this review, we discuss resistance to antibody-based therapies against the EGFR and HER2, similarities between these resistance profiles, and strategies to overcome resistance to HER family targeting monoclonal antibody therapy.

  20. Induced systemic resistance (ISR) in plants: mechanism of action.

    Science.gov (United States)

    Choudhary, Devendra K; Prakash, Anil; Johri, B N

    2007-12-01

    Plants possess a range of active defense apparatuses that can be actively expressed in response to biotic stresses (pathogens and parasites) of various scales (ranging from microscopic viruses to phytophagous insect). The timing of this defense response is critical and reflects on the difference between coping and succumbing to such biotic challenge of necrotizing pathogens/parasites. If defense mechanisms are triggered by a stimulus prior to infection by a plant pathogen, disease can be reduced. Induced resistance is a state of enhanced defensive capacity developed by a plant when appropriately stimulated. Systemic acquired resistance (SAR) and induced systemic resistance (ISR) are two forms of induced resistance wherein plant defenses are preconditioned by prior infection or treatment that results in resistance against subsequent challenge by a pathogen or parasite. Selected strains of plant growth-promoting rhizobacteria (PGPR) suppress diseases by antagonism between the bacteria and soil-borne pathogens as well as by inducing a systemic resistance in plant against both root and foliar pathogens. Rhizobacteria mediated ISR resembles that of pathogen induced SAR in that both types of induced resistance render uninfected plant parts more resistant towards a broad spectrum of plant pathogens. Several rhizobacteria trigger the salicylic acid (SA)-dependent SAR pathway by producing SA at the root surface whereas other rhizobacteria trigger different signaling pathway independent of SA. The existence of SA-independent ISR pathway has been studied in Arabidopsis thaliana, which is dependent on jasmonic acid (JA) and ethylene signaling. Specific Pseudomonas strains induce systemic resistance in viz., carnation, cucumber, radish, tobacco, and Arabidopsis, as evidenced by an enhanced defensive capacity upon challenge inoculation. Combination of ISR and SAR can increase protection against pathogens that are resisted through both pathways besides extended protection to a

  1. Radiation-hard ceramic Resistive Plate Chambers for forward TOF and T0 systems

    Science.gov (United States)

    Akindinov, A.; Dreyer, J.; Fan, X.; Kämpfer, B.; Kiselev, S.; Kotte, R.; Garcia, A. Laso; Malkevich, D.; Naumann, L.; Nedosekin, A.; Plotnikov, V.; Stach, D.; Sultanov, R.; Voloshin, K.

    2017-02-01

    Resistive Plate Chambers with ceramic electrodes are the main candidates for a use in precise multi-channel timing systems operating in high-radiation conditions. We report the latest R&D results on these detectors aimed to meet the requirements of the forward T0 counter at the CBM experiment. RPC design, gas mixture, limits on the bulk resistivity of ceramic electrodes, efficiency, time resolution, counting rate capabilities and ageing test results are presented.

  2. Ciprofloxacin-resistant Escherichia coli in Central Greece: mechanisms of resistance and molecular identification

    Directory of Open Access Journals (Sweden)

    Mavroidi Angeliki

    2012-12-01

    Full Text Available Abstract Background Fluoroquinolone resistant E. coli isolates, that are also resistant to other classes of antibiotics, is a significant challenge to antibiotic treatment and infection control policies. In Central Greece a significant increase of ciprofloxacin-resistant Escherichia coli has occurred during 2011, indicating the need for further analysis. Methods A total of 106 ciprofloxacin-resistant out of 505 E. coli isolates consecutively collected during an eight months period in a tertiary Greek hospital of Central Greece were studied. Antimicrobial susceptibility patterns and mechanisms of resistance to quinolones were assessed, whereas selected isolates were further characterized by multilocus sequence typing and β-lactamase content. Results Sequence analysis of the quinolone-resistance determining region of the gyrA and parC genes has revealed that 63% of the ciprofloxacin-resistant E. coli harbored a distinct amino acid substitution pattern (GyrA:S83L + D87N; ParC:S80I + E84V, while 34% and 3% carried the patterns GyrA:S83L + D87N; ParC:S80I and GyrA:S83L + D87N; ParC:S80I + E84G respectively. The aac (6’-1b-cr plasmid-mediated quinolone resistance determinant was also detected; none of the isolates was found to carry the qnrA, qnrB and qnrS. Genotyping of a subset of 35 selected ciprofloxacin-resistant E. coli by multilocus sequence typing has revealed the presence of nine sequence types; ST131 and ST410 were the most prevalent and were exclusively correlated with hospital and health care associated infections, while strains belonging to STs 393, 361 and 162 were associated with community acquired infections. The GyrA:S83L + D87N; ParC:S80I + E84V substitution pattern was found exclusively among ST131 ciprofloxacin-resistant E. coli. Extended-spectrum β-lactamase-positive ST131 ciprofloxacin-resistant isolates produced CTX-M-type enzymes; eight the CTX-M-15 and one the CTX-M-3 variant. CTX-M-1 like and KPC-2 enzymes were detected

  3. Breast cancer and possible mechanisms of therapy resistance

    Directory of Open Access Journals (Sweden)

    Ana-Maria Florea

    2013-03-01

    Full Text Available Breast cancer represents one of the most common cancers in women and is a major life threatening illness found all over the world. Therapy approaches include irradiation and surgery, with chemotherapy considered an important strategy to treat breast cancer. Platinum based anticancer drugs, such as cisplatin (cis-di-amino-dichloride-platin, CDDP, carboplatin, orthoplatin, etc., have been successfully used in breast cancer therapy because they activate multiple mechanisms to induce apoptosis in tumor cells. Nevertheless, during chemotherapy, drug resistance frequently develops; this impairs the successful treatment of breast cancer and often leads to patients’ decease. While combinations of anticancer drugs used in chemotherapy regimens reduced the occurrence of drug resistance (e.g. doxorubicin + docetaxel, doxorubicin + cyclophosphamide, docetaxel + herceptin + carboplatin the molecular mechanism of those effects are not completely understood. Here we review possible mechanisms related to breast cancer treatment and resistance to current therapies as well as possible new therapeutic targets (e.g. calcium signaling which could be used in the future.

  4. Evaluation of Rice Germplasm for Resistance to the Small Brown Planthopper(Laodelphax striatellus)and Analysis of Resistance Mechanism

    Institute of Scientific and Technical Information of China (English)

    DUAN Can-xing; ZHANG Shi-xian; LEI Cai-lin; CHENG Zhi-jun; CHEN Qing; ZHAI Hu-qu; WAN Jian-min

    2008-01-01

    One hundred and thirty-eight rice accessions were screened for resistance to the small brown planthopper(SBPH)resistance to SBPH were detected,accounting for 18.1%of the total accessions,which included 2 highly resistant,9 resistant and 14 moderately resistant varieties.Compared with indica rice,japonica rice was more susceptible to SBPH.Antixenosis test,antibiosis test and correlation analysis were performed to elucidate the resistance mechanism.The resistant check Rathu Heenati(RHT),highly resistant varieties Mudgo and Kasalath,and resistant variety IR36 expressed strong antixenosis and antibiosis against SBPH,indicating the close relationship between resistance level and these two resistance mechanisms in the four rice varieties.Antibiosis was the dominant resistance pattern in the resistant varieties Daorenqiao and Yangmaogu due to their high antibiosis but low antixenosis.Dular,ASD7 and Milyang 23 had relatively strong antixenosis and antibiosis,indicating the two resistance mechanisms were significant in these three varieties.The resistant DV85 expressed relatively high level of antixenosis but low antibiosis,whereas Zhaiyeqing 8 and Guiyigu conferred only moderate antibiosis and antixenosis to SBPH,suggesting tolerance in these three varieties.Antibiosis and antixenosis governed the resistance to SBPH in the moderately resistant accession 9311.Antixenosis was the main resistance type in V20A.Tolerance was considered to be an important resistance mechanism in Minghui 63 and Yangjing 9538 due to their poor antibiosis and antixenosis resistance.The above accessions with strong antibiosis or antixenosis were the ideal materials for the resistance breeding.

  5. Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance.

    Science.gov (United States)

    Yang, Jian-Zeng; Ma, Shu-Rong; Rong, Xiao-Li; Zhu, Mei-Ju; Ji, Qiu-Ye; Meng, Ling-Jie; Gao, Yi-Yao; Yang, Yu-Dan; Wang, Yan

    2016-10-01

    Multidrug resistance (MDR) is a challenge for the treatment of cancer and the underlying molecular mechanisms remain elusive. The current study exposed MG63 osteosarcoma cells to increasing concentrations of vincristine (VCR) to establish four VCR‑resistant MG63/VCR cell sublines (MG63/VCR1, 2, 3 and 4). The drug resistance indices (RI) of these sublines was detected with the CCK‑8 assay and determined to be163, 476, 1,247, and 2,707‑fold higher than that of parental cells, respectively. These sublines also exhibited cross‑resistance to doxorubicin, paclitaxel and pirarubicin. With increased RI, the proliferative capacity of these sublines was gradually reduced and cell morphology was also altered, characterized by increased formation of pseudopodia and long cytoplasmic processes at opposite poles. However, the migration capacity and expression of certain drug resistance‑associated genes were not in accordance with the increased RI; multidrug resistance protein 1 (MDR1) expression was significantly increased in these sublines compared with parental cells. However, in the highly resistant MG63/VCR3 and MG63/VCR4 cells, MDR‑associated protein 1, topoisomerase II and LIM domain kinase 1 levels were significantly reduced compared with the moderately resistant MG63/VCR2 cells. Expression of glutathione S‑transferase‑π mRNA was determined using reverse transcription‑quantitative polymerase chain reaction and determined that it was not changed between MG63 and MG63/VCR cells. The data of the present study demonstrated that the molecular alterations of drug resistance may change with the degree of drug resistance. Taking cell morphology into consideration, the intratumor clonal and phenotypic heterogeneity may be responsible for drug resistance. These MG63/VCR sublines may be a valuable tool to assess drug resistance and the underlying mechanisms, and to identify novel drug resistance‑associated genes or strategies to overcome MDR in human

  6. Embryo mechanics: balancing force production with elastic resistance during morphogenesis.

    Science.gov (United States)

    Davidson, Lance A

    2011-01-01

    Morphogenesis requires the spatial and temporal control of embryo mechanics, including force production and mechanical resistance to those forces, to coordinate tissue deformation and large-scale movements. Thus, biomechanical processes play a key role in directly shaping the embryo. Additional roles for embryo mechanics during development may include the patterning of positional information and to provide feedback to ensure the success of morphogenetic movements in shaping the larval body and organs. To understand the multiple roles of mechanics during development requires familiarity with engineering principles of the mechanics of structures, the viscoelastic properties of biomaterials, and the integration of force and stress within embryonic structures as morphogenesis progresses. In this chapter, we review the basic engineering principles of biomechanics as they relate to morphogenesis, introduce methods for quantifying embryo mechanics and the limitations of these methods, and outline a formalism for investigating the role of embryo mechanics in birth defects. We encourage the nascent field of embryo mechanics to adopt standard engineering terms and test methods so that studies of diverse organisms can be compared and universal biomechanical principles can be revealed.

  7. Luminescence and radiation resistance of undoped NaI crystals

    Energy Technology Data Exchange (ETDEWEB)

    Shiran, N., E-mail: shiran@isc.kharkov.com; Boiaryntseva, I.; Gektin, A.; Gridin, S.; Shlyakhturov, V.; Vasuykov, S.

    2014-11-15

    Highlights: • The performance of NaI scintillators depends on luminescence properties. • A criterion of crystals’ purity level is radiation colorability at room temperature. • The traces of the most dangerous impurities were detected. • Crucial role in efficiency of pure NaI scintillator play the crystal perfection. - Abstract: Undoped NaI single crystal is an excellent scintillator at low temperature. However, scintillation parameters of different quality crystals vary in a wide range, significantly exceeding measurement error. Experimental data demonstrate the features of luminescence, radiation induced coloration, and afterglow dependence on the quality of nominally pure crystals. It is found that defects level that allows to elucidate artefacts introduced by traces of harmful impurities corresponds to 3 × 10{sup 15} cm{sup −3} that significantly overhead accuracy of chemical and absorption analysis. It is shown that special raw material treatment before and during the single crystal growth allows to reach NaI purity level that avoids impurities influence to the basic luminescence data.

  8. DNA Repair and Photoprotection: Mechanisms of Overcoming Environmental Ultraviolet Radiation Exposure in Halophilic Archaea

    Directory of Open Access Journals (Sweden)

    Daniel L. Jones

    2017-09-01

    Full Text Available Halophilic archaea push the limits of life at several extremes. In particular, they are noted for their biochemical strategies in dealing with osmotic stress, low water activity and cycles of desiccation in their hypersaline environments. Another feature common to their habitats is intense ultraviolet (UV radiation, which is a challenge that microorganisms must overcome. The consequences of high UV exposure include DNA lesions arising directly from bond rearrangement of adjacent bipyrimidines, or indirectly from oxidative damage, which may ultimately result in mutation and cell death. As such, these microorganisms have evolved a number of strategies to navigate the threat of DNA damage, which we differentiate into two categories: DNA repair and photoprotection. Photoprotection encompasses damage avoidance strategies that serve as a “first line of defense,” and in halophilic archaea include pigmentation by carotenoids, mechanisms of oxidative damage avoidance, polyploidy, and genomic signatures that make DNA less susceptible to photodamage. Photolesions that do arise are addressed by a number of DNA repair mechanisms that halophilic archaea efficiently utilize, which include photoreactivation, nucleotide excision repair, base excision repair, and homologous recombination. This review seeks to place DNA damage, repair, and photoprotection in the context of halophilic archaea and the solar radiation of their hypersaline environments. We also provide new insight into the breadth of strategies and how they may work together to produce remarkable UV-resistance for these microorganisms.

  9. Piezoelectric resonators with mechanical damping and resistance in current conduction

    Institute of Scientific and Technical Information of China (English)

    Yook-Kong; YONG; Mihir; S; PATEL

    2007-01-01

    A novel design method for high Q piezoelectric resonators was presented and proposed using the 3-D equations of linear piezoelectricity with quasi-electrostatic approximation which include losses attributed to mechanical damping in solid and resistance in current conduction. There is currently no finite element software for estimating the Q of a resonator without apriori assumptions of the resonator impedance or damping. There is a necessity for better and more realistic modeling of resonators and filters due to miniaturization and the rapid advances in frequency ranges in telecommunication.We presented new three-dimensional finite element models of quartz and barium titanate resonators with mechanical damping and resistance in current conduction. Lee, Liu and Ballato's 3-D equations of linear piezoelectricity with quasi-electro- static approximation which include losses attributed to mechanical damping in solid and resistance in current conduction were formulated in a weak form and implemented in COMSOL. The resulting finite element model could predict the Q and other electrical parameters for any piezoelectric resonator without apriori assumptions of damping or resistance. Forced and free vibration analyses were performed and the results for the Q and other electrical parameters were obtained. Comparisons of the Q and other electrical parameters obtained from the free vibration analysis with their corresponding values from the forced vibration analysis were found to be in excellent agreement. Hence, the frequency spectra obtained from the free vibration analysis could be used for designing high Q resonators. Results for quartz thickness shear AT-cut and SC-cut resonators and thickness stretch poled barium titanate resonators were presented. An unexpected benefit of the model was the prediction of resonator Q with energy losses via the mounting supports.

  10. Identifying the Proteins that Mediate the Ionizing Radiation Resistance of Deinococcus Radiodurans R1

    Energy Technology Data Exchange (ETDEWEB)

    Battista, John R

    2010-02-22

    The primary objectives of this proposal was to define the subset of proteins required for the ionizing radiation (IR) resistance of Deinococcus radiodurans R1, characterize the activities of those proteins, and apply what was learned to problems of interest to the Department of Energy.

  11. Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy

    Directory of Open Access Journals (Sweden)

    Mohamed El-Tanani

    2016-03-01

    Full Text Available Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1, and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.

  12. Molecular mechanisms of metabolic resistance to synthetic and natural xenobiotics.

    Science.gov (United States)

    Li, Xianchun; Schuler, Mary A; Berenbaum, May R

    2007-01-01

    Xenobiotic resistance in insects has evolved predominantly by increasing the metabolic capability of detoxificative systems and/or reducing xenobiotic target site sensitivity. In contrast to the limited range of nucleotide changes that lead to target site insensitivity, many molecular mechanisms lead to enhancements in xenobiotic metabolism. The genomic changes that lead to amplification, overexpression, and coding sequence variation in the three major groups of genes encoding metabolic enzymes, i.e., cytochrome P450 monooxygenases (P450s), esterases, and glutathione-S-transferases (GSTs), are the focus of this review. A substantial number of the adaptive genomic changes associated with insecticide resistance that have been characterized to date are transposon mediated. Several lines of evidence suggest that P450 genes involved in insecticide resistance, and perhaps insecticide detoxification genes in general, may share an evolutionary association with genes involved in allelochemical metabolism. Differences in the selective regime imposed by allelochemicals and insecticides may account for the relative importance of regulatory or structural mutations in conferring resistance.

  13. Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab.

    Science.gov (United States)

    Brand, Toni M; Iida, Mari; Wheeler, Deric L

    2011-05-01

    The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase belonging to the HER family of receptor tyrosine kinases. Receptor activation upon ligand binding leads to down stream activation of the PI3K/AKT, RAS/RAF/MEK/ERK and PLCγ/PKC pathways that influence cell proliferation, survival and the metastatic potential of tumor cells. Increased activation by gene amplification, protein overexpression or mutations of the EGFR has been identified as an etiological factor in a number of human epithelial cancers (e.g., NSCLC, CRC, glioblastoma and breast cancer). Therefore, targeting the EGFR has been intensely pursued as a cancer treatment strategy over the last two decades. To date, five EGFR inhibitors, including three small molecule tyrosine kinase inhibitors (TKIs) and two monoclonal antibodies have gained FDA approval for use in oncology. Both approaches to targeting the EGFR have shown clinical promise and the anti-EGFR antibody cetuximab is used to treat HNSCC and CRC. Despite clinical gains arising from use of cetuximab, both intrinsic resistance and the development of acquired resistance are now well recognized. In this review we focus on the biology of the EGFR, the role of EGFR in human cancer, the development of antibody-based anti-EGFR therapies and a summary of their clinical successes. Further, we provide an in depth discussion of described molecular mechanisms of resistance to cetuximab and potential strategies to circumvent this resistance.

  14. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

    Directory of Open Access Journals (Sweden)

    Asma Ahmed

    2015-12-01

    Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  15. Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy.

    Science.gov (United States)

    El-Tanani, Mohamed; Dakir, El-Habib; Raynor, Bethany; Morgan, Richard

    2016-03-14

    Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES) to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1), and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.

  16. Diet-Induced Obesity and the Mechanism of Leptin Resistance.

    Science.gov (United States)

    Engin, Atilla

    2017-01-01

    Leptin signaling blockade by chronic overstimulation of the leptin receptor or hypothalamic pro-inflammatory responses due to elevated levels of saturated fatty acid can induce leptin resistance by activating negative feedback pathways. Although, long form leptin receptor (Ob-Rb) initiates leptin signaling through more than seven different signal transduction pathways, excessive suppressor of cytokine signaling-3 (SOCS-3) activity is a potential mechanism for the leptin resistance that characterizes human obesity. Because the leptin-responsive metabolic pathways broadly integrate with other neurons to control energy balance, the methods used to counteract the leptin resistance has extremely limited effect. In this chapter, besides the impairment of central and peripheral leptin signaling pathways, limited access of leptin to central nervous system (CNS) through blood-brain barrier, mismatch between high leptin and the amount of leptin receptor expression, contradictory effects of cellular and circulating molecules on leptin signaling, the connection between leptin signaling and endoplasmic reticulum (ER) stress and self-regulation of leptin signaling has been discussed in terms of leptin resistance.

  17. On the mechanism of chloroquine resistance in Plasmodium falciparum.

    KAUST Repository

    Chinappi, Mauro

    2010-11-19

    Resistance to chloroquine of malaria strains is known to be associated with a parasite protein named PfCRT, the mutated form of which is able to reduce chloroquine accumulation in the digestive vacuole of the pathogen. Whether the protein mediates extrusion of the drug acting as a channel or as a carrier and which is the protonation state of its chloroquine substrate is the subject of a scientific debate. We present here an analytical approach that explores which combination of hypotheses on the mechanism of transport and the protonation state of chloroquine are consistent with available equilibrium experimental data. We show that the available experimental data are not, by themselves, sufficient to conclude whether the protein acts as a channel or as a transporter, which explains the origin of their different interpretation by different authors. Interestingly, though, each of the two models is only consistent with a subset of hypotheses on the protonation state of the transported molecule. The combination of these results with a sequence and structure analysis of PfCRT, which strongly suggests that the molecule is a carrier, indicates that the transported species is either or both the mono and di-protonated forms of chloroquine. We believe that our results, besides shedding light on the mechanism of chloroquine resistance in P. falciparum, have implications for the development of novel therapies against resistant malaria strains and demonstrate the usefulness of an approach combining systems biology strategies with structural bioinformatics and experimental data.

  18. Mechanisms linking brain insulin resistance to Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Maria Niures P.S. Matioli

    Full Text Available Several studies have indicated that Diabetes Mellitus (DM can increase the risk of developing Alzheimer's disease (AD. This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection.

  19. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  20. [Ecology and mechanisms of bacterial resistance to antibiotics in peritonitis].

    Science.gov (United States)

    Edern, Anita; Fines-Guyon, Marguerite; Castrale, Cindy; Ficheux, Maxence; Ryckelynck, Jean-Philippe; Lobbedez, Thierry

    2012-11-01

    Peritonitis remains a common complication of peritoneal dialysis. The aim of our study is to describe the mechanisms of antibiotic resistance in bacteria isolated during peritonitis in peritoneal dialysis, to determine whether antibiotic therapy proposed by the International Society for Peritoneal Dialysis (ISPD) is adapted to the mechanisms of resistance. All causative microorganisms of peritonitis, isolated in 106 dialysis patients and reported 170 episodes of peritonitis, during the study period (01/01/2005 to 31/12/2010) were reviewed. According to the usual classification, twelve groups of microorganism were created. An interpretive reading of antibiograms was performed in each group to identify resistance phenotypes. The species most frequently isolated are coagulase-negative staphylococci (n=73) of which 46 had PBP2a (penicillin-binding protein). Many Enterobacteriaceae were also isolated (n=45), they are susceptible to third generation cephalosporins with the exception of Enterobacteriaceae producing an extended spectrum β-lactamase (ESBL) or a cephalosporinase. Except for staphylococci, probabilistic antibiotic therapy recommended by the ISPD to treat peritonitis is effective. Indeed, many staphylococci producing a PBP2a, a first-generation cephalosporin cannot be administered in all cases. It is therefore necessary to identify patients with a strain of staphylococcus producing a PBP2a, it must be treated by vancomycin.

  1. Mechanisms of Induced Resistance in Barley Against Drechslera teres.

    Science.gov (United States)

    Lyngs Jørgensen, H J; Lübeck, P S; Thordal-Christensen, H; de Neergaard, E; Smedegaard-Petersen, V

    1998-07-01

    ABSTRACT Quantitative and qualitative histopathological methods and molecular analyses were used to study the mechanisms by which preinoculation with either of the nonbarley pathogens, Bipolaris maydis and Septoria nodorum, inhibited growth of Drechslera teres. Collectively, our data suggest that induced resistance is the principal mechanism responsible for impeding the pathogen. The enhancement of resistance in the host was primarily manifested during penetration by D. teres, and after penetration, where growth of D. teres ceased soon after development of infection vesicles. Thus, 24 h after pretreatment with B. maydis or S. nodorum, the penetration frequency from D. teres appressoria was reduced from 42.7% in the controls to 9.5 and 14.8%, respectively. The reductions were associated with increased formation of fluorescent papillae in induced cells (early defense reaction). The postpenetrational inhibition of D. teres completely stopped fungal growth and was apparently linked to an enhancement of multicellular hypersensitive responses in inducer-treated leaves (late defense reaction). Papillae formation and multicellular hypersensitive reactions were also observed in fully susceptible, noninduced control leaves, but they were inadequate to stop fungal progress. Northern blots from leaves treated with either inducer alone support the conclusion that induced resistance is involved in suppression of D. teres by increased formation of papillae and hypersensitive reactions. Thus, the blots showed strong expression of several defense response genes that are involved in these reactions in barley attacked by Erysiphe graminis f. sp. hordei.

  2. Progresses in the Mechanism of Resistance to Fusarium Wilt in Cucumber(Cucumis sativus L.)

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xingang; WU Fengzhi; WANG Xuezheng; YUAN Ye

    2008-01-01

    Fusarium wilt caused by Fusarium oxysporum f.sp.cucumerinum (Owen) is one of the most devastating diseases in cucumber production worldwide.Recent progresses in the mechanism of resistance to Fusarium wilt in cucumber were reviewed in this paper,including pathogenic mechanism of Fusarium oxysporum,the resistance mechanism of cucumber,the heredity of resistance,and the location of resistance genes.Following works should be the location and cloning of resistance genes with molecular biologic methods.

  3. Mechanical radiation detection via sub-Brownian lever deflections

    Science.gov (United States)

    Hammig, Mark David

    2005-07-01

    A micromechanical lever that deflects in response to the impacts of charged particles is proposed as a means of improving upon the capabilities of existing radiation detection technology. When a particle strikes an object, momentum is transferred to the impacted body. The resulting body motion can be correlated to the energy of the incident particle. The momentum detector offers promise as a highly discriminating, high-resolution tool for ion sensing. Advances required to successfully realize a spectroscopic capability have been completed; specifically, techniques for reproducibly fabricating micromechanical structures have been optimized, and an instrument that measures miniscule deflections has been developed. Even absent substantial refinement efforts, the novel coupled-cavity optical detector can resolve lever motions on the order of 1--10 picometers. A method by which the Brownian motion of the lever can be stilled has been proven which elicits reductions sufficient to measure heavy-ion impact, the deflections from which may be several orders of magnitude below the thermal vibration amplitude. Using active forcing techniques, the Brownian vibration of the microlevers has been reduced from room temperature (288 K) to sub-Kelvin temperatures, for levers vibrating in air. The mechanical factors that limit the noise reduction magnitude are discussed and methods of surmounting those limitations are identified.

  4. Fluoroquinolone resistance mechanisms of Shigella flexneri isolated in Bangladesh.

    Directory of Open Access Journals (Sweden)

    Ishrat J Azmi

    Full Text Available To investigate the prevalence and mechanisms of fluoroquinolone resistance in Shigella species isolated in Bangladesh and to compare with similar strains isolated in China.A total of 3789 Shigella isolates collected from Clinical Microbiology Laboratory of icddr,b, during 2004-2010 were analyzed for antibiotic susceptibility. Analysis of plasmids, plasmid-mediated quinolone-resistance genes, PFGE, and sequencing of genes of the quinolone-resistance-determining regions (QRDR were conducted in representative strains isolated in Bangladesh and compared with strains isolated in Zhengding, China. In addition, the role of efflux-pump was studied by using the efflux-pump inhibitor carbonyl cyanide-m-chlorophenylhydrazone (CCCP.Resistance to ciprofloxacin in Shigella species increased from 0% in 2004 to 44% in 2010 and S. flexneri was the predominant species. Of Shigella spp, ciprofloxacin resistant (CipR strains were mostly found among S. flexneri (8.3%, followed by S. sonnei (1.5%. Within S. flexneri (n = 2181, 14.5% were resistance to ciprofloxacin of which serotype 2a was predominant (96%. MIC of ciprofloxacin, norfloxacin, and ofloxacin were 6-32 mg/L, 8-32 mg/L, and 8-24 mg/L, respectively in S. flexneri 2a isolates. Sequencing of QRDR genes of resistant isolates showed double mutations in gyrA gene (Ser83Leu, Asp87Asn/Gly and single mutation in parC gene (Ser80Ile. A difference in amino acid substitution at position 87 was found between strains isolated in Bangladesh (Asp87Asn and China (Asp87Gly except for one. A novel mutation at position 211 (His→Tyr in gyrA gene was detected only in the Bangladeshi strains. Susceptibility to ciprofloxacin was increased by the presence of CCCP indicating the involvement of energy dependent active efflux pumps. A single PFGE type was found in isolates from Bangladesh and China suggesting their genetic relatedness.Emergence of fluoroquinolone resistance in Shigella undermines a major challenge in current

  5. Fluoroquinolone Resistance Mechanisms of Shigella flexneri Isolated in Bangladesh

    Science.gov (United States)

    Azmi, Ishrat J.; Khajanchi, Bijay K.; Akter, Fatema; Hasan, Trisheeta N.; Shahnaij, Mohammad; Akter, Mahmuda; Banik, Atanu; Sultana, Halima; Hossain, Mohammad A.; Ahmed, Mohammad K.; Faruque, Shah M.; Talukder, Kaisar A.

    2014-01-01

    Objective To investigate the prevalence and mechanisms of fluoroquinolone resistance in Shigella species isolated in Bangladesh and to compare with similar strains isolated in China. Methods A total of 3789 Shigella isolates collected from Clinical Microbiology Laboratory of icddr,b, during 2004–2010 were analyzed for antibiotic susceptibility. Analysis of plasmids, plasmid-mediated quinolone-resistance genes, PFGE, and sequencing of genes of the quinolone-resistance-determining regions (QRDR) were conducted in representative strains isolated in Bangladesh and compared with strains isolated in Zhengding, China. In addition, the role of efflux-pump was studied by using the efflux-pump inhibitor carbonyl cyanide-m-chlorophenylhydrazone (CCCP). Results Resistance to ciprofloxacin in Shigella species increased from 0% in 2004 to 44% in 2010 and S. flexneri was the predominant species. Of Shigella spp, ciprofloxacin resistant (CipR) strains were mostly found among S. flexneri (8.3%), followed by S. sonnei (1.5%). Within S. flexneri (n = 2181), 14.5% were resistance to ciprofloxacin of which serotype 2a was predominant (96%). MIC of ciprofloxacin, norfloxacin, and ofloxacin were 6–32 mg/L, 8–32 mg/L, and 8–24 mg/L, respectively in S. flexneri 2a isolates. Sequencing of QRDR genes of resistant isolates showed double mutations in gyrA gene (Ser83Leu, Asp87Asn/Gly) and single mutation in parC gene (Ser80Ile). A difference in amino acid substitution at position 87 was found between strains isolated in Bangladesh (Asp87Asn) and China (Asp87Gly) except for one. A novel mutation at position 211 (His→Tyr) in gyrA gene was detected only in the Bangladeshi strains. Susceptibility to ciprofloxacin was increased by the presence of CCCP indicating the involvement of energy dependent active efflux pumps. A single PFGE type was found in isolates from Bangladesh and China suggesting their genetic relatedness. Conclusions Emergence of fluoroquinolone resistance in Shigella

  6. ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer

    Science.gov (United States)

    2016-05-01

    Award  Number:    W81XWH-10-1-0582 TITLE:       ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer...5a.  CONTRACT  NUMBER   ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer 5b.  GRANT  NUMBER   W81XWH...SUPPLEMENTARY  NOTES 14. ABSTRACT The  research  goals  of  this  grant  proposal  are  to:  1)  investigate  the  effect  of   ETS  gene  fusions  on  radiation

  7. Ras Labs.-CASIS-ISS NL experiment for synthetic muscle: resistance to ionizing radiation

    Science.gov (United States)

    Rasmussen, Lenore; Sandberg, Eric; Albers, Leila N.; Rodriguez, Simone; Gentile, Charles A.; Meixler, Lewis D.; Ascione, George; Hitchner, Robert; Taylor, James; Hoffman, Dan; Cylinder, David; Moy, Leon; Mark, Patrick S.; Prillaman, Daniel L.; Nordarse, Robert; Menegus, Michael J.; Ratto, Jo Ann; Thellen, Christopher; Froio, Danielle; Furlong, Cosme; Razavi, Payam; Valenza, Logan; Hablani, Surbhi; Fuerst, Tyler; Gallucci, Sergio; Blocher, Whitney; Liffland, Stephanie

    2016-04-01

    In anticipation of deep space travel, new materials are being explored to assist and relieve humans in dangerous environments, such as high radiation, extreme temperature, and extreme pressure. Ras Labs Synthetic Muscle - electroactive polymers (EAPs) that contract and expand at low voltages - which mimic the unique gentle-yet-strong nature of human tissue, is a potential asset to manned space travel through protective gear and human assist robotics and for unmanned space exploration through deep space. Generation 3 Synthetic Muscle was proven to be resistant to extreme temperatures, and there were indications that these materials may also be radiation resistant. The purpose of the Ras Labs-CASIS-ISS Experiment is to test the radiation resistivity of the third and fourth generation of these EAPs, as well as to make them even more radiation resistant or radiation hardened. On Earth, exposure of the Generation 3 and Generation 4 EAPs to a Cs-137 radiation source for 47.8 hours with a total dose of 305.931 kRad of gamma radiation was performed at the US Department of Energy's Princeton Plasma Physics Laboratory (PPPL) at Princeton University, followed by pH, peroxide, Shore Hardness Durometry, and electroactivity testing to determine the inherent radiation resistivity of these contractile EAPs and to determine whether the EAPs could be made even more radiation resistant through the application of appropriate additives and coatings. The on Earth preliminary tests determined that selected Ras Labs EAPs were not only inherently radiation resistant, but with the appropriate coatings and additives, could be made even more radiation resistant. Gforce testing to over 10 G's was performed at US Army's ARDEC Labs, with excellent results, in preparation for space flight to the International Space Station National Laboratory (ISS-NL). Selected samples of Generation 3 and Generation 4 Synthetic Muscle™, with various additives and coatings, were launched to the ISS-NL on April

  8. Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE).

    Science.gov (United States)

    Goodman, K E; Simner, P J; Tamma, P D; Milstone, A M

    2016-01-01

    The Centers for Disease Control and Prevention (CDC) defines carbapenem-resistant Enterobacteriaceae (CRE) based upon a phenotypic demonstration of carbapenem resistance. However, considerable heterogeneity exists within this definitional umbrella. CRE may mechanistically differ by whether they do or do not produce carbapenemases. Moreover, patients can acquire CRE through multiple pathways: endogenously through antibiotic selective pressure on intestinal microbiota, exogenously through horizontal transmission or through a combination of these factors. Some evidence suggests that non-carbapenemase-producing CRE may be more frequently acquired by antibiotic exposure and carbapenemase-producing CRE via horizontal transmission, but definitive data are lacking. This review examines types of CRE resistance mechanisms, antibiotic exposure and horizontal transmission pathways of CRE acquisition, and the implications of these heterogeneities to the development of evidence-based CRE healthcare epidemiology policies. In our Expert Commentary & Five-Year View, we outline specific nosocomial CRE knowledge gaps and potential methodological approaches for their resolution.

  9. Radiation resistance of lactobacilli isolated from radurized meat relative to growth and environment.

    Science.gov (United States)

    Hastings, J W; Holzapfel, W H; Niemand, J G

    1986-10-01

    Of 113 lactobacilli isolated from radurized (5 kGy) minced meat, 7 Lactobacillus sake strains, 1 L. curvatus strain, and 1 L. farciminis strain were used for radiation resistance studies in a semisynthetic substrate (i.e., modified MRS broth). Five reference Lactobacillus spp., one Staphylococcus aureus strain, and one Salmonella typhimurium strain were used for comparative purposes. All L. sake isolates exhibited the phenomenon of being more resistant to gamma-irradiation in the exponential (log) phase than in the stationary phase of their growth cycles by a factor of 28%. Four references strains also exhibited this phenomenon, with L. sake (DSM 20017) showing a 68% increase in resistance in the log phase over the stationary phase. This phenomenon was not common to all bacteria tested and is not common to all strains with high radiation resistance. Four L. sake isolates and three reference strains were used in radiation sensitivity testing in a natural food system (i.e., meat). The bacteria were irradiated in minced meat and packaged under four different conditions (air, vacuum, CO2, and N2). Organisms exhibited the highest death rate (lowest D10 values [doses required to reduce the logarithm of the bacterial population by 1] ) under CO2 packaging conditions, but resistance to irradiation was increased under N2. The D10 values of the isolates were generally greater than those of the reference strains. The D10 values were also higher (approximately two times) in meat than in semisynthetic growth medium.

  10. Resistance of colorectal cancer cells to radiation and 5-FU is associated with MELK expression

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seungho [Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Ku, Ja-Lok, E-mail: kujalok@snu.ac.kr [Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

    2011-08-26

    Highlights: {yields} MELK expression significantly increased when the cells are exposed to radiation or 5-FU. {yields} Suppression of MELK caused cell cycle changes and decrease in proliferation. {yields} Radiation or 5-FU treatment after MELK suppression by siRNA induced growth inhibition. -- Abstract: It was reported that the local recurrence would be caused by cancer stem cells acquiring chemo- and radio-resistance. Recently, one of the potential therapeutic targets for colorectal and other cancers has been identified, which is maternal embryonic leucine zipper kinase (MELK). MELK is known as an embryonic and neural stem cell marker, and associated with the cell survival, cell proliferation, and apoptosis. In this study, SNU-503, which is a rectal cancer cell line, was treated with radiation or 5-fluorouracil (5-FU), and elevation of the MELK expression level was observed. Furthermore, the cell line was pre-treated with small interfering RNA (siRNA) against MELK mRNA before treatment of radiation or 5-FU and its effects on cell cycle and proliferation were observed. We demonstrated that knockdown of MELK reduced the proliferation of cells with radiation or 5-FU treatment. In addition, MELK suppression caused changes in cell cycle. In conclusion, MELK could be associated with increased resistance of colorectal cancer cells against radiation and 5-FU.

  11. Activation of chemical biological defense mechanisms and remission of vital oxidative injury by low dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yamaoka, K. [Okayama University Medical School, Okayama (Japan); Nomura, T. [Central Research Institute of Electric Power Industry, Tokyo (Japan); Kojima, S. [Science University of Tokyo, Chiba (Japan)

    2000-05-01

    still be evaluated. Hence, we studied the effect of low-dose X-ray irradiation on the synthesis of glutathione peroxidase (GSHP{sub x}), which is an antioxidant that catalyzes this reaction. The results suggest that H{sub 2}O{sub 2} produced by increased SOD activity can be detoxicated into H{sub 2}O and O{sub 2} due to simultaneous enhancement of the GSHP{sub x} activity by X-ray irradiation at 20 cGy, in contrast to irradiation at 400 cGy. The results also show the enhancement in enzyme activities by induction of their synthesis shortly after irradiation at 20 cGy. Moreover, as this phenomenon was observed in BALB/c mice (which are more radiation sensitive compared to other mouse strains) and radiation-resistant C57BL/6NJcl mice, it was considered to be a common phenomenon in the rat spleen. Remission of vital oxidative injury by low dose radiation: (1) We studied the effects of a single post whole-body low-dose radiation (50 cGy of {gamma}-ray) on mice with ferric nitrilotriacetate (Fe{sup 3+} - NTA)-induced transient hepatopathy. As a result, low-dose radiation accelerated the rate of recovery. Based on the changes in glutamic oxaloacetic transaminase activities, glutamic pyruvic transaminase activities and liquid peroxide levels, it was shown that hepatopathy improved by low dose radiation 3 hours after Fe{sup 3+} - NTA administration. This may be because of the enhancement of antioxidant agents such as total glutathione (GSH+GSSG), glutathione peroxidase, glutathione reductase and {gamma}-glutamylcysteine synthetase by low-dose radiation. These findings suggest that low-dose radiation relieved functional disorder at least in the livers of mice with active oxygen species related diseases. (2) Indications for treatment at the Misasa Hot Spring, a radon producing radioactive spring, include hypertension, diabetes mellitus and pain. To clarify its mechanisms of action on these conditions, we evaluated dynamic changes in blood components such as vasoactive substances

  12. Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances cellular radiation resistance

    DEFF Research Database (Denmark)

    D’Andrea, Filippo P.; Safwat, Akmal; Kassem, Moustapha;

    2011-01-01

    BackgroundCancer stem cells are thought to be a radioresistant population and may be the seeds for recurrence after radiotherapy. Using tumorigenic clones of retroviral immortalized human mesenchymal stem cell with small differences in their phenotype, we investigated possible genetic expression...... that could explain cancer stem cell radiation resistance. MethodsTumorigenic mesenchymal cancer stem cell clones BB3 and CE8 were irradiated at varying doses and assayed for clonogenic surviving fraction. Altered gene expression before and after 2Gy was assessed by Affymetric exon chip analysis and further...... found the genes involved in cancer, proliferation, DNA repair and cell death. ConclusionsThe higher radiation resistance in clone CE8 is likely due to NNMT overexpression. The higher levels of NNMT could affect the cellular damage resistance through depletion of the accessible amounts of nicotinamide...

  13. Damage Avoidance and Repair Mechanisms of Extreme Halophiles to Ionizing Radiation

    Science.gov (United States)

    2013-07-01

    tolerance   to   desiccation  that...abilities.   Early   work   on   the   desiccation   resistance   of   extremely   radiation-­‐resistant   bacteria   revealed...imparts  IR  resistance  to  these  organisms.  The  distribution  of  extremely   IR  and   desiccation

  14. Herceptin resistance database for understanding mechanism of resistance in breast cancer patients.

    Science.gov (United States)

    Ahmad, Sahil; Gupta, Sudheer; Kumar, Rahul; Varshney, Grish C; Raghava, Gajendra P S

    2014-03-27

    Monoclonal antibody Trastuzumab/Herceptin is considered as frontline therapy for Her2-positive breast cancer patients. However, it is not effective against several patients due to acquired or de novo resistance. In last one decade, several assays have been performed to understand the mechanism of Herceptin resistance with/without supplementary drugs. This manuscript describes a database HerceptinR, developed for understanding the mechanism of resistance at genetic level. HerceptinR maintains information about 2500 assays performed against various breast cancer cell lines (BCCs), for improving sensitivity of Herceptin with or without supplementary drugs. In order to understand Herceptin resistance at genetic level, we integrated genomic data of BCCs that include expression, mutations and copy number variations in different cell lines. HerceptinR will play a vital role in i) designing biomarkers to identify patients eligible for Herceptin treatment and ii) identification of appropriate supplementary drug for a particular patient. HerceptinR is available at http://crdd.osdd.net/raghava/herceptinr/.

  15. Nanoparticle mechanics: deformation detection via nanopore resistive pulse sensing

    Science.gov (United States)

    Darvish, Armin; Goyal, Gaurav; Aneja, Rachna; Sundaram, Ramalingam V. K.; Lee, Kidan; Ahn, Chi Won; Kim, Ki-Bum; Vlahovska, Petia M.; Kim, Min Jun

    2016-07-01

    Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various liposomes inside nanopores. We observed a significant difference in resistive pulse characteristics between soft liposomes and rigid polystyrene nanoparticles especially at higher applied voltages. We used theoretical simulations to demonstrate that the difference can be explained by shape deformation of liposomes as they translocate through the nanopores. Comparing our results with the findings from electrodeformation experiments, we demonstrated that the rigidity of liposomes can be qualitatively compared using resistive pulse characteristics. This application of nanopores can provide new opportunities to study the mechanics at the nanoscale, to investigate properties of great value in fundamental biophysics and cellular mechanobiology, such as virus deformability and fusogenicity, and in applied sciences for designing novel drug/gene delivery systems.Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various

  16. Resistant mechanism study of benzalkonium chloride selected Salmonella Typhimurium mutants.

    Science.gov (United States)

    Guo, Wei; Cui, Shenghui; Xu, Xiao; Wang, Haoyan

    2014-02-01

    Benzalkonium chloride is one of the invaluable biocides that is extensively used in healthcare settings as well as in the food processing industry. After exposing wild-type Salmonella Typhimurium 14028s or its AcrAB inactivation mutant to gradually increasing levels of benzalkonium chloride, resistance mutants S-41, S-150, S-AB-23, S-AB-38, and S-AB-73 were selected and these mutants also showed a 2-64-fold stable minimum inhibitory concentration (MIC) increase to chloramphenicol, ciprofloxacin, nalidixic acid, and tetracycline. In S-41 and S-150, the expression of acrB was increased 2.7- and 7.6-fold, and ΔtolC or ΔacrAB mutants of S-41 and S-150 showed the same MICs to all tested antimicrobials as the equivalent Salmonella Typhimurium 14028s mutants. However, in S-AB-23, S-AB-38, and S-AB-73, the expression of acrF was increased 96-, 230-, and 267-fold, respectively, and ΔtolC or ΔacrEF mutants of S-AB-23, S-AB-38, and S-AB-73 showed the similar MICs to all tested antimicrobials as the ΔtolC mutant of Salmonella Typhimurium 14028s. Our data showed that constitutively over-expressed AcrAB working through TolC was the main resistance mechanism in ST14028s benzalkonium chloride resistance mutants. However, after AcrAB had been inactivated, benzalkonium chloride-resistant mutants could still be selected and constitutively over-expressed, AcrEF became the dominant efflux pump working through TolC and being responsible for the increasing antimicrobial resistance. These data indicated that different mechanisms existed for acrB and acrF constitutive over-expression. Since exposure to benzalkonium chloride may lead to Salmonella mutants with a decreased susceptibility to quinolones, which is currently one of the drugs of choice for the treatment of life-threatening salmonelosis, research into the pathogenesis and epidemiology of the benzalkonium chloride resistance mutants will be of increasing importance.

  17. Molecular resistance mechanisms of macrolide-resistant invasive Streptococcus pneumoniae isolates from Alaska, 1986 to 2010.

    Science.gov (United States)

    Rudolph, Karen; Bulkow, Lisa; Bruce, Michael; Zulz, Tammy; Reasonover, Alisa; Harker-Jones, Marcella; Hurlburt, Debby; Hennessy, Thomas

    2013-11-01

    The rapid emergence of antibiotic-resistant pneumococcal strains has reduced treatment options. The aim of this study was to determine antimicrobial susceptibilities, serotype distributions, and molecular resistance mechanisms among macrolide-resistant invasive pneumococcal isolates in Alaska from 1986 to 2010. We identified cases of invasive pneumococcal disease in Alaska from 1986 to 2010 through statewide population-based laboratory surveillance. All invasive pneumococcal isolates submitted to the Arctic Investigations Program laboratory were confirmed by standard microbiological methods and serotyped by slide agglutination and the Quellung reaction. MICs were determined by the broth microdilution method, and macrolide-resistant genotypes were determined by multiplex PCR. Among 2,923 invasive pneumococcal isolates recovered from 1986 to 2010, 270 (9.2%) were nonsusceptible to erythromycin; 177 (66%) erythromycin-nonsusceptible isolates demonstrated coresistance to penicillin, and 167 (62%) were multidrug resistant. The most frequent serotypes among the macrolide-resistant isolates were serotypes 6B (23.3%), 14 (20.7%), 19A (16.7%), 9V (8.9%), 19F (6.3%), 6A (5.6%), and 23F (4.8%). mef and erm(B) genes were detected in 207 (77%) and 32 (12%) of the isolates, respectively. Nineteen (7%) of the erythromycin-nonsusceptible isolates contained both mef and erm(B) genotypes; 15 were of serotype 19A. There was significant year-to-year variation in the proportion of isolates that were nonsusceptible to erythromycin (P resistance among pneumococcal isolates from Alaska is mediated predominantly by mef genes, and this has not changed significantly over time. However, there was a statistically significant increase in the proportion of isolates that possess both erm(B) and mef, primarily due to serotype 19A isolates.

  18. Silicon space solar cells: progression and radiation-resistance analysis

    Science.gov (United States)

    Rehman, Atteq ur; Lee, Sang Hee; Lee, Soo Hong

    2016-02-01

    In this paper, an overview of the solar cell technology based on silicon for applications in space is presented. First, the space environment and its effects on the basis of satellite orbits, such as geostationary earth orbit (GEO) and low earth orbit (LEO), are described. The space solar cell technology based on silicon-based materials, including thin-film silicon solar cells, for use in space was appraised. The evolution of the design for silicon solar cell for use in space, such as a backsurface field (BSF), selective doping, and both-side passivation, etc., is illustrated. This paper also describes the nature of radiation-induced defects and the models proposed for understanding the output power degradation in silicon space solar cells. The phenomenon of an anomalous increase in the short-circuit current ( I sc) in the fluence irradiation range from 2 × 1016 cm-2 to 5 × 1016 cm-2 is also described explicitly from the view point of the various presented models.

  19. Radiation resistance of sequencing chips for in situ life detection.

    Science.gov (United States)

    Carr, Christopher E; Rowedder, Holli; Lui, Clarissa S; Zlatkovsky, Ilya; Papalias, Chris W; Bolander, Jarie; Myers, Jason W; Bustillo, James; Rothberg, Jonathan M; Zuber, Maria T; Ruvkun, Gary

    2013-06-01

    Life beyond Earth may be based on RNA or DNA if such life is related to life on Earth through shared ancestry due to meteoritic exchange, such as may be the case for Mars, or if delivery of similar building blocks to habitable environments has biased the evolution of life toward utilizing nucleic acids. In this case, in situ sequencing is a powerful approach to identify and characterize such life without the limitations or expense of returning samples to Earth, and can monitor forward contamination. A new semiconductor sequencing technology based on sensing hydrogen ions released during nucleotide incorporation can enable massively parallel sequencing in a small, robust, optics-free CMOS chip format. We demonstrate that these sequencing chips survive several analogues of space radiation at doses consistent with a 2-year Mars mission, including protons with solar particle event-distributed energy levels and 1 GeV oxygen and iron ions. We find no measurable impact of irradiation at 1 and 5 Gy doses on sequencing quality nor on low-level hardware characteristics. Further testing is required to study the impacts of soft errors as well as to characterize performance under neutron and gamma irradiation and at higher doses, which would be expected during operation in environments with significant trapped energetic particles such as during a mission to Europa. Our results support future efforts to use in situ sequencing to test theories of panspermia and/or whether life has a common chemical basis.

  20. Development of radiation-resistant magnet coils for high-intensity beam lines

    Science.gov (United States)

    Tanaka, K. H.; Yamanoi, Y.; Noumi, H.; Takasaki, M.; Saitoh, Y.; Kato, K.; Yokoi, T.; Tsukada, S.; Tanno, H.

    1994-07-01

    In connection with the Japanese Hadron Facility (JHF) project, the development of new types of radiation-resistant magnet coils has been continued at KEK. One major program is the design and production of a mineral insulation cable (MIC) with a larger maximum current. We have already developed a 2000A-class MIC having a square-cross-section hollow conductor. A sample magnet coil was fabricated with this MIC. Tests of its stability and reliability are under progress. We are now planning to develop a 3000A-class MIC. The other program is R/D work on a completely inorganic wrapping insulation material which can be used like the usual type glass-fiber tape pre-impregnated with epoxy-resin. After tests of the mechanical strength and electric insulation of many combinations of tapes and bonds, we found a pure (99%) alumina-fiber tape pre-impregnated with inorganic cement that is suitable for a magnet coil insulator after thermal curing.

  1. Development of radiation resistant grades of beryllium for nuclear and fusion facilities

    Energy Technology Data Exchange (ETDEWEB)

    Kupriyanov, I.B.; Gorokhov, V.A.; Nikolaev, G.N. [Russia Research Institute of Inorganic Materials, Moscow (Russian Federation)

    1995-09-01

    R&D results on beryllium with high radiation resistance obtained recently are described in this report. The data are presented on nine different grades of isotropic beryllium manufactured by VNIINM and distinguished by both initial powder characteristics and properties of billets, made of these powders. The average grain size of the investigated beryllium grades varied from 8 to 26 {mu}m, the content of beryllium oxide was 0.9 - 3.9 wt.%, the dispersity of beryllium oxide - 0.04 - 0.5 {mu}m, tensile strength -- 250 - 650 MPa. All materials were irradiated in SM - 2 reactor over the temperature range 550 - 780{degrees}C. The results of the investigation showed, that HIP beryllium grades are less susceptible to swelling at higher temperatures in comparison with hot pressed and extruded grades. Beryllium samples, having the smallest grain size, demonstrated minimal swelling, which was less than 0.8 % at 750{degrees}C and Fs = 3.7 {center_dot}10{sup 21} cm{sup -2} (E>0.1 MeV). The mechanical properties, creep and microstructure parameters, measured before and after irradiation, are presented.

  2. Radiation resistivity of BGO crystals due to low-energy gamma-rays

    CERN Document Server

    Kozma, P

    2003-01-01

    Radiation resistivity of 4x4x30 mm sup 3 BGO crystals from three suppliers has been studied for doses 10 sup 4 Gy (10 sup 6 rad) and 10 sup 5 Gy (10 sup 7 rad). Radiation hardness was examined by the measurement of optical transmission through BGO crystals before and after sup 6 sup 0 Co gamma-ray irradiations. The absolute degradation of transmission for 10 sup 4 and 10 sup 5 Gy doses at 480 nm wavelength of the peak emission of BGO, was found to be lower than 3.4% and 7.5%, respectively. The results have been also compared with radiation hardness measurements for a large volume diameter 30x30 mm sup 3 BGO crystal as well as another heavy scintillation crystals: fluorides and tungstates. Complete recovery of BGO radiation damage was observed only after few days.

  3. Sunlight-exposed biofilm microbial communities are naturally resistant to chernobyl ionizing-radiation levels.

    Science.gov (United States)

    Ragon, Marie; Restoux, Gwendal; Moreira, David; Møller, Anders Pape; López-García, Purificación

    2011-01-01

    The Chernobyl accident represents a long-term experiment on the effects of exposure to ionizing radiation at the ecosystem level. Though studies of these effects on plants and animals are abundant, the study of how Chernobyl radiation levels affect prokaryotic and eukaryotic microbial communities is practically non-existent, except for a few reports on human pathogens or soil microorganisms. Environments enduring extreme desiccation and UV radiation, such as sunlight exposed biofilms could in principle select for organisms highly resistant to ionizing radiation as well. To test this hypothesis, we explored the diversity of microorganisms belonging to the three domains of life by cultivation-independent approaches in biofilms developing on concrete walls or pillars in the Chernobyl area exposed to different levels of radiation, and we compared them with a similar biofilm from a non-irradiated site in Northern Ireland. Actinobacteria, Alphaproteobacteria, Bacteroidetes, Acidobacteria and Deinococcales were the most consistently detected bacterial groups, whereas green algae (Chlorophyta) and ascomycete fungi (Ascomycota) dominated within the eukaryotes. Close relatives to the most radio-resistant organisms known, including Rubrobacter species, Deinococcales and melanized ascomycete fungi were always detected. The diversity of bacteria and eukaryotes found in the most highly irradiated samples was comparable to that of less irradiated Chernobyl sites and Northern Ireland. However, the study of mutation frequencies in non-coding ITS regions versus SSU rRNA genes in members of a same actinobacterial operational taxonomic unit (OTU) present in Chernobyl samples and Northern Ireland showed a positive correlation between increased radiation and mutation rates. Our results show that biofilm microbial communities in the most irradiated samples are comparable to non-irradiated samples in terms of general diversity patterns, despite increased mutation levels at the single

  4. Investigation of Radiation Resistant Polymer Photodetectors for Space Applications

    Science.gov (United States)

    2002-09-11

    Phys. Lett., Vol. 298, 315-9, (1998). 12. A. L. Linsebigler, G. Lu and J. T. Yates, " Photocatalysis on TiO2 Surfaces: Principles, Mechanisms and...7 2. Diagram of a molecular dye-sensitized TiO2 PV cell. 10 3. Chemical structure of tris(4,7-diphenyl-1,10-phenanthroline) ruthenium...photovoltaic dye-sensitized PV cell behavior. 13 6. Photovoltaic output of Ru complex Ru(ph2Phen)3Cl2 stained- TiO2 PV cell, for a TiO2 film thickness

  5. Assessment of Resistance of Bacillus Horneckiae Endospores to UV Radiation and Function of Their Extraneous Layer in Resistance

    Science.gov (United States)

    Zachariah, Malcolm M.; Vaishampayan, Parag

    2011-01-01

    Spore-forming microbes are highly resistant to various physical and chemical conditions, which include ionizing and UV radiation, desiccation and oxidative stress, and the harsh environment of outer space or planetary surfaces. The spore's resistance might be due to their metabolically dormant state, and/or by the presence of a series of protective structures that encase the interior-most compartment, the core, which houses the spore chromosome. These spores have multiple layers surrounding the cell that are not found in vegetative cells, and some species have an outer layer of proteins and glycoproteins termed the "exosporium" or a fibrous "extraneous layer" (EL). Bacillus horneckiae is an EL-producing novel sporeformer isolated from a Phoenix spacecraft assembly clean room, and it has previously demonstrated resistance to UV radiation up to 1000 J/m(sup 2). The EL appears to bind B. horneckiae spores into large aggregations, or biofilms, and may confer some UV resistance to the spores. Multiple culturing and purification schemes were tried to achieve high purity spores because vegetative cells would skew UV resistance results. An ethanol-based purification scheme produced high purity spores. Selective removal of the EL from spores was attempted with two schemes: a chemical extraction method and physical extraction (sonication). Results from survival rates in the presence and absence of the external layer will provide a new understanding of the role of biofilms and passive resistance that may favor survival of biological systems in aggressive extra-terrestrial environments. The chemical extraction method decreased viable counts of spores and lead to an inconclusive change UV resistance relative to non-extracted spores. The physical extraction method lead to non-aggregated spores and did not alter viability; however, it produced UV resistance profiles similar to non-extracted spores. In addition to the EL-removal study, samples of B. horneckiae spores dried on

  6. Mechanisms of resistance and tolerance to Mycosphaerella graminicola in wheat.

    Science.gov (United States)

    El Chartouni, Léa; Randoux, B; Duyme, F; Renard-Merlier, D; Tisserant, B; Bourdon, N; Pillon, V; Sanssené, J; Durand, R; Halama, P; Reignault, Ph

    2009-01-01

    The aim of this study was to investigate the infection process of M. graminicola and the defence mechanisms related to active oxygen species (AOS) in five French wheat cultivars. These cultivars exhibited various resistant levels to M. graminicola infection: Maxyl, Caphorn and Gen11 are susceptible cultivars, whereas Capnor and Gen23 show high levels of quantitative resistances. In addition, Capnor, Gen23 and Gen11 are tolerant cultivars, i.e., their yield performance was less affected by infection compared to non-tolerant cultivars. Cultivars were inoculated with the IPO323 reference M. graminicola strain. First wheat leaves were collected 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 days after inoculation. The cytological and antioxidant response of the cultivars were both studied over the whole time course. Although infection occurred mainly through stomata, direct penetration attempts were also scored. Moreover, papilla formation turned out to be very rare. Assays for changes in peroxydase (PO), glutathione-S-transferase (GST) and lipoxygenase (LOX) activities allowed us to compare their levels in the five French wheat cultivars regarding to their resistance and/or tolerance towards M. graminicola infection. PO and GST were correlated to necrosis probably as a consequence of detoxification and LOX was related to some of the germination process steps. We also showed that significant differences for several biochemical parameters exist between the studied cultivars in non inoculated conditions but these differences were less important in the presence of the fungus.

  7. Molecular mechanisms of insulin resistance in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Mark W Douglas; Jacob George

    2009-01-01

    It is now widely recognized that chronic hepatitis C (CHC) is associated with insulin resistance (IR) and type 2 diabetes, so can be considered a metabolic disease. IR is most strongly associated with hepatitis C virus (HCV) genotype 1, in contrast to hepatic steatosis, which is associated with genotype 3 infection. Apart from the well-described complications of diabetes, IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma. More recently, it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined. This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.

  8. Investigation of gamma-ray fingerprint identifying mechanism for the types of radiation sources

    CERN Document Server

    Liu Su Ping; Gu Dang Chang; Gong-Jian; Hao Fan Hua; Hu Guang Chun

    2002-01-01

    Radiation fingerprints sometimes can be used to label and identify the radiation resources. For instance, in a future nuclear reduction treaty that requires verification of irreversible dismantling of reduced nuclear warheads, the radiation fingerprints of nuclear warheads are expected to play a key role in labelling and identifying the reduced warheads. It would promote the development of nuclear warheads deep-cuts verification technologies if authors start right now some investigations on the issues related to the radiation fingerprints. The author dedicated to the investigation of gamma-ray fingerprint identifying mechanism for the types of radiation resources. The purpose of the identifying mechanism investigation is to find a credible way to tell whether any two gamma-ray spectral fingerprints that are under comparison are radiated from the same resource. The authors created the spectrum pattern comparison (SPC) to study the comparability of the two radiation fingerprints. Guided by the principle of SPC,...

  9. [Cellular and molecular mechanisms of radiation-induced brain injury: can peripheral markers be detected?].

    Science.gov (United States)

    Piskunov, A K; Nikitin, K V; Potapov, A A

    2015-01-01

    Investigation of the mechanisms of radiation-induced brain injury is a relevant fundamental objective of radiobiology and neuroradiology. Damage to the healthy brain tissue is the key factor limiting the application of radiation therapy in patients with nervous systems neoplasms. Furthermore, postradiation brain injury can be clinically indiscernible from continued tumor growth and requires differential diagnosis. Thus, there exists high demand for biomarkers of radiation effects on the brain in neurosurgery and radiobiology. These markers could be used for better understanding and quantifying the effects of ionizing radiation on brain tissues, as well as for elaborating personalized therapy. Despite the high demand, biomarkers of radiation-induced brain injury have not been identified thus far. The cellular and molecular mechanisms of the effect of ionizing radiation on the brain were analyzed in this review in order to identify potential biomarkers of radiation-induced injury to nervous tissue.

  10. Resistance in the mosquito, Culex quinquefasciatus, and possible mechanisms for resistance.

    Science.gov (United States)

    Xu, Qiang; Liu, Huqi; Zhang, Lee; Liu, Nannan

    2005-11-01

    Two mosquito strains of Culex quinquefasciatus (Say), MAmCq(G0) and HAmCq(G0), were collected from Mobile and Huntsville, Alabama, respectively. MAmCq(G0) and HAmCq(G0) were further selected in the laboratory with permethrin for one and three generations, respectively. The levels of resistance to permethrin in MAmCq(G1) (after one-generation selection) and HAmCq(G3) (after three-generation selection) increased rapidly. Resistance to permethrin in MAmCq(G1) and HAmCq(G3) was partially suppressed by piperonyl butoxide (PBO), S,S,S-tributylphosphorotrithioate (DEF) and diethyl maleate (DEM), inhibitors of cytochrome P450 monooxygenases, hydrolases and glutathione S-transferases (GST), respectively, suggesting these three enzyme families are important in conferring permethrin resistance in both strains. A substitution of leucine to phenylalanine (L to F) resulting from a single nucleotide polymorphism (SNP), termed the kdr mutation, in the para-homologous sodium channel gene has been reported as a very common mutation associated with pyrethroid resistance of insects. A 341-bp sodium channel gene fragment, where the kdr mutation resides, was generated by PCR from genomic DNAs of Cx. quinquefasciatus strains. We found that the kdr mutation was present in both permethrin-selected and unselected HAmCq and MAmCq mosquito populations, suggesting that the kdr mutation plays the role in permethrin resistance. There was no significant change in the frequency and heterozygosity of the A to T SNP for the kdr allele between permethrin-selected and unselected MAmCq and HAmCq mosquitoes, indicating that other mechanisms are involved in the evolution of resistance in mosquitoes selected by permethrin in the laboratory. Copyright 2005 Society of Chemical Industry.

  11. Increasing the radiation resistance of single-crystal silicon epitaxial layers

    Directory of Open Access Journals (Sweden)

    Kurmashev Sh. D.

    2014-12-01

    Full Text Available The authors investigate the possibility of increasing the radiation resistance of silicon epitaxial layers by creating radiation defects sinks in the form of dislocation networks of the density of 109—1012 m–2. Such networks are created before the epitaxial layer is applied on the front surface of the silicon substrate by its preliminary oxidation and subsequent etching of the oxide layer. The substrates were silicon wafers KEF-4.5 and KDB-10 with a diameter of about 40 mm, grown by the Czochralski method. Irradiation of the samples was carried out using electron linear accelerator "Electronics" (ЭЛУ-4. Energy of the particles was 2,3—3,0 MeV, radiation dose 1015—1020 m–2, electron beam current 2 mA/m2. It is shown that in structures containing dislocation networks, irradiation results in reduction of the reverse currents by 5—8 times and of the density of defects by 5—10 times, while the mobility of the charge carriers is increased by 1,2 times. Wafer yield for operation under radiation exposure, when the semiconductor structures are formed in the optimal mode, is increased by 7—10% compared to the structures without dislocation networks. The results obtained can be used in manufacturing technology for radiation-resistant integrated circuits (bipolar, CMOS, BiCMOS, etc..

  12. Molecular fingerprinting of radiation resistant tumors: Can we apprehend and rehabilitate the suspects?

    Directory of Open Access Journals (Sweden)

    Gaar Micah

    2009-07-01

    Full Text Available Abstract Radiation therapy continues to be one of the more popular treatment options for localized prostate cancer. One major obstacle to radiation therapy is that there is a limit to the amount of radiation that can be safely delivered to the target organ. Emerging evidence suggests that therapeutic agents targeting specific molecules might be combined with radiation therapy for more effective treatment of tumors. Recent studies suggest that modulation of these molecules by a variety of mechanisms (e.g., gene therapy, antisense oligonucleotides, small interfering RNA may enhance the efficacy of radiation therapy by modifying the activity of key cell proliferation and survival pathways such as those controlled by Bcl-2, p53, Akt/PTEN and cyclooxygenase-2. In this article, we summarize the findings of recent investigations of radiosensitizing agents in the treatment of prostate cancer.

  13. Hypergravity experiments to evaluate gravity resistance mechanisms in plants.

    Science.gov (United States)

    Soga, Kouichi; Yano, Sachiko; Matsumoto, Shouhei; Hoson, Takayuki

    2015-01-01

    Hypergravity generated by centrifugal acceleration is the only practical method to modify the magnitude of gravitational acceleration for a sufficient duration on Earth and has been used to analyze the nature and mechanism of graviresponse, particularly gravity resistance, in plants. Plant organs are generally resistant to gravitational acceleration. Hypergravity produced from centrifugation speeds in the range of 10-300 × g, which is easily produced by a benchtop centrifuge, is often used during plant experiments. After centrifugation, the plant material is fixed with suitable fixatives in appropriate sample storage containers such as the Chemical Fixation Bag. The material is then analyzed with a variety of methods, depending on the purpose of the experiment. Plant material fixed with the RNAlater(®) solution can be sequentially used for determining the mechanical properties of the cell wall, for RNA extraction (which is necessary for gene expression analysis), for estimating the enzyme activity of the cell wall proteins, and for determining the levels as well as the compositions of cell wall polysaccharides. The plant material can also be used directly for microscopic observation of cellular components such as cortical microtubules.

  14. Radiation Resistance of Fluorine-Implanted PNP Using Gated-Controlled Lateral PNP Transistor Structure

    Institute of Scientific and Technical Information of China (English)

    Xin Wang; Wu Lu; Wu-Ying Ma; Qi Guo; Zhi-Kuan Wang; Cheng-Fa He; Mo-Han Liu

    2016-01-01

    The radiation damage responses of fluorinated and non-fluorinated lateral PNP transistors are studied with specially designed gated-controlled lateral PNP transistors that allow for the extraction of the oxide trapped charge (Not) and interface trap (Nit) densities.All the samples are exposed in the Co-60γ ray with the dose rate of 0.5 Gy(Si)/s.After the irradiation,the buildup of Not and Nit of the samples with total dose is investigated by the gate sweep test technique.The results show that the radiation resistance of fluorinated lateral PNP transistors is significantly enhanced compared with the non-fluorinated ones.

  15. Unusual resistance to ionizing radiation of the viruses of kuru, Creutzfeldt-Jakob disease, and scrapie.

    Science.gov (United States)

    Gibbs, C J; Gajdusek, D C; Latarjet, R

    1978-01-01

    The titers of several preparations of kuru. Creutzfeldt-Jacob disease, and scrapie viruses were reduced by only 1/10th or less by high doses of gamma radiation of 50 kGy and by only 1/10th-1/1000th or less for 200 kGy. This unusual radiation resistance of the two human viruses further links them with the scrapie virus and suggests that the genetic information of all three viruses is considerably smaller than that of any other known viruses of mammals. PMID:104301

  16. Determination of metabolic resistance mechanisms in pyrethroid-resistant and fipronil-tolerant brown dog ticks.

    Science.gov (United States)

    Eiden, A L; Kaufman, P E; Oi, F M; Dark, M J; Bloomquist, J R; Miller, R J

    2017-09-01

    Rhipicephalus sanguineus (Latreille) (Ixodida: Ixodidae) is a three-host dog tick found worldwide that is able to complete its' entire lifecycle indoors. Options for the management of R. sanguineus are limited and its' control relies largely on only a few acaricidal active ingredients. Previous studies have confirmed permethrin resistance and fipronil tolerance in R. sanguineus populations, commonly conferred by metabolic detoxification or target site mutations. Herein, five strains of permethrin-resistant and three strains of fipronil-tolerant ticks were evaluated for metabolic resistance using synergists to block metabolic enzymes. Synergist studies were completed with triphenyl phosphate (TPP) for esterase inhibition, piperonyl butoxide (PBO) for cytochrome P450 inhibition, and diethyl maleate (DEM) for glutathione-S-transferase inhibition. Additionally, increased esterase activity was confirmed using gel electrophoresis. The most important metabolic detoxification mechanism in permethrin-resistant ticks was increased esterase activity, followed by increased cytochrome P450 activity. The inhibition of metabolic enzymes did not have a marked impact on fipronil-tolerant tick strains. © 2017 The Royal Entomological Society.

  17. Study of the resistance mechanisms to ultraviolet light in Escherichia Coli. III. Genetic mapping of a mutation that confers resistance to radiation; Mecanismos de resistencia a luz ultravioleta en Escherichia coli. III. Mapeo genetico de una mutacion que confiere resistencia a radiacion

    Energy Technology Data Exchange (ETDEWEB)

    Alcantara D, D. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    1996-08-15

    Inside this third work with respect to the investigation of the process of adaptation of different subcultures of Escherichia coli, to the UV light, its are present the obtained results in the identification of the gene or genes implied in the resistance to UV of one of the 5 populations derived for repeated exposure to growing dose of UV light of E. coli PQ30. Those obtained data indicate that the causing mutation of the phenotype is located in a single gene, since the insert of the fragment of DNA miniTn5 in this gene, causes the lost one from the resistance and the return to the original phenotype. The gene in question is denominated radA, located in the minute 99.6 of the chromosome of E. coli and required for the efficient repair of double ruptures in the DNA. (Author)

  18. Chromosome aberrations as biomarkers of radiation exposure: Modelling basic mechanisms

    Science.gov (United States)

    Ballarini, F.; Ottolenghi, A.

    The space radiation environment is a mixed field consisting of different particles having different energies, including high charge and energy (HZE) ions. Conventional measurements of absorbed doses may not be sufficient to completely characterise the radiation field and perform reliable estimates of health risks. Biological dosimetry, based on the observation of specific radiation-induced endpoints (typically chromosome aberrations), can be a helpful approach in case of monitored exposure to space radiation or other mixed fields, as well as in case of accidental exposure. Furthermore, various ratios of aberrations (e.g. dicentric chromosomes to centric rings and complex exchanges to simple exchanges) have been suggested as possible fingerprints of radiation quality, although all of them have been subjected to some criticisms. In this context a mechanistic model and a Monte Carlo code for the simulation of chromosome aberration induction were developed. The model, able to provide dose-responses for different aberrations (e.g. dicentrics, rings, fragments, translocations, insertions and other complex exchanges), was further developed to assess the dependence of various ratios of aberrations on radiation quality. The predictions of the model were compared with available data, whose experimental conditions were faithfully reproduced. Particular attention was devoted to the scoring criteria adopted in different laboratories and to possible biases introduced by interphase death and mitotic delay. This latter aspect was investigated by taking into account both metaphase data and data obtained with Premature Chromosome Condensation (PCC).

  19. Neoplastic human embryonic stem cells as a model of radiation resistance of human cancer stem cells.

    Science.gov (United States)

    Dingwall, Steve; Lee, Jung Bok; Guezguez, Borhane; Fiebig, Aline; McNicol, Jamie; Boreham, Douglas; Collins, Tony J; Bhatia, Mick

    2015-09-08

    Studies have implicated that a small sub-population of cells within a tumour, termed cancer stem cells (CSCs), have an enhanced capacity for tumour formation in multiple cancers and may be responsible for recurrence of the disease after treatment, including radiation. Although comparisons have been made between CSCs and bulk-tumour, the more important comparison with respect to therapy is between tumour-sustaining CSC versus normal stem cells that maintain the healthy tissue. However, the absence of normal known counterparts for many CSCs has made it difficult to compare the radiation responses of CSCs with the normal stem cells required for post-radiotherapy tissue regeneration and the maintenance of tissue homeostasis. Here we demonstrate that transformed human embryonic stem cells (t-hESCs), showing features of neoplastic progression produce tumours resistant to radiation relative to their normal counterpart upon injection into immune compromised mice. We reveal that t-hESCs have a reduced capacity for radiation induced cell death via apoptosis and exhibit altered cell cycle arrest relative to hESCs in vitro. t-hESCs have an increased expression of BclXL in comparison to their normal counterparts and re-sensitization of t-hESCs to radiation upon addition of BH3-only mimetic ABT737, suggesting that overexpression of BclXL underpins t-hESC radiation insensitivity. Using this novel discovery platform to investigate radiation resistance in human CSCs, our study indicates that chemotherapy targeting Bcl2-family members may prove to be an adjuvant to radiotherapy capable of targeting CSCs.

  20. Large-Scale Procurement of Radiation Resistant Single-Mode Optical Fibers for CERN

    CERN Document Server

    Guillermain, Elisa; Kuhnhenn, Jochen; Ricci, Daniel; Weinand, Udo

    2015-01-01

    2400 km of special radiation resistant optical fibres were procured by CERN (European Organization for Nuclear Research), for the installation of more than 55 km of optical fibre cables in the accelerator complex underground during the Long Shutdown 1 (LS1). In the frame of this large-scale industrial production, a thorough quality assurance plan (QAP) was put in place and followed at each step of the process. In-depth qualification of optical fibres preceded the 17-month procurement process. All supplied batches were tested for their resistance to radiation, leading to more than 65 quality control irradiation tests. During the cable assembly process and the installations works, a full traceability down to the optical fibre level was ensured. The actions put in place in the frame of the QAP led to successful installation works and to full respect of the LS1 planning.

  1. A novel fast response and radiation-resistant scintillator detector for beam loss monitor

    Science.gov (United States)

    Ji, Y.; Tang, Z.; Li, C.; Li, X.; Shao, M.

    2017-07-01

    At high luminosity area, beam loss monitor with fast response and high radiation resistance is crucial for accelerator operation. In this article, we report the design and test results of a fast response and radiation-resistant scintillator detector as the beam loss monitor for high luminosity collider, especially at low energy region such as RFQ. The detector is consisted of a 2 cm× 2 cm× 0.5 cm LYSO crystal readout by a 6 mm × 6 mm Silicon photomultiplier. Test results from various radioactive sources show that the detector has good sensitivity to photons from tens of keV to several MeV with good linearity and energy resolution (23% for 60 keV γ-ray). For field test, two such detectors are installed outside of the vacuum chamber shell of an 800 MeV electron storage ring. The details of the test and results are introduced.

  2. Mechanisms of virus resistance and antiviral activity of snake venoms

    Directory of Open Access Journals (Sweden)

    JVR Rivero

    2011-01-01

    Full Text Available Viruses depend on cell metabolism for their own propagation. The need to foster an intimate relationship with the host has resulted in the development of various strategies designed to help virus escape from the defense mechanisms present in the host. Over millions of years, the unremitting battle between pathogens and their hosts has led to changes in evolution of the immune system. Snake venoms are biological resources that have antiviral activity, hence substances of significant pharmacological value. The biodiversity in Brazil with respect to snakes is one of the richest on the planet; nevertheless, studies on the antiviral activity of venom from Brazilian snakes are scarce. The antiviral properties of snake venom appear as new promising therapeutic alternative against the defense mechanisms developed by viruses. In the current study, scientific papers published in recent years on the antiviral activity of venom from various species of snakes were reviewed. The objective of this review is to discuss the mechanisms of resistance developed by viruses and the components of snake venoms that present antiviral activity, particularly, enzymes, amino acids, peptides and proteins.

  3. New mechanism of radiation polarization in Seyfert-1 AGNs

    CERN Document Server

    Silant'ev, N A; Piotrovich, M Yu; Natsvlishvili, T M; Buliga, S D

    2016-01-01

    In most of Seyfert-1 active galactic nucei (AGN) the optical linear continuum polarization degree is usually small (less than 1%) and the polarization position angle is nearly parallel to the AGN radio-axis. However, there are many types-1 AGNs with unexplained intermediate values for both positional angles and polarization degrees. Our explanation of polarization degree and positional angle of Seyfert-1 AGNs focuses on the reflection of non-polarized radiation from sub-parsec jets in optically thick accretion discs. The presence of a magnetic field surrounding the scattering media will induce Faraday rotation of the polarization plane that may explain the intermediate values of positional angles if there is a magnetic field component normal to the accretion disc. The Faraday rotation depolarization effect in disc diminishes the competition between polarization of the reflected radiation with the parallel component of polarization and the perpendicular polarization from internal radiation of disc (the Milne p...

  4. Modification of silicone sealant to improve gamma radiation resistance, by addition of protective agents

    Science.gov (United States)

    González-Pérez, Giovanni; Burillo, Guillermina

    2013-09-01

    Poly (dimethylsiloxane) (PDMS) sealant (SS) was modified with the addition of different protective compounds to conserve its physical-chemical properties during gamma irradiation. 2-Vinyl naphthalene (2-VN), bisphenol-A (BPA) and poly (vinyl carbazole) (PVK) were used to evaluate radiation protection through the crosslinking effect of radiation. The samples were irradiated with doses from 100 kGy to 500 kGy at room temperature in air, with a 60Co gamma source, and the changes in molecular weight, thermal behavior, elastic properties and infrared spectra (FTIR-ATR) absorbance analysis were determined. The molecular weight of unmodified silicone sealant increases with the absorbed dose because of crosslinking as predominant effect. However, the crosslinking effect was inhibited with the addition of protective agent due to the aromatic compounds present. Modified silicone sealant films present better radiation resistance than unmodified system.

  5. Energetics and the resistive tearing mode - Effects of Joule heating and radiation

    Science.gov (United States)

    Steinolfson, R. S.

    1983-01-01

    The contribution of energy flux to the dynamics of magnetic field reconnection is analytically studied in order to determine the influence of Joule heating and radiation on the linear development of the tearing instability in slab geometry. A temperature-dependent Coulomb-like resistivity is used to provide the coupling between the dynamics and the energy equation. Analytical expressions are derived for the growth rates utilizing constant-psi and long-wavelength approximations. The solutions indicate the occurrence of several modes in addition to the usual tearing mode, several of which have relatively slow, complex growth rates. At large values of the magnetic Reynolds number, there are at least two modes with purely exponential growth when the radiative loss decreases with increasing temperature. If the radiation is neglected, the Joule heating alone also results in two modes with real, positive growth at large S. Below a particular value of S, all the modes are generally stabilized.

  6. Radiation-Resistant Hybrid Lotus Effect for Achieving Photoelectrocatalytic Self-Cleaning Anticontamination Coatings

    Science.gov (United States)

    Taylor, Edward W.; Pirich, Ronald G.

    2011-01-01

    An experiment involving radiation-resistant hydrophobic coatings is planned for space exposure and experimental testing on the International Space Station (ISS) in 2011. The Lotus biocide coatings are designed for supporting space exploration missions. This innovation is an antibacterial, anti-contamination, and self-cleaning coating that uses nano-sized semiconductor semimetal oxides to neutralize biological pathogens and toxic chemicals, as well as to mitigate dust accumulation (see figure). The Lotus biocide coating is thin (approximately microns thick), lightweight, and the biocide properties will not degrade with time or exposure to biological or chemical agents. The biocide is stimulated chemically (stoichiometric reaction) through exposure to light (photocatalysis), or by an applied electric field (electrocatalysis). The hydrophobic coating samples underwent preliminary high-energy proton and alpha-ray (helium ion) irradiations at the Lawrence Berkeley National Laboratory 88" cyclotron and demonstrated excellent radiation resistance for a portion of the Galactic Cosmic Ray (GRC) and Solar Proton spectrum. The samples will undergo additional post-flight studies when returned to Earth to affirm further the radiation resistance properties of the space exposed coatings.

  7. Processing characteristic and radiation resistance of various epoxy insulation materials for superconducting magnets

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zhixiong [Key Laboratory of Cryogenics, TIPC, CAS, Beijing 100190 (China); Li, Jingwen [Key Laboratory of Cryogenics, TIPC, CAS, Beijing 100190 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Huang, Chuanjun [Key Laboratory of Cryogenics, TIPC, CAS, Beijing 100190 (China); Huang, Rongjin [Key Laboratory of Cryogenics, TIPC, CAS, Beijing 100190 (China); State Key Laboratory of Technologies in Space Cryogenic Propellants, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Li, Laifeng, E-mail: laifengli@mail.ipc.ac.cn [Key Laboratory of Cryogenics, TIPC, CAS, Beijing 100190 (China); State Key Laboratory of Technologies in Space Cryogenic Propellants, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190 (China)

    2013-11-15

    Highlights: • We studied the processing properties of various epoxy matrices. • We studied the radiation resistance of TGPAP-based and DGEBF-based composites. • TGPAP-based systems are more suitable for VPI process than DGEBF-based systems. • TGPAP systems present more radiation resistant than DGEBF systems. -- Abstract: Glass fiber reinforced epoxy-based composites were developed as insulating materials for fusion superconducting magnets. The processing properties of various epoxy matrices were investigated in terms of the isothermal viscosity at 45 °C. The interlaminar shear strength (ILSS) at 77 K and the thermal expansion coefficient (CTE) of the composites were assessed before and after gamma irradiation at ambient temperature up to 10 MGy. It is found that the TGPAP-based systems showed lower initial viscosities, longer working life and higher radiation resistance compared to the DGEBF-based systems with the same modifier. Furthermore, there was no significant effect of the irradiation dose on the CTE of the composites.

  8. DNA Protection Protein, a Novel Mechanism of Radiation Tolerance: Lessons from Tardigrades

    Directory of Open Access Journals (Sweden)

    Takuma Hashimoto

    2017-06-01

    Full Text Available Genomic DNA stores all genetic information and is indispensable for maintenance of normal cellular activity and propagation. Radiation causes severe DNA lesions, including double-strand breaks, and leads to genome instability and even lethality. Regardless of the toxicity of radiation, some organisms exhibit extraordinary tolerance against radiation. These organisms are supposed to possess special mechanisms to mitigate radiation-induced DNA damages. Extensive study using radiotolerant bacteria suggested that effective protection of proteins and enhanced DNA repair system play important roles in tolerability against high-dose radiation. Recent studies using an extremotolerant animal, the tardigrade, provides new evidence that a tardigrade-unique DNA-associating protein, termed Dsup, suppresses the occurrence of DNA breaks by radiation in human-cultured cells. In this review, we provide a brief summary of the current knowledge on extremely radiotolerant animals, and present novel insights from the tardigrade research, which expand our understanding on molecular mechanism of exceptional radio-tolerability.

  9. DNA Protection Protein, a Novel Mechanism of Radiation Tolerance: Lessons from Tardigrades

    Science.gov (United States)

    Hashimoto, Takuma; Kunieda, Takekazu

    2017-01-01

    Genomic DNA stores all genetic information and is indispensable for maintenance of normal cellular activity and propagation. Radiation causes severe DNA lesions, including double-strand breaks, and leads to genome instability and even lethality. Regardless of the toxicity of radiation, some organisms exhibit extraordinary tolerance against radiation. These organisms are supposed to possess special mechanisms to mitigate radiation-induced DNA damages. Extensive study using radiotolerant bacteria suggested that effective protection of proteins and enhanced DNA repair system play important roles in tolerability against high-dose radiation. Recent studies using an extremotolerant animal, the tardigrade, provides new evidence that a tardigrade-unique DNA-associating protein, termed Dsup, suppresses the occurrence of DNA breaks by radiation in human-cultured cells. In this review, we provide a brief summary of the current knowledge on extremely radiotolerant animals, and present novel insights from the tardigrade research, which expand our understanding on molecular mechanism of exceptional radio-tolerability. PMID:28617314

  10. SULFATE RESISTANCE MECHANISM OF HIGH-PERFORMANCE CONCRETE CONTAINING NCI

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    It is found that the incorporation of Nitrite Corrosion Inhibitor (NCI) greatly weakens the resistance of mixtures to sulfate attack.To study the mechanism of this phenomenon,in this paper,the influence of NCI additionon on the cement paste and microstructure change of high performance concrete specimens is studied by means of quantitative XRD,SEM tests.The results demonstrate that the incorporation of NCI accelerates the formation of calcium hydroxide and ettringite crystals,and weakens the pore refinement effect caused by the secondary hydration reaction of fly ash and microsilica.At the age up to one year,the relative crystal quantity in mixture containing NCI is always higher than that in control mixture.The reasons for the degradation in sulfate resisitance of mixtures may be attributed to the increase and stability of the calcium hydroxide and ettringite crystals formed and the weakening of secondary hydration reaction.Based on the results,conclusion can be drawn that NCI should be used cautiously in practical engineering where high resistance to sulfate attack is required.

  11. Trastuzumab: updated mechanisms of action and resistance in breast cancer

    Directory of Open Access Journals (Sweden)

    Francois X. Claret

    2012-06-01

    Full Text Available HER2-postitive breast cancer has the second-poorest prognosis among breast cancer subtypes. One of the most effective targeted therapies for patients with HER2-positive breast cancer is trastuzumab-based. However, primary or acquired resistance to trastuzumab has been a major obstacle in the clinical management of this disease. Therefore, to better control HER2-postitive breast cancer, it is necessary to gain a deeper understanding of trastuzumab’s actions and the pathways that cancer cells use to dodge its effects. In this review, we attempt to give an overview of the widely accepted and currently proposed molecular mechanisms for these actions and highlight recent advances in our understanding of HER2 targeted therapies.

  12. Molecular Epidemiology of Aspergillus fumigatus Isolates Harboring the TR34/L98H Azole Resistance Mechanism.

    NARCIS (Netherlands)

    Camps, S.M.T.; Rijs, A.J.M.M.; Klaassen, C.H.; Meis, J.F.G.M.; O'Gorman, C.M.; Dyer, P.S.; Melchers, W.J.G.; Verweij, P.E.

    2012-01-01

    A rapid emergence of azole resistance has been observed in Aspergillus fumigatus in The Netherlands over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves the TR(34)/L98H mutations in cyp51A. This resistance mechanism is now also increasingly being

  13. Elimination of Listeria monocytogenes in sausage meat by combination treatment: Radiation and radiation-resistant bacteriocins

    Science.gov (United States)

    Turgis, Mélanie; Stotz, Viviane; Dupont, Claude; Salmieri, Stéphane; Khan, Ruhul A.; Lacroix, Monique

    2012-08-01

    Two new bacteria were isolated from human feces and were designated MT 104 and MT 162. They were able to produce bacteriocins that are active against five strains of Listeria monocytogenes. Bacteriocins produced by these isolated strains had 100% and 82.35% residual activity when they were treated by gamma radiation at doses of 4 and 40 kGy, respectively. A reduction of 1.0, 1.5 and 3 log CFU/g of L. monocytogenes was observed in sausage meat when treated with bacteriocins from MT 104, MT 162, and nisin, respectively. For synergic effect, the D10 value in presence of the bacteriocins produced by MT 104 showed a 1.08 fold increased relative sensitivity of L. monocytogenes as compared to control after 5 days. The highest synergic effect was observed in presence of nisin which led to 1.61 fold increased relative sensitivity. Combined treatments with nisin and γ-irradiation showed a synergic antimicrobial effect in meat after 24 h and 5 days of storage. A synergic effect was observed only after 5 days at 4 °C for the bacteriocin from MT 104, as compared to the bacteriocin produced by MT 162 that had only an additive antimicrobial effect in all conditions.

  14. Suppression of Sclerostin Alleviates Radiation-Induced Bone Loss by Protecting Bone-Forming Cells and Their Progenitors Through Distinct Mechanisms

    Science.gov (United States)

    Chandra, Abhishek; Lin, Tiao; Young, Tiffany; Tong, Wei; Ma, Xiaoyuan; Tseng, Wei-Ju; Kramer, Ina; Kneissel, Michaela; Levine, Michael A; Zhang, Yejia; Cengel, Keith; Liu, X. Sherry; Qin, Ling

    2017-01-01

    Focal radiotherapy is frequently associated with skeletal damage within the radiation field. Our previous in vitro study showed that activation of Wnt/β-catenin pathway can overcome radiation-induced DNA damage and apoptosis of osteoblastic cells. Neutralization of circulating sclerostin with a monoclonal antibody (Scl-Ab) is an innovative approach for treating osteoporosis by enhancing Wnt/β-catenin signaling in bone. Together with the fact that focal radiation increases sclerostin amount in bone, we sought to determine whether weekly treatment with Scl-Ab would prevent focal radiotherapy-induced osteoporosis in mice. Micro-CT and histomorphometric analyses demonstrated that Scl-Ab blocked trabecular bone structural deterioration after radiation by partially preserving osteoblast number and activity. Consistently, trabecular bone in sclerostin null mice was resistant to radiation via the same mechanism. Scl-Ab accelerated DNA repair in osteoblasts after radiation by reducing the number of γ-H2AX foci, a DNA double-strand break marker, and increasing the amount of Ku70, a DNA repair protein, thus protecting osteoblasts from radiation-induced apoptosis. In osteocytes, apart from using similar DNA repair mechanism to rescue osteocyte apoptosis, Scl-Ab restored the osteocyte canaliculi structure that was otherwise damaged by radiation. Using a lineage tracing approach that labels all mesenchymal lineage cells in the endosteal bone marrow, we demonstrated that radiation damage to mesenchymal progenitors mainly involves shifting their fate to adipocytes and arresting their proliferation ability but not inducing apoptosis, which are different mechanisms from radiation damage to mature bone forming cells. Scl-Ab treatment partially blocked the lineage shift but had no effect on the loss of proliferation potential. Taken together, our studies provide proof-of-principle evidence for a novel use of Scl-Ab as a therapeutic treatment for radiation-induced osteoporosis and

  15. Assessment of cytotoxic effect mechanisms of gas-discharge plasma radiation

    OpenAIRE

    Ivanova I.P.; Trofimova S.V.; Vedunova М.V.; Zhabereva А.S.; Bugrova M.L.; Piskaryov I.M.; Karpel Vel Leitner N.

    2014-01-01

    The aim of the investigation was to assess the mechanisms of cytotoxic effect of gas-discharge plasma radiation on lymphosarcoma and breast cancer cells. Materials and Methods. The experiment was carried out on the strains of rat lymphosarcoma (LSR) and breast cancer (RMK1) cells. 4 ml of cell suspension at (4–6)·106/ml concentration was exposed to gas-discharge plasma radiation in various time modes. Plasma radiation was generated by impulse device with the following set characteristics:...

  16. Mutational and acquired carbapenem resistance mechanisms in multidrug resistant Pseudomonas aeruginosa clinical isolates from Recife, Brazil

    Science.gov (United States)

    Cavalcanti, Felipe Lira de Sá; Mirones, Cristina Rodríguez; Paucar, Elena Román; Montes, Laura Álvarez; Leal-Balbino, Tereza Cristina; de Morais, Marcia Maria Camargo; Martínez-Martínez, Luis; Ocampo-Sosa, Alain Antonio

    2015-01-01

    An investigation was carried out into the genetic mechanisms responsible for multidrug resistance in nine carbapenem-resistant Pseudomonas aeruginosaisolates from different hospitals in Recife, Brazil. Susceptibility to antimicrobial agents was determined by broth microdilution. Polymerase chain reaction (PCR) was employed to detect the presence of genes encoding β-lactamases, aminoglycoside-modifying enzymes (AMEs), 16S rRNA methylases, integron-related genes and OprD. Expression of genes coding for efflux pumps and AmpC cephalosporinase were assessed by quantitative PCR. The outer membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The blaSPM-1, blaKPC-2 and blaGES-1 genes were detected in P. aeruginosaisolates in addition to different AME genes. The loss of OprD in nine isolates was mainly due to frameshift mutations, premature stop codons and point mutations. An association of loss of OprD with the overexpression of MexAB-OprM and MexXY-OprM was observed in most isolates. Hyper-production of AmpC was also observed in three isolates. Clonal relationship of the isolates was determined by repetitive element palindromic-PCR and multilocus sequence typing. Our results show that the loss of OprD along with overexpression of efflux pumps and β-lactamase production were responsible for the multidrug resistance in the isolates analysed. PMID:26676375

  17. Analysis and utilization of plant antioxidative mechanism by radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Haeng Soon; Kwak, Sang Soo; Kwon, Hye Gyung [Korea Research Institute of Bioscience and Biotechnology, Taejon (Korea)

    1999-03-01

    The gamma radiation-induced changes of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) in callus cultures of cassava (Manihot esculenta) and sweet potato (Ipomoea batatas) were investigated. Both cell lines irradiated with 50 and 70 Gy on 7 days after subculture inhibited significantly the cell growth by 50% and 80% at 14 days after treatment (DAT), respectively. In 70 Gy irradiated with cassava calli SOD and POD specific activities increased by 4 and 2.5 folds at 14 DAT, respectively, whereas CAT activity was not affected. When sweet potato calli were irradiated 10 Gy POD activity showed the highest at 14 DAT, whereas the CAT activity was not affected. In the transgenic tobacco plants that overexpress swpal encoding anionic POD cDNA or swpnl encoding neutral POD cDNA, POD and SOD activities were not significantly increased after {gamma}-radiation treatment, but swpal-plants showed a higher activity than that of swpnl-or non-transgenic plants. Plant growth was severely inhibited showing a well correlation with the dose of radiation. Specially, {gamma}-radiation affected growth of shoot apical meristem. (author). 32 refs., 7 figs.

  18. Triggering star formation by both radiative and mechanical AGN feedback

    Institute of Scientific and Technical Information of China (English)

    Chao Liu; Zhao-Ming Gan; Fu-Guo Xie

    2013-01-01

    We perform two dimensional hydrodynamic numerical simulations to study the positive active galactic nucleus (AGN) feedback which triggers,rather than suppresses,star formation.Recently,it was shown by Nayakshin et al.and Ishibashi et al.that star formation occurs when the cold interstellar medium (ISM) is squeezed by the impact of mass outflow or radiation pressure,respectively.Mass outflow is ubiquitous in this astrophysical context,and radiation pressure is also important if the AGN is luminous.For the first time in this subject,we incorporate both mass outflow feedback and radiative feedback into our model.Consequently,the ISM is shocked into shells by the AGN feedback,and these shells soon fragment into clumps and filaments because of Rayleigh-Taylor and thermal instabilities.We have two major findings:(1)the star formation rate can indeed be very large in the clumps and filaments.However,the resultant star formation rate density is too large compared with previous works,which is mainly because we ignore the fact that most of the stars that are formed would be disrupted when they move away from the galactic center.(2) Although radiation pressure feedback has a limited effect,when mass outflow feedback is also included,they reinforce each other.Specifically,in the gas-poor case,mass outflow is always the dominant contributor to feedback.

  19. Clarithromycin Resistance Mechanisms of Epidemic β-Lactamase-Nonproducing Ampicillin-Resistant Haemophilus influenzae Strains in Japan.

    Science.gov (United States)

    Seyama, Shoji; Wajima, Takeaki; Nakaminami, Hidemasa; Noguchi, Norihisa

    2016-05-01

    The aim of this study was to clarify the clarithromycin resistance mechanisms of β-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae strains. In all clarithromycin-resistant strains, the transcript level of acrB was significantly elevated, and these strains had a frameshift mutation in acrR Introduction of the acrR mutation into H. influenzae Rd generated a clarithromycin-resistant transformant with the same MIC as the donor strain. Our results indicate that the acrR mutation confers clarithromycin resistance by the increasing the transcription of acrB.

  20. Carcinoembryonic Antigen Expression and Resistance to Radiation and 5-Fluorouracil-Induced Apoptosis and Autophagy.

    Science.gov (United States)

    Eftekhar, Ebrahim; Jaberie, Hajar; Naghibalhossaini, Fakhraddin

    2016-01-01

    Understanding the mechanism of tumor resistance is critical for cancer therapy. In this study, we investigated the effect of carcinoembryonic antigen (CEA) overexpression on UV-and 5-fluorouracil (5-FU)-induced apoptosis and autophagy in colorectal cancer cells. We used histone deacetylase (HDAC) inhibitor, NaB and DNA demethylating agent, 5-azacytidine (5-AZA) to induce CEA expression in HT29/219 and SW742 colorectal cancer cell lines. MTT assay was used to measure IC50 value of the cells exposed to graded concentrations of 5- FU with either 0.1 mM NaB or 1 μM 5-AZA for 72 h . Using CHO- and SW742-CEA transfectants, we also investigated the effect of CEA expression on UV- and 5-FU-induced apoptosis and autophagy. Treatment of HT29/219 cell line with NaB and 5-AZA increased CEA expression by 29% and 31%, respectively. Compared with control cells, the IC50 value for 5-FU of NaB and 5-AZA-treated cells increased by 40% and 57%, respectively. Treatment of SW742 cells with NaB or 5-AZA increased neither CEA expression nor the IC50 value for 5-FU. In comparison to parental cells, CEA expression also significantly protected transfected cells against UV-induced apoptosis. Decreased proportions of autophagy and apoptosis were also observed in 5-FU treated SW742- and CHO-CEA transfectants. We conclude that CEA expression can effectively protect colorectal cancer cells against radiation and drug-induced apoptosis and autophagy.

  1. Distribution of radiation resistances of microbiological contaminants of a cotton-based medical product

    Science.gov (United States)

    Yan Aoshuang; Tallentire, Alan

    1995-02-01

    A distribution of radiation resistances of microorganisms has been compiled from the results of D 10 determinations of isolates recovered from a cotton-based medical product. In all, 250 organisms were isolated from a total microbial population of around 21,000 organisms present on about 170 g of product. D 10 values of the isolates fall within the range of 0.5 to 3.6 kGy. The findings indicate that organisms having a D 10 value greater than 3.6 kGy occur amongst contaminants on this cotton product at a probability of less than 1 in 5000. The overall resistance of the population of organisms found in the present study is somewhat less than that of the 'Standard Distribution of Resistances' used in 'AAMI dose setting methods'.

  2. Mechanisms of direct detonation initiation via thermal explosion of radiatively heated gas-particles layer

    Science.gov (United States)

    Efremov, V. P.; Ivanov, M. F.; Kiverin, A. D.; Yakovenko, I. S.

    Conceptual approach of detonation wave direct initiation by external radiative heating of microparticles locally suspended in flammable gaseous mixture is proposed. Combustion waves and detonation initiation mechanisms in the congestion regions of microparticles heated by radiation are studied numerically. Necessary criteria on geometrical scales of gas-particles layer and spatial uniformity of particles distribution for successful detonation initiation are formulated.

  3. Mechanisms of resistance and cross-resistance to agrochemicals in the fairy shrimp Thamnocephalus platyurus (Crustacea: Anostraca).

    Science.gov (United States)

    Brausch, John M; Smith, Philip N

    2009-05-05

    Extensive pesticide usage in the Southern High Plains has led to the development of resistance in many pest species, as well as some non-target organisms. Thamnocephalus platyurus derived from agriculturally impacted watersheds are between two and three times less sensitive to commonly applied agrochemicals than T. platyurus from native grassland watersheds. Biological mechanisms that convey such resistance are currently unknown. This study identified the contribution of metabolic enzymes to T. platyurus pesticide resistance using the synergists piperonyl butoxide (PBO) and S,S,S-tributyl phosphorotrithioate (DEF) to inhibit cytochrome P450s or hydrolases, respectively. Inhibition of cytochrome P450s and hydrolases partially restored cyfluthrin and DDT sensitivity in T. platyurus, suggesting other resistance inferring mechanism(s) were also involved. However, inhibition of hydrolases with DEF completely restored methyl parathion sensitivity in pesticide resistant T. platyurus. DDT resistance paralleled cyfluthrin resistance, but did not for methyl parathion resistance. These data suggest that the primary mechanism for the development of resistance to agrochemicals in T. platyurus is due to increased metabolic detoxification.

  4. Radiation response of human lung cancer cells with inherent and acquired resistance to cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Twentyman, P.R.; Wright, K.A.; Rhodes, T. (MRC Clinical Oncology and Radiotherapeutics Unit, Cambridge (England))

    1991-02-01

    We have derived sublines of three human lung cancer cell lines with acquired resistance to cisplatin. The cisplatin resistant sublines of NCI-H69 (small cell), COR-L23 (large cell), and MOR (adenocarcinoma) show 5.3 fold, 3.1 fold, and 3.8 fold resistance, respectively, determined in a 6-day MTT assay. Although the parent lines show a wide range of glutathione content per cell, the sublines each show similar values to their corresponding parent line. Radiation response curves have been obtained using a soft agar clonogenic assay. Values obtained for the parent lines (95% CL in parentheses) were: NCI-H69: Do = 0.99 Gy (0.87-1.16), n = 2.9 (1.6-5.2), GSH = 14 ng/10(4) cells; COR-L23: Do = 1.23 Gy (1.05-1.49), n = 1.3 (0.7-2.2), GSH = 47 ng/10(4) cells; MOR: Do = 1.66 Gy (1.48-1.88), n = 3.0 (1.9-4.8), GSH = 86 ng/10(4) cells. The cisplatin resistant variants of NCI-H69 and COR-L23 showed 31% and 63% increases, respectively, in Do compared to their parent lines, whereas no change in radiation response was seen in MOR. In this panel of lines, therefore, although there is a correlation between glutathione content and radiosensitivity of the parent cell lines, acquired resistance to cisplatin is not accompanied by increased glutathione content. However, two of the three cisplatin resistant lines do show a significantly reduced radiosensitivity.

  5. Radiation Resistance of XLPE Nano-dielectrics for Advanced Reactor Applications

    Energy Technology Data Exchange (ETDEWEB)

    Duckworth, Robert C [ORNL; Polyzos, Georgios [ORNL; Paranthaman, Mariappan Parans [ORNL; Aytug, Tolga [ORNL; Leonard, Keith J [ORNL; Sauers, Isidor [ORNL

    2014-01-01

    Recently there has been renewed interest in nuclear reactor safety, particularly as commercial reactors are approaching 40 years service and lifetime extensions are considered, as well as for new reactor building projects around the world. The materials that are currently used in cabling for instrumentation, reactor control, and communications include cross-linked polyethylene (XLPE), ethylene propylene rubber (EPR), polyvinyl chloride (PVC), neoprene, and chlorosulfonated polyethylene. While these materials show suitable radiation tolerance in laboratory tests, failures before their useful lifetime occur due to the combined environmental effects of radiation, temperature and moisture, or operation under abnormal conditions. In addition, the extended use of commercial reactors beyond their original service life places a greater demand on insulating materials to perform beyond their current ratings in these nuclear environments. Nanocomposite materials that are based on XLPE and other epoxy resins incorporating TiO2, MgO, SiO2, and Al2O3 nanoparticles are being fabricated using a novel in-situ method established at ORNL to demonstrate materials with increased resistance to radiation. As novel nanocomposite dielectric materials are developed, characterization of the non-irradiated and irradiated nanodielectrics will lead to a knowledge base that allow for dielectric materials to be engineered with specific nanoparticle additions for maximum benefit to wide-variety of radiation environments found in nuclear reactors. This paper presents the initial findings on the development of XLPE-based SiO2 nano-composite dielectrics in the context of electrical performance and radiation degradation.

  6. [Photosynthetic responses of wheat and pea seedlings to enhanced UV-C radiation and their resistances].

    Science.gov (United States)

    Li, Xue-Mei; Zhang, Li-Hong; He, Xing-Yuan; Hao, Lin

    2007-03-01

    With wheat and pea seedlings as test materials, this paper studied the effects of UV-C radiation on their leaf photosynthetic characteristics and antioxidant enzyme activities. The results showed that enhanced UV-C radiation could markedly decrease the photosynthetic rate (Pn) , stomatal conductance (Gs), intercellular CO2 concentration (Ci), transpiration rate (Tr) and carboxylation efficiency (CE) of pea leaves, but for wheat leaves, these parameters were increased first and decreased then. Under UV-C condition, the CO2 compensation point of leaf was increased for pea, but decreased first and increased then for wheat. With the increasing duration of UV-C radiation, the antioxidant enzyme activities of both test plants increased first and decreased then, except that the POD activity of pea and SOD activity of wheat decreased gradually. All of these suggested that wheat had a stronger resistance to short-time UV-C radiation than pea, but, with the prolonged duration of UV-C radiation, the photosynthesis and antioxidant enzyme activities of wheat and pea were all decreased.

  7. Mechanism of resistance to macrolide-lincosamide-streptogramin antibiotics in Streptococcus thermophilus

    Science.gov (United States)

    Resistance to macrolide-lincosamide-streptogramin (MLS) group antibiotics in the dairy bacterium Streptococcus thermophilus (ST) is documented but the mechanism of resistance has not been elucidated. MIC values for erythromycin (Erm), azithromycin (Azm), tylosin (Tyl), spiramycin (Spm), pristinamyci...

  8. Stability and Degradation Mechanisms of Radiation-Grafted Polymer Electrolyte Membranes for Water Electrolysis.

    Science.gov (United States)

    Albert, Albert; Lochner, Tim; Schmidt, Thomas J; Gubler, L

    2016-06-22

    Radiation-grafted membranes are a promising alternative to commercial membranes for water electrolyzers, since they exhibit lower hydrogen crossover and area resistance, better mechanical properties, and are of potentially lower cost than perfluoroalkylsulfonic acid membranes, such as Nafion. Stability is an important factor in view of the expected lifetime of 40 000 h or more of an electrolyzer. In this study, combinations of styrene (St), α-methylstyrene (AMS), acrylonitrile (AN), and 1,3-diisopropenylbenzene (DiPB) are cografted into 50 μm preirradiated poly(ethylene-co-tetrafluoroethylene) (ETFE) base film, followed by sulfonation to produce radiation-grafted membranes. The stability of the membranes with different monomer combinations is compared under an accelerated stress test (AST), and the degradation mechanisms are investigated. To mimic the conditions in an electrolyzer, in which the membrane is always in contact with liquid water at elevated temperature, the membranes are immersed in water for 5 days at 90 °C, so-called thermal stress test (TST). In addition to testing in air atmosphere tests are also carried out under argon to investigate the effect of the absence of oxygen. The water is analyzed with UV-vis spectroscopy and ion chromatography. The ion exchange capacity (IEC), swelling degree, and Fourier transform infrared (FTIR) spectra of the membranes are compared before and after the test. Furthermore, energy-dispersive X-ray (EDX) spectroscopic analysis of the membrane cross-section is performed. Finally, the influence of the TST to the membrane area resistance and hydrogen crossover is measured. The stability increases along the sequence St/AN, St/AN/DiPB, AMS/AN, and AMS/AN/DiPB grafted membrane. The degradation at the weak-link, oxygen-induced degradation, and hydrothermal degradation are proposed in addition to the "swelling-induced detachment" reported in the literature. By mitigating the possible paths of degradation, the AMS

  9. Evidence for involvement of cytosolic thioredoxin peroxidase in the excessive resistance of Sf9 Lepidopteran insect cells against radiation-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Shashank Hambarde

    Full Text Available Lepidopteran insect cells display 50-100 times higher radioresistance compared to human cells, and reportedly have more efficient antioxidant system that can significantly reduce radiation-induced oxidative stress and cell death. However, the antioxidant mechanisms that contribute substantially to this excessive resistance still need to be understood thoroughly. In this study, we investigated the role of thioredoxin peroxidase (TPx in high-dose γ-radiation response of Sf9 cell line derived from Spodoptera frugiperda, the Fall armyworm. We identified a TPx orthologue (Sf-TPx in Spodoptera system, with primarily cytosolic localization. Gamma-irradiation at 500 Gy dose significantly up-regulated Sf-TPx, while higher doses (1000 Gy-2000 Gy had no such effect. G2/M checkpoint induced following 500 Gy was associated with transition of Sf-TPx decamer into enzymatically active dimer. Same effect was observed during G2/M block induced by 5 nM okadaic acid or 10 µM CDK1 (cycline dependent kinase-1 inhibitor roscovitine, thus indicating that radiation-induced Sf-TPx activity is mediated by CDKs. Accumulation of TPx dimer form during G2/M checkpoint might favour higher peroxidase activity facilitating efficient survival at this dose. Confirming this, higher lethal doses (1000 Gy-2000 Gy caused significantly less accumulation of dimer form and induced dose-dependent apoptosis. A ∼50% knock-down of Sf-TPx by siRNA caused remarkable increase in radiation-induced ROS as well as caspase-3 dependent radiation-induced apoptosis, clearly implying TPx role in the radioresistance of Sf9 cells. Quite importantly, our study demonstrates for the first time that thioredoxin peroxidase contributes significantly in the radioresistance of Lepidopteran Sf9 insect cells, especially in their exemplary resistance against radiation-induced apoptosis. This is an important insight into the antioxidant mechanisms existing in this highly stress-resistant model cell system.

  10. Evidence for involvement of cytosolic thioredoxin peroxidase in the excessive resistance of Sf9 Lepidopteran insect cells against radiation-induced apoptosis.

    Science.gov (United States)

    Hambarde, Shashank; Singh, Vijaypal; Chandna, Sudhir

    2013-01-01

    Lepidopteran insect cells display 50-100 times higher radioresistance compared to human cells, and reportedly have more efficient antioxidant system that can significantly reduce radiation-induced oxidative stress and cell death. However, the antioxidant mechanisms that contribute substantially to this excessive resistance still need to be understood thoroughly. In this study, we investigated the role of thioredoxin peroxidase (TPx) in high-dose γ-radiation response of Sf9 cell line derived from Spodoptera frugiperda, the Fall armyworm. We identified a TPx orthologue (Sf-TPx) in Spodoptera system, with primarily cytosolic localization. Gamma-irradiation at 500 Gy dose significantly up-regulated Sf-TPx, while higher doses (1000 Gy-2000 Gy) had no such effect. G2/M checkpoint induced following 500 Gy was associated with transition of Sf-TPx decamer into enzymatically active dimer. Same effect was observed during G2/M block induced by 5 nM okadaic acid or 10 µM CDK1 (cycline dependent kinase-1) inhibitor roscovitine, thus indicating that radiation-induced Sf-TPx activity is mediated by CDKs. Accumulation of TPx dimer form during G2/M checkpoint might favour higher peroxidase activity facilitating efficient survival at this dose. Confirming this, higher lethal doses (1000 Gy-2000 Gy) caused significantly less accumulation of dimer form and induced dose-dependent apoptosis. A ∼50% knock-down of Sf-TPx by siRNA caused remarkable increase in radiation-induced ROS as well as caspase-3 dependent radiation-induced apoptosis, clearly implying TPx role in the radioresistance of Sf9 cells. Quite importantly, our study demonstrates for the first time that thioredoxin peroxidase contributes significantly in the radioresistance of Lepidopteran Sf9 insect cells, especially in their exemplary resistance against radiation-induced apoptosis. This is an important insight into the antioxidant mechanisms existing in this highly stress-resistant model cell system.

  11. Neoplastic cell transformation by high-LET radiation - Molecular mechanisms

    Science.gov (United States)

    Yang, Tracy Chui-Hsu; Craise, Laurie M.; Tobias, Cornelius A.; Mei, Man-Tong

    1989-01-01

    Quantitative data were collected on dose-response curves of cultured mouse-embryo cells (C3H10T1/2) irradiated with heavy ions of various charges and energies. Results suggests that two breaks formed on DNA within 80 A may cause cell transformation and that two DNA breaks formed within 20 A may be lethal. From results of experiments with restriction enzymes which produce DNA damages at specific sites, it was found that DNA double strand breaks are important primary lesions for radiogenic cell transformation and that blunt-ended double-strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship for high-LET radiation is similar to that for HGPRT locus mutation, chromosomal deletion, and cell transformation, indicating that common lesions may be involved in these radiation effects.

  12. Theory of the high base resistivity n(+)pp(+) silicon solar cell and its application to radiation damage effects

    Science.gov (United States)

    Goradia, C.; Weinberg, I.

    1985-01-01

    Particulate radiation in space is a principal source of silicon solar cell degradation, and an investigation of cell radiation damage at higher base resistivities appears to have implication toward increasing solar cell and, therefore, useful satellite lifetimes in the space environment. However, contrary to expectations, it has been found that for cells with resistivities of 84 and 1250 ohm cm, the radiation resistance decreases as cell base resistivity increases. An analytical solar-cell computer model was developed with the objective to determine the reasons for this unexpected behavior. The present paper has the aim to describe the analytical model and its use in interpreting the behavior, under irradiation, of high-resistivity solar cells. Attention is given to boundary conditions at the space-charge region edges, cell currents, cell voltages, the generation of the theoretical I-V characteristic, experimental results, and computer calculations.

  13. Sunlight-Exposed Biofilm Microbial Communities Are Naturally Resistant to Chernobyl Ionizing-Radiation Levels

    Science.gov (United States)

    Ragon, Marie; Restoux, Gwendal; Moreira, David; Møller, Anders Pape; López-García, Purificación

    2011-01-01

    Background The Chernobyl accident represents a long-term experiment on the effects of exposure to ionizing radiation at the ecosystem level. Though studies of these effects on plants and animals are abundant, the study of how Chernobyl radiation levels affect prokaryotic and eukaryotic microbial communities is practically non-existent, except for a few reports on human pathogens or soil microorganisms. Environments enduring extreme desiccation and UV radiation, such as sunlight exposed biofilms could in principle select for organisms highly resistant to ionizing radiation as well. Methodology/Principal Findings To test this hypothesis, we explored the diversity of microorganisms belonging to the three domains of life by cultivation-independent approaches in biofilms developing on concrete walls or pillars in the Chernobyl area exposed to different levels of radiation, and we compared them with a similar biofilm from a non-irradiated site in Northern Ireland. Actinobacteria, Alphaproteobacteria, Bacteroidetes, Acidobacteria and Deinococcales were the most consistently detected bacterial groups, whereas green algae (Chlorophyta) and ascomycete fungi (Ascomycota) dominated within the eukaryotes. Close relatives to the most radio-resistant organisms known, including Rubrobacter species, Deinococcales and melanized ascomycete fungi were always detected. The diversity of bacteria and eukaryotes found in the most highly irradiated samples was comparable to that of less irradiated Chernobyl sites and Northern Ireland. However, the study of mutation frequencies in non-coding ITS regions versus SSU rRNA genes in members of a same actinobacterial operational taxonomic unit (OTU) present in Chernobyl samples and Northern Ireland showed a positive correlation between increased radiation and mutation rates. Conclusions/Significance Our results show that biofilm microbial communities in the most irradiated samples are comparable to non-irradiated samples in terms of general

  14. Sunlight-exposed biofilm microbial communities are naturally resistant to chernobyl ionizing-radiation levels.

    Directory of Open Access Journals (Sweden)

    Marie Ragon

    Full Text Available BACKGROUND: The Chernobyl accident represents a long-term experiment on the effects of exposure to ionizing radiation at the ecosystem level. Though studies of these effects on plants and animals are abundant, the study of how Chernobyl radiation levels affect prokaryotic and eukaryotic microbial communities is practically non-existent, except for a few reports on human pathogens or soil microorganisms. Environments enduring extreme desiccation and UV radiation, such as sunlight exposed biofilms could in principle select for organisms highly resistant to ionizing radiation as well. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we explored the diversity of microorganisms belonging to the three domains of life by cultivation-independent approaches in biofilms developing on concrete walls or pillars in the Chernobyl area exposed to different levels of radiation, and we compared them with a similar biofilm from a non-irradiated site in Northern Ireland. Actinobacteria, Alphaproteobacteria, Bacteroidetes, Acidobacteria and Deinococcales were the most consistently detected bacterial groups, whereas green algae (Chlorophyta and ascomycete fungi (Ascomycota dominated within the eukaryotes. Close relatives to the most radio-resistant organisms known, including Rubrobacter species, Deinococcales and melanized ascomycete fungi were always detected. The diversity of bacteria and eukaryotes found in the most highly irradiated samples was comparable to that of less irradiated Chernobyl sites and Northern Ireland. However, the study of mutation frequencies in non-coding ITS regions versus SSU rRNA genes in members of a same actinobacterial operational taxonomic unit (OTU present in Chernobyl samples and Northern Ireland showed a positive correlation between increased radiation and mutation rates. CONCLUSIONS/SIGNIFICANCE: Our results show that biofilm microbial communities in the most irradiated samples are comparable to non-irradiated samples in

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-28

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

  16. Effects of structure multiplicity on mechanism of radiation crosslinking of polymers

    Science.gov (United States)

    Lihua, Zhang; Maotang, Zhou; Donglin, Chen

    1994-09-01

    In an attempt to explore the effects of structural multiplicity of polymers on the mechanism of radiation crosslinking, the adaptability of the Charlesby-Pinner's equation and its various modified versions are examined. It is recognized that both chemical and morphological multiplicity of polymer structure result in the multiplicity of crosslinking mechanism, and that any single equation can only be applicable to a certain step of the whole radiation process.

  17. Mechanism of radiation crosslinking of polymers and its relationship with structural multiplicity

    Science.gov (United States)

    Lihua, Zhang; Maotang, Zhou; Donglin, Chen

    1993-07-01

    In an attempt to explore the effect of structural multiplicity of polymers on the mechanism of radiation crosslinking, the adaptability of the Charlesby-Pinner's equation and its various modified versions are examined. It is recognized that both chemical and morphological multiplicity of polymer structure results in the multiplicity of crosslinking mechanism, and that any single equation can only be applicable to a certain step of the whole radiation process.

  18. Physiological mechanisms of acute intestinal radiation death. Technical report, 1 June 1983-1 June 1986

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, K.L.; Geraci, J.P.

    1986-06-01

    The overall objective was to clarify the role of fluid and electrolyte loss, bile-duct ligation, radiation-damaged intestinal mucosa, bacterial toxemia and their interrelationships on radiation-induced gastrointestinal death. Using specific pathogen-free CD-1 male rats, this study found that endogenous enteric bacteria did not play a significant role in pure intestinal radiation death. Bile acids, per se, were shown to play little role in intestinal radiation death, but the inability of the denuded mucosa to absorb fluid and electrolytes, thereby producing hypovolemic shock, was the major mechanism.

  19. Gene expression arrays as a tool to unravel mechanisms of normal tissue radiation injury and prediction of response

    Institute of Scientific and Technical Information of China (English)

    Jacqueline JCM Kruse; Fiona A Stewart

    2007-01-01

    Over the past 5 years there has been a rapid increase in the use of microarray technology in the field of cancer research. The majority of studies use microarray analysis of tumor biopsies for profiling of molecular characteristics in an attempt to produce robust classifiers for prognosis. There are now several published gene sets that have been shown to predict for aggressive forms of breast cancer, where patients are most likely to benefit from adjuvant chemotherapy and tumors most likely to develop distant metastases, or be resistant to treatment. The number of publications relating to the use of microarrays for analysis of normal tissue damage, after cancer treatment or genotoxic exposure, is much more limited. A PubMed literature search was conducted using the following keywords and combination of terms: radiation, normal tissue, microarray, gene expression profiling, prediction. With respect to normal tissue radiation injury, microarrays have been used in three ways: (1) to generate gene signatures to identify sensitive and resistant populations (prognosis); (2) to identify sets of biomarker genes for estimating radiation exposure, either accidental or as a result of terrorist attack (diagnosis); (3) to identify genes and pathways involved in tissue response to injury (mechanistic). In this article we will review all (relevant) papers that covered our literature search criteria on microarray technology as it has been applied to normal tissue radiation biology and discuss how successful this has been in defining predisposition markers for radiation sensitivity or how it has helped us to unravel molecular mechanisms leading to acute and late tissue toxicity. We also discuss some of the problems and limitations in application and interpretation of such data.

  20. Mechanisms of Radiation Damage Generated by Ionizing Radiation in Optical Waveguides

    Science.gov (United States)

    1988-09-01

    SUMMARY OF APPENDIX B "Optical scattering and SPR study of ZBLAN glass : Dependence on preparation and processing methods" LMater. Sci. Forum 19-20...studied the types of centers created by ionizing radiation in ZBLAN (ZrF 4, BaF 2 , LaF 3, AlF 3 , and NaF) glass . Samples of ZBLAN were prepared using...radiation-induced centers in ZBLAN glass depend strongly on the glass -processing conditions. For example, ZBLAN glasses processed with CC14 yield paramagnetic

  1. 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.

  2. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L. [Dept.of Radiation Oncology, Henry Ford Health System, Detroit (United States)

    2014-09-15

    To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

  3. The utilize of gamma radiation on the examination of mechanical properties of polymeric materials

    Directory of Open Access Journals (Sweden)

    F. Greškovič

    2012-04-01

    Full Text Available The article deals about the application area of radiation crosslinking of plastics, which follows after the injection moulding. The main objective of the presented article is the research of influence irradiation dosage on mechanical properties of materials: PP filled by 15 % of mineral filler – talc. Mechanical properties - tensile strength and impact strength by Charpy were examined in dependence on absorbed dose of the gamma rays on various conditions and were compared with non-irradiated samples. Radiation processing involves mainly the use of either electron beams from electron accelerators or gamma radiation from Cobalt-60 sources.

  4. A Low-Power, Radiation-Resistant, Silicon-Drift-Detector Array for Extraterrestrial Element Mapping

    Energy Technology Data Exchange (ETDEWEB)

    Ramsey B. D.; De Geronimo G.; Gaskin, J.A.; Elsner, R.F.; Chen, W.; Carini, G.A.; Keister, J.; Li, S.; Li, Z.; Siddons, D.P.; Smith, G.

    2012-02-08

    We are developing a modular Silicon Drift Detector (SDD) X-Ray Spectrometer (XRS) for measuring the abundances of light surface elements (C to Fe) fluoresced by ambient radiation on remote airless bodies. The value of fluorescence spectrometry for surface element mapping is demonstrated by its inclusion on three recent lunar missions and by exciting new data that have recently been announced from the Messenger Mission to Mercury. The SDD-XRS instrument that we have been developing offers excellent energy resolution and an order of magnitude lower power requirement than conventional CCDs, making much higher sensitivities possible with modest spacecraft resources. In addition, it is significantly more radiation resistant than x-ray CCDs and therefore will not be subject to the degradation that befell recent lunar instruments. In fact, the intrinsic radiation resistance of the SDD makes it applicable even to the harsh environment of the Jovian system where it can be used to map the light surface elements of Europa. In this paper, we first discuss our element-mapping science-measurement goals. We then derive the necessary instrument requirements to meet these goals and discuss our current instrument development status with respect to these requirements.

  5. Study of surface properties of ATLAS12 strip sensors and their radiation resistance

    Energy Technology Data Exchange (ETDEWEB)

    Mikestikova, M., E-mail: mikestik@fzu.cz [Academy of Sciences of the Czech Republic, Institute of Physics, Na Slovance 2, 18221 Prague 8 (Czech Republic); Allport, P.P.; Baca, M.; Broughton, J.; Chisholm, A.; Nikolopoulos, K.; Pyatt, S.; Thomas, J.P.; Wilson, J.A. [School of Physics and Astronomy, University of Birmingham, Birmingham B15 2TT (United Kingdom); Kierstead, J.; Kuczewski, P.; Lynn, D. [Brookhaven National Laboratory, Physics Department and Instrumentation Division, Upton, NY 11973-5000 (United States); Hommels, L.B.A. [Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Ullan, M. [Centro Nacional de Microelectronica (IMB-CNM, CSIC), Campus UAB-Bellaterra, 08193 Barcelona (Spain); Bloch, I.; Gregor, I.M.; Tackmann, K. [DESY, Notkestrasse 85, 22607 Hamburg (Germany); Hauser, M.; Jakobs, K.; Kuehn, S. [Physikalisches Institut, Universität Freiburg, Hermann-Herder-Str. 3, D-79104 Freiburg (Germany); and others

    2016-09-21

    A radiation hard n{sup +}-in-p micro-strip sensor for the use in the Upgrade of the strip tracker of the ATLAS experiment at the High Luminosity Large Hadron Collider (HL-LHC) has been developed by the “ATLAS ITk Strip Sensor collaboration” and produced by Hamamatsu Photonics. Surface properties of different types of end-cap and barrel miniature sensors of the latest sensor design ATLAS12 have been studied before and after irradiation. The tested barrel sensors vary in “punch-through protection” (PTP) structure, and the end-cap sensors, whose stereo-strips differ in fan geometry, in strip pitch and in edge strip ganging options. Sensors have been irradiated with proton fluences of up to 1×10{sup 16} n{sub eq}/cm{sup 2}, by reactor neutron fluence of 1×10{sup 15} n{sub eq}/cm{sup 2} and by gamma rays from {sup 60}Co up to dose of 1 MGy. The main goal of the present study is to characterize the leakage current for micro-discharge breakdown voltage estimation, the inter-strip resistance and capacitance, the bias resistance and the effectiveness of PTP structures as a function of bias voltage and fluence. It has been verified that the ATLAS12 sensors have high breakdown voltage well above the operational voltage which implies that different geometries of sensors do not influence their stability. The inter-strip isolation is a strong function of irradiation fluence, however the sensor performance is acceptable in the expected range for HL-LHC. New gated PTP structure exhibits low PTP onset voltage and sharp cut-off of effective resistance even at the highest tested radiation fluence. The inter-strip capacitance complies with the technical specification required before irradiation and no radiation-induced degradation was observed. A summary of ATLAS12 sensors tests is presented including a comparison of results from different irradiation sites. The measured characteristics are compared with the previous prototype of the sensor design, ATLAS07. - Highlights:

  6. Mechanisms and significance of fungicide resistance Mecanismos e significância da resistência a fungicidas

    Directory of Open Access Journals (Sweden)

    Holger B. Deising

    2008-06-01

    Full Text Available In this review article, we show that occurrence of fungicide resistance is one of the most important issues in modern agriculture. Fungicide resistance may be due to mutations of genes encoding fungicide targets (qualitative fungicide resistance or to different mechanisms that are induced by sub-lethal fungicide stress. These mechanisms result in different and varying levels of resistance (quantitative fungicide resistance. We discuss whether or not extensive use of fungicides in agricultural environments is related to the occurrence of fungicide resistance in clinical environments. Furthermore, we provide recommendations of how development of fungicide resistant pathogen populations may be prevented or delayed.A ocorrência de resistência a fungicidas é uma das mais importantes conseqüências da agricultura moderna. Este fato pode ser resultado de mutações em genes codificadores de resistência a fungicidas (resistência quantitativa ou a diferentes mecanismos que são induzidos por stresse devido a doses subletais dos produtos utilizados. Estes mecanismos produzem diferentes e variados níveis de resistência (resistência quantitativa. Também é discutido se o uso extensivo de fungicidas em ambientes agricultáveis é relacionado ou não com a ocorrência de resistência em ambientes clínicos. Além disso, também são fornecidas recomendações de como prevenir ou mesmo retardar o desenvolvimento de resistência a fungicidas em patógenos.

  7. Transfer of innate resistance and susceptibility to Leishmania donovani infection in mouse radiation bone marrow chimaeras

    Energy Technology Data Exchange (ETDEWEB)

    Crocker, P.R.; Blackwell, J.M.; Bradley, D.J. (London School of Hygiene and Tropical Medicine (UK))

    1984-07-01

    Reciprocal radiation bone marrow chimaeras were made between H-2-compatible strains of mice innately resistant or susceptible to visceral leishmaniasis. In initial experiments, susceptibility but not resistance to Leishmania donovani could be transferred with donor bone marrow into irradiated recipients. In subsequent experiments it was possible to transfer both resistance and susceptibility. This was achieved either by selecting more radiosensitive mouse strains as susceptible recipients, or alternatively by increasing the irradiation dose for the susceptible recipients used in the initial experiments. Using the higher irradiation dose, successful transfer of resistance and susceptibility between congenic mice carrying the Lshsup(r) and Lshsup(s) alleles on the more radioresistant B10 genetic background provided firm evidence that the results obtained in this study were specifically related to expression of the Lsh gene. It is concluded that Lsh gene-controlled resistance and susceptibility to L. donovani is determined by bone marrow-derived cells. The cell type(s) involved is likely to be of the macrophage lineage.

  8. ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells.

    Science.gov (United States)

    Vaidyanathan, Aparajitha; Sawers, Lynne; Gannon, Anne-Louise; Chakravarty, Probir; Scott, Alison L; Bray, Susan E; Ferguson, Michelle J; Smith, Gillian

    2016-08-09

    Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays. Paclitaxel-resistant cells were cross-resistant to olaparib, doxorubicin and rucaparib but not to veliparib or AZD2461. Resistance correlated with increased ABCB1 expression and was reversible following treatment with the ABCB1 inhibitors verapamil and elacridar. Active efflux of paclitaxel, olaparib, doxorubicin and rucaparib was confirmed in drug-resistant cells and in ABCB1-expressing bacterial membranes. We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients.

  9. Mechanism of low-level microwave radiation effect on nervous system.

    Science.gov (United States)

    Hinrikus, Hiie; Bachmann, Maie; Karai, Denis; Lass, Jaanus

    2017-01-01

    The aim of this study is to explain the mechanism of the effect of low-level modulated microwave radiation on brain bioelectrical oscillations. The proposed model of excitation by low-level microwave radiation bases on the influence of water polarization on hydrogen bonding forces between water molecules, caused by this the enhancement of diffusion and consequences on neurotransmitters transit time and neuron resting potential. Modulated microwave radiation causes periodic alteration of the neurophysiologic parameters and parametric excitation of brain bioelectric oscillations. The experiments to detect logical outcome of the mechanism on physiological level were carried out on 15 human volunteers. The 450-MHz microwave radiation modulated at 7, 40 and 1000 Hz frequencies was applied at the field power density of 0.16 mW/cm(2). A relative change in the EEG power with and without radiation during 10 cycles was used as a quantitative measure. Experimental data demonstrated that modulated at 40 Hz microwave radiation enhanced EEG power in EEG alpha and beta frequency bands. No significant alterations were detected at 7 and 1000 Hz modulation frequencies. These results are in good agreement with the theory of parametric excitation of the brain bioelectric oscillations caused by the periodic alteration of neurophysiologic parameters and support the proposed mechanism. The proposed theoretical framework has been shown to predict the results of experimental study. The suggested mechanism, free of the restrictions related to field strength or time constant, is the first one providing explanation of low-level microwave radiation effects.

  10. Adaptive response in human blood lymphocytes exposed to non-ionizing radiofrequency fields: resistance to ionizing radiation-induced damage.

    Science.gov (United States)

    Sannino, Anna; Zeni, Olga; Romeo, Stefania; Massa, Rita; Gialanella, Giancarlo; Grossi, Gianfranco; Manti, Lorenzo; Vijayalaxmi; Scarfì, Maria Rosaria

    2014-03-01

    The aim of this preliminary investigation was to assess whether human peripheral blood lymphocytes which have been pre-exposed to non-ionizing radiofrequency fields exhibit an adaptive response (AR) by resisting the induction of genetic damage from subsequent exposure to ionizing radiation. Peripheral blood lymphocytes from four healthy donors were stimulated with phytohemagglutinin for 24 h and then exposed for 20 h to 1950 MHz radiofrequency fields (RF, adaptive dose, AD) at an average specific absorption rate of 0.3 W/kg. At 48 h, the cells were subjected to a challenge dose (CD) of 1.0 or 1.5 Gy X-irradiation (XR, challenge dose, CD). After a 72 h total culture period, cells were collected to examine the incidence of micronuclei (MN). There was a significant decrease in the number of MN in lymphocytes exposed to RF + XR (AD + CD) as compared with those subjected to XR alone (CD). These observations thus suggested a RF-induced AR and induction of resistance to subsequent damage from XR. There was variability between the donors in RF-induced AR. The data reported in our earlier investigations also indicated a similar induction of AR in human blood lymphocytes that had been pre-exposed to RF (AD) and subsequently treated with a chemical mutagen, mitomycin C (CD). Since XR and mitomycin-C induce different kinds of lesions in cellular DNA, further studies are required to understand the mechanism(s) involved in the RF-induced adaptive response.

  11. Resistivity, ESR, and Radiation Shielding Properties of the Volcanic Rock Materials

    Directory of Open Access Journals (Sweden)

    Çiğdem Nuhoğlu

    2014-01-01

    Full Text Available Pumices have been used in cement, concrete, brick, and ceramic industries as an additive and aggregate material. It will be important to study pumice types by using a different tool as EPR which is a new technique for related material to be used for industrial aims. Electron spin resonance (ESR spectra of the pumice types were taken by EMX-type spectrometer. Also, the current-voltage (I-V and surface resistivity probe stand of the thin films was studied using a four-point probe measurements. The relationship between radiation shielding properties of the pumice samples and their surface resistivity, chemical, and electrokinetic properties was evaluated using simple regression analysis. Simple regression analysis indicated a strong correlation between surface resistivity and density and SiO2, Fe2O3, CaO, MgO, and TiO2 content of pumice samples in this study. It is found that a correlation between determined g-factor by EPR spectroscopy and radiation shielding is established for pumice samples.

  12. Application of living radical polymerization to the synthesis of resist polymers for radiation lithography

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Takashi [Nitto Denko Co. LTD., Shimohozumi 1-1-2, Ibaraki, Osaka 567-8680 (Japan); Ichikawa, Tsuneki [Division of Materials Chemistry, Graduate school of Engineering, Hokkaido University, Sapporo 060-8628 (Japan)]. E-mail: ichikawa@eng.hokudai.ac.jp

    2005-07-01

    Poly(styrene) and poly(methyl acrylate) with benzyl ester of carboxylic acid at the center of the polymer skeletons were synthesized by living radical polymerization for developing a new type of radiation resist with high resistivity to plasma etching and high sensitivity and spatial resolution to ionizing radiations. The initiators were benzyl esters with two functional groups for living radical polymerization on the benzyl and the carboxylic sides. Introduction of benzyl ester to the polymer skeletons changed the polymers from cross-link type to scission type upon {gamma}-irradiation. Irradiation of the polymers resulted in the binary change of the molecular weight, due to dissociative capture of secondary electrons by the benzyl ester, as M{sub n}R{sub 1}COOCH(C{sub 6}H{sub 5})R{sub 2}M{sub n}+e{sup -}->M{sub n}R{sub 1}COO{sup -}+{sup {center_dot}}CH(C{sub 6}H{sub 5})R{sub 2}M{sub n}. The generated polymer fragments were not decomposed by further irradiation, which suggests that the synthesized polymers have high resistivity to plasma etching.

  13. Clinical epidemiology and resistance mechanisms of carbapenem-resistant Acinetobacter baumannii, French Guiana, 2008-2014.

    Science.gov (United States)

    Mahamat, Aba; Bertrand, Xavier; Moreau, Brigitte; Hommel, Didier; Couppie, Pierre; Simonnet, Christine; Kallel, Hatem; Demar, Magalie; Djossou, Felix; Nacher, Mathieu

    2016-07-01

    This study investigated the clinical epidemiology and resistance mechanisms of Acinetobacter baumannii and characterised the clonal diversity of carbapenem-resistant A. baumannii (CRAB) during an ICU-associated outbreak at Cayenne Hospital, French Guiana. All non-duplicate A. baumannii isolates from 2008 to 2014 were tested for antibiotic susceptibility by disk diffusion. Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on CRAB. Of the 441 A. baumannii isolates, most were from males (54.0%) and were detected mainly from the ICU (30.8%) and medicine wards (21.8%). In the ICU, strains were mainly isolated from the respiratory tract (44.1%) and bloodstream (14.0%), whereas in medicine wards they mainly were from wound/drainage (36.5%) and bloodstream (25.0%). A. baumannii showed the greatest susceptibility to piperacillin/tazobactam (92.7%), imipenem (92.5%), colistin (95.6%) and amikacin (97.2%), being lower in the ICU and medicine wards compared with other wards. An outbreak of OXA-23-producing CRAB occurred in the 13-bed ICU in 2010. CRAB strains were more co-resistant to other antimicrobials compared with non-CRAB. Molecular genetics analysis revealed five sequence types [ST78, ST107 and ST642 and two new STs (ST830 and ST831)]. Analysis of PFGE profiles indicated cross-transmissions of CRAB within the ICU, between the ICU and one medicine ward during transfer of patients, and within that medicine ward. This study provides the first clinical and molecular data of A. baumannii from French Guiana and the Amazon basin. The ICU was the highest risk unit of this nosocomial outbreak of OXA-23-producing CRAB, which could subsequently disseminate within the hospital.

  14. Radiation resistance of thin-film solar cells for space photovoltaic power

    Science.gov (United States)

    Woodyard, James R.; Landis, Geoffrey A.

    1991-01-01

    Copper indium diselenide, cadmium telluride, and amorphous silicon alloy solar cells have achieved noteworthy performance and are currently being studied for space power applications. Cadmium sulfide cells had been the subject of much effort but are no longer considered for space applications. A review is presented of what is known about the radiation degradation of thin film solar cells in space. Experimental cadmium telluride and amorphous silicon alloy cells are reviewed. Damage mechanisms and radiation induced defect generation and passivation in the amorphous silicon alloy cell are discussed in detail due to the greater amount of experimental data available.

  15. Characterization of resistance mechanisms to powdery mildew (Erysiphe betae) in beet (Beta vulgaris).

    Science.gov (United States)

    Fernández-Aparicio, Mónica; Prats, Elena; Emeran, Amero A; Rubiales, Diego

    2009-04-01

    Beet powdery mildew incited by Erysiphe betae is a serious foliar fungal disease of worldwide distribution causing losses of up to 30%. In the present work, we searched for resistance in a germplasm collection of 184 genotypes of Beta vulgaris including fodder (51 genotypes), garden (60 genotypes), leaf (51 genotypes), and sugar (22 genotypes) beet types. Resistant genotypes were identified in the four beet types under study. In addition, mechanisms underlying resistance were dissected through histological studies. These revealed different resistance mechanisms acting at different fungal developmental stages, i.e., penetration resistance, early and late cell death, or posthaustorial resistance. Most genotypes were able to hamper fungal development at several stages. The later are interesting for breeding aiming to resistance durability. Furthermore, characterization of defense mechanisms will be useful for further cellular and molecular studies to unravel the bases of resistance in this species.

  16. Origin and evolution of antibiotic resistance: the common mechanisms of emergence and spread in water bodies

    Directory of Open Access Journals (Sweden)

    Agnese eLupo

    2012-01-01

    Full Text Available The environment, and especially fresh water, constitutes a reactor where the evolution and the rise of new resistances occur. In rivers or streams, bacteria from different sources such as urban, industrial and agricultural waste, probably selected by intensive antibiotic usage, are collected and mixed with environmental species. This may cause two effects on the development of antibiotic resistances: First, the contamination of water by antibiotics or other pollutants lead to the rise of resistance due to selection processes. For instance, of strains over-expressing broad range defensive mechanisms, such as efflux pumps. Second, since environmental species are provided with intrinsic antibiotic resistance mechanisms, the mixture with allochthonous species is likely to cause genetic exchange. In this context, the role of phages and integrons for the spread of resistance mechanisms appears significant. Allochthonous species could acquire new resistances from environmental donors and introduce the newly acquired resistance mechanisms into the clinics. This is illustrated by clinically relevant resistance mechanisms, such as the fluoroquinolones resistance genes qnr. Freshwater appears to play an important role in the emergence and in the spread of antibiotic resistances, highlighting the necessity for strategies of water quality improvement. Moreover, further knowledge is needed to better understand the role of the environment as reservoir of antibiotic resistances and to assess the risk of spread of antibiotic resistances via water bodies.

  17. ARE EPIGENETIC MECHANISMS INVOLVED IN RADIATION-INDUCED BYSTANDER EFFECTS?

    Directory of Open Access Journals (Sweden)

    Carmel eMothersill

    2012-05-01

    Full Text Available The non-targeted effects of ionizing radiation including bystander effects and genomic instability are unique in that no classic mutagenic event occurs in the cell showing the effect. In the case of bystander effects, cells which were not in the field affected by the radiation show high levels of mutations, chromosome aberrations and membrane signaling changes leading to what is termed horizontal transmission of mutations and information which may be damaging while in the case of genomic instability, generations of cells derived from an irradiated progenitor appear normal but then lethal and non-lethal mutations appear in distant progeny. This is known as vertical transmission. In both situations high yields of non-clonal mutations leading to distant occurrence of mutation events both in space and time. This precludes a mutator phenotype or other conventional explanation and appear to indicate a generalized form of stress induced mutatgenesis which is well documented in bacteria. This review will discuss the phenomenology of what we term non-targeted effects, and will consider to what extent they challenge conventional ideas in genetics and epigenetics.

  18. Obesity, insulin resistance and comorbidities – Mechanisms of association

    Science.gov (United States)

    Castro, Ana Valeria B.; Kolka, Cathryn M.; Kim, Stella P.; Bergman, Richard N.

    2015-01-01

    Overall excess of fat, usually defined by the body mass index, is associated with metabolic (e.g. glucose intolerance, type 2 diabetes mellitus (T2DM), dyslipidemia) and non-metabolic disorders (e.g. neoplasias, polycystic ovary syndrome, non-alcoholic fat liver disease, glomerulopathy, bone fragility etc.). However, more than its total amount, the distribution of adipose tissue throughout the body is a better predictor of the risk to the development of those disorders. Fat accumulation in the abdominal area and in non-adipose tissue (ectopic fat), for example, is associated with increased risk to develop metabolic and non-metabolic derangements. On the other hand, observations suggest that individuals who present peripheral adiposity, characterized by large hip and thigh circumferences, have better glucose tolerance, reduced incidence of T2DM and of metabolic syndrome. Insulin resistance (IR) is one of the main culprits in the association between obesity, particularly visceral, and metabolic as well as non-metabolic diseases. In this review we will highlight the current pathophysiological and molecular mechanisms possibly involved in the link between increased VAT, ectopic fat, IR and comorbidities. We will also provide some insights in the identification of these abnormalities. PMID:25211442

  19. Heat enhancement of radiation resistivity of evaporated CsI, KI and KBr photocathodes

    CERN Document Server

    Tremsin, A S

    2000-01-01

    The photoemissive stability of as-deposited and heat-treated CsI, KI and KBr evaporated thin films under UV radiation is examined in this paper. After the deposition, some photocathodes were annealed for several hours at 90 deg. C in vacuum and their performance was then compared to the performance of non-heated samples. We observed that the post-evaporation thermal treatment not only increases the photoyield of CsI and KI photocathodes in the spectral range of 115-190 nm, but also reduces CsI, KI and KBr photocurrent degradation that occurs after UV irradiation. KBr evaporated layers appeared to be more radiation-resistant than CsI and KI layers. Post-deposition heat treatment did not result in any significant variation of KBr UV sensitivity.

  20. Conceptual design of a versatile radiation tolerant integrated signal conditioning circuit for resistive sensors

    Energy Technology Data Exchange (ETDEWEB)

    Leroux, P. [Katholieke Hogeschool Kempen, Kleinhoefstraat 4, B-2440 Geel (Belgium); Katholieke Universiteit Leuven, Dept. ESAT-MICAS, Kasteelpark Arenberg 10, B-3001 Heverlee (Belgium); SCK-CEN, Belgian Nuclear Research Centre, Boeretang 200, B-2400 Mol (Belgium); Sterckx, J. [Katholieke Hogeschool Kempen, Kleinhoefstraat 4, B-2440 Geel (Belgium); Van Uffelen, M.; Damiani, C. [Fusion 4 Energy, Ed. B3, c/Josep, no 2, Torres Diagonal Litoral, 08019 Barcelona (Spain)

    2011-07-01

    This paper presents the design of a radiation tolerant configurable discrete time CMOS signal conditioning circuit for use with resistive sensors like strain gauge pressure sensors. The circuit is intended to be used for remote handling in harsh environments in the International Thermonuclear Experimental fusion Reactor (ITER). The design features a 5 V differential preamplifier using a Correlated Double Sampling (CDS) architecture at a sample rate of 20 kHz and a 24 V discrete time post amplifier. The gain is digitally controllable between 27 and 400 in the preamplifier and between 1 and 8 in the post amplifier. The nominal input referred noise voltage is only 8.5 {mu}V while consuming only 1 mW. The circuit has a simulated radiation tolerance of more than 1 MGy. (authors)

  1. Eletromagnetic radiation and the mechanical reactions arising from it

    CERN Document Server

    Schott, G A

    1912-01-01

    Fundamental equations of the electron theory ; transformation of the potentials ; other types of solution ; physical interpretation of the solutions obtained ; illustrative examples ; remarks on the solutions obtained and on the methods of calculating the potentials in general ; periodic motions ; on the distant field due to a moving charge ; pseudo-periodic and aperiodic motions ; on the field near the orbit of a moving charge or group ; the mechanical forces acting on electric charges in motion ; the motion of groups of electric charges ; on the Doppler effect ; on the disturbed motion of a ring of electrons ; on the field close to a point charge in motion ; the mechanical force exterted by an electron on itself ; the mechanical explanation of the electron ; the mechanics of the Lorentz electron ; problems illustrative of the motion of the Lorentz electron.

  2. Study of surface properties of ATLAS12 strip sensors and their radiation resistance

    Science.gov (United States)

    Mikestikova, M.; Allport, P. P.; Baca, M.; Broughton, J.; Chisholm, A.; Nikolopoulos, K.; Pyatt, S.; Thomas, J. P.; Wilson, J. A.; Kierstead, J.; Kuczewski, P.; Lynn, D.; Hommels, L. B. A.; Ullan, M.; Bloch, I.; Gregor, I. M.; Tackmann, K.; Hauser, M.; Jakobs, K.; Kuehn, S.; Mahboubi, K.; Mori, R.; Parzefall, U.; Clark, A.; Ferrere, D.; Sevilla, S. Gonzalez; Ashby, J.; Blue, A.; Bates, R.; Buttar, C.; Doherty, F.; McMullen, T.; McEwan, F.; O'Shea, V.; Kamada, S.; Yamamura, K.; Ikegami, Y.; Nakamura, K.; Takubo, Y.; Unno, Y.; Takashima, R.; Chilingarov, A.; Fox, H.; Affolder, A. A.; Casse, G.; Dervan, P.; Forshaw, D.; Greenall, A.; Wonsak, S.; Wormald, M.; Cindro, V.; Kramberger, G.; Mandić, I.; Mikuž, M.; Gorelov, I.; Hoeferkamp, M.; Palni, P.; Seidel, S.; Taylor, A.; Toms, K.; Wang, R.; Hessey, N. P.; Valencic, N.; Hanagaki, K.; Dolezal, Z.; Kodys, P.; Bohm, J.; Stastny, J.; Bevan, A.; Beck, G.; Milke, C.; Domingo, M.; Fadeyev, V.; Galloway, Z.; Hibbard-Lubow, D.; Liang, Z.; Sadrozinski, H. F.-W.; Seiden, A.; To, K.; French, R.; Hodgson, P.; Marin-Reyes, H.; Parker, K.; Jinnouchi, O.; Hara, K.; Sato, K.; Hagihara, M.; Iwabuchi, S.; Bernabeu, J.; Civera, J. V.; Garcia, C.; Lacasta, C.; Marti i Garcia, S.; Rodriguez, D.; Santoyo, D.; Solaz, C.; Soldevila, U.

    2016-09-01

    A radiation hard n+-in-p micro-strip sensor for the use in the Upgrade of the strip tracker of the ATLAS experiment at the High Luminosity Large Hadron Collider (HL-LHC) has been developed by the "ATLAS ITk Strip Sensor collaboration" and produced by Hamamatsu Photonics. Surface properties of different types of end-cap and barrel miniature sensors of the latest sensor design ATLAS12 have been studied before and after irradiation. The tested barrel sensors vary in "punch-through protection" (PTP) structure, and the end-cap sensors, whose stereo-strips differ in fan geometry, in strip pitch and in edge strip ganging options. Sensors have been irradiated with proton fluences of up to 1×1016 neq/cm2, by reactor neutron fluence of 1×1015 neq/cm2 and by gamma rays from 60Co up to dose of 1 MGy. The main goal of the present study is to characterize the leakage current for micro-discharge breakdown voltage estimation, the inter-strip resistance and capacitance, the bias resistance and the effectiveness of PTP structures as a function of bias voltage and fluence. It has been verified that the ATLAS12 sensors have high breakdown voltage well above the operational voltage which implies that different geometries of sensors do not influence their stability. The inter-strip isolation is a strong function of irradiation fluence, however the sensor performance is acceptable in the expected range for HL-LHC. New gated PTP structure exhibits low PTP onset voltage and sharp cut-off of effective resistance even at the highest tested radiation fluence. The inter-strip capacitance complies with the technical specification required before irradiation and no radiation-induced degradation was observed. A summary of ATLAS12 sensors tests is presented including a comparison of results from different irradiation sites. The measured characteristics are compared with the previous prototype of the sensor design, ATLAS07.

  3. [Mechanism of the radiation-protective effect of indralin].

    Science.gov (United States)

    Vasin, M V; Chernov, G A; Koroleva, L V; L'vova, T S; Abramov, M M; Antipov, V V; Suvorov, N N

    1996-01-01

    Pharmacological test demonstrated that radioprotective activity of indralin occurs by interaction with alpha-adrenoreceptor. Radioprotective effect of indralin decreased by alpha-adrenoblocker, aminazine and theophylline. Normobaric hyperoxia during irradiation reduced radioprotective effect of indralin in doses about ED50. In experiment with mice and rats it was shown that indralin induced acute hypoxia, impaired oxygen consumption and heat production by 30-46%, spleen bloodflow to 26.3% of control level, rectal temperature by 1.5-2 degrees C (mouse). After 30-min indralin raised resistance of mice to hypoxic hypoxia that is believed due to rapid development of biochemical adaptive process in hypoxic cells.

  4. Resistance to antivirals in human cytomegalovirus: mechanisms and clinical significance.

    Science.gov (United States)

    Pérez, J L

    1997-09-01

    Long term therapies needed for managing human cytomegalovirus (HCMV) infections in immunosupressed patients provided the background for the emergence of the resistance to antivirals active against HCMV. In addition, laboratory selected mutants have also been readily achieved. Both clinical and laboratory resistant strains share the same determinants of resistance. Ganciclovir resistance may be due to a few mutations in the HCMV UL97 gene and/or viral DNA pol gene, the former being responsible for about 70% of clinical resistant isolates. Among them, V464, V594, S595 and F595 are the most frequent mutations. Because of their less extensive clinical use, much less is known about resistance to foscarnet and cidofovir (formerly, HPMPC) but in both cases, it has been associated to mutations in the DNA pol. Ganciclovir resistant strains showing DNA pol mutations are cross-resistant to cidofovir and their corresponding IC50 are normally higher than those from strains harboring only mutations at the UL97 gene. To date, foscarnet resistance seems to be independent of both ganciclovir and cidofovir resistance.

  5. CMOS pixel sensors on high resistive substrate for high-rate, high-radiation environments

    Science.gov (United States)

    Hirono, Toko; Barbero, Marlon; Breugnon, Patrick; Godiot, Stephanie; Gonella, Laura; Hemperek, Tomasz; Hügging, Fabian; Krüger, Hans; Liu, Jian; Pangaud, Patrick; Peric, Ivan; Pohl, David-Leon; Rozanov, Alexandre; Rymaszewski, Piotr; Wang, Anqing; Wermes, Norbert

    2016-09-01

    A depleted CMOS active pixel sensor (DMAPS) has been developed on a substrate with high resistivity in a high voltage process. High radiation tolerance and high time resolution can be expected because of the charge collection by drift. A prototype of DMAPS was fabricated in a 150 nm process by LFoundry. Two variants of the pixel layout were tested, and the measured depletion depths of the variants are 166 μm and 80 μm. We report the results obtained with the prototype fabricated in this technology.

  6. CMOS pixel sensors on high resistive substrate for high-rate, high-radiation environments

    Energy Technology Data Exchange (ETDEWEB)

    Hirono, Toko, E-mail: thirono@uni-bonn.de [Physikalisches Institute der Universität Bonn, Bonn (Germany); Barbero, Marlon; Breugnon, Patrick; Godiot, Stephanie [CPPM, Aix-Marseille Universite, CNRS/IN2P3, Marseille (France); Gonella, Laura; Hemperek, Tomasz; Hügging, Fabian; Krüger, Hans [Physikalisches Institute der Universität Bonn, Bonn (Germany); Liu, Jian; Pangaud, Patrick [CPPM, Aix-Marseille Universite, CNRS/IN2P3, Marseille (France); Peric, Ivan [IPE, Karlsruher Institut für Technologie, Karlsruhe (Germany); Pohl, David-Leon [Physikalisches Institute der Universität Bonn, Bonn (Germany); Rozanov, Alexandre [CPPM, Aix-Marseille Universite, CNRS/IN2P3, Marseille (France); Rymaszewski, Piotr [Physikalisches Institute der Universität Bonn, Bonn (Germany); Wang, Anqing [CPPM, Aix-Marseille Universite, CNRS/IN2P3, Marseille (France); Wermes, Norbert [Physikalisches Institute der Universität Bonn, Bonn (Germany)

    2016-09-21

    A depleted CMOS active pixel sensor (DMAPS) has been developed on a substrate with high resistivity in a high voltage process. High radiation tolerance and high time resolution can be expected because of the charge collection by drift. A prototype of DMAPS was fabricated in a 150 nm process by LFoundry. Two variants of the pixel layout were tested, and the measured depletion depths of the variants are 166 μm and 80 μm. We report the results obtained with the prototype fabricated in this technology.

  7. High-fat load: mechanism(s) of insulin resistance in skeletal muscle.

    Science.gov (United States)

    Lark, D S; Fisher-Wellman, K H; Neufer, P D

    2012-12-01

    Skeletal muscle from sedentary obese patients is characterized by depressed electron transport activity, reduced expression of genes required for oxidative metabolism, altered mitochondrial morphology and lower overall mitochondrial content. These findings imply that obesity, or more likely the metabolic imbalance that causes obesity, leads to a progressive decline in mitochondrial function, eventually culminating in mitochondrial dissolution or mitoptosis. A decrease in the sensitivity of skeletal muscle to insulin represents one of the earliest maladies associated with high dietary fat intake and weight gain. Considerable evidence has accumulated to suggest that the cytosolic ectopic accumulation of fatty acid metabolites, including diacylglycerol and ceramides, underlies the development of insulin resistance in skeletal muscle. However, an alternative mechanism has recently been evolving, which places the etiology of insulin resistance in the context of cellular/mitochondrial bioenergetics and redox systems biology. Overnutrition, particularly from high-fat diets, generates fuel overload within the mitochondria, resulting in the accumulation of partially oxidized acylcarnitines, increased mitochondrial hydrogen peroxide (H2O2) emission and a shift to a more oxidized intracellular redox environment. Blocking H2O2 emission prevents the shift in redox environment and preserves insulin sensitivity, providing evidence that the mitochondrial respiratory system is able to sense and respond to cellular metabolic imbalance. Mitochondrial H2O2 emission is a major regulator of protein redox state, as well as the overall cellular redox environment, raising the intriguing possibility that elevated H2O2 emission from nutrient overload may represent the underlying basis for the development of insulin resistance due to disruption of normal redox control mechanisms regulating protein function, including the insulin signaling and glucose transport processes.

  8. Radiation induced defects and thermoluminescence mechanism in aluminum oxide

    Energy Technology Data Exchange (ETDEWEB)

    Atobe, K.; Kobayashi, T.; Awata, T. [Naruto Univ. of Education, Tokushima (Japan); Okada, M. [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst; Nakagawa, M. [Kagawa Univ., Faculty of Education, Takamatsu, Kagawa (Japan)

    2001-01-01

    The thermoluminescence of the irradiated aluminum oxides were measured to study the radiation induced defects and their behaviors. Neutron and {gamma}-ray irradiation were performed for a shingle crystal of the high purity aluminum oxide. The thermoluminescence glow curve and its activation energy were measured. The spectroscopy measurement on the thermoluminescence and the absorption are also carried out. The observed 430 and 340 nm peaks are discussed relating to the F{sup +} and F centers, respectively. Activation state of the F center transits to 3P state through 1P state by emitting phonons. Trapped electron on 3P state emits phonon of 2.9 eV (430 nm) during transition to the ground state. The above reaction can be written by the equation. F{sup +} + e {yields} (F){sup *} {yields} F + h{nu}(2.9 eV, 470 nm). (Katsuta, H.)

  9. Mechanisms of resistance to spinosad in the western flower thrip, Frankliniella occidentalis (Pergande) (Thysanoptera:Thripidae)

    Institute of Scientific and Technical Information of China (English)

    Shu-Yun Zhang; Satoshi Kono; Tamotsu Murai; Tadashi Miyata

    2008-01-01

    Cross-resistance, resistance mechanisms, and mode of inheritance of spinosad resistance were studied in the western flower thrip, Frankliniella occidentalis (Pergande).Spinosad (naturalyte insecticide) showed low cross-resistance to prothiophos (organophosphorus insecticide) and chlorphenapyr (respiratory inhibitor) showed some cross-resistance to thiocyclam (nereistoxin). The synergists PBO (piperonyl butoxide),DEM (diethyl maleate), and DEF (s,s,s-tributyl phosphorotrithioate) did not show any synergism on the toxicity of spinosad in the resistant strain (ICS), indicating that metabolicmediated detoxification was not responsible for the spinosad resistance, suggesting that spinosad may reduce sensitivity of the target site: the nicotinic acetylcholine receptor and GABA receptor. Following reciprocal crosses, dose-response lines and dominance ratios indicated that spinosad resistance was incompletely dominant and there were no maternal effects. The results of backcross showed that spinosad resistance did not fit a single-gene hypothesis, suggesting that resistance was influenced by several genes.

  10. Development of TRAIL Resistance by Radiation-Induced Hypermethylation of DR4 CpG Island in Recurrent Laryngeal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Cheol [Department of Otorhinolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Department of Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Lee, Won Hyeok [Department of Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Min, Young Joo [Department of Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Cha, Hee Jeong [Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Han, Myung Woul [Department of Otorhinolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Chang, Hyo Won [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Sun-A [Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Seung-Ho [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Seong Who, E-mail: swhokim@gmail.com [Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Sang Yoon, E-mail: sykim3715@gmail.com [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Biomedical Research Institute, Korea Institute of Science and Technology, Seoul (Korea, Republic of)

    2014-04-01

    Purpose: There are limited therapeutic options for patients with recurrent head and neck cancer after radiation therapy failure. To assess the use of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) as a salvage chemotherapeutic agent for recurrent cancer after radiation failure, we investigated the effect of clinically relevant cumulative irradiation on TRAIL-induced apoptosis. Methods and Materials: Using a previously established HN3 cell line from a laryngeal carcinoma patient, we generated a chronically irradiated HN3R isogenic cell line. Viability and apoptosis in HN3 and HN3R cells treated with TRAIL were analyzed with MTS and PI/annexin V-FITC assays. Western blotting and flow cytometry were used to determine the underlying mechanism of TRAIL resistance. DR4 expression was semiquantitatively scored in a tissue microarray with 107 laryngeal cancer specimens. Methylation-specific polymerase chain reaction and bisulfite sequencing for DR4 were performed for genomic DNA isolated from each cell line. Results: HN3R cells were more resistant than HN3 cells to TRAIL-induced apoptosis because of significantly reduced levels of the DR4 receptor. The DR4 staining score in 37 salvage surgical specimens after radiation failure was lower in 70 surgical specimens without radiation treatment (3.03 ± 2.75 vs 5.46 ± 3.30, respectively; P<.001). HN3R cells had a methylated DR4 CpG island that was partially demethylated by the DNA demethylating agent 5-aza-2′-deoxycytidine. Conclusion: Epigenetic silencing of the TRAIL receptor by hypermethylation of a DR4 CpG island might be an underlying mechanism for TRAIL resistance in recurrent laryngeal carcinoma treated with radiation.

  11. Molecular mechanisms of insulin resistance and associated diseases.

    Science.gov (United States)

    Mlinar, Barbara; Marc, Janja; Janez, Andrej; Pfeifer, Marija

    2007-01-01

    Insulin resistance is a state in which higher than normal concentrations of insulin are required for normal response. The most common underlying cause is central obesity, although primary insulin resistance in normal-weight individuals is also possible. Excess abdominal adipose tissue has been shown to release increased amounts of free fatty acids which directly affect insulin signalling, diminish glucose uptake in muscle, drive exaggerated triglyceride synthesis and induce gluconeogenesis in the liver. Other factors presumed to play the role in insulin resistance are tumour necrosis factor alpha, adiponectin, leptin, IL-6 and some other adipokines. Hyperinsulinaemia which accompanies insulin resistance may be implicated in the development of many pathological states, such as hypertension and hyperandrogenaemia. Insulin resistance underlies metabolic syndrome and is further associated with polycystic ovary syndrome and lipodystrophies. When beta-cells fail to secrete the excess insulin needed, diabetes mellitus type 2 emerges, which is, besides coronary heart disease, the main complication of insulin resistance and associated diseases.

  12. Contact resistance at ceramic interfaces and its dependence on mechanical load

    DEFF Research Database (Denmark)

    Koch, Søren; Hendriksen, P.V.

    2004-01-01

    Low contact resistance between individual components is important for solid oxide fuel cell stacks if high performance is to be achieved. Several mechanisms may result in high contact resistance, e.g., current constriction due to low area of contact and formation of resistive phases between...

  13. Quantum-mechanical treatment of an electron undergoing synchrotron radiation.

    Science.gov (United States)

    White, D.

    1972-01-01

    The problem of an electron moving perpendicular to an intense magnetic field is approached from the framework of quantum mechanics. A numerical solution to the related rate equations describing the probabilities of occupation of the electron's energy states is put forth along with the expected errors involved. The quantum-mechanical approach is found to predict a significant amount of energy broadening with time for an initially monoenergetic electron beam entering a region of an intense magnetic field as long as the product of initial energy and magnetic field is of order 50 MG BeV or larger.

  14. The evolution of antibiotic resistance: insight into the roles of molecular mechanisms of resistance and treatment context.

    Science.gov (United States)

    Maclean, R Craig; Hall, Alex R; Perron, Gabriel G; Buckling, Angus

    2010-08-01

    The widespread use of antibiotics has markedly improved public health over the last 60 years. However, the efficacy of antibiotic treatment is rapidly decreasing as a result of the continual spread of antibiotic resistance in pathogen populations. The evolution of antibiotic resistance is an amazingly simple example of adaptation by natural selection, and there is growing interest among evolutionary biologists in using evolutionary principles to help understand and combat the spread of resistance in pathogen populations. In this article, we review recent progress in our understanding of the underlying evolutionary forces that drive antibiotic resistance. Recent work has shown that both the mechanisms of antibiotic action and resistance, as well as the treatment context in which resistance evolves, influence the evolution of resistance in predictable ways. We argue that developing predictive models of resistance evolution that can be used to prevent the spread of resistance in pathogen populations requires integrating the treatment context and the molecular biology of resistance into the same evolutionary framework.

  15. Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. I. Common molecular mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Borg, D.C.

    1984-01-01

    Some aspects of molecular mechanisms common to radiation and chemical carcinogenesis are discussed, particularly the DNA damage done by these agents. Emphasis is placed on epidemiological considerations and on dose-response models used in risk assessment to extrapolate from experimental data obtained at high doses to the effects from long-term, low-level exposures. 3 references, 6 figures. (ACR)

  16. Active noise canceling system for mechanically cooled germanium radiation detectors

    Science.gov (United States)

    Nelson, Karl Einar; Burks, Morgan T

    2014-04-22

    A microphonics noise cancellation system and method for improving the energy resolution for mechanically cooled high-purity Germanium (HPGe) detector systems. A classical adaptive noise canceling digital processing system using an adaptive predictor is used in an MCA to attenuate the microphonics noise source making the system more deployable.

  17. Mechanisms of PGPR-induced resistance against pathogens

    NARCIS (Netherlands)

    Loon, L.C. van; Bakker, P.A.H.M.; Pieterse, C.M.J.

    1997-01-01

    Plant growth-promoting rhizobacteria can suppress diseases through antagonism between the bacteria and soilborne pathogens, as well as by inducing a systemic resistance in the plant against both root and foliar pathogens. Specific Pseudomonas strains induce systemic resistance in carnation, cucumber

  18. Molecular mechanism of glucocorticoid resistance in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Sara De Iudicibus; Raffaella Franca; Stefano Martelossi; Alessandro Ventura; Giuliana Decorti

    2011-01-01

    Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in moderate to severe active Crohn’s disease and ulcerative colitis. Despite their extensive therapeutic use and the proven effectiveness, consider-able clinical evidence of wide inter-individual differences in GC efficacy among patients has been reported, in particular when these agents are used in inflammatory diseases. In recent years, a detailed knowledge of the GC mechanism of action and of the genetic variants affecting GC activity at the molecular level has arisen from several studies. GCs interact with their cytoplasmic receptor, and are able to repress inflammatory gene expression through several distinct mechanisms. The glucocorticoid receptor (GR) is therefore crucial for the effects of these agents: mutations in the GR gene (NR3C1, nuclear re-ceptor subfamily 3, group C, member 1) are the primary cause of a rare, inherited form of GC resistance; in ad-dition, several polymorphisms of this gene have been described and associated with GC response and toxicity. However, the GR is not self-standing in the cell and the receptor-mediated functions are the result of a complex interplay of GR and many other cellular partners. The latter comprise several chaperonins of the large coopera-tive hetero-oligomeric complex that binds the hormone-free GR in the cytosol, and several factors involved in the transcriptional machinery and chromatin remodeling, that are critical for the hormonal control of target genes transcription in the nucleus. Furthermore, variants in the principal effectors of GCs (e.g. cytokines and their regulators) have also to be taken into account for a com-prehensive evaluation of the variability in GC response. Polymorphisms in genes involved in the transport and/or metabolism of these hormones have also been

  19. Mechanism of Hydrophilicity by Radiation-Induced Surface Activation

    Science.gov (United States)

    Honjo, Yoshio; Furuya, Masahiro; Takamasa, Tomoji; Okamoto, Koji

    When a metal oxide is irradiated by gamma rays, the irradiated surface becomes hydrophilic. This surface phenomenon is called as radiation-induced surface activation (RISA) hydrophilicity. In order to investigate gamma ray-induced and photoinduced hydrophilicity, the contact angles of water droplets on a titanium dioxide surface were measured in terms of irradiation intensity and time for gamma rays of cobalt-60 and for ultraviolet rays. Reciprocals of the contact angles increased in proportion to the irradiation time before the contact angles reached its super-hydrophilic state. The irradiation time dependency is equal to each other qualitatively. In addition, an effect of ambient gas was investigated. In pure argon gas, the contact angle remains the same against the irradiation time. This clearly indicates that certain humidity is required in ambient gas to take place of RISA hydrophilicity. A single crystal titanium dioxide (100) surface was analyzed by X-ray photoelectron spectrometry (XPS). After irradiation with gamma rays, a peak was found in the O1s spectrum, which indicates the adsorption of dissociative water to a surface 5-fold coordinate titanium site, and the formation of a surface hydroxyl group. We conclude that the RISA hydrophilicity is caused by chemisorption of the hydroxyl group on the surface.

  20. Analysis and utilization of plant antioxidative mechanism by radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Haeng-Soon; Kwon, Seock-Yoon; Shin, Seung-Yung [Korea Research Institute of Bioscience and Biotechnology, Taejeon (Korea)

    2001-04-01

    In an attempt to analysis the POD isoenzymes (swpa1, swpa2, swpa3, and swpn1) expression in response to gamma-irradiation in sweet potato. In suspension cells POD isoenzymes was highly expressed at 6 h postirradiation, and the transcript levels increased at 0 and 6 h at 50 Gy in plants. POD isoenzymes expression in response to irradiation appears not to be regulated in a different manner in cultured cells and plants. The gamma radiation-induced changes of proteins in tobacco suspension cells were investigated by SDS-PAGE. In tobacco cultured cells gamma irradiation did not significantly change the protein patterns. This indicates that the gamma irradiation-induced protein was not highly expressed or might be overlap with others. In the tobacco transgenic plants simultaneously expressing SOD and/or APX in chloroplast, the specific activities of SOD and APX of gamma-irradiated plants increased according to the dose of gamma-irradiation. These results indicate that antioxidative genes depends on antioxidative isoenzymes differently respond to gamma irradiation in transgenic tobacco plant lines. 35 refs., 9 figs. (Author)

  1. Correlation of Radiation Dosage With Mechanical Properties of Thin Films

    Science.gov (United States)

    Newton, R. L.

    2003-01-01

    The objective of this investigation was to examine the relationship between irradiation level (proton dose), microstructure, and stress levels in chemical vapor deposited diamond and polysilicon film using crosssectioned specimens. However, the emphasis was placed on the diamond specimen because diamond holds much promise for use in advanced technologies. The use of protons allows not only the study of the charged particle that may cause the most microstructural damage in Earth-orbit microelectromechanical systems (MEMS) devices, but also allows the study of relatively deeply buried damage inside the diamond material. Using protons allows these studies without having to resort to megaelectronvolt implant energies that may create extensive damage due to the high energy that is needed for the implantation process. Since 1 MEMS devices operating in space will not have an opportunity to reverse radiation damage via annealing, only nonannealed specimens were investigated. The following three high spatial resolution techniques were used to examine these relationships: (I) Scanning electron microscopy, (2) micro-Raman spectroscopy, and (3) micro x-ray diffraction.

  2. Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae

    OpenAIRE

    2014-01-01

    The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible ...

  3. Whole brain radiation-induced cognitive impairment: pathophysiological mechanisms and therapeutic targets.

    Science.gov (United States)

    Lee, Yong Woo; Cho, Hyung Joon; Lee, Won Hee; Sonntag, William E

    2012-07-01

    Radiation therapy, the most commonly used for the treatment of brain tumors, has been shown to be of major significance in tu-mor control and survival rate of brain tumor patients. About 200,000 patients with brain tumor are treated with either partial large field or whole brain radiation every year in the United States. The use of radiation therapy for treatment of brain tumors, however, may lead to devastating functional deficits in brain several months to years after treatment. In particular, whole brain radiation therapy results in a significant reduction in learning and memory in brain tumor patients as long-term consequences of treatment. Although a number of in vitro and in vivo studies have demonstrated the pathogenesis of radiation-mediated brain injury, the cel-lular and molecular mechanisms by which radiation induces damage to normal tissue in brain remain largely unknown. Therefore, this review focuses on the pathophysiological mechanisms of whole brain radiation-induced cognitive impairment and the iden-tification of novel therapeutic targets. Specifically, we review the current knowledge about the effects of whole brain radiation on pro-oxidative and pro-inflammatory pathways, matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) system and extracellular matrix (ECM), and physiological angiogenesis in brain. These studies may provide a foundation for defin-ing a new cellular and molecular basis related to the etiology of cognitive impairment that occurs among patients in response to whole brain radiation therapy. It may also lead to new opportunities for therapeutic interventions for brain tumor patients who are undergoing whole brain radiation therapy.

  4. [Resistance to UV radiation of microorganisms isolated from the rock biotopes of the Antarctic region].

    Science.gov (United States)

    Romanovskaia, V A; Tashirev, A B; Shilin, S O; Chernaia, N A

    2010-01-01

    Microbiological analysis of terrestrial biotopes of the Antarctic Region has shown, that vertical rocks of the Antarctic islands open for the Sun were characterized by special microcenoses. The wide distribution of pigmented microorganisms in the rock Antarctic samples, a higher frequency of their occurrence, the total number and biologic diversity, than in other Antarctic biotopes, has been demonstrated. For the first time the presence of bacteria and yeast, resistant to high doses of UV radiation on the vertical rocks in the Antarctic Region was shown. The lethal doze of UV radiation for the Antarctic pink pigmented Methylobacterium strains exceeded 200-300 J/m2, for coal-black yeast--500-800 J/m2, for red yeast--1200-1500 J/m2. The distinctions in lethal UV effect against strains of Methylobacterium isolated from the regions with different climate have not been found. Probably, adaptation of the rock microcenosis to extreme factors of the environment proceeds by natural selection of microorganisms, which resistance to this factor is genetically determined.

  5. Mechanism Of Resistance Of Evolved Glyphosate-Resistant Palmer Amaranth (Amaranthus Palmeri L.)

    Science.gov (United States)

    Evolved glyphosate resistance in weedy species represents a challenge for the continued success and utility of glyphosate-resistant crops. The first case of evolved glyphosate resistance in Palmer amaranth was a population from the U.S. state of Georgia, which was previously reported to have amplif...

  6. Multiple resistance and biochemical mechanisms of pyridaben resistance in Tetranychus urticae (Acari: Tetranychidae).

    Science.gov (United States)

    Kim, Young-Joon; Park, Hyung-Man; Cho, Jum-Rae; Ahn, Young-Joon

    2006-06-01

    A field colony of Tetranychus urticae (Koch) (Acari: Tetranychidae) resistant to pyridaben was selected with pyridaben successively for 20 generations to produce the PR-20 strain. Resistance and multiple resistance levels of the PR-20 strain to 15 acaricides were determined using a spray bioassay. The PR-20 strain was extremely resistant to pyridaben (resistance ratio [RR] = 240]. The strain exhibited extremely strong resistance to fenpyroximate (RR=373) and acrinathrin (RR=329) and strong resistance to benzoximate (RR=84). An RR = 10-40 was observed with abamectin, fenazaquin, fenbutatin oxide, fenpropathrin, and tebufenpyrad. The PR-20 strain showed low levels of resistance (RR <10) to azocyclotin, bromopropylate, chlorfenapyr, dicofol, milbemectin, and propargite. Synergist experiments with different metabolic inhibitors revealed that piperonyl butoxide (PBO), a mixed function oxidase (MFO) inhibitor, had the greatest effect on pyridaben resistance. PBO significantly caused pyridaben resistance in the PR-20 strain to drop to the full susceptibility level of the susceptible (S) strain. However, there was no significant difference in MFO activities measured using a model substrate between the S and PR-20 strains. These results suggest that use of certain acaricides with little multiple resistance or PBO will be useful for the management of pyridaben resistance in the field.

  7. Effect of solar radiation on multidrug resistant E. coli strains and antibiotic mixture photodegradation in wastewater polluted stream

    Energy Technology Data Exchange (ETDEWEB)

    Rizzo, L., E-mail: l.rizzo@unisa.it [Department of Civil Engineering, University of Salerno, via Ponte don Melillo, 1-84084 Fisciano (Italy); Fiorentino, A. [Department of Civil Engineering, University of Salerno, via Ponte don Melillo, 1-84084 Fisciano (Italy); Anselmo, A. [Pluriacque, via Alento, 84060 Prignano Cilento (Italy)

    2012-06-15

    The effect of solar radiation on the inactivation of multidrug resistant Escherichia coli (MDR) strains selected from an urban wastewater treatment plant (UWWTP) effluent and the change of their resistance to a mixture of three antibiotics (evaluated in terms of minimum inhibit concentration (MIC)) in wastewater polluted stream were investigated. The solar photodegradation of the mixture of the three target antibiotics (amoxicillin (AMX), ciprofloxacin (CPX), and sulfamethoxazole (SMZ)) was also evaluated. Additionally, since UWWTP effluents are possible sources of antibiotics and antibiotic resistant bacteria, the disinfection by conventional chlorination process of the UWWTP effluent inoculated with MDR strains was investigated too. Solar radiation poorly affected the inactivation of the two selected antibiotic resistant E. coli strains (40 and 60% after 180 min irradiation). Moreover, solar radiation did not affect strain resistance to AMX (MIC > 256 {mu}g/mL) and SMZ (MIC > 1024 {mu}g/mL), but affected resistance of the lower resistance strain to CPX (MIC decreased by 33% but only after 180 min of irradiation). Chlorination of wastewater sample strongly decreased the number of the two selected antibiotic resistant E. coli strains (99.667 and 99.999%), after 60 min of contact time at 2.0 mg/L initial chlorine concentration, but the resistance of survived colonies to antibiotics was unchanged. Finally, the solar photodegradation rate of the antibiotic mixture (1 mg/L initial concentration respectively) resulted in the following order (half-life time): CPX (t{sub 1/2} = 24 min) < AMX (t{sub 1/2} = 99 min) < SMZ (t{sub 1/2} = 577 min). Accordingly, the risk of the development of resistance to SMZ in surface water is significantly higher compared to CPX and AMX. - Highlights: Black-Right-Pointing-Pointer Solar radiation did not affect E. coli strain resistance to AMX and SMZ. Black-Right-Pointing-Pointer Solar radiation affected the resistance of one E. coli strain

  8. A mechanical model for giant radiating dike swarms

    Science.gov (United States)

    Minakov, Alexander; Yarushina, Viktoriya; Faleide, Jan Inge

    2016-04-01

    The Large Igneous Provinces (LIP) is believed to form as results of plume-lithosphere interaction. A recognizable diagnostic feature of the LIP is a swarm of dikes (100 - 1000 km -long) radiating from a single or several focal regions. The models for formation of these dike swarms are mainly based on Venusian analogues (associated with coronae structures) since on Earth these paleo-structures are presumably less likely to preserve due to erosion and later tectonics. The existing explanation for the geometry of dikes (in horizontal plane) is based on assumption that in a far-field shear stress the dikes are normal to the least principal stress. A small overpressure related to the lithospheric magma reservoir is also assumed. However, this type of models implies several limitations: 1) the dike emplacement is considered as a purely elastic process, 2) all dikes are assumed to intrude simultaneously (no interaction with neighboring dikes). On the other hand, recent geophysical observations suggest that the dikes that apparently belong to the same magmatic event can intersect and can be affected by each other and local crustal heterogeneity. In this study, we attribute the geometry of dikes to irreversible plastic deformation including the path-dependence. We use finite-element elastoplastic simulations to predict the fracture pattern related to the plume-lithosphere interaction. The rheology is governed by a non-associated Mohr-Coulomb plastic flow law. The accuracy of the numerical results is benchmarked versus 2D plane strain analytical solutions for combined shear and internal pressure loads. We apply our model to the case of the High Arctic LIP. Here, the location of the dike intrusions is based on the interpretation of magnetic anomalies supported by geological and seismic data in the Barents Sea together with timing constraints using U-Pb isotopic ages. The developed model provides a framework for future high-resolution structural and geochronological studies to

  9. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, Tyler J. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bowen, Stephen R. [Departments of Radiation Oncology and Radiology, University of Washington, Seattle, Washington (United States); Deveau, Michael A. [Department of Small Animal Clinical Sciences, Texas A& M University, College Station, Texas (United States); Kubicek, Lyndsay [Angell Animal Medical Center, Boston, Massachusetts (United States); White, Pamela [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bentzen, Søren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Chappell, Richard J. [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Forrest, Lisa J. [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Jeraj, Robert, E-mail: rjeraj@wisc.edu [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States)

    2015-03-15

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV{sub max}; SUV{sub mean}) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R{sup 2}. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV{sub mean} (P=.018), and midtreatment FLT SUV{sub max} (P=.006). Large decreases in FLT SUV{sub mean} from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV{sub max} (P=.022) in

  10. Mechanism analysis of radiation generated by the beam-plasma interaction in a vacuum diode

    Science.gov (United States)

    Zengchao, Ji; Shixiu, Chen; Shen, Gao

    2017-01-01

    When we were studying the vacuum switch, we found that the vacuum diode can radiate a broadband microwave. The vacuum diode is comprised of a cathode with a trigger device and planar anode, there is not a metallic bellows waveguide structure in this device, so the radiation mechanism of the vacuum diode is different from the plasma filled microwave device. It is hard to completely imitate the theory of the plasma filled microwave device. This paper analyzes the breakdown process of the vacuum diode, establishes the mathematical model of the radiating microwave from the vacuum diode. Based on the analysis of the dispersion relation in the form of a refractive index, the electromagnetic waves generated in the vacuum diode will resonate. The included angle between the direction of the electromagnetic radiation and the initial motion direction of electron beam is 45 degrees. The paper isolates the electrostatic effect from the beam-plasma interaction when the electromagnetic radiation occurs. According to above analyses, the dispersion relations of radiation are obtained by solving the wave equation. The dispersion curves are also obtained based on the theoretical dispersion relations. The theoretical dispersion curves are consistent with the actual measurement time-frequency maps of the radiation. Theoretical deduction and experiments indicate that the reason for microwave radiating from the vacuum diode can be well explained by the interaction of the electron beam and magnetized plasma. Supported by National Nature Science Foundation of China (No. 11075123), the Young Scientists Fund of Nature Science Foundation of China (No. 51207171).

  11. Deep sequencing of pyrethroid-resistant bed bugs reveals multiple mechanisms of resistance within a single population.

    Science.gov (United States)

    Adelman, Zach N; Kilcullen, Kathleen A; Koganemaru, Reina; Anderson, Michelle A E; Anderson, Troy D; Miller, Dini M

    2011-01-01

    A frightening resurgence of bed bug infestations has occurred over the last 10 years in the U.S. and current chemical methods have been inadequate for controlling this pest due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in U.S. bed bug populations, making it extremely difficult to develop intelligent strategies for their control. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I) and metabolic resistance to pyrethroid insecticides. Using LD(50) bioassays, we determined that resistance ratios for Richmond strain bed bugs were ∼5200-fold to the insecticide deltamethrin. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible) and Richmond (resistant) bed bugs revealed several candidate cytochrome P450 and carboxylesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance.

  12. Deep sequencing of pyrethroid-resistant bed bugs reveals multiple mechanisms of resistance within a single population.

    Directory of Open Access Journals (Sweden)

    Zach N Adelman

    Full Text Available A frightening resurgence of bed bug infestations has occurred over the last 10 years in the U.S. and current chemical methods have been inadequate for controlling this pest due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in U.S. bed bug populations, making it extremely difficult to develop intelligent strategies for their control. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I and metabolic resistance to pyrethroid insecticides. Using LD(50 bioassays, we determined that resistance ratios for Richmond strain bed bugs were ∼5200-fold to the insecticide deltamethrin. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible and Richmond (resistant bed bugs revealed several candidate cytochrome P450 and carboxylesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance.

  13. Alternate efflux pump mechanism may contribute to drug resistance in extensively drug-resistant isolates of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Akbar Kanji

    2016-01-01

    Conclusion: Our data show an nsSNP in the drrA efflux pump gene that may result in upregulation of drug efflux mechanisms in MTB strains. It is therefore imperative to understand the mechanism of efflux and its role in drug resistance, which will enable the identification of new drug targets and development of new drug regimens to counteract the drug efflux mechanism of MTB.

  14. Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links

    Science.gov (United States)

    Samuel, Varman T.; Shulman, Gerald I.

    2012-01-01

    Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance. PMID:22385956

  15. Mechanical strength of low-tempepvature-irradiated polyimides: A five-to-tenfold improvement in dose-resistance over epoxies

    Science.gov (United States)

    Coltman, R. R.; Klabunde, C. E.

    Neutronics calculations by Engholm [1] show that without additional shielding even the first fusion test reactors such as the Fusion Engineering Device may produce lifetime doses at magnet insulator locations that exceed the radiation tolerance of glass-fabric-filled (gff) epoxies now used. To explore the possible use of an alternative insulator, the mechanical strength of pure and recently available gff polyimides was studied as a function of gamma-ray irradiation at 4.9 K to 100 MGy (10 10 rads). After a postirradiation anneal at 307 K the flexure and compressive strengths of the gff materials measured at 77 K were reduced by up to 40% for 100 MGy while the pure material changed little. Testing done at 300 K gave similar results, but all stress values were about 40% less. Compared to earlier epoxy studies [2] we find that, overall, the gff polyimides are 5 to 10 times more radiation resistant than comparably prepared gff epoxies.

  16. Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance.

    Directory of Open Access Journals (Sweden)

    Alexander L Greninger

    Full Text Available Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA. These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described. Here we compare the genomes of 11 total parent-daughter strains of Staphylococcus aureus for which specific selection by serial passaging with ceftaroline or ceftobiprole was used to identify novel non-mecA mechanisms of resistance. All 5 ceftaroline-resistant strains, derived from 5 different parental strains, contained mutations directly upstream of the pbp4 gene (coding for the PBP4 protein, including four with the same thymidine insertion located 377 nucleotides upstream of the promoter site. In 4 of 5 independent ceftaroline-driven selections, we also isolated mutations to the same residue (Asn138 in PBP4. In addition, mutations in additional candidate genes such as ClpX endopeptidase, PP2C protein phosphatase and transcription terminator Rho, previously undescribed in the context of resistance to ceftaroline or ceftobiprole, were detected in multiple selections. These genomic findings suggest that non-mecA mechanisms, while yet to be encountered in the clinical setting, may also be important in mediating resistance to 5th-generation cephalosporins.

  17. Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance

    Science.gov (United States)

    Chan, Liana C.; Hamilton, Stephanie M.; Chambers, Henry F.; Chiu, Charles Y.

    2016-01-01

    Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA). These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described. Here we compare the genomes of 11 total parent-daughter strains of Staphylococcus aureus for which specific selection by serial passaging with ceftaroline or ceftobiprole was used to identify novel non-mecA mechanisms of resistance. All 5 ceftaroline-resistant strains, derived from 5 different parental strains, contained mutations directly upstream of the pbp4 gene (coding for the PBP4 protein), including four with the same thymidine insertion located 377 nucleotides upstream of the promoter site. In 4 of 5 independent ceftaroline-driven selections, we also isolated mutations to the same residue (Asn138) in PBP4. In addition, mutations in additional candidate genes such as ClpX endopeptidase, PP2C protein phosphatase and transcription terminator Rho, previously undescribed in the context of resistance to ceftaroline or ceftobiprole, were detected in multiple selections. These genomic findings suggest that non-mecA mechanisms, while yet to be encountered in the clinical setting, may also be important in mediating resistance to 5th-generation cephalosporins. PMID:26890675

  18. Physiological mechanism of resistance to anthracnose of different ...

    African Journals Online (AJOL)

    DR TONUKARI NYEROVWO

    2012-01-26

    Jan 26, 2012 ... Table 1. The varieties of C. oleifera. Number Sampling location Origin. Name. Natural resistance ..... Disord Drug Targets 6: 273-281. Crawford GH, Sciacca JR ... canines suffering from cutaneous skin disease. Schweiz Arch.

  19. Mechanisms of Helicobacter pylori antibiotic resistance and molecular testing

    OpenAIRE

    Toshihiro eNishizawa; Hidekazu eSuzuki

    2014-01-01

    Antibiotic resistance in Helicobacter pylori (H. pylori) is the main factor affecting the efficacy of current treatment methods against infection caused by this organism. The traditional culture methods for testing bacterial susceptibility to antibiotics are expensive and require 10 to 14 days. Since resistance to clarithromycin, fluoroquinolone, and tetracycline seems to be exclusively caused by specific mutations in a small region of the responsible gene, molecular methods offer an attracti...

  20. Mechanisms and Biological Costs of Bacterial Resistance to Antimicrobial Peptides

    OpenAIRE

    Lofton Tomenius, Hava

    2016-01-01

    The global increasing problem of antibiotic resistance necessarily drives the pursuit and discovery of new antimicrobial agents. Antimicrobial peptides (AMPs) initially seemed like promising new drug candidates. Already members of the innate immune system, it was assumed that they would be bioactive and non-toxic. Their common trait for fundamental, non-specific mode of action also seemed likely to reduce resistance development. In this thesis, we demonstrate the ease with which two species o...

  1. Mechanisms of macrophage activation in obesity-induced insulin resistance

    OpenAIRE

    Odegaard, Justin I.; Chawla, Ajay

    2008-01-01

    Chronic inflammation is now recognized as a key step in the pathogenesis of obesity-induced insulin resistance and type 2 diabetes mellitus. This low-grade inflammation is mediated by the inflammatory (classical) activation of recruited and resident macrophages that populate metabolic tissues, including adipose tissue and liver. These findings have led to the concept that infiltration and activation of adipose tissue macrophages is causally linked to obesity-induced insulin resistance. Studie...

  2. THE INVESTIGATION OF INFLUENCE OF LASER RADIATION ON THE STRUCTURE AND MECHANICAL PROPERTIES OF COMPOSITE ELECTROLYTIC NICKEL COATING

    Directory of Open Access Journals (Sweden)

    V. A. Zabludovsky

    2013-09-01

    Full Text Available Purpose. Investigation of laser radiation effect on the structure and mechanical properties of electrodeposited nickel composite coatings containing ultrafine diamonds. Methodology. Electrodeposition of nickel films was carried out with the addition of a standard solution of ultrafine diamonds (UFD on laser-electrolytic installation, built on the basis of the gas-discharge CO2 laser. Mechanical testing the durability of coatings were performed on a machine with reciprocating samples in conditions of dry friction against steel. The spectral microanalysis of the elemental composition of the film - substrate was performed on REMMA-102-02. Findings. Research of nickel coatings and modified ultrafine diamond electrodeposited under external stimulation laser demonstrated the dependence of the structure and mechanical properties of composite electrolytic coating (CEC, and the qualitative and quantitative distribution of nanodiamond coprecipitated from an electrodeposition method. Originality. The effect of laser light on the process of co-precipitation of the UFD, which increases the micro-hardness and wear resistance of electrolytic nickel coatings was determined. Practical value. The test method of laser-stimulated composite electrolytic nickel electrodeposition coating is an effective method of local increase in wear resistance of metal coatings, which provides durability save performance (functional properties of the surface.

  3. A review of control methods and resistance mechanisms in stored-product insects.

    Science.gov (United States)

    Boyer, S; Zhang, H; Lempérière, G

    2012-04-01

    This review describes the major stored-product insect species and their resistance to insecticides. The economic importance of the control of those pests is highlighted with a loss of more than one billion US dollars per year worldwide. A detailed common description of species resistance throughout the world has been developed, and we observed 28 recurrent studied species involved in resistance cases disseminated on the five continents. The different mechanisms, including behavioral resistance, were studied particularly on Oryzaephilus surinamensis. The role of detoxifying enzymes and studies on the genetic resistance, involving the kdr mutation mechanisms and the transmission of the genes of resistance, are also described. A chapter clarifying definitions on cross and multiple resistance is enclosed.

  4. Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods.

    Science.gov (United States)

    Osei Sekyere, J; Govinden, U; Bester, L A; Essack, S Y

    2016-09-01

    A literature review was undertaken to ascertain the molecular basis for tigecycline and colistin resistance mechanisms and the experimental basis for the detection and delineation of this resistance particularly in carbapenemase-producing Gram-negative bacteria. Pubmed, Google Scholar and Science Direct were searched with the keywords colistin, tigecycline, resistance mechanisms and detection methods. Trans-complementation and comparative MIC studies, mass spectrometry, chromatography, spectrofluorometry, PCR, qRT-PCR and whole genome sequencing (WGS) were commonly used to determine tigecycline and colistin resistance mechanisms, specifically modifications in the structural and regulatory efflux (acrAB, OqxAB, kpgABC adeABC-FGH-IJK, mexAB-XY-oprJM and soxS, rarA robA, ramRAB marRABC, adeLRS, mexRZ and nfxb) and lipid A (pmrHFIJFKLM, lpxA, lpxC lpxD and mgrB, pmrAB, phoPQ,) genes respectively. Mutations in the ribosomal 16S rRNA operon rrnBC, also yielded resistance to tigecycline through target site modifications. The mcr-1 gene conferring resistance to colistin was identified via WGS, trans-complementation and a murine thigh infection model studies. Common detection methods are mainly antibiotic sensitivity testing with broth microdilution while molecular identification tools are mostly PCR and WGS. Spectrofluorometry, MALDI-TOF MS, micro-array and real-time multiplex PCR hold much promise for the future as new detection tools.

  5. Multiple mechanisms increase levels of resistance in Rapistrum rugosum to ALS herbicides

    Directory of Open Access Journals (Sweden)

    Zhara M Hatami

    2016-02-01

    Full Text Available Rapistrum rugosum (turnip weed is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM, a sulfonylurea (SU belonging to the acetolactate synthase (ALS inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose–response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF for resistant (R populations was 2.5 to 6.6 fold higher than susceptible (S plant. Neither foliar retention, nor 14C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1, in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (resistance factors were from 28 to 38 and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT, pyrimidinyl-thiobenzoate (PTB and triazolopyrimidine (TP, with no cross-resistance to imidazolinone (IMI. Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM.

  6. Insecticide resistance mechanisms in the green peach aphid Myzus persicae (Hemiptera: Aphididae I: A transcriptomic survey.

    Directory of Open Access Journals (Sweden)

    Andrea X Silva

    Full Text Available BACKGROUND: Insecticide resistance is one of the best examples of rapid micro-evolution found in nature. Since the development of the first synthetic insecticide in 1939, humans have invested considerable effort to stay ahead of resistance phenotypes that repeatedly develop in insects. Aphids are a group of insects that have become global pests in agriculture and frequently exhibit insecticide resistance. The green peach aphid, Myzus persicae, has developed resistance to at least seventy different synthetic compounds, and different insecticide resistance mechanisms have been reported worldwide. METHODOLOGY/PRINCIPAL FINDINGS: To further characterize this resistance, we analyzed genome-wide transcriptional responses in three genotypes of M. persicae, each exhibiting different resistance mechanisms, in response to an anti-cholinesterase insecticide. The sensitive genotype (exhibiting no resistance mechanism responded to the insecticide by up-regulating 183 genes primarily ones related to energy metabolism, detoxifying enzymes, proteins of extracellular transport, peptidases and cuticular proteins. The second genotype (resistant through a kdr sodium channel mutation, up-regulated 17 genes coding for detoxifying enzymes, peptidase and cuticular proteins. Finally, a multiply resistant genotype (carrying kdr and a modified acetylcholinesterase, up-regulated only 7 genes, appears not to require induced insecticide detoxification, and instead down-regulated many genes. CONCLUSIONS/SIGNIFICANCE: This study suggests strongly that insecticide resistance in M. persicae is more complex that has been described, with the participation of a broad array of resistance mechanisms. The sensitive genotype exhibited the highest transcriptional plasticity, accounting for the wide range of potential adaptations to insecticides that this species can evolve. In contrast, the multiply resistant genotype exhibited a low transcriptional plasticity, even for the expression

  7. Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

    Science.gov (United States)

    Lehtinen, Sonja; Blanquart, François; Croucher, Nicholas J.; Turner, Paul; Lipsitch, Marc; Fraser, Christophe

    2017-01-01

    Understanding how changes in antibiotic consumption affect the prevalence of antibiotic resistance in bacterial pathogens is important for public health. In a number of bacterial species, including Streptococcus pneumoniae, the prevalence of resistance has remained relatively stable despite prolonged selection pressure from antibiotics. The evolutionary processes allowing the robust coexistence of antibiotic sensitive and resistant strains are not fully understood. While allelic diversity can be maintained at a locus by direct balancing selection, there is no evidence for such selection acting in the case of resistance. In this work, we propose a mechanism for maintaining coexistence at the resistance locus: linkage to a second locus that is under balancing selection and that modulates the fitness effect of resistance. We show that duration of carriage plays such a role, with long duration of carriage increasing the fitness advantage gained from resistance. We therefore predict that resistance will be more common in strains with a long duration of carriage and that mechanisms maintaining diversity in duration of carriage will also maintain diversity in antibiotic resistance. We test these predictions in S. pneumoniae and find that the duration of carriage of a serotype is indeed positively correlated with the prevalence of resistance in that serotype. These findings suggest heterogeneity in duration of carriage is a partial explanation for the coexistence of sensitive and resistant strains and that factors determining bacterial duration of carriage will also affect the prevalence of resistance. PMID:28096340

  8. Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-kappaB survival pathway signaling.

    Science.gov (United States)

    Weston, Victoria J; Austen, Belinda; Wei, Wenbin; Marston, Eliot; Alvi, Azra; Lawson, Sarah; Darbyshire, Philip J; Griffiths, Mike; Hill, Frank; Mann, Jill R; Moss, Paul A H; Taylor, A Malcolm R; Stankovic, Tatjana

    2004-09-01

    To investigate possible causes of the variable response to treatment in pediatric B-precursor acute lymphoblastic leukemia (ALL) and to establish potential novel therapeutic targets, we used ionizing radiation (IR) exposure as a model of DNA damage formation to identify tumors with resistance to p53-dependent apoptosis. Twenty-one of 40 ALL tumors responded normally to IR, exhibiting accumulation of p53 and p21 proteins and cleavage of caspases 3, 7, and 9 and of PARP1. Nineteen tumors exhibited apoptotic resistance and lacked PARP1 and caspase cleavage; although 15 of these tumors had normal accumulation of p53 and p21 proteins, examples exhibited abnormal expression of TRAF5, TRAF6, and cIAP1 after IR, suggesting increased NF-kappaB prosurvival signaling as the mechanism of apoptotic resistance. The presence of a hyperactive PARP1 mutation in one tumor was consistent with such increased NF-kappaB activity. PARP1 inhibition restored p53-dependent apoptosis after IR in these leukemias by reducing NF-kappaB DNA binding and transcriptional activity. In the remaining 4 ALL tumors, apoptotic resistance was associated with a TP53 mutation or with defective activation of p53. We conclude that increased NF-kappaB prosurvival signaling is a frequent mechanism by which B-precursor ALL tumors develop apoptotic resistance to IR and that PARP1 inhibition may improve the DNA damage response of these leukemias.

  9. Low-radiation environment affects the development of protection mechanisms in V79 cells.

    Science.gov (United States)

    Fratini, E; Carbone, C; Capece, D; Esposito, G; Simone, G; Tabocchini, M A; Tomasi, M; Belli, M; Satta, L

    2015-05-01

    Very little is known about the influence of environmental radiation on living matter. In principle, important information can be acquired by analysing possible differences between parallel biological systems, one in a reference-radiation environment (RRE) and the other in a low-radiation environment (LRE). We took advantage of the unique opportunity represented by the cell culture facilities at the Gran Sasso National Laboratories of the Istituto Nazionale di Fisica Nucleare, where environment dose rate reduction factors in the underground (LRE), with respect to the external laboratory (RRE), are as follows: 10(3) for neutrons, 10(7) for directly ionizing cosmic rays and 10 for total γ-rays. Chinese hamster V79 cells were cultured for 10 months in both RRE and LRE. At the end of this period, all the cultures were kept in RRE for another 6 months. Changes in the activities of antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX) and spontaneous mutation frequency at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus were investigated. The results obtained suggest that environmental radiation might act as a trigger of defence mechanisms in V79 cells, specifically those in reference conditions, showing a higher degree of defence against endogenous damage as compared to cells grown in a very low-radiation environment. Our findings corroborate the hypothesis that environmental radiation contributes to the development of defence mechanisms in today living organisms/systems.

  10. Simultaneous breakdown of multiple antibiotic resistance mechanisms in S. aureus.

    Science.gov (United States)

    Kaneti, Galoz; Sarig, Hadar; Marjieh, Ibrahim; Fadia, Zaknoon; Mor, Amram

    2013-12-01

    In previous studies, the oligo-acyl-lysyl (OAK) C12(ω7)K-β12 added to cultures of gram-positive bacteria exerted a bacteriostatic activity that was associated with membrane depolarization, even at high concentrations. Here, we report that multidrug-resistant Staphylococcus aureus strains, unlike other gram-positive species, have reverted to the sensitive phenotype when exposed to subminimal inhibitory concentrations (sub-MICs) of the OAK, thereby increasing antibiotics potency by up to 3 orders of magnitude. Such chemosensitization was achieved using either cytoplasm or cell-wall targeting antibiotics. Moreover, eventual emergence of resistance to antibiotics was significantly delayed. Using the mouse peritonitis-sepsis model, we show that on single-dose administration of oxacillin and OAK combinations, death induced by a lethal staphylococcal infection was prevented in a synergistic manner, thereby supporting the likelihood for synergism to persist under in vivo conditions. Toward illuminating the molecular basis for these observations, we present data arguing that sub-MIC OAK interactions with the plasma membrane can inhibit proton-dependent signal transduction responsible for expression and export of resistance factors, as demonstrated for β-lactamase and PBP2a. Collectively, the data reveal a potentially useful approach for overcoming antibiotic resistance and for preventing resistance from emerging as readily as when bacteria are exposed to an antibiotic alone.

  11. Low-dose radiation enhances susceptibility to cisplatin in resistant ovarian cancer cells via downregulation of ERCC1 and Bcl-2

    Institute of Scientific and Technical Information of China (English)

    Xiaoran Liu; Donghai Liang; Tao Jiang; Qing Dong; Hongsheng Yu 

    2016-01-01

    Objective Ovarian cancer is one of the leading causes of mortality in patients with malignant gyneco-logical tumors. After surgical intervention for ovarian cancer, cisplatin (DDP)-based chemotherapy is the first-line treatment. However, a major chal enge to treating ovarian cancer is the development of chemore-sistance. Thus, the first aim of this study was to determine whether low-dose radiation could enhance the susceptibility of resistant ovarian cancer cel s to DDP. The second aim was to provide new strategies for treating DDP-resistant ovarian cancer by examining its mechanism. Methods A cel counting kit-8 (CCK8) assay was performed to measure cel proliferation. Flow cytometry was utilized to quantify the apoptosis of DDP-resistant ovarian cancer cel s (SKOV3/DDP) using Annexin V and propidium iodide staining. Real-time quantitative (qPCR) was used to analyze the messenger RNA (mRNA) expression levels of excision repair cross complementing-group 1 (ERCC1) and B-cel lymphoma 2 (Bcl-2) in SKOV3/DDP. Results The IC50 values of the control, conventional-dose, and low-dose groups were 9.367 ± 0.16, 9.289 ± 0.16, and 3.847 ± 0.15, respectively (P Conclusion Low-dose radiation enhanced the sensitivity of resistant ovarian cancer cel s to DDP, pos-sibly by decreasing the DNA repair capacity of tumor cel s and promoting apoptosis.

  12. Late radiation-induced heart disease after radiotherapy. Clinical importance, radiobiological mechanisms and strategies of prevention.

    Science.gov (United States)

    Andratschke, Nicolaus; Maurer, Jean; Molls, Michael; Trott, Klaus-Rüdiger

    2011-08-01

    The clinical importance of radiation-induced heart disease, in particular in post-operative radiotherapy of breast cancer patients, has been recognised only recently. There is general agreement, that a co-ordinated research effort would be needed to explore all the potential strategies of how to reduce the late risk of radiation-induced heart disease in radiotherapy. This approach would be based, on one hand, on a comprehensive understanding of the radiobiological mechanisms of radiation-induced heart disease after radiotherapy which would require large-scale long-term animal experiments with high precision local heart irradiation. On the other hand - in close co-operation with mechanistic in vivo research studies - clinical studies in patients need to determine the influence of dose distribution in the heart on the risk of radiation-induced heart disease. The aim of these clinical studies would be to identify the critical structures within the organ which need to be spared and their radiation sensitivity as well as a potential volume and dose effect. The results of the mechanistic studies might also provide concepts of how to modify the gradual progression of radiation damage in the heart by drugs or biological molecules. The results of the studies in patients would need to also incorporate detailed dosimetric and imaging studies in order to develop early indicators of impending radiation-induced heart disease which would be a pre-condition to develop sound criteria for treatment plan optimisation. Copyright © 2010. Published by Elsevier Ireland Ltd.

  13. Blackbody radiation, conformal symmetry, and the mismatch between classical mechanics and electromagnetism

    Energy Technology Data Exchange (ETDEWEB)

    Boyer, Timothy H [Department of Physics, City College of the City University of New York, New York, NY 10031 (United States)

    2005-02-25

    The blackbody radiation problem within classical physics is reviewed. It is again suggested that conformal symmetry is the crucial unrecognized aspect, and that only scattering by classical electromagnetic systems will provide equilibrium at the Planck spectrum. It is pointed out that the several calculations of radiation scattering using nonlinear mechanical systems do not preserve the Boltzmann distribution under adiabatic change of a parameter, and this fact seems at variance with our expectations in connection with derivations of Wien's displacement theorem. By contrast, the striking properties of charged particle motion in a Coulomb potential or in a uniform magnetic field suggest the possibility that these systems will fit with classical thermal radiation. It may be possible to give a full scattering calculation in the case of cyclotron motion in order to provide the needed test of the connection between conformal symmetry and classical thermal radiation.

  14. Antimicrobial resistance in veterinary medicine: mechanisms and bacterial agents with the greatest impact on human health

    Directory of Open Access Journals (Sweden)

    Ketrin Cristina da Silva

    2013-06-01

    Full Text Available Many retrospective and prospective studies have been performed to understand the emergence and dissemination of antibiotic-resistant microorganisms. The rates of antimicrobial drug resistance among bacterial pathogens are high and now represent a worldwide concern, both in human medicine and veterinary practices. The aim of this review is to describe the mechanisms of antibiotic resistance and the risks associated with antimicrobial use in animal production. Pathogens with major impacts on human and animal health are discussed, including multidrug-resistant and extensively drug-resistant Gram-negative and Gram-positive bacteria

  15. Radiation-induced genomic instability: Are epigenetic mechanisms the missing link?

    Energy Technology Data Exchange (ETDEWEB)

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    2011-02-01

    Purpose: This review examines the evidence for the hypothesis that epigenetics are involved in the initiation and perpetuation of radiation-induced genomic instability (RIGI). Conclusion: In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, unirradiated progeny cells display phenotypic changes at delayed times after radiation of the parental cell. RIGI is thought to be important in the process of carcinogenesis, however, the mechanism by which this occurs remains to be elucidated. In the genomically unstable clones developed by Morgan and colleagues, radiation-induced mutations, double-strand breaks, or changes in mRNA levels alone could not account for the initiation or perpetuation of RIGI. Since changes in the DNA sequence could not fully explain the mechanism of RIGI, inherited epigenetic changes may be involved. Epigenetics are known to play an important role in many cellular processes and epigenetic aberrations can lead to carcinogenesis. Recent studies in the field of radiation biology suggest that the changes in methylation patterns may be involved in RIGI. Together these clues have led us to hypothesize that epigenetics may be the missing link in understanding the mechanism behind RIGI.

  16. The radioprotective effect and mechanism of captopril on radiation induced-heart damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Seung Hee; Lee, Kyung Ja; Koo, Hea Soo [Ewha Womans University, Seoul (Korea, Republic of)

    2004-03-15

    Captopril (angiotension converting enzyme inhibitor) is known to have a radioprotective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotective effect and mechanism of captopril in the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. The histopathological changes and immunohistochemical stains (TNF {alpha} , TGF {beta} 1, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema ({rho} = 0.082) and fibrin deposit ({rho} = 0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit ({rho} = 0.047) in the atrium, and the interstitial fibrin deposit ({rho} = 0.019) and edema ({rho} = 0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of TNF- {alpha} , TGF- {beta} 1, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial TNF- {alpha} and TGF- {beta} 1, in the radiation alone group continuously increased. The expressions of TNF- {alpha} , TGF- {beta} 1, and PDGF were decreased in the combined

  17. Membrane fouling in a membrane bioreactor: High filtration resistance of gel layer and its underlying mechanism.

    Science.gov (United States)

    Chen, Jianrong; Zhang, Meijia; Li, Fengquan; Qian, Lei; Lin, Hongjun; Yang, Lining; Wu, Xilin; Zhou, Xiaoling; He, Yiming; Liao, Bao-Qiang

    2016-10-01

    A membrane bioreactor (MBR) was continuously operated to investigate mechanisms of fouling caused by the gel layer in this study. Agar was used as a model foulant for gel layer formation, and filtration resistance of gel layers was systematically assessed. The results showed that gel layer possessed unusually high specific filtration resistance (SFR) and high measured porosity as compared with cake layer. Current knowledge cannot explain the contradiction between high filtration resistance and high porosity of gel layer. A new fouling mechanism based on Flory-Huggins theory was then proposed. Filtration resistance of agar gel layer was found to be independent of pH and ionic strength, but linearly increase with gel thickness. The results are accordant with the mechanism deductions. Simulation of the mechanism model showed that the filtration resistance induced by mixing chemical potential variation was comparable to the experimental data of filtration resistance of agar gel layer, indicating that the proposed mechanism is the predominant mechanism responsible for the high filtration resistance of gel layer. The proposed mechanism was further verified from the bound water viewpoint.

  18. The study of resistant mechanisms and reversal in an imatinib resistant Ph+ acute lymphoblastic leukemia cell line.

    Science.gov (United States)

    Xing, Hongyun; Yang, Xi; Liu, Ting; Lin, Juan; Chen, Xiaoyi; Gong, Yuping

    2012-04-01

    In this study, we established an imatinib resistant Ph+ acute lymphoblastic leukemia (ALL) cell line SUP-B15/RI in vitro and studied the mechanism of imatinib resistance. Our results showed that the BCR-ABL1 fusion gene and the mdr1 gene were 6.1 times and 1.7 times, respectively, as high as that of parental SUP-B15 cell line. We found no mutation in the Abl kinase domain of SUP-B15/RI. Furthermore, the detection of cell signaling pathway of PI3K/AKT/mTOR, RAS/RAF, NF-κB, JNK and STAT showed the up-regulation of phosphorylation of AKT, mTOR, P70S6K, and RAF, ERK, and MEK, down-regulation of PTEN and 4EBP-1, and no change in other cell signaling pathways in SUP-B15/RI. However, dasatinib and nilotinib showed partial resistance. Interestingly, bortezomib had no resistance. Imatinib combination with rapamycin had synergistic effect on overcoming the resistance. Altogether, over-expression of BCR-ABL1 and mdr1 gene were involved in the resistance mechanisms, and up-regulation of the cell signaling pathways of PI3K/AKT/mTOR, RAS/RAF in SUP-B15/RI cell line may be correlated with them. The SUP-B15/RI cell line was also resistant to the second generation tyrosine kinase, dasatinib, and nilotinib, not bortezomib. The combination of imatinib with rapamycin can partially overcome the resistance and blockade of the ubiquitin-proteasome can be also a promising pathway to overcome imatinib resistance. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Reversible resistance induced by FLT3 inhibition: a novel resistance mechanism in mutant FLT3-expressing cells.

    Directory of Open Access Journals (Sweden)

    Ellen Weisberg

    Full Text Available Clinical responses achieved with FLT3 kinase inhibitors in acute myeloid leukemia (AML are typically transient and partial. Thus, there is a need for identification of molecular mechanisms of clinical resistance to these drugs. In response, we characterized MOLM13 AML cell lines made resistant to two structurally-independent FLT3 inhibitors.MOLM13 cells were made drug resistant via prolonged exposure to midostaurin and HG-7-85-01, respectively. Cell proliferation was determined by Trypan blue exclusion. Protein expression was assessed by immunoblotting, immunoprecipitation, and flow cytometry. Cycloheximide was used to determine protein half-life. RT-PCR was performed to determine FLT3 mRNA levels, and FISH analysis was performed to determine FLT3 gene expression.We found that MOLM13 cells readily developed cross-resistance when exposed to either midostaurin or HG-7-85-01. Resistance in both lines was associated with dramatically elevated levels of cell surface FLT3 and elevated levels of phosphor-MAPK, but not phospho-STAT5. The increase in FLT3-ITD expression was at least in part due to reduced turnover of the receptor, with prolonged half-life. Importantly, the drug-resistant phenotype could be rapidly reversed upon withdrawal of either inhibitor. Consistent with this phenotype, no significant evidence of FLT3 gene amplification, kinase domain mutations, or elevated levels of mRNA was observed, suggesting that protein turnover may be part of an auto-regulatory pathway initiated by FLT3 kinase activity. Interestingly, FLT3 inhibitor resistance also correlated with resistance to cytosine arabinoside. Over-expression of FLT3 protein in response to kinase inhibitors may be part of a novel mechanism that could contribute to clinical resistance.

  20. Radiation resistance and parameters of activation of aluminium-magnesium-scandium and aluminium-magnesium-vanadium alloys under neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, L.I.; Ivanov, V.V.; Lazorenko, V.M.; Platov, Yu.M.; Tovtin, V.I.; Toropova, L.S. (A.A. Baikov Inst. of Metallurgy, Academy of Sciences, Moscow (Russia))

    1992-09-01

    Alloys Al-2.24Mg-0.223Sc-0.04Zr, Al-2.24Mg-0.12Sc-0.04Zr, and Al-2.24Mg-0.05V (at.%) annealed at 150deg C and 400deg C were irradiated at [approx equal] 70 and [approx equal] 150deg C in the SM-2 reactor. The maximum neutron fluence was 4.7x10[sup 24] m[sup -2] (E > 0.1 MeV). The tensile tests were carried out in the temperature range 20 to 350deg C. Alloy Al-2.24 Mg-0.23Sc-0.04Zr annealed at 400deg C and alloy Al-2.24Mg-0.12Sc-0.04Zr annealed at 150deg C at all test temperatures retained good mechanical properties after irradiation. The mechanisms for the radiation resistance of aluminium-scandium and aluminium-magnesium-scandium alloys are discussed. Calculations of induced radioactivity and its decay behaviour after shutdown in aluminium and Al-2.24Mg-(0.12-0.23)Sc alloys were carried out. Composition of the radionuclides in these materials after irradiation in the SM-2 reactor were also determined using a gamma-spectroscopy technique. (orig.).

  1. Radiation resistance and parameters of activation of aluminium-magnesium-scandium and aluminium-magnesium-vanadium alloys under neutron irradiation

    Science.gov (United States)

    Ivanov, L. I.; Ivanov, V. V.; Lazorenko, V. M.; Platov, Yu. M.; Tovtin, V. I.; Toropova, L. S.

    1992-09-01

    Alloys Al2.24Mg0.23Sc0.04Zr, Al2.24Mg0.12Sc0.04Zr, and Al2.24Mg0.05V (at.)) annealed at 150°C and 400°C were irradiated ≈70 and ≈150°C in the SM-2 reactor. The maximum neutron fluence was 4.7×1024 m-2 (E > 0.1 MeV). The tensile tests were carried out in the temperature range 20 to 350°C. Alloy Al2.24Mg0.23Sc0.04Zr annealed at 400°C and alloy Al2.24Mg0.12Sc0.04Zr annealed at 150°C at all test temperature, retained good mechanical properties after irradiation. The mechanisms for the radiation resistance of aluminiumscandium and aluminiummagnesiumscandium alloys are discussed. Calculations of induced radioactivity and its decay behaviour after shutdown in aluminium and Al2.24Mg(0.12-0.23)Sc alloys were carried out. Composition of the radionuclides in these materials after irradiation in the SM-2 reactor were also determined using a gamma-spectroscopy technique.

  2. Radiation health consequences for astronauts: mechanisms, monitoring and prevention

    Science.gov (United States)

    Neyfakh, E.

    During space flights crews are exposed chronically to uneven irradiation of enhanced bioefficiency following with significant elevation for chromosomal aberrations as minimum. To protect in space rationally monitoring and preventing of health radiogenic individual primary consequences for astronauts are of high importance. Majority of Chernobyl-touched population has some common etiologic radiogenic mechanisms and radioloads with astronauts ones during long-term missions and former is able to be used well as the close ground-level model. Primary radiogenic deviations. Two radiogenic pathologies as lipoperoxic ( LP ) stress with coupled deficits for essential bioantioxidants ( BAO ) were typical for chronic low-dose Chernobyl-touched contingents. When BAO expenditure had led to their subnormal levels, radiogenic free radical chain -b ranched LP processes occurred in vivo hyperbolically. Catabolites and their free radicals of the abnormal LP cascade are known to be toxic, mutagenic / carcinogenic and teratogenic factors as such, as they are for retinol and tocopherol deficiencies. Both coupled pathogenic factors interrelated synergistically. Simultaneous dysbalances for LP and / or BAO systems were evaluated as the cause and markers for metabolic disregulations. Human LP stress was proved to be the most radiosensible known marker to mo nitor least invasively of blood microsamples in a ground lab via the developed PC Program. But for capsule conditions the best approach is assumed to be LP monitoring via skin ultraweak green-blue chemiluminescence ( CL ) caused by recombination of peroxyl radicals. CL from surfaces of organs was embedded first ( E. Neyfakh, 1964 - 71 ) to reflect their internal LP velocities in vivo and it is the non-invasive on-line simple method of the highest sensitivity, supplying with data transmissible to the ground directly. Related deviations. a) Radiogenic hypermutagenesis: LP catabolites and their free radicals are responsible for direct DNA

  3. Effect of solar radiation on multidrug resistant E. coli strains and antibiotic mixture photodegradation in wastewater polluted stream.

    Science.gov (United States)

    Rizzo, L; Fiorentino, A; Anselmo, A

    2012-06-15

    The effect of solar radiation on the inactivation of multidrug resistant Escherichia coli (MDR) strains selected from an urban wastewater treatment plant (UWWTP) effluent and the change of their resistance to a mixture of three antibiotics (evaluated in terms of minimum inhibit concentration (MIC)) in wastewater polluted stream were investigated. The solar photodegradation of the mixture of the three target antibiotics (amoxicillin (AMX), ciprofloxacin (CPX), and sulfamethoxazole (SMZ)) was also evaluated. Additionally, since UWWTP effluents are possible sources of antibiotics and antibiotic resistant bacteria, the disinfection by conventional chlorination process of the UWWTP effluent inoculated with MDR strains was investigated too. Solar radiation poorly affected the inactivation of the two selected antibiotic resistant E. coli strains (40 and 60% after 180 min irradiation). Moreover, solar radiation did not affect strain resistance to AMX (MIC>256 μg/mL) and SMZ (MIC>1024 μg/mL), but affected resistance of the lower resistance strain to CPX (MIC decreased by 33% but only after 180 min of irradiation). Chlorination of wastewater sample strongly decreased the number of the two selected antibiotic resistant E. coli strains (99.667 and 99.999%), after 60 min of contact time at 2.0 mg/L initial chlorine concentration, but the resistance of survived colonies to antibiotics was unchanged. Finally, the solar photodegradation rate of the antibiotic mixture (1mg/L initial concentration respectively) resulted in the following order (half-life time): CPX (t(1/2)=24 min)resistance to SMZ in surface water is significantly higher compared to CPX and AMX. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Acaricide resistance and resistance mechanisms in Tetranychus urticae populations from rose greenhouses in the Netherlands

    NARCIS (Netherlands)

    Khajehali, J.; Van Nieuwenhuyse, P.; Demaeght, P.; Tirry, L.; Van Leeuwen, T.

    2011-01-01

    BACKGROUND: Spider mites are important crop pests that rapidly develop resistance to acaricides. To investigate whether acaricide resistance is a threat to greenhouse rose culture in the Netherlands, the susceptibility of 15 strains of Tetranychus urticae was tested to several currently used acarici

  5. Acaricide resistance and resistance mechanisms in Tetranychus urticae populations from rose greenhouses in the Netherlands

    NARCIS (Netherlands)

    Khajehali, J.; Van Nieuwenhuyse, P.; Demaeght, P.; Tirry, L.; Van Leeuwen, T.

    2011-01-01

    BACKGROUND: Spider mites are important crop pests that rapidly develop resistance to acaricides. To investigate whether acaricide resistance is a threat to greenhouse rose culture in the Netherlands, the susceptibility of 15 strains of Tetranychus urticae was tested to several currently used

  6. Mechanisms of quinolone resistance in Salmonella spp. / Mecanismos de resistência às quinolonas em Salmonella spp.

    Directory of Open Access Journals (Sweden)

    Tereza Cristina Rocha Moreira de Oliveira

    2010-07-01

    Full Text Available Salmonellosis is a common and widespread zoonotic disease of humans and a frequent cause of foodborne disease. Treatment of severe and systemic salmonellosis is usually done with fluoroquinolones. In this review resistance mechanisms of Salmonella to quinolones are discussed. Single point mutations in the quinolone resistant determining region (QRDR of the gyrA gene may be sufficient to generate high levels of resistance to non-fluorated quinolones and also may decrease the fluoroquinolones susceptibility. Other resistance mechanisms that should be considered are mutations in parC gene, the possibility of acquiring resistance through plasmidial transference and hyper-expression of efflux pumps. Fluoroquinolones resistance is still relatively uncommon in Salmonella compared to other species belonging to the Enterobacteriaceae family. However, the more careful use of fluoroquinolones in veterinary and human medicine is essential to decrease the selective pressure which can avoid the emergence and spread of resistant clones and consequently maintain the clinical efficacy of this group of antibiotics.A salmonelose é uma zoonose de importância mundial e uma das mais freqüentes doenças de origem alimentar. As fluoroquinolonas são a principal opção para o tratamento de salmoneloses graves ou sistêmicas. Esta revisão de literatura teve como objetivo apresentar os principais mecanismos envolvidos na resistência de Salmonella spp a estes antimicrobianos. Mutações de ponto na Região Determinante de Resistência à Quinolona (QRDR do gene gyrA podem gerar altos níveis de resistência a quinolonas não-fluoradas, além de reduzir a suscetibilidade as fluoroquinolonas. Outros mecanismos de resistência que também precisam ser considerados são as mutações no gene parC, a possibilidade do envolvimento de plasmídios de resistência e o sistema de efluxo ativo. A resistência às fluoroquinolonas ainda é incomum em Salmonella spp., quando

  7. Inheritance and mechanism of resistance to herbicides inhibiting acetolactate synthase in Sonchus oleraceus L.

    Science.gov (United States)

    Boutsalis, P; Powles, S B

    1995-07-01

    A biotype of Sonchus oleraceus L. (Compositae) has developed resistance to herbicides inhibiting acetolactate synthase (ALS) following field selection with chlorsulfuron for 8 consecutive years. The aim of this study was to determine the inheritance and mechanism of resistance in this biotype. Determination of ALS activity and inhibition kinetics revealed that Km and Vmax did not vary greatly between the resistant and susceptible biotypes. ALS extracted from the resistant biotype was resistant to five ALS-inhibiting herbicides in an in vitro assay. ALS activity from the resistant biotype was 14 19, 2, 3 and 3 times more resistant to inhibition by chlorsulfuron, sulfometuron, imazethapyr, imazapyr and flumetsulam, respectively, than the susceptible biotype. Hybrids between the resistant and a susceptible biotype were produced, and inheritance was followed through the F1, F2 and F3 generations. F1 hybrids displayed a uniform intermediate level of resistance between resistant and susceptible parents. Three distinct phenotypes, resistant, intermediate and susceptible, were identified in the F2 generation following chlorsulfuron application. A segregation ratio of 1∶2∶1 was observed, indicative of the action of a single, nuclear, incompletely dominant gene. F3 families, derived from intermediate F2 individuals, segregated in a similar manner. Resistance to herbicides inhibiting ALS in this biotype of S. oleraceus is due to the effect of a single gene coding for a resistant form of the target enzyme, ALS.

  8. Radiation dose dependent change in physiochemical, mechanical and barrier properties of guar gum based films.

    Science.gov (United States)

    Saurabh, Chaturbhuj K; Gupta, Sumit; Bahadur, Jitendra; Mazumder, S; Variyar, Prasad S; Sharma, Arun

    2013-11-06

    Mechanical and water vapor barrier properties of biodegradable films prepared from radiation processed guar gum were investigated. Films prepared from GG irradiated up to 500 Gy demonstrated significantly higher tensile strength as compared to non-irradiated control films. This improvement in tensile strength observed was demonstrated to be due to the ordering of polymer structures as confirmed by small angle X-ray scattering analysis. Exposure to doses higher than 500 Gy, however, resulted in a dose dependent decrease in tensile strength. A dose dependent decrease in puncture strength with no significant differences in the percent elongation was also observed at all the doses studied. Water vapor barrier properties of films improved up to 15% due to radiation processing. Radiation processing at lower doses for improving mechanical and barrier properties of guar based packaging films is demonstrated here for the first time. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Evaluation of radiation resistance of the bacterial contaminants from femoral heads processed for allogeneic transplantation

    Science.gov (United States)

    Singh, Rita; Singh, Durgeshwer

    2009-09-01

    Femoral heads excised during surgery were obtained from patients who had a fractured neck of the femur and were processed as bone allograft. The bacterial contaminants were isolated from femoral heads at different stages of processing and identified based on morphological characteristics and biochemical tests. Bacterial contaminants on bone were mainly Gram-positive bacilli and cocci (58.3%). Twenty-four isolates from bone samples were screened for resistance to radiation. The D10 values for Gram-negative bacteria isolated from femoral heads ranged from 0.17 to 0.65 kGy. Higher D10 values 0.56-1.04 kGy were observed for Gram-positive bacterial isolates.

  10. Evaluation of radiation resistance of the bacterial contaminants from femoral heads processed for allogeneic transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Rita [Radiation Dosimetry and Processing Group, Defence Laboratory, Jodhpur 342011 (India)], E-mail: singhritadr@yahoo.com; Singh, Durgeshwer [Radiation Dosimetry and Processing Group, Defence Laboratory, Jodhpur 342011 (India)

    2009-09-15

    Femoral heads excised during surgery were obtained from patients who had a fractured neck of the femur and were processed as bone allograft. The bacterial contaminants were isolated from femoral heads at different stages of processing and identified based on morphological characteristics and biochemical tests. Bacterial contaminants on bone were mainly Gram-positive bacilli and cocci (58.3%). Twenty-four isolates from bone samples were screened for resistance to radiation. The D{sub 10} values for Gram-negative bacteria isolated from femoral heads ranged from 0.17 to 0.65 kGy. Higher D{sub 10} values 0.56-1.04 kGy were observed for Gram-positive bacterial isolates.

  11. Radiation-resistant composite scintillators based on GSO and GPS grains

    Science.gov (United States)

    Boyarintsev, A. Yu.; Galunov, N. Z.; Gerasymov, Ia. V.; Karavaeva, N. L.; Krech, A. V.; Levchuk, L. G.; Popov, V. F.; Sidletskiy, O. Ts.; Sorokin, P. V.; Tarasenko, O. A.

    2017-01-01

    The effect of irradiation on the scintillation light output, optical transmittance, and luminescent spectra of composite scintillators based on grains of single crystals Gd2SiO5:Ce (GSO) and Gd2Si2O7:Ce (GPS) is studied. The dielectric gel Sylgard-184 is the base and the binder for the grains inside the composite scintillator. The paper presents and analyzes the results obtained for the scintillators exposed by 10 MeV electrons from the linear electron accelerator at room temperature. The exposure doses D≤250 Mrad. The dose rate is 0.2 or 1500 Mrad/h. The study has shown that the composite scintillators based on the grains of GSO and GPS are radiation-resistant over the range of the irradiation.

  12. Improvements of stress controllability and radiation resistance by adding carbon to boron-nitride

    Energy Technology Data Exchange (ETDEWEB)

    Nakaishi, M.; Sugishima, K. (Fujitsu Limited, Advanced Technology Div., Nakahara-ku, Kawasaki 211 (JP)); Yamada, M. (Stanford Electronics Lab., Stanford Univ., Stanford, CA (US))

    1990-07-01

    The addition of an atom having different bonding radii to a matrix film is an effective method for changing the stress of the film. In a plasma-enhanced CVD of BN, it is difficult to obtain tensile stress except for extremely boron-rich films. The controllability of tensile stress in BN film was improved by introducing a small amount of carbon into the BN matrix, using plasma-enhanced CVD between 400{degrees} and 500{degrees}C. The authors have obtained transparent films with high Young's modulus and tensile stress. They report that the radiation resistance of BNC deposited at 400{degrees}C was improved five times better than that of BN deposited by low-pressure CVD at similar temperatures.

  13. New insight on the high radiation resistance of UO2 against fission fragments

    Science.gov (United States)

    Szenes, G.

    2016-12-01

    Track radii are derived for semiconductors from a temperature distribution Θ(r) in which the width of the distribution is the only materials parameter. Analysis of track data for GeS, InP, GaAs and GaN show that the projectile velocity has no effect on track radii in semiconductors. Due to the missing velocity effect, the threshold for track formation, Set = 20 keV/nm is high in semiconducting UO2 in the whole range of projectile velocities. This is the origin of the high radiation resistance for fission fragments. Consequences for the simulation experiments with insulating CeO2 are discussed. It is verified that sputtering is described accurately by the Arrhenius equation for various materials including UO2. The ion-induced surface potential has a strong effect on the activation energy.

  14. 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.

  15. Radiation induced oxidative degradation of polymers—III. Effect of radiation on mechanical properties

    Science.gov (United States)

    Seguchi, Tadao; Arakawa, Kazuo; Ito, Masayuki; Hayakawa, Naohiro; Machi, Sueo

    The changes of mechanical properties of various kinds of polyethylene (PE) and ethylene-propylene copolymer (EPR) with the irradiation in air, in oxygen of 10 atm, and under vacuum were investigated. The decrease in the elongation ( E b) and the tensile strength ( T b) of PE by the irradiation in oxygen is larger than under vacuum. The changes of E b well reflect the degradation of PE. In case of EPR, the T b decreases sharply with dose in any environments, and the E b decreases under vacuum to a larger extent than in oxygen. The modulus at 200% elongation of EPR increases with dose under vacuum, but decreases in oxygen. When the samples were irradiated in air, the changes of the mechanical properties were the intermediate between oxygen and vacuum and dependent on the ratio of oxidation and non-oxidation layers in the film. The antioxidant (Irganox 1010 or DPPD) mixed in polymers was found to retard effectively the polymer degradation by the irradiation in oxygen.

  16. Mechanisms of Resistance to Endocrine Therapy in Breast Cancer: Focus on Signaling Pathways, miRNAs and Genetically Based Resistance

    Science.gov (United States)

    García-Becerra, Rocío; Santos, Nancy; Díaz, Lorenza; Camacho, Javier

    2013-01-01

    Breast cancer is the most frequent malignancy diagnosed in women. Approximately 70% of breast tumors express the estrogen receptor (ER). Tamoxifen and aromatase inhibitors (AIs) are the most common and effective therapies for patients with ERα-positive breast cancer. Alone or combined with chemotherapy, tamoxifen significantly reduces disease progression and is associated with more favorable impact on survival in patients. Unfortunately, endocrine resistance occurs, either de novo or acquired during the course of the treatment. The mechanisms that contribute to hormonal resistance include loss or modification in the ERα expression, regulation of signal transduction pathways, altered expression of specific microRNAs, balance of co-regulatory proteins, and genetic polymorphisms involved in tamoxifen metabolic activity. Because of the clinical consequences of endocrine resistance, new treatment strategies are arising to make the cells sensitive to tamoxifen. Here, we will review the current knowledge on mechanisms of endocrine resistance in breast cancer cells. In addition, we will discuss novel therapeutic strategies to overcome such resistance. Undoubtedly, circumventing endocrine resistance should help to improve therapy for the benefit of breast cancer patients. PMID:23344024

  17. Adaptation of the black yeast Wangiella dermatitidis to ionizing radiation: molecular and cellular mechanisms.

    Directory of Open Access Journals (Sweden)

    Kelly L Robertson

    Full Text Available Observations of enhanced growth of melanized fungi under low-dose ionizing radiation in the laboratory and in the damaged Chernobyl nuclear reactor suggest they have adapted the ability to survive or even benefit from exposure to ionizing radiation. However, the cellular and molecular mechanism of fungal responses to such radiation remains poorly understood. Using the black yeast Wangiella dermatitidis as a model, we confirmed that ionizing radiation enhanced cell growth by increasing cell division and cell size. Using RNA-seq technology, we compared the transcriptomic profiles of the wild type and the melanin-deficient wdpks1 mutant under irradiation and non-irradiation conditions. It was found that more than 3000 genes were differentially expressed when these two strains were constantly exposed to a low dose of ionizing radiation and that half were regulated at least two fold in either direction. Functional analysis indicated that many genes for amino acid and carbohydrate metabolism and cell cycle progression were down-regulated and that a number of antioxidant genes and genes affecting membrane fluidity were up-regulated in both irradiated strains. However, the expression of ribosomal biogenesis genes was significantly up-regulated in the irradiated wild-type strain but not in the irradiated wdpks1 mutant, implying that melanin might help to contribute radiation energy for protein translation. Furthermore, we demonstrated that long-term exposure to low doses of radiation significantly increased survivability of both the wild-type and the wdpks1 mutant, which was correlated with reduced levels of reactive oxygen species (ROS, increased production of carotenoid and induced expression of genes encoding translesion DNA synthesis. Our results represent the first functional genomic study of how melanized fungal cells respond to low dose ionizing radiation and provide clues for the identification of biological processes, molecular pathways and

  18. Antibiotic susceptibility and molecular mechanisms of macrolide resistance in streptococci isolated from adult cystic fibrosis patients.

    Science.gov (United States)

    Thornton, Christina S; Grinwis, Margot E; Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2015-11-01

    The cystic fibrosis (CF) airways are colonized by polymicrobial communities with high bacterial load and are influenced by frequent antibiotic exposures. This community includes diverse streptococci, some of which have been directly or indirectly associated with pulmonary exacerbations. As many streptococci are naturally competent, horizontal transfer of antibiotic-resistant determinants coupled with frequent and/or chronic antibiotic exposure may contribute to high resistance rates. In this study, we assessed antibiotic resistance in 413 streptococcal isolates from adult CF patients against nine antibiotics relevant in CF treatment. We observed very low rates of cephalosporin resistance [cefepime and ceftriaxone ( resistance to tetracycline (∼34%) and sulfamethoxazole/trimethoprim (∼45%). The highest rate of antibiotic resistance was to the macrolides [azithromycin (56.4%) and erythromycin (51.6%)]. We also investigated the molecular mechanisms of macrolide resistance and found that only half of our macrolide-resistant streptococci isolates contained the mef (efflux pump) or erm (methylation of 23S ribosomal target site) genes. The majority of isolates were, however, found to have point mutations at position 2058 or 2059 of the 23S ribosomal subunit - a molecular mechanism of resistance not commonly reported in the non-pyogenic and non-pneumococcal streptococci, and unique in comparison with previous studies. The high rates of resistance observed here may result in poor outcomes where specific streptococci are contributing to CF airway disease and serve as a reservoir of resistance genes within the CF airway microbiome.

  19. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Winyoo Chowanadisai

    Full Text Available The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05 (S2 Table. Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.

  20. Molecular Mechanisms of Antibiotic Resistance in Helicobacter pylori

    NARCIS (Netherlands)

    M.M. Gerrits (Monique)

    2004-01-01

    textabstractAn estimated 4 to 5 million individuals in the Netherlands are actively infected with Helicobacter pylori. Eradication of this bacterium becomes more difficult as the prevalence of antibiotic resistance is increasing worldwide. Most H. pylori infections are now diagnosed by non-invasi

  1. Mechanism of Trypanosoma brucei gambiense resistance to human serum

    DEFF Research Database (Denmark)

    Uzureau, Pierrick; Uzureau, Sophie; Lecordier, Laurence

    2013-01-01

    GP), which prevents APOL1 toxicity and induces stiffening of membranes upon interaction with lipids. Two additional features contribute to resistance to TLFs: reduction of sensitivity to APOL1 requiring cysteine protease activity, and TbHpHbR inactivation due to a L210S substitution. According...