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Sample records for rad53 determining radioresistance

  1. Protein oxidation implicated as the primary determinant of bacterial radioresistance.

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    Michael J Daly

    2007-04-01

    Full Text Available In the hierarchy of cellular targets damaged by ionizing radiation (IR, classical models of radiation toxicity place DNA at the top. Yet, many prokaryotes are killed by doses of IR that cause little DNA damage. Here we have probed the nature of Mn-facilitated IR resistance in Deinococcus radiodurans, which together with other extremely IR-resistant bacteria have high intracellular Mn/Fe concentration ratios compared to IR-sensitive bacteria. For in vitro and in vivo irradiation, we demonstrate a mechanistic link between Mn(II ions and protection of proteins from oxidative modifications that introduce carbonyl groups. Conditions that inhibited Mn accumulation or Mn redox cycling rendered D. radiodurans radiation sensitive and highly susceptible to protein oxidation. X-ray fluorescence microprobe analysis showed that Mn is globally distributed in D. radiodurans, but Fe is sequestered in a region between dividing cells. For a group of phylogenetically diverse IR-resistant and IR-sensitive wild-type bacteria, our findings support the idea that the degree of resistance is determined by the level of oxidative protein damage caused during irradiation. We present the case that protein, rather than DNA, is the principal target of the biological action of IR in sensitive bacteria, and extreme resistance in Mn-accumulating bacteria is based on protein protection.

  2. DNA replication checkpoint signaling depends on a Rad53-Dbf4 N-terminal interaction in Saccharomyces cerevisiae.

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    Chen, Ying-Chou; Kenworthy, Jessica; Gabrielse, Carrie; Hänni, Christine; Zegerman, Philip; Weinreich, Michael

    2013-06-01

    Dbf4-dependent kinase (DDK) and cyclin-dependent kinase (CDK) are essential to initiate DNA replication at individual origins. During replication stress, the S-phase checkpoint inhibits the DDK- and CDK-dependent activation of late replication origins. Rad53 kinase is a central effector of the replication checkpoint and both binds to and phosphorylates Dbf4 to prevent late-origin firing. The molecular basis for the Rad53-Dbf4 physical interaction is not clear but occurs through the Dbf4 N terminus. Here we found that both Rad53 FHA1 and FHA2 domains, which specifically recognize phospho-threonine (pT), interacted with Dbf4 through an N-terminal sequence and an adjacent BRCT domain. Purified Rad53 FHA1 domain (but not FHA2) bound to a pT Dbf4 peptide in vitro, suggesting a possible phospho-threonine-dependent interaction between FHA1 and Dbf4. The Dbf4-Rad53 interaction is governed by multiple contacts that are separable from the Cdc5- and Msa1-binding sites in the Dbf4 N terminus. Importantly, abrogation of the Rad53-Dbf4 physical interaction blocked Dbf4 phosphorylation and allowed late-origin firing during replication checkpoint activation. This indicated that Rad53 must stably bind to Dbf4 to regulate its activity.

  3. Analysis of the tolerance to DNA alkylating damage in MEC1 and RAD53 checkpoint mutants of Saccharomyces cerevisiae.

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    Alfonso Gallego-Sánchez

    Full Text Available Checkpoint response, tolerance and repair are three major pathways that eukaryotic cells evolved independently to maintain genome stability and integrity. Here, we studied the sensitivity to DNA damage in checkpoint-deficient budding yeast cells and found that checkpoint kinases Mec1 and Rad53 may modulate the balance between error-free and error-prone branches of the tolerance pathway. We have consistently observed that mutation of the RAD53 counterbalances error-free and error-prone branches upon exposure of cells to DNA damage induced either by MMS alkylation or by UV-radiation. We have also found that the potential Mec1/Rad53 balance modulation is independent from Rad6/Rad18-mediated PCNA ubiquitylation, as mec1Δ or rad53Δ mutants show no defects in the modification of the sliding clamp, therefore, we infer that it is likely exerted by acting on TLS polymerases and/or template switching targets.

  4. Rad53-Mediated Regulation of Rrm3 and Pif1 DNA Helicases Contributes to Prevention of Aberrant Fork Transitions under Replication Stress

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    Silvia Emma Rossi

    2015-10-01

    Full Text Available Replication stress activates the Mec1ATR and Rad53 kinases. Rad53 phosphorylates nuclear pores to counteract gene gating, thus preventing aberrant transitions at forks approaching transcribed genes. Here, we show that Rrm3 and Pif1, DNA helicases assisting fork progression across pausing sites, are detrimental in rad53 mutants experiencing replication stress. Rrm3 and Pif1 ablations rescue cell lethality, chromosome fragmentation, replisome-fork dissociation, fork reversal, and processing in rad53 cells. Through phosphorylation, Rad53 regulates Rrm3 and Pif1; phospho-mimicking rrm3 mutants ameliorate rad53 phenotypes following replication stress without affecting replication across pausing elements under normal conditions. Hence, the Mec1-Rad53 axis protects fork stability by regulating nuclear pores and DNA helicases. We propose that following replication stress, forks stall in an asymmetric conformation by inhibiting Rrm3 and Pif1, thus impeding lagging strand extension and preventing fork reversal; conversely, under unperturbed conditions, the peculiar conformation of forks encountering pausing sites would depend on active Rrm3 and Pif1.

  5. Notch Promotes Radioresistance of Glioma Stem Cells

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    Wang, Jialiang; Wakeman, Timothy P.; Latha, Justin D.; Hjelmeland, Anita B.; Wang, Xiao-Fan; White, Rebekah R.; Rich, Jeremy N.; Sullenger, Bruce A.

    2010-01-01

    Radiotherapy represents the most effective nonsurgical treatments for gliomas. Yet, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study, we showed that inhibition of Notch pathway with gamma-secretase inhibitors (GSIs) rendered the glioma st...

  6. Tid1/Rdh54 translocase is phosphorylated through a Mec1- and Rad53-dependent manner in the presence of DSB lesions in budding yeast.

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    Ferrari, Matteo; Nachimuthu, Benjamin Tamilselvan; Donnianni, Roberto Antonio; Klein, Hannah; Pellicioli, Achille

    2013-05-01

    Saccharomyces cerevisiae cells with a single double-strand break (DSB) activate the ATR/Mec1-dependent checkpoint response as a consequence of extensive ssDNA accumulation. The recombination factor Tid1/Rdh54, a member of the Swi2-like family proteins, has an ATPase activity and may contribute to the remodelling of nucleosomes on DNA. Tid1 dislocates Rad51 recombinase from dsDNA, can unwind and supercoil DNA filaments, and has been implicated in checkpoint adaptation from a G2/M arrest induced by an unrepaired DSB. Here we show that both ATR/Mec1 and Chk2/Rad53 kinases are implicated in the phosphorylation of Tid1 in the presence of DNA damage, indicating that the protein is regulated during the DNA damage response. We show that Tid1 ATPase activity is dispensable for its phosphorylation and for its recruitment near a DSB, but it is required to switch off Rad53 activation and for checkpoint adaptation. Mec1 and Rad53 kinases, together with Rad51 recombinase, are also implicated in the hyper-phosphorylation of the ATPase defective Tid1-K318R variant and in the efficient binding of the protein to the DSB site. In summary, Tid1 is a novel target of the DNA damage checkpoint pathway that is also involved in checkpoint adaptation.

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

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    Ida Nielsen

    Full Text Available The conserved family of RecQ DNA helicases consists of caretaker tumour suppressors, that defend genome integrity by acting on several pathways of DNA repair that maintain genome stability. In budding yeast, Sgs1 is the sole RecQ helicase and it has been implicated in checkpoint responses, replisome stability and dissolution of double Holliday junctions during homologous recombination. In this study we investigate a possible genetic interaction between SGS1 and RAD9 in the cellular response to methyl methane sulphonate (MMS induced damage and compare this with the genetic interaction between SGS1 and RAD24. The Rad9 protein, an adaptor for effector kinase activation, plays well-characterized roles in the DNA damage checkpoint response, whereas Rad24 is characterized as a sensor protein also in the DNA damage checkpoint response. Here we unveil novel insights into the cellular response to MMS-induced damage. Specifically, we show a strong synergistic functionality between SGS1 and RAD9 for recovery from MMS induced damage and for suppression of gross chromosomal rearrangements, which is not the case for SGS1 and RAD24. Intriguingly, it is a Rad53 independent function of Rad9, which becomes crucial for genome maintenance in the absence of Sgs1. Despite this, our dissection of the MMS checkpoint response reveals parallel, but unequal pathways for Rad53 activation and highlights significant differences between MMS- and hydroxyurea (HU-induced checkpoint responses with relation to the requirement of the Sgs1 interacting partner Topoisomerase III (Top3. Thus, whereas earlier studies have documented a Top3-independent role of Sgs1 for an HU-induced checkpoint response, we show here that upon MMS treatment, Sgs1 and Top3 together define a minor but parallel pathway to that of Rad9.

  8. Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma

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    Zhang, Hongfang; Luo, Honglei; Jiang, Zhenzhen; Yue, Jing; Hou, Qiang; Xie, Ruifei; Wu, Shixiu

    2016-01-01

    The efficacy of radiotherapy, one major treatment modality for esophageal squamous cell carcinoma (ESCC) is severely attenuated by radioresistance. Epithelial-to-mesenchymal transition (EMT) is a cellular process that determines therapy response and tumor progression. However, whether EMT is induced by ionizing radiation and involved in tumor radioresistance has been less studied in ESCC. Using multiple fractionated irradiation, the radioresistant esophageal squamous cancer cell line KYSE-150R had been established from its parental cell line KYSE-150. We found KYSE-150R displayed a significant EMT phenotype with an elongated spindle shape and down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker N-cadherin in comparison with KYSE-150. Furthermore, KYSE-150R also possessed some stemness-like properties characterized by density-dependent growth promotion and strong capability for sphere formation and tumorigenesis in NOD-SCID mice. Mechanical studies have revealed that WISP1, a secreted matricellular protein, is highly expressed in KYSE-150R and mediates EMT-associated radioresistance both in ESCC cells and in xenograft tumor models. Moreover, WISP1 has been demonstrated to be closely associated with the EMT phenotype observed in ESCC patients and to be an independent prognosis factor of ESCC patients treated with radiotherapy. Our study highlighted WISP1 as an attractive target to reverse EMT-associated radioresistance in ESCC and can be used as an independent prognostic factor of patients treated with radiotherapy. PMID:27125498

  9. Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr

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    Fedrigo Carlos A

    2011-11-01

    Full Text Available Abstract Background Radiation therapy is routinely prescribed for high-grade malignant gliomas. However, the efficacy of this therapeutic modality is often limited by the occurrence of radioresistance, reflected as a diminished susceptibility of the irradiated cells to undergo cell death. Thus, cells have evolved an elegant system in response to ionizing radiation induced DNA damage, where p53, Hsp70 and/or EGFr may play an important role in the process. In the present study, we investigated whether the content of p53, Hsp70 and EGFr are associated to glioblastoma (GBM cell radioresistance. Methods Spheroids from U-87MG and MO59J cell lines as well as spheroids derived from primary culture of tumor tissue of one GBM patient (UGBM1 were irradiated (5, 10 and 20 Gy, their relative radioresistance were established and the p53, Hsp70 and EGFr contents were immunohistochemically determined. Moreover, we investigated whether EGFr-phospho-Akt and EGFr-MEK-ERK pathways can induce GBM radioresistance using inhibitors of activation of ERK (PD098059 and Akt (wortmannin. Results At 5 Gy irradiation UGBM1 and U-87MG spheroids showed growth inhibition whereas the MO59J spheroid was relatively radioresistant. Overall, no significant changes in p53 and Hsp70 expression were found following 5 Gy irradiation treatment in all spheroids studied. The only difference observed in Hsp70 content was the periphery distribution in MO59J spheroids. However, 5 Gy treatment induced a significant increase on the EGFr levels in MO59J spheroids. Furthermore, treatment with inhibitors of activation of ERK (PD098059 and Akt (wortmannin leads to radiosensitization of MO59J spheroids. Conclusions These results indicate that the PI3K-Akt and MEK-ERK pathways triggered by EGFr confer GBM radioresistance.

  10. Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma.

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    Zhang, Hongfang; Luo, Honglei; Jiang, Zhenzhen; Yue, Jing; Hou, Qiang; Xie, Ruifei; Wu, Shixiu

    2016-07-01

    The efficacy of radiotherapy, one major treatment modality for esophageal squamous cell carcinoma (ESCC) is severely attenuated by radioresistance. Epithelial-to-mesenchymal transition (EMT) is a cellular process that determines therapy response and tumor progression. However, whether EMT is induced by ionizing radiation and involved in tumor radioresistance has been less studied in ESCC. Using multiple fractionated irradiation, the radioresistant esophageal squamous cancer cell line KYSE-150R had been established from its parental cell line KYSE-150. We found KYSE-150R displayed a significant EMT phenotype with an elongated spindle shape and down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker N-cadherin in comparison with KYSE-150. Furthermore, KYSE-150R also possessed some stemness-like properties characterized by density-dependent growth promotion and strong capability for sphere formation and tumorigenesis in NOD-SCID mice. Mechanical studies have revealed that WISP1, a secreted matricellular protein, is highly expressed in KYSE-150R and mediates EMT-associated radioresistance both in ESCC cells and in xenograft tumor models. Moreover, WISP1 has been demonstrated to be closely associated with the EMT phenotype observed in ESCC patients and to be an independent prognosis factor of ESCC patients treated with radiotherapy. Our study highlighted WISP1 as an attractive target to reverse EMT-associated radioresistance in ESCC and can be used as an independent prognostic factor of patients treated with radiotherapy. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  11. Sp1-mediated transcriptional activation of miR-205 promotes radioresistance in esophageal squamous cell carcinoma

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    Tong, Xin; Li, Jingjing; Zhang, Sujie; Liu, Xing; Wang, Lingxiong; Wu, Liangliang; Chen, Rui; Wei, Huafeng; Li, Bohua; Li, Cheng; Yang, Yunsheng; Steer, Clifford J.; Zhao, Jian; Guo, Yajun

    2017-01-01

    Radiotherapy for esophageal squamous cell carcinoma (ESCC) patients is limited by resistance to ionizing radiation (IR). However, the roles and mechanisms of microRNAs in radioresistance are obscure. Here, we investigated that microRNA-205 (miR-205) was upregulated in radioresistant (RR) ESCC cells compared with the parental cells. Overexpression of miR-205 promoted colony survival post-IR, whereas depletion of miR-205 sensitized ESCC cells to IR in vitro and in vivo. Further, we demonstrated that miR-205 promoted radioresistance by enhancing DNA repair, inhibiting apoptosis and activating epithelial-mesenchymal transition (EMT). Mechanistically, miR-205, upregulated post-IR, was demonstrated to be activated by Sp1 in parallel with its host gene, miR-205HG, both of which showed a perfect correlation. We also identified and validated phosphatase and tensin homolog (PTEN), as a target of miR-205 that promoted radioresistance via PI3K/AKT pathway. Lastly, increased miR-205 expression was closely associated with decreased PTEN expression in ESCC tissues and miR-205 expression predicted poor prognosis in patients with ESCC. Taken together, these findings identify miR-205 as a critical determinant of radioresistance and a biomarker of prognosis. The Sp1-mediated transcriptional activation of miR-205 promotes radioresistance through PTEN via PI3K/AKT pathway in ESCC. Inhibition of miR-205 expression may be a new strategy for radiotherapy in ESCC. PMID:27974696

  12. Characterization of radioresistant variant from U251 human glioblastoma cell line and the role of antioxdant enzymes in its radioresistancy

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    Lee, Hyung Chahn; Park, In Chul; Park, Myung Jin; Woo, Sang Hyeok; Rhee, Chang Hum; Hong, Seok-II [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-07-01

    To investigate the radioresistant mechanism in glioblastoma multiforme(GBM), we isolated the radioresistant clone (RRC) from U251 human glioblastoma cell line by exposing to repeated fractions of 3 Gy {gamma}-radiation for six months. RRC had higher radioresistance than the parent cell line as measured by clonogenic survival assay. FACS analysis showed that RRC had a delayed G2 arrest after radiation. Antioxidant enzymes, such as SOD, catalase, glutathione peroxidase (GPX), glutathione reductase (GR), were activated up to 5 folds in RRC after radiation. Erk 1/2 activation was higher in RRC than in the parent cell. Therefore, radioresistancy in RRC might be due to the delayed cell cycle, the coordinated high activation of antioxidant enzyme rather than a single enzyme alone,and higher activation of Erk 1/2.

  13. The Brain Microenvironment Preferentially Enhances the Radioresistance of CD133+ Glioblastoma Stem-like Cells

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    Muhammad Jamal

    2012-02-01

    Full Text Available Brain tumor xenografts initiated from glioblastoma (GBM CD133+ tumor stem-like cells (TSCs are composed of TSC and non-TSC subpopulations, simulating the phenotypic heterogeneity of GBMs in situ. Given that the discrepancies between the radiosensitivity of GBM cells in vitro and the treatment response of patients suggest a role for the microenvironment in GBM radioresistance, we compared the response of TSCs and non-TSCs irradiated under in vitro and orthotopic conditions. As a measure of radioresponse determined at the individual cell level, γH2AX and 53BP1 foci were quantified in CD133+ cells and their differentiated (CD133- progeny. Under in vitro conditions, no difference was detected between CD133+ and CD133- cells in foci induction or dispersal after irradiation. However, irradiation of orthotopic xenografts initiated from TSCs resulted in the induction of fewer γH2AX and 53BP1 foci in CD133+ cells compared to their CD133- counterparts within the same tumor. Xenograft irradiation resulted in a tumor growth delay of approximately 7 days with a corresponding increase in the percentage of CD133+ cells at 7 days after radiation, which persisted to the onset of neurologic symptoms. These results suggest that, although the radioresponse of TSCs and non-TSCs does not differ under in vitro growth conditions, CD133+ cells are relatively radioresistant under intracerebral growth conditions. Whereas these findings are consistent with the suspected role for TSCs as a determinant of GBM radioresistance, these data also illustrate the dependence of the cellular radioresistance on the brain microenvironment.

  14. Cytotoxicity and radiosensitization effect of TRA-8 on radioresistant human larynx squamous carcinoma cells.

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    Wu, F; Hu, Y; Long, J; Zhou, Y J; Zhong, Y H; Liao, Z K; Liu, S Q; Zhou, F X; Zhou, Y F; Xie, C H

    2009-02-01

    TRAIL induces apoptosis in a variety of tumorigenic and transformed cell lines, but not in many normal cells. Recent studies have demonstrated that death receptor 5 (DR5), one of the two death receptors bound by TRAIL, showed expression in most malignantly transformed cells. This study evaluated effects of a monoclonal antibody (TRA-8) to human death receptor 5, combined with ionizing radiation, on radioresistant human larynx squamous carcinoma cell line (Hep-2R). Cells were treated with TRA-8 alone or in combination with radiation, cell viability inhibition was measured by MTT assay, and the induction of apoptosis was determined by Annexin V staining. Radionsensitivity of Hep-2R cells treated with TRA-8 were investigated with long-term clonogenic assays. Regulation of DR5 expression in cells after radiation was analyzed by indirect immunofluorescence using murine TRA-8 in combination with flow cytometry. The results suggested that TRA-8 enhanced radionsensitivity of Hep-2R cells, and that TRA-8 regulated Hep-2R cell cycle arrest at G2/M phase. Irradiation up-regulated the expression of DR5, and when combined with TRA-8 yielded optimal survival benefit. Therefore, TRA-8 can be used in combination with irradiation in radioresistant human larynx squamous carcinoma cells. Monoclonal antibodies such as TRA-8 may play an important role in the development of an effective treatment strategy for patients with radioresistant cancers.

  15. Multiple factors conferring high radioresistance in insect Sf9 cells.

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    Cheng, I-Cheng; Lee, How-Jing; Wang, T C

    2009-05-01

    Sf9, a lepidopteran cell line isolated from the fall armyworm, Spodoptera frugiperda, was shown to be significantly more resistant to growth inhibition and apoptosis induction effects of x-ray irradiation than several human cell lines of different origins. The single-cell electrophoresis technique revealed that Sf9 cells showed lower x-ray irradiation-induced DNA damage as well as better efficiency at repairing these damages. In addition, Sf9 cells were lower in both background and x-ray irradiation-induced intracellular oxidative stress, in which the higher intracellular level of reduced glutathione seemed to play a major role. The significance of oxidative stress in determining the radioresistance of Sf9 cells was confirmed by their being more resistant to hydrogen peroxide while equally susceptible to other non-reactive oxygen species of N-nitroso alkylating agents when compared with a human cell line. Although the Sf9 and human cell lines were equally susceptible to the lethal effects of N-nitroso alkylating agents, the components of DNA damage-induced and the repair enzymes involved significantly differ. This phenomenon is also discussed in this report.

  16. Cancer-associated adipocytes promotes breast tumor radioresistance

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    Bochet, Ludivine; Meulle, Aline [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Institut National de la Sante et de la Recherche Medicale, INSERM U1048, 1 Avenue du Pr Jean Poulhes, BP 84225, F-31432 Toulouse Cedex (France); Imbert, Sandrine [CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Salles, Bernard [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Valet, Philippe [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); Institut National de la Sante et de la Recherche Medicale, INSERM U1048, 1 Avenue du Pr Jean Poulhes, BP 84225, F-31432 Toulouse Cedex (France); Muller, Catherine, E-mail: muller@ipbs.fr [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France)

    2011-07-22

    Highlights: {yields} Tumor-surrounding adipocytes contribute to breast cancer progression. {yields} Breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance. {yields} Increased in Chk1 phosphorylation is observed in irradiated co-cultivated tumor cells. {yields} IL-6 is over-expressed in tumor cells co-cultivated with adipocytes. {yields} IL-6 exposure confers increased Chk1 phosphorylation and radioresistance in tumor cells. -- Abstract: Mature adipocytes are excellent candidates to influence tumor behavior through heterotypic signaling processes since these cells produce hormones, growth factors, cytokines and other molecules, a heterogeneous group of molecules named adipokines. Using a 2D coculture system, we demonstrate that breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance and an earlier and higher increase in the effector kinase Chk1, a phenotype that was associated with decreased cell death as compared to tumor cells grown alone. Interestingly, the adipocytes-induced tumor changes taking place during the coculture time preceding the exposure to IR were sufficient to confer the radioresistant effect. Notorious among the changes brought by adipocytes was the significant increase of IL-6 expression in tumor cells, whose activity may well account for the observed tumor cell protection from IR toxicity. Indeed, our data confirmed the protective role of this cytokine as tumor cells incubated after irradiation with recombinant IL-6 exhibit an increased in Chk1 phosphorylation and a radioresistant phenotype, thus far recapitulating the effects observed in the presence of adipocytes. Our current study sheds light on a new role of tumor-surrounding adipocytes in fostering a radioresistant phenotype in breast tumors, a finding that might have important clinical implications in obese patients that frequently exhibit aggressive diseases.

  17. Radioresistance in murine solid tumors induced by interleukin-1

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    Braunschweiger, P.G.; Basrur, V.; Santos, O.; Adessa, A.; Houdek, P.; Markoe, A.M. [Univ. of Miami School of Medicine, Miami, FL (United States)

    1996-02-01

    Interleukin-1 (IL-1) has radioprotective activity in hematopoietic lineages and in other normal cell renewal systems, but little is known about the effects of IL-1{alpha} on the radiosensitivity of tumor cell populations. The present studies were conducted to investigate the effects of IL-1{alpha} on the radiosensitivity of clonogenic cells in RIF-1 and SCC-7 tumors. Radioresistance was detected within 2-4 h after administration of IL-1{alpha} (0.5 {mu}g/mouse, ip) and characterized by increases in D{sub 0}, D{sub q}, {alpha}/{Beta} and SF2. This radioresistance was similar to that seen in tumors rendered totally hypoxic before X irradiation. Tirapazamine, a hypoxic cell cytotoxin, and IL-1{alpha} had synergistic schedule-dependent antitumor activity in vivo, suggesting that IL-1-induced radioresistance in vivo is due to hypoxia. Radioresistance induced by IL-1{alpha} was transient, and the data suggested reoxygenation within 12 h. In vitro, IL-1{alpha} had no direct effect on the radiosensitivity of SCC-7 cells in tissue culture under aerobic conditions. However, an increase in D{sub 0}, {alpha}/{Beta} and SF2 was seen in clonogenic tumor cells from primary cultures treated with IL-1{alpha} under aerobic conditions. Superoxide dismutase and catalase prevented the induction of radioresistance by IL-1{alpha} in vitro, suggesting that oxidative responses from tumor macrophages after administration of IL-1{alpha} may be responsible for induced radioresistance by IL-1 in vitro. Although oxidant stress induced by IL-1 may play an important role in the activity of IL-1{alpha} both in vivo and in vitro in our models, the mechanisms by which such responses modulate tumor radiosensitivity in vivo and in vitro are likely quite different. 32 refs., 6 figs., 1 tab.

  18. Hypoxia promotes radioresistance of CD133-positive Hep-2 human laryngeal squamous carcinoma cells in vitro.

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    Wang, Maoxin; Li, Xiaoming; Qu, Yongtao; Xu, Ou; Sun, Qingjia

    2013-07-01

    Hypoxia promotes the radioresistance of laryngeal carcinomas and CD133 is one of the markers expressed by tumor-initiating, human laryngeal carcinoma cells. In order to investigate whether CD133-positive Hep-2 cells exhibit a radioresistant phenotype and to determine whether hypoxia promotes this phenotype, we performed a series of experiments. Hep-2 cells, and Hep-2 cells stably expressing hypoxia-inducible factor (HIF)-targeted small interfering RNA (siRNA) were cultured under hypoxic and normoxic conditions and were treated with varying doses of γ-rays (0, 5, 10, 15 and 20 Gy). MTT and cell cycle assays were subsequently performed. Using fluorescence-activated cell sorting (FACS), CD133-positive Hep-2 cells and CD133-positive HIF-siRNA Hep-2 cells were isolated. These cells were grown as spheres under hypoxic and normoxic conditions for MTT and soft agar colony formation assays. The expression levels of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), survivin, p53 and ataxia-telangiectasia mutated (ATM) were also assayed using flow cytometry. The data showed that the growth of Hep-2 cells exposed to hypoxic conditions and treated with 10 Gy radiation (group A) was less compared to that of groups B-D (PHep-2 cells grown under hypoxic conditions and exposed to irradiation (group E) (P0.05). In conclusion, CD133-positive Hep-2 cells exhibited a radioresistant phenotype that was enhanced with hypoxia. Furthermore, an increase in DNA-PK activity was associated with this enhancement.

  19. HAb18G/CD147 promotes radioresistance in hepatocellular carcinoma cells: a potential role for integrin β1 signaling.

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    Wu, Jiao; Li, Yong; Dang, Ya-Zheng; Gao, Hong-Xiang; Jiang, Jian-Li; Chen, Zhi-Nan

    2015-02-01

    Radiotherapy has played a limited role in the treatment of hepatocellular carcinoma (HCC) due to the risk of tumor radioresistance. A previous study in our laboratory confirmed that CD147 interacts with integrin β1 and plays an important role in modulating the malignant properties of HCC cells. In this study, we further evaluated the role of CD147 in the radioresistance of HCC and as a potential target for improving radiosensitivity. Upon irradiation, the colony formation, apoptosis, cell-cycle distribution, migration, and invasion of SMMC-7721, CD147-knockout SMMC-7721, HepG2, and CD147-knockdown HepG2 cells were determined. A nude mouse xenograft model and a metastatic model of HCC were used to detect the role of CD147 in radioresistance in vivo. Deletion of HAb18G/CD147 significantly enhanced the radiosensitivity of SMMC-7721 and HepG2 cells, and knocking out HAb18G/CD147 in SMMC-7721 cells attenuated irradiation-enhanced migration and invasion. The knockout and antibody blockade of CD147 decreased the tumor growth and metastatic potentials of HCC cells under irradiation. CD147-deleted SMMC-7721 cells showed diminished levels of calpain, cleaved talin, active integrin β1, and decreased p-FAK (Tyr397) and p-Akt (Ser473) levels. FAK and PI3K inhibitors, as well as integrin β1 antibodies, increased the radiation-induced apoptosis of SMMC-7721 cells. Our data provide evidence for CD147 as an important determinant of radioresistance via the regulation of integrin β1 signaling. Inhibition of the HAb18G/CD147 integrin interaction may improve the efficiency of radiosensitivity and provide a potential new approach for HCC therapy.

  20. Role of Natural Radiosensitizers and Cancer Cell Radioresistance: An Update

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    Arif Malik

    2016-01-01

    Full Text Available Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds.

  1. Protein Oxidation Implicated as the Primary Determinant of Bacterial Radioresistance

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    2007-04-01

    the facultative anaerobic, radio- resistant bacterium Lactobacillus plantarum [1,22] accumulates 20–25 mM Mn(II) [23]. For an irradiated cell...in dH2O at 0 8C and pre-conditioned to be anaerobic, H2O2 was released by D. radiodurans (;23 105 M) and L. plantarum (;6 3 105 M), in which the...non-irradiated D. radiodurans or L. plantarum control samples, nor by irradiated S. oneidensis (Figure 5A), which accumulates substantially more Fe

  2. GDF15 contributes to radioresistance and cancer stemness of head and neck cancer by regulating cellular reactive oxygen species via a SMAD-associated signaling pathway

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    Lee, Li-Yu; Fan, Kang-Hsing; Lu, Ya-Ching; Li, Yi-Chen; Chiang, Chang-Hsu; You, Guo-Rung; Chen, Hsin-Ying; Cheng, Ann-Joy

    2017-01-01

    Radiotherapy is an integral part for the treatment of head and neck cancer (HNC), while radioresistance is a major cause leads to treatment failure. GDF15, a member of the TGF-β superfamily, is hypothesized to participate in various types of homeostasis. However, the potential role of this molecule in regulation of radiosensitivity remains unclear. In this study, we demonstrated that GDF15 contributed to radioresistance of HNC, as determined by both gain- and lost-of-functional experiments. These results were achieved by the induction of mitochondrial membrane potential and suppression of intracellular reactive oxygen species (ROS). We further showed that GDF15 facilitated the conversion of cancer stemness, as assessed by the promotion of CD44+ and ALDH1+ cell populations and spheroid cell formation. At molecular level, GDF15 conferred to these cellular functions was through phosphorylated SMAD1 proteins to elite downstream signaling molecules. These cellular results were further confirmed in a tumor xenograft mouse study. Taken together, our results demonstrated that GDF15 contributed to radioresistance and cancer stemness by regulating cellular ROS levels via a SMAD-associated signaling pathway. GDF15 may serve as a prediction marker of radioresistance and a therapeutic target for the development of radio-sensitizing agents for the treatment of refractory HNC. PMID:27903972

  3. Microbial radio-resistance of Salmonella Typhimurium in egg increases due to repetitive irradiation with electron beam

    Energy Technology Data Exchange (ETDEWEB)

    Tesfai, Adiam T.; Beamer, Sarah K.; Matak, Kristen E. [West Virginia University, Division of Animal and Nutritional Sciences, PO Box 6108, Morgantown, WV 26508 (United States); Jaczynski, Jacek, E-mail: Jacek.Jaczynski@mail.wvu.ed [West Virginia University, Division of Animal and Nutritional Sciences, PO Box 6108, Morgantown, WV 26508 (United States)

    2011-04-15

    Ionizing radiation improves food safety. However, foodborne pathogens develop increased resistance in response to sub-lethal stresses such as heat, pH, antibiotics, etc. Therefore, it is hypothesized that foodborne pathogens may develop increased radio-resistance to electron beam (e-beam) radiation. The objective was to determine if D{sub 10}-value for Salmonella Typhimurium in de-shelled raw egg (egg white and yolk mixed together) increases due to repetitive processing with e-beam at sub-lethal doses. Survivors were enumerated on non-selective (TSA) and selective (XLD) media. Survivors from the highest dose were isolated and used in subsequent e-beam cycle. This process was repeated four times for a total of five e-beam cycles. D{sub 10}-values for S. Typhimurium enumerated on TSA and XLD following each e-beam cycle were calculated as inverse reciprocal of the slope of survivor curves. D{sub 10}-values for the ATCC strain were 0.59{+-}0.031 and 0.46{+-}0.022 kGy on TSA and XLD, respectively. However, following the fifth e-beam cycle, the respective D{sub 10}-values increased (P<0.05) to 0.69{+-}0.026 and 0.61{+-}0.029 kGy, respectively. S. Typhimurium showed a trend (P>0.05) to develop radio-resistance faster on selective media, likely due to facilitated selection of radio-resistant cells within microbial population following each e-beam cycle. For all five e-beam cycles, S. Typhimurium had higher (P<0.05) D{sub 10}-values on non-selective media, indicating that sub-lethal injury followed by cellular repair and recovery are important for radio-resistance and inactivation of this microorganism. This study demonstrated that e-beam efficiently inactivates S. Typhimurium in raw egg; however, similar to other inactivation techniques and factors affecting microbial growth, S. Typhimurium develops increased radio-resistance if repetitively processed with e-beam at sub-lethal doses.

  4. Incidence, radioresistance, and behavior of Psychrobacter spp. in rabbit meat.

    Science.gov (United States)

    Rodríguez-Calleja, José M; Patterson, Margaret F; García-López, Isabel; Santos, Jesús A; Otero, Andrés; García-López, María-Luisa

    2005-03-01

    The relative incidence of Psychrobacter spp. in rabbit meat, the radioresistance of these bacteria, and the growth of nonirradiated and irradiated psychrobacter isolates, alone and in coculture, during chilled storage of inoculated sterile rabbit meat was investigated. Psychrobacter spp. accounted for 4.2% of the storage psychrotrophic flora of 30 rabbit carcasses. The radiation D10-values of 10 Psychrobacter isolates, irradiated at 4 degrees C in minced rabbit meat, ranged from 0.8 to 2.0 kGy, with significant (P meat, but when the fastest growing strain was cocultured with Pseudomonas fluorescens and Brochothrix thermosphacta isolates, maximum cell densities and growth rates were significantly (P meat, surviving cells of both Psychrobacter strains decreased for a period of 5 to 7 days and then resumed multiplication that, at day 12, resulted in a similar increase (1.6 to 1.7 log CFU/g) over initial survivor numbers. When irradiated in combination with the spoilage bacteria, one of the strains required 12 days to reach initial numbers. In conclusion, Psychrobacter spp. are radioresistant nonsporeforming bacteria with a low relative incidence among the storage flora of rabbit meat, unable to compete with food spoilage bacteria in this ecosystem and apparently not a major contributor to the spoilage of rabbit meat after irradiation.

  5. miR-214 promotes radioresistance in human ovarian cancer cells by targeting PETN.

    Science.gov (United States)

    Zhang, Qin; Zhang, Shuxiang

    2017-08-31

    Ovarian cancer is one of the leading causes of death among gynecological malignancies. Increasing evidence indicate that dysregulation of microRNAs (miRNAs) plays an important role in tumor radioresistance. The aim of the present study is to investigate whether microRNA-214 (miR-214) was involved in radioresistance of human ovarian cancer. Here, we showed that miR-214 was significantly up-regulated in ovarian cancer tissues and radioresistance ovarian cancer cell lines. Transfection of miR-214 agomir in radiosensitive ovarian cancer cell lines promoted them for resistance to ionizing radiation, whereas transfection of miR-214 antagomir in radioresistance ovarian cancer cell lines sensitized them to ionizing radiation again. Furthermore, we found miR-214 effectively promoted tumor radioresistance in xenograft animal experiment. Western blotting and quantitative real-time PCR demonstrated that miR-214 negatively regulated PTEN in radioresistance ovarian cancer cell lines and ovarian cancer tissues. Taken together, our data conclude that miR-214 contributes to radioresistance of ovarian cancer by directly targeting PTEN. © 2017 The Author(s).

  6. Altered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinoma.

    Science.gov (United States)

    Lynam-Lennon, Niamh; Maher, Stephen G; Maguire, Aoife; Phelan, James; Muldoon, Cian; Reynolds, John V; O'Sullivan, Jacintha

    2014-01-01

    Neoadjuvant chemoradiation therapy (CRT) is increasingly the standard of care for locally advanced oesophageal cancer. A complete pathological response to CRT is associated with a favourable outcome. Radiation therapy is important for local tumour control, however, radioresistance remains a substantial clinical problem. We hypothesise that alterations in mitochondrial function and energy metabolism are involved in the radioresistance of oesophageal adenocarcinoma (OAC). To investigate this, we used an established isogenic cell line model of radioresistant OAC. Radioresistant cells (OE33 R) demonstrated significantly increased levels of random mitochondrial mutations, which were coupled with alterations in mitochondrial function, size, morphology and gene expression, supporting a role for mitochondrial dysfunction in the radioresistance of this model. OE33 R cells also demonstrated altered bioenergetics, demonstrating significantly increased intracellular ATP levels, which was attributed to enhanced mitochondrial respiration. Radioresistant cells also demonstrated metabolic plasticity, efficiently switching between the glycolysis and oxidative phosphorylation energy metabolism pathways, which were accompanied by enhanced clonogenic survival. This data was supported in vivo, in pre-treatment OAC tumour tissue. Tumour ATP5B expression, a marker of oxidative phosphorylation, was significantly increased in patients who subsequently had a poor pathological response to neoadjuvant CRT. This suggests for the first time, a role for specific mitochondrial alterations and metabolic remodelling in the radioresistance of OAC.

  7. Altered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Niamh Lynam-Lennon

    Full Text Available Neoadjuvant chemoradiation therapy (CRT is increasingly the standard of care for locally advanced oesophageal cancer. A complete pathological response to CRT is associated with a favourable outcome. Radiation therapy is important for local tumour control, however, radioresistance remains a substantial clinical problem. We hypothesise that alterations in mitochondrial function and energy metabolism are involved in the radioresistance of oesophageal adenocarcinoma (OAC. To investigate this, we used an established isogenic cell line model of radioresistant OAC. Radioresistant cells (OE33 R demonstrated significantly increased levels of random mitochondrial mutations, which were coupled with alterations in mitochondrial function, size, morphology and gene expression, supporting a role for mitochondrial dysfunction in the radioresistance of this model. OE33 R cells also demonstrated altered bioenergetics, demonstrating significantly increased intracellular ATP levels, which was attributed to enhanced mitochondrial respiration. Radioresistant cells also demonstrated metabolic plasticity, efficiently switching between the glycolysis and oxidative phosphorylation energy metabolism pathways, which were accompanied by enhanced clonogenic survival. This data was supported in vivo, in pre-treatment OAC tumour tissue. Tumour ATP5B expression, a marker of oxidative phosphorylation, was significantly increased in patients who subsequently had a poor pathological response to neoadjuvant CRT. This suggests for the first time, a role for specific mitochondrial alterations and metabolic remodelling in the radioresistance of OAC.

  8. Was Earth Ever Infected by Martian Biota? Clues from Radioresistant Bacteria

    Science.gov (United States)

    Pavlov, Anatoly K.; Kalinin, Vitaly L.; Konstantinov, Alexei N.; Shelegedin, Vladimir N.; Pavlov, Alexander A.

    2006-12-01

    Here we propose that the radioresistance (tolerance to ionizing radiation) observed in several terrestrial bacteria has a martian origin. Multiple inconsistencies with the current view of radioresistance as an accidental side effect of tolerance to desiccation are discussed. Experiments carried out 25 years ago were reproduced to demonstrate that "ordinary" bacteria can develop high radioresistance ability after multiple cycles of exposure to high radiation dosages followed by cycles of recovery of the bacterial population. We argue that "natural" cycles of this kind could have taken place only on the martian surface, and we hypothesize that Mars microorganisms could have developed radioresistance in just several million years' time and, subsequently, have undergone transfer to Earth by way of martian meteorites. Our mechanism implies multiple and frequent exchanges of biota between Mars and Earth.

  9. Cytogenetic Effects of Low Dose Radiation in Mammalian Cells Analysis of the Phenomenon Hypersensitivity and Induced Radioresistence

    CERN Document Server

    Shmakova, N L; Nasonova, E A; Krasavin, E A; Rsjanina, A V

    2001-01-01

    The induction of cytogenetic damage after irradiation of chinese hamster cells and human melanoma cells within dose range 1-200 cGy was studied. The anaphase and metaphase analysis of chromosome damage and micronuclei test were applied. The hypersensitivity (HRS) at doses below 20 cGy and the increased radioresistence at higher doses (IR) were shown with all cytogenetic criteria for both cell lines. The phenomenon of HRS/IR was reproduced in synchronic as well as in asynchronic population of chinese hamster cells. This fact shows that HRS was caused by high radiosensitivity of all cells and can not be explained by any differential sensitivity of cells in different phases of the cell cycle. So it was supposed that the increasing radioresistence is determined by the inclusion of the inducible repair processes in all cells. This conclusion agress with the fact that there was no evidence of HRS on dose-effect curves and that some part of pre-existent damage was repaired after preliminary irradiation with low dose...

  10. Unusual radioresistance of nitrogen-fixing cultures of Anabaena strains

    Indian Academy of Sciences (India)

    Harinder Singh; Tonina Fernandes; Shree Kumar Apte

    2010-09-01

    Nitrogen-fixing cultures of two species of the filamentous, heterocystous cyanobacterium Anabaena, namely Anabaena sp. strain L-31 and Anabaena torulosa were found to be highly tolerant to 60Co gamma radiation. No adverse effect on diazotrophic growth and metabolism were observed up to a dose of 5 kGy. At higher doses, radiation tolerance showed a correspondence with the inherent osmotolerance, with Anabaena L-31 being the more radiation tolerant as well as osmotolerant strain. In Anabaena L-31, exposure to 6 kGy of gamma rays resulted in genome disintegration, but did not reduce viability. Irradiation delayed heterocyst differentiation and nitrogen fixation, and marginally affected diazotrophic growth. All the affected parameters recovered after a short lag, without any discernible post-irradiation phenotype. The radiation tolerance of these Gram-negative photoautodiazotrophs is comparable with that of the adiazotrophic photoautotrophic cyanobacterium Chroococcidiopsis or adiazotrophic heterotroph Deinococcus radiodurans. This is the first report of extreme radioresistance in nitrogen-fixing Anabaena cultures.

  11. Glioblastoma Stem Cells Microenvironment: The Paracrine Roles of the Niche in Drug and Radioresistance

    Directory of Open Access Journals (Sweden)

    Alessia Fidoamore

    2016-01-01

    Full Text Available Among all solid tumors, the high-grade glioma appears to be the most vascularized one. In fact, “microvascular hyperplasia” is a hallmark of GBM. An altered vascular network determines irregular blood flow, so that tumor cells spread rapidly beyond the diffusion distance of oxygen in the tissue, with the consequent formation of hypoxic or anoxic areas, where the bulk of glioblastoma stem cells (GSCs reside. The response to this event is the induction of angiogenesis, a process mediated by hypoxia inducible factors. However, this new capillary network is not efficient in maintaining a proper oxygen supply to the tumor mass, thereby causing an oxygen gradient within the neoplastic zone. This microenvironment helps GSCs to remain in a “quiescent” state preserving their potential to proliferate and differentiate, thus protecting them by the effects of chemo- and radiotherapy. Recent evidences suggest that responses of glioblastoma to standard therapies are determined by the microenvironment of the niche, where the GSCs reside, allowing a variety of mechanisms that contribute to the chemo- and radioresistance, by preserving GSCs. It is, therefore, crucial to investigate the components/factors of the niche in order to formulate new adjuvant therapies rendering more efficiently the gold standard therapies for this neoplasm.

  12. Cancer Stem Cells and Radioresistance: Rho/ROCK Pathway Plea Attention

    Science.gov (United States)

    Pranatharthi, Annapurna; Ross, Cecil

    2016-01-01

    Radiation is the most potent mode of cancer therapy; however, resistance to radiation therapy results in tumor relapse and subsequent fatality. The cancer stem cell (CSC), which has better DNA repair capability, has been shown to contribute to tumor resistance and is an important target for treatment. Signaling molecules such as Notch, Wnt, and DNA repair pathways regulate molecular mechanisms in CSCs; however, none of them have been translated into therapeutic targets. The RhoGTPases and their effector ROCK-signaling pathway, though important for tumor progression, have not been well studied in the context of radioresistance. There are reports that implicate RhoA in radioresistance. ROCK2 has also been shown to interact with BRCA2 in the regulation of cell division. Incidentally, statins (drug for cardiovascular ailment) are functional inhibitors of RhoGTPases. Studies suggest that patients on statins have a better prognosis in cancers. Data from our lab suggest that ROCK signaling regulates radioresistance in cervical cancer cells. Collectively, these findings suggest that Rho/ROCK signaling may be important for radiation resistance. In this review, we enumerate the role of Rho/ROCK signaling in stemness and radioresistance and highlight the need to explore these molecules for a better understanding of radioresistance and development of therapeutics. PMID:27597870

  13. Cancer Stem Cells and Radioresistance: Rho/ROCK Pathway Plea Attention

    Directory of Open Access Journals (Sweden)

    Annapurna Pranatharthi

    2016-01-01

    Full Text Available Radiation is the most potent mode of cancer therapy; however, resistance to radiation therapy results in tumor relapse and subsequent fatality. The cancer stem cell (CSC, which has better DNA repair capability, has been shown to contribute to tumor resistance and is an important target for treatment. Signaling molecules such as Notch, Wnt, and DNA repair pathways regulate molecular mechanisms in CSCs; however, none of them have been translated into therapeutic targets. The RhoGTPases and their effector ROCK-signaling pathway, though important for tumor progression, have not been well studied in the context of radioresistance. There are reports that implicate RhoA in radioresistance. ROCK2 has also been shown to interact with BRCA2 in the regulation of cell division. Incidentally, statins (drug for cardiovascular ailment are functional inhibitors of RhoGTPases. Studies suggest that patients on statins have a better prognosis in cancers. Data from our lab suggest that ROCK signaling regulates radioresistance in cervical cancer cells. Collectively, these findings suggest that Rho/ROCK signaling may be important for radiation resistance. In this review, we enumerate the role of Rho/ROCK signaling in stemness and radioresistance and highlight the need to explore these molecules for a better understanding of radioresistance and development of therapeutics.

  14. Comparative ultrastructure analysis of radiation-induced radioresistant laryngeal cancer hep-2 cell line.

    Science.gov (United States)

    Yang, Bo; Tang, Fuqiu; Zhang, Bicheng; Zhao, Yong; Ding, Shifang; Rao, Zhiguo

    2014-08-01

    Radioresistance is one of the main reasons for the failure of radiotherapy in laryngeal cancer. However, the mechanisms of radioresistance of tumor cells have remained elusive. This study was conducted to identify the ultrastructural changes of radiation-induced radioresistant laryngeal cancer hep-2 cell line. First, a radioresistant hep-2R cell line was generated after prolonged exposure to γ-rays for 60 Gy (6 Gy/day, 2 days/week) and was confirmed by clonogenic assay. Next, the ultrastructural differences between hep-2R cells and hep-2 cells were compared by transmission electron microscopy. Finally, the results showed that hep-2R cells showed significant resistance to radiation compared with parental hep-2 cells. Increased cell nucleus atypia, more rough endoplasmic reticulum and less mitochondria were observed in hep-2R cells. The amount of microvilli of hep-2R was similar to hep-2 cell. In summary, these ultrastructural differences revealed the morphological mechanism that hep-2R cells had stronger radioresistance than hep-2 cells.

  15. Tumor senescence and radioresistant tumor-initiating cells (TICs): let sleeping dogs lie!

    Science.gov (United States)

    Zafarana, Gaetano; Bristow, Robert G

    2010-01-01

    Preclinical data from cell lines and experimental tumors support the concept that breast cancer-derived tumor-initiating cells (TICs) are relatively resistant to ionizing radiation and chemotherapy. This could be a major determinant of tumor recurrence following treatment. Increased clonogenic survival is observed in CD24-/low/CD44+ TICs derived from mammosphere cultures and is associated with (a) reduced production of reactive oxygen species, (b) attenuated activation of γH2AX and CHK2-p53 DNA damage signaling pathways, (c) reduced propensity for ionizing radiation-induced apoptosis, and (d) altered DNA double-strand or DNA single-strand break repair. However, recent data have shed further light on TIC radioresistance as irradiated TICs are resistant to tumor cell senescence following DNA damage. Taken together, the cumulative data support a model in which DNA damage signaling and repair pathways are altered in TICs and lead to an altered mode of cell death with unique consequences for long-term clonogen survival. The study of TIC senescence lays the foundation for future experiments in isogenic models designed to directly test the capacity for senescence and local control (that is, not solely local regression) and spontaneous metastases following treatment in vivo. The study also supports the targeting of tumor cell senescence pathways to increase TIC clonogen kill if the targeting also maintains the therapeutic ratio.

  16. WE-E-BRE-10: Level of Breast Cancer Stem Cell Correlated with Tumor Radioresistence: An Indication for Individualized Breast Cancer Therapy Adapted to Cancer Stem Cell Fractions

    Energy Technology Data Exchange (ETDEWEB)

    Qi, S; Pajonk, F; McCloskey, S; Low, D; Kupelian, P; Steinberg, M; Sheng, K [UCLA, Los Angeles, CA (United States)

    2014-06-15

    Purposes: The presence of cancer stem cells (CSCs) in a solid tumor could result in poor tumor control probability. The purposes are to study CSC radiosensitivity parameters α and β and their correlation to CSC levels to understand the underlying radioresistance mechanisms and enable individualized treatment design. Methods: Four established breast cancer cell lines (MCF-7, T47D, MDA-MB-231, and SUM159PT) were irradiated in vitro using single radiation doses of 0, 2, 4, 6, 8 or 10 Gy. The fractions of CSCs in each cell lines were determined using cancer stem cell markers. Mammosphere assays were also performed to better estimate the number of CSCs and represent the CSC repopulation in a human solid tumor. The measured cell surviving fractions were fitted using the Linear-quadratic (LQ) model with independent fitting parameters: α-TC, β-TC (TCs), α-CSC, β-CSC (CSCs), and fs (the percentage of CSCs in each sample). Results: The measured fs increased following the irradiation by MCF-7 (0.1%), T47D (0.9%), MDA-MB-231 (1.18%) and SUM159T (2.46%), while decreasing surviving curve slopes were observed, indicating greater radioresistance, in the opposite order. The fitting yielded the radiosensitive parameters for the MCF-7: α-TC=0.1±0.2Gy{sup −1}, β-TC= 0.08 ±0.14Gy{sup −2}, α-CSC=0.04±0.07Gy{sup −1}, β-CSC =0.02±0.3Gy{sup −2}; for the SUM159PT, α-TC=0.08±0.25 Gy{sup −1}, β-TC=0.02±0.02Gy{sup −2}, α-CSC=0.04±0.18Gy{sup −1}, β-CSC =0.004±0.24Gy{sup −2}. In the mammosphere assay, where fs were higher than the corresponding cell line assays, there was almost no shoulder found in the surviving curves (more radioresistant in mammosphere assays) yielding β-CSC of approximately 0. Conclusion: Breast cancer stem cells were more radioresistant characterized by smaller α and β values compared to differentiated breast cancer cells. Percentage of breast cancer stem cells strongly correlated to overall tumor radioresistance. This observation

  17. Establishment and Characterization of a Radioresistant Human Squamous Carcinoma Cell Line Induced by Radiation

    Institute of Scientific and Technical Information of China (English)

    Zhi-Guo LUO; Fu-Xiang ZHOU; Zhen CAO; Jin DAI; Ming-Sheng ZHANG; Jian-Ping WU; Cong-Hua XIE; Yun-Feng ZHOU

    2005-01-01

    @@ 1 Introduction Radiotherapy is one of the major clinical treatments for malignant tumors. Radio-sensitivity is the key element in controlling radioresistant tumor cells, so is an important content of radiotherapy basic research to make clear the mechanism of radioresistance[1]. There are many factors affecting the radiosensitivity such as hereditary background, growth environment, and others. It' s difficult to weigh such mixed factors. In this study, a radioresistant cell line Hep-2R has been obtained and characterized from its parental line Hep-2 known as human larynx squamous carcinoma cell line after long-term radiation induction. The Hep-2R and its parental line Hep-2 have offered a good model for the research of radiosensitivity.

  18. Stable radioresistance in ataxia-telangiectasia cells containing DNA from normal human cells

    Energy Technology Data Exchange (ETDEWEB)

    Kapp, L.N.; Painter, R.B. (California Univ., San Francisco, CA (USA). Lab. of Radiobiology)

    1989-11-01

    SV40-transformed ataxia-telangiectasia (AT) cells were transfected with a cosmid containing a normal human DNA library and selectable marker, the neo gene, which endows successfully transformed mammalian cells with resistance to the antibiotic G418. Cells from this line were irradiated with 50 Gy of X-rays and fused with non-transfected AT cells. Among the G418-resistant colonies recovered was one stably resistant to radiation. Resistance to ionizing radiation of both primary transfectant line and its fusion derivative was intermediate between that of AT cells and normal cells, as assayed by colony-forming ability and measurement of radiation-induced G{sub 2} chromatic aberrations; both cell lines retained AT-like radioresistant DNA synthesis. Results suggest that, because radioresistance in transfected cells was not as great as in normal human cells, two hallmarks of AT, radiosensitivity and radioresistant DNA synthesis, may still be the result of a single defective AT gene. (author).

  19. ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and serves as a prognostic marker for laryngeal cancer.

    Science.gov (United States)

    Choe, Min Ho; Min, Joong Won; Jeon, Hong Bae; Cho, Dong-Hyung; Oh, Jeong Su; Lee, Hyun Gyu; Hwang, Sang-Gu; An, Sungkwan; Han, Young-Hoon; Kim, Jae-Sung

    2015-02-20

    Although targeting radioresistant tumor cells is essential for enhancing the efficacy of radiotherapy, the signals activated in resistant tumors are still unclear. This study shows that ERp57 contributes to radioresistance of laryngeal cancer by activating STAT3. Increased ERp57 was associated with the radioresistant phenotype of laryngeal cancer cells. Interestingly, increased interaction between ERp57 and STAT3 was observed in radioresistant cells, compared to the control cells. This physical complex is required for the activation of STAT3 in the radioresistant cells. Among STAT3-regulatory genes, Mcl-1 was predominantly regulated by ERp57. Inhibition of STAT3 activity with a chemical inhibitor or siRNA-mediated depletion of Mcl-1 sensitized radioresistant cells to irradiation, suggesting that the ERp57-STAT3-Mcl-1 axis regulates radioresistance of laryngeal cancer cells. Furthermore, we observed a positive correlation between ERp57 and phosphorylated STAT3 or Mcl-1 and in vivo interactions between ERp57 and STAT3 in human laryngeal cancer. Importantly, we also found that increased ERp57-STAT3 complex was associated with poor prognosis in human laryngeal cancer, indicating the prognostic role of ERp57-STAT3 regulation. Overall, our data suggest that ERp57-STAT3 regulation functions in radioresistance of laryngeal cancer, and targeting the ERp57-STAT3 pathway might be important for enhancing the efficacy of radiotherapy in human laryngeal cancer.

  20. mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

    Science.gov (United States)

    Luo, Judong; Wang, Wenjie; Tang, Yiting; Zhou, Dandan; Gao, Yi; Zhang, Qi; Zhou, Xifa; Zhu, Hui; Xing, Ligang; Yu, Jinming

    2017-01-01

    Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies worldwide. Radiotherapy plays a critical role in the curative management of inoperable ESCC patients. However, radioresistance restricts the efficacy of radiotherapy for ESCC patients. The molecules involved in radioresistance remain largely unknown, and new approaches to sensitize cells to irradiation are in demand. Technical advances in analysis of mRNA and methylation have enabled the exploration of the etiology of diseases and have the potential to broaden our understanding of the molecular pathways of ESCC radioresistance. In this study, we constructed radioresistant TE-1 and Eca-109 cell lines (TE-1/R and Eca-109/R, respectively). The radioresistant cells showed an increased migration ability but reduced apoptosis and cisplatin sensitivity compared with their parent cells. mRNA and methylation profiling by microarray revealed 1192 preferentially expressed mRNAs and 8841 aberrantly methylated regions between TE-1/R and TE-1 cells. By integrating the mRNA and methylation profiles, we related the decreased expression of transcription factor Sall2 with a corresponding increase in its methylation in TE-1/R cells, indicating its involvement in radioresistance. Upregulation of Sall2 decreased the growth and migration advantage of radioresistant ESCC cells. Taken together, our present findings illustrate the mRNA and DNA methylation changes during the radioresistance of ESCC and the important role of Sall2 in esophageal cancer malignancy. PMID:28367244

  1. Ring-like nucleoid does not play a key role in radioresistance of Deinococcus radiodurans

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The conclusion based on transmission electron microscopy, "the tightly packed ring-like nucleoid of the Deinococcus radiodurans R1 is a key to radioresistance", has instigated lots of debates. In this study, according to the previous research of PprI’s crucial role in radioresistance of D. radiodurans, we have attempted to examine and compare the nucleoid morphology differences among wild-type D. ra-diodurans R1 strain, pprI function-deficient mutant (YR1), and pprI function-complementary strains (YR1001, YR1002, and YR1004) before and after exposure to ionizing irradiation. Fluorescence mi-croscopy images indicate: (1) the majority of nucleoid structures in radioresistant strain R1 cells ex-hibit the tightly packed ring-like morphology, while the pprI function-deficient mutant YR1 cells carrying predominate ring-like structure represent high sensitivity to irradiation; (2) as an extreme radioresistant strain similar to wild-type R1, pprI completely function-complementary strain YR1001 almost displays the loose and irregular nucleoid morphologies. On the other hand, another radioresistant pprI partly function-complementary strain YR1002’s nucleiods exhibit about 60% ring-like structure; (3) a PprI C-terminal deletion strain YR1004 consisting of approximately 60% of ring-like nucleoid is very sensi-tive to radiation. Therefore, our present experiments do not support the conclusion that the ring-like nucleoid of D. radiodurans does play a key role in radioresistance.

  2. Identification of radioresistance-related molecules in laryngeal cancer cells using proteomic and EST data mining approach

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Sung; Hong, Eun Hee; Yoon, Hong Sik; Yang, Kyung Mi; Hwang, Sang Gu [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-05-15

    Laryngeal cancer is the largest subgroup of head and neck cancer which is the sixth most prevalent cancer in the world. Radiotherapy is known as a major treatment modality of laryngeal caner in conjunction with surgery and chemotherapy. Clinical radiotherapy is generally based on the treatment of fractionated radiation (commonly 2 Gy daily to total 60-70 Gy) to the cancer. This chronic treatment can trigger tumor-adaptive radioresistance contributing cancer recurrence following radiotherapy. Unfortunately, approximately 15 % of laryngeal cancers after radiotherapy acquire radioresistance. However, little is known about the molecular markers and mechanisms underlying tumor-adaptive radioresistance. In the present study, we established the radioresistant model system using HEp-2 cell line and identified radioresistance-related molecules by using the analysis of laryngeal cancer expressed sequence tag (EST) data bases and two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)

  3. IL-6/STAT3/TWIST inhibition reverses ionizing radiation-induced EMT and radioresistance in esophageal squamous carcinoma.

    Science.gov (United States)

    Zang, Chunbao; Liu, Xujie; Li, Bing; He, Yanqiong; Jing, Shen; He, Yujia; Wu, Wenli; Zhang, Bingqian; Ma, Shuhong; Dai, Weiwei; Li, Shaolin; Peng, Zhiping

    2017-02-14

    The acquisition of radioresistance by esophageal squamous carcinoma (ESC) cells during radiotherapy may lead to cancer recurrence and poor survival. Previous studies have demonstrated that ionizing radiation (IR) induces epithelial-mesenchymal transition (EMT) of ESC cells accompanied by increased migration, invasion, and radioresistance. However, the underlying molecular mechanisms of IR-induced EMT and radioresistance are not well established, hampering the development of potential solutions. To address this issue, we investigated the role of the IL-6/STAT3/TWIST signaling pathway in IR-induced EMT. We found not only the pathway was activated during IR-induced EMT but also STAT3 inhibition or Twist depletion reversed the EMT process and attenuated radioresistance. These results improve our understanding of the underlying mechanisms involved in IR-induced EMT and suggest potential interventions to prevent EMT-induced acquisition of radioresistance.

  4. Dysregulation of IRP1-mediated iron metabolism causes gamma ray-specific radioresistance in leukemia cells.

    Directory of Open Access Journals (Sweden)

    Kurtis J Haro

    Full Text Available Iron is required for nearly all organisms, playing important roles in oxygen transport and many enzymatic reactions. Excess iron, however, can be cytotoxic. Emerging evidence suggests that radioresistance can be achieved in lower organisms by the protection of proteins, but not DNA, immediately following ionizing radiation (IR exposure, allowing for improved DNA repair. One potential mechanism for protein protection is controlling and limiting the amount of free iron in cells, as has been demonstrated in the extremophile Deinococcus Radiodurans, reducing the potential for oxidative damage to proteins during exposure to IR. We found that iron regulatory protein 1 (IRP1 expression was markedly reduced in human myeloid leukemia HL60 cells resistant to low linear energy transfer (LET gamma rays, but not to high LET alpha particles. Stable knockdown of IRP1 by short-hairpin RNA (shRNA interference in radiosensitive parental cells led to radioresistance to low LET IR, reduced intracellular Fenton chemistry, reduced protein oxidation, and more rapid DNA double-strand break (DSB repair. The mechanism of radioresistance appeared to be related to attenuated free radical-mediated cell death. Control of intracellular iron by IRPs may be a novel radioresistance mechanism in mammalian cells.

  5. DNA repair and cytokines: TGF-beta, IL-6, and thrombopoietin as different biomarkers of radioresistance

    Directory of Open Access Journals (Sweden)

    Francesca Bianca Aiello

    2016-07-01

    Full Text Available Double strand breaks (DSBs induced by radiotherapy are highly cytotoxic lesions, leading to chromosomal aberrations and cell death. ATM-dependent DNA-damage response, non-homologous end joining, and homologous recombination pathways coordinately contribute to repairing DSBs in higher eukaryotes. It is known that the expression of DSB repair genes is increased in tumors which is one of the main reasons for radioresistance. The inhibition of DSB repair pathways may be useful to increase tumor cell radiosensitivity and may target stem cell-like cancer cells, known to be the most radioresistant tumor components. Commonly overexpressed in neoplastic cells, cytokines confer radioresistance by promoting proliferation, survival, invasion, and angiogenesis. Unfortunately, tumor irradiation increases the expression of various cytokines displaying these effects, including transforming growth factor-beta and interlukin-6. Recently the capabilities of these cytokines to support DNA repair pathways and the ATM-dependent DNA response have been demonstrated. Thrombopoietin, essential for megakaryopoiesis and very important for hematopoietic stem cell homeostasis, has also been found to promote DNA repair in a highly selective manner. These findings reveal a novel mechanism underlying cytokine-related radioresistance, which may be clinically relevant. Therapies targeting specific cytokines may be used to improve radiosensitivity. Specific inhibitors may be chosen in consideration of different tumor microenvironments. Thrombopoietin may be useful in fending off irradiation-induced loss of hematopoietic stem cells.

  6. Inhibition of Glut1 by WZB117 sensitizes radioresistant breast cancer cells to irradiation.

    Science.gov (United States)

    Zhao, Fei; Ming, Jia; Zhou, Yan; Fan, Linjun

    2016-05-01

    Breast cancer is the most common type of cancer with high incidence in women. Currently, identifying new therapies that selectively inhibit tumor growth without damaging normal tissue are a major challenge of cancer research. One of the features of cancer cells is that they do not consume more oxygen even under normal oxygen circumstances but prefer to aerobic glycolysis through the enhanced catabolism of glucose and glutamine. In this study, we investigate the mechanisms of the radioresistance in breast cancer cells. Human breast cancer cells MDA-MB-231 and MCF-7 were treated with radiation alone, Glut1 inhibitor alone or the combination of both to evaluate cell glucose metabolism and apoptosis. By the establishment of radioresistant cell line, we investigate the mechanisms of the combined treatments of radiation with Glut1 inhibitor in the radioresistant cells. The glucose metabolism and the expression of Glut1 are significantly stimulated by radiotherapy. We report the radioresistant breast cancer cells exhibit upregulated Glut1 expression and glucose metabolism. In addition, we observed overexpression of Glut1 renders breast cancer cells resistant to radiation and knocking down of Glut1 sensitizes breast cancer cells to radiation. We treated breast cancer cells with radiation and WZB117 which inhibits Glut1 expression and glucose metabolism and found the combination of WZB117 and radiation exhibits synergistically inhibitory effects on breast cancer cells. Finally, we demonstrate the inhibition of Glut1 re-sensitizes the radioresistant cancer cells to radiation. This study reveals the roles of Glut1 in the radiosensitivity of human breast cancer. It will provide new mechanisms and strategies for the sensitization of cancer cells to radiotherapy through regulation of glucose metabolism.

  7. CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ke, Chien-Chih [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); Liu, Ren-Shyan [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); NRPGM, Molecular and Genetic Imaging Core, Taipei (China); National Yang-Ming University, School of Medicine, Taipei (China); Taipei Veterans General Hospital, National PET/Cyclotron Center, Taipei (China); National Yang-Ming University, Department of Biomedical Imaging and Radiological Sciences, Taipei (China); Yang, An-Hang [Taipei Veterans General Hospital, Department of Pathology and Laboratory Medicine, Taipei (China); National Yang-Ming University, Department of Pathology, School of Medicine, Taipei (China); Liu, Ching-Sheng [National Yang-Ming University Medical School, Department of Nuclear Medicine, School of Medicine, Taipei (China); Chi, Chin-Wen [National Yang-Ming University, Institute of Pharmacology, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Medical Research and Education, Taipei (China); Tseng, Ling-Ming [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Tsai, Yi-Fan [Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Ho, Jennifer H. [Taipei Medical University, Graduate Institute of Clinical Medicine, Taipei (China); Taipei Medical University-Wan Fang Medical Center, Department of Ophthalmology, Taipei (China); Taipei Medical University-Wan Fang Medical Center, Center for Stem Cell Research, Taipei (China); Lee, Chen-Hsen [NRPGM, Molecular and Genetic Imaging Core, Taipei (China); National Yang-Ming University, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Lee, Oscar K. [Taipei Veterans General Hospital, Department of Orthopedics, Taipei (China); National Yang-Ming University, Stem Cell Research Center, Taipei (China); Taipei Veterans General Hospital, Department of Medical Research and Education, Taipei (China)

    2013-01-15

    {sup 131}I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133{sup +} cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis. Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression. The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133{sup +} cells and higher radioresistance. After {gamma}-irradiation of the cells, the CD133{sup +} population was enriched due to the higher apoptotic rate of CD133{sup -} cells. In vivo {sup 131}I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133{sup +} cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8. This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133{sup +} cells. (orig.)

  8. Reciprocal Regulation of Hypoxia-Inducible Factor 2α and GLI1 Expression Associated With the Radioresistance of Renal Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jiancheng [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wu, Kaijie [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Gao, Dexuan [Department of Urology, Shandong Provincial Hospital affiliated with Shandong University, Ji' nan (China); Zhu, Guodong; Wu, Dapeng; Wang, Xinyang; Chen, Yule; Du, Yuefeng; Song, Wenbin; Ma, Zhenkun [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Authement, Craig; Saha, Debabrata [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hsieh, Jer-Tsong, E-mail: jt.hsieh@utsouthwestern.edu [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); He, Dalin, E-mail: dalinhe@yahoo.com [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China)

    2014-11-15

    Purpose: Renal cell carcinoma (RCC) is often considered a radioresistant tumor, but the molecular mechanism underlying its radioresistance is poorly understood. This study explored the roles of hypoxia-inducible factor 2α (HIF2α) and sonic hedgehog (SHH)-GLI1 signaling in mediating the radioresistance of RCC cells and to unveil the interaction between these 2 signaling pathways. Methods and Materials: The activities of SHH-GLI1 signaling pathway under normoxia and hypoxia in RCC cells were examined by real-time polymerase chain reaction, Western blot, and luciferase reporter assay. The expression of HIF2α and GLI1 in RCC patients was examined by immunohistochemistry, and their correlation was analyzed. Furthermore, RCC cells were treated with HIF2α-specific shRNA (sh-HIF2α), GLI1 inhibitor GANT61, or a combination to determine the effect of ionizing radiation (IR) on RCC cells based on clonogenic assay and double-strand break repair assay. Results: RCC cells exhibited elevated SHH-GLI1 activities under hypoxia, which was mediated by HIF2α. Hypoxia induced GLI1 activation through SMO-independent pathways that could be ablated by PI3K inhibitor or MEK inhibitor. Remarkably, the SHH-GLI1 pathway also upregulated HIF2α expression in normoxia. Apparently, there was a positive correlation between HIF2α and GLI1 expression in RCC patients. The combination of sh-HIF2α and GLI1 inhibitor significantly sensitized RCC cells to IR. Conclusions: Cross-talk between the HIF2α and SHH-GLI1 pathways was demonstrated in RCC. Cotargeting these 2 pathways, significantly sensitizing RCC cells to IR, provides a novel strategy for RCC treatment.

  9. Stathmin1 increases radioresistance by enhancing autophagy in non-small-cell lung cancer cells

    Directory of Open Access Journals (Sweden)

    Zhang X

    2016-04-01

    Full Text Available Xi Zhang,1,2 Jingfen Ji,3 Yu Yang,4 Juan Zhang,2 Liangfang Shen1 1Department of Oncology, Xiangya Hospital of Central South University, 2Department of Oncology, The Third Xiangya Hospital of Central South University, 3Department of General Surgery, The Second Xiangya Hospital of Central South University, 4Department of Oncology, 163 Hospital of PLA, Changsha, Hunan, People’s Republic of China Abstract: Radioresistance has been demonstrated to be involved in the poor prognosis of patients with non-small-cell lung cancer (NSCLC. However, the underlying mechanism remains largely unclear. Investigation on special therapeutic targets associated with radioresistance shows promises for the enhancement of clinical radiotherapy effect toward NSCLC. This study aimed to reveal the role of Stathmin1 (STMN1 in radioresistance in NSCLC as well as the underlying mechanism. Our data showed that the protein levels of STMN1 were significantly upregulated in NSCLC cells subjected to radiation, accompanied with the activation of autophagy. Knockdown of STMN1 expression enhanced the sensitivity of NSCLC cells to X-ray, and the radiation-induced autophagy was also inhibited. Molecular mechanism investigation showed that knockdown of STMN1 expression upregulated the activity of phosphoinositide 3-kinase (PI3K/mammalian target of rapamycin (mTOR signaling pathway in NSCLC cells. Moreover, the activation of PI3K/mTOR signaling showed an inhibitory effect on the autophagy and radioresistance induced by STMN1 in NSCLC cells. In addition, luciferase reporter assay data indicated that STMN1 was a direct target gene of miR-101, which had been reported to be an inhibitor of autophagy. Based on these data, we suggest that as a target gene of miR-101, STMN1 promotes the radioresistance by induction of autophagy through PI3K/mTOR signaling pathway in NSCLC. Therefore, STMN1 may become a potential therapeutic target for NSCLC radiotherapy. Keywords: radioresistance, non

  10. MicroRNAs: association with radioresistant and potential uses of natural remedies as green gene therapeutic approaches.

    Science.gov (United States)

    Jothy, Subramanion L; Chen, Yeng; Vijayarathna, Soundararajan; Kanwar, Jagat R; Sasidharan, Sreenivasan

    2015-01-01

    Radiotherapy plays an essential primary role in cancer patients. Regardless of its significant advances in treatment options, tumor recurrence and radio-resistance in cancer cells still occur in a high percentage of patients. Furthermore, the over expression of miRNAs accompanies the development of radio-resistant cancer cells. Consequently, miRNAs might serve as therapeutic targets for the treatment of radio-resistance in cancer cells. The findings of the current research also signify that the use of a natural anti-miRNA substance could inhibit specific miRNAs, and, concurrently, these natural remedies could exhibit radioprotective activity against the healthy cells during radiotherapy. Therefore, in this review, we have reported the association of miRNAs with radio-resistance and the potential uses of natural remedies as green gene therapeutic approaches, as well as radioprotectors against the adverse effects of irradiation on healthy cells during radiotherapy.

  11. Identification of genes involved in radioresistance of nasopharyngeal carcinoma by integrating gene ontology and protein-protein interaction networks.

    Science.gov (United States)

    Guo, Ya; Zhu, Xiao-Dong; Qu, Song; Li, Ling; Su, Fang; Li, Ye; Huang, Shi-Ting; Li, Dan-Rong

    2012-01-01

    Radioresistance remains one of the important factors in relapse and metastasis of nasopharyngeal carcinoma. Thus, it is imperative to identify genes involved in radioresistance and explore the underlying biological processes in the development of radioresistance. In this study, we used cDNA microarrays to select differential genes between radioresistant CNE-2R and parental CNE-2 cell lines. One hundred and eighty-three significantly differentially expressed genes (pgenes were upregulated and 45 genes were downregulated in CNE-2R. We further employed publicly available bioinformatics related software, such as GOEAST and STRING to examine the relationship among differentially expressed genes. The results show that these genes were involved in type I interferon-mediated signaling pathway biological processes; the nodes tended to have high connectivity with the EGFR pathway, IFN-related pathways, NF-κB. The node STAT1 has high connectivity with other nodes in the protein-protein interaction (PPI) networks. Finally, the reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and Western blotting. The results were consistent with the microarray data. Our study suggests that microarrays combined with gene ontology and protein interaction networks have great value in the identification of genes of radioresistance in nasopharyngeal carcinoma; genes involved in several biological processes and protein interaction networks may be relevant to NPC radioresistance; in particular, the verified genes CCL5, STAT1-α, STAT2 and GSTP1 may become potential biomarkers for predicting NPC response to radiotherapy.

  12. Pivotal role for skin transendothelial radio-resistant anti-inflammatory macrophages in tissue repair

    Science.gov (United States)

    Barreiro, Olga; Cibrian, Danay; Clemente, Cristina; Alvarez, David; Moreno, Vanessa; Valiente, Íñigo; Bernad, Antonio; Vestweber, Dietmar; Arroyo, Alicia G; Martín, Pilar; von Andrian, Ulrich H; Sánchez Madrid, Francisco

    2016-01-01

    Heterogeneity and functional specialization among skin-resident macrophages are incompletely understood. In this study, we describe a novel subset of murine dermal perivascular macrophages that extend protrusions across the endothelial junctions in steady-state and capture blood-borne macromolecules. Unlike other skin-resident macrophages that are reconstituted by bone marrow-derived progenitors after a genotoxic insult, these cells are replenished by an extramedullary radio-resistant and UV-sensitive Bmi1+ progenitor. Furthermore, they possess a distinctive anti-inflammatory transcriptional profile, which cannot be polarized under inflammatory conditions, and are involved in repair and remodeling functions for which other skin-resident macrophages appear dispensable. Based on all their properties, we define these macrophages as Skin Transendothelial Radio-resistant Anti-inflammatory Macrophages (STREAM) and postulate that their preservation is important for skin homeostasis. DOI: http://dx.doi.org/10.7554/eLife.15251.001 PMID:27304075

  13. Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells

    OpenAIRE

    Fisher, Carolyn J.; Goswami, Prabhat C.

    2008-01-01

    In recent years, cellular redox environment gained significant attention as a critical regulator of cellular responses to oxidative stress. Cellular redox environment is a balance between production of reactive oxygen species and their removal by antioxidant enzymes. We investigated the hypothesis that mitochondrial antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells. Vector-control and manganese superoxide dismutase (MnSOD) overexpressing human pancreatic c...

  14. Recovery and radio-resistance in mice after external irradiation; Restauration et radio-resistance chez la souris apres irradiation externe

    Energy Technology Data Exchange (ETDEWEB)

    Le Guillou, S. [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1965-07-01

    The author presents a literature study concerning recovery from external irradiation and an analysis of experimental data (which appear to suggest the idea of a radio-resistance in animals), as well as the hypotheses put forward for explaining this phenomenon. The author then describes an experiment carried out on mice whose LD 50/30 days increased from 1005 to 1380 rads and for which it was shown that an increase occurs in the number of certain anti-bodies circulating after a low dose of {gamma} irradiation. (author) [French] L'auteur presente une etude bibliographique de la restauration apres irradiation externe et une analyse des donnees experimentales qui paraissent suggerer la notion de radioresistance chez les animaux ainsi que les hypotheses cherchant a expliquer ce phenomene. Il relate ensuite une experience realisee sur des souris dont la DL 50/30 jours est passee de 1005 a 1380 rads et dans laquelle est montree l'augmentation de certains anticorps circulant apres une faible dose d'irradiation gamma. (auteur)

  15. Fractionated radiation exposure amplifies the radioresistant nature of prostate cancer cells

    Science.gov (United States)

    McDermott, N.; Meunier, A.; Mooney, B.; Nortey, G.; Hernandez, C.; Hurley, S.; Lynam-Lennon, N.; Barsoom, S. H.; Bowman, K. J.; Marples, B.; Jones, G. D. D.; Marignol, L.

    2016-01-01

    The risk of recurrence following radiation therapy remains high for a significant number of prostate cancer patients. The development of in vitro isogenic models of radioresistance through exposure to fractionated radiation is an increasingly used approach to investigate the mechanisms of radioresistance in cancer cells and help guide improvements in radiotherapy standards. We treated 22Rv1 prostate cancer cells with fractionated 2 Gy radiation to a cumulative total dose of 60 Gy. This process selected for 22Rv1-cells with increased clonogenic survival following subsequent radiation exposure but increased sensitivity to Docetaxel. This RR-22Rv1 cell line was enriched in S-phase cells, less susceptible to DNA damage, radiation-induced apoptosis and acquired enhanced migration potential, when compared to wild type and aged matched control 22Rv1 cells. The selection of radioresistant cancer cells during fractionated radiation therapy may have implications in the development and administration of future targeted therapy in conjunction with radiation therapy. PMID:27703211

  16. Sensitization of Radioresistant Prostate Cancer Cells by Resveratrol Isolated from Arachis hypogaea Stems

    Science.gov (United States)

    Kao, Min-Chuan; Lo, U-Ging; Lin, Li-Chiung; Lin, Chun-Jung; Chang, Sheau-Jiun; Chen, Chia-Chang; Hsieh, Jer-Tsong; Lin, Ho; Tang, Chih-Hsin; Lai, Chih-Ho

    2017-01-01

    Resveratrol (RV, 3,4ʹ,5-trihydroxystilbene) is naturally produced by a wide variety of plants including grapes and peanuts (Arachis hypogaea). However, the yield of RV from peanut stem and its potential radiosensitizing effects in prostate cancer (PCa) have not been well investigated. In this study, we characterized RV in peanut stem extract (PSE) for the first time and showed that both RV and PSE dose-dependently induced cell death in DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells with the radioresistant phenotype. Furthermore, the combination of radiation with either RV or PSE induced the death of radioresistant PCa cells through delayed repair of radiation-induced DNA double-strand break (DSB) and prolonged G2/M arrest, which induced apoptosis. The administration of RV and PSE effectively enhanced radiation therapy in the shDAB2IP PCa xenograft mouse model. These results demonstrate the promising synergistic effect of RV and PSE combined with radiation in the treatment of radioresistant PCa. PMID:28081154

  17. Radio-resistance induced by nitric oxide to heavy ion irradiation in A172 human glioma cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qingming; ZHANG Hong; ZHANG Xingxia

    2007-01-01

    To investigate effects of nitric oxide on cellular radio-sensitivity, three human glioma cell lines, i.e. A172,A172 transfected green fluorescence protein (EGFP) gene (EA172) and A172 transfected inducible nitric oxide synthesis (iNOS) gene (iA172), were irradiated by 12C6+ ions to 0, 1 or 2Gy. Productions of nitric oxide and glutathione (GSH) in A172, EA172 and iA172 were determined by chemical methods, cell cycle was analyzed by flow cytometry at the 24th hour after irradiation, and survival fraction of the cells was measured by colorimetric MTT assay at the 5th day after irradiation. The results showed that the concentrations of nitric oxide and GSH in iA172 were significantly higher than in A172 and EA172; the G2/M stage arrest induced by the 12C6+ ion irradiation was observed in A172 and EA172 but not in iA172 at the 24th hour after exposure; and the survival fraction of iA172 was higher than that of EA172 and iA172. Data suggest that the radio-sensitivity of the A172 was reduced after the iNOS gene transfection.The increase of GSH production and the change of cellular signals such as the cell cycle control induced by nitric oxide may be involved in this radio-resistance.

  18. Deubiquitinase USP9x Confers Radioresistance through Stabilization of Mcl-1

    Directory of Open Access Journals (Sweden)

    Donatella Trivigno

    2012-10-01

    Full Text Available Myeloid cell leukemia sequence 1 (Mcl-1, an antiapoptotic member of the Bcl-2 family, is often overexpressed in tumor cells limiting the therapeutic success. Mcl-1 differs from other Bcl-2 members by its high turnover rate. Its expression level is tightly regulated by ubiquitylating and deubiquitylating enzymes. Interaction of Mcl-1 with certain Bcl-2 homology domain 3 (BH3-only members of the Bcl-2 family can limit the access to Mcl-1 ubiquitin ligase E3 and stabilizes the antiapoptotic protein. In addition, the overexpression of the deubiquitinase ubiquitin-specific protease 9x (USP9x can result in the accumulation of Mcl-1 by removing poly-ubiquitin chains from Mcl-1 preventing its proteasomal degradation. Analyzing radiation-induced apoptosis in Jurkat cells, we found that Mcl-1 was downregulated more efficiently in sensitive parental cells than in a resistant subclone. The decline of Mcl-1 correlated with cell death induction and clonogenic survival. Knockdown of BH3-only proteins Bim, Puma, and Noxa did not affect Mcl-1 level or radiation-induced apoptosis. However, ionizing radiation resulted in activation of USP9x and enhanced deubiquitination of Mcl-1 in the radioresistant cells preventing fast Mcl-1 degradation. USP9x knockdown enhanced radiation-induced decrease of Mcl-1 and sensitized the radioresistant cells to apoptosis induction, whereas USP9x knockdown alone did not change Mcl-1 level in unirradiated cells. Together, our results indicate that radiation-induced activation of USP9x inhibits Mcl-1 degradation and apoptosis resulting in increased radioresistance.

  19. Enhanced radiation response in radioresistant MCF-7 cells by targeting peroxiredoxin II

    Directory of Open Access Journals (Sweden)

    Diaz AJG

    2013-10-01

    Full Text Available Anthony Joseph Gomez Diaz,1 Daniel Tamae,2 Yun Yen,3 JianJian Li,4 Tieli Wang1 1Department of Chemistry and Biochemistry, California State University at Dominguez Hills, Carson, CA, 2Center of Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, 3Department of Clinical and Molecular Pharmacology, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA, 4Department of Radiation Oncology, University of California Davis, Sacramento, CA, USA Abstract: In our previous study, we identified that a protein target, peroxiredoxin II (PrxII, is overexpressed in radioresistant MCF+FIR3 breast-cancer cells and found that its expression and function is associated with breast-cancer radiation sensitivity or resistance. Small interference RNA (siRNA targeting PrxII gene expression was able to sensitize MCF+FIR3 radioresistant breast-cancer cells to ionizing radiation. The major focus of this work was to investigate how the radiation response of MCF+FIR3 radioresistant cells was affected by the siRNA that inhibits PrxII gene expression. Our results, presented here, show that silencing PrxII gene expression increased cellular toxicity by altering cellular thiol status, inhibiting Ca2+ efflux from the cells, and perturbing the intracellular Ca2+ homeostasis. By combining radiotherapy and siRNA technology, we hope to develop new therapeutic strategies that may have potential to enhance the efficacy of chemotherapeutic agents due to this technology's property of targeting to specific cancer-related genes. Keywords: siRNA, PrxII, radiation resistance, Ca2+, MCF+FIR3

  20. Identification of Martian biota using their radioresistance ability and specific isotopic composition

    Science.gov (United States)

    Pavlov, A. K.; Kalinin, V.; Konstantinov, A.; Shelegedin, V.; Pavlov, A. A.

    2003-04-01

    Because of a thin atmosphere and weak magnetic field, Martian surface is a subject to high levels of ionizing radiation. On the other hand, variations in Martian obliquity produce the global climate oscillations (with the main period ~120000 years) of the great magnitude. Martian biota would accumulate large radiation dosage during the periods of cold climate, when it would be in the dormant state and would rebuild its population during the periods of warm climate. Therefore, all types of hypothetical Martian microorganisms living in subsurface layers of soil have to posses very high radiation tolerance. In our experiments, we find that "ordinary" bacteria (Escherichia coli and two species of Bacillus ) can develop radioresistance ability after a number of cycles of exposure to the high (almost lethal) radiation dosages, followed by recovery of the bacterial population. We show that natural cycles of this kind could take place only on Mars. On the other hand, high radiation tolerance is hardly necessary for the survival in any natural environment on Earth. A few number of terrestrial microorganisms (radioresistant bacteria) posses this peculiar ability (Deinococus radiodurance , Rubrobacter radiotolerance, Rubrobacter xylanophilus ). The radiation background on Earth, including vicinity of natural nuclear reactor Oklo is many orders of magnitude lower than the lethal dose for these microorganisms. We show that such radioresistance can be "trained" only in the Martian conditions. Therefore, we propose that Earth has been infected several times by the Martian biota on Martian meteorites. We propose that high radioresistance could be a strong sign of the Martian origin for potential microorganisms acquired in the sample return missions. Another way to identify "Martian" microorganisms and exclude contamination in returned samples involves analysis of the radionuclides abundance (being produced by the high energy cosmic rays in the Martian soil). We show that these

  1. The role of depressed metabolism in increased radio-resistance

    Science.gov (United States)

    Musacchia, X. J.

    1975-01-01

    The results of experiments on hamsters and rats to determine physiological responses to various temperature conditions are presented. The experimental methods described are considered to be applicable to future mammalian experiments in space. Renal function was examined in the golden hamster as a function of body temperature. Hamsters were also acclimated to heat and metabolic rates, body temperature, skin temperature, cardiac distribution and whole body hematocrits were measured. In addition, the effects of heat stress on the intestinal transport of sugars in the hamster and rat were studied. The biological effects of prolonged space flight and methods of simulating weightlessness are also discussed.

  2. Radioresistant cell strain of human fibrosarcoma cells obtained after long-term exposure to X-rays

    Energy Technology Data Exchange (ETDEWEB)

    Wei, K.; Kodym, R. [Univ. of Vienna (Austria). Department of Radiotherapy and Radiobiology; Jin Cuizheng [Institute of Radiation Medicine, Beijing (China)

    1998-07-01

    A radioresistant cell strain from human fibrosarcoma HT1080 has been obtained after prolonged exposure to x-rays for 7 months (2 Gy per day, 5 days per week). This new strain, HT1080R, differs from HT1080 in a significantly increased ability of clonogenical survival, with coefficient {alpha} decreasing from 0.161 to 0.123 Gy{sup -1} and coefficient {beta} decreasing from 0.0950 to 0.0565 Gy{sup -2}. Furthermore, the radioresistance of HT1080R proved to be stable in long-term passaged cultures as well as in frozen samples. Differences between the two cell lines are also observed in the G-banded karyotype; the new cell line shows monosomy of chromosome 17 and loss of 5p{sup +} and 11q{sup +} present in the parental cells. These data suggest that the radioresistance may have been caused by radiation-induced cell mutation and that the resistant cells may have been selected by repeated irradiations. In order to characterize this new strain, the ability of the cells to rejoin DNA double-strand breaks, the cell cycle distribution and the amount of apoptosis after irradiation have been estimated; however, no differences are observed between these two cell strains. Although the mechanism of the elevated radioresistance remains unknown, this pair of cell strains can provide a new model system for further investigations with regard to the mechanisms of cellular radioresistance. The results also show that any type of irradiation similar to the schedules used in radiotherapy can lead to the formation and selection of more radioresistant cell clones in vitro, a phenomenon with possible implications for radiotherapy. (orig.) With 3 figs., 1 tab., 13 refs.

  3. Targeting radioresistant breast cancer cells by single agent CHK1 inhibitor via enhancing replication stress

    Science.gov (United States)

    Du, Zhanwen; Gao, Jinnan; Yang, Shuming; Gorityala, Shashank; Xiong, Xiahui; Deng, Ou; Ma, Zhefu; Yan, Chunhong; Susana, Gonzalo; Xu, Yan; Zhang, Junran

    2016-01-01

    Radiotherapy (RT) remains a standard therapeutic modality for breast cancer patients. However, intrinsic or acquired resistance limits the efficacy of RT. Here, we demonstrate that CHK1 inhibitor AZD7762 alone significantly inhibited the growth of radioresistant breast cancer cells (RBCC). Given the critical role of ATR/CHK1 signaling in suppressing oncogene-induced replication stress (RS), we hypothesize that CHK1 inhibition leads to the specific killing for RBCC due to its abrogation in the suppression of RS induced by oncogenes. In agreement, the expression of oncogenes c-Myc/CDC25A/c-Src/H-ras/E2F1 and DNA damage response (DDR) proteins ATR/CHK1/BRCA1/CtIP were elevated in RBCC. AZD7762 exposure led to significantly higher levels of RS in RBCC, compared to the parental cells. The mechanisms by which CHK1 inhibition led to specific increase of RS in RBCC were related to the interruptions in the replication fork dynamics and the homologous recombination (HR). In summary, RBCC activate oncogenic pathways and thus depend upon mechanisms controlled by CHK1 signaling to maintain RS under control for survival. Our study provided the first example where upregulating RS by CHK1 inhibitor contributes to the specific killing of RBCC, and highlight the importance of the CHK1 as a potential target for treatment of radioresistant cancer cells. PMID:27167194

  4. Isolation and characterization of radioresistant mutants in Bacillus subtilis and Bacillus thuringiensis

    Energy Technology Data Exchange (ETDEWEB)

    Kalinin, V.L.; Petrov, V.N.; Petrova, T.M. (AN SSSR, Leningrad. Inst. Yadernoj Fiziki)

    Vegetative cells of Bac. thuringiensis var. galleriae (the wild-type strain 351) are much more sensitive to lethal effects of UV light and /sup 60/Co-..gamma..-rays than those of Bac. subtilis (the wild-type strain 168). This difference is less pronounced for spores of these strains. By means of repeated ..gamma..-irradiation-regrowth cycles radioresistant mutants of Bac. thuringiensis Gamsup(r) 14 and Bac. subtilis Gamsup(r) 9 were selected. The vegetative cells of these mutants are correspondingly 19 times and 3.9 times more resistant to lethal effects of ..gamma..-radiation than the cells of the parental strains. The resistance of the Gamsup(r) mutant cells to lethal effects of UV light and H/sub 2/O/sub 2/ is also increased. The spores of the Gamsup(r) 14 mutant are 1.5-1.7 times more resistant to ..gamma..-radiation and UV light than the wild-type spores. The radioresistant mutants and the parental strains do not vary in their capacity for host-cell reactivation of UV- or ..gamma..-irradiated phages Tg13 and 105.

  5. Conditional radioresistance of Tet-inducible manganese superoxide dismutase bone marrow stromal cell lines.

    Science.gov (United States)

    Epperly, Michael W; Chaillet, J Richard; Kalash, Ronny; Shaffer, Ben; Goff, Julie; Franicola, Darcy; Zhang, Xichen; Dixon, Tracy; Houghton, Frank; Wang, Hong; Berhane, Hebist; Romero, Cynthia; Kim, Jee-Hong; Greenberger, Joel S

    2013-08-01

    Mitochondrial targeted manganese superoxide dismutase is a major antioxidant enzyme, the levels of which modulate the response of cells, tissues and organs to ionizing irradiation. We developed a Tet-regulated MnSOD mouse (MnSOD(tet)) to examine the detailed relationship between cellular MnSOD concentration and radioresistance and carried out in vitro studies using bone marrow culture derived stromal cell lines (mesenchymal stem cells). Homozygous MnSOD(tet/tet) cells had low levels of MnSOD, reduced viability and proliferation, increased radiosensitivity, elevated overall antioxidant stores, and defects in cell proliferation and DNA strand-break repair. Doxycycline (doxy) treatment of MnSOD(tet/tet) cells increased MnSOD levels and radioresistance from ñ of 2.79 ± 1.04 to 8.69 ± 1.09 (P = 0.0060) and normalized other biologic parameters. In contrast, MnSOD(tet/tet) cells showed minimal difference in baseline and radiation induced mRNA and protein levels of TGF-β, Nrf2 and NF-κB and radiation induced cell cycle arrest was not dependent upon MnSOD level. These novel MnSOD(tet/tet) mouse derived cells should be valuable for elucidating several parameters of the oxidative stress response to ionizing radiation.

  6. Neuropilin 1 expression correlates with the Radio-resistance of human non-small-cell lung cancer cells.

    Science.gov (United States)

    Dong, Juan Cong; Gao, Hui; Zuo, Si Yao; Zhang, Hai Qin; Zhao, Gang; Sun, Shi Long; Han, Hai Ling; Jin, Lin Lin; Shao, Li Hong; Wei, Wei; Jin, Shun Zi

    2015-09-01

    The purpose of this study was to determine the correlation between over-expression of the neuropilin 1 (NRP1) gene and growth, survival, and radio-sensitivity of non-small cell lung carcinoma (NSCLC) cells. 3-[4,5-dimethylthylthiazol-2-yl]-2,5 diphenyltetrazolium broide (MTT) and colony assays were then performed to determine the effect of NRP1 inhibition on the in vitro growth of NSCLC cells. The Annexin V-Fluorescein Isothiocyanate (FITC) apoptosis detection assay was performed to analyse the effect of NRP1 enhancement on apoptosis of NSCLC cells. Transwell invasion and migration assays were employed to examine the metastatic ability of A549 cells post X-ray irradiation. In addition, Western blot assays were carried out to detect the protein level of VEGFR2, PI3K and NF-κB. Finally, to examine the effect of shNRP1 on proliferation and radio-sensitivity in vivo, a subcutaneous tumour formation assay in nude mice was performed. Microvessel density in tumour tissues was assessed by immunohistochemistry. The stable transfected cell line (shNRP1-A549) showed a significant reduction in colony-forming ability and proliferation not only in vitro, but also in vivo. Moreover, shRNA-mediated NRP1 inhibition also significantly enhanced the radio-sensitivity of NSCLC cells both in vitro and in vivo. The over-expression of NRP1 was correlated with growth, survival and radio-resistance of NSCLC cells via the VEGF-PI3K- NF-κB pathway, and NRP1 may be a molecular therapeutic target for gene therapy or radio-sensitization of NSCLC.

  7. Telomere-binding protein TPP1 modulates telomere homeostasis and confers radioresistance to human colorectal cancer cells.

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    Lei Yang

    Full Text Available BACKGROUND: Radiotherapy is one of the major therapeutic strategies in cancer treatment. The telomere-binding protein TPP1 is an important component of the shelterin complex at mammalian telomeres. Our previous reports showed that TPP1 expression was elevated in radioresistant cells, but the exact effects and mechanisms of TPP1 on radiosensitivity is unclear. PRINCIPAL FINDINGS: In this study, we found that elevated TPP1 expression significantly correlated with radioresistance and longer telomere length in human colorectal cancer cell lines. Moreover, TPP1 overexpression showed lengthened telomere length and a significant decrease of radiosensitivity to X-rays. TPP1 mediated radioresistance was correlated with a decreased apoptosis rate after IR exposure. Furthermore, TPP1 overexpression showed prolonged G2/M arrest mediated by ATM/ATR-Chk1 signal pathway after IR exposure. Moreover, TPP1 overexpression accelerated the repair kinetics of total DNA damage and telomere dysfunction induced by ionizing radiation. CONCLUSIONS: We demonstrated that elevated expressions of TPP1 in human colorectal cancer cells could protect telomere from DNA damage and confer radioresistance. These results suggested that TPP1 may be a potential target in the radiotherapy of colorectal cancer.

  8. CpG oligodeoxyribonucleotide 7909 enhances radiosensitivity via downregulating Oct-4 expression in radioresistant lung cancer cells.

    Science.gov (United States)

    Xing, Na; Qiao, Tiankui; Zhuang, Xibing; Yuan, Sujuan; Zhang, Qi; Xu, Guoxiong

    2015-01-01

    Radiotherapy is a powerful cure for local advanced non-small cell lung cancer. However, radioresistance and tumor relapse still occur in a high proportion of patients. Octamer-4 (Oct-4), a transcription factor of the POU family, plays a key role in maintaining chemoradioresistant properties and regulating cancer progression. In this study, we demonstrated that Oct-4 expression was significantly increased in radioresistant H460 (H460R) cell line. CpG oligodeoxyribonucleotide (CpG-ODN) 7909 sensitized H460R cells when combined with irradiation treatment. The clonogenic capacity was significantly decreased, and the values of D0 and Dq were lower than those of irradiation alone group. The sensitive enhancement ratio (SER) of D0 was 1.224. This combined treatment led to a dramatic reduction in Oct-4 expression in a dose-dependent manner and also showed increased percentage of cells in the radiosensitive G2/M phase relative to either treatment alone. These results identified that Oct-4 was involved in radioresistance. CpG-ODN 7909 could enhance radiosensitivity partly through downregulating Oct-4 expression in radioresistant lung cancer cells.

  9. CpG oligodeoxyribonucleotide 7909 enhances radiosensitivity via downregulating Oct-4 expression in radioresistant lung cancer cells

    Directory of Open Access Journals (Sweden)

    Xing N

    2015-06-01

    Full Text Available Na Xing,1 Tiankui Qiao,1 Xibing Zhuang,1 Sujuan Yuan,1 Qi Zhang,1 Guoxiong Xu2 1Department of Oncology, 2Center Laboratory, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China Abstract: Radiotherapy is a powerful cure for local advanced non-small cell lung cancer. However, radioresistance and tumor relapse still occur in a high proportion of patients. Octamer-4 (Oct-4, a transcription factor of the POU family, plays a key role in maintaining chemoradioresistant properties and regulating cancer progression. In this study, we demonstrated that Oct-4 expression was significantly increased in radioresistant H460 (H460R cell line. CpG oligodeoxyribonucleotide (CpG-ODN 7909 sensitized H460R cells when combined with irradiation treatment. The clonogenic capacity was significantly decreased, and the values of D0 and Dq were lower than those of irradiation alone group. The sensitive enhancement ratio (SER of D0 was 1.224. This combined treatment led to a dramatic reduction in Oct-4 expression in a dose-dependent manner and also showed increased percentage of cells in the radiosensitive G2/M phase relative to either treatment alone. These results identified that Oct-4 was involved in radioresistance. CpG-ODN 7909 could enhance radiosensitivity partly through downregulating Oct-4 expression in radioresistant lung cancer cells. Keywords: CpG-ODN, Oct-4, lung cancer, TLR9, radiosensitivity

  10. Identification of differential gene expression profiles of radioresistant lung cancer cell line established by fractionated ionizing radiation in vitro

    Institute of Scientific and Technical Information of China (English)

    XU Qing-yong; GAO Yuan; LIU Yan; YANG Wei-zhi; XU Xiang-ying

    2008-01-01

    Background Radiotherapy plays a critical role in the management of non-small cell lung cancer (NSCLC). This study was conducted to identify gene expression profiles of acquired radioresistant NSCLC cell line established by fractionated ionizing radiation (FIR) by cDNA microarray.Methods The human lung adenocarcinoma cell line Anip973 was treated with high energy X-ray to receive 60 Gy in 4 Gy fractions. The radiosensitivity of Anip973R and its parental line were measured by clonogenic assay. Gene expression profiles of Anip973R and its parental line were analyzed using cDNA microarray consisting of 21 522 human genes.Identified partly different expressive genes were validated by quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR).Results Fifty-nine upregulated and 43 downregulated genes were identified to radio-resistant Anip973R. Up-regulated genes were associated with DNA damage repair (DDB2), extracellular matrix (LOX), cell adhesion (CDH2), and apoptosis (CRYAB). Down-regulated genes were associated with angiogenesis (GBP-1), immune response (CD83), and calcium signaling pathway (TNNC1). Subsequent validation of selected eleven genes (CD24, DDB2, IGFBP3, LOX,CDH2, CRYAB, PROCR, ANXA1 DCN, GBP-1 and CD83) by Q-RT-PCR was consistent with microarray analysis.Conclusions Fractionated ionizing radiation can lead to the development of radiation resistance. Altered gene profiles of radioresistant cell line may provide new insights into mechanisms underlying clinical radioresistance for NSCLC.

  11. HIF-1α inhibition by siRNA or chetomin in human malignant glioma cells: effects on hypoxic radioresistance and monitoring via CA9 expression

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    Bache Matthias

    2010-11-01

    Full Text Available Abstract Background Hypoxia induces activation of the HIF-1 pathway and is an essential characteristic of malignant gliomas. Hypoxia has been linked to tumor progression, therapy resistance and poor prognosis. However, little is known about the impact of HIF-1α inhibition on radioresistance of malignant glioma. Methods In this study, we investigated the effects of the inhibition of HIF-1α on cell survival and radiosensitivity in U251MG and U343MG glioma cells, using two different strategies. HIF-1α inhibition was achieved by siRNA targeting of HIF-1α or via chetomin, a disruptor of interactions between HIF-1α and p300. The inhibition of the HIF-1 pathway was monitored by quantitative real-time PCR and Western blot analyses of the expression levels of HIF-1α and CA9. CA9 expression was investigated as a potential indicator of the efficacy of HIF-1 inhibition and the resulting radiosensitivity of malignant glioma cell lines was determined by clonogenic assay after irradiation under normoxic (2-10 Gy or hypoxic (2-15 Gy conditions. Results Although siRNA and chetomin show distinct modes of action, both attenuated the hypoxia-induced radioresistance of malignant glioma cell lines U251MG (DMF10: 1.35 and 1.18 and U343MG (DMF10: 1.78 and 1.48. However, siRNA and chetomin showed diverse effects on radiosensitivity under normoxic conditions in U251MG (DMF10: 0.86 and 1.35 and U343MG (DMF10: 1.33 and 1.02 cells. Conclusions Results from this in vitro study suggest that inhibition of HIF-1α is a promising strategy to sensitize human malignant gliomas to radiotherapy and that CA9 could serve as an indicator of effective HIF-1-related radiosensitization.

  12. Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

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    Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O. [Lab. de Radiobiologie, Service de Radio-Oncologie, CHUV, Lausanne (Switzerland); Knebel Doeberitz, M. von [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Inst. fuer Virusforschung

    1998-02-01

    The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [Deutsch] Das Ziel dieser Studie lag darin, die Rolle der HPV-18-Gene E6 und E7 in bezug auf die Strahlenempfindlichkeit von menschlichen Zervixkarzinomzellen zu untersuchen. Wir verwendeten zwei menschliche Zervixkarzinomzellinien, C4-1 und SW 756, in welchen die Expression der viralen Gene HPV 18 E6 und E7 mit Dexamethason moduliert werden kann: In C4-1 bewirkt die Behandlung mit Dexamethason eine Erhoehung der Expression dieser Gene, in SW 756 eine Verminderung. Die Wirkung auf die Wachstumsfaehigkeit der Zellen und auf die Wachstumshemmung durch die Bestrahlung wurde unter Verwendung eines klonogenen Assays bestimmt. Dexamethason bewirkte eine erhoehte Wachstumsfaehigkeit der C4-1 Zellen, ohne die Wachstumsfaehigkeit der SW-756-Zellen zu beeinflussen, wie schon frueher beschrieben. Die Resistenz beider Zellinien gegenueber Bestrahlung wurde erhoeht. Somit besteht in den C4-1-Zellen eine Korrelation der Expression der viralen Gene mit der Zunahme der Strahlenresistenz, wogegen in den SW-756-Zellen die Abnahme der Expression im Gegensatz zu

  13. Nanomedicine to overcome radioresistance in glioblastoma stem-like cells and surviving clones.

    Science.gov (United States)

    Séhédic, Delphine; Cikankowitz, Annabelle; Hindré, François; Davodeau, François; Garcion, Emmanuel

    2015-04-01

    Radiotherapy is one of the standard treatments for glioblastoma, but its effectiveness often encounters the phenomenon of radioresistance. This resistance was recently attributed to distinct cell contingents known as glioblastoma stem-like cells (GSCs) and dominant clones. It is characterized in particular by the activation of signaling pathways and DNA repair mechanisms. Recent advances in the field of nanomedicine offer new possibilities for radiosensitizing these cell populations. Several strategies have been developed in this direction, the first consisting of encapsulating a contrast agent or synthesizing metal-based nanocarriers to concentrate the dose gradient at the level of the target tissue. In the second strategy the physicochemical properties of the vectors are used to encapsulate a wide range of pharmacological agents which act in synergy with the ionizing radiation to destroy the cancerous cells. This review reports on the various molecular anomalies present in GSCs and the predominant role of nanomedicines in the development of radiosensitization strategies.

  14. Radioresistance of granulation tissue-derived cells from skin wounds combined with total body irradiation.

    Science.gov (United States)

    Dai, Tingyu; Chen, Zelin; Tan, Li; Shi, Chunmeng

    2016-04-01

    Combined radiation and wound injury (CRWI) occurs following nuclear explosions and accidents, radiological or nuclear terrorism, and radiation therapy combined with surgery. CRWI is complicated and more difficult to heal than single injuries. Stem cell‑based therapy is a promising treatment strategy for CRWI, however, sourcing stem cells remains a challenge. In the present study, the granulation tissue-derived cells (GTCs) from the skin wounds (SWs) of CRWI mice (C‑GTCs) demonstrated a higher radioresistance to the damage caused by combined injury, and were easier to isolate and harvest when compared with bone marrow‑derived mesenchymal stromal cells (BMSCs). Furthermore, the C-GTCs exhibited similar stem cell-associated properties, such as self-renewal and multilineage differentiation capacity, when compared with neonatal dermal stromal cells (DSCs) and GTCs from unirradiated SWs. Granulation tissue, which is easy to access, may present as an optimal autologous source of stem/progenitor cells for therapeutic applications in CRWI.

  15. Microarray analysis of DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252Cf neutron and X-rays

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    Yang Zhen-Zhou

    2010-02-01

    Full Text Available Abstract Background The aim of the study was to obtain stable radioresistant sub-lines from the human cervical cancer cell line HeLa by prolonged exposure to 252Cf neutron and X-rays. Radioresistance mechanisms were investigated in the resulting cells using microarray analysis of DNA damage repair genes. Methods HeLa cells were treated with fractionated 252Cf neutron and X-rays, with a cumulative dose of 75 Gy each, over 8 months, yielding the sub-lines HeLaNR and HeLaXR. Radioresistant characteristics were detected by clone formation assay, ultrastructural observations, cell doubling time, cell cycle distribution, and apoptosis assay. Gene expression patterns of the radioresistant sub-lines were studied through microarray analysis and verified by Western blotting and real-time PCR. Results The radioresistant sub-lines HeLaNR and HeLaXR were more radioresisitant to 252Cf neutron and X-rays than parental HeLa cells by detecting their radioresistant characteristics, respectively. Compared to HeLa cells, the expression of 24 genes was significantly altered by at least 2-fold in HeLaNR cells. Of these, 19 genes were up-regulated and 5 down-regulated. In HeLaXR cells, 41 genes were significantly altered by at least 2-fold; 38 genes were up-regulated and 3 down-regulated. Conclusions Chronic exposure of cells to ionizing radiation induces adaptive responses that enhance tolerance of ionizing radiation and allow investigations of cellular radioresistance mechanisms. The insights gained into the molecular mechanisms activated by these "radioresistance" genes will lead to new therapeutic targets for cervical cancer.

  16. Reversal effect of GnT-V on the radioresistance of human nasopharyngeal carcinoma cells by alteration β1, 6-GlcNAc branched N-glycans.

    Science.gov (United States)

    Wu, Jun-Bo; Shen, Li; Qiu, Li; Duan, Qi-Wen; Luo, Zhi-Guo; Dong, Xiao-Xia

    2015-01-01

    Radiotherapy is the primary treatment for human nasopharyngeal carcinoma (NPC), yet radioresistance remains a major obstacle to successful treatment in many cases. N-acetylglucosaminyltransferase V (GnT-V), which synthesizes β1, 6-GlcNAc branched N-glycans, is closely related to the radiosensitivity of NPC cells. However, a better understanding of the functional role of GnT-V in NPC radioresistance and the related mechanisms is urgently needed. In the present study, a radioresistant NPC cell line, CNE-2R, was established by repeated γ-irradiation. We found that GnT-V levels, as well as β1, 6-GlcNAc branched N-glycans were significantly increased in the CNE-2R cells as compared with that in the parental cells. Meanwhile, knockdown of GnT-V in the CNE-2R cells enhanced cell radiosensitivity and inhibited the formation of β1, 6-branched N-glycans. In addition, the regulated expression of GnT-V in the CNE-2R cells converted the heterogeneous N-glycosylated forms of CD147. Furthermore, swainsonine, an inhibitor of N-glycan biosynthesis, was also able to reverse the radioresistance of the CNE-2R cells. Taken together, the present study revealed a novel mechanism of GnT-V as a regulator of radioresistance in NPC cells, which may be useful for fully understanding the biological role of N-glycans in NPC radioresistance.

  17. A calcium-insensitive attenuated nitrosative stress response contributes significantly in the radioresistance of Sf9 insect cells.

    Science.gov (United States)

    Suman, Shubhankar; Seth, Rakesh Kumar; Chandna, Sudhir

    2011-09-01

    Lepidopteran insects/insect cells display 50-100 times higher radioresistance than humans, and are evolutionarily closest to mammals amongst all radioresistant organisms known. Compared to mammalian cells, Lepidopteran cells (TN-368, Sf9) display more efficient antioxidant system and DNA repair and suffer considerably less radiation-induced DNA/cytogenetic damage and apoptosis. Recent studies indicate that a considerably lower radiation-induced oxidative stress may significantly reduce macromolecular damage in Lepidopteran cells. Since nitrosative stress contributes in radiation-induced cellular damage, we investigated its nature in the γ-irradiated Sf9 cells (derived from Spodoptera frugiperda; order Lepidoptera; family Noctuidae) and compared with BMG-1 human cell line having significant NOS expression. Radiation induced considerably less ROS/RNS in Sf9 cells, which remained unchanged on treatment with NOS inhibitor l-NMMA. Surprisingly, growth of Sf9 cultures or irradiation could not induce NO or its metabolites, indicating negligible basal/radiation-induced NOS activity that remained unchanged even after supplementation with arginine. Cytosolic calcium release following high-dose (1000-2000Gy at 61.1cGys(-1)) γ-irradiation or H(2)O(2) (250μM) treatment also failed to generate NO in Sf9 cells having high constitutive levels of calmodulin, whereas BMG-1 cells displayed considerable calcium-dependent NO generation even following 10Gy dose. These results strongly imply the lack of calcium-mediated NOS activity in Sf9 cells. Addition of exogenous NO from GSH-NO caused considerable increase in radiation-induced apoptosis, indicating significant contribution of constitutively attenuated nitrosative stress response into the radioresistance of Lepidopteran cells. Our study demonstrates for the first time that a calcium-insensitive, attenuated nitrosative stress response may contribute significantly in the unusual radioresistance displayed by Lepidopteran insect cells.

  18. CpG oligodeoxyribonucleotide 7909 enhances radiosensitivity via downregulating Oct-4 expression in radioresistant lung cancer cells

    OpenAIRE

    Xing N; Qiao T; Zhuang X; Yuan S; Zhang Q; Xu G

    2015-01-01

    Na Xing,1 Tiankui Qiao,1 Xibing Zhuang,1 Sujuan Yuan,1 Qi Zhang,1 Guoxiong Xu2 1Department of Oncology, 2Center Laboratory, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China Abstract: Radiotherapy is a powerful cure for local advanced non-small cell lung cancer. However, radioresistance and tumor relapse still occur in a high proportion of patients. Octamer-4 (Oct-4), a transcription factor of the POU family, plays a key role in maintaining chemoradioresista...

  19. Molecular mechanisms of low dose ionizing radiation-induced hormesis, adaptive responses, radioresistance, bystander effects, and genomic instability.

    Science.gov (United States)

    Tang, Feng Ru; Loke, Weng Keong

    2015-01-01

    To review research progress on the molecular mechanisms of low dose ionizing radiation (LDIR)-induced hormesis, adaptive responses, radioresistance, bystander effects, and genomic instability in order to provide clues for therapeutic approaches to enhance biopositive effects (defined as radiation-induced beneficial effects to the organism), and control bionegative effects (defined as radiation-induced harmful effects to the organism) and related human diseases. Experimental studies have indicated that Ataxia telangiectasia-mutated (ATM), extracellular signal-related kinase (ERK), mitogen-activated protein kinase (MAPK), phospho-c-Jun NH(2)-terminal kinase (JNK) and protein 53 (P53)-related signal transduction pathways may be involved in LDIR-induced hormesis; MAPK, P53 may be important for adaptive response; ATM, cyclooxygenase-2 (COX-2), ERK, JNK, reactive oxygen species (ROS), P53 for radioresistance; COX-2, ERK, MAPK, ROS, tumor necrosis factor receptor alpha (TNFα) for LDIR-induced bystander effect; whereas ATM, ERK, MAPK, P53, ROS, TNFα-related signal transduction pathways are involved in LDIR-induced genomic instability. These results suggest that different manifestations of LDIR-induced cellular responses may have different signal transduction pathways. On the other hand, LDIR-induced different responses may also share the same signal transduction pathways. For instance, P53 has been involved in LDIR-induced hormesis, adaptive response, radioresistance and genomic instability. Current data therefore suggest that caution should be taken when designing therapeutic approaches using LDIR to induce beneficial effects in humans.

  20. Association of reactive oxygen species levels and radioresistance in cancer stem cells.

    Science.gov (United States)

    Diehn, Maximilian; Cho, Robert W; Lobo, Neethan A; Kalisky, Tomer; Dorie, Mary Jo; Kulp, Angela N; Qian, Dalong; Lam, Jessica S; Ailles, Laurie E; Wong, Manzhi; Joshua, Benzion; Kaplan, Michael J; Wapnir, Irene; Dirbas, Frederick M; Somlo, George; Garberoglio, Carlos; Paz, Benjamin; Shen, Jeannie; Lau, Sean K; Quake, Stephen R; Brown, J Martin; Weissman, Irving L; Clarke, Michael F

    2009-04-09

    The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.

  1. The E3 Ligase CHIP Mediates p21 Degradation to Maintain Radioresistance.

    Science.gov (United States)

    Biswas, Kuntal; Sarkar, Sukumar; Du, Kangping; Brautigan, David L; Abbas, Tarek; Larner, James M

    2017-06-01

    Lung cancer resists radiotherapy, making it one of the deadliest forms of cancer. Here, we show that human lung cancer cell lines can be rendered sensitive to ionizing radiation (IR) by RNAi knockdown of C-terminus of Hsc70-interacting protein (CHIP/STUB1), a U-box-type E3 ubiquitin ligase that targets a number of stress-induced proteins. Mechanistically, ubiquitin-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor, p21 protein, is reduced by CHIP knockdown, leading to enhanced senescence of cells in response to exposure to IR. Cellular senescence and sensitivity to IR is prevented by CRISPR/Cas9-mediated deletion of the p21 gene (CDKN1A) in CHIP knockdown cells. Conversely, overexpression of CHIP potentiates p21 degradation and promotes greater radioresistance of lung cancer cells. In vitro and cell-based assays demonstrate that p21 is a novel and direct ubiquitylation substrate of CHIP that also requires the CHIP-associated chaperone HSP70. These data reveal that the inhibition of the E3 ubiquitin ligase CHIP promotes radiosensitivity, thus suggesting a novel strategy for the treatment of lung cancer.Implications: The CHIP-HSP70-p21 ubiquitylation/degradation axis identified here could be exploited to enhance the efficacy of radiotherapy in patients with non-small cell lung cancer. Mol Cancer Res; 15(6); 651-9. ©2017 AACR. ©2017 American Association for Cancer Research.

  2. Effect of individual and group housing of mice on the level of radioresistance

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    Dorozhkina O.V.

    2015-12-01

    Full Text Available Aim: to examine the effect of individual and group housing of mice on radioresistance. Material and methods. Effects of individual and group housing of mice on immunity and blood systems were studied on ICR (CD-1 and C57BI6 male mice before and after proton irradiation. Results. Group housing of intact animals resulted in a decline in the number of nucleated cells in the femur bone marrow and thymus mass. The irradiation with proton with energy of 171 MeV at a dose of 1 Gy causes a statistically significant greater reduction of the number of nucleated cells in the femur bone marrow in group-housed mice. A trend toward greater safety of the number of leukocytes in the peripheral blood and higher proliferative activity of bone marrow cells, as well as lower level of aberrant mitoses have been noted in individually-housed mice. Reduction processes in the recovery period of radiation sickness take place at a greater rate in group-housed mice. Conclusion. Group housing of male mice causes increased sensitivity of the blood and immunity systems to the effects of radiation and at the same time accelerates processes of radiation recovery.

  3. Modeling the Relationship between Fluorodeoxyglucose Uptake and Tumor Radioresistance as a Function of the Tumor Microenvironment

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    Jeho Jeong

    2014-01-01

    Full Text Available High fluorodeoxyglucose positron emission tomography (FDG-PET uptake in tumors has often been correlated with increasing local failure and shorter overall survival, but the radiobiological mechanisms of this uptake are unclear. We explore the relationship between FDG-PET uptake and tumor radioresistance using a mechanistic model that considers cellular status as a function of microenvironmental conditions, including proliferating cells with access to oxygen and glucose, metabolically active cells with access to glucose but not oxygen, and severely hypoxic cells that are starving. However, it is unclear what the precise uptake levels of glucose should be for cells that receive oxygen and glucose versus cells that only receive glucose. Different potential FDG uptake profiles, as a function of the microenvironment, were simulated. Predicted tumor doses for 50% control (TD50 in 2 Gy fractions were estimated for each assumed uptake profile and for various possible cell mixtures. The results support the hypothesis of an increased avidity of FDG for cells in the intermediate stress state (those receiving glucose but not oxygen compared to well-oxygenated (and proliferating cells.

  4. Modeling the Relationship between Fluorodeoxyglucose Uptake and Tumor Radioresistance as a Function of the Tumor Microenvironment

    Science.gov (United States)

    Deasy, Joseph O.

    2014-01-01

    High fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in tumors has often been correlated with increasing local failure and shorter overall survival, but the radiobiological mechanisms of this uptake are unclear. We explore the relationship between FDG-PET uptake and tumor radioresistance using a mechanistic model that considers cellular status as a function of microenvironmental conditions, including proliferating cells with access to oxygen and glucose, metabolically active cells with access to glucose but not oxygen, and severely hypoxic cells that are starving. However, it is unclear what the precise uptake levels of glucose should be for cells that receive oxygen and glucose versus cells that only receive glucose. Different potential FDG uptake profiles, as a function of the microenvironment, were simulated. Predicted tumor doses for 50% control (TD50) in 2 Gy fractions were estimated for each assumed uptake profile and for various possible cell mixtures. The results support the hypothesis of an increased avidity of FDG for cells in the intermediate stress state (those receiving glucose but not oxygen) compared to well-oxygenated (and proliferating) cells. PMID:25276223

  5. Critical analysis of salvage radical prostatectomy in the management of radioresistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Seabra, Daniel; Faria, Eliney; Dauster, Breno; Rodrigues, Gunther; Fava, Gilberto [Pio XII Foundation, Barretos, SP (Brazil). Section of Urology], e-mail: daniel.seabra@terra.com.br

    2009-01-15

    Purpose: To critically evaluate salvage radical prostatectomy (SRP) in the treatment of patients with recurrent prostate cancer (PCa). Materials and Methods: From January 2005 to June 2007, we assessed patients with recurrent localized PCa. Recurrence was suspected when there were three or more successive increases in prostate specific antigen (PSA) after nadir. After the routine imagery examinations, and once localized PCa was confirmed, patients were offered SRP. Following surgery, we evaluated bleeding, rectal injury, urinary incontinence or obstruction and impotence. PSA values were measured at 1, 3, 6, months and thereafter twice a year. Results: Forty-two patients underwent SRP. The average age was 61 years. Following radiotherapy , the mean PSA nadir was 1.5 ng/mL (0.57-5.5). The mean prostate specific antigen doubling time (PSA-DT) was 14 months (6-20). Prior to SRP, the mean PSA was 5.7 ng/mL (2.9-18). The pathologic staging was pT2a: 13%; pT2b: 34%; pT2c: 27%; pT3a: 13%; and pT3b: 13%. Bleeding > 600 mL occurred in 14% of the cases; urethral stenosis in 50%; and urinary incontinence (two or more pads/day) in 72%. The mean follow-up post-SRP ranged from 6 to 30 months. The PSA level rose in 9, of which 6 had PSA-DT < 10 months. Conclusions: SRP is a feasible method in the management of localized radioresistant PCa. PSA-DT has shown to be important for the selection and SRP should not be performed if PSA-DT > 10 months. Due to its increased morbidity, SRP should be only offered to the patients who are more concerned about survival rather than quality of life. (author)

  6. Ultrafractionation does not improve the results of radiotherapy in radioresistant murine DDL1 lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Krause, M.; Prager, J.; Hessel, F.; Dorner, D. [TU Dresden (Germany). Clinic for Radiotherapy and Radiation Oncology; Wohlfarth, J.; Baumann, M. [TU Dresden (Germany). Clinic for Radiotherapy and Radiation Oncology; TU Dresden (Germany). Experimental Center; Haase, M. [TU Dresden (Germany). Inst. of Pathology; Joiner, M.C. [Wayne State University, Detroit, MI (United States). Dept. of Radiation Oncology

    2005-08-01

    Background and purpose: Low-dose hyperradiosensitivity (HRS), i.e., a relatively higher efficacy of doses {<=}0.5 Gy compared to doses >1 Gy, has been shown in a number of tumor cell lines in vitro. Therefore ultrafractionated irradiation, i.e., application of very low doses per fraction, has been proposed to improve the effects of radiotherapy. The present study investigates ultrafractionation (UF) in radioresistant murine DDL1T-cell lymphoma in mice. Material and methods: UF was performed with 0.4 Gy per fraction, three fractions per day at 7 days per week, and conventional fractionation (CF) with 1.68 Gy per fraction, one fraction per day at 5 days per week. Tumor growth delay was evaluated for 2, 4 and 6 weeks of irradiation as time that tumors needed to reach fivefold the starting volume (GD{sub V5}). Results: GD{sub V5} was not significantly different between UF and CF. The composite median relative GD{sub V5} calculated for all tumors irradiated in the present study was 1.00 [95% confidence interval 0.99; 1.08] in the CF and 0.99 [0.92; 1.01] in the UF arm (p=0.24). Conclusion: UF was not more efficient than CF in DDL1 tumors. Taken together with previous experiments on human A7 glioblastoma, which showed a negative effect of UF on local tumor control, the preclinical data obtained in this laboratory so far do not support the use of ultrafractionated schedules in radiotherapy. (orig.)

  7. Anhydrobiosis-associated nuclear DNA damage and repair in the sleeping chironomid: linkage with radioresistance.

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    Oleg Gusev

    Full Text Available Anhydrobiotic chironomid larvae can withstand prolonged complete desiccation as well as other external stresses including ionizing radiation. To understand the cross-tolerance mechanism, we have analyzed the structural changes in the nuclear DNA using transmission electron microscopy and DNA comet assays in relation to anhydrobiosis and radiation. We found that dehydration causes alterations in chromatin structure and a severe fragmentation of nuclear DNA in the cells of the larvae despite successful anhydrobiosis. Furthermore, while the larvae had restored physiological activity within an hour following rehydration, nuclear DNA restoration typically took 72 to 96 h. The DNA fragmentation level and the recovery of DNA integrity in the rehydrated larvae after anhydrobiosis were similar to those of hydrated larvae irradiated with 70 Gy of high-linear energy transfer (LET ions ((4He. In contrast, low-LET radiation (gamma-rays of the same dose caused less initial damage to the larvae, and DNA was completely repaired within within 24 h. The expression of genes encoding the DNA repair enzymes occurred upon entering anhydrobiosis and exposure to high- and low-LET radiations, indicative of DNA damage that includes double-strand breaks and their subsequent repair. The expression of antioxidant enzymes-coding genes was also elevated in the anhydrobiotic and the gamma-ray-irradiated larvae that probably functions to reduce the negative effect of reactive oxygen species upon exposure to these stresses. Indeed the mature antioxidant proteins accumulated in the dry larvae and the total activity of antioxidants increased by a 3-4 fold in association with anhydrobiosis. We conclude that one of the factors explaining the relationship between radioresistance and the ability to undergo anhydrobiosis in the sleeping chironomid could be an adaptation to desiccation-inflicted nuclear DNA damage. There were also similarities in the molecular response of the larvae to

  8. The radioresistance to killing of A1-5 cells derives from activation of the Chk1 pathway

    Science.gov (United States)

    Hu, B.; Zhou, X. Y.; Wang, X.; Zeng, Z. C.; Iliakis, G.; Wang, Y.

    2001-01-01

    Checkpoints respond to DNA damage by arresting the cell cycle to provide time for facilitating repair. In mammalian cells, the G(2) checkpoint prevents the Cdc25C phosphatase from removing inhibitory phosphate groups from the mitosis-promoting kinase Cdc2. Both Chk1 and Chk2, the checkpoint kinases, can phosphorylate Cdc25C and inactivate its in vitro phosphatase activity. Therefore, both Chk1 and Chk2 are thought to regulate the activation of the G(2) checkpoint. Here we report that A1-5, a transformed rat embryo fibroblast cell line, shows much more radioresistance associated with a much stronger G(2) arrest response when compared with its counterpart, B4, although A1-5 and B4 cells have a similar capacity for nonhomologous end-joining DNA repair. These phenotypes of A1-5 cells are accompanied by a higher Chk1 expression and a higher phosphorylation of Cdc2. On the other hand, Chk2 expression increases slightly following radiation; however, it has no difference between A1-5 and B4 cells. Caffeine or UCN-01 abolishes the extreme radioresistance with the strong G(2) arrest and at the same time reduces the phosphorylation of Cdc2 in A1-5 cells. In addition, Chk1 but not Chk2 antisense oligonucleotide sensitizes A1-5 cells to radiation-induced killing and reduces the G(2) arrest of the cells. Taken together these results suggest that the Chk1/Cdc25C/Cdc2 pathway is the major player for the radioresistance with G(2) arrest in A1-5 cells.

  9. Heterogeneous X-ray survival characteristics of lymphocytes in prolymphocytic leukaemia. Mathematical analysis distinguishing delayed cell death and true radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Thomson, A.E.R.; O' Connor, T.W.E.; Slater, N.G.P. (Division of Haematology, United Medical and Dental Schools of Guy' s and St. Thomas' Hospitals, London (United Kingdom)); Peel, W.E. (Computing Services, Manchester Metropolitan University, Manchester (United Kingdom))

    1994-10-01

    The survival of non-dividing (G[sub 0]) leukaemic lymphocytes in culture is generally too short for their radiosensitivity to be quantitatively assessed, since lethally X-irradiated cells may show a long delay before manifestations of cell death ('interphase death') are seen. Counts of surviving cells well therefore include both lethally-hit cells (apparent survivors), and real survivors which have not been lethally hit. Death rates of irradiated leukaemic and normal cells show great variation between individuals, so that comparisons of radiosensitivity between different cell populations based on surviving cell counts at a single time-point are invalid. In this study the supposed radioresistance of prolymphocytic leukaemia lymphocytes was examined in 6 patients with B-cell disease. Survival curves were plotted from serial observations made over several days after graded X-irradiation (0-1000 cGy). We attempted to interpret these radiation responses in terms of their dose dependence (intrinsic radiosensitivity) and time dependence (cell death rate) characteristics using the best-fitting of four mathematical models, all based on classical 'single-hit' target theory. The apparent radioresistance shown in 4 cases could be explained by very slow death rates (T[sub 172] values 55-205 h) of cells proving otherwise radiosensitive (D37 values 38-123 cGy). Genuine radioresistance was found in only 1 case (actual D37 value above 2000 cGy). B ignoring delayed cell death in clinical assessments, pathological lymphocytes could be mistakenly categorized as resistant to elimination by radiotherapy. (au) (30 refs.).

  10. The acquired radioresistance in HeLa cells under conditions mimicking hypoxia was attenuated by a decreased expression of HIF subunit genes induced by RNA interference

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    Doi, Nobutaka [Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194 (Japan); New Products Research & Development, Gene Engineering Division, NIPPON GENE Co., Ltd. (Japan); Ogawa, Ryohei, E-mail: ogawa@med.u-toyama.ac.jp [Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194 (Japan); Cui, Zheng-Guo [Department of Public Health, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama (Japan); Morii, Akihiro; Watanabe, Akihiko [Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama (Japan); Kanayama, Shinji; Yoneda, Yuko [New Products Research & Development, Gene Engineering Division, NIPPON GENE Co., Ltd. (Japan); Kondo, Takashi [Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194 (Japan)

    2015-05-01

    The cancer cells residing in the hypoxic layer are resistant to radiation and these are ones responsible for cancer recurrence after radiation therapy. One of the reasons why hypoxic cancer cells acquire radioresistance may be attributable to changes in the gene expression profile by the activation of hypoxia inducible factors (HIFs). However, the details underlying this process remain unknown. In this study, we investigated the effects of knockdown of HIF subunit genes to elucidate how HIF subunit genes may be involved in the radioresistance acquired by HeLa cells following exposure to a hypoxia mimic. Interestingly, HIF-1α and HIF-2α seemed mutually complementary for each other when either of them was suppressed. We thus suppressed the expression of both genes simultaneously. To do this, we developed a short hairpin RNA (shRNA) targeting a high homology region between HIF-1α and HIF-2α. It was shown that the expression of the shRNA effectively suppressed the acquisition of radioresistance following the hypoxia mimic. Moreover, it was confirmed that suppression of both subunits resulted in the downregulation of stem cell markers and the suppression of spheroid formation during the hypoxia mimicking-conditions. This shRNA-mediated knockdown method targeting a common region shared by a family of genes may offer a new candidate cancer treatment. - Highlights: • Incubation with CoCl{sub 2} confers radioresistance to HeLa cells. • Both HIF-1α and HIF-2α are involved in the acquisition of radioresistance. • An shRNA to a homology region of HIF-1α and HIF-2α suppressed the radioresistance. • The shRNA decreased cells with stem cell markers and a stem cell phenotype.

  11. Protein expression of nucleophosmin, annexin A3 and nm23-H1 correlates with human nasopharyngeal carcinoma radioresistance in vivo.

    Science.gov (United States)

    Qu, Song; Li, Xiao-Yu; Liang, Zhong-Guo; Li, Ling; Huang, Shi-Ting; Li, Jia-Quan; Li, Dan-Rong; Zhu, Xiao-Dong

    2016-07-01

    Radioresistance is a significant obstacle in the treatment of endemic nasopharyngeal carcinoma (NPC). The present study aimed to identify proteins associated with radioresistance in NPC in vitro and in vivo. Proteomics analyses were conducted to screen for differentially-expressed proteins (DEPs) in parental CNE-2 cells and CNE-2R cells. Using proteomics approaches, 16 DEPs were identified. Of these DEPs, nucleophosmin (NPM1), annexin A3 and nm23-H1, were verified using western blot analyses. The tumorigenicity was investigated using mouse xenograft tumorigenicity assays, and tumor growth curves were generated. The protein expression of NPM1, annexin A3 and nm23-H1 was examined by immunohistochemically staining tumor tissues. NPM1 and annexin A3 protein levels were downregulated in the CNE-2R cells, whereas nm23-H1 expression was upregulated. In vivo tests showed that compared with the CNE-2 tumors, CNE-2R tumor growth was significantly retarded (PA3 expression was significantly lower in non-irradiated (NIR)-CNE-2R tumors compared with NIR-CNE-2 tumors (PA3 and nm23-H1 expression correlated with the cellular and tumor radioresponse. These proteins are involved in the regulation of intracellular functions, including stress responses, cell proliferation and DNA repair. However, further clinical evaluations are required.

  12. Enzymes involved in DNA ligation and end-healing in the radioresistant bacterium Deinococcus radiodurans

    Directory of Open Access Journals (Sweden)

    Shevelev Igor V

    2007-08-01

    Full Text Available Abstract Background Enzymes involved in DNA metabolic events of the highly radioresistant bacterium Deinococcus radiodurans are currently examined to understand the mechanisms that protect and repair the Deinococcus radiodurans genome after extremely high doses of γ-irradiation. Although several Deinococcus radiodurans DNA repair enzymes have been characterised, no biochemical data is available for DNA ligation and DNA endhealing enzymes of Deinococcus radiodurans so far. DNA ligases are necessary to seal broken DNA backbones during replication, repair and recombination. In addition, ionizing radiation frequently leaves DNA strand-breaks that are not feasible for ligation and thus require end-healing by a 5'-polynucleotide kinase or a 3'-phosphatase. We expect that DNA ligases and end-processing enzymes play an important role in Deinococcus radiodurans DNA strand-break repair. Results In this report, we describe the cloning and expression of a Deinococcus radiodurans DNA ligase in Escherichia coli. This enzyme efficiently catalyses DNA ligation in the presence of Mn(II and NAD+ as cofactors and lysine 128 was found to be essential for its activity. We have also analysed a predicted second DNA ligase from Deinococcus radiodurans that is part of a putative DNA repair operon and shows sequence similarity to known ATP-dependent DNA ligases. We show that this enzyme possesses an adenylyltransferase activity using ATP, but is not functional as a DNA ligase by itself. Furthermore, we identified a 5'-polynucleotide kinase similar to human polynucleotide kinase that probably prepares DNA termini for subsequent ligation. Conclusion Deinococcus radiodurans contains a standard bacterial DNA ligase that uses NAD+ as a cofactor. Its enzymatic properties are similar to E. coli DNA ligase except for its preference for Mn(II as a metal cofactor. The function of a putative second DNA ligase remains unclear, but its adenylyltransferase activity classifies it as a

  13. Identification of CD133-positive radioresistant cells in atypical teratoid/rhabdoid tumor.

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    Shih-Hwa Chiou

    Full Text Available Atypical teratoid/rhabdoid tumor (AT/RT is an extremely malignant neoplasm in the central nervous system (CNS which occurs in infancy and childhood. Recent studies suggested that CD133 could be considered a marker for brain cancer stem-like cells (CSCs. However, the role of CD133 in AT/RT has never been investigated. Herein we report the isolation of CD133-positive cells (CD133(+, found to have the potential to differentiate into three germ layer tissues, from tissues of nine AT/RT patients. The migration/invasion/malignancy and radioresistant capabilities of CD133(+ were significantly augmented when compared to CD133(-. The clinical data showed that the amount of CD133(+ in AT/RTs correlated positively with the degree of resistance to radiation therapy. Using cDNA microarray analysis, the genotoxic-response profiles of CD133(+ and CD133(- irradiated with 10 Gy ionizing radiation (IR were analyzed 0.5, 2, 6, 12 and 24 h post-IR. We then validated these microarray data and showed increased phosphorylation after IR of p-ATM, p-RAD17, and p-CHX2 as well as increased expression of BCL-2 protein in CD133(+ compared to CD133(-. Furthermore, we found that CD133(+ can effectively resist IR with cisplatin- and/or TRAIL-induced apoptosis. Immunohistochemical analysis confirmed the up-regulated expression of p-ATM and BCL-2 proteins in IR-treated CD133(+ xenotransgrafts in SCID mice but not in IR-treated CD133(-. Importantly, the effect of IR in CD133(+ transplanted mice can be significantly improved by a combination of BCL-2 siRNA with debromohymenialdisine, an inhibitor of checkpoint kinases. In sum, this is the first report indicating that CD133(+ AT/RT cells demonstrate the characteristics of CSCs. The IR-resistant and anti-apoptotic properties in CD133(+ may reflect the clinical refractory malignancy of AT/RTs and thus the activated p-ATM pathway and BCL-2 expression in CD133(+ could be possible targets to improve future treatment of deadly diseases

  14. DANGER is involved in high glucose-induced radioresistance through inhibiting DAPK-mediated anoikis in non-small cell lung cancer.

    Science.gov (United States)

    Kwon, TaeWoo; Youn, HyeSook; Son, Beomseok; Kim, Daehoon; Seong, Ki Moon; Park, Sungkyun; Kim, Wanyeon; Youn, BuHyun

    2016-02-09

    18F-labeled fluorodeoxyglucose (FDG) uptake during FDG positron emission tomography seems to reflect increased radioresistance. However, the exact molecular mechanism underlying high glucose (HG)-induced radioresistance is unclear. In the current study, we showed that ionizing radiation-induced activation of the MEK-ERK-DAPK-p53 signaling axis is required for anoikis (anchorage-dependent apoptosis) of non-small cell lung cancer (NSCLC) cells in normal glucose media. Phosphorylation of DAPK at Ser734 by ERK was essential for p53 transcriptional activity and radiosensitization. In HG media, overexpressed DANGER directly bound to the death domain of DAPK, thus inhibiting the catalytic activity of DAPK. In addition, inhibition of the DAPK-p53 signaling axis by DANGER promoted anoikis-resistance and epithelial-mesenchymal transition (EMT), resulting in radioresistance of HG-treated NSCLC cells. Notably, knockdown of DANGER enhanced anoikis, EMT inhibition, and radiosensitization in a mouse xenograft model of lung cancer. Taken together, our findings offered evidence that overexpression of DANGER and the subsequent inhibitory effect on DAPK kinase activity are critical responses that account for HG-induced radioresistance of NSCLC.

  15. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

    Directory of Open Access Journals (Sweden)

    López Jacqueline

    2012-01-01

    Full Text Available Abstract Background Cancer-initiating cells (CICs are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I. Methods Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP. Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. Results CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB DNA repair machinery and the metabolism of reactive oxygen species (ROS. Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR. Conclusions We characterized a self-renewing subpopulation of CICs found among

  16. MiR-20a Induces Cell Radioresistance by Activating the PTEN/PI3K/Akt Signaling Pathway in Hepatocellular Carcinoma

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    Zhang, Yuqin [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province (China); Zheng, Lin [Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province (China); Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province (China); Ding, Yi [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province (China); Li, Qi [Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province (China); Wang, Rong [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province (China); Liu, Tongxin; Sun, Quanquan [Department of Radiation Oncology, Cancer Hospital, Hangzhou, Zhejiang Province (China); Yang, Hua [Department of Radiation Oncology, Nanhai Hospital, Southern Medical University, Guangzhou, Guangdong Province (China); Peng, Shunli [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province (China); Wang, Wei, E-mail: wangwei9500@hotmail.com [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province (China); Chen, Longhua, E-mail: chenlhsmu@126.com [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province (China)

    2015-08-01

    Purpose: To investigate the role of miR-20a in hepatocellular carcinoma (HCC) cell radioresistance, which may reveal potential strategies to improve treatment. Methods and Materials: The expression of miR-20a and PTEN were detected in HCC cell lines and paired primary tissues by quantitative real-time polymerase chain reaction. Cell radiation combined with colony formation assays was administrated to discover the effect of miR-20a on radiosensitivity. Bioinformatics prediction and luciferase assay were used to identify the target of miR-20a. The phosphatidylinositol 3-kinase inhibitor LY294002 was used to inhibit phosphorylation of Akt, to verify whether miR-20a affects HCC cell radioresistance through activating the PTEN/PI3K/Akt pathway. Results: MiR-20a levels were increased in HCC cell lines and tissues, whereas PTEN was inversely correlated with it. Overexpression of miR-20a in Bel-7402 and SMMC-7721 cells enhances their resistance to the effect of ionizing radiation, and the inhibition of miR-20a in HCCLM3 and QGY-7701 cells sensitizes them to it. PTEN was identified as a direct functional target of miR-20a for the induction of radioresistance. Overexpression of miR-20a activated the PTEN/PI3K/Akt signaling pathway. Additionally, the kinase inhibitor LY294002 could reverse the effect of miR-20a–induced radioresistance. Conclusion: MiR-20a induces HCC cell radioresistance by activating the PTEN/PI3K/Akt pathway, which suggests that miR-20a/PTEN/PI3K/Akt might represent a target of investigation for developing effective therapeutic strategies against HCC.

  17. Spatio-temporal changes in glutathione and thioredoxin redox couples during ionizing radiation-induced oxidative stress regulate tumor radio-resistance.

    Science.gov (United States)

    Patwardhan, R S; Sharma, D; Checker, R; Thoh, M; Sandur, S K

    2015-10-01

    Ionizing radiation (IR)-induced oxidative stress in tumor cells is effectively managed by constitutive and inducible antioxidant defense systems. This study was initiated to understand the relative contribution of different redox regulatory systems in determining the tumor radio-resistance. In this study, human T-cell lymphoma (Jurkat) cells were exposed to IR (4 Gy) and monitored for the spatio-temporal changes in cellular redox regulatory parameters. We monitored the changes in the levels of reactive oxygen species (ROS) (total, mitochondrial, primary, and secondary), thiols (total, surface, and intracellular), GSH/GSSG ratio, antioxidant enzyme activity viz. thioredoxin (Trx), Trx reductase (TrxR), glutathione peroxidase, and glutathione reductase with respect to time. We have also measured protein glutathionylation. We observed that tumor cells mount a biphasic response after IR exposure which can be divided into early (0-6 h) and late (16-48 h) responses in terms of changes in cellular redox parameters. During early response, constitutively active GSH and Trx systems respond to restore cellular redox balance to pre-exposure levels and help in activation of redox-sensitive transcription factor Nrf-2. During late response, increase in the levels of antioxidants GSH and Trx rescue cells against IR-mediated damage. We observed that disruption of either glutathione or thioredoxin metabolism led to partial impairment of ability of cells to survive against IR-induced damage. But simultaneous disruption of both the pathways significantly increased radio sensitivity of Jurkat cells. This highlighted the importance of these two antioxidant pathways in regulating redox homeostasis under conditions of IR-induced oxidative stress.

  18. Pim-3 contributes to radioresistance through regulation of the cell cycle and DNA damage repair in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiang-Yuan; Wang, Zhen [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Li, Bei [Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Zhang, Ying-Jian, E-mail: yjzhang111@aliyun.com [Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Li, Ying-Yi, E-mail: liyingyi@fudan.edu.cn [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China)

    2016-04-22

    Resistance of cancer cells to chemoradiotherapy is a major clinical problem in pancreatic cancer treatment. Therefore, understanding the molecular basis of cellular resistance and identifying novel targets are essential for improving treatment efficacy for pancreatic cancer patients. Previous studies have demonstrated a significant role for Pim-3 in pancreatic cancer survival against gemcitabine-induced genotoxic stress. Here, we observed that radiation treatment enhanced Pim-3 expression in human pancreatic cancer cells in vitro. Stable overexpression of Pim-3 in pancreatic cancer cells significantly protected cells against radiation treatment by attenuating G2/M phase cell cycle arrest and DNA damage response. Silencing of Pim-3 expression significantly elevated the phosphorylation of histone variant H2AX, a marker of DNA double strand breaks, and decreased the activation of ataxia-telangiectasia-mutated (ATM) kinase, along with its downstream targets, eventually enhancing the radiosensitivity of human pancreatic cancer cells in vitro and in vivo. Hence, we demonstrated a novel function for Pim-3 in human pancreatic cancer cell survival against radiation. Targeting Pim-3 may be a promising way to improve treatment efficacy in combination with radiotherapy in human pancreatic cancer. - Highlights: • This is first study to demonstrate that Pim-3 is endogenously induced by ionizing radiation in pancreatic cancer cells, and Pim-3 overexpression enhanced radioresistance of pancreatic cancer cells both in vitro and in vivo. • This is first study to provide evidence that radioresistance induced by Pim-3 is mainly attributed to Pim-3 induces activation of ATM, which subsequently activates checkpoint 1, leading to amplification of DNA repair through cell cycle arrest and DNA repair pathways. • This is first study to indicate that targeting Pim-3 may be a promising strategy to provide better treatment efficacy in combination with radiotherapy in human pancreatic

  19. Genome-wide analyses of radioresistance-associated miRNA expression profile in nasopharyngeal carcinoma using next generation deep sequencing.

    Directory of Open Access Journals (Sweden)

    Guo Li

    Full Text Available BACKGROUND: Rapidly growing evidence suggests that microRNAs (miRNAs are involved in a wide range of cancer malignant behaviours including radioresistance. Therefore, the present study was designed to investigate miRNA expression patterns associated with radioresistance in NPC. METHODS: The differential expression profiles of miRNAs and mRNAs associated with NPC radioresistance were constructed. The predicted target mRNAs of miRNAs and their enriched signaling pathways were analyzed via biological informatical algorithms. Finally, partial miRNAs and pathways-correlated target mRNAs were validated in two NPC radioreisitant cell models. RESULTS: 50 known and 9 novel miRNAs with significant difference were identified, and their target mRNAs were narrowed down to 53 nasopharyngeal-/NPC-specific mRNAs. Subsequent KEGG analyses demonstrated that the 53 mRNAs were enriched in 37 signaling pathways. Further qRT-PCR assays confirmed 3 down-regulated miRNAs (miR-324-3p, miR-93-3p and miR-4501, 3 up-regulated miRNAs (miR-371a-5p, miR-34c-5p and miR-1323 and 2 novel miRNAs. Additionally, corresponding alterations of pathways-correlated target mRNAs were observed including 5 up-regulated mRNAs (ICAM1, WNT2B, MYC, HLA-F and TGF-β1 and 3 down-regulated mRNAs (CDH1, PTENP1 and HSP90AA1. CONCLUSIONS: Our study provides an overview of miRNA expression profile and the interactions between miRNA and their target mRNAs, which will deepen our understanding of the important roles of miRNAs in NPC radioresistance.

  20. High linear-energy-transfer radiation can overcome radioresistance of glioma stem-like cells to low linear-energy-transfer radiation

    Science.gov (United States)

    Hirota, Yuki; Masunaga, Shin-Ichiro; Kondo, Natsuko; Kawabata, Shinji; Hirakawa, Hirokazu; Yajima, Hirohiko; Fujimori, Akira; Ono, Koji; Kuroiwa, Toshihiko; Miyatake, Shin-Ichi

    2014-01-01

    Ionizing radiation is applied as the standard treatment for glioblastoma multiforme (GBM). However, radiotherapy remains merely palliative, not curative, because of the existence of glioma stem cells (GSCs), which are regarded as highly radioresistant to low linear-energy-transfer (LET) photons. Here we analyzed whether or not high-LET particles can overcome the radioresistance of GSCs. Glioma stem-like cells (GSLCs) were induced from the GBM cell line A172 in stem cell culture medium. The phenotypes of GSLCs and wild-type cells were confirmed using stem cell markers. These cells were irradiated with 60Co gamma rays or reactor neutron beams. Under neutron-beam irradiation, high-LET proton particles can be produced through elastic scattering or nitrogen capture reaction. Radiosensitivity was assessed by a colony-forming assay, and the DNA double-strand breaks (DSBs) were assessed by a histone gamma-H2AX focus detection assay. In stem cell culture medium, GSLCs could form neurosphere-like cells and express neural stem cell markers (Sox2 and Musashi) abundantly in comparison with their parental cells. GSLCs were significantly more radioresistant to gamma rays than their parental cells, but neutron beams overcame this resistance. There were significantly fewer gamma-H2AX foci in the A172 GSLCs 24 h after irradiation with gamma rays than in their parental cultured cells, while there was no apparent difference following neutron-beam irradiation. High-LET radiation can overcome the radioresistance of GSLCs by producing unrepairable DNA DSBs. High-LET radiation therapy might have the potential to overcome GBM's resistance to X-rays in a clinical setting. PMID:23955054

  1. Differential roles of ATF-2 in survival and DNA repair contributing to radioresistance induced by autocrine soluble factors in A549 lung cancer cells.

    Science.gov (United States)

    Desai, Sejal; Kumar, Amit; Laskar, S; Pandey, B N

    2014-11-01

    Radioresistance is one of the obstacles to the effective radiotherapy for non-small cell lung cancer. Soluble factors in the tumour microenvironment are often implicated in radioresistance but the underpinning mechanism(s) remain largely elusive. We herein studied the wholesome effect of autocrine cytokines and growth factors in the form of self-conditioned medium (CM) on the radiosensitivity of A549 cells. A549 cells grown in CM exhibited radioresistance which was associated with increased survival and DNA repair. CM induced pro-survival pathways through increased intracellular cAMP and phosphorylation of JNK and p38. Downstream to JNK/p38 signalling, ATF-2 phosphorylated at Thr69/71 was accompanied with its increased transcriptional activity in CM treated cells. Pre-treatment with cAMP inhibitor and silencing of ATF-2 abrogated the CM-induced survival. Interestingly, in cells treated with CM followed by radiation, ATF-2 was found to be switched over from transcription factor to DNA damage response protein. In CM treated cells, after γ-radiation p-ATF-2(Thr69/71) and subsequently the transcriptional activity of ATF-2 were declined with simultaneous rise in p-ATF-2(Ser490/498). Immunoprecipitation/immunoblotting and inhibitor studies showed that phosphorylation of ATF-2 at Ser490/498 was mediated by ATM. Moreover, p-ATF-2(Ser490/498) was found to be co-localised with γ-H2AX in DNA repair foci in CM-treated cells. The DNA repair activity of ATF-2 was assisted with higher activity MRN complex in cells grown in CM. Our study revealed that, autocrine soluble factors regulate dual but differential role of ATF-2 as a transcription factor or DNA repair protein, which collectively culminate in radioresistance of A549 cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Decursin reduce radio-resistance of hypoxic regions under the proton beam therapy by induced HIF-1α degradation

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    Jung, Myung Hwan; Kim, Kye Ryung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    Protons induce cancer-cell apoptosis in vitro and block blood vessel formation in vivo through the generation of reactive oxygen species (ROS). The fact that proton severely inhibits blood vessel development in zebrafish embryos suggests a higher sensitivity of vascular endothelial cells to proton beam. Decursin, a coumarin compound, was originally isolated from Angelica gigas Nakai (Dang Gui). A. gigas root has been traditionally used in Korean folk medicine for the treatment of anemia and other common diseases. In previous reports, decursin was reported to exhibit anti-tumor activity against various cancer cells and to inhibit the activities of the androgen and androgen-receptor (AR) signaling pathway in prostate cancer, induction of cell cycle arrest and apoptosis in various cancer cells, such as prostate, breast, bladder, and colon cancer cells. Decursin also inhibits VEGF-induced angiogenesis through the suppression of the VEGFR-2-signaling pathway. However, the mechanism of decursin mediates change of HIF-1α activities is not clear. In this research, we identified regulations of the HIF-1α and the anti-angiogenesis effects of decursin in proton-beam-irradiated human lung cancer, prostate cancer and Hepatic cancer cells. We investigated the underlying mechanisms of positive effects of protonbeam-induced anti-angiogenesis. Our data indicate that the groups co-treated with decursin and a proton-beam had significant reduced HIF-1α activity compared with the groups treated with only a proton beam under the hypoxic condition caused by DFX(desferrioxamine). Decursin was found to induced HIF-1α degradation. Therefore, we suggest that decursin may be a potential candidate for use as a sensitizer for proton-beaminduced cell apoptosis. Here we have shown that decursin successfully reduced HIF-1α stability under hypoxic condition by induced desferrioxamine. We showed novel candidates for anti-angiogenic compound, decursin, leading to complete inhibition of radio-resistance

  3. Prenatal diagnosis of ataxia-telangiectasia and Nijmegen Breakage Syndrome by the assay of radioresistant DNA synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Kleijer, W.J.; Kraan, M. van der; Los, F.J. [Erasmus Univ., Rotterdam (Netherlands). Dept. of Clinical Genetics; Jaspers, N.G.J. [Erasmus Univ., Rotterdam (Netherlands). Lab. of Cell Biology and Genetics

    1994-12-01

    Prenatal diagnosis was performed in 16 pregnancies at risk of ataxia-telangiectasia (A-T) or Nijmegen Breakage Syndrome (NBS). Radioresistant DNA synthesis (RDS) was investigated in cultured chorionic villus (CV) cells and/or amniotic fluid (AF) cells. In four pregnancies, an affected foetus was diagnosed with increased RDS in cultured CV cells. In three of the four cases confirmation of the diagnosis was obtained by analysis of AF cells and/or skin fibroblasts from the foetus cultured after termination of the pregnancy; in the fourth case a fibroblast culture from the aborted foetus failed. In one case, only AF cells could be analysed in a late stage of pregnancy; pregnancy was terminated due to intermediate/equivocal results but the foetus fibroblasts showed normal RDS. Normal RDS was demonstrated in the other 11 pregnancies at 25% risk either by analysis of CB cells (nine cases) or of AF cells (two cases). In some cases the (normal) results on the CV cells were corroborated by subsequent analysis of Af cells. The results suggest that RDS analysis of CV cells allows reliable prenatal diagnosis of A-T/NBS. However, amniocentesis may be necessary to confirm normal results on CV cells if the foetus is female (because of the risk of maternal cell contamination) or in the rare case of equivocal results. (author).

  4. Functional analysis of the sbcD (dr1921) gene of the extremely radioresistant bacterium Deinococcus radiodurans

    Institute of Scientific and Technical Information of China (English)

    HU YiHuai; MA ChenYu; TIAN Bing; LIN Jun; HUA YueJin

    2007-01-01

    In eukaryotes, the Mre11-Rad50-Nbs1 (MRN) complex, which resides at the crossroads of DNA repair and checkpoint signaling, rapidly forms prominent foci at damage sites following double-strand break (DSB) induction. This complex carries out the initial processing of the DSB ends. Mutations in the genes that encode components of this complex result in DNA-damage hypersensitivity, genomic instability, telomere shortening, and aberrant meiosis. Therefore, the MR proteins are highly conserved during evolution. The bacterial orthologs of Mre11 and Rad50 are the SbcD and SbcC proteins, respectively. Deinococcus radiodurans, an extremely radioresistant bacterium, is able to mend hundreds of radiation-induced DSBs. The SbcD and SbcC proteins were identified as the products of the Dr1921 and Dr1922 genes. Disruption of the sbcD gene, by direct reverse-orientation insertional mutagenesis technology, remarkably increases the cells'sensitivity to various types of DNA damaging agents, such as ionizing radiation, ultraviolet irradiation, hydrogen peroxide, and mitomycin C. We also provide evidence that the drSbcD protein plays an important role in both growth and DNA repair in this organism, especially in repair of DSBs generated after cellular exposure to 6000 Gy of IR. These results demonstrate that the drSbcD protein plays an important role in DSBs repair in D. radiodurans.

  5. SIX1 overexpression predicts poor prognosis and induces radioresistance through AKT signaling in esophageal squamous cell carcinoma

    Science.gov (United States)

    He, Zheng; Li, Guang; Tang, Lingrong; Li, Yaming

    2017-01-01

    The Sineoculis homeobox homolog 1 (SIX1) protein has been found to be overexpressed in several human cancers. However, its expression pattern and biological roles in esophageal squamous cell carcinoma (ESCC) remain unexplored. This study examined the clinical significance of SIX1 in 119 ESCC tissues. It was found that SIX1 protein was upregulated in 36.9% (44/119) cases. SIX1 overexpression was an independent predictor for short survival of ESCC patients. siRNA knockdown and plasmid transfection were carried out in ESCC cell lines. SIX1 depletion inhibited cell growth, invasion, and colony formation, whereas its overexpression facilitated in vivo and in vitro cell growth, invasion, and colony formation. The apoptosis rate induced by X-ray irradiation was substantially increased by SIX1 knockdown in Eca-109 cells. Ectopic overexpression of SIX1 in TE-1 cells dramatically enhanced resistance to irradiation. Western blot analysis showed that SIX1 depletion downregulated cyclin E, matrix metalloproteinase-2 (MMP-2), Bcl-2 expression and upregulated Bim expression. SIX1 overexpression exhibited the opposite effect on these proteins. In addition, it was found that SIX1 could positively regulate extracellular signal-regulated kinase (ERK) and AKT signaling pathway. ERK inhibitor abolished the effect of SIX1 on MMP-2 expression. AKT inhibitor treatment blocked the role of SIX1 on anti-apoptotic protein Bcl-2. In conclusion, this study demonstrates that SIX1 overexpression predicts poor survival in ESCC patients and confers radioresistance through activation of AKT signaling pathways. PMID:28260921

  6. Differential Bystander Signaling Between Radioresistant Chondrosarcoma Cells and Fibroblasts After X-Ray, Proton, Iron Ion and Carbon Ion Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Wakatsuki, Masaru, E-mail: wa@mbe.nifty.com [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts (United States); Magpayo, Nicole; Kawamura, Hidemasa; Held, Kathryn D. [Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts (United States)

    2012-09-01

    Purpose: Chondrosarcoma is well known as a radioresistant tumor, but the mechanisms underlying that resistance are still unclear. The bystander effect is well documented in the field of radiation biology. We investigated the bystander response induced by X-rays, protons, carbon ions, and iron ions in chondrosarcoma cells using a transwell insert co-culture system that precludes physical contact between targeted and bystander cells. Methods and Materials: Human chondrosarcoma cells were irradiated with 0.1-, 0.5-, 1-, and 2-Gy X-rays, protons, carbon ions or iron ions using a transwell insert co-culture system. Formation of micronuclei and p53 binding protein 1 staining in bystander and irradiated cells were analyzed and bystander signaling between mixed cultures of chondrosarcoma cells, and normal human skin fibroblasts was investigated. Results: In this study, we show that the fraction of cells with DNA damages in irradiated chondrosarcoma cells showed dose-dependent increases with all beams. However, the fraction of cells with DNA damages in all bystander chondrosarcoma cells did not show any change from the levels in control cells. In the bystander signaling between mixed cultures of chondrosarcoma cells and fibroblasts, the amount of micronucleus formation in all bystander chondrosarcoma cells co-cultured with irradiated fibroblasts were the same as the levels for control cells. However, all bystander fibroblasts co-cultured with irradiated chondrosarcoma cells showed significant increases in the fraction of micronucleated cells compared to the rate of control cells. Conclusions: We conclude that chondrosarcoma cells in the transwell insert co-culture system could release bystander stimulations but could not develop bystander responses.

  7. Autocrine regulation of glioblastoma cell cycle progression, viability and radioresistance through the VEGF-VEGFR2 (KDR) interplay.

    Science.gov (United States)

    Knizetova, Petra; Ehrmann, Jiri; Hlobilkova, Alice; Vancova, Iveta; Kalita, Ondrej; Kolar, Zdenek; Bartek, Jiri

    2008-08-15

    Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and progression of malignant brain tumors. Given the significance of tumor microenvironment in general, and the established role of paracrine VEGF signaling in glioblastoma (GBM) biology in particular, we explored the potential autocrine control of human astrocytoma behavior by VEGF. Using a range of cell and molecular biology approaches to study a panel of astrocytoma (grade III and IV/GBM)-derived cell lines and a series of clinical specimens from low- and high-grade astrocytomas, we show that co-expression of VEGF and VEGF receptors (VEGFRs) occurs commonly in astrocytoma cells. We found VEGF secretion and VEGF-induced biological effects (modulation of cell cycle progression and enhanced viability of glioblastoma cells) to function in an autocrine manner. Morevover, we demonstrated that the autocrine VEGF signaling is mediated via VEGFR2 (KDR), and involves co-activation of the c-Raf/MAPK, PI3K/Akt and PLC/PKC pathways. Blockade of VEGFR2 by the selective inhibitor (SU1498) abrogated the VEGF-mediated enhancement of astrocytoma cell growth and viability under unperturbed culture conditions. In addition, such interference with VEGF-VEGFR2 signaling potentiated the ionizing radiation-induced tumor cell death. In clinical specimens, both VEGFRs and VEGF were co-expressed in astroglial tumor cells, and higher VEGF expression correlated with tumor progression, thereby supporting the relevance of functional VEGF-VEGFR signaling in vivo. Overall, our results are consistent with a potential autocrine role of the VEGF-VEGFR2 (KDR) interplay as a factor contributing to malignant astrocytoma growth and radioresistance, thereby supporting the candidacy of this signaling cascade as a therapeutic target, possibly in combination with radiotherapy.

  8. Radiosensitivity of keratinocytes from tongue and skin; enhanced radioresistance following serial cultivation

    Energy Technology Data Exchange (ETDEWEB)

    Parkinson, E.K.; Hume, W.J.; Potten, C.S.

    1986-01-01

    A study has been carried out of the radiation response of keratinocytes from human skin, mouse skin and mouse tongue to 0-10 Gy of ..gamma..-radiation, carried out in suspension at 20/sup 0/C. The Dsub(o)values for primary cultures of keratinocytes was similar to those obtained in vivo for mice, suggesting that this in vitro assay could be used to measure the sensitivity of keratinocytes treated with various cytotoxic agents. Sensitivity appears to change on subculturing and hence subcultures may be less appropriate for determining in vivo cell sensitivities.

  9. Identification and functional analysis of a phytoene desaturase gene from the extremely radioresistant bacterium Deinococcus radiodurans.

    Science.gov (United States)

    Xu, Zhenjian; Tian, Bing; Sun, Zongtao; Lin, Jun; Hua, Yuejin

    2007-05-01

    The phytoene-related desaturases are the key enzymes in the carotenoid biosynthetic pathway. The gene encoding phytoene desaturase in the deinoxanthin synthesis pathway of Deinococcus radiodurans was identified and characterized. Two putative phytoene desaturase homologues (DR0861 and DR0810) were identified by analysis of conserved amino acid regions, and the former displayed the highest identity (68 %) with phytoene desaturase of the cyanobacterium Gloeobacter violaceus. DR0861 gene knockout and dinucleotide-binding motif deletion resulted in the arrest of lycopene synthesis and the accumulation of phytoene. The colourless DR0861 knockout mutant became more sensitive to acute ionizing radiation and oxygen stress. Complementation of the mutant with a heterologous or homologous gene restored its pigment and resistance. The desaturase activity of DR0861 (crtI) was further confirmed by the assay of enzyme activity in vitro and heterologous expression in Escherichia coli containing crtE and crtB genes (responsible for phytoene synthesis) from Erwinia uredovora. In addition, the amount of lycopene synthesis in E. coli resulting from the expression of crtI from D. radiodurans was determined, and this had significant dose-dependent effects on the survival rate of E. coli exposed to hydrogen peroxide and ionizing radiation.

  10. CREB mediates ICAM-3: inducing radio-resistance, cell growth and migration/invasion of the human nonsmall cell lung cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Kuk; So, Kwang Sup; Bae, In Hwa; Um, Hong Duck [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-05-15

    The ICAM family proteins comprises cell surface molecules that are homologous to NCAM and are members of the single passed type 1 immunoglobulin superfamily (IgSF) that are anchored at the cellular membrane. The ICAM family consists of five subfamilies (ICAM-1 to ICAM-5) of heavily glycosylated cell surface receptors with common functional or structural homology. The extracellular domains of ICAM protein have roles in immune response and inflammation through various cell-cell interactions. The cytoplasmic tail residues of ICAM-3 participate in intracellular signaling such as calcium mobilization and tyrosine phosphorylation. Interestingly, the ICAM proteins appear to have a dual role in cancer. ICAM molecules may target and block tumor progression by stimulation of an immune response such as leukocyte activation. Conversely, other investigations have shown that ICAM molecules are involved in cancer malignancy because their increased expressions are associated with a poor diagnosis, lower survival rates and invasion in several cancers including melanoma, breast cancer and leukemia. We have also reported that an increase of ICAM-3 expression in several cancer cells and specimens of cervical cancer patient induce enhanced radio-resistance by the activation of focal adhesion kinase (FAK) and promote cancer cell proliferation by the activation of Akt and p44/42 MAPK. Therefore, these previous reports imply that ICAM-3 has various undefined roles in cancer. In this study, we investigated whether ICAM-3 increase cell migration and invasion through CREB activation and CREB has a role of increase of radioresistance and cell growth.

  11. E2F is involved in radioresistance of carbon ion induced apoptosis via Bax/caspase 3 signal pathway in human hepatoma cell.

    Science.gov (United States)

    Xie, Yi; Si, Jing; Wang, Yu-Pei; Li, Hong-Yan; Di, Cui-Xia; Yan, Jun-Fang; Ye, Yan-Cheng; Zhang, Yan-Shan; Zhang, Hong

    2017-05-13

    Deletion of p53, most common genetic alteration, is observed in human tumors and reported to lead to improve in cell radioresistance. Heavy-ion irradiation (IR) could induce p53(-/-) cancer cells apoptosis. However, little is known regarding the molecular mechanism in this type of cell apoptosis. The present studies have focused on mechanisms state of signaling pathways as an activator of the cell fate decisions induced by heavy ion IR without p53. Carbon ion IR could induce up-regulation of E2F1 expression in cancer cells. This phenomenon was not observed in X-ray IR group. Up-regulation of E2F1 could cause a higher reduction in clonogenic survival, low level of cellular activity, G2 /M phase arrest, promotion of apoptosis rate, up-regulation of phosphor-Rb, Bax, and cleaved-caspase 3 proteins expressions without p53. Changes of E2F1 expressions could partly alter radioresistance in cancer cells. The results were suggested that heavy ion IR could induce p53(-/-) cancer cells apoptosis via E2F1 signal pathway. Our study provides a scientific rationale for the clinical use of heavy ion as radiotherapy in patients with p53-deficient tumors, which are often resistant to radiotherapy. © 2017 Wiley Periodicals, Inc.

  12. SHP-1 overexpression increases the radioresistance of NPC cells by enhancing DSB repair, increasing S phase arrest and decreasing cell apoptosis.

    Science.gov (United States)

    Pan, Xiaofen; Mou, Jingjing; Liu, Sha; Sun, Ziyi; Meng, Rui; Zhou, Zhenwei; Wu, Gang; Peng, Gang

    2015-06-01

    The present study aimed to investigate the influence of SHP-1 on the radioresistance of the nasopharyngeal carcinoma (NPC) cell line CNE-2 and the relevant underlying mechanisms. The human NPC cell line CNE-2 was transfected with a lentivirus that contained the SHP-1 gene or a nonsense sequence (referred to as LP-H1802Lv201 and LP-NegLv201 cells, respectively). Cells were irradiated with different ionizing radiation (IR) doses. Cell survival, DNA double-strand breaks (DSBs), apoptosis, cell cycle distribution, and the expression of related proteins were assessed using colony formation assay, immunofluorescent assays (IFAs), flow cytometry (FCM) and western blot analyses, respectively. Compared with the control (CNE-2 cells) and LP-NegLv201 cells, LP-H1802Lv201 cells were more resistant to IR. IFAs showed that IR caused less histone H2AX phosphorylation (γH2AX) and RAD51 foci in the LP-H1802Lv201 cells. Compared with the control and LP-NegLv201 cells, LP-H1802Lv201 cells showed increased S phase arrest. After IR, the apoptotic rate of the LP-H1802Lv201 cells was lower in contrast to the control and LP-NegLv201 cells. Western blot analyses showed that IR increased the phosphorylation of ataxia telangiectasia mutated (ATM) kinase, checkpoint kinase 2 (CHK2), ataxia telangiectasia and Rad3-related (ATR) protein, checkpoint kinase 1 (CHK1) and p53. In LP-H1802Lv201 cells, the phosphorylation levels of ATM and CHK2 were significantly increased while the p53 phosphorylation level was decreased compared to these levels in the control and LP-NegLv201 cells. Phosphorylation of ATR and CHK1 did not show significant differences in the three cell groups. Overexpression of SHP-1 in the CNE-2 cells led to radioresistance and the radioresistance was related to enhanced DNA DSB repair, increased S phase arrest and decreased cell apoptosis.

  13. Determining

    Directory of Open Access Journals (Sweden)

    Bahram Andarzian

    2015-06-01

    Full Text Available Wheat production in the south of Khuzestan, Iran is constrained by heat stress for late sowing dates. For optimization of yield, sowing at the appropriate time to fit the cultivar maturity length and growing season is critical. Crop models could be used to determine optimum sowing window for a locality. The objectives of this study were to evaluate the Cropping System Model (CSM-CERES-Wheat for its ability to simulate growth, development, grain yield of wheat in the tropical regions of Iran, and to study the impact of different sowing dates on wheat performance. The genetic coefficients of cultivar Chamran were calibrated for the CSM-CERES-Wheat model and crop model performance was evaluated with experimental data. Wheat cultivar Chamran was sown on different dates, ranging from 5 November to 9 January during 5 years of field experiments that were conducted in the Khuzestan province, Iran, under full and deficit irrigation conditions. The model was run for 8 sowing dates starting on 25 October and repeated every 10 days until 5 January using long-term historical weather data from the Ahvaz, Behbehan, Dezful and Izeh locations. The seasonal analysis program of DSSAT was used to determine the optimum sowing window for different locations as well. Evaluation with the experimental data showed that performance of the model was reasonable as indicated by fairly accurate simulation of crop phenology, biomass accumulation and grain yield against measured data. The normalized RMSE were 3%, 2%, 11.8%, and 3.4% for anthesis date, maturity date, grain yield and biomass, respectively. Optimum sowing window was different among locations. It was opened and closed on 5 November and 5 December for Ahvaz; 5 November and 15 December for Behbehan and Dezful;and 1 November and 15 December for Izeh, respectively. CERES-Wheat model could be used as a tool to evaluate the effect of sowing date on wheat performance in Khuzestan conditions. Further model evaluations

  14. TGF-β and Hypoxia/Reoxygenation Promote Radioresistance of A549 Lung Cancer Cells through Activation of Nrf2 and EGFR

    Directory of Open Access Journals (Sweden)

    Sae-lo-oom Lee

    2016-01-01

    Full Text Available Although many studies have examined the roles of hypoxia and transforming growth factor- (TGF- β separately in the tumor microenvironment, the effects of simultaneous treatment with hypoxia/reoxygenation and TGF-β on tumor malignancy are unclear. Here, we investigated the effects of redox signaling and oncogenes on cell proliferation and radioresistance in A549 human lung cancer cells in the presence of TGF-β under hypoxia/reoxygenation conditions. Combined treatment with TGF-β and hypoxia activated epidermal growth factor receptor (EGFR and nuclear factor (erythroid-derived 2-like 2 (Nrf2, a redox-sensitive transcription factor. Interestingly, Nrf2 knockdown suppressed the effects of combined treatment on EGFR phosphorylation. In addition, blockade of EGFR signaling also suppressed induction of Nrf2 following combined treatment with hypoxia and TGF-β, indicating that the combined treatment induced positive crosstalk between Nrf2 and EGFR. TGF-β and hypoxia/reoxygenation increased the accumulation of reactive oxygen species (ROS, while treatment with N-acetyl-L-cysteine abolished the activation of Nrf2 and EGFR. Treatment with TGF-β under hypoxic conditions increased the proliferation of A549 cells compared with that after vehicle treatment. Moreover, cells treated with the combined treatment exhibited resistance to ionizing radiation (IR, and knockdown of Nrf2 increased IR-induced cell death under these conditions. Thus, taken together, our findings suggested that TGF-β and hypoxia/reoxygenation promoted tumor progression and radioresistance of A549 cells through ROS-mediated activation of Nrf2 and EGFR.

  15. Cell division cycle 25 homolog c effects on low-dose hyper-radiosensitivity and induced radioresistance at elevated dosage in A549 cells.

    Science.gov (United States)

    Zhao, Yanxia; Cui, Yingshan; Han, Jun; Ren, Jinghua; Wu, Gang; Cheng, Jing

    2012-09-01

    The underlying mechanisms behind both low-dose hyper-radiosensitivity (HRS) and induced radioresistance (IRR), generally occurring at elevated radiation levels, remain unclear; however, elucidation of the relationship between cell cycle division 25 homolog c (Cdc25c) phosphatase and HRS/IRR may provide important insights into this process. Two cell lines with disparate HRS status, A549 and SiHa cells, were selected as cell models for comparison of dose-dependent Cdc25c phosphatase expression subsequent to low-dose irradiation. Knockdown of Cdc25c in A549 cells was mediated by transfection with a pGCsi-RAN-U6neo vector containing hairpin siRNA sequences. S216-phosphorylated Cdc25c protein [p-Cdc25c (Ser216)], cell survival and mitotic ratio were measured by western blot, colony-forming assay and histone H3 phosphorylation analysis. Variant p-Cdc25c (Ser216) expression was observed in the two cell lines after irradiation. The p-Cdc25c (Ser216) expression noted in SiHa cells after administration of 0-1 Gy radiation was similar to the radioresistance model; however, in A549 cells, the dose response for the phosphorylation of the Cdc25c Ser216 residue overlapped the level required to overcome the HRS response. Furthermore, Cdc25c repression prior to low-dose radiation induced more distinct HRS and prevented the development of IRR. The dose required to overcome the HRS response coincided with the effect of early G2-phase checkpoint arrest in A549 cells (approximately 0.3 Gy), and Cdc25c knockdown in A549 cells (approximately 0.5 Gy) corresponded to the phosphorylation of the Cdc25c Ser216 residue. Resultant data confirmed that dose-dependent Cdc25c phosphatase does effectively act as an early G2-phase checkpoint, thus indicating mechanistic importance in the HRS to IRR transition in A549 cells.

  16. Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Hong Shik; Hong, Eun-Hee [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Su-Jae [Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Baek, Jeong-Hwa [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Lee, Chang-Woo [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Yim, Ji-Hye; Um, Hong-Duck [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Hwang, Sang-Gu, E-mail: sgh63@kcch.re.kr [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2013-09-27

    Highlights: •HRP-3 is a radiation- and anticancer drug-responsive protein in A549 cells. •Depletion of HRP-3 induces apoptosis of radio- and chemoresistant A549 cells. •Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. •Depletion of HRP-3 enhances ROS-dependent p53 activation and PUMA expression. -- Abstract: Biomarkers based on functional signaling have the potential to provide greater insight into the pathogenesis of cancer and may offer additional targets for anticancer therapeutics. Here, we identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistance-related gene and characterized the molecular mechanism by which its encoded protein regulates the radio- and chemoresistant phenotype of lung cancer-derived A549 cells. Knockdown of HRP-3 promoted apoptosis of A549 cells and potentiated the apoptosis-inducing action of radio- and chemotherapy. This increase in apoptosis was associated with a substantial generation of reactive oxygen species (ROS) that was attributable to inhibition of the Nrf2/HO-1 antioxidant pathway and resulted in enhanced ROS-dependent p53 activation and p53-dependent expression of PUMA (p53 upregulated modulator of apoptosis). Therefore, the HRP-3/Nrf2/HO-1/ROS/p53/PUMA cascade is an essential feature of the A549 cell phenotype and a potential radiotherapy target, extending the range of targets in multimodal therapies against lung cancer.

  17. PprA, a pleiotropic protein for radioresistance, works through DNA gyrase and shows cellular dynamics during postirradiation recovery in Deinococcus radiodurans

    Indian Academy of Sciences (India)

    Swathi Kota; Vijaya Kumar Charaka; H. S. Misra

    2014-08-01

    PprA, a pleiotropic protein involved in radioresistance of Deinococcus radiodurans was detected in multiprotein DNA processing complex identified from this bacterium. pprA mutant expressing GFP-PprA could restore its wild type resistance of radiation. Under normal conditions, GFP-PprA expressing cells showed PprA localization on both septum trapped nucleoids (STN) and nucleoids located elsewhere (MCN). Cell exposed to 4 kGy radiation showed nearly 2 h growth lag and during this growth arrest phase, the majority of the cells had GFP-PprA located on MCN. While in late phase (∼120 min) PIR cells, when cells are nearly out of growth arrest, PprA was maximally found with STN. These cells when treated with nalidixic acid showed diffused localization of PprA across the septum. gyrA disruption mutant of D. radiodurans showed growth inhibition, which increased further in gyrA pprA mutant. Interestingly, gyrA mutant showed ∼20-fold less resistance to radiation as compared to wild type, which did increase further in gyrA pprA mutant. These results suggested that PprA localization undergoes a dynamic change during PIR, and its localization on nucleoid near septum and functional interaction with gyrase A might suggest a mechanism that could explain PprA role in genome segregation possibly through topoisomerase II.

  18. Genomic amplification of Fanconi anemia complementation group A (FancA) in head and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance and clinical relevance.

    Science.gov (United States)

    Hess, Julia; Unger, Kristian; Orth, Michael; Schötz, Ulrike; Schüttrumpf, Lars; Zangen, Verena; Gimenez-Aznar, Igor; Michna, Agata; Schneider, Ludmila; Stamp, Ramona; Selmansberger, Martin; Braselmann, Herbert; Hieber, Ludwig; Drexler, Guido A; Kuger, Sebastian; Klein, Diana; Jendrossek, Verena; Friedl, Anna A; Belka, Claus; Zitzelsberger, Horst; Lauber, Kirsten

    2017-02-01

    Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance. Silencing of FancA expression in HNSCC cell lines with genomic gains on 16q23-24 resulted in significantly impaired clonogenic survival upon irradiation. Conversely, overexpression of FancA in immortalized keratinocytes conferred increased survival accompanied by improved DNA repair, reduced accumulation of chromosomal translocations, but no hyperactivation of the FA/BRCA-pathway. Downregulation of interferon signaling as identified by microarray analyses, enforced irradiation-induced senescence, and elevated production of the senescence-associated secretory phenotype (SASP) appeared to be candidate mechanisms contributing to FancA-mediated radioresistance. Data of the TCGA HNSCC cohort confirmed the association of gains on 16q24.3 with FancA overexpression and impaired overall survival. Importantly, transcriptomic alterations similar to those observed upon FancA overexpression in vitro strengthened the clinical relevance. Overall, FancA amplification and overexpression appear to be crucial for radiotherapeutic failure in HNSCC.

  19. FoxM1 Promotes Stemness and Radio-Resistance of Glioblastoma by Regulating the Master Stem Cell Regulator Sox2.

    Science.gov (United States)

    Lee, Yeri; Kim, Kang Ho; Kim, Dong Geon; Cho, Hee Jin; Kim, Yeonghwan; Rheey, Jinguen; Shin, Kayoung; Seo, Yun Jee; Choi, Yeon-Sook; Lee, Jung-Il; Lee, Jeongwu; Joo, Kyeung Min; Nam, Do-Hyun

    2015-01-01

    Glioblastoma (GBM) is the most aggressive and most lethal brain tumor. As current standard therapy consisting of surgery and chemo-irradiation provides limited benefit for GBM patients, novel therapeutic options are urgently required. Forkhead box M1 (FoxM1) transcription factor is an oncogenic regulator that promotes the proliferation, survival, and treatment resistance of various human cancers. The roles of FoxM1 in GBM remain incompletely understood, due in part to pleotropic nature of the FoxM1 pathway. Here, we show the roles of FoxM1 in GBM stem cell maintenance and radioresistance. ShRNA-mediated FoxM1 inhibition significantly impeded clonogenic growth and survival of patient-derived primary GBM cells with marked downregulation of Sox2, a master regulator of stem cell phenotype. Ectopic expression of Sox2 partially rescued FoxM1 inhibition-mediated effects. Conversely, FoxM1 overexpression upregulated Sox2 expression and promoted clonogenic growth of GBM cells. These data, with a direct binding of FoxM1 in the Sox2 promoter region in GBM cells, suggest that FoxM1 regulates stemness of primary GBM cells via Sox2. We also found significant increases in FoxM1 and Sox2 expression in GBM cells after irradiation both in vitro and in vivo orthotopic tumor models. Notably, genetic or a small-molecule FoxM1 inhibitor-mediated FoxM1 targeting significantly sensitized GBM cells to irradiation, accompanying with Sox2 downregulation. Finally, FoxM1 inhibition combined with irradiation in a patient GBM-derived orthotopic model significantly impeded tumor growth and prolonged the survival of tumor bearing mice. Taken together, these results indicate that the FoxM1-Sox2 signaling axis promotes clonogenic growth and radiation resistance of GBM, and suggest that FoxM1 targeting combined with irradiation is a potentially effective therapeutic approach for GBM.

  20. Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines

    Science.gov (United States)

    Choi, Yeo-Jin; Baek, Ga-Young; Park, Hae-Ran; Jo, Sung-Kee; Jung, Uhee

    2016-01-01

    The control of radioresistance and metastatic potential of surviving cancer cells is important for improving cancer eradication by radiotheraphy. The distal-less homeobox2 (DLX2) gene encodes for a homeobox transcription factor involved in morphogenesis and its deregulation was found in human solid tumors and hematologic malignancies. Here we investigated the role of DLX2 in association with radiation-induced epithelial to mesenchymal transition (EMT) and stem cell-like properties and its regulation by Smad2/3 signaling in irradiated A549 and MDA-MB-231 human cancer cell lines. In irradiated A549 and MDA-MB-231 cells, EMT was induced as demonstrated by EMT marker expression, phosphorylation of Smad2/3, and migratory and invasive ability. Also, irradiated A549 and MDA-MB-231 cells showed increased cancer stem cells (CSCs) marker. Interestingly, DLX2 was overexpressed upon irradiation. Therefore, we examined the role of DLX2 in radiation-induced EMT and radioresistance. The overexpression of DLX2 alone induced EMT, migration and invasion, and CSC marker expression. The reduced colony-forming ability in irradiated cells was partially restored by DLX2 overexpression. On the other hand, the depletion of DLX2 using si-RNA abolished radiation-induced EMT, CSC marker expression, and phosphorylation of Smad2/3 in irradiated A549 and MDA-MB-231 cells. Also, depletion of DLX2 increased the radiation sensitivity in both cell lines. Moreover, knockdown of Smad2/3, a key activator of TGF-β1 pathway, abrogated the radiation-induced DLX2 expression, indicating that radiation-induced DLX2 expression is dependent on Smad2/3 signaling. These results demonstrated that DLX2 plays a crucial role in radioresistance, radiation-induced EMT and CSC marker expression, and the expression of DLX2 is regulated by Smad2/3 signaling in A549 and MDA-MB-231 cell lines. PMID:26799321

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  2. Single Strand Annealing Plays a Major Role in RecA-Independent Recombination between Repeated Sequences in the Radioresistant Deinococcus radiodurans Bacterium.

    Science.gov (United States)

    Ithurbide, Solenne; Bentchikou, Esma; Coste, Geneviève; Bost, Bruno; Servant, Pascale; Sommer, Suzanne

    2015-10-01

    The bacterium Deinococcus radiodurans is one of the most radioresistant organisms known. It is able to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Our work aims to highlight the genes involved in recombination between 438 bp direct repeats separated by intervening sequences of various lengths ranging from 1,479 bp to 10,500 bp to restore a functional tetA gene in the presence or absence of radiation-induced DNA double strand breaks. The frequency of spontaneous deletion events between the chromosomal direct repeats were the same in recA+ and in ΔrecA, ΔrecF, and ΔrecO bacteria, whereas recombination between chromosomal and plasmid DNA was shown to be strictly dependent on the RecA and RecF proteins. The presence of mutations in one of the repeated sequence reduced, in a MutS-dependent manner, the frequency of the deletion events. The distance between the repeats did not influence the frequencies of deletion events in recA+ as well in ΔrecA bacteria. The absence of the UvrD protein stimulated the recombination between the direct repeats whereas the absence of the DdrB protein, previously shown to be involved in DNA double strand break repair through a single strand annealing (SSA) pathway, strongly reduces the frequency of RecA- (and RecO-) independent deletions events. The absence of the DdrB protein also increased the lethal sectoring of cells devoid of RecA or RecO protein. γ-irradiation of recA+ cells increased about 10-fold the frequencies of the deletion events, but at a lesser extend in cells devoid of the DdrB protein. Altogether, our results suggest a major role of single strand annealing in DNA repeat deletion events in bacteria devoid of the RecA protein, and also in recA+ bacteria exposed to ionizing radiation.

  3. Single Strand Annealing Plays a Major Role in RecA-Independent Recombination between Repeated Sequences in the Radioresistant Deinococcus radiodurans Bacterium.

    Directory of Open Access Journals (Sweden)

    Solenne Ithurbide

    2015-10-01

    Full Text Available The bacterium Deinococcus radiodurans is one of the most radioresistant organisms known. It is able to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Our work aims to highlight the genes involved in recombination between 438 bp direct repeats separated by intervening sequences of various lengths ranging from 1,479 bp to 10,500 bp to restore a functional tetA gene in the presence or absence of radiation-induced DNA double strand breaks. The frequency of spontaneous deletion events between the chromosomal direct repeats were the same in recA+ and in ΔrecA, ΔrecF, and ΔrecO bacteria, whereas recombination between chromosomal and plasmid DNA was shown to be strictly dependent on the RecA and RecF proteins. The presence of mutations in one of the repeated sequence reduced, in a MutS-dependent manner, the frequency of the deletion events. The distance between the repeats did not influence the frequencies of deletion events in recA+ as well in ΔrecA bacteria. The absence of the UvrD protein stimulated the recombination between the direct repeats whereas the absence of the DdrB protein, previously shown to be involved in DNA double strand break repair through a single strand annealing (SSA pathway, strongly reduces the frequency of RecA- (and RecO- independent deletions events. The absence of the DdrB protein also increased the lethal sectoring of cells devoid of RecA or RecO protein. γ-irradiation of recA+ cells increased about 10-fold the frequencies of the deletion events, but at a lesser extend in cells devoid of the DdrB protein. Altogether, our results suggest a major role of single strand annealing in DNA repeat deletion events in bacteria devoid of the RecA protein, and also in recA+ bacteria exposed to ionizing radiation.

  4. Potential role for LINAC-based stereotactic radiosurgery for the treatment of 5 or more radioresistant melanoma brain metastases.

    Science.gov (United States)

    Frakes, Jessica M; Figura, Nicholas B; Ahmed, Kamran A; Juan, Tzu-Hua; Patel, Neha; Latifi, Kujtim; Sarangkasiri, Siriporn; Strom, Tobin J; Chinnaiyan, Prakash; Rao, Nikhil G; Etame, Arnold B

    2015-11-01

    Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) is a treatment option for patients with melanoma in whom brain metastases have developed. Very limited data are available on treating patients with ≥5 lesions. The authors sought to determine the effectiveness of SRS in patients with ≥5 melanoma brain metastases. A retrospective analysis of metastatic melanoma treated with SRS in a single treatment session for ≥5 lesions was performed. Magnetic resonance imaging studies were reviewed post-SRS to evaluate local control (LC). Disease progression on imaging was defined using the 2009 Response Evaluation Criteria in Solid Tumors (RECIST). Survival curves were calculated from the date of brain metastases diagnosis or the date of SRS by using the Kaplan-Meier (KM) method. Univariate and multivariate analysis (UVA and MVA, respectively) were performed using the Cox proportional-hazards model. The authors identified 149 metastatic brain lesions treated in 28 patients. The median patient age was 60.5 years (range 38-83 years), and the majority of patients (24 [85.7%]) had extracranial metastases. Four patients (14.3%) had received previous whole-brain radiotherapy (WBRT), and 11 (39.3%) had undergone previous SRS. The median planning target volume (PTV) was 0.34 cm3 (range 0.01-12.5 cm3). Median follow-up was 6.3 months (range 1-46 months). At the time of treatment, 7% of patients were categorized as recursive partitioning analysis (RPA) Class I, 89% as RPA Class II, and 4% as RPA Class III. The rate of local failure was 11.4%. Kaplan-Meier LC estimates at 6 and 12 months were 91.3% and 82.2%, respectively. A PTV volume≥0.34 cm3 was a significant predictor of local failure on UVA (HR 16.1, 95% CI 3.2-292.6, ptreatment. The RPA class was a significant predictor of KM OS estimates from the date of treatment (p=0.02). Patients who did not receive WBRT after SRS treatment had decreased OS on MVA (HR 3.5, 95% CI 1.1-12.0, p=0.03), and patients who did not

  5. 人宫颈癌获得性放射抗拒细胞株(Hela-R)DNA修复能力的观察%Observation of the DNA repair capability of acquired radioresistant cell line from human cervical carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    刘晨; 庞学利

    2013-01-01

    目的 观察人宫颈癌获得性放射抗拒细胞株(Heal-R)与其亲本细胞(Hela)DNA修复能力的差异.方法 采用克隆形成实验测定细胞的放射敏感性;CCK-8细胞增殖实验检测增殖情况,流式细胞术检测凋亡及周期变化,彗星实验及5-乙基-2′-脱氧尿苷(EdU)掺入检测DNA的修复能力.结果 Hela-R细胞株的平均致死剂量显著高于Hela细胞株.X射线照射后,Hela-R细胞株早、晚期凋亡率均低于 Hela细胞.24、48、72 h Hela和Hela-R细胞株的光密度值(OD)值分别为1.13±0.12、1.46±0.13(P<0.05);1.34±0.07、1.20±0.07(P<0.05); 1.58±0.07、1.48±0.07(P<0.05).Hela-R细胞株放疗后12~48 h G2期细胞显著增多.Hela-R细胞株放疗后24 h与48 h,彗星尾长均短于Hela细胞株.X射线照射1 h后,Hela-R细胞株EdU荧光强度为121.32±39.67(P<0.01),高于Hela细胞株.结论 Hela-R较Hela细胞株具有显著的放射抗拒性,DNA损伤修复能力的增强是其产生的重要机制之一.%Objective To observe the difference of DNA repair capability between the radioresistant cell (Hela R) line and its parents cell(Hela) line. Methods The radiosensitivity was measured with colony formation. CCK 8 cell proliferation assay was used to detect proliferation after radiation. Flow cytometry was used to detect the change of apoptosis and cell cycle after radiation. Comet assay and incorporation of ethynyl deoxyuridine were used to detect DNA repair capability. Results The mean lethal dose of Hela R was significantly superior to its parental cell (Hela). After irradiation,Hela R cell line's early apoptotic rate and late apop totic rate were significantly less than the Hela cells. CCK 8 proliferation experiment showed that Hela and Hela R cell's OD value, respectively,in 24,48 and 72 hours,were 1. 13 ± 0. 12 and 1. 46 ± 0. 13 (P<0. 05);1.34±0. 07 and 1. 20 ± 0. 07 (P<0. 05) ; 1. 58 ± 0. 07 and 1. 48±0. 07(P<0. 05). Hela R's G2 phase rate was significantly higher than Hela

  6. Bcl-w, a Radio-resistant Protein, Promotes the Gastric Cancer Cell Migration by inducing the phosphorylation of Focal Adhesion Kinase

    Energy Technology Data Exchange (ETDEWEB)

    Bae, In Hwa; Yoon, Sung Hwan; Um, Hong Duck [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2008-05-15

    Gastric cancer is one of the leading malignancies in many countries and lethal for the high incidence of recurrence even after drastic surgical resection. Because local invasion and subsequent metastasis contributes to the failure of anticancer treatments of gastric cancer, a better understanding of the mechanisms involved in tumor invasiveness within the stomach seems to be essential for the control of this disease. Bcl-w is a prosurvival member of the Bcl-2 protein family, and thus protects cells from {gamma}-irradiation. Recent reports suggest that Bcl-w can be upregulated in gastric cancer cells in a manner associated with the infiltrative (diffuse) types of the tumor. An analysis of Bcl-w function consistently revealed that Bcl-w can also promote the migratory and invasive potentials of gastric cancer cells. While it was shown that Bcl-w increases the invasiveness of cancer cells by sequentially inducing PI3K, Akt, SP1, and MMP-2, cellular components involved in Bcl-w-induced cell migration remain to be determined. This was the reason why we undertook the present study, which shows that FAK is a critical mediator of the cell migration induced by Bcl-w.

  7. A radio-resistant perforin-expressing lymphoid population controls allogeneic T cell engraftment, activation, and onset of graft-versus-host disease in mice.

    Science.gov (United States)

    Davis, Joanne E; Harvey, Michael; Gherardin, Nicholas A; Koldej, Rachel; Huntington, Nicholas; Neeson, Paul; Trapani, Joseph A; Ritchie, David S

    2015-02-01

    Immunosuppressive pretransplantation conditioning is essential for donor cell engraftment in allogeneic bone marrow transplantation (BMT). The role of residual postconditioning recipient immunity in determining engraftment is poorly understood. We examined the role of recipient perforin in the kinetics of donor cell engraftment. MHC-mismatched BMT mouse models demonstrated that both the rate and proportion of donor lymphoid cell engraftment and expansion of effector memory donor T cells in both spleen and BM were significantly increased within 5 to 7 days post-BMT in perforin-deficient (pfn(-/-)) recipients, compared with wild-type. In wild-type recipients, depletion of natural killer (NK) cells before BMT enhanced donor lymphoid cell engraftment to that seen in pfn(-/-) recipients. This demonstrated that a perforin-dependent, NK-mediated, host-versus-graft (HVG) effect limits the rate of donor engraftment and T cell activation. Radiation-resistant natural killer T (NKT) cells survived in the BM of lethally irradiated mice and may drive NK cell activation, resulting in the HVG effect. Furthermore, reduced pretransplant irradiation doses in pfn(-/-) recipients permitted long-term donor lymphoid cell engraftment. These findings suggest that suppression of perforin activity or selective depletion of recipient NK cells before BMT could be used to improve donor stem cell engraftment, in turn allowing for the reduction of pretransplant conditioning.

  8. Establishment and dynamic in vivo imaging of a radioresistant,GFP-labelled xenograft tumor model of human nasopharyngeal carcinoma in mouse%绿色荧光蛋白标记的鼻咽癌放射抗拒性裸鼠移植瘤模型的建立及其活体成像观察

    Institute of Scientific and Technical Information of China (English)

    黄小鹏; 马慧; 朱小东; 葛莲英; 曲颂; 李龄; 郭亚; 赵伟; 黎丹戎

    2013-01-01

    Objective To establish a GFP-labelled radioresistant xenograft tumor model of human nasopharyngeal carcinoma(NPC) and build the foundation for further study. Methods Lentivirus was used to establish a stable,radioresistant human NPC cell line expressing GFP(GFP-CNE-2R)and a corresponding non-radioresistant cell line(GFP-CNE-2).Both lines were subcutaneously implanted into BALB/c-nu nude mice;when the tumors had reached 1 cm in size,the animals were irradiated with 10 Gy in 1 fraction.Tumor proliferation and metastasis were analyzed in vivo using dynamic imaging technology. Results GFP-CNE-2R and GFP-CNE-2 lines were successfully established,and clone formation assays showed GFP-CNE-2R cells to be radioresistant.Xenograft tumors were grown from GFP-CNE-2R and GFP-CNE-2 cells,and growth of GFP-CNE-2R tumors was not significantly inhibited by radiation. Conclusion GFP-CNE-2R xenograft tumors are more radioresistant than GFP-CNE-2 xenograft tumors.%目的:建立绿色荧光蛋白(green fluorescent protein,GFP)标记的鼻咽癌放射抗拒性裸鼠移植瘤模型,为后续研究奠定基础。方法将以慢病毒转染的方法建立稳定表达GFP标记的人鼻咽低分化鳞癌细胞株GFP-CNE-2和放射抗拒性细胞株GFP-CNE-2R接种至裸鼠体内,建立皮下移植的肿瘤模型。待肿瘤直径约为1 cm时给予相同剂量10 Gy的X射线一次性照射,通过小动物活体成像仪观察移植瘤的生长和转移情况。结果成功建立了稳定表达GFP标记的放射抗拒性及放射敏感的人鼻咽低分化鳞癌细胞株GFP-CNE-2R和GFP-CNE-2。克隆形成实验显示GFP-CNE-2R细胞株具有放射抗拒性。GFP-CNE-2R和GFP-CNE-2细胞的皮下成瘤率均为100%,证实建模成功。相对于GFP-CNE-2裸鼠移植瘤, GFP-CNE-2R移植瘤的生长受照射抑制不明显。结论相对于GFP-CNE-2裸鼠移植瘤,GFP-CNE-2R裸鼠移植瘤具有更强的放射抗拒性。

  9. The mechanism of Deinococcus radiodurans pprI gene in enhancing mice radioresistance to γ-rays%耐辐射球菌pprI基因对γ射线损伤小鼠的抗辐射机制

    Institute of Scientific and Technical Information of China (English)

    陈婷婷; 张西志; 汪步海; 花威; 杨占山

    2013-01-01

    Objective To investigate the mechanism of Deinococcus radiodurans pprI gene in enhancing mice radioresistance to γ-rays by transfecting it in vivo.Methods The male Kunming mice were randomly divided into control group,irradiated group,pCMV-HA transfected group and pCMV-HA-pprI transfected group.The pCMV-HA-pprI plasmid contained pprI gene was injected into the muscle of mice which were exposed to total 6 Gy of γ-ray irradiation.After injection,the in vivo gene electroporation technology was used to transfect the pprI gene into the cells,and Western blot was used to identify the PprI protein,mammalian homolog protein Rad51 corresponding to recA gene downstream of pprI,and protein Rad52.Results In the muscle of the mice of transfected pCMV-HA-pprI group,the protein PprI expressed significantly at 1 d post-irradiation,but there was no expression of pprI gene 7 d post-irradiation and in other groups.In the mice of transfected with pCMV-HA-pprI,the expression of Rad51 protein was significantly increased in the lungs at 1,7 and 14 d post-irradiation,and significantly increased in the liver at 1 and 28 d post-irradiation and increased in the kidneys at 1 and 14 d post-irradition.However,there was no obvious change of Rad52 protein expression in the lungs and livers of mice in all groups.Conlusions The prokaryotic gene pprI could act on the mammalian homologisation analogues rad51 gene downstream of recA gene and then increase the expression level of protein Rad51 which results in the enhancement of radioresistance.%目的 研究耐辐射球菌pprI基因活体电转染在哺乳动物γ射线放射损伤中发挥抗辐射作用的机制.方法 采用雄性昆明种小鼠,随机区组法分为健康对照组、单纯照射组、空载体转染组和基因转染组.将自行构建的含有pprI基因的pCMV-HA-pprI质粒注入接受6 Gyγ射线照射的小鼠肌肉内,然后采用活体基因电转导技术将该基因导入细胞内,应用Western blot法对PprI蛋白及其

  10. Study of multidrug resistance and radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Yoon Koo; Yoo, Young Do

    1999-04-01

    We investigated the mechanism of 5-FU, adriamycin, radiation resistance in Korean gastric cancer cells. First we investigated the relation between Rb and multidrug resistance. Rb stable transfectants exhibited 5- to 10- fold more resistance to adriamycin than the control cells. These Rb transfectants showed increased MDR1 expression. We also investigated up-regulation in radiation-resistant tumor tissues. HSP27, MRP-8, GST, and NKEF-B were up-regulated in radiation resistant tumor. Expression of NKEF-B was also increased by radiation exposure in Head and Neck cells. These results demonstrated that NKEF-B is a stress response protein and it may have an important role in radiation resistance.

  11. Overcoming the Mechanism of Radioresistance in Neuroblastoma

    Science.gov (United States)

    2014-06-01

    apoptosis at the next mitosis . The hypothesis was investigated initially in subcutaneous tumors and then an orthotopic tumor model. Conventional standard...phase cell cycle checkpoint. Failure to activate this radioprotective checkpoint means that proliferating G2-phase cells enter mitosis with unrepaired...early G2-phase cell cycle checkpoint and DNA damage is repaired before cells enter mitosis . This effect was not seen in MX-IXC cells than did not

  12. 反复照射建立食管癌放射抗性细胞系方法的重复性和稳定性研究%Repeatability and stability of repeated irradiation method to establish the radioresistant esophageal cancer cell line

    Institute of Scientific and Technical Information of China (English)

    杨延灵; 薛晓英; 冉玉格; 张玉峰; 李锋; 杨晔

    2015-01-01

    Objective To study the repeatability and stability of repeated irradiation method to establish the radioresistant esophageal cancer cell line and to observe the variation of radiosensitivity between the radioresistant cell line and its parental cell line.Methods A radioresistant cell line,TE13R120,was established from a human esophageal squamous cancer cell line TE13 by repeated irradiation,120 Gy in total dose.Colony formation assay was used to calculate the radiation biology parameters and detect radiation resistance.Besides,multi-target single-hit model was adopted to fit dose-survival curve of TE13 and TE13R120 cell.The cells were cultrured for 8 d,the cell growth curve was drawn to calculate the population doubling time of TE13 and TE13R120 cell.Results After radiation by 120 Gy in total dose,TE13R120 cell line showed significant radioresistance compared with its parental cells TE13.The D0 ,Dq,and N of TE13R120 showed siguificant radioresitance as compared with those of TE13(2.36,2.17,2.50 vs 1.90,1.11,1.80),but SF2 ,a/β were lover in the former cell line(0.53,2.67 vs 0.73,8.00).The population doubling time of TE13R120 was 20.70 h,longer than its parental cell line TE13 (17.67 h).The results were similar with those of the first establish line.Conclusion The radioresistant cell line established by repeated radiation exposures and gradually screening is reliable since it can build a stable cell line with radioresistant phenotype.%目的:探讨射线反复照射方法建立食管癌放射抗性细胞系的重复性及稳定性,并观察辐射抗性细胞与其亲代细胞之间的放射敏感性的差异。方法应用射线对人食管鳞状细胞癌细胞 TE13进行反复照射,累计剂量120 Gy,建立具有放射抗性的细胞系 TE13R120。采用细胞克隆形成实验测定2种细胞的放射生物学参数,检测其辐射抗性,采用单击多靶模型拟合存活曲线。经连续8 d培养细胞,绘制2

  13. Determinants of intrinsic radiosensitivity of mammalian cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Radford, I.R. [Peter MacCallum Cancer Institute, East Melbourne, VIC (Australia). Research Division

    1998-12-31

    Differences in the radiosensitivity of normal and cancerous cells could arise in various ways. Although there is no compelling data to support the view, the currently prevailing opinion is that differences in radiosensitivity are related to differences in some aspect of enzymatic DNA repair. A test of the importance of possible differences in enzymatic DNA repair in determining relative radiosensitivity would be to compare lethality in cells containing equivalent numbers of DNA lesions. Six cell lines were used in these studies: two Chinese hamster (CHO and V79) and a monkey (Vero) fibroblast-like line, a mouse melanoma line (B16-F1), and a rat (RUC-2) and a human (SQ-20B) carcinoma line. This group of cell lines displays a wide range of sensitivities to external beam low-LET radiation, ranging from the relatively radiosensitive B16-F1 and Vero lines through to the highly radioresistant RUC-2 line. However, it is important to note that none of the lines has a demonstrated defect in enzymatic DNA repair and that all appear to die by necrosis following a lethal radiation insult. Despite having significantly different radiosensitivities, CHO and V79 cells showed comparable responses to DNA-associated {sup 125}I-decays with D{sub o} values of around 65. More surprisingly, the radiosensitive B16-F1 line and the radioresistant RUC-2 line both had responses with D{sub o} values of around 133 {sup 125}I-decays. The factor of two difference between the D{sub o} values for these two pairs of cell lines is probably attributable to CHO and V79 cells being pseudo-diploid whereas B 16-F1 and RUC2 appear to have derived from tetraploid cells. The generality of the above result, for DNA lesions of different quality, was tested by comparing the sensitivities of CHO and V79 cells to DNA-associated {sup 3}H-decays. Again, consistent with the {sup 125}I-decay data, there was no significant difference in the D{sub o} values for these lines. Our {sup 3}H- and {sup 125}I-decay data are

  14. A preliminary study of the role of miR-193a-3p in radioresistance of esophageal cancer cells%miR-193a-3p在食管癌细胞放射抵抗作用的初步研究

    Institute of Scientific and Technical Information of China (English)

    孟芳; 钱立庭; 丁伯金; 周解平

    2016-01-01

    目的:探讨miR⁃193a⁃3p在食管鳞癌放射耐受性机制中的作用。方法通过6 MV X射线对4个食管癌细胞系进行照射,采用MTT法检测出相对敏感系及耐受系细胞;茎环引物实时定量PCR法检测miR⁃193a⁃3p、miR⁃155、miR⁃22⁃3p在2个细胞中的表达,miR⁃193a⁃3p作为表达差异较为明显的 microRNA 被挑选进行下一步研究。分别合成并转染 miR⁃193a⁃3p 的 mimic (3PM)或antagomiR (3PA)序列及小干扰RNA (si⁃LOXL4)以提高或抑制其在细胞中的表达水平,MTT法和流式细胞分析术检测miR⁃193a⁃3p及其下游基因LOXL4对于放射敏感性的影响。结果筛选出相对放射敏感细胞系( KYSE510)及耐受细胞系( KYSE410);miR⁃193a⁃3p在两系细胞中的表达水平差异显著高于miR⁃155、miR⁃22⁃3p (1.00∶21.13);KYSE510细胞中转染mimic提高其表达后,与对照组相比,其放射敏感性降低,细胞凋亡比例显著下降11.10%(P<0.05),而 KYSE410细胞中转染 antagomiR后,其敏感性增加( P<0.05)。作为miR⁃193a⁃3p的下游基因,LOXL4的表达抑制也受到miR⁃193a⁃3p的调控,转染si⁃LOXL4降低其表达,与对照组相比放射敏感性也降低,细胞凋亡比例下降7.07%( P<0.05)。结论 miR⁃193a⁃3p可能通过调控基因LOXL4促进食管癌细胞放射耐受性。%Objective To investigate the role of miR⁃193a⁃3p in the radioresistance of esophageal squamous cell carcinoma ( ESCC) . Methods MTT assay was used to identify the cell lines with the highest radiosensitivity and radioresistance in four esophageal cancer cell lines exposed to irradiation of 6 MV X⁃ray. Stem⁃loop quantitative real⁃time PCR was used to measure the expression levels of miR⁃193a⁃3p, miR⁃155, and miR⁃22⁃3P in the two cell lines. Further studies were performed on miR⁃193a⁃3p because of the substantial difference in its expression between

  15. Fermion Determinants

    OpenAIRE

    Fry, M. P.

    2001-01-01

    The current status of bounds on and limits of fermion determinants in two, three and four dimensions in QED and QCD is reviewed. A new lower bound on the two-dimensional QED determinant is derived. An outline of the demonstration of the continuity of this determinant at zero mass when the background magnetic field flux is zero is also given.

  16. Radiosensitization effect of cyclooxygenase-2 inhibitor NS398 on radioresistant esophageal cancer cell xenografts in nude mice%NS398对放射抗拒食管癌裸鼠移植瘤的放射增敏作用

    Institute of Scientific and Technical Information of China (English)

    车少敏; 张晓智; 陈鑫; 杨蕴一; 惠蓓娜

    2012-01-01

    Objective To investigate the radiosensitization effect of cyclooxygenase-2 inhibitor NS398 on radioresistant esophageal cancer cell xenografts in nude mice. Methods The model of xenograft tumor was established by subcutaneous inoculation of cell suspensions into the nude mice. We compared the tumorigenetic ability between esophageal EcalO9 cells and EcalO9R 50 Gy cells (which received a total irradiation dose of 50 Gy). The EcalO9R 50 Gy cell-bearing nude mice were divided randomly into 4 groups: NS398 treatment group, radiation group, NS398+radiation group and the control group. The volume and weight change of tumors were recorded during the 14 days of intervention. The tumor inhibition rate and radiosensitization ratio (E/O) were calculated. Results Ecal09R 50 Gy cells displayed 40 times higher tumorigenetic ability than EcalO9 cells in vivo. The treatment of NS398 plus radiation could significantly inhibit the growth of Ecal09R 50 Gy cell nude xenografts, particularly with the most obvious decrease of tumor volume and weight (P<0.05). The E/O of 1.5 mg/kg NS398 was 1.61 O1.4). Conclusion NS398 could enhance the radiosensitivity of radioresistant Ecal09R 50 Gy cells in vivo, and more in-depth signal conduction mechanisms need further study.%目的 研究COX-2抑制剂NS398对放射抗拒食管癌细胞裸鼠移植瘤的放射增敏作用.方法 采用食管癌细胞悬液裸鼠皮下接种法建立裸鼠移植瘤模型,比较食管Eca109细胞和放射抗拒Eca109R 50 Gy细胞(接受总剂量50 Gy照射)的致瘤能力.选取接种Eca109R 50 Gy细胞荷瘤裸鼠,随机分为NS398组、放射组、NS398+放射组和对照组.在干预的14d中记录移植瘤体积、重量,计算各组肿瘤抑制率和NS398的放射增敏比值(E/O).结果 Eca109R 50 Gy细胞比Eca109细胞裸鼠体内致瘤能力高出40倍.NS398+放射治疗能显著抑制裸鼠移植瘤的生长,体积缩小和瘤重减轻最为明显(P<0.05).1.5 mg/kg NS398的放射增敏比值E/O=1.61(>1

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-01-01

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

  18. Sex determination

    OpenAIRE

    McCullagh, W. McK. H.

    2013-01-01

    How the sex of offspring is determined has puzzled philosophers and scientists for millennia. Modern science has identified both genetic and environmental factors, but the question is still not yet fully answered.

  19. 2. Determinants

    African Journals Online (AJOL)

    Sitwala

    ... P.O Box 50110, Lusaka. National Food and Nutrition Commission, Ministry of Health, Lusaka ... malnourished case of admissions among HIV infected children and were .... However, service factors emerged as important determinants during.

  20. Comparison of protein patterns of xrs-5, a radiosensitive Chinese hamster ovary cell line, and CHO-K1, its radioresistant parent, using two-dimensional gel-electrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, J.M. (Miami Univ., Oxford, OH (USA). Dept. of Zoology)

    1991-01-01

    X-ray sensitive strains of Chinese hamster ovary cell lines have been used to analyze radiation repair mechanisms. One cell line, xrs-5, has been shown to be very sensitive to ionizing radiation and radical forming chemical mutagens. This sensitivity is thought to be a result a mutation in the DNA double strand break (DSB) repair mechanism, and its characterization has been a goal of several repair mechanism studies. Using two-dimensional gel electrophoresis, we have detected a protein (MW approximately 55KD) in the DNA/Nuclear Matrix (nucleoid) cell fraction of CHO-Kl cells that is absent in the nucleoid fraction of xrs-5. This protein is present, however, in both CHO-Kl and xrs-5 whole cell protein maps. To determine whether the 55KD protein is responsible for the radiosensitive and defective DSB repair phenotype of xrs-5 cells, studies are now underway to analyze revertants of xrs-5 that are proficient in DSB repair. Furthermore, an effort to sequence the protein in question is planned. 23 refs., 2 figs.

  1. 耐辐射球菌pprI基因真核表达载体的构建及其抗辐射作用%Construction of eukaryotic expression vector carrying pprI gene of Deinococcus radiodurans and its radioresistant effect

    Institute of Scientific and Technical Information of China (English)

    文玲; 施怡; 任丽丽; 丛瑛; 杨占山

    2014-01-01

    目的 研究耐辐射球菌pprI原核基因的真核表达载体的构建及其转染对离体真核细胞急性放射损伤的防护作用.方法 应用DNA重组技术构建pEGFP-c1-pprI质粒;采用脂质体转染技术分别将空载体质粒pEGFP-c1和重组质粒pEGFP-c1-pprI转入人肺上皮细胞系Beas-2B细胞,筛选稳定转染细胞系;应用集落形成实验检测受照转染细胞的生存能力;流式细胞仪检测细胞周期和凋亡率的变化;荧光显微镜观察受照细胞ROS荧光强度;免疫荧光实验观察受照细胞不同时间γ-H2AX焦点数目.结果 成功地构建了pprI原核基因的真核表达载体,并在Beas-2B细胞中表达了PprI融合蛋白,建立了稳定转染细胞系.与空白对照组和空载体组相比,细胞克隆生存曲线显示转染了pprI基因的Beas-2B细胞经不同剂量辐射,其存活分数SF增加,该曲线参数D0、Dq、N增高;转染了pprI基因的Beas-2B细胞受照后的ROS的荧光强度和不同时间(1、2、4 h) γ-H2AX的焦点数均显著减低(F=16.73、19.47、6.94,P<0.05);此外,该细胞G2期阻滞(F=139.73、237.92,P<0.05)和凋亡率显著减低(F=626.02、2 052,P<0.05).结论 耐辐射球菌pprI原核基因可在离体真核细胞中稳定表达,并且显著提高受照真核细胞的辐射抗性.%Objective To construct the eukaryotic expression vector of pprI gene from Deinococcus radiodurans R1 and investigate its radioresistant effects in eukaryotic cells.Methods A recombinant vector pEGFP-c1-pprI was constructed by DNA recombinant technique.The empty vector pEGFP-c1 and the pEGFP-c1-pprI were transferred into human lung epithelial cells Beas-2B by LipofectamineTM 2000,respectively.Then the infected cells were screened in order to develop a cell line with stable expression of pprI gene.Cell survival rate was tested by clone-forming assay.Cell cycle distribution and apoptosis were detected by a flow cytometry.The fluorescence intensity of reactive oxygen species (ROS

  2. Construction and validation of a dose-response curve using the comet assay to determine human radiosensitivity to ionizing radiation.

    Science.gov (United States)

    Güerci, A; Zúñiga, L; Marcos, R

    2011-01-01

    Individual radiosensitivity is an individual characteristic associated with an increased reaction to ionizing radiation. The purpose of our work is to establish a dose-response curve useful to classify individuals as radiosensitive or radioresistant. Thus, a dose-response curve was constructed by measuring in vitro responses to increasing doses (0 to 8 Gy) of gamma radiation in the comet assay. The obtained curve fit well with a linear equation in the range of 0 to 8 Gy. The overall dose-response curve was constructed for percent DNA in tail, as a measure of the genetic damage induced by irradiation. To probe the goodness of the constructed curve, a validation study was carried out with whole blood from two donors in a blind study. Results show that, for the two applied doses (2 and 6 Gy), the obtained values fit well inside the interval of confidence of the curve. In conclusion, our results demonstrate the usefulness of the comet assay in determining individual responses to defined doses of gamma radiation. The standard dose-response curve constructed may be used to detect individuals departing from reference values.

  3. RADIORESISTANCE OF THE TUMOR AND ITS SOLUTIONS (LITERATURE REVIEW

    Directory of Open Access Journals (Sweden)

    Yu. A. Barsukov

    2015-01-01

    Full Text Available Presented article is a review of domestic and foreign literature on the application of radiomodifying drugs with electron-affinic properties (metronidazole and its derivatives with the aim of increasing the effectiveness of radiation therapy. The mechanism of action and properties of the electron-affinic drugs of is described. Special attention is paid to the creation of a new medicinal form of metronidazole with the hydrogel-based biopolymer and its inclusion in combined treatment of resectable and locally advanced rectal cancer.

  4. Review of anticancer and antioxidant activities of radioresistant ...

    African Journals Online (AJOL)

    Prof. Ogunji

    process counts on the economic base of the biotechnological industries and their ... composed of amino acids, betain, sugar and heteroside derivatives (Lentzen et al., 2006). .... This bacterium is exceptionally resistant to DNA-damaging agents, such as .... will prove a support to our biological system to balance metabolism.

  5. Influencing upon Mammalian Radioresistance with Biologically Active Drug Respistim Plus

    Science.gov (United States)

    2009-10-01

    in the structure and function of DNA, proteins, cell death, mutations [1, 10]. At the heart of these processes are generated free radicals. Oxidative...changes of functional tissues: spleen, liver, bone marrow. Changes in the relative weights are clearly in the spleen and thymus. Spleen is important...Jackson W.E., Grace M.B., Prasanna P.G.S., Sandgren D.J., Ledney G.D. : “ Amylase and blood cell-count-hematological radiation-injury biomarkers in a

  6. Cyclic nucleotides and radioresistance. Report 2. Effect of cyclic nucleotides on mammalian radioresistance and tissular oxygen tension. [X rays; mice

    Energy Technology Data Exchange (ETDEWEB)

    Kulinskii, V.I.

    1978-01-01

    In experiments on mice, 3',5'-AMP, N/sup 6/,O/sup 2/-dibutyryl-3',5'-AMP (DB), 2',3'-AMP, theophylline, papaverine, imidazole, and nicotinate presented neither a sensitizing or radioprotective (RPE) effect. However, preadministration of ..beta..-adrenolytic agents revealed a moderate RPE in DB. Probably, along with the RPE, there is an antiprotective component in the action of cyclic nucleotides (CN), which is expressed via ..beta..-receptors. The absence of RPE in 3',5'-AMP, 2',3'-AMP, DB, theophylline, and phentolamine is combined with decline of tissular pO/sub 2/. The significance of this phenomenon is discussed.

  7. 一株新的耐辐射菌Deinococcus guangxiensis sp.nov.的分离鉴定及耐辐射特性分析%Isolation and identification of a new radiation-resistant bacterium Deinococcus guangxiensis sp.nov. and analysis of its radioresistant character

    Institute of Scientific and Technical Information of China (English)

    孙继华; 申佩弘; 晁红军; 武波

    2009-01-01

    [目的]从广西大学辐射中心辐射源附近被常年辐射的水样中分离并鉴定出新的耐辐射菌株,并对其耐辐射特性进行研究.[方法]通过GBM培养基分离培养得到一株新的耐辐射菌株,命名为WGR700T.应用生理生化试验,脂肪酸含量,(G+C)mol%含量测定以及16S rRNA序列同源性分析等方法对菌株进行鉴定,同时对WGRT00T的耐辐射特性进行分析.[结果]菌株WGR700T为革兰氏阴性,杆状,没有鞭毛,不能运动,厌氧并能产生红色素.最佳生长温度和PH分别为37~C和pH7.0,主要的呼吸醌是MK-8,细胞壁内还有鸟氨酸,主要脂肪酸为16:lω7c,16:0,15:lω6c,iso.15:0和iso-17:0.G+C含量为64.7mol%.菌株WGR700T具有很强的uV(>728 J/m2)和电离辐射抗性(Dm=9.8 kGy).菌株WGR700T和奇异球菌属(Deinococcus)内其它菌种16S rRNA有很高的相似性(87.1-95.6%).[结论]根据16S rRNA及生理生化特征区别,菌株WGR700T应是奇异球菌属的一个新种,命名为Deinococcus guangxiensis sp.nov.模式菌株为WGR700T(=CGMCCI.7045T:CICC 10360T=JCM 15082T).%[Objective] To isolate and identify a new ionizing-radiation resistant strain capable of surviving under highly ionizing radiation conditions as UV and gamol/La radiation and to characterize its radioresistant properties. [Methods] The isolates were sampled from Radiation Centre of Guangxi University, Nanning, China, and the medium used for isolation and cultivation of the bacterium was General Bacterial Medium (GBM). The new ionizing-radiation resistant strain WGR700T was identified by its morphology, biochemical and physiological characteristics, fatty acids, G+ C content of DNA, UV and gamol/La radiation resistance and 16S rRNA gene sequence homology. [Results] The strain WGR700T is of rod-shape, Gram-negative, non- spore-forming, non motile, aerobic and red-pigmented. The optimum temperature and pH for strain WGR700T growth is 37℃ and pH7.0, respectively. The predominant respiratory quinone is MK-8

  8. Genomics of sex determination.

    Science.gov (United States)

    Zhang, Jisen; Boualem, Adnane; Bendahmane, Abdelhafid; Ming, Ray

    2014-04-01

    Sex determination is a major switch in the evolutionary history of angiosperm, resulting 11% monoecious and dioecious species. The genomic sequences of papaya sex chromosomes unveiled the molecular basis of recombination suppression in the sex determination region, and candidate genes for sex determination. Identification and analyses of sex determination genes in cucurbits and maize demonstrated conservation of sex determination mechanism in one lineage and divergence between the two systems. Epigenetic control and hormonal influence of sex determination were elucidated in both plants and animals. Intensive investigation of potential sex determination genes in model species will improve our understanding of sex determination gene network. Such network will in turn accelerate the identification of sex determination genes in dioecious species with sex chromosomes, which are burdensome due to no recombination in sex determining regions. The sex determination genes in dioecious species are crucial for understanding the origin of dioecy and sex chromosomes, particularly in their early stage of evolution.

  9. Recurrence Relations and Determinants

    CERN Document Server

    Janjic, Milan

    2011-01-01

    We examine relationships between two minors of order n of some matrices of n rows and n+r columns. This is done through a class of determinants, here called $n$-determinants, the investigation of which is our objective. We prove that 1-determinants are the upper Hessenberg determinants. In particular, we state several 1-determinants each of which equals a Fibonacci number. We also derive relationships among terms of sequences defined by the same recurrence equation independently of the initial conditions. A result generalizing the formula for the product of two determinants is obtained. Finally, we prove that the Schur functions may be expressed as $n$-determinants.

  10. SIS - Status Determination

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Status Determination dataset within the Species Information System (SIS) contains information related to overfishing, overfished, and approaching overfished...

  11. Standardization of hormone determinations.

    Science.gov (United States)

    Stenman, Ulf-Håkan

    2013-12-01

    Standardization of hormone determinations is important because it simplifies interpretation of results and facilitates the use of common reference values for different assays. Progress in standardization has been achieved through the introduction of more homogeneous hormone standards for peptide and protein hormones. However, many automated methods for determinations of steroid hormones do not provide satisfactory result. Isotope dilution-mass spectrometry (ID-MS) has been used to establish reference methods for steroid hormone determinations and is now increasingly used for routine determinations of steroids and other low molecular weight compounds. Reference methods for protein hormones based on MS are being developed and these promise to improve standardization.

  12. Determinants of State Aid

    NARCIS (Netherlands)

    Buiren, K.; Brouwer, E.

    2010-01-01

    From economic theory we derive a set of hypotheses on the determination of state aid. Econometric analysis on EU state aid panel data is carried out to test whether the determinants we expect on the basis of theory, correspond to the occurrence of state aid in practice in the EU. We find that politi

  13. Plant Sex Determination.

    Science.gov (United States)

    Pannell, John R

    2017-03-06

    Sex determination is as important for the fitness of plants as it is for animals, but its mechanisms appear to vary much more among plants than among animals, and the expression of gender in plants differs in important respects from that in most animals. In this Minireview, I provide an overview of the broad variety of ways in which plants determine sex. I suggest that several important peculiarities of plant sex determination can be understood by recognising that: plants show an alternation of generations between sporophytic and gametophytic phases (either of which may take control of sex determination); plants are modular in structure and lack a germ line (allowing for a quantitative expression of gender that is not common in animals); and separate sexes in plants have ultimately evolved from hermaphroditic ancestors. Most theorising about sex determination in plants has focused on dioecious species, but we have much to learn from monecious or hermaphroditic species, where sex is determined at the level of modules, tissues or cells. Because of the fundamental modularity of plant development and potentially important evolutionary links between monoecy and dioecy, it may be useful to relax the distinction often made between 'developmental sex determination' (which underpins the development of male versus female flowers in monoecious species) and 'genetic sex determination' (which underpins the separation of males and females in dioecious species, often mediated by a genetic polymorphism and sex chromosomes). I also argue for relaxing the distinction between sex determination involving a genetic polymorphism and that involving responses to environmental or hormonal cues, because non-genetic cues might easily be converted into genetic switches.

  14. Airborne geoid determination

    DEFF Research Database (Denmark)

    Forsberg, René; Olesen, Arne Vestergaard; Bastos, L.

    2000-01-01

    Airborne geoid mapping techniques may provide the opportunity to improve the geoid over vast areas of the Earth, such as polar areas, tropical jungles and mountainous areas, and provide an accurate "seam-less" geoid model across most coastal regions. Determination of the geoid by airborne methods......-suited for geoid determination, with high-frequency survey and downward continuation noise being offset by the low-pass gravity to geoid filtering operation. In the paper the basic principles of airborne geoid determination are outlined, and examples of results of recent airborne gravity and geoid surveys...

  15. Determinants of Actor Rationality

    DEFF Research Database (Denmark)

    Ellegaard, Chris

    Industrial companies must exercise influence on their suppliers (or supplier actors). Actor rationality is a central theme connected to this management task. In this article, relevant literature is studied with the purpose of shedding light on determinants of actor rationality. Two buyer......-supplier relations are investigated in a multiple case study, leading to the proposal of various additional factors that determine and shape actor rationality. Moreover a conceptual model of rationality determinants in the buyer-supplier relation is proposed, a model that may help supply managers analyse...

  16. Attitude measurements and determination

    Science.gov (United States)

    Foliard, J.

    Satellite attitude determination using an inertial reference system is explained. The utility of being able to determine attitude is outlined. Construction of an attitude matrix from the Euler and Cardan angles of the satellite-Earth system is illustrated. Static and dynamic analysis methods are shown. The sensors employed when using the Sun, Earth's magnetic field, the Earth, and the stars as reference direction are described.

  17. Brain Death Determination.

    Science.gov (United States)

    Spinello, Irene M

    2015-09-01

    In the United States, each year 1% to 2% of deaths are brain deaths. Considerable variation in the practice of determining brain death still remains, despite the publication of practice parameters in 1995 and an evidence-based guideline update in 2010. This review is intended to give bedside clinicians an overview of definition, the causes and pitfalls of misdiagnosing brain death, and a focus on the specifics of the brain death determination process.

  18. Determining postural stability

    Science.gov (United States)

    Lieberman, Erez (Inventor); Forth, Katharine E. (Inventor); Paloski, William H. (Inventor)

    2011-01-01

    A method for determining postural stability of a person can include acquiring a plurality of pressure data points over a period of time from at least one pressure sensor. The method can also include the step of identifying a postural state for each pressure data point to generate a plurality of postural states. The method can include the step of determining a postural state of the person at a point in time based on at least the plurality of postural states.

  19. Protein Nitrogen Determination

    Science.gov (United States)

    Nielsen, S. Suzanne

    The protein content of foods can be determined by numerous methods. The Kjeldahl method and the nitrogen combustion (Dumas) method for protein analysis are based on nitrogen determination. Both methods are official for the purposes of nutrition labeling of foods. While the Kjeldahl method has been used widely for over a hundred years, the recent availability of automated instrumentation for the Dumas method in many cases is replacing use of the Kjeldahl method.

  20. ITAR: A modified TAR method to determine depth dose distribution for an ophthalmic device that performs kilovoltage x-ray pencil-beam stereotaxy

    Energy Technology Data Exchange (ETDEWEB)

    Hanlon, Justin, E-mail: jhanlon@orayainc.com; Chell, Erik; Firpo, Michael; Koruga, Igor [Oraya Therapeutics, Inc., Newark, California 94560 (United States)

    2014-02-15

    Purpose: New technology has been developed to treat age-related macular degeneration (AMD) using 100 kVp pencil-beams that enter the patient through the radio-resistant sclera with a depth of interest between 1.6 and 2.6 cm. Measurement of reference and relative dose in a kilovoltage x-ray beam with a 0.42 cm diameter field size and a 15 cm source to axis distance (SAD) is a challenge that is not fully addressed in current guidelines to medical physicists. AAPM's TG-61 gives dosimetry recommendations for low and medium energy x-rays, but not all of them are feasible to follow for this modality. Methods: An investigation was conducted to select appropriate equipment for the application. PTW's Type 34013 Soft X-Ray Chamber (Freiburg, Germany) and CIRS's Plastic Water LR (Norfolk, VA) were found to be the best available options. Attenuation curves were measured with minimal scatter contribution and thus called Low Scatter Tissue Air Ratio (LSTAR). A scatter conversion coefficient (C{sub scat}) was derived through Monte Carlo radiation transport simulation using MCNPX (LANL, Los Alamos, NM) to quantify the difference between a traditional TAR curve and the LSTAR curve. A material conversion coefficient (C{sub mat}) was determined through experimentation to evaluate the difference in attenuation properties between water and Plastic Water LR. Validity of performing direct dosimetry measurements with a source to detector distance other than the treatment distance, and therefore a different field size due to a fixed collimator, was explored. A method—Integrated Tissue Air Ratio (ITAR)—has been developed that isolates each of the three main radiological effects (distance from source, attenuation, and scatter) during measurement, and integrates them to determine the dose rate to the macula during treatment. Results: LSTAR curves were determined to be field size independent within the range explored, indicating that direct dosimetry measurements may be

  1. Spacecraft Attitude Determination

    DEFF Research Database (Denmark)

    Bak, Thomas

    This thesis describes the development of an attitude determination system for spacecraft based only on magnetic field measurements. The need for such system is motivated by the increased demands for inexpensive, lightweight solutions for small spacecraft. These spacecraft demands full attitude...... determination based on simple, reliable sensors. Meeting these objectives with a single vector magnetometer is difficult and requires temporal fusion of data in order to avoid local observability problems. In order to guaranteed globally nonsingular solutions, quaternions are generally the preferred attitude...... is a detailed study of the influence of approximations in the modeling of the system. The quantitative effects of errors in the process and noise statistics are discussed in detail. The third contribution is the introduction of these methods to the attitude determination on-board the Ørsted satellite...

  2. Determinants of marriage dissolution

    Science.gov (United States)

    Rahim, Mohd Amirul Rafiq Abu; Shafie, Siti Aishah Mohd; Hadi, Az'lina Abdul; Razali, Nornadiah Mohd; Azid @ Maarof, Nur Niswah Naslina

    2015-10-01

    Nowadays, the number of divorce cases among Muslim couples is very worrisome whereby the total cases reported in 2013 increased by half of the total cases reported in the previous year. The questions on the true key factors of dissolution of marriage continue to arise. Thus, the objective of this study is to reveal the factors that contribute to the dissolution of marriage. A total of 181 cases and ten potential determinants were included in this study. The potential determinants considered were age at marriage of husband and wife, educational level of husband and wife, employment status of husband and wife, income of husband and wife, the number of children and the presence at a counseling session. Logistic regression analysis was used to analyze the data. The findings revealed that four determinants, namely the income of husband and wife, number of children and the presence at a counselling session were significant in predicting the likelihood of divorce among Muslim couples.

  3. Inertinite fusibility determination

    Energy Technology Data Exchange (ETDEWEB)

    Philip Bennett; Daniel Rigg [ALS-ACIRL (Australia)

    2008-08-15

    The project was to develop a simple tool todetermine the fusibility of inertinite in Australian coals. The first step in determining the fusible inertinite component is to convert the petrographic analysis to a mass basis. Using mineralogical data determined by QEMSCAN on selected float sink samples of the each coal arelationship between the ash with minerals wasdetermined.. The calculated densities of vitrinite and inertinite for eight coals tested showed similar relationships with rank (carbon %daf) to those given by van Krevelen. It is recommended the relationships derived by curve fit to the data of van Krevelen be used to determine the density of the maceral groups. Step two in determining the fusible inertinite is to estimate the loss of volatile components during carbonisation. Degassing experiments were conducted in small cast iron 'mini pots' to determine the yield of coke and to prepare coke samples for coke microtexture analysis. The mini pot coke tests shows that more of the inertinite can be fused when in close proximity to vitrinite. This project wasextended to include the examination of the data from ACARP project C12057 in which twelve coals were coked in a pilot scale oven and coke microtexture analysis was conducted on the cokes. There is good agreement between the calculated coke yields and the actual pilot scale coke yield using the coke yield determinations approaches given above. The predicted coke yield based on the pilot scale correlation and the measured volatile matter is very good. All pilot oven cokes show that more than 50% of the semifusinite is fusible with some having more than 90% of the semifusinite fusible. Several different methods for the prediction of fused carbon in coke were evaluated using the pilot scale data. The minerals in the coal seem to have a slight influence on fused carbon when dispersed evenly through the coal. This influence is not seen in the pilot scale tests.

  4. Sex determination in amphibians.

    Science.gov (United States)

    Nakamura, Masahisa

    2009-05-01

    The heterogametic sex is male in all mammals, whereas it is female in almost all birds. By contrast, there are two heterogametic types (XX/XY and ZZ/ZW) for genetic sex determination in amphibians. Though the original heterogametic sex was female in amphibians, the two heterogametic types were probably interchangeable, suggesting that sex chromosomes evolved several times in this lineage. Indeed, the frog Rana rugosa has the XX/XY and ZZ/ZW sex-determining systems within a single species, depending on the local population in Japan. The XY and ZW geographic forms with differentiated sex chromosomes probably have a common origin as undifferentiated sex chromosomes resulted from the hybridization between the primary populations of West Japan and Kanto forms. It is clear that the sex chromosomes are still undergoing evolution in this species group. Regardless of the presence of a sex-determining gene in amphibians, the gonadal sex of some species can be changed by sex steroids. Namely, sex steroids can induce the sex reversal, with estrogens inducing the male-to-female sex reversal, whereas androgens have the opposite effect. In R. rugosa, gonadal activity of CYP19 (P450 aromatase) is correlated with the feminization of gonads. Of particular interest is that high levels of CYP19 expression are observed in indifferent gonads at time before sex determination. Increases in the expression of CYP19 in female gonads and CYP17 (P450 17alpha-hydroxylase/C17-20 lyase) in male gonads suggest that the former plays an important role in phenotypic female determination, whereas the latter is needed for male determination. Thus, steroids could be the key factor for sex determination in R. rugosa. In addition to the role of sex steroids in gonadal sex determination in this species, Foxl2 and Sox3 are capable of promoting CYP19 expression. Since both the genes are autosomal, another factor up-regulating CYP19 expression must be recruited. The factor, which may be located on the X or W

  5. Ion Mass Determination

    DEFF Research Database (Denmark)

    2010-01-01

    An apparatus (100) is described for determining the mass of ions, the apparatus configured to hold a plasma (101 ) having a plasma potential. The apparatus (100) comprises an electrode (102) having a surface extending in a surface plane and an insulator (104) interfacing with the electrode (102...

  6. SPECTROPHOTOMETRIC DETERMINATION OF PIZOTEFIN ...

    African Journals Online (AJOL)

    B. S. Chandravanshi

    common additives by applying the standard addition technique. The developed methods have been validated statistically for ... Several analytical methods have been reported for the determination of PZT in pure drug, ... (Kontron Instruments, Munchen, Germany) with a scanning speed of 200 nm/min and a band width of 2.0 ...

  7. Ultrasonic Determination Of Recrystallization

    Science.gov (United States)

    Generazio, Edward R.

    1988-01-01

    State of recrystallization identified. Measurement of ultrasonic attenuation shows promise as means of detecting recrystallization in metal. Technique applicable to real-time acoustic monitoring of thermomechanical treatments. Starting with work-hardened material, one ultrasonically determines effect of annealing, using correlation between ultrasonic attenuation and temperature.

  8. Determinants of Disciplinary Discontent.

    Science.gov (United States)

    Hargens, Lowell L.; Kelly-Wilson, Lisa

    1994-01-01

    Data from the 1984 Carnegie survey of faculty at U.S. universities show substantial disciplinary variation in pessimism that one's field is stagnant. Field-level variations in both anomie and consensus exert strong effects on average levels of scholarly pessimism within fields and are stronger determinants of scholarly pessimism than individual…

  9. Determining TOC in Waters

    Science.gov (United States)

    Kehoe, Thomas J.

    1977-01-01

    The instrumental method for detecting total organic carbon (TOC) in water samples is detailed. The method's limitations are discussed and certain precautions that must be taken are emphasized. The subject of TOC versus COD and BOD is investigated and TOC is determined to be a valid indication of biological demand. (BT)

  10. Colorimetric Determination of Hydroxylurea

    Institute of Scientific and Technical Information of China (English)

    ZHANGYu; ZHUZhao-wu

    2003-01-01

    Hydroxyurea is able to form colored complex with amminoprusside (TPF) which has strong absorption at 500 nm suitable for the colorimetric determination of hydroxyurea. Present paper studies the effects of temperature, quantity of buffer solution, quantity of TPF used and so on, on the complex absorption.

  11. Determination of Fat Content

    Science.gov (United States)

    Carpenter, Charles

    The term "lipid" refers to a group of compounds that are sparingly soluble in water, but show variable solubility in a number of organic solvents (e.g., ethyl ether, petroleum ether, acetone, ethanol, methanol, benzene). The lipid content of a food determined by extraction with one solvent may be quite different from the lipid content as determined with another solvent of different polarity. Fat content is determined often by solvent extraction methods (e.g., Soxhlet, Goldfish, Mojonnier), but it also can be determined by nonsolvent wet extraction methods (e.g., Babcock, Gerber), and by instrumental methods that rely on the physical and chemical properties of lipids (e.g., infrared, density, X-ray absorption). The method of choice depends on a variety of factors, including the nature of the sample (e.g., dry versus moist), the purpose of the analysis (e.g., official nutrition labeling or rapid quality control), and instrumentation available (e.g., Babcock uses simple glassware and equipment; infrared requires an expensive instrument).

  12. Determinants of Disciplinary Discontent.

    Science.gov (United States)

    Hargens, Lowell L.; Kelly-Wilson, Lisa

    1994-01-01

    Data from the 1984 Carnegie survey of faculty at U.S. universities show substantial disciplinary variation in pessimism that one's field is stagnant. Field-level variations in both anomie and consensus exert strong effects on average levels of scholarly pessimism within fields and are stronger determinants of scholarly pessimism than individual…

  13. Gender determination in populus

    Energy Technology Data Exchange (ETDEWEB)

    McLetchie, D.N. [Univ. of Kentucky, Lexington, KY (United States). Dept. of Biological Sciences; Tuskan, G.A. [Oak Ridge National Lab., TN (United States)

    1994-12-31

    Gender, the expression of maleness or femaleness, in dioecious plants has been associated with changes in morphology, physiology, ecological position, and commercial importance of several species, including members of the Salicaceae family. Various mechanisms have been proposed to explain the expression of gender in Salicaceae, including sex chromosomes, simple Mendelian genes, quantitative genes, environment, and genotype-by-environment interactions. Published reports would favor a genetic basis for gender. The objective of this study was to identify molecular markers associated with gender in a segregating family of hybrid poplars. Bulked segregant analysis and chi-squared analysis were used to test for the occurrence of sex chromosomes, individual loci, and chromosome ratios (i.e., ploidy levels) as the mechanisms for gender determination. Examination of 2488 PCR based RAPD markers from 1219 primers revealed nine polymorphic bands between male and female bulked samples. However, linkage analysis indicated that none of these markers were significantly associated with gender. Chisquared results for difference in male-to-female ratios between diploid and triploid genotypes also revealed no significant differences. These findings suggest gender is not controlled via sex chromosomes, simple Mendelian loci or ratios of autosome to gender-determining loci. It is possible that gender is determined genetically by regions of the genome not sampled by the tested markers or by a complex of loci operating in an additive threshold manner or in an epistatic manner. It is also possible that gender is determined environmentally at an early zygote stage, canalizing gender expression.

  14. Determinants for gallstone formation

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Monsted; Sorensen, Lars Tue; Jørgensen, Torben

    2016-01-01

    associations were found for blood pressure, smoking, alcohol consumption, HDL cholesterol, or triglycerides in meta-analyses. Conclusions: Age, female sex, BMI, non-HDL cholesterol, and polyps are independent determinants for gallstone formation. Incident gallstones and the metabolic syndrome share common risk...

  15. Absolute Neutrino Mass Determination

    CERN Document Server

    Päs, H

    2001-01-01

    We discuss four approaches to the determination of absolute neutrino mass. These are the measurement of the zero-neutrino double beta decay rate, of the tritium decay end-point spectrum, of the cosmic ray spectrum above the GZK cutoff, and the cosmological measurement of the power spectrum governing the CMB and large scale structure. The first two approaches are sensitive to the mass eigenstates coupling to the electron neutrino, whereas the latter two are sensitive to the heavy component of the cosmic neutrino background. All mass eigenstates are related by the $\\Delta m^2$'s inferred from neutrino oscillation data. Consequently, the potential for absolute mass determination of each of the four approaches is correlated with the other three, in ways that we point out.

  16. Somatic sex determination.

    Science.gov (United States)

    Zarkower, David

    2006-02-10

    C. elegans occurs in two natural sexes, the XX hermaphrodite and the XO male, which differ extensively in anatomy, physiology, and behavior. All somatic differences between the sexes result from the differential activity of a "global" sex determination regulatory pathway. This pathway also controls X chromosome dosage compensation, which is coordinated with sex determination by the action of the three SDC proteins. The SDC proteins control somatic and germline sex by transcriptional repression of the her-1 gene. HER-1 is a secreted protein that controls a regulatory module consisting of a transmembrane receptor, TRA-2, three intracellular FEM proteins, and the zinc finger transcription factor TRA-1. The molecular workings of this regulatory module are still being elucidated. Similarity of TRA-2 to patched receptors and of TRA-1 to GLI proteins suggests that parts of the global pathway originally derived from a Hedgehog signaling pathway. TRA-1 controls all aspects of somatic sexual differentiation, presumably by regulating a variety of tissue- and cell-specific downstream targets, including the cell death regulator EGL-1 and the male sexual regulator MAB-3. Sex determination evolves rapidly, and conservation of sexual regulators between phyla has been elusive. An apparent exception involves DM domain proteins, including MAB-3, which control sexual differentiation in nematodes, arthropods, and vertebrates. Important issues needing more study include the detailed molecular mechanisms of the global pathway, the identities of additional sexual regulators acting in the global pathway and downstream of TRA-1, and the evolutionary history of the sex determination pathway. Recently developed genetic and genomic technologies and comparative studies in divergent species have begun to address these issues.

  17. What determines our behavior

    OpenAIRE

    Marko Radovan

    2001-01-01

    In article Ajzen-Fishbein's attitude-behavior model called 'Theory of reasoned action' and Albert Bandura's Model of reciprocal determinism are presented. Both models are a part of social-cognitive paradigm which characterizes behavior with evaluation of different goals. Ajzen and Fishbein (1973; 1980) proposed that specific behavior are predictable from specific behavioral intentions. These intentions are a function of two components: the attitude toward the act in question a...

  18. Alpha and Beta Determinations

    CERN Document Server

    Dunietz, Isard

    1999-01-01

    Because the Bd -> J/psi Ks asymmetry determines only sin(2 beta), a discrete ambiguity in the true value of beta remains. This note reviews how the ambiguity can be removed. Extractions of the CKM angle alpha are discussed next. Some of the methods require very large data samples and will not be feasible in the near future. In the near future, semi-inclusive CP-violating searches could be undertaken, which are reviewed last.

  19. What determines family structure?

    OpenAIRE

    Blau, David M.; van der Klaauw, Wilbert

    2010-01-01

    We estimate the effects of policy and labor market variables on the fertility, union formation and dissolution, type of union (cohabiting versus married), and partner choices of the NLSY79 cohort of women. These demographic behaviors interact to determine the family structure experienced by the children of these women: living with the biological mother and the married or cohabiting biological father, a married or cohabiting step father, or no man. We find that the average wage rates available...

  20. ECOLOGICAL BUILDING DESIGN DETERMINANTS

    Directory of Open Access Journals (Sweden)

    Ali Vakili-Ardebili

    2010-11-01

    Full Text Available The sustainable building design process is driven on the basis of a range of design eco-indicators. Consideration of a multitude of eco-determinants, such as environment, economy, resources, energy consumption and society values in addition to design characteristics and contexts, makes the process of ecological design even more complex. A large number of eco-drivers are extracted from the literature and current design practices. To gain a better insight on eco-design determinants, a survey focusing on the use of eco-design drivers has been conducted with various architects in the UK. The factor analysis method was used to remove redundant data from the survey. Through the factor analysis approach, 115 eco-determinants are grouped into six main clusters. This article presents the process, analysis and findings of this work. The extracted eco-indicators and their associated clusters can be used to improve the process of ecological building design. DOI: 10.3763/aedm.2008.0096 Source: Architectural Engineering and Design Management, Volume 6, Number 2, 2010 , pp. 111-131(21

  1. Gender determination using cheiloscopy

    Directory of Open Access Journals (Sweden)

    B N Padmavathi

    2013-01-01

    Full Text Available Background: Although lip prints have been used as an evidence for human identification in forensic science, there exists a doubt about its role in gender determination. Aims: The present study was designed for documenting common patterns, as well as their variation in the study population, with objective of evaluating uniqueness of the lip print pattern among the study population, as well as to evaluate the possibility of gender determination. Study Design: Two hundred and thirty five lip prints were collected from volunteers among out patients of Darshan Dental College and Hospital, as well as community dental care camps of rural areas around Udaipur. Materials and Methods: Lip prints were recorded with transparent overlay and transferred on to a bond paper. It was then photographed using a Canon EOS 55OD 16 mega pixel digital camera. Software Picasa 3.6 and Microsoft Picture Manager were used to digitally enhance the quality and magnify the image bearing the groove pattern. Lip prints were later analyzed. Statistical Analysis: Pearson chi square test was adopted for statistical analysis and probability (P value was calculated. Conclusion: In our study, none of the lip prints were identical, thus confirming the role of lip prints in individual identification. Dots, reticular and complex patterns were significant in gender determination.

  2. Serine/Threonine kinase MLK4 determines Mesenchymal Identity in Glioma Stem Cells in an NF-κB-dependent manner

    Science.gov (United States)

    Kim, Sung-Hak; Ezhilarasan, Ravesanker; Phillips, Emma; Gallego-Perez, Daniel; Sparks, Amanda; Taylor, David; Ladner, Katherine; Furuta, Takuya; Sabit, Hemragul; Chhipa, Rishi; Cho, Ju Hwan; Mohyeldin, Ahmed; Beck, Samuel; Kurozumi, Kazuhiko; Kuroiwa, Toshihiko; Iwata, Ryoichi; Asai, Akio; Kim, Jonghwan; Sulman, Erik P.; Cheng, Shiyuan; Lee, L.James; Nakada, Mitsutoshi; Guttridge, Denis; DasGupta, Biplab; Goidts, Violaine; Bhat, Krishna P.; Nakano, Ichiro

    2016-01-01

    SUMMARY Activation of NF-kB induces mesenchymal (MES) trans-differentiation and radio-resistance in glioma stem cells (GSCs), but molecular mechanisms for NF-kB activation in GSCs are currently unknown. Here we report that mixed lineage kinase 4 (MLK4) is overexpressed in MES but not proneural (PN) GSCs. Silencing MLK4 suppresses self-renewal, motility, tumorigenesis, and radio-resistance of MES GSCs via a loss of the MES signature. MLK4 binds and phosphorylates the NF-κB regulator IKKα, leading to activation of NF-κB signaling in GSCs. MLK4 expression is inversely correlated with patient prognosis in MES, but not PN high-grade gliomas. Collectively, our results uncover MLK4 as an upstream regulator of NF-kB signaling and a potential molecular target for the MES subtype of GBMs. PMID:26859459

  3. Spectrophotometric Determination of Ezetimibe

    Directory of Open Access Journals (Sweden)

    P. Baby Sudha Lakshmi

    2010-01-01

    Full Text Available Two simple, sensitive, selective and accurate spectro-photometric methods (Method A and Method B for the determination of eztimibe in bulk drug and pharmaceutical formulations (tablets have been described. Method A and B are based on the redox/complex formation reaction of drug with 1,10-phenanthroline and hexacyano-ferrate(III in presence of ferric chloride to form coloured chromogens exhibiting λmax at 510 and 740 nm respectively. The results of analysis for the two methods have been validated statistically and by recovery studies. The results are compared with those obtained using UV spectrophotometric method in alcohol at 231.7 nm.

  4. Determination of radar MTF

    Energy Technology Data Exchange (ETDEWEB)

    Chambers, D. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    The ultimate goal of the Current Meter Array (CMA) is to be able to compare the current patterns detected with the array with radar images of the water surface. The internal wave current patterns modulate the waves on the water surface giving a detectable modulation of the radar cross-section (RCS). The function relating the RCS modulations to the current patterns is the Modulation Transfer Function (MTF). By comparing radar images directly with co-located CMA measurements the MTF can be determined. In this talk radar images and CMA measurements from a recent experiment at Loch Linnhe, Scotland, will be used to make the first direct determination of MTF for an X and S band radar at low grazing angles. The technical problems associated with comparing radar images to CMA data will be explained and the solution method discussed. The results suggest the both current and strain rate contribute equally to the radar modulation for X band. For S band, the strain rate contributes more than the current. The magnitude of the MTF and the RCS modulations are consistent with previous estimates when the wind is blowing perpendicular to the radar look direction.

  5. Determinants of Discretionary Investments

    Directory of Open Access Journals (Sweden)

    K. S. Sujit

    2016-03-01

    Full Text Available Theoretical and empirical studies have focused on discretionary investments such as research and development (R&D and advertisement as value-creating activities. This empirical research article examines the determinants of the discretionary investment policy of food sector firms in India. The study aims to analyze the impact of financial policies and firm characteristics on the discretionary investment strategy of the food industry firms. The article uses the partial least squares structural equation modeling (PLS-SEM to understand the drivers of discretionary investment policy of food sector firms. The study finds that investment policy of firms is a major determinant of profitability of food sector firms. Higher investments in capital expenditures and working capital result in higher profitability. Management efficiency significantly influences firm profitability. The results suggest that riskier firms in food sector might focus on R&D investments as a strategy to generate more cash flows. Size of firm is negatively related to R&D intensity. Smaller firms in food sector tend to invest more in R&D. The study does not provide evidence to suggest that profitable firms invest more in R&D activities.

  6. Determination of Survivable Fires

    Science.gov (United States)

    Dietrich, D. L.; Niehaus, J. E.; Ruff, G. A.; Urban, D. L.; Takahashi, F.; Easton, J. W.; Abbott, A. A.; Graf, J. C.

    2012-01-01

    At NASA, there exists no standardized design or testing protocol for spacecraft fire suppression systems (either handheld or total flooding designs). An extinguisher's efficacy in safely suppressing any reasonable or conceivable fire is the primary benchmark. That concept, however, leads to the question of what a reasonable or conceivable fire is. While there exists the temptation to over-size' the fire extinguisher, weight and volume considerations on spacecraft will always (justifiably) push for the minimum size extinguisher required. This paper attempts to address the question of extinguisher size by examining how large a fire a crew member could successfully survive and extinguish in the confines of a spacecraft. The hazards to the crew and equipment during an accidental fire include excessive pressure rise resulting in a catastrophic rupture of the vehicle skin, excessive temperatures that burn or incapacitate the crew (due to hyperthermia), carbon dioxide build-up or other accumulation of other combustion products (e.g. carbon monoxide). Estimates of these quantities are determined as a function of fire size and mass of material burned. This then becomes the basis for determining the maximum size of a target fire for future fire extinguisher testing.

  7. Cheiloscopy for sex determination

    Directory of Open Access Journals (Sweden)

    Shailesh M Gondivkar

    2009-01-01

    Full Text Available Background: Identification of an individual is a pre-requisite for certification of death and for personal, social and legal reasons. The study of lip-prints (cheiloscopy was thought of as a method of identification of a person. It is safe to assume that cheiloscopy, in its present stage of development, has become a means of criminalistic identification dealing with lip-prints. Objective: The objective of the study was to check for any peculiar lip patterns in relation to the sex of the individual and determine the most common lip patterns in the Indian population. Materials and Methods: This study was conducted on 140 subjects, which included 70 males and 70 females, in the age group of 0-70 years. After applying lip stick evenly, the lip-print of each subject was obtained on a simple bond paper by researcher number 1. The lip-print was then analyzed and interpreted by researcher number 2 to determine the sex of individuals. Results: We found that 67 of the actual 70 lip-prints of females were correctly identified and 65 of the 70 males were correctly diagnosed as males. Type C (47.14% was the most commonly occurring trend in females whereas Type B (70% was the most commonly occurring trend in males. Conclusion: Along with other traditional methods, cheiloscopy can also serve as very important tool in the identification of a person based on the characteristic arrangement of lines appearing on the red part of the lips.

  8. Determinants of International Competiveness

    Directory of Open Access Journals (Sweden)

    Hojjat Mehdi

    2014-02-01

    Full Text Available International competitiveness is a main source of economic advancement which results in higher standards of living. This paper examines the determinants of international competitiveness as it defines international competitiveness and discusses two common conceptions that are required to achieve higher level of economic competitiveness: government policies and culture. It further explains a research methodology which is known as “Innovation Matrix”. Data is collected from two areas:  competitiveness and culture. After describing two sets of data, the researcher tests two hypotheses: (1 long-term economic growth is a function of government policies and (2 culture plays an insignificant role in gaining competitiveness and economic growth. In conclusion, the paper makes recommendations as how a country can improve its economic competitiveness.

  9. What determines our behavior

    Directory of Open Access Journals (Sweden)

    Marko Radovan

    2001-06-01

    Full Text Available In article Ajzen-Fishbein's attitude-behavior model called 'Theory of reasoned action' and Albert Bandura's Model of reciprocal determinism are presented. Both models are a part of social-cognitive paradigm which characterizes behavior with evaluation of different goals. Ajzen and Fishbein (1973; 1980 proposed that specific behavior are predictable from specific behavioral intentions. These intentions are a function of two components: the attitude toward the act in question and percieved normative expectations of reference group. On the other hand Bandura (1986; 1997 claims that person's motivation for a specific behavior and direction toward a specific social object respectively, reflects perception of his or hers self-efficacy beliefs. Some of the findings concerning the synthesis of the two models are also reviewed.

  10. FDI DETERMINANTS IN BRICS

    Directory of Open Access Journals (Sweden)

    Sebastian-Andrei LABES

    2015-08-01

    Full Text Available In the past two decades the volume of Foreign Direct Investments increased substantially becoming a phenomenon that characterizes the economic environment in the emerging markets. The aim of this working paper is to investigate the Foreign Direct Investments Inflows in the BRICS economies. The research study employs a Panel Data analysis on a sample of 5 countries, the BRICS economies Brazil, Russia, India, China and South Africa and a time series from 1992-2012. The variables taken in consideration are Trade Openness, GDP per capita, Population, Exchange Rate and Human Capital. Our results indicate that the most significant determinants of FDI Inflows are Trade Openness, GDP per capita and Exchange Rate. The value of this work is that it investigates the factors that contribute to the increase of FDI inflows towards the most important emerging economies in the world.

  11. Determinants of Network Outcomes

    DEFF Research Database (Denmark)

    Ysa, Tamyko; Sierra, Vicenta; Esteve, Marc

    2014-01-01

    networks. We go beyond current work by testing a path model for the determinants of network outcomes and considering the interactions between the constructs: management strategies, trust, complexity, and facilitative leadership. Our results suggest that management strategies have a strong effect on network......The literature on network management is extensive. However, it generally explores network structures, neglecting the impact of management strategies. In this article we assess the effect of management strategies on network outcomes, providing empirical evidence from 119 urban revitalization...... outcomes and that they enhance the level of trust. We also found that facilitative leadership has a positive impact on network management as well as on trust in the network. Our findings also show that complexity has a negative impact on trust. A key finding of our research is that managers may wield more...

  12. Orbit Determination Toolbox

    Science.gov (United States)

    Carpenter, James R.; Berry, Kevin; Gregpru. Late; Speckman, Keith; Hur-Diaz, Sun; Surka, Derek; Gaylor, Dave

    2010-01-01

    The Orbit Determination Toolbox is an orbit determination (OD) analysis tool based on MATLAB and Java that provides a flexible way to do early mission analysis. The toolbox is primarily intended for advanced mission analysis such as might be performed in concept exploration, proposal, early design phase, or rapid design center environments. The emphasis is on flexibility, but it has enough fidelity to produce credible results. Insight into all flight dynamics source code is provided. MATLAB is the primary user interface and is used for piecing together measurement and dynamic models. The Java Astrodynamics Toolbox is used as an engine for things that might be slow or inefficient in MATLAB, such as high-fidelity trajectory propagation, lunar and planetary ephemeris look-ups, precession, nutation, polar motion calculations, ephemeris file parsing, and the like. The primary analysis functions are sequential filter/smoother and batch least-squares commands that incorporate Monte-Carlo data simulation, linear covariance analysis, measurement processing, and plotting capabilities at the generic level. These functions have a user interface that is based on that of the MATLAB ODE suite. To perform a specific analysis, users write MATLAB functions that implement truth and design system models. The user provides his or her models as inputs to the filter commands. The software provides a capability to publish and subscribe to a software bus that is compliant with the NASA Goddard Mission Services Evolution Center (GMSEC) standards, to exchange data with other flight dynamics tools to simplify the flight dynamics design cycle. Using the publish and subscribe approach allows for analysts in a rapid design center environment to seamlessly incorporate changes in spacecraft and mission design into navigation analysis and vice versa.

  13. Determining Determiner Sequencing A Syntactic Analysis for English

    CERN Document Server

    Hockey, B A; Hockey, Beth Ann; Egedi, Dania

    1994-01-01

    Previous work on English determiners has primarily concentrated on their semantics or scoping properties rather than their complex ordering behavior. The little work that has been done on determiner ordering generally splits determiners into three subcategories. However, this small number of categories does not capture the finer distinctions necessary to correctly order determiners. This paper presents a syntactic account of determiner sequencing based on eight independently identified semantic features. Complex determiners, such as genitives, partitives, and determiner modifying adverbials, are also presented. This work has been implemented as part of XTAG, a wide-coverage grammar for English based in the Feature-Based, Lexicalized Tree Adjoining Grammar (FB-LTAG) formalism.

  14. Perceived positions determine crowding.

    Science.gov (United States)

    Maus, Gerrit W; Fischer, Jason; Whitney, David

    2011-01-01

    Crowding is a fundamental bottleneck in object recognition. In crowding, an object in the periphery becomes unrecognizable when surrounded by clutter or distractor objects. Crowding depends on the positions of target and distractors, both their eccentricity and their relative spacing. In all previous studies, position has been expressed in terms of retinal position. However, in a number of situations retinal and perceived positions can be dissociated. Does retinal or perceived position determine the magnitude of crowding? Here observers performed an orientation judgment on a target Gabor patch surrounded by distractors that drifted toward or away from the target, causing an illusory motion-induced position shift. Distractors in identical physical positions led to worse performance when they drifted towards the target (appearing closer) versus away from the target (appearing further). This difference in crowding corresponded to the difference in perceived positions. Further, the perceptual mislocalization was necessary for the change in crowding, and both the mislocalization and crowding scaled with drift speed. The results show that crowding occurs after perceived positions have been assigned by the visual system. Crowding does not operate in a purely retinal coordinate system; perceived positions need to be taken into account.

  15. Perceived positions determine crowding.

    Directory of Open Access Journals (Sweden)

    Gerrit W Maus

    Full Text Available Crowding is a fundamental bottleneck in object recognition. In crowding, an object in the periphery becomes unrecognizable when surrounded by clutter or distractor objects. Crowding depends on the positions of target and distractors, both their eccentricity and their relative spacing. In all previous studies, position has been expressed in terms of retinal position. However, in a number of situations retinal and perceived positions can be dissociated. Does retinal or perceived position determine the magnitude of crowding? Here observers performed an orientation judgment on a target Gabor patch surrounded by distractors that drifted toward or away from the target, causing an illusory motion-induced position shift. Distractors in identical physical positions led to worse performance when they drifted towards the target (appearing closer versus away from the target (appearing further. This difference in crowding corresponded to the difference in perceived positions. Further, the perceptual mislocalization was necessary for the change in crowding, and both the mislocalization and crowding scaled with drift speed. The results show that crowding occurs after perceived positions have been assigned by the visual system. Crowding does not operate in a purely retinal coordinate system; perceived positions need to be taken into account.

  16. Pediatric brain death determination.

    Science.gov (United States)

    Mathur, Mudit; Ashwal, Stephen

    2015-04-01

    Clinical guidelines for the determination of brain death in children were first published in 1987. These guidelines were revised in 2011 under the auspices of the Society of Critical Care Medicine, the American Academy of Pediatrics, and the Child Neurology Society, and provide the minimum standards that must be satisfied before brain death can be declared in infants and children. After achieving physiologic stability and exclusion of confounders, two examinations including apnea testing separated by an observation period (24 hours for term newborns up to 30 days of age, and 12 hours for infants and children from 31 days up to 18 years) are required to establish brain death. Apnea testing should demonstrate a final arterial PaCO2 20 mm Hg above the baseline and ≥ 60 mm Hg with no respiratory effort during the testing period. Ancillary studies (electroencephalogram and radionuclide cerebral blood flow) are not required to establish brain death and are not a substitute for the neurologic examination. The committee concluded that ancillary studies may be used (1) when components of the examination or apnea testing cannot be completed, (2) if uncertainty about components of the neurologic examination exists, (3) if a medication effect may be present, or (4) to reduce the interexamination observation period. When ancillary studies are used, a second clinical examination and apnea test should still be performed and components that can be completed must remain consistent with brain death.

  17. Age determination of raccoons

    Science.gov (United States)

    Grau, G.A.; Sanderson, G.C.; Rogers, J.P.

    1970-01-01

    Age criteria, based on 61 skulls and eye lenses from 103 known-age captives, are described for separating raccoons (Procyon lotor) into eight age-classes as follows: young-of-the-year, 1, 2, 3, 4, 5, 6-7, > 7 years. Criteria studied were eye lens nitrogen, cranial suture closure, tooth wear and incisor cementum layers. Lens nitrogen increased rapidly up to 12 months of age, but at much reduced rate thereafter. Total lens nitrogen was useful only in separating young-of-the-year from adults. The closure sequence for five cranial sutures accurately divided the total known-age sample of males into seven groups, and the adults into five groups. The tooth wear criteria divided the known-age sample into five relative age groups, but aging of individuals by this method was inaccurate. Histological sectioning of known-age teeth was the best method of observing layering in the cementum tissue. The technique of basing estimation of age on cementum ring counts, although subjective, was accurate for aging individuals through their fourth year but tended to underestimate the age of animals over 4 years old. However, suture closure or tooth wear can be used to identify males over 4 years old. In field studies, technical difficulties limit the utility of age estimation by cementum layers. Maximum root thickness of the lower canine was accurate in determining the sex of individuals from 5 months to ,at least 48 months of age.

  18. VSOP-2 Orbit Determination

    Science.gov (United States)

    Takeuchi, H.; VSOP-2 Orbit Determination Sub-Working Group

    2009-08-01

    Precise orbit determination (POD) is a key factor to enable phase referencing observations with Astro-G. A POD accuracy of 30 cm is required for efficient X-band phase referencing observations, accuracy of 6 cm for K-band observations, and accuracy of 3 cm for Q-band observations. For the POD, Astro-G will be equipped with a GPS/Galileo receiver and a SLR (Satellite Laser Ranging) retroreflector array. Four POD antennas will be equipped on four sides of the satellite body, to cover all directions. The SLR will be used as a complement to the GPS at middle-to-high altitude. Because the refroreflector array should always face to the Earth direction, it will be set up on the Ka-link antenna gimbal. The most significant perturbing force for the Astro-G is solar radiation pressure (SRP). The reflectivity of each surface component should be preliminary measured in detail to model the SRP. The estimated achievable POD accuracy at apogee is 10 ˜ 30 cm in nominal case. Phase referencing observations in K- or Q-band can be performed if the enough amount of SLR tracking data can be obtained at high altitudes.

  19. A highly conserved repeated chromosomal sequence in the radioresistant bacterium Deinococcus radiodurans SARK.

    Science.gov (United States)

    Lennon, E; Gutman, P D; Yao, H L; Minton, K W

    1991-03-01

    A DNA fragment containing a portion of a DNA damage-inducible gene from Deinococcus radiodurans SARK hybridized to numerous fragments of SARK genomic DNA because of a highly conserved repetitive chromosomal element. The element is of variable length, ranging from 150 to 192 bp, depending on the absence or presence of one or two 21-bp sequences located internally. A putative translational start site of the damage-inducible gene is within the reiterated element. The element contains dyad symmetries that suggest modes of transcriptional and/or translational control.

  20. Radioresistant Sf9 insect cells display moderate resistance against cumene hydroperoxide.

    Science.gov (United States)

    Kumar, Jyoti Swaroop; Suman, Shubhankar; Singh, Vijaypal; Chandna, Sudhir

    2012-08-01

    Lepidopteran insect cells serve as excellent model to study stress responses and are known to display resistance against DNA damaging agents including ionizing radiation; however, limited information is available on the effects of membrane damaging agents in these cells. In this study, we investigated the response of Sf9 cells (derived from ovaries of Spodoptera frugiperda; order Lepidoptera) to cumene hydroperoxide (CHPx), compared to human BMG-1 cells. CHPx treatment at doses lethal for human cells also caused typical necrosis in Sf9. Severe necrosis in human BMG-1 cells was observed at 125 μM, whereas similar effect in Sf9 cells was observed at 250 μM. In Sf9 cells, CHPx (250 μM) induced negligible changes in mitochondrial membrane potential and intracellular reactive oxygen species, while moderate effect was observed on intracellular calcium distribution. Reduced DNA damage and lipid (including cardiolipin) oxidation was observed in Sf9 cells that could be due to moderate total antioxidant status and constitutive/induced glutathione S-transferase activity. This study importantly demonstrates that Lepidopteran insect cells having extensive resistance towards DNA damaging agents show only moderately higher resistance to membrane damaging agents. A stronger reducing environment involving efficient antioxidant system seems to contribute significantly in this response.

  1. Neuroendorine differentiation in prostate cancer: A mechanism of radioresistance and treatment failure

    Directory of Open Access Journals (Sweden)

    Chang-Deng eHu

    2015-04-01

    Full Text Available Neuroendocrine differentiation (NED in prostate cancer is a well recognized phenotypic change by which prostate cancer cells transdifferentiate into neuroendocrine-like (NE-like cells. NE-like cells lack the expression of androgen receptor and prostate specific antigen, and are resistant to treatments. In addition, NE-like cells secrete peptide hormones and growth factors to support the growth of surrounding tumor cells in a paracrine manner. Accumulated evidence has suggested that NED is associated with disease progression and poor prognosis. The importance of NED in prostate cancer progression and therapeutic response is further supported by the fact that therapeutic agents, including androgen deprivation therapy, chemotherapeutic agents, and radiotherapy, also induce NED. We will review the work supporting the overall hypothesis that therapy-induced NED is a mechanism of resistance to treatments, as well as discuss the relationship between therapy-induced NED and therapy-induced senescence, epithelial-to-mesenchymal transition, and cancer stem cells. Furthermore, we will use radiation-induced NED as a model to explore several NED-based targeting strategies for development of novel therapeutics. Finally, we propose future studies that will specifically address therapy-induced NED in the hope that a better treatment regimen for prostate cancer can be developed.

  2. Complete genome sequence of the orange-red pigmented, radioresistant Deinococcus proteolyticus type strain (MRPT)

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, A [U.S. Department of Energy, Joint Genome Institute; Zeytun, Ahmet [Los Alamos National Laboratory (LANL); Yasawong, Montri [HZI - Helmholtz Centre for Infection Research, Braunschweig, Germany; Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Hammon, Nancy [U.S. Department of Energy, Joint Genome Institute; Deshpande, Shweta [U.S. Department of Energy, Joint Genome Institute; Cheng, Jan-Fang [U.S. Department of Energy, Joint Genome Institute; Han, Cliff [Los Alamos National Laboratory (LANL); Tapia, Roxanne [Los Alamos National Laboratory (LANL); Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Liolios, Konstantinos [U.S. Department of Energy, Joint Genome Institute; Pagani, Ioanna [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Mikhailova, Natalia [U.S. Department of Energy, Joint Genome Institute; Pati, Amrita [U.S. Department of Energy, Joint Genome Institute; Chen, Amy [U.S. Department of Energy, Joint Genome Institute; Palaniappan, Krishna [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Jeffries, Cynthia [Oak Ridge National Laboratory (ORNL); Brambilla, Evelyne-Marie [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Rohde, Manfred [HZI - Helmholtz Centre for Infection Research, Braunschweig, Germany; Sikorski, Johannes [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Pukall, Rudiger [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Goker, Markus [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Bristow, James [U.S. Department of Energy, Joint Genome Institute; Eisen, Jonathan [U.S. Department of Energy, Joint Genome Institute; Markowitz, Victor [U.S. Department of Energy, Joint Genome Institute; Hugenholtz, Philip [U.S. Department of Energy, Joint Genome Institute; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Klenk, Hans-Peter [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute

    2012-01-01

    Deinococcus proteolyticus (ex Kobatake et al. 1973) Brook and Murray 1981 is one of currently 47 species in the genus Deinococcus within the family Deinococcaceae. Strain MRPTT was isolated from faeces of Lama glama; it shares with various other species of the genus the extreme radiation resistance, with D. proteolyticus being resistant up to 1.5 Mrad of gamma radiation. Strain MRPT{sup T} is of further interest for its carotenoid pigment. The genome presented here is only the fifth completed genome sequence of a member of the genus Deinococcus (and the forth type strain) to be published, and will hopefully contribute to a better understanding of how members of this genus adapted to high gamma- or UV ionizing-radiation. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 2,886,836 bp long genome with its four large plasmids of 97 kbp, 132 kbp, 196 kbp and 315 kbp harbours 2,741 protein-coding and 58 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project.

  3. Radiation Induces Cathepsin S through ROS-IFN-{gamma} Pathways: Involvement of Cellular Radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Haeng Ran; Lee, Yun-Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Joon [Korea University, Seoul (Korea, Republic of)

    2008-05-15

    Ionizing radiation can elicit an activated phenotype that promotes rapid and persistent remodeling of the extracellular matrix (ECM) through the induction of proteases and growth factors, as well as in response to chronic production of reactive oxygen species (ROS). In addition, the results of previously conducted cDNA microarrays and real-time RT-PCR analysis (unpublished) suggest that radiation-induced mammary tumors were specifically induced by cathepsin S (CTSS), but that dimethylbenz(a)anthracene (DMBA)-induced mammary tumors were not. CTSS is a lysosomal cystein protease that is synthesized as an inactive precursor (36kDa) and activated in the acidic environment of lysosomes by proteolytic cleavage of its propeptide. In this study, we further investigate the mechanism by which CTSS is induced by radiation as well as its function.

  4. The radioresistance kinase TLK1B protects the cells by promoting repair of double strand breaks

    Directory of Open Access Journals (Sweden)

    De Benedetti Arrigo

    2005-09-01

    Full Text Available Abstract Background The mammalian protein kinase TLK1 is a homologue of Tousled, a gene involved in flower development in Arabidopsis thaliana. The function of TLK1 is not well known, although knockout of the gene in Drosophila or expression of a dominant negative mutant in mouse cells causes loss of nuclear divisions and missegregation of chromosomes probably, due to alterations in chromatin remodeling capacity. Overexpression of TLK1B, a spliced variant of the TLK1 mRNA, in a model mouse cell line increases it's resistance to ionizing radiation (IR or the radiomimetic drug doxorubicin, also likely due to changes in chromatin remodeling. TLK1B is translationally regulated by the availability of the translation factor eIF4E, and its synthesis is activated by IR. The reason for this mechanism of regulation is likely to provide a rapid means of promoting repair of DSBs. TLK1B specifically phosphorylates histone H3 and Asf1, likely resulting in changes in chromatin structure, particularly at double strand breaks (DSB sites. Results In this work, we provide several lines of evidence that TLK1B protects the cells from IR by facilitating the repair of DSBs. First, the pattern of phosphorylation and dephosphorylation of H2AX and H3 indicated that cells overexpressing TLK1B return to pre-IR steady state much more rapidly than controls. Second, the repair of episomes damaged with DSBs was much more rapid in cells overexpressing TLK1B. This was also true for repair of genomic damage. Lastly, we demonstrate with an in vitro repair system that the addition of recombinant TLK1B promotes repair of a linearized plasmid incubated with nuclear extract. In addition, TLK1B in this in vitro system promotes the assembly of chromatin as shown by the formation of more highly supercoiled topomers of the plasmid. Conclusion In this work, we provide evidence that TLK1B promotes the repair of DSBs, likely as a consequence of a change in chromatin remodeling capacity that must precede the assembly of repair complexes at the sites of damage.

  5. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage

    Science.gov (United States)

    Artati, Anna; Adamski, Jerzy

    2016-01-01

    Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF) to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease. PMID:27959944

  6. Carotenoid 3',4'-desaturase is involved in carotenoid biosynthesis in the radioresistant bacterium Deinococcus radiodurans.

    Science.gov (United States)

    Tian, Bing; Sun, Zongtao; Xu, Zhenjian; Shen, Shaochuan; Wang, Hu; Hua, Yuejin

    2008-12-01

    Deinococcus radiodurans strain R1 synthesizes deinoxanthin, a unique carotenoid product, which contributes to cell resistance following various stresses. The biosynthetic pathway of deinoxanthin is unclear, although several enzymes are presumed to be involved. The gene (dr2250) predicted by gene homologue analysis to encode carotenoid 3',4'-desaturase (CrtD) was deleted to investigate its function. A mutant deficient in the gene homologue of crtLm (dr0801) was also constructed to verify the catalytic function of the gene product in the native host. Carotenoid analysis of the resultant mutants verified that DR2250 encodes carotenoid 3',4'-desaturase, which catalyses the C-3',4'-desaturation of the monocyclic precursor of deinoxanthin but not acyclic carotenoids. Mutation of the gene homologue of crtLm (dr0801) resulted in accumulation of lycopene, confirming that it encodes the lycopene cyclase in the native host. The lack of CrtD decreased the antioxidant capacity of the mutant deficient in dr2250 compared with the wild-type, indicating that the C-3',4'-desaturation step contributes to the antioxidant capacity of deinoxanthin in D. radiodurans.

  7. Genetic background of enhanced radioresistance in an anhydrobiotic insect: transcriptional response to ionizing radiations and desiccation.

    Science.gov (United States)

    Ryabova, Alina; Mukae, Kyosuke; Cherkasov, Alexander; Cornette, Richard; Shagimardanova, Elena; Sakashita, Tetsuya; Okuda, Takashi; Kikawada, Takahiro; Gusev, Oleg

    2017-01-01

    It is assumed that resistance to ionizing radiation, as well as cross-resistance to other abiotic stresses, is a side effect of the evolutionary-based adaptation of anhydrobiotic animals to dehydration stress. Larvae of Polypedilum vanderplanki can withstand prolonged desiccation as well as high doses of ionizing radiation exposure. For a further understanding of the mechanisms of cross-tolerance to both types of stress exposure, we profiled genome-wide mRNA expression patterns using microarray techniques on the chironomid larvae collected at different stages of desiccation and after exposure to two types of ionizing radiation-70 Gy of high-linear energy transfer (LET) ions ((4)He) and the same dose of low-LET radiation (gamma rays). In expression profiles, a wide transcriptional response to desiccation stress that much exceeded the amount of up-regulated transcripts to irradiation exposure was observed. An extensive group of coincidently up-regulated overlapped transcripts in response to desiccation and ionizing radiation was found. Among this, overlapped set of transcripts was indicated anhydrobiosis-related genes: antioxidants, late embryogenesis abundant (LEA) proteins, and heat-shock proteins. The most overexpressed group was that of protein-L-isoaspartate/D-aspartate O-methyltransferase (PIMT), while probes, corresponding to LEA proteins, were the most represented. Performed functional analysis showed strongly enriched gene ontology terms associated with protein methylation. In addition, active processes of DNA repair were detected. We assume that the cross-tolerance of the sleeping chironomid to both desiccation and irradiation exposure comes from a complex mechanism of adaptation to anhydrobiosis.

  8. Crypt base columnar stem cells in small intestines of mice are radioresistant

    NARCIS (Netherlands)

    Hua, G.; Thin, T.H.; Feldman, R.; Haimovitz-Friedman, A.; Clevers, H.; Fuks, Z.; Kolesnick, R.

    2012-01-01

    BACKGROUND & AIMS: Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that t

  9. Mechanisms Governing DDK Regulation of the Initiation of DNA Replication

    Directory of Open Access Journals (Sweden)

    Larasati

    2016-12-01

    Full Text Available The budding yeast Dbf4-dependent kinase (DDK complex—comprised of cell division cycle (Cdc7 kinase and its regulatory subunit dumbbell former 4 (Dbf4—is required to trigger the initiation of DNA replication through the phosphorylation of multiple minichromosome maintenance complex subunits 2-7 (Mcm2-7. DDK is also a target of the radiation sensitive 53 (Rad53 checkpoint kinase in response to replication stress. Numerous investigations have determined mechanistic details, including the regions of Mcm2, Mcm4, and Mcm6 phosphorylated by DDK, and a number of DDK docking sites. Similarly, the way in which the Rad53 forkhead-associated 1 (FHA1 domain binds to DDK—involving both canonical and non-canonical interactions—has been elucidated. Recent work has revealed mutual promotion of DDK and synthetic lethal with dpb11-1 3 (Sld3 roles. While DDK phosphorylation of Mcm2-7 subunits facilitates their interaction with Sld3 at origins, Sld3 in turn stimulates DDK phosphorylation of Mcm2. Details of a mutually antagonistic relationship between DDK and Rap1-interacting factor 1 (Rif1 have also recently come to light. While Rif1 is able to reverse DDK-mediated Mcm2-7 complex phosphorylation by targeting the protein phosphatase glycogen 7 (Glc7 to origins, there is evidence to suggest that DDK can counteract this activity by binding to and phosphorylating Rif1.

  10. Determinants for grading Malaysian rice

    Science.gov (United States)

    ChePa, Noraziah; Yusoff, Nooraini; Ahmad, Norhayati

    2016-08-01

    Due to un-uniformity of rice grading practices in Malaysia, zones which actively producing rice in Malaysia are using their own way of grading rice. Rice grading is important in determining rice quality and its subsequent price in the market. It is an important process applied in the rice production industry with the purpose of ensuring that the rice produced for the market meets the quality requirements of consumer. Two important aspects that need to be considered in determining rice grades are grading technique and determinants to be used for grading (usually referred as rice attributes). This article proposes the list of determinants to be used in grading Malaysian rice. Determinants were explored through combination of extensive literature review and series of interview with the domain experts and practitioners. The proposed determinants are believed to be beneficial to BERNAS in improving the current Malaysian rice grading process.

  11. Emulsion stability: determination from turbidity

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, S.R.; Fogler, H.S.

    1981-01-01

    The relationship between particle size and concentration and turbidity has been developed for a polydispersed system. The stability of acoustically prepared emulsions of C36H74 in water were determined from turbidimetry and found to be in agreement with the stability determined by the freezing method. The turbidimetry method can be used for determining the stability of various emulsions easily and inexpensively. 11 references.

  12. Zinc Determination in Pleural Fluid

    OpenAIRE

    Nazan DEMİR; DEMİR, Yaşar

    2000-01-01

    In this study, an enzymatic zinc determination method was applied to pleural fluid, the basis of which was the regaining of the activity of apo carbonic anhydrase by the zinc present in the sample. The method was used for pleural fluid zinc determination in order to show the application to body fluids other than serum. For this purpose, pleural fluids were obtained from 20 patients and zinc concentrations were determined. Carbonic anhydrase was purified by affinity chromatography from bovine ...

  13. Star trackers for attitude determination

    DEFF Research Database (Denmark)

    Liebe, Carl Christian

    1995-01-01

    One problem comes to all spacecrafts using vector information. That is the problem of determining the attitude. This paper describes how the area of attitude determination instruments has evolved from simple pointing devices into the latest technology, which determines the attitude by utilizing...... a CCD camera and a powerful microcomputer. The instruments are called star trackers and they are capable of determining the attitude with an accuracy better than 1 arcsecond. The concept of the star tracker is explained. The obtainable accuracy is calculated, the numbers of stars to be included...

  14. Power, Ideology, and Technological Determinism

    Directory of Open Access Journals (Sweden)

    David J. Hess

    2015-12-01

    Full Text Available A Commentary on Taylor Dotson’s “Technological Determinism and Permissionless Innovation as Technocratic Governing Mentalities: Psychocultural Barriers to the Democratization of Technology”

  15. Decision Taking versus Action Determination

    NARCIS (Netherlands)

    Bergstra, J.A.

    2012-01-01

    Decision taking is discussed in the context of the role it may play for various types of agents, and it is contrasted with action determination. Some remarks are made about the role of decision taking and action determination in the ongoing debate concerning the reverse polder development of the

  16. Determining a healthcare organization's value.

    Science.gov (United States)

    Hahn, W

    1994-08-01

    As the consolidation activity among healthcare providers increases, it becomes more important than ever for healthcare financial managers to understand how to determine a healthcare organization's fair market value. There are many methods of determining an organization's value, but three general methods are the foundation of all others: the market comparable method, the underlying assets method, and the income, or cash flow, method.

  17. Statelessness determination: the Swiss experience

    Directory of Open Access Journals (Sweden)

    Karen Hamann

    2017-02-01

    Full Text Available While a detailed law on statelessness determination is recommended by UNHCR and others, Swiss practice in statelessness determination has evolved without one. Despite this, Swiss practice has been shown to be rather progressive, at least in some areas of statelessness recognition and includes better treatment of the stateless in comparison with refugees.

  18. POSITIVE MOTIVATION DETERMINANTS IN PSYCHOLOGY

    Directory of Open Access Journals (Sweden)

    Svyatoslav Vasilyevich KOTOV

    2014-01-01

    Full Text Available The paper considered the study of determinants of moti-vation and operation achievement. The paper revealed (with description in details the following factors: want for competence and self-determination, orientation in purpose of live, values, self-efficacy, resilience, and in-trinsic motivation. The study rationalized psychology regularities in the above determinants and the part they played in shaping resilience, personal mental wellbeing and further reinforcement of achievement motivation where the levels at the value scale of an individual served for the basis, those described in details in this paper. All the above determinants of positive motivation enable the individual to get over inner personal tensions, to become an autotelic free person. This paper reviewed the deter-minants of positive motivation in both Russian and for-eign studies of psychologists.

  19. Precise Orbit Determination for ALOS

    Science.gov (United States)

    Nakamura, Ryo; Nakamura, Shinichi; Kudo, Nobuo; Katagiri, Seiji

    2007-01-01

    The Advanced Land Observing Satellite (ALOS) has been developed to contribute to the fields of mapping, precise regional land coverage observation, disaster monitoring, and resource surveying. Because the mounted sensors need high geometrical accuracy, precise orbit determination for ALOS is essential for satisfying the mission objectives. So ALOS mounts a GPS receiver and a Laser Reflector (LR) for Satellite Laser Ranging (SLR). This paper deals with the precise orbit determination experiments for ALOS using Global and High Accuracy Trajectory determination System (GUTS) and the evaluation of the orbit determination accuracy by SLR data. The results show that, even though the GPS receiver loses lock of GPS signals more frequently than expected, GPS-based orbit is consistent with SLR-based orbit. And considering the 1 sigma error, orbit determination accuracy of a few decimeters (peak-to-peak) was achieved.

  20. Boundary determinations for trivariate solids

    Energy Technology Data Exchange (ETDEWEB)

    Duchaineau, M; Joy, K I

    1999-05-14

    The trivariate tensor-product B-spline solid is a direct extension of the B-spline patch and has been shown to be useful in the creation and visualization of free-form geometric solids. Visualizing these solid objects requires the determination of the boundary surface of the solid, which is a combination of parametric and implicit surfaces. This paper presents a method that determines the implicit boundary surface by examination of the Jacobian determinant of the defining B-spline function. Using an approximation to this determinant, the domain space is adaptively subdivided until a mesh can be determined such that the boundary surface is close to linear in the cells of the mesh. A variation of the marching cubes algorithm is then used to draw the surface. Interval approximation techniques are used to approximate the Jacobian determinant and to approximate the Jacobian determinant gradient for use in the adaptive subdivision methods. This technique can be used to create free-form solid objects, useful in geometric modeling applications.

  1. Determining Covers in Combinational Circuits

    Directory of Open Access Journals (Sweden)

    Ljubomir Cvetkovic

    2011-05-01

    Full Text Available In this paper we propose a procedure for determining 0- or 1-cover of an arbitrary line in a combinational circuit. When determining a cover we do not need Boolean expression for the line; only the circuit structure is used. Within the proposed procedure we use the tools of the cube theory, in particular, some operations defined on cubes. The procedure can be applied for determining 0- and 1- covers of output lines in programmable logic devices. Basically, this procedure is a method for the analysis of a combinational circuit.

  2. Determinant of Poverty in Ethiopia

    African Journals Online (AJOL)

    preferred customer

    Teshome Kebede and M. K. Sharma: Determinant of Poverty in Ethiopia. 114. 1. ... share of the population that is multidimensional poor, adjusted by the intensity ... nutrition, as well as clothing, housing and health care and education that can.

  3. Refugee status determination: three challenges

    Directory of Open Access Journals (Sweden)

    Martin Jones

    2009-04-01

    Full Text Available Refugee status determination (RSD, which is vital to the protection of so many asylum seekers worldwide, is at best an imperfect, haphazard and challenging process. It merits greater attention and appropriate reform.

  4. Network mapping and usage determination

    CSIR Research Space (South Africa)

    Senekal, FP

    2007-07-01

    Full Text Available A large computer network such as the Internet contains millions of computers, services and users, interconnected in a complicated and ever changing web. This article provides an introduction to network mapping and usage determination – the study...

  5. Sample size determination and power

    CERN Document Server

    Ryan, Thomas P, Jr

    2013-01-01

    THOMAS P. RYAN, PhD, teaches online advanced statistics courses for Northwestern University and The Institute for Statistics Education in sample size determination, design of experiments, engineering statistics, and regression analysis.

  6. Bell Numbers, Determinants and Series

    Indian Academy of Sciences (India)

    P K Saikia; Deepak Subedi

    2013-05-01

    In this article, we study Bell numbers and Uppuluri Carpenter numbers. We obtain various expressions and relations between them. These include polynomial recurrences and expressions as determinants of certain matrices of binomial coefficients.

  7. Poverty determinants in Isla Grande

    National Research Council Canada - National Science Library

    William Orlando Prieto Bustos

    2011-01-01

      This document contrasts the estimations of a nonlinear fixed effects model for determining poverty with a linear fixed event model for income generation for a sample of 136 persons using data panels for 2007 and 2009...

  8. Orbit Determination Analysis for SSAPurposes

    OpenAIRE

    2015-01-01

    Space Situational Awareness (SSA) is the characterization of the space environmentand of space activities. The fundament of SSA is the access to information about theorbit of space objects. There exist several techniques to determine the orbit of objects inspace, both from space-based and from ground-based observations. This Master's Thesisproject aims at investigating orbit determinations from ground-based radar observations.In particular, the use of the EISCAT Ultra-High-Frequency (UHF) inc...

  9. Cytokine determinants of viral tropism

    OpenAIRE

    McFadden, Grant; Mohamed, Mohamed R.; Rahman, Masmudur M.; Bartee, Eric

    2009-01-01

    The specificity of a given virus for a ceil type, tissue or species — collectively known as viral tropism — is an important factor in determining the outcome of viral infection in any particular host. Owing to the increased prevalence of zoonotic infections and the threat of emerging and re-emerging pathogens, gaining a better understanding of the factors that determine viral tropism has become particularly important. In this Review, we summarize our current understanding of the central role ...

  10. Gender determination of avian embryo

    Science.gov (United States)

    Daum, Keith A.; Atkinson, David A.

    2002-01-01

    Disclosed is a method for gender determination of avian embryos. During the embryo incubation process, the outer hard shells of eggs are drilled and samples of allantoic fluid are removed. The allantoic fluids are directly introduced into an ion mobility spectrometer (IMS) for analysis. The resulting spectra contain the relevant marker peaks in the positive or negative mode which correlate with unique mobilities which are sex-specific. This way, the gender of the embryo can be determined.

  11. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    <正>20102326 Cai Shuwei(Nanjing Institute of Geology and Mineral Resources,Nanjing 210016,China);Zhang Fei Determination of Trace Tin in Geochemical Materials by Platform GFAAS(Resources Survey & Environment,ISSN1671-4814,CN32-1640/N,30(4),2009,p.297-300,3 tables,6 refs.)Key words:atomic absorption spectra,tinA platform graphite furnace atomic absorption spectrometry(GFAAS)method was established for the determination of trace tin in geochemical samples.By using of magnesium nitrate,palladium nitrate and ammonium nitrate selected as the matrix modifier,the optimum conditions of analysis were studied.The analysis results of the national geochemical standard samples determined by the method are coincided well with the standard values of the samples.20102327 Chen Sulan(Jiangsu Environmental Monitoring Center,Nanjing 210036,China)Progress on Determination Method of Molybdenum in Environmental Samples(Journal of Geology,ISSN1674-3636,CN32-1796/P,33(4),2009,p.411-416,38 refs.)Key words:chemical analysis,molybdenumAccording to a long research on determination method of molybdenum in China,the author summarized the main determination methods of molybdenum for environmental samples.The methods in common use included photometry,catalytic polarography,flame atomic absorption spectrometry,graphite furnace atomic absorption spectrometry,inductively coupled

  12. Sex determination in flowering plants.

    Science.gov (United States)

    Dellaporta, S L; Calderon-Urrea, A

    1993-10-01

    In many ways, plants offer unique systems through which to study sex determination. Because the production of unisexual flowers has evolved independently in many plant species, different and novel mechanisms may be operational. Hence, there is probably not one unifying mechanism that explains sex determination in plants. Advances in our understanding of sex determination will come from the analysis of the genetics, molecular biology, and biochemistry of genes controlling sexual determination in plants. Several excellent model systems for bisexual floral development (Arabidopsis and Antirrhinum), monoecy (maize), and dioecy (Silene, asparagus, and mercury) are available for such analyses. The important questions that remain concern the mechanism of action of sex determination genes and their interrelationship, if any, with homeotic genes that determine the sexual identity of floral organ primordia. At the physiological level, the connection between hormone signaling and sexuality is not well understood, although significant correlations have been discovered. Finally, once the genes that regulate these processes are identified, cloned, and studied, new strategies for the manipulation of sexuality in plants should be forthcoming.

  13. determination of physio determination of physio-chemical properties ...

    African Journals Online (AJOL)

    eobe

    The objectives were to determine the physical, chemical ... seed oil exhibited good chemical properties for biodiesel production with a viscosity of 46.58mpa/s at 30oC,. Free Fatty Acid (FFA) ... production than animal fats and used/blended oils.

  14. A Predictive Framework for Determining How Journalists Determine News.

    Science.gov (United States)

    Gaudino, James L.

    To determine how to articulate a concrete definition of the substance of the journalist's occupation, this paper offers a propositional framework of news value based on Kurt Lewin's gatekeeper model. First, the paper follows the established suggestion that news decisions are best studied from a gatekeeping perspective or that "news is…

  15. Determining distances using asteroseismic methods

    CERN Document Server

    Aguirre, V Silva; Basu, S; Campante, T L; Chaplin, W J; Huber, D; Miglio, A; Serenelli, A M; WG#1, KASC

    2012-01-01

    Asteroseismology has been extremely successful in determining the properties of stars in different evolutionary stages with a remarkable level of precision. However, to fully exploit its potential, robust methods for estimating stellar parameters are required and independent verification of the results is needed. In this talk, I present a new technique developed to obtain stellar properties by coupling asteroseismic analysis with the InfraRed Flux Method. Using two global seismic observables and multi-band photometry, the technique determines masses, radii, effective temperatures, bolometric fluxes, and thus distances for field stars in a self-consistent manner. Applying our method to a sample of solar-like oscillators in the {\\it Kepler} field that have accurate {\\it Hipparcos} parallaxes, we find agreement in our distance determinations to better than 5%. Comparison with measurements of spectroscopic effective temperatures and interferometric radii also validate our results, and show that our technique can ...

  16. Sex Determination Mechanisms in Fish

    Institute of Scientific and Technical Information of China (English)

    ZHANG Quanqi; SUN Xiaohua; QI Jie; WANG Zhigang; WANG Xinglian; WANG Xubo; ZHAI Teng

    2009-01-01

    In fish, sex determination (SD) system shows high variation. The SD mechanisms include environmental and genetic regulation. The research on SD system and related genes in intensively studied fish species was reviewed. Although some genes have been described as sex-related, only DMRTlbY can be considered as a master sex determination gene and none of them has been util-ized in aquaculture. The variation of fish SD system, the importance of sex-related genes in evolution research and the relations be-tween environmental factors and sex-related genes were also discussed. The fish sex determination mechanism remains largely un-known. Further research needs to be done considering the significance of fish SD studies in basic and applied aspects.

  17. Lessons for Inductive Germline Determination

    Science.gov (United States)

    Seervai, Riyad N.H.; Wessel, Gary M.

    2015-01-01

    SUMMARY Formation of the germline in an embryo marks a fresh round of reproductive potential, yet the developmental stage and location within the embryo where the primordial germ cells (PGCs) form differs wildly among species. In most animals, the germline is formed either by an inherited mechanism, in which maternal provisions within the oocyte drive localized germ-cell fate once acquired in the embryo, or an inductive mechanism that involves signaling between cells that directs germ-cell fate. The inherited mechanism has been widely studied in model organisms such as Drosophila melanogaster, Caenorhabditis elegans, Xenopus laevis, and Danio rerio. Given the rapid generation time and the effective adaptation for laboratory research of these organisms, it is not coincidental that research on these organisms has led the field in elucidating mechanisms for germline specification. The inductive mechanism, however, is less well understood and is studied primarily in the mouse (Mus musculus). In this review, we compare and contrast these two fundamental mechanisms for germline determination, beginning with the key molecular determinants that play a role in the formation of germ cells across all animal taxa. We next explore the current understanding of the inductive mechanism of germ-cell determination in mice, and evaluate the hypotheses for selective pressures on these contrasting mechanisms. We then discuss the hypothesis that the transition between these determination mechanisms, which has happened many times in phylogeny, is more of a continuum than a binary change. Finally, we propose an analogy between germline determination and sex determination in vertebrates—two of the milestones of reproduction and development—in which animals use contrasting strategies to activate similar pathways. PMID:23450642

  18. Lessons for inductive germline determination.

    Science.gov (United States)

    Seervai, Riyad N H; Wessel, Gary M

    2013-08-01

    Formation of the germline in an embryo marks a fresh round of reproductive potential, yet the developmental stage and location within the embryo where the primordial germ cells (PGCs) form differs wildly among species. In most animals, the germline is formed either by an inherited mechanism, in which maternal provisions within the oocyte drive localized germ-cell fate once acquired in the embryo, or an inductive mechanism that involves signaling between cells that directs germ-cell fate. The inherited mechanism has been widely studied in model organisms such as Drosophila melanogaster, Caenorhabditis elegans, Xenopus laevis, and Danio rerio. Given the rapid generation time and the effective adaptation for laboratory research of these organisms, it is not coincidental that research on these organisms has led the field in elucidating mechanisms for germline specification. The inductive mechanism, however, is less well understood and is studied primarily in the mouse (Mus musculus). In this review, we compare and contrast these two fundamental mechanisms for germline determination, beginning with the key molecular determinants that play a role in the formation of germ cells across all animal taxa. We next explore the current understanding of the inductive mechanism of germ-cell determination in mice, and evaluate the hypotheses for selective pressures on these contrasting mechanisms. We then discuss the hypothesis that the transition between these determination mechanisms, which has happened many times in phylogeny, is more of a continuum than a binary change. Finally, we propose an analogy between germline determination and sex determination in vertebrates-two of the milestones of reproduction and development-in which animals use contrasting strategies to activate similar pathways.

  19. MEANS FOR DETERMINING CENTRIFUGE ALIGNMENT

    Science.gov (United States)

    Smith, W.Q.

    1958-08-26

    An apparatus is presented for remotely determining the alignment of a centrifuge. The centrifage shaft is provided with a shoulder, upon which two followers ride, one for detecting radial movements, and one upon the shoulder face for determining the axial motion. The followers are attached to separate liquid filled bellows, and a tube connects each bellows to its respective indicating gage at a remote location. Vibrations produced by misalignment of the centrifuge shaft are transmitted to the bellows, and tbence through the tubing to the indicator gage. This apparatus is particularly useful for operation in a hot cell where the materials handled are dangerous to the operating personnel.

  20. AGROCLIMATIC DETERMINANTS OF IRRIGATION NEEDS

    Directory of Open Access Journals (Sweden)

    Leszek Łabędzki

    2016-05-01

    Full Text Available The paper is a review of the so far used in Poland methods and criteria for assessing the needs of irrigation for planning purposes, the assessment because of the agroclimatic conditions and taking into account the soil water retention. Irrigation needs of the most are determined taking into account crop water deficits. This is the factor that is characterized by a shortage of precipitation in relation to the water requirements of crops. Some methods use only the meteorological parameters that determine the state of the atmosphere-soil-plant system, and some also take into account soil water retention and its availability for plants.

  1. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    <正>20110144 Hu Lan(Anhui Institute of Geological Experiment,Hefei 230001,China);Liu Yueyou Determination of Micro-amount of Bismuth in Polymetallic Ores by Hydride Generation-Atomic Fluorescence Spectrometry with Alkaline Mode(Rock and Mineral Analysis,ISSN0254-5357,CN11-2131/TD,29(1),2010,p.87-88,2 tables,10 refs.)Key words:atomic fluorescence spectrometry,bismuthA method for the determination of micro-amount of bismuth in polymetallic ores by hydride gen

  2. The Determinants of Food Choice

    DEFF Research Database (Denmark)

    Leng, Gareth; Adan, Roger A. H.; Belot, Michele

    2017-01-01

    , we need to be able to make valid predictions about the consequences of proposed interventions, and for this, we need a better understanding of the determinants of food choice. These determinants include dietary components (e.g. highly palatable foods and alcohol), but also diverse cultural and social...... pressures, cognitive-affective factors (perceived stress, health attitude, anxiety and depression), and familial, genetic and epigenetic influences on personality characteristics. In addition, our choices are influenced by an array of physiological mechanisms, including signals to the brain from...

  3. Determinants of Soviet Household Income

    Directory of Open Access Journals (Sweden)

    by Kenneth Smith

    2007-06-01

    Full Text Available World Values Survey data are used to examine household income in the Soviet Union. The data, gathered Summer/Fall 1990, provide a rare opportunity to empirically examine microeconomic factors influencing a Soviet household’s position in the regional/national income distribution. The survey contains data - collected regionally - from the three Baltic republics, Belarus, and the Moscow region. The data indicate certain patterns that existed and determined Soviet household income though there are often considerable regional variations. Further, there are marked differences between income distribution determinants in the Soviet Union and the U.S. and West Germany though similarities exist as well

  4. Self-Determination and Bilingualism

    Science.gov (United States)

    Landry, Rodrigue; Allard, Real; Deveau, Kenneth

    2009-01-01

    This article focuses on additive bilingualism for minority group children, more specifically the development of strong literacy skills in English and in the children's language. The personal autonomization language learning (PALL) model is presented. It specifies eight testable hypotheses. Self-determination theory (SDT) is central in the PALL…

  5. Self-Determination and Choice

    Science.gov (United States)

    Wehmeyer, Michael L.; Abery, Brian H.

    2013-01-01

    Promoting self-determination and choice opportunities for people with intellectual and developmental disabilities has become best practice in the field. This article reviews the research and development activities conducted by the authors over the past several decades and provides a synthesis of the knowledge in the field pertaining to efforts to…

  6. Determining FDI Flows into Scandinavia

    DEFF Research Database (Denmark)

    Kottaridi, Constantina; Bernhard Nielsen, Bo

    2003-01-01

    AbstractIn a recent global competitiveness report by the IMF, the four Nordic countries all ranked in top ten, attesting to the region?s growing attractiveness as a host location for MNCs. This paper investigates the driving forces determining foreign direct investment flows into Scandinavia. We...

  7. Socioeconomic determinants of first names

    NARCIS (Netherlands)

    Bloothooft, G.; Onland, D.

    2011-01-01

    Modern naming practices in the Netherlands between 1982 and 2005 were studied on the basis of 1409 popular first names, divided into fourteen name groups determined by the common preferences of parents for the names involved. Socioeconomic variables such as family income, parents' level of education

  8. Self-Determination after Kosovo

    DEFF Research Database (Denmark)

    Wolff, Stefan; Rodt, Annemarie Peen

    2013-01-01

    that has significant regional and global implications beyond the territory to which it is applied. Detailing these implications in relation to the case of Kosovo, we make a broader argument that, even if secession is one mechanism to resolve self-determination disputes, this does not do away with the need...

  9. Determinants of fertility in Ethiopia

    African Journals Online (AJOL)

    Methods: For this study, the linear mixed model was used to determine factors affecting ... The 2011 Ethiopian demographic and health survey data was used for this study. ... is the most important factor in population dynamics. It .... Estimation of and the is done using either the analysis of variance (ANOVA) method, or the.

  10. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    20160934Jin Tingting(Testing Center,Yunnan Bureau of Nonferrous Geology,Kunming650216,China);Wang Xuewei The Assessment of Uncertainty in Determination of Al2O3in Fe Ore by ICP-OES(Yunnan Geology,ISSN1004-1885,CN53-1041/P,34(2),

  11. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    <正>20090947 Fan Haifeng(State Key Laboratory of Ore Deposit Geochemistry,Guiyang Institute of Geochemistry,Chinese Academy of Sciences,Guiyang 550002,China);Wen Hanjie Determination of Total Selenium in Geological Samples by HG-AFS after Enrichment with Thiol Cotton Fiber(Acta Min-

  12. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    20152386 Hao Yuanfang(Shenyang Institute of Geology and Mineral Resources,CGS,Shenyang 110032,China);Xu Yingkui Determination of Calcium Oxide in Nickel Ores with EDTA Titration(Geology and Resources,ISSN1671-1947,CN21-1458/P,23(6),2014,p.580-582,2tables,6 refs.)

  13. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>20131550 Bai Jinfeng(Institute of Geophysical and Geochemical Exploration,Chinese Academy of Geological Sciences,Langfang 065000,China);Bo Wei Determination of 36Elements in Geochemical Samples by High Resolution Inductively Coupled Plasma-Mass Spectrometry(Rock and Mineral Analysis,ISSN0254-5357,CN11-2131/TD,31(5),2012,p.814

  14. VOLTAMMETRIC DETERMINATION OF CHLORAMPHENICOL AT ...

    African Journals Online (AJOL)

    a

    A sensitive square wave voltammetric method for the determination of ... involve UV-spectroscopy and HPLC, but have limited selectivity and ore often subjected to ..... The effect of the preservative associated with CAP in its pure form and its ...

  15. What Determines Joint Venture Termination?

    DEFF Research Database (Denmark)

    Nielsen, Bo Bernhard

    2012-01-01

    Joint venture (JV) research continues to flourish as researchers seek to advance our understanding of why so many JVs fail. Cui and Kumar (this issue) take a contingency approach to explain how and why business relatedness may provide new insights as to what determines JV termination...

  16. Determining Salinity by Simple Means.

    Science.gov (United States)

    Schlenker, Richard M.

    This paper describes the construction and use of a simple salinometer. The salinometer is composed, mainly, of a milliammeter and a battery and uses the measurement of current flow to determine the salinity of water. A complete list of materials is given, as are details of construction and operation of the equipment. The use of the salinometer in…

  17. Sex determination in the Hymenoptera

    NARCIS (Netherlands)

    Heimpel, George E.; de Boer, Jetske G.

    2008-01-01

    The dominant and ancestral mode of sex determination in the Hymenoptera is arrhenotokous parthenogenesis, in which diploid females develop from fertilized eggs and haploid males develop from unfertilized eggs. We discuss recent progress in the understanding of the genetic and cytoplasmic mechanisms

  18. Structure determination of enterovirus 71

    OpenAIRE

    Plevka, Pavel; Perera, Rushika; Cardosa, Jane; Kuhn, Richard J.; Rossmann, Michael G

    2012-01-01

    Determination of the orientation of the enterovirus 71 virions in the crystal required the calculation of a locked rotation function that included only icosahedral threefold and fivefold symmetry axes. Otherwise, misleading high rotation-function values were produced by accidental alignment of icosahedral and crystallographic twofold axes.

  19. Determining distances using asteroseismic methods

    DEFF Research Database (Denmark)

    Aguirre, Victor Silva; Casagrande, L.; Basu, Sarbina

    2013-01-01

    Asteroseismology has been extremely successful in determining the properties of stars in different evolutionary stages with a remarkable level of precision. However, to fully exploit its potential, robust methods for estimating stellar parameters are required and independent verification of the r...

  20. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    20160255 Wang Na(Tianjin Center of Geological Survey,China Geological Survey,Tianjin 300170,China);Teng Xinhua Determination of Low-Content Iron Carbonate in Stream Sediments by Flame Atomic Absorption Spectrometry with Aluminum Chloride Extraction(Rock and Mineral Analysis,ISSN0254-5357,CN11-2131/TD,34(2),2015,p.229

  1. Determining distances using asteroseismic methods

    DEFF Research Database (Denmark)

    Aguirre, Victor Silva; Casagrande, L.; Basu, Sarbina;

    2013-01-01

    Asteroseismology has been extremely successful in determining the properties of stars in different evolutionary stages with a remarkable level of precision. However, to fully exploit its potential, robust methods for estimating stellar parameters are required and independent verification of the r...

  2. Cohesin in determining chromosome architecture

    Energy Technology Data Exchange (ETDEWEB)

    Haering, Christian H., E-mail: christian.haering@embl.de [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: rolf.jessberger@tu-dresden.de [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)

    2012-07-15

    Cells use ring-like structured protein complexes for various tasks in DNA dynamics. The tripartite cohesin ring is particularly suited to determine chromosome architecture, for it is large and dynamic, may acquire different forms, and is involved in several distinct nuclear processes. This review focuses on cohesin's role in structuring chromosomes during mitotic and meiotic cell divisions and during interphase.

  3. Determinants and Polynomial Root Structure

    Science.gov (United States)

    De Pillis, L. G.

    2005-01-01

    A little known property of determinants is developed in a manner accessible to beginning undergraduates in linear algebra. Using the language of matrix theory, a classical result by Sylvester that describes when two polynomials have a common root is recaptured. Among results concerning the structure of polynomial roots, polynomials with pairs of…

  4. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    <正>20140786Deng Zhenping(Institute of Karst Geology,Chinese Academy of Geological Sciences,Guilin 541004,China);Yang Wen-qiong Application of Stripping Voltammetry with a Solid Amalgam Electrode for Determination of Copper in a Tracer and Groundwater Tracing Experiment(Rock and Mineral Analy-

  5. Sex determination using maxillary sinus

    Directory of Open Access Journals (Sweden)

    Ranjith Kumar Kanthem

    2015-01-01

    Full Text Available Background: Individual identification is a subtle concept and often one of the most important priorities in mass disasters, road accidents, air crashes, fires, and even in the investigation of criminal cases. Matching specific features detected on the cadaver with data recorded during the life of an individual is an important aspect in forensics, and can be performed by fingerprint analysis, deoxyribonucleic acid matching, anthropological methods, radiological methods and other techniques which can facilitate age and sex identification. Sinus radiography is one such method that has been used for determination of the sex of an individual. Hence, an attempt is being made to use the different dimensions of the maxillary sinus in the determination of sex using coronal and axial sections of plain computed tomography (CT scan. Materials and Methods: A total of 30 patients including 17 male and 13 female, visiting the Outpatient Department of the Mamata General Hospital were included as the study subjects. The dimensions of right and left maxillary sinuses of 30 subjects from plain CT were measured using SYNGO software and statistical analysis was done. Results: Sex determination using height, length, width, and volume of the maxillary sinus on both sides showed statistically significant results with a higher percentage of sexual dimorphism in the case of volume. Conclusion: Volume of the right maxillary sinus can be used as accurate diagnostic parameter for sex determination.

  6. Self-determination after Kosovo

    DEFF Research Database (Denmark)

    . As such, the case of Kosovo has sharpened the focus and intensified the debate on the issue of self-determination conflicts and how they are managed by the international community. This volume contributes to this debate by examining Kosovo in historical and contemporary comparative perspective...

  7. Empirical determinants of relationship lending

    Directory of Open Access Journals (Sweden)

    Sahar Loukil

    2016-12-01

    Full Text Available We study the determinants of the incidence of relationship lending. For our study, we combine established insights from the study of Elsas with empirical banking relationship lending literature. We relate loan contract and borrower characteristics to self-assessments of Tunisian banks with respect to the existence of close relationship. Using detailed loan contract information from Tunisian banks and a questionnaire addressed to loan officers, we report the first comprehensive evidence on the development of relationship lending. We find that access to information, the ability to influence the manager, and the solvency of the company are relevant factors. While the exclusivity and the duration of the relationship, classic measures of the existence of close ties with the bank, are not determining factors. So these proxy measures should be used with caution in future empirical works.

  8. TAX PAYMENTS DETERMINANTS IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Lazar Sebastian

    2015-07-01

    Full Text Available Using a fixed effects panel data estimation model in order to account for individual firm heterogeneity, the paper investigates the determinants of corporate tax payments for Romanian non-financial companies listed at Bucharest Stock Exchange over twelve years period (2000 – 2011, adopting a new approach, the natural logarithms of corporate income taxes actually paid as dependent variable. This removes the inherent flaws of firm specific effective tax rates, while establishing a more comparable field for subsequent similar research. All the determinants investigated were found as having an impact, albeit at different level of significance. Capital intensity, leverage and labour intensity were found as having a negative effect, while profitability and size have a positive impact. The findings correspond in general to conventional theory. Moreover, the paper produces evidence concerning the impact of loss carry-forward provisions on firm tax payments.

  9. Countably determined compact abelian groups

    CERN Document Server

    Dikranjan, Dikran

    2008-01-01

    For an abelian topological group G let G^* be the dual group of all continuous characters endowed with the compact open topology. A subgroup D of G determines G if the restriction homomorphism G^* --> D^* of the dual groups is a topological isomorphism. Given a scattered compact subset X of an infinite compact abelian group G such that |X|determined by its countable subgroup must be metrizable. This gives a negative answer to questions of Comfort, Hernandez, Macario, Raczkowski and Trigos-Arrieta, as well as provides short proofs of main results established in three manuscripts by these authors.

  10. Determining Knots by Minimizing Energy

    Institute of Scientific and Technical Information of China (English)

    Cai-Ming Zhang; Hui-Jian Han; Fuhua Frank Cheng

    2006-01-01

    A new method for determining knots to construct polynomial curves is presented. At each data point, a quadric curve which passes three consecutive points is constructed. The knots for constructing the quadric curve are determined by minimizing the internal strain energy, which can be regarded as a function of the angle. The function of the angle is expanded as a Taylor series with two terms, then the two knot intervals between the three consecutive points are defined by linear expression. Between the two consecutive points, there are two knot intervals, and the combination of the two knot intervals is used to define the final knot interval. A comparison of the new method with several existing methods is included.

  11. Cell elasticity determines macrophage function.

    Directory of Open Access Journals (Sweden)

    Naimish R Patel

    Full Text Available Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report that macrophage elasticity is a major determinant of innate macrophage function. Macrophage elasticity is modulated not only by classical biologic activators such as LPS and IFN-γ, but to an equal extent by substrate rigidity and substrate stretch. Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function.

  12. General Relativity, Time and Determinism

    CERN Document Server

    Isenberg, James

    2016-01-01

    Einstein's theory of general relativity models the physical universe using spacetimes which satisfy Einstein's gravitational field equations. To date, Einstein's theory has been enormously successful in modeling observed gravitational phenomena, both at the astrophysical and the cosmological levels. The collection of spacetime solutions of Einstein's equations which have been effectively used for modeling the physical universe is a very small subset of the full set of solutions. Among this larger set, there are many spacetimes in which strange phenomena related to time are present: There are solutions containing regions in which determinism and the predictability of experimental outcomes breaks down (the Taub-NUT spacetimes), and there others in which the breakdown of determinism occurs everywhere (the G\\"odel universe). Should the existence of these strange solutions lead us to question the usefulness of Einstein's theory in modeling physical phenomena? Should it instead lead us to seriously search for stran...

  13. Determining Geometric Accuracy in Turning

    Institute of Scientific and Technical Information of China (English)

    Kwong; Chi; Kit; A; Geddam

    2002-01-01

    Mechanical components machined to high levels of ac cu racy are vital to achieve various functional requirements in engineering product s. In particular, the geometric accuracy of turned components play an important role in determining the form, fit and function of mechanical assembly requiremen ts. The geometric accuracy requirements of turned components are usually specifi ed in terms of roundness, straightness, cylindricity and concentricity. In pract ice, the accuracy specifications achievable are infl...

  14. Factors that determine job performance

    Directory of Open Access Journals (Sweden)

    Georgeta Amalasunta Iacob

    2010-12-01

    Full Text Available In today's context is seeking various solutions to determine that employees receive performance at work. Most of the hand is to motivate people in terms of promoting strategic management objectives. Only that the motivation and objectives involved a number of factors that can influence the performance of employees much more than motivation itself. The case study presented in this study will prove this.

  15. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    <正>20101621 Chen Heping (Nanyang Geology Testing & Research Center of Henan Province, Nanyang 473000, China); Sha Yanmei Simultaneous Determination of Major and Minor Elements in Carbonates by Inductively Coupled Plasma-Atomic Emission Spectrometry with Multi-direction Viewing Mode (Rock and Mineral Analysis, ISSN0254-5357, CN11-2131/TD, 28(4), 2009, p.367-369, 5 tables, 10 refs.)

  16. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>20080934 Cai Yuman(Geological Survey of Jiangsu Province,Nanjing 210018,China);Lu Lijuan Determination of Carbonate(Anhydride Carbonate)in Natural Gypsum by Acid-Base Titration(Jiangsu Geology,ISSN1003-6474,CN32-1258/P,31(2),2007,p.127-129,3 illus.,8 refs.)Key words:titration,carbonatesThe authors establish a method of acid-base ti

  17. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    <正>20122362 Cai Shuwei ( Nanjing Institute of Geology and Mineral Resources,Nanjing 210016,China );Zhu Jiaping Evaluating on Uncertainty of Determination of Manganese Contents in Groundwater by Inductively Coupled Plasma Atomic Emission Spectrometry ( Resources Survey & Environment,ISSN1671-4814,CN32-1640 / N,32 ( 4 ), 2011,p.307-310,2tables,8refs. ) Key words:inductively coupled plasma atomic emission spectroscopy,manganese

  18. Weight Maintenance: Determinants of Success

    Science.gov (United States)

    2005-12-15

    submitted in partial fulfillment of the requirements for the degree of MASTER OF DIETETIC ADMINISTRATION In Nutrition and Food Sciences Approved: Tamara...Determinants Of Success by Cynthia Mitchell, Master of Dietetic Administration Utah State University, 2005 Major Professor: Tamara Vitale Department...a concern. Current data suggest that these foods are often higher in energy, fat and sodium, but deficient in fiber , vitamins A and C and folate

  19. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    <正>20111673 Cao Ban(Zhejiang Institute of Geological & Mineral Resources,Hangzhou 310007,China);Ma Jun Determination of 16 Polycyclic Aromatic Hydrocarbons in Groundwater by High Performance Liquid Chromatography with Fluorescence-Ultraviolet Detector(Rock and Mineral Analysis,ISSN0254-5357,CN11-2131/TD,29(5),2010,p.539-542,2 illus.,4 tables,15 refs.)Key words:liquid chromatography,polycyclic aromatic hydrocarbons,fluorescence analysis

  20. Performance appraisal: dimensions and determinants

    OpenAIRE

    2012-01-01

    The determinants of the dimensions that shape a formal system of performance appraisal are studied in relation to a sample of Spanish manufacturing establishments. In particular, the factors that influence the measures used to evaluate performance, the person who carries out such appraisal and its frequency are analysed. Our results show that the characteristics of the establishment exert a significant influence on the configuration of performance appraisal. Specifically, we find that the use...

  1. Genetic modification and genetic determinism

    OpenAIRE

    Vorhaus Daniel B; Resnik David B

    2006-01-01

    Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound....

  2. System for determining biofuel concentration

    Energy Technology Data Exchange (ETDEWEB)

    Huff, Shean P.; Janke, Christopher James; Kass, Michael D.; Lewis, Sr, Samuel Arthur; Pawel, Steven J; Theiss, Timothy J.

    2016-09-13

    A measurement device or system configured to measure the content of biofuels within a fuel blend. By measuring a state of a responsive material within a fuel blend, a biofuel content of the fuel blend may be measured. For example, the solubility of a responsive material to biofuel content within a fuel blend, may affect a property of the responsive material, such as shape, dimensional size, or electrical impedance, which may be measured and used as a basis for determining biofuel content.

  3. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    <正>20140215Hu Ming(No.608Team,Bureau of Nonferrous Metals Geological Exploration of Jilin Province,Changchun 130507,China);Wang Zhongwei Determination of Geochemical Exploration Samples of Multiple Target Area by Hydride Atomic Fluorescent Spectrometry(Jilin Geology,ISSN1001-2427,CN22-1099/P,32(1),2013,p.120-124,2illus.,6tables,5refs.)

  4. Determining Σ-Λ mixing

    Energy Technology Data Exchange (ETDEWEB)

    Horsley, R. [Edinburgh Univ. (United Kingdom). School of Physics and Astronomy; Najjar, J. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Nakamura, Y. [RIKEN Advanced Institute for Computational Science, Kobe (Japan); Perlt, H.; Schiller, A. [Leipzig Univ. (Germany). Inst. fuer Theoretische Physik; Pleiter, D. [Forschungszentrum Juelich GmbH (Germany). Juelich Supercomputing Centre (JSC); Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Rakow, P.E.L. [Liverpool Univ. (United Kingdom). Theoretical Physics Div.; Schierholz, G. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Stueben, H. [Hamburg Univ. (Germany). Regionales Rechenzentrum; Zanotti, J.M. [Adelaide Univ. (Australia). CSSM, School of Chemistry and Physics

    2014-12-15

    SU2 isospin breaking effects in baryon octet (and decuplet) masses are due to a combination of up and down quark mass differences and electromagnetic effects. These mass differences are small. Between the Sigma and Lambda the mass splitting is much larger, but this is mostly due to their different wavefunctions. However there is now also mixing between these states. We determine the QCD mixing matrix and hence find the mixing angle and mass splitting.

  5. Meteorological determinants of air quality

    Science.gov (United States)

    Turoldo, F.; Del Frate, S.; Gallai, I.; Giaiotti, D. B.; Montanari, F.; Stel, F.; Goi, D.

    2010-09-01

    Air quality is the result of complex phenomena, among which the major role is played by human emissions of pollutants. Atmospheric processes act as determinants, e.g., modulating, dumping or amplifying the effects of emissions as an orchestra's director does with musical instruments. In this work, a series of small-scale and meso-scale meteorological determinants of air-quality are presented as they are observed in an area characterized by complex orography (Friuli Venezia Giulia, in the north-eastern side of Italy). In particular, attention is devoted to: i) meso-scale flows favouring the persistence of high concentrations of particulate matter; ii) meso-scale periodic flows (breezes) favouring high values of particulate matter; iii) local-scale thermodynamic behaviour favouring high atmospheric values of nitrogen oxides. The effects of these different classes of determinants are shown through comparisons between anthropic emissions (mainly traffic) and ground-based measurements. The relevance of complex orography (relatively steep relieves near to the sea) is shown for the meso-scale flows and, in particular, for local-scale periodic flows, which favour the increase of high pollutants concentrations mainly in summer, when the breezes regime is particularly relevant. Part of these results have been achieved through the ETS - Alpine Space EU project iMONITRAF!

  6. Gender determination by odontometric method.

    Science.gov (United States)

    Litha; Girish, H C; Murgod, Sanjay; Savita, J K

    2017-01-01

    Gender determination is central in establishing personal identification from human skeletal remains. The study was conducted to find out the accuracy with which gender can be determined by odontometric methods. To investigate the mesiodistal (MD) and buccolingual (BL) dimensions of all the teeth of permanent dentition to find new parameters to differentiate between male and female teeth and to assess whether each type of linear measurement can be used independently in odontometric sex differentiation. The study was conducted at a dental college on a composite group of 500 individuals comprising 250 males and 250 females. Impressions of upper and lower jaws were made with alginate impression material and casts prepared with dental stone. A digital Vernier calliper was used to measure the BL and MD dimensions of all the upper teeth except the third molars. The results were subjected to statistical analysis using univariate analysis and linear stepwise discriminant function analysis to find the variables which discriminate gender significantly. The MD and BL dimensions between males and females were statistically significant. The predicted value for correct classification of gender was also statistically significant. The ability to differentiate gender in the population using stepwise discriminant functions was found to be very high with 99.8% accuracy with males showing statistically larger teeth than females. This is similar to the near 100% success in gender determination using pelvic and skull bones.

  7. Gender determination from pulpal tissue

    Directory of Open Access Journals (Sweden)

    Manisha M. Khorate

    2014-01-01

    Full Text Available Objective: To evaluate the diagnostic performance of X (Barr body [BB] and Y (F body [FB] chromosomes observed in dental pulp tissue for gender determination of an individual. Materials and Methods: The study was carried out on 100 teeth (50 male and 50 female, which were indicated for extraction. The teeth were sectioned at various intervals (within 12 h to 49 days post-extraction, and the pulpal tissue was obtained. Two slides for each pulp tissue were prepared, one for 5% Quinacrine dihydrochloride stain (FB and the other for Hemotoxylin and Eosin stain (BB. The slides were then observed under the fluorescent microscope for FB and under the light microscope for the BB respectively. Results: Gender determination from human pulp is possible up to 7 weeks. The percentage of FB and BB decrease gradually as the time interval increases. Further, an equation was derived from the data based on the canonical discriminant function coefficients. Conclusion: The determination of gender based on a joint search for the presence or absence of X (BB and Y (FB Chromosome is a reliable and cost-effective technique.

  8. Efficient, sparse biological network determination

    Directory of Open Access Journals (Sweden)

    Papachristodoulou Antonis

    2009-02-01

    Full Text Available Abstract Background Determining the interaction topology of biological systems is a topic that currently attracts significant research interest. Typical models for such systems take the form of differential equations that involve polynomial and rational functions. Such nonlinear models make the problem of determining the connectivity of biochemical networks from time-series experimental data much harder. The use of linear dynamics and linearization techniques that have been proposed in the past can circumvent this, but the general problem of developing efficient algorithms for models that provide more accurate system descriptions remains open. Results We present a network determination algorithm that can treat model descriptions with polynomial and rational functions and which does not make use of linearization. For this purpose, we make use of the observation that biochemical networks are in general 'sparse' and minimize the 1-norm of the decision variables (sum of weighted network connections while constraints keep the error between data and the network dynamics small. The emphasis of our methodology is on determining the interconnection topology rather than the specific reaction constants and it takes into account the necessary properties that a chemical reaction network should have – something that techniques based on linearization can not. The problem can be formulated as a Linear Program, a convex optimization problem, for which efficient algorithms are available that can treat large data sets efficiently and uncertainties in data or model parameters. Conclusion The presented methodology is able to predict with accuracy and efficiency the connectivity structure of a chemical reaction network with mass action kinetics and of a gene regulatory network from simulation data even if the dynamics of these systems are non-polynomial (rational and uncertainties in the data are taken into account. It also produces a network structure that can

  9. Determination of the Limiting Magnitude

    Science.gov (United States)

    Kingery, Aaron; Blaauw, Rhiannon

    2017-01-01

    The limiting magnitude of an optical camera system is an important property to understand since it is used to find the completeness limit of observations. Limiting magnitude depends on the hardware and software of the system, current weather conditions, and the angular speed of the objects observed. If an object exhibits a substantial angular rate during the exposure, its light spreads out over more pixels than the stationary stars. This spreading causes the limiting magnitude to be brighter when compared to the stellar limiting magnitude. The effect, which begins to become important when the object moves a full width at half max during a single exposure or video frame. For targets with high angular speeds or camera systems with narrow field of view or long exposures, this correction can be significant, up to several magnitudes. The stars in an image are often used to measure the limiting magnitude since they are stationary, have known brightness, and are present in large numbers, making the determination of the limiting magnitude fairly simple. In order to transform stellar limiting magnitude to object limiting magnitude, a correction must be applied accounting for the angular velocity. This technique is adopted in meteor and other fast-moving object observations, as the lack of a statistically significant sample of targets makes it virtually impossible to determine the limiting magnitude before the weather conditions change. While the weather is the dominant factor in observing satellites, the limiting magnitude for meteors also changes throughout the night due to the motion of a meteor shower or sporadic source radiant across the sky. This paper presents methods for determining the limiting stellar magnitude and the conversion to the target limiting magnitude.

  10. Soil carbon determination by thermogravimetrics.

    Science.gov (United States)

    Pallasser, Robert; Minasny, Budiman; McBratney, Alex B

    2013-01-01

    Determination of soil constituents and structure has a vital role in agriculture generally. Methods for the determination of soil carbon have in particular gained greater currency in recent times because of the potential that soils offer in providing offsets for greenhouse gas (CO2-equivalent) emissions. Ideally, soil carbon which can also be quite diverse in its makeup and origin, should be measureable by readily accessible, affordable and reliable means. Loss-on-ignition is still a widely used method being suitably simple and available but may have limitations for soil C monitoring. How can these limitations be better defined and understood where such a method is required to detect relatively small changes during soil-C building? Thermogravimetric (TGA) instrumentation to measure carbonaceous components has become more interesting because of its potential to separate carbon and other components using very precise and variable heating programs. TGA related studies were undertaken to assist our understanding in the quantification of soil carbon when using methods such as loss-on-ignition. Combining instrumentation so that mass changes can be monitored by mass spectrometer ion currents has elucidated otherwise hidden features of thermal methods enabling the interpretation and evaluation of mass-loss patterns. Soil thermogravimetric work has indicated that loss-on-ignition methods are best constrained to temperatures from 200 to 430 °C for reliable determination for soil organic carbon especially where clay content is higher. In the absence of C-specific detection where mass only changes are relied upon, exceeding this temperature incurs increasing contributions from inorganic sources adding to mass losses with diminishing contributions related to organic matter. The smaller amounts of probably more recalcitrant organic matter released at the higher temperatures may represent mineral associated material and/or simply more refractory forms.

  11. Soil carbon determination by thermogravimetrics

    Directory of Open Access Journals (Sweden)

    Robert Pallasser

    2013-02-01

    Full Text Available Determination of soil constituents and structure has a vital role in agriculture generally. Methods for the determination of soil carbon have in particular gained greater currency in recent times because of the potential that soils offer in providing offsets for greenhouse gas (CO2-equivalent emissions. Ideally, soil carbon which can also be quite diverse in its makeup and origin, should be measureable by readily accessible, affordable and reliable means. Loss-on-ignition is still a widely used method being suitably simple and available but may have limitations for soil C monitoring. How can these limitations be better defined and understood where such a method is required to detect relatively small changes during soil-C building? Thermogravimetric (TGA instrumentation to measure carbonaceous components has become more interesting because of its potential to separate carbon and other components using very precise and variable heating programs. TGA related studies were undertaken to assist our understanding in the quantification of soil carbon when using methods such as loss-on-ignition. Combining instrumentation so that mass changes can be monitored by mass spectrometer ion currents has elucidated otherwise hidden features of thermal methods enabling the interpretation and evaluation of mass-loss patterns. Soil thermogravimetric work has indicated that loss-on-ignition methods are best constrained to temperatures from 200 to 430 °C for reliable determination for soil organic carbon especially where clay content is higher. In the absence of C-specific detection where mass only changes are relied upon, exceeding this temperature incurs increasing contributions from inorganic sources adding to mass losses with diminishing contributions related to organic matter. The smaller amounts of probably more recalcitrant organic matter released at the higher temperatures may represent mineral associated material and/or simply more refractory forms.

  12. Angle independent velocity spectrum determination

    DEFF Research Database (Denmark)

    2014-01-01

    An ultrasound imaging system (100) includes a transducer array (102) that emits an ultrasound beam and produces at least one transverse pulse-echo field that oscillates in a direction transverse to the emitted ultrasound beam and that receive echoes produced in response thereto and a spectral vel...... velocity estimator (110) that determines a velocity spectrum for flowing structure, which flows at an angle of 90 degrees and flows at angles less than 90 degrees with respect to the emitted ultrasound beam, based on the received echoes....

  13. Determination of pigments in vegetables.

    Science.gov (United States)

    Schoefs, Benoît

    2004-10-29

    Plant pigments are responsible for the shining color of plant tissues. They are also found in animal tissues and, eventually in transformed food products as additives. These pigments have an important impact on the commercial value of products, because the colors establish the first contact with the consumer. In addition plant pigments may have an influence on the health of the consumers. Pigments are labile: they can be easily altered, and even destroyed. Analytical processes have been developed to determine pigment composition. The aim of this paper is to provide a brief overview of these methods.

  14. New frontiers in PDF determination

    CERN Document Server

    CERN. Geneva

    2016-01-01

    Parton Distribution Functions (PDFs) are a crucial input at the LHC, their uncertainty often being the limiting factor in the accuracy of theoretical predictions. At the same time the LHC is delivering a number of precise measurements that have the potential to greatly constrain these functions. I will give an overview on the theory behind and on the state of the art of PDF determination. I will then mention the new theoretical and methodological challenges in modern PDF fits and explore the precision frontiers opened by the accuracy of the LHC data.

  15. Health inequality - determinants and policies

    DEFF Research Database (Denmark)

    Diderichsen, Finn; Andersen, Ingelise; Manual, Celie;

    2012-01-01

    The review ”Health inequality – determinants and policies” identifies key-areas to be addressed with the aim to reduce the social inequality in health. The general life expectancy has steadily been increasing, but the data reveals marked social inequalities in health as well as life expectancy....... The review seeks to identify the causes of this social inequality. The analysis finds 12 areas of great importance for the inequality in health. This is i.e. early child development, schooling and education, the health behavior of the population, and the role of the health system. Within each of the 12 areas...

  16. Genetic modification and genetic determinism.

    Science.gov (United States)

    Resnik, David B; Vorhaus, Daniel B

    2006-06-26

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  17. Determinants of agricultural holdings sustainability

    Directory of Open Access Journals (Sweden)

    Wioletta Wrzaszcz

    2012-04-01

    Full Text Available Agricultural policy in the European Union, at the Community level, as well as Member Countries, increasingly emphasize the issue of sustainable development of agriculture. This is a response to the multiplying threats to the environment. Referring to this problem, it was justified to estimate the level of agricultural holdings sustainability (on the basis of FADN data and recognize its determinants. There was applied multidimensional statistical analysis and logistic regression. The research indicated that identification of environmentally friendly agriculture with low profit production is ungrounded.

  18. Photodamage determination of human hair.

    Science.gov (United States)

    Fernández, Estibalitz; Barba, Clara; Alonso, Cristina; Martí, Meritxell; Parra, José Luis; Coderch, Luisa

    2012-01-05

    Sunlight on human hair causes photo-degradation. This results in bleaching due to melanin oxidation through free radicals, and induces keratin impairment. Protein degradation, tryptophan degradation, lipidic peroxidation and electron paramagnetic resonance can be used to evaluate proteic and lipidic photodecomposition and free radical formation in hair fibres subjected to antioxidant action and different UV intensities. All these methodologies have been optimised to determine protein, lipid and melanin degradation in hair subjected to different UV intensities. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Determination of Effective Thoracic Mass

    Directory of Open Access Journals (Sweden)

    Jeffrey H. Marcus

    1996-01-01

    Full Text Available Effective thoracic mass is an important parameter in specifying mathematical and mechanical models (such as crash dummies of humans exposed to impact conditions. A method is developed using a numerical optimizer to determine effective thoracic mass (and mass distribution given a number of acceleration signals and a force signal response. Utilizing previously reported lateral and frontal impact tests with human cadaveric test specimens in a number of different conditions, the effective thoracic mass is computed. The effective thoracic masses are then computed for a variety of crash dummies exposed to identical test conditions.

  20. Determination of triclosan in foodstuffs.

    Science.gov (United States)

    Sanches-Silva, Ana; Sendón-García, Raquel; López-Hernández, Julia; Paseiro-Losada, Perfecto

    2005-01-01

    A reverse-phase high-performance liquid chromatographic (RP-HPLC) method coupled with an ultraviolet detector was developed to determine triclosan which had migrated into foodstuffs from packaging materials. The method includes extraction with hexane, followed by evaporation to dryness and residue re-dissolution in ACN 90%. Chromatographic separation was performed with a Kromasil 100 C18 column (15 cm x 0.4 cm ID, 5 microm particle size) at 30 degrees C and using ACN and water as mobile phases. Regarding recoveries, good results (higher than 83% and lower than 112%) were obtained for the three representative food matrixes selected (orange juice, chicken breast meat, and Gouda cheese).

  1. Structure determination of enterovirus 71

    Energy Technology Data Exchange (ETDEWEB)

    Plevka, Pavel; Perera, Rushika; Cardosa, Jane; Kuhn, Richard J.; Rossmann, Michael G. (Purdue); (Sentinext)

    2013-02-20

    Enterovirus 71 is a picornavirus that causes hand, foot and mouth disease but may induce fatal neurological illness in infants and young children. Enterovirus 71 crystallized in a body-centered orthorhombic space group with two particles in general orientations in the crystallographic asymmetric unit. Determination of the particle orientations required that the locked rotation function excluded the twofold symmetry axes from the set of icosahedral symmetry operators. This avoided the occurrence of misleading high rotation-function values produced by the alignment of icosahedral and crystallographic twofold axes. Once the orientations and positions of the particles had been established, the structure was solved by molecular replacement and phase extension.

  2. Determinants of Bilingualism among Children

    OpenAIRE

    Chiswick, Barry R.; Gindelsky, Marina

    2014-01-01

    This paper analyzes the determinants of bilingualism (i.e., speaks a language other than English at home) among children age 5 to 18 years in the American Community Survey, 2005-2011. Two groups of children are considered: those born in the US (native born) and foreign-born children who immigrated prior to age 14 (the 1.5 generation). The analyses are conducted overall, within genders, and within racial and ethnic groups. Bilingualism is more prevalent if the parents are foreign born, less pr...

  3. Structural determination of argon trimer

    Directory of Open Access Journals (Sweden)

    Xiguo Xie

    2015-09-01

    Full Text Available Rare gas clusters are model systems to investigate structural properties at finite size. However, their structures are difficult to be determined with available experimental techniques because of the strong coupling between the vibration and the rotation. Here we experimentally investigated multiple ionization and fragmentation dynamics of argon trimer by ultrashort intense laser fields and reconstructed their structures with Coulomb explosion technique. The measured structure distribution was compared with our finite-temperature ab initio calculations and the discrepancy was discussed. The present study provides a guidance for the development of theoretical methods for exploring the geometric structure of rare gas clusters.

  4. Accurate determination of antenna directivity

    DEFF Research Database (Denmark)

    Dich, Mikael

    1997-01-01

    The derivation of a formula for accurate estimation of the total radiated power from a transmitting antenna for which the radiated power density is known in a finite number of points on the far-field sphere is presented. The main application of the formula is determination of directivity from power......-pattern measurements. The derivation is based on the theory of spherical wave expansion of electromagnetic fields, which also establishes a simple criterion for the required number of samples of the power density. An array antenna consisting of Hertzian dipoles is used to test the accuracy and rate of convergence...

  5. Gravimetric determination of phospholipid concentration.

    Science.gov (United States)

    Tejera-Garcia, Roberto; Connell, Lisa; Shaw, Walter A; Kinnunen, Paavo K J

    2012-09-01

    Accurate determination of lipid concentrations is an obligatory routine in a research laboratory engaged in studies using this class of biomaterials. For phospholipids, this is frequently accomplished using the phosphate assay (Bartlett, G.R. Phosphorus Assay in Column Chromatography. J. Biol. Chem. 234, 466-468, 1959). Given the purity of the currently commercially available synthetic and isolated natural lipids, we have observed that determination of the dry weight of lipid stock solutions provides the fastest, most accurate, and generic method to assay their concentrations. The protocol described here takes advantage of the high resolution and accuracy obtained by modern weighing technology. We assayed by this technique the concentrations of a number of phosphatidylcholine samples, with different degrees of acyl chain saturation and length, and in different organic solvents. The results were compared with those from Bartlett assay, (31)P NMR, and Langmuir compression isotherms. The data obtained show that the gravimetric assay yields lipid concentrations with a resolution similar or better than obtained by the other techniques.

  6. Computational Intelligence Determines Effective Rationality

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Rationality is a fundamental concept in economics. Most researchers will accept that human beings are not fully rational.Herbert Simon suggested that we are "bounded rational". However, it is very difficult to quantify "bounded rationality", and therefore it is difficult to pinpoint its impact to all those economic theories that depend on the assumption of full rationality. Ariel Rubinstein proposed to model bounded rationality by explicitly specifying the decision makers' decision-making procedures. This paper takes a computational point of view to Rubinstein's approach. From a computational point of view, decision procedures can be encoded in algorithms and heuristics. We argue that, everything else being equal, the effective rationality of an agent is determined by its computational power - we refer to this as the computational intelligence determines effective rationality (CIDER) theory. This is not an attempt to propose a unifying definition of bounded rationality. It is merely a proposal of a computational point of view of bounded rationality. This way of interpreting bounded rationality enables us to (computationally) reason about economic systems when the full rationality assumption is relaxed.

  7. 42 CFR 405.715 - Reconsidered determination.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Reconsidered determination. 405.715 Section 405.715... Part A § 405.715 Reconsidered determination. (a) In reconsidering an initial determination, the CMS shall review such initial determination, the evidence and findings upon which such determination was...

  8. 14 CFR 314.16 - Final determination.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Final determination. 314.16 Section 314.16... REGULATIONS EMPLOYEE PROTECTION PROGRAM Determination of Qualifying Dislocation § 314.16 Final determination... determination and, within 3 business days after the determination, serve a copy of the order on the persons...

  9. 42 CFR 405.803 - Initial determination.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Initial determination. 405.803 Section 405.803....803 Initial determination. (a) Carriers make initial determinations regarding claims for benefits under Medicare Part B. (b) An initial determination for purposes of this subpart includes determinations...

  10. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    <正>20091570 Ge Yunjin(College of Geo-Resource and Information,China University of Petroleum,Dongying 257061,China);Chen Yong Advance in Low Temperature Phase Transition and Raman Spectrum Technique in Composition Determination of Fluid Inclusions(Rock and Mineral Analysis,ISSN0254-5357,CN11-2131/TD,27(3),2008,p.207-210,22 refs.)Key words:fluid inclusions,Raman spectraThe principle and development of low-temperature analytical techniques for fluid inclusions were expounded.The traditional low-temperature analytical technology mainly focused on the measurement of inorganic salt using congealed microthermometry,but now it is developed to semi-quantitative and quantitative analysis of fluid inclusions using in-situ cryogenic Raman spectrometry.

  11. Determination of Human Hemoglobin Derivatives.

    Science.gov (United States)

    Attia, Atef M M; Ibrahim, Fatma A A; Abd El-Latif, Noha A; Aziz, Samir W; Abdelmottaleb Moussa, Sherif A; Elalfy, Mohsen S

    2015-01-01

    The levels of the inactive hemoglobin (Hb) pigments [such as methemoglobin (metHb), carboxyhemoglobin (HbCO) and sulfohemoglobin (SHb)] and the active Hb [in the oxyhemoglobin (oxyHb) form] as well as the blood Hb concentration in healthy non pregnant female volunteers were determined using a newly developed multi-component spectrophotometric method. The results of this method revealed values of SHb% in the range (0.0727-0.370%), metHb% (0.43-1.0%), HbCO% (0.4-1.52%) and oxyHb% (97.06-98.62%). Furthermore, the results of this method revealed values of blood Hb concentration in the range (12.608-15.777 g/dL). The method is highly sensitive, accurate and reproducible.

  12. Determinants of fatigue and stress

    Directory of Open Access Journals (Sweden)

    Brähler Elmar

    2011-07-01

    Full Text Available Abstract Background Fatigue can be triggered by previous perceived stress which may lead to impairment of performance and function. The purpose of the study was to investigate the relationship between fatigue and perceived stress. Method Health determinants including sociodemographic factors for associations between fatigue and perceived stress in the general population (N = 2,483 are outlined. Fatigue and stress were assessed with the Chalder Fatigue Scale (CFS and the Perceived Stress Questionnaire (PSQ. Results Within the general population, 25.9% of male and 34.5% of female respondents reported moderate fatigue during the last six months; 9.7% of subjects reported substantial fatigue lasting six months or longer. An adjusted regression analysis (R2corr = .28, p Conclusion We conclude that the two conditions overlap most in terms of socio-economic status and self-perceived health status.

  13. Genetic modification and genetic determinism

    Directory of Open Access Journals (Sweden)

    Vorhaus Daniel B

    2006-06-01

    Full Text Available Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  14. AC polarographic determination of cloxacillin.

    Science.gov (United States)

    Núñez-Vergara, L J; Silva, M M; Squella, J A

    1982-11-01

    Hydrolysis of cloxacillin at pH 4.0 yields an electroactive product which can be determined by polarography. Depending on the concentration of cloxacillin, one of 2 peaks was obtained: The potential ac peaks for a 4.36 mM cloxacillin solution were peak I, -0.23 V and peak II, -0.13 V. For analytical purposes, the first peak was used. A linear relationship was established for levels of cloxacillin between 2.2 X 10(-5) and 2.2 X 10(-3)M. Average recovery was 98.8% (SD 1.8), indicating satisfactory accuracy for the method. Individual capsule and composite assays as well as interference tests are described.

  15. Structural determinants of glomerular permeability.

    Science.gov (United States)

    Deen, W M; Lazzara, M J; Myers, B D

    2001-10-01

    Recent progress in relating the functional properties of the glomerular capillary wall to its unique structure is reviewed. The fenestrated endothelium, glomerular basement membrane (GBM), and epithelial filtration slits form a series arrangement in which the flow diverges as it enters the GBM from the fenestrae and converges again at the filtration slits. A hydrodynamic model that combines morphometric findings with water flow data in isolated GBM has predicted overall hydraulic permeabilities that are consistent with measurements in vivo. The resistance of the GBM to water flow, which accounts for roughly half that of the capillary wall, is strongly dependent on the extent to which the GBM surfaces are blocked by cells. The spatial frequency of filtration slits is predicted to be a very important determinant of the overall hydraulic permeability, in keeping with observations in several glomerular diseases in humans. Whereas the hydraulic resistances of the cell layers and GBM are additive, the overall sieving coefficient for a macromolecule (its concentration in Bowman's space divided by that in plasma) is the product of the sieving coefficients for the individual layers. Models for macromolecule filtration reveal that the individual sieving coefficients are influenced by one another and by the filtrate velocity, requiring great care in extrapolating in vitro observations to the living animal. The size selectivity of the glomerular capillary has been shown to be determined largely by the cellular layers, rather than the GBM. Controversial findings concerning glomerular charge selectivity are reviewed, and it is concluded that there is good evidence for a role of charge in restricting the transmural movement of albumin. Also discussed is an effect of albumin that has received little attention, namely, its tendency to increase the sieving coefficients of test macromolecules via steric interactions. Among the unresolved issues are the specific contributions of the

  16. Complexometric determination, Part II: Complexometric determination of Cu2+-ions

    Directory of Open Access Journals (Sweden)

    Rajković Miloš B.

    2002-01-01

    Full Text Available A copper-selective electrode of the coated wire type based on sulphidized copper wire was applied successfully for determining Cu(II ions by complexometric titration with the disodium salt of EDTA (complexon III. By the formation of internal complex compounds with the Cu(II ion, the copper concentration in the solution decreases, and all this is followed by a change of potential of the indicator system Cu-DWISE (or Cu-EDWISE/SCE. At the terminal point of titration, when all the Cu(II ions are already utilized for the formation of the complex with EDTA, there occurs a steep rise of potential, thus enabling us, through the first or second derivative to note the quantity of copper that is present in the solution. Copper-selective electrode showed a responsivity towards titration with EDTA as a complexing agent, with the absence of "fatigue" due to a great number of repeated measurings. Errors occurring during quantitative measurements were more a characteristic of the overall procedure which involve, because of the impossibility of the complete absence of subjectivity, a constant error, and the reproducibility of the results confirmed this fact. The disodium salt of EDTA appeared as a very efficient titrant in all titrations and with various concentrations ot Cu(II ions in the solution, with somewhat weaker response at lower concentrations in the solution.

  17. Determinants of female sexual orgasms

    Directory of Open Access Journals (Sweden)

    Osmo Kontula

    2016-10-01

    Full Text Available Background: The pursuit of sexual pleasure is a key motivating factor in sexual activity. Many things can stand in the way of sexual orgasms and enjoyment, particularly among women. These are essential issues of sexual well-being and gender equality. Objective: This study presents long-term trends and determinants of female orgasms in Finland. The aim is to analyze the roles of factors such as the personal importance of orgasms, sexual desire, masturbation, clitoral and vaginal stimulation, sexual self-esteem, communication with partner, and partner’s sexual techniques. Design: In Finland, five national sex surveys that are based on random samples from the central population register have been conducted. They are representative of the total population within the age range of 18–54 years in 1971 (N=2,152, 18–74 years in 1992 (N=2,250, 18–81 years in 1999 (N=1,496, 18–74 years in 2007 (N=2,590, and 18–79 years in 2015 (N=2,150. Another dataset of 2,049 women in the age group of 18–70 years was collected in 2015 via a national Internet panel. Results: Contrary to expectations, women did not have orgasms that are more frequent by increasing their experience and practice of masturbation, or by experimenting with different partners in their lifetime. The keys to their more frequent orgasms lay in mental and relationship factors. These factors and capacities included orgasm importance, sexual desire, sexual self-esteem, and openness of sexual communication with partners. Women valued their partner’s orgasm more than their own. In addition, positive determinants were the ability to concentrate, mutual sexual initiations, and partner’s good sexual techniques. A relationship that felt good and worked well emotionally, and where sex was approached openly and appreciatively, promoted orgasms. Conclusion: The findings indicate that women differ greatly from one another in terms of their tendency and capacity to experience orgasms. The

  18. Determinants of female sexual orgasms.

    Science.gov (United States)

    Kontula, Osmo; Miettinen, Anneli

    2016-01-01

    The pursuit of sexual pleasure is a key motivating factor in sexual activity. Many things can stand in the way of sexual orgasms and enjoyment, particularly among women. These are essential issues of sexual well-being and gender equality. This study presents long-term trends and determinants of female orgasms in Finland. The aim is to analyze the roles of factors such as the personal importance of orgasms, sexual desire, masturbation, clitoral and vaginal stimulation, sexual self-esteem, communication with partner, and partner's sexual techniques. In Finland, five national sex surveys that are based on random samples from the central population register have been conducted. They are representative of the total population within the age range of 18-54 years in 1971 (N=2,152), 18-74 years in 1992 (N=2,250), 18-81 years in 1999 (N=1,496), 18-74 years in 2007 (N=2,590), and 18-79 years in 2015 (N=2,150). Another dataset of 2,049 women in the age group of 18-70 years was collected in 2015 via a national Internet panel. Contrary to expectations, women did not have orgasms that are more frequent by increasing their experience and practice of masturbation, or by experimenting with different partners in their lifetime. The keys to their more frequent orgasms lay in mental and relationship factors. These factors and capacities included orgasm importance, sexual desire, sexual self-esteem, and openness of sexual communication with partners. Women valued their partner's orgasm more than their own. In addition, positive determinants were the ability to concentrate, mutual sexual initiations, and partner's good sexual techniques. A relationship that felt good and worked well emotionally, and where sex was approached openly and appreciatively, promoted orgasms. The findings indicate that women differ greatly from one another in terms of their tendency and capacity to experience orgasms. The improvements in gender equality and sexual education since the 1970s have not helped women

  19. Determinants of female sexual orgasms

    Science.gov (United States)

    Kontula, Osmo; Miettinen, Anneli

    2016-01-01

    Background The pursuit of sexual pleasure is a key motivating factor in sexual activity. Many things can stand in the way of sexual orgasms and enjoyment, particularly among women. These are essential issues of sexual well-being and gender equality. Objective This study presents long-term trends and determinants of female orgasms in Finland. The aim is to analyze the roles of factors such as the personal importance of orgasms, sexual desire, masturbation, clitoral and vaginal stimulation, sexual self-esteem, communication with partner, and partner’s sexual techniques. Design In Finland, five national sex surveys that are based on random samples from the central population register have been conducted. They are representative of the total population within the age range of 18–54 years in 1971 (N=2,152), 18–74 years in 1992 (N=2,250), 18–81 years in 1999 (N=1,496), 18–74 years in 2007 (N=2,590), and 18–79 years in 2015 (N=2,150). Another dataset of 2,049 women in the age group of 18–70 years was collected in 2015 via a national Internet panel. Results Contrary to expectations, women did not have orgasms that are more frequent by increasing their experience and practice of masturbation, or by experimenting with different partners in their lifetime. The keys to their more frequent orgasms lay in mental and relationship factors. These factors and capacities included orgasm importance, sexual desire, sexual self-esteem, and openness of sexual communication with partners. Women valued their partner’s orgasm more than their own. In addition, positive determinants were the ability to concentrate, mutual sexual initiations, and partner’s good sexual techniques. A relationship that felt good and worked well emotionally, and where sex was approached openly and appreciatively, promoted orgasms. Conclusion The findings indicate that women differ greatly from one another in terms of their tendency and capacity to experience orgasms. The improvements in gender

  20. 放射抗拒人鼻咽癌细胞系的建立及其抗拒机制的初步探讨%Establishment of Radioresistant Nasopharyngeal Carcinoma Cell Lines and Preliminary Discussion of Their Radioresistance Mechanism

    Institute of Scientific and Technical Information of China (English)

    李燕娴; 曾木圣; 麦海强; 罗东华; 杨婧; 曹卡加; 郭翔; 莫浩元

    2013-01-01

    [目的]建立放射抗拒人鼻咽癌细胞系模型并观察人鼻咽癌细胞经X射线反复照射后放射敏感性的变化及初步探讨其放射抗拒的机制.[方法]利用X射线对人鼻咽癌细胞HONE-1、SUNE2细胞系进行照射,采用剂量梯度法确定其亚致死照射剂量后,每次照射1次亚致死剂量,共照射5次或以上(HONE-1:6Gy×5次,SUNE2:4Gy×7次).采用克隆形成实验等测定所得的HONE-1-IR,SUNE2-IR细胞系及其亲代细胞HONE-1、SUNE2的放射敏感性、细胞周期特征及SP细胞比例.[结果]与亲代细胞HONE-1,SUNE2相比,HONE-1-IR、SUNE2-IR细胞的D0、Dq及SF2值均增大,HONE-1-IR细胞的放射抗拒性(D0)是HONE-1细胞的1.336倍,SUNE2-IR的D0值为SUNE2的1.094倍,表现出一定的放射抗拒性;HONE-1-IR、SUNE2-IR的S期细胞比例较其亲代细胞HONE-1、SUNE2明显增高(HONE-1-IR ys HONE-1:43.56%vs 23.08%,P=-0.002;SUNE2-IR vs SUNE2:32.64%vs 19.20%,P=0.029),G2/M期细胞比例明显降低(HONE-1-IRvsHONE-1:13.65%vs29.51%,P=0.002;SUNE2-IR vs SUNE2:10.25%vs22.63%,P=0.026),而G0/G1期细胞比例则无明显差异(P=0.735,P=0.572);HONE-1-IR细胞的SP细胞比例较HONE-1细胞明显增高(3.96%vs 0.02%),而SUNE2-IR细胞与SUNE2细胞的SP细胞比例分别为0.27%、0.06%.[结论]人鼻咽癌细胞株HONE-1、SUNE2经亚致死剂量X射线多次照射后而建立的后代细胞HONE-1-IR、SUNE2-IR具有一定的放射抗拒性;HONE-1-IR、SUNE2-IR细胞显示出与亲代细胞不同的细胞周期特征,放射抗拒性也可能与SP细胞比例增高有关,值得进一步探讨.

  1. Indicators of radioresistance modified by radioprotective agents report 1. delta. pO/sub 2/ as indicator of degree of mexamine-induced enhancement of radioresistance of rat bone marrow. [X rays

    Energy Technology Data Exchange (ETDEWEB)

    Rozhdestvenskii, L.M.; Nikolaeva, S.I.

    1978-01-01

    The indicator approach to evaluation of effects of radioprotective agents is substantiated. A correlation was obtained between hypoxic and radioprotective effects of mexamine, given 5 min prior to irradiation, in rat bone marrow cells in vivo. An evaluation was made of both mean effectiveness of varying degrees of hypoxia and effectiveness in an individual animal on the basis of the DMF criterion.

  2. Determination of Lead by Electrochemistry

    Institute of Scientific and Technical Information of China (English)

    HE YuFeng; ZHANG Zhang; MA YongJun; KANG JingWan

    2001-01-01

    @@ Lead is one of the poisonous trace element for human body. It is important to find a way for measuring content of lead. Deternination of lead by electrochemistry is one of a method[1]. In this paper, lead is determined by single-sweep polarography. The absorption behavior of meso-tetra (4-sulfonylphenyl) porphyrin (H2TPPS4) complex with lead ion has also been studied.In Na2B4O7-NaOH solution with pH=l 0.5, the reduction peaks of the ligand are P1 (Ep1=-0.38V), P2 (Ep2=-1.04V), which potentials are obtained vs. S.C.E. When lead ion has been added into above solution. The peak current of P1 and P2 decrease, and a new reduction peak P3 (Ep3=-1.10 V) appears. It shows that the TPPS4-Pb(Ⅱ) complex forms,and this method can be applied to study the complex.

  3. Determination of Lead by Electrochemistry

    Institute of Scientific and Technical Information of China (English)

    HE; YuFeng

    2001-01-01

    Lead is one of the poisonous trace element for human body. It is important to find a way for measuring content of lead. Deternination of lead by electrochemistry is one of a method[1]. In this paper, lead is determined by single-sweep polarography. The absorption behavior of meso-tetra (4-sulfonylphenyl) porphyrin (H2TPPS4) complex with lead ion has also been studied.In Na2B4O7-NaOH solution with pH=l 0.5, the reduction peaks of the ligand are P1 (Ep1=-0.38V), P2 (Ep2=-1.04V), which potentials are obtained vs. S.C.E. When lead ion has been added into above solution. The peak current of P1 and P2 decrease, and a new reduction peak P3 (Ep3=-1.10 V) appears. It shows that the TPPS4-Pb(Ⅱ) complex forms,and this method can be applied to study the complex.……

  4. Oxisterol determination in selected coffees.

    Science.gov (United States)

    Turchetto, E; Lercker, G; Bortolomeazzi, R

    1993-01-01

    The main aim of green-coffee processing techniques, such as decaffeination and roasting, is always to maintain a very high level of quality in taste and flavor, the beverage's most important characteristics to consumers. Oxidative alterations of coffee lipids, which can occur in roasting, exert a very marked influence on these quality traits. Determining the extent of oxidation thus can provide an indication of the product's potential shelf-life and reveal traces of any newly-formed oxidative products that might prove nutritionally unsafe. Yet, while much attention has recently been focused on certain by-products induced by cholesterol oxidation and their proven toxicity as risk factors in atherosclerosis and cancer, oxidated phytosterols have largely gone unnoticed, being considered along with beta-sitosterol as not very dangerous in that neither is absorbed by the intestinal tract. The present study investigates the substances derived from phytosterol oxidation (oxisterols) in samples of regular and decaffeinated commercial coffees. The findings show that oxisterols were absent in some samples and that the traces of oxidate phytosterols detected in others were well below the threshold considered as toxicologically active.

  5. [Sodium determination in biological fluids].

    Science.gov (United States)

    Cristol, J-P; Balint, B; Canaud, B; Daurés, M-F

    2007-09-01

    Electrolyte disorders are frequently observed in nephrology and intensive care unit department and Na determination is routinely performed in biochemistry laboratories. Three methods are currently available. Flame photometry remains the reference method. With this method the serum sample is diluted before the actual measurement is obtained. Results are expressed as molarity (per Liter of plasma). Potentiometric methods have an increasing importance due to the advances in ion sensitive (selective) electrodes (ISE). Whereas the instruments for routine chemical analysis typically use indirect potentiometry (involving te dilution of samples) to measure sodium levels, the equipment for measuring arterial blood gases use direct potentiometry without any dilution. Thus, results obtained with indirect potentiometry are expressed in molarity (per liter of plasma) while results obtained with direct potentiometry are initially given in morality (per kg of plasma water) then converted in molarity. Analytical performances are in all cases satisfactory and therefore all the methods could be used in both normal and pathological ranges. Methods involving sample dilution such as flame photometry or indirect potentiometry, the serum sodium value would be expected to be low in case of decrease plasma water (pseudohyponatremia). By contrast, with direct potentiometry where no sample dilution takes place, no interference would be expected since the activity of sodium in the water phase only is being measured. Thus, the classical pseudohyponatremia observed with hyperlipemia or paraproteinemia are not further observed with direct potentiometry. These differences in methodology should be taken into account to explain discrepancies between results obtained with classical biochemistry analyser and with blood gas apparatus.

  6. Geographic Determinants of Chinese Urbanization

    Science.gov (United States)

    Mccord, G. C.; Christensen, P.

    2011-12-01

    In the first years of the 21st century, the human race became primarily urban for the first time in history. With countries like India and China rapidly undergoing structural change from rural agricultural-based economies to urbanized manufacturing- and service-based economies, knowing where the coming waves of urbanization will occur would be of interest for infrastructure planning and for modeling consequences for ecological systems. We employ spatial econometric methods (geographically weighted regression, spatial lag models, and spatial errors models) to estimate two determinants of urbanization in China. The first is the role of physical geography, measured as topography-adjusted distance to major ports and suitability of land for agriculture. The second is the spatial agglomeration effect, which we estimate with a spatial lag model. We find that Chinese urbanization between 1990 and 2000 exhibited important spatial agglomeration effects, as well as significant explanatory power of nearby agricultural suitability and distance to ports, both in a nationwide model and in a model of local regression estimates. These results can help predict the location of new Chinese urbanization, and imply that climate change-induced changes in agricultural potential can affect the spatial distribution of urban areas.

  7. Determination of virginiamycin in feeds.

    Science.gov (United States)

    Ragheb, H S; Black, L J; Waisner, D L

    1979-05-01

    Virginiamycin was extracted from the feed by ethanol-pH 2.5 phosphate buffer (1 + 1). The pH during extraction was adjusted (when necessary) to between 4 and 5. Sample dilutions and the standard dose response line were prepared to contain ethanol pH 6 phosphate buffer (2 + 8), and the test organism was Sarcina lutea. Three feeds (a poultry ration, a swine finishing ration, and a swine starter ration) showed virginiamycin recovery of 88.8--108.9% when standard solutions were added at concentrations of 4.54--90.8 g/ton. The coefficient of variation (4--20%) was larger for low potency feeds (10 g/ton) compared to the higher feeds (100 g/ton). Similarly, excellent recovery was obtained when the swine starter feed was fortified by a commercial premix. Amprolium, roxarsone, and monensin can be present at 20 times the concentration of virginiamycin with little or no interference in the antibiotic determination. Lasalocid at 10 times the concentration of virginiamycin caused a slightly positive bias (recovery, 107.4%).

  8. Weapons barrel life cycle determination

    Directory of Open Access Journals (Sweden)

    Nebojša Pene Hristov

    2013-10-01

    Full Text Available This article describes the dynamic processes within the gun barrel during the firing process in exploitation. It generally defines the basic principles of constructing tube elements, and shows the distortion of the basic geometry of the tube interior due to wear as well as the impact it causes during exploitation. The article also defines basic empirical models as well as a model based on fracture mechanics for the calculation of a use-life of the barrel, and other elements essential for the safe use of the barrel as the basic weapon element. Erosion causes are analysed in order to control and reduce wear and prolong the lifetime of the gun barrel. It gives directions for the reparation of barrels with wasted resources. In conclusion, the most influential elements of tube wear are given as well as possible modifications of existing systems, primarily propellant charges, with a purpose of prolonging lifetime of gun barrels. The guidelines for a proper determination of the lifetime based on the barrel condition assessment are given as well. INTRODUCTION The barrel as the basic element of each weapon is described as well as the processes occurring during the firing that have impulsive character and are accompanied by large amounts of energy. The basic elements of barrel and itheir constructive characteristics are descibed. The relation between Internal ballistics, ie calculation of the propellant gas pressure in the firing process, and structural elements defined by the barrel material resistance is shown. In general, this part of the study explains the methodology of the gun barrel structural elements calculation, ie. barrel geometry, taking into account the degrees of safety in accordance with Military Standards.   TUBE WEAR AND DEFORMATIONS The weapon barrel gradually wears out during exploitation due to which it no longer satisfies the set requirements. It is considered that the barrel has experienced a lifetime when it fails to fulfill the

  9. Microenvironment Determinants of Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Zhang Chenyu

    2011-02-01

    Full Text Available Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis.

  10. Genetic determinants of plasma triglycerides

    Science.gov (United States)

    Johansen, Christopher T.; Kathiresan, Sekar; Hegele, Robert A.

    2011-01-01

    Plasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might help specify new directions for therapeutic interventions. Recent genome-wide association studies (GWAS) have identified both known and novel loci associated with plasma TG concentration. However, genetic variation at these loci explains only ∼10% of overall TG variation within the population. As the GWAS approach may be reaching its limit for discovering genetic determinants of TG, alternative genetic strategies, such as rare variant sequencing studies and evaluation of animal models, may provide complementary information to flesh out knowledge of clinically and biologically important pathways in TG metabolism. Herein, we review genes recently implicated in TG metabolism and describe how some of these genes likely modulate plasma TG concentration. We also discuss lessons regarding plasma TG metabolism learned from various genomic and genetic experimental approaches. Treatment of patients with moderate to severe hypertriglyceridemia with existing therapies is often challenging; thus, gene products and pathways found in recent genetic research studies provide hope for development of more effective clinical strategies. PMID:21041806

  11. Computational advances in nanostructure determination

    Science.gov (United States)

    Farrow, Christopher Lyn

    The atomic pair distribution function (PDF) and extended x-ray absorption fine structure (EXAFS) techniques fill a hole in conventional crystallographic analysis, which resolves the average long-range structure of a material but inadequately determines deviations from the average. These techniques provide structural information on the sub-nanometer scale and are helping characterize modern materials. Despite their successes, PDF and EXAFS often fall short of adequately describing complex nanostructured materials. Parallel PDF and EXAFS refinement, or corefinement, is one attempt at extending the applicability of these techniques. Corefinement combines the best parts of PDF and EXAFS, the chemical-specific and short-range detail of EXAFS and the short and intermediate-range information from the PDF. New ab initio methods are also being employed to find structures from the PDF. These techniques use the bond length information encoded in the PDF to assemble structures without a model. On another front, new software has been developed to introduce the PDF method to a larger community. Broad awareness of the PDF technique will help drive its future development.

  12. Chromosomal instability determines taxane response

    DEFF Research Database (Denmark)

    Swanton, C.; Nicke, B.; Schuett, M.

    2009-01-01

    Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromos...... resistance but carboplatin sensitivity, indicating that CIN may determine MTS response in vivo. Thus, pretherapeutic assessment of CIN may optimize treatment stratification and clinical trial design using these agents....... chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells. Overexpression of these "CIN-survival'' genes is associated with poor outcome in estrogen receptor......-positive breast cancer and occurs frequently in basal-like and Her2-positive cases. In diploid cells, but not in chromosomally unstable cells, paclitaxel causes repression of CIN-survival genes, followed by cell death. In the OV01 ovarian cancer clinical trial, a high level of CIN was associated with taxane...

  13. 49 CFR 107.221 - Determination.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Determination. 107.221 Section 107.221... PROGRAM PROCEDURES Preemption Waiver of Preemption Determinations § 107.221 Determination. (a) After... Chief Counsel issues a determination. (b) The Chief Counsel may issue a waiver of preemption only on...

  14. 49 CFR 107.209 - Determination.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Determination. 107.209 Section 107.209... PROGRAM PROCEDURES Preemption Preemption Determinations § 107.209 Determination. (a) Upon consideration of the application and other relevant information received, the Chief Counsel issues a determination. (b...

  15. 36 CFR 223.36 - Volume determination.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Volume determination. 223.36... Volume determination. (a) Timber sale contracts may provide for volume determination by scaling... the contract or permit provides for the determination of volume by tree measurement and the timber has...

  16. 45 CFR 12a.4 - Suitability determination.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Suitability determination. 12a.4 Section 12a.4... PROPERTY TO ASSIST THE HOMELESS § 12a.4 Suitability determination. (a) Suitability determination. Within 30... determination to the landholding agency. Properties that are under lease, contract, license, or agreement by...

  17. 36 CFR 902.60 - Initial determination.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Initial determination. 902.60... INFORMATION ACT Time Limitations § 902.60 Initial determination. (a) An initial determination whether or not... workdays in accordance with § 902.62. (b) Upon making initial determination, the Administrative Officer...

  18. 40 CFR 231.5 - Recommended determination.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Recommended determination. 231.5... 404(c) PROCEDURES § 231.5 Recommended determination. (a) The Regional Administrator or his designee... public notice of the proposed determination, either withdraw the proposed determination or prepare a...

  19. 42 CFR 405.810 - Review determination.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Review determination. 405.810 Section 405.810....810 Review determination. Subject to the provisions of §§ 405.807 through 405.809, the carrier shall... determination affirming or revising in whole or in part the findings and determination in question. ...

  20. 14 CFR 415.7 - Payload determination.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Payload determination. 415.7 Section 415.7... TRANSPORTATION LICENSING LAUNCH LICENSE General § 415.7 Payload determination. A payload determination is... determination. Either a launch license applicant or a payload owner or operator may request a review of its...

  1. 49 CFR 397.211 - Preemption determination.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Preemption determination. 397.211 Section 397.211... MATERIALS; DRIVING AND PARKING RULES Preemption Procedures § 397.211 Preemption determination. (a) Upon... determination. (b) Notwithstanding that an application for a determination has not been filed under § 397.205...

  2. 49 CFR 512.16 - Class determinations.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false Class determinations. 512.16 Section 512.16... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONFIDENTIAL BUSINESS INFORMATION Agency Determination § 512.16 Class determinations. (a) The Chief Counsel may issue class determinations of categories of...

  3. Determination of free growth hormone.

    Science.gov (United States)

    Frystyk, Jan; Andreasen, Caroline Marie; Fisker, Sanne

    2008-08-01

    Approximately 50% of circulating GH is bound to the high-affinity GH-binding protein (GHBP), which is known to affect the pharmacokinetics, bioactivity, and quantitative determination of GH. Nevertheless, the presence of GHBP is rarely taken into account in the clinical use of GH measurements. Our objective was to develop an assay for free GH in serum. We used ultrafiltration by centrifugation. Due to the small molecular difference between GH and GHBP, the size of GHBP and GHBP-GH complexes was increased by preincubation of serum with a monoclonal GHBP antibody (MAb 263). The ultrafiltration membrane almost completely retained all GHBP (>98.5%) and allowed free passage of unbound GH (>98.4%). Addition of increasing concentrations of GHBP reduced free GH dose dependently, and measured and calculated levels of free GH changed in parallel. During an insulin-tolerance test, free and total GH changed in parallel in all individuals (n = 11) and their peak values as well as area under the curve values were positively correlated (r = 0.89; P < 0.001 and r = 0.92; P < 0.001, respectively). Of note, the relative levels of free GH (calculated as the area under the curve of free to total GH) was inversely correlated with GHBP (r = -0.94; P < 0.001). It is possible to measure free GH in human serum. Free GH correlated positively with total GH and inversely with GHBP. Measurement of free GH may be a helpful future tool in the management of GH disorders and in studies of GH-GHBP interrelationships.

  4. Determinants of obsessive compulsive disorder

    Directory of Open Access Journals (Sweden)

    Sateesh Rangarao Koujalgi

    2015-01-01

    Full Text Available Background: The family has a significant role both in the genesis and prognosis of obsessive-compulsive disorder (OCD. Early identification, treatment and prevention of relapse in patients with OCD have important therapeutic and psychosocial implications. Hence, to study and determine family factors like high expressed emotion (EE and family dysfunction are essential. These two factors play a significant role in the relapse and course of OCD. Aim: The aim was to study the relationship between family function, EE and OCD. Materials and Methods: The sample included 30 patients who were diagnosed with OCD using International Classification of Diseases-10 Diagnostic Criteria for Research criteria. Yale-Brown obsessive compulsive scale was used to assess the severity of OCD. EE was assessed in cases using Family Emotional Involvement and Criticism Scale and family function was assessed in cases using the family interaction pattern scale (FIPS. Statistical analysis was performed using Statistical Packages for Social Science. Patient and caregivers of the patients were assessed on self-developed socio-demographic proforma. Pearson co-relation co-efficient test was used to study the correlation between OCD, high EE and family dysfunction. Results: The result showed that there are significant correlations between high EE, family dysfunction and OCD. The Pearson correlation co-efficient between OCD and EE shows a significant correlation between the high EE of the caregiver and OCD with P < 0.01. The Pearson correlation co-efficient between OCD and Family Interaction Pattern Scale shows a significant correlation between the family dysfunction of the caregiver and OCD. Conclusion: Impaired family function and high EE in caregivers associated with OCD. Thus clinical interventions may improve the functional abilities of the caregivers.

  5. Tackling the diversity of sex determination.

    Science.gov (United States)

    Wedekind, Claus; Stelkens, Rike B

    2010-02-23

    A workshop on 'The evolution of sex determination systems' was held at a remote place in the Swiss Alps from 17 to 20 June 2009. It brought together theoreticians and empiricists, the latter ranging from molecular geneticists to evolutionary ecologists, all trying to understand key aspects of sex determination. The topics discussed included the evolutionary origins of sex determination, the diversity of sex determination mechanisms in different taxa, and the transition from genotypic to environmental sex determination and vice versa.

  6. In situ real-time evaluation of radiation-responsive promoters in the extremely radioresistant microbe Deinococcus radiodurans

    Indian Academy of Sciences (India)

    Narasimha Anaganti; Bhakti Basu; Shree Kumar Apte

    2016-06-01

    A third generation promoter probe shuttle vector pKG was constructed, using the green fluorescent protein as a reporter, for in situ evaluation of Deinococcal promoter activity in Escherichia coli or Deinococcus radiodurans. The construct yielded zero background fluorescence in both the organisms, in the absence of promoter sequences. Fifteen deinococcal promoters, either harbouring Radiation and Desiccation Response Motif (RDRM) or not, were cloned in vector pKG. Only the RDRM-promoter constructs displayed (i) gamma radiation inducible GFP expression in D. radiodurans, following gamma irradiation, (ii) DdrO-mediated repression of GFP expression in heterologous E. coli, or (iii) abolition in GFP induction following gamma irradiation, in pprI mutant of D. radiodurans. Utility of pKG vector for real-time in situ assessment of deinococcal promoter function was, thus, successfully demonstrated.

  7. Plant traits determine forest flammability

    Science.gov (United States)

    Zylstra, Philip; Bradstock, Ross

    2016-04-01

    Carbon and nutrient cycles in forest ecosystems are influenced by their inherent flammability - a property determined by the traits of the component plant species that form the fuel and influence the micro climate of a fire. In the absence of a model capable of explaining the complexity of such a system however, flammability is frequently represented by simple metrics such as surface fuel load. The implications of modelling fire - flammability feedbacks using surface fuel load were examined and compared to a biophysical, mechanistic model (Forest Flammability Model) that incorporates the influence of structural plant traits (e.g. crown shape and spacing) and leaf traits (e.g. thickness, dimensions and moisture). Fuels burn with values of combustibility modelled from leaf traits, transferring convective heat along vectors defined by flame angle and with plume temperatures that decrease with distance from the flame. Flames are re-calculated in one-second time-steps, with new leaves within the plant, neighbouring plants or higher strata ignited when the modelled time to ignition is reached, and other leaves extinguishing when their modelled flame duration is exceeded. The relative influence of surface fuels, vegetation structure and plant leaf traits were examined by comparing flame heights modelled using three treatments that successively added these components within the FFM. Validation was performed across a diverse range of eucalypt forests burnt under widely varying conditions during a forest fire in the Brindabella Ranges west of Canberra (ACT) in 2003. Flame heights ranged from 10 cm to more than 20 m, with an average of 4 m. When modelled from surface fuels alone, flame heights were on average 1.5m smaller than observed values, and were predicted within the error range 28% of the time. The addition of plant structure produced predicted flame heights that were on average 1.5m larger than observed, but were correct 53% of the time. The over-prediction in this

  8. Determination and control of schistosomiasis

    Directory of Open Access Journals (Sweden)

    Frederico Simões Barbosa

    1995-04-01

    Full Text Available The subject of this conference reflects the scientific community's interest in seeking to understand the complex causal web whose various social, economic, and biological components interact in the production and reproduction of schistosomiasis and its control in relation to community participation. From the onset, the author stresses the impossibility of dealing separately with community participation, as if social components were just one more "weapon" in the arsenal for schistosomiasis control. This study begins with a brief historical review of the 71 years of control activities with this endemic disease, stressing the enormous efforts and huge expenditures in this field vis-à-vis the limited results, despite the extraordinary technological development of specific, classical control inputs such as new treatment drugs and molluscicides. The article then discusses the various strategies used in control programs, emphasizing ideological consistencies and contradictions. Interactions at the macro and micro levels are discussed, as are the determinants and risk factors involved in producing the disease's endemicity. Unequal occupation of space leaves the segregated portion of the population exposed to extremely favorable conditions for transmission of the disease. This raises the issue of how to control an endemic disease which is so closely linked to the way of life imposed on the population. The study challenges the classical control model and suggests an alternative model now undergoing medium-term investigation in the States of Espirito Santo, and Pernambuco, Brazil. The author concludes that we do not need new strategies, but a new control model, contrary to the prevailing classical model in both concept and practice. From the conceptual point of view, the new model mentioned above is different from others in that schistosomiasis control is seen from a social perspective stressing the population's accumulated knowledge in addition to the

  9. Determination of retinal surface area.

    Science.gov (United States)

    Nagra, Manbir; Gilmartin, Bernard; Thai, Ngoc Jade; Logan, Nicola S

    2017-09-01

    Previous attempts at determining retinal surface area and surface area of the whole eye have been based upon mathematical calculations derived from retinal photographs, schematic eyes and retinal biopsies of donor eyes. 3-dimensional (3-D) ocular magnetic resonance imaging (MRI) allows a more direct measurement, it can be used to image the eye in vivo, and there is no risk of tissue shrinkage. The primary purpose of this study is to compare, using T2-weighted 3D MRI, retinal surface areas for superior-temporal (ST), inferior-temporal (IT), superior-nasal (SN) and inferior-nasal (IN) retinal quadrants. An ancillary aim is to examine whether inter-quadrant variations in area are concordant with reported inter-quadrant patterns of susceptibility to retinal breaks associated with posterior vitreous detachment (PVD). Seventy-three adult participants presenting without retinal pathology (mean age 26.25 ± 6.06 years) were scanned using a Siemens 3-Tesla MRI scanner to provide T2-weighted MR images that demarcate fluid-filled internal structures for the whole eye and provide high-contrast delineation of the vitreous-retina interface. Integrated MRI software generated total internal ocular surface area (TSA). The second nodal point was used to demarcate the origin of the peripheral retina in order to calculate total retinal surface area (RSA) and quadrant retinal surface areas (QRSA) for ST, IT, SN, and IN quadrants. Mean spherical error (MSE) was -2.50 ± 4.03D and mean axial length (AL) 24.51 ± 1.57 mm. Mean TSA and RSA for the RE were 2058 ± 189 and 1363 ± 160 mm(2) , respectively. Repeated measures anova for QRSA data indicated a significant difference within-quadrants (P area/mm increase in AL. Although the differences between QRSAs are relatively small, there was evidence of concordance with reported inter-quadrant patterns of susceptibility to retinal breaks associated with PVD. The data allow AL to be converted to QRSAs, which will assist further

  10. Effect of radiation on normal hematopoiesis and on viral induced cancers of the hematopoietic system. Three-year technical progress report, August 1, 1973--April 30, 1976. [X radiation, mice

    Energy Technology Data Exchange (ETDEWEB)

    OKunewick, J.P.

    1976-01-01

    In studies conducted during the first three-year segment of this contract, it was observed that in the process of viral leukemogenesis the affected animals became more radioresistant than normal. Initial studies into the reason for the enhanced radioresistance implicated an increase in the number of pluripotent stem cells as one possible cause. During the current period, studies were carried out to further define the effect of the virus on stem cells and their kinetics using exposure to tritiated thymidine (/sup 3/HTdR) in vivo and in vitro. In addition, separate studies were initiated in an attempt to determine if the immune system played a part in the radioresistance, as well as what the effects might be of immune manipulations on the disease during the oncogenic period. Finally, studies were also undertaken to assess the sensitivity of the virus itself to radiation in vitro and in vivo to radiation and treatment with cells transplanted from viral resistant mice.

  11. A determinant of generalized Fibonacci numbers

    CERN Document Server

    Krattenthaler, Christian

    2012-01-01

    We evaluate a determinant of generalized Fibonacci numbers, thus providing a common generalization of several determinant evaluation results that have previously appeared in the literature, all of them extending Cassini's identity for Fibonacci numbers.

  12. Extractive spectrophotometric method for the determination of ...

    African Journals Online (AJOL)

    Extractive spectrophotometric method for the determination of carbaryl in environmental samples. ... Bulletin of the Chemical Society of Ethiopia ... method has been developed for its determination in environmental samples viz. soil, water and ...

  13. Tackling the diversity of sex determination.

    OpenAIRE

    Wedekind, C; Stelkens, R. B.

    2010-01-01

    A workshop on ‘The evolution of sex determination systems’ was held at a remote place in the Swiss Alps from 17 to 20 June 2009. It brought together theoreticians and empiricists, the latter ranging from molecular geneticists to evolutionary ecologists, all trying to understand key aspects of sex determination. The topics discussed included the evolutionary origins of sex determination, the diversity of sex determination mechanisms in different taxa, and the transition from genotypic to envir...

  14. 40 CFR 13.39 - Agency determination.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Agency determination. 13.39 Section 13... Referral of Debts to IRS for Tax Refund Offset § 13.39 Agency determination. (a) Following review of the evidence, EPA will issue a written decision. (b) If EPA either sustains or amends its determination, it...

  15. 7 CFR 1499.3 - Eligibility determination.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Eligibility determination. 1499.3 Section 1499.3 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT... determination. (a) An entity will be eligible to become a participant only after FAS determines that the entity...

  16. 36 CFR 908.33 - Final determination.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Final determination. 908.33... DEVELOPMENT AREA Review Procedure § 908.33 Final determination. (a) The Chairman or designee(s) shall make a final determination on the claim within 45 days of receipt of the file from the Director of Real Estate...

  17. 18 CFR 349.6 - Determination.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Determination. 349.6 Section 349.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... PROPOSED REMEDIES § 349.6 Determination. If no formal hearing is had the matter in issue will be determined...

  18. 19 CFR 212.26 - Determination.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Determination. 212.26 Section 212.26 Customs... IMPLEMENTATION OF THE EQUAL ACCESS TO JUSTICE ACT Procedures for Considering Applications § 212.26 Determination. The presiding officer shall issue a recommended determination on the application within 90 days after...

  19. 12 CFR 339.8 - Determination fees.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Determination fees. 339.8 Section 339.8 Banks... IN AREAS HAVING SPECIAL FLOOD HAZARDS § 339.8 Determination fees. (a) General. Notwithstanding any... hazard area. A determination fee may also include, but is not limited to, a fee for life-of-loan...

  20. 38 CFR 36.4707 - Determination fees.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Determination fees. 36...) LOAN GUARANTY Sale of Loans, Guarantee of Payment, and Flood Insurance § 36.4707 Determination fees. (a... will be located in a special flood hazard area. A determination fee may also include, but is not...

  1. 29 CFR 34.46 - Final Determination.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Final Determination. 34.46 Section 34.46 Labor Office of the... TRAINING PARTNERSHIP ACT OF 1982, AS AMENDED (JTPA) Compliance Procedures § 34.46 Final Determination. (a... period established by the Letter of Findings, Notice to Show Cause or Initial Determination; or (2) The...

  2. 12 CFR 614.4950 - Determination fees.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Determination fees. 614.4950 Section 614.4950... Insurance Requirements § 614.4950 Determination fees. (a) General. Notwithstanding any Federal or State law... or will be located in a special flood hazard area. A determination fee may also include, but is not...

  3. 49 CFR 89.45 - Department determination.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Department determination. 89.45 Section 89.45... Referral of Debts to IRS for Tax Refund Offset § 89.45 Department determination. (a) Following review of... supporting rationale. (b) If the Department either sustains or amends its determination, it shall notify the...

  4. 12 CFR 760.8 - Determination fees.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Determination fees. 760.8 Section 760.8 Banks... HAVING SPECIAL FLOOD HAZARDS § 760.8 Determination fees. (a) General. Notwithstanding any Federal or... flood hazard area. A determination fee may also include, but is not limited to, a fee for life-of-loan...

  5. 12 CFR 572.8 - Determination fees.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Determination fees. 572.8 Section 572.8 Banks... FLOOD HAZARDS § 572.8 Determination fees. (a) General. Notwithstanding any Federal or State law other... flood hazard area. A determination fee may also include, but is not limited to, a fee for life-of-loan...

  6. 7 CFR 1599.3 - Eligibility determination.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Eligibility determination. 1599.3 Section 1599.3 Agriculture Regulations of the Department of Agriculture (Continued) FOREIGN AGRICULTURAL SERVICE, DEPARTMENT... Eligibility determination. (a) An entity will be eligible to become a participant only after FAS determines...

  7. 45 CFR 150.219 - Final determination.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Final determination. 150.219 Section 150.219... Are Failing To Substantially Enforce HIPAA Requirements § 150.219 Final determination. If, after... the State a written notice of its final determination. The notice includes the following: (a...

  8. 28 CFR 301.305 - Initial determination.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Initial determination. 301.305 Section... COMPENSATION Compensation for Work-Related Physical Impairment or Death § 301.305 Initial determination. A... determination, including the reasons therefore, together with notification of the right to appeal the...

  9. 45 CFR 96.41 - General determination.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false General determination. 96.41 Section 96.41 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.41 General determination. (a) The Department has determined...

  10. 16 CFR 901.7 - Adverse determination.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Adverse determination. 901.7 Section 901.7... APPLICATION FOR EXEMPTION FROM THE PROVISIONS OF THE ACT § 901.7 Adverse determination. (a) If, after... of the information before it that it cannot make a favorable determination in connection with the...

  11. 37 CFR 501.7 - Agency determination.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Agency determination. 501.7... UNIFORM PATENT POLICY FOR RIGHTS IN INVENTIONS MADE BY GOVERNMENT EMPLOYEES § 501.7 Agency determination... left with the employee, the agency shall notify the employee of this determination. In cases pursuant...

  12. 12 CFR 404.15 - Initial determination.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Initial determination. 404.15 Section 404.15... the Privacy Act of 1974 § 404.15 Initial determination. (a) Time for processing. The Freedom of... the requester of any processing fee. (2) A denial is a determination to withhold any requested record...

  13. 40 CFR 1042.825 - Baseline determination.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Baseline determination. 1042.825... Provisions for Remanufactured Marine Engines § 1042.825 Baseline determination. (a) For the purpose of this... not valid. (f) Use good engineering judgment for all aspects of the baseline determination. We may...

  14. 5 CFR 1216.206 - Final determination.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Final determination. 1216.206 Section... PROCEEDINGS Demands or Requests for Testimony and Production of Documents § 1216.206 Final determination. The General Counsel makes the final determination on demands to requests to employees for production of...

  15. 28 CFR 44.303 - Determination.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Determination. 44.303 Section 44.303... Enforcement Procedures § 44.303 Determination. (a) Within 120 days of the receipt of a charge, the Special... the end of the 120-day period, the Special Counsel shall issue letters of determination by certified...

  16. 12 CFR 404.8 - Initial determination.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Initial determination. 404.8 Section 404.8... Disclosure of Records Under the Freedom of Information Act. § 404.8 Initial determination. (a) Authority to..., review, and the initial determination. (b) Referrals to other government agencies. A requested record in...

  17. 49 CFR 1018.95 - Board determination.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false Board determination. 1018.95 Section 1018.95... determination. (a) Following review of the evidence, the Board will issue a written decision which will include... determination, it shall notify the debtor of its intent to refer the debt to the IRS for offset against the...

  18. 21 CFR 26.9 - Equivalence determination.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Equivalence determination. 26.9 Section 26.9 Food... Specific Sector Provisions for Pharmaceutical Good Manufacturing Practices § 26.9 Equivalence determination... document insufficient evidence of equivalence, lack of opportunity to assess equivalence or a determination...

  19. 44 CFR 68.11 - Determination.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Determination. 68.11 Section... § 68.11 Determination. The board shall render its written decision within 45 days after the conclusion... Administrator for review and approval. The Administrator shall make the final base flood elevation determination...

  20. 5 CFR 2417.206 - Final determination.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Final determination. 2417.206 Section... Requests for Testimony and Production of Documents § 2417.206 Final determination. The Chairman of the FLRA, or the Chairman's designee, makes the final determination on demands or requests to employees thereof...

  1. 18 CFR 41.6 - Determination.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Determination. 41.6 Section 41.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF....6 Determination. If no formal hearing is had the matter in issue will be determined by the...

  2. 36 CFR 902.61 - Final determination.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Final determination. 902.61 Section 902.61 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION FREEDOM OF INFORMATION ACT Time Limitations § 902.61 Final determination. A determination with respect to any appeal made...

  3. 18 CFR 158.6 - Determination.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Determination. 158.6 Section 158.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT....6 Determination. If no formal hearing is had the matter in issue will be determined by the...

  4. 45 CFR 150.217 - Preliminary determination.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Preliminary determination. 150.217 Section 150.217... Are Failing To Substantially Enforce HIPAA Requirements § 150.217 Preliminary determination. If, at... designees). (b) Notifies the State of CMS's preliminary determination that the State has failed to...

  5. 33 CFR 136.309 - Advertisement determinations.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Advertisement determinations. 136... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Designation of Source and Advertisement § 136.309 Advertisement determinations. (a) The Director, NPFC, determines for each incident the type, geographic...

  6. 40 CFR 2.207 - Class determinations.

    Science.gov (United States)

    2010-07-01

    ... Confidentiality of Business Information § 2.207 Class determinations. (a) The General Counsel may make and issue a class determination under this section if he finds that— (1) EPA possesses, or is obtaining, related... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Class determinations. 2.207 Section...

  7. Fermion Determinants: Some Recent Analytic Results

    CERN Document Server

    Fry, M P

    2004-01-01

    The use of known analytic results for the continuum fermion determinants in QCD and QED as benchmarks for zero lattice spacing extrapolations of lattice fermion determinants is proposed. Specifically, they can be used as a check on the universality hypothesis relating the continuum limits of the na\\"{\\i}ve, staggered and Wilson fermion determinants.

  8. Genetic and pharmacogenetic determinants of cardiovascular disease

    NARCIS (Netherlands)

    Verschuren, Jeffrey Johan Willem

    2013-01-01

    This thesis, titled ‘Genetic and pharmacogenetic determinants of cardiovascular disease’ is divided in three sections. In section one the genetic determinants of coronary restenosis are explored. In the first genome-wide association study on this condition, in the GENetic DEterminants of Restenosis

  9. Stability of waves using the Fredholm determinant

    CERN Document Server

    Karambal, Issa

    2011-01-01

    We present a new method for reducing the Fredholm determinant associated with an underlying Birman-Schwinger operator to a finite dimensional determinant. Moreover, we compute explicitly the connection between the Fredholm determinant and the Evans function for travelling wave problems of all orders, in one dimension

  10. Sequence Classification: 889055 [

    Lifescience Database Archive (English)

    Full Text Available during DNA replication stress, where it forms a replication-pausing complex with Tof1p and is phosphorylated...point protein found at replication forks, required for DNA replication; also required for Rad53p activation

  11. Liquidity Determinants of Moroccan Banking Industry

    OpenAIRE

    FERROUHI, El Mehdi; LEHADIRI, Abderrassoul

    2013-01-01

    This paper analyzes the behavior of Moroccan bank’s liquidity during the period 2001 – 2012. The research aims to identify the determinants of Moroccan bank’s liquidity. We first evaluate Moroccan banks’ liquidity positions through different liquidity ratios to determine the effects of financial crisis on bank’s liquidity. We then highlight the effect of banks’ size on banks’ liquidity. Finally, we identify determinants of Moroccan bank’s liquidity using panel data regression. From results ob...

  12. Sex determination in forensic odontology: A review.

    Science.gov (United States)

    Ramakrishnan, K; Sharma, Subramanya; Sreeja, C; Pratima, D Bhavani; Aesha, I; Vijayabanu, B

    2015-08-01

    Forensic odontology is the application of dental principles to legal issues. Sex determination is a subdivision of forensic odontology and it is very important especially when information relating to the deceased is unavailable. Sex determination becomes the first priority in the process of identification of a person by a forensic investigator in the case of mishaps, chemical and nuclear bomb explosions, natural disasters crime investigations, and ethnic studies. This article reviews upon the various methods used in sex determination.

  13. Zero Triple Product Determined Matrix Algebras

    Directory of Open Access Journals (Sweden)

    Hongmei Yao

    2012-01-01

    triple product in the aforementioned definition is replaced by Jordan triple product, then A is called zero Jordan triple product determined. This paper mainly shows that matrix algebra Mn(B, n≥3, where B is any commutative unital algebra even different from the above mentioned commutative unital algebra C, is always zero triple product determined, and Mn(F, n≥3, where F is any field with chF≠2, is also zero Jordan triple product determined.

  14. DETERMINANTS OF CUSTOMER LOYALTY. A THEORETICAL APPROACH

    OpenAIRE

    Claudia Bobâlcă

    2014-01-01

    The purpose of the research is to investigate the determinants of customer loyalty. The research objectives are: (1) to identify the factors that affect customer loyalty; (2) to identify the relations between the determinants of loyalty and loyalty construct. We used an exploratory research based on a documentary study. The main determinants of customer loyalty that are identified and studied in past researchers are: satisfaction, trust, commitment, involvement, perceived risk, switching cost...

  15. Sex determination in forensic odontology: A review

    Science.gov (United States)

    Ramakrishnan, K.; Sharma, Subramanya; Sreeja, C.; Pratima, D. Bhavani; Aesha, I.; Vijayabanu, B.

    2015-01-01

    Forensic odontology is the application of dental principles to legal issues. Sex determination is a subdivision of forensic odontology and it is very important especially when information relating to the deceased is unavailable. Sex determination becomes the first priority in the process of identification of a person by a forensic investigator in the case of mishaps, chemical and nuclear bomb explosions, natural disasters crime investigations, and ethnic studies. This article reviews upon the various methods used in sex determination. PMID:26538886

  16. Determinant Factors of Dividend Payments in Brazil

    National Research Council Canada - National Science Library

    Forti, Cristiano Augusto Borges; Peixoto, Fernanda Maciel; Alves, Denis Lima e

    2015-01-01

    .... Relationships between Dividends/Total Assets and potential determinants discussed in the literature, including firm size, corporate governance, profitability, leverage, market to book, liquidity...

  17. Determination of arginine catabolism by salivary pellet

    Directory of Open Access Journals (Sweden)

    M.A. Hoogenkamp

    2014-01-01

    Changing from the use of the toxic, environmentally hazardous, mercury containing Nessler's reagent to a colorimetric enzyme assay achieved a safer and greener determination of ammonium concentration.

  18. Can body volume be determined by PET?

    Science.gov (United States)

    Hentschel, Michael; Paul, Dominik; Korsten-Reck, Ulrike; Mix, Michael; Müller, Frank; Merk, Stefan; Moser, Ernst; Brink, Ingo

    2005-05-01

    To avoid dependence on body weight, the standardised uptake value (SUV) in positron emission tomography (PET) can instead be normalised to the lean body mass (LBM), which can be determined from body volume and mass. This study was designed to answer the following questions: Firstly, can the total body volume in principle be determined using PET? Secondly, is the precision of this measurement comparable to that achieved using an established standard method. Ten patients were examined during oncological whole-body PET examinations. The whole-body volume of the patients was determined from the transmission scan in PET. Air displacement plethysmography with BOD POD was used for comparison as the standard method of volume determination. In all patients, the whole-body volumes could be determined using PET and the standard method. Bland and Altman [23] analysis for agreement between the volumes determined by the two methods (presentation of differences vs means) revealed a very small difference of -0.14 l. With a mean patient volume of 71.81+/-15.93 l, the relative systematic error is only <0.1%. On this basis, equality of the volume values determined by the two methods can be assumed. PET can be used as a supplementary method for experimental determination of whole-body volume and total body fat in tumour patients. The fat content can be used to calculate the LBM and to determine body weight-independent SUVs (SUV(LBM)).

  19. Can body volume be determined by PET?

    Energy Technology Data Exchange (ETDEWEB)

    Hentschel, Michael; Paul, Dominik; Mix, Michael; Moser, Ernst; Brink, Ingo [University Hospital Freiburg, Division of Nuclear Medicine, Section of Positron Emission Tomography, Freiburg (Germany); Korsten-Reck, Ulrike [University Hospital Freiburg, Division of Sports Medicine, Freiburg (Germany); Mueller, Frank [PET-Institute Rhein-Neckar, Ludwigshafen (Germany); Merk, Stefan [Kantonsspital Basel, Division of Nuclear Medicine, Basel (Switzerland)

    2005-04-01

    To avoid dependence on body weight, the standardised uptake value (SUV) in positron emission tomography (PET) can instead be normalised to the lean body mass (LBM), which can be determined from body volume and mass. This study was designed to answer the following questions: Firstly, can the total body volume in principle be determined using PET? Secondly, is the precision of this measurement comparable to that achieved using an established standard method. Ten patients were examined during oncological whole-body PET examinations. The whole-body volume of the patients was determined from the transmission scan in PET. Air displacement plethysmography with BOD POD was used for comparison as the standard method of volume determination. In all patients, the whole-body volumes could be determined using PET and the standard method. Bland and Altman [23] analysis for agreement between the volumes determined by the two methods (presentation of differences vs means) revealed a very small difference of -0.14 l. With a mean patient volume of 71.81{+-}15.93 l, the relative systematic error is only <0.1%. On this basis, equality of the volume values determined by the two methods can be assumed. PET can be used as a supplementary method for experimental determination of whole-body volume and total body fat in tumour patients. The fat content can be used to calculate the LBM and to determine body weight-independent SUVs (SUV{sub LBM}). (orig.)

  20. Selectivity of catalytic methods of determination.

    Science.gov (United States)

    Otto, M; Mueller, H; Werner, G

    1978-03-01

    By means of catalytic analytical methods, extremely low levels can be determined at low cost and with a high sensitivity that is equal to that of physical methods of trace analysis. The selectivity of the catalytic determinations, is, however, usually rather lower than that of other methods of trace analysis. The selectivity can sometimes be improved by modification of the indicator reaction through variation of the reagents and their concentrations, or by use of masking reagents or activators, or by combination with a separation method. Modification of the indicator reaction can be exemplified by the selective determination of osmium and ruthenium by their catalysis of the nitrate oxidation of 1-naphthylamine. By variation of the nitrate concentration and the use of 1,10-phenanthroline and 8-hydroxyquinoline as complexing agents it is possible to determine these two elements simultaneously. An especially significant increase in the selectivity is made possible by use of a preliminary separation step. If the ion to be determined is separated by solvent extraction and then catalytically determined directly in the extract, a very specific determination is possible; this technique has been called "extractive catalytic determination". This method has been used for determination of molybdenum (0.5 ng/ml) in sea-water, iron (5 ng/ml) in heavy metal salts, and copper (3 ng/ml) in the presence of numerous elements.

  1. Determination production costs using PBC method

    Directory of Open Access Journals (Sweden)

    Todić Vladimir V.

    2014-01-01

    Full Text Available Basic characteristics of modern markets make requirements in quality increasing, decreasing prices and shortening delivery of products. In the middle of this requirements are production costs for whose determination are developed many traditional and alternative methods including PBC method (Process Based Costing. This method enables precisely locating and calculating indirect production costs, and with determined direct costs enables determination of total production costs. This paper shows usage of PBC method for determination production costs for three forms of processing cutting tools.

  2. TLC determination of functionality in prepolymers

    Science.gov (United States)

    Potts, J. E., Jr.; Ashcraft, A. C.

    1973-01-01

    Application of thin-layer chromatographics provides rapid qualitative determination of functional distribution in experimental prepolymer. Functionality distribution is of fundamental importance for it determines; (1) manner in which given carboxyl-terminated prepolymer will cure and (2) physical properties of resulting product.

  3. 38 CFR 75.116 - Secretary determination.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Secretary determination. 75.116 Section 75.116 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) INFORMATION SECURITY MATTERS Data Breaches § 75.116 Secretary determination. (a) Upon receipt of...

  4. 77 FR 72385 - Honey From China; Determination

    Science.gov (United States)

    2012-12-05

    ... From the Federal Register Online via the Government Publishing Office INTERNATIONAL TRADE COMMISSION Honey From China; Determination On the basis of the record \\1\\ developed in the subject five-year... an expedited review (77 FR 65204, October 25, 2012). The Commission transmitted its determination in...

  5. 5 CFR 1631.7 - Initial determination.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Initial determination. 1631.7 Section 1631.7 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD AVAILABILITY OF RECORDS... determination. The FOIA Officer shall have the authority to approve or deny requests received pursuant to these...

  6. Framing the Future: Self-Determination

    Science.gov (United States)

    Wehmeyer, Michael L.

    2015-01-01

    There is an established and still-growing evidence base that promoting self-determination has positive school and post-school benefits for students with disabilities, and yet efforts to do so remain sporadic, at best. This article examines the evidence that promoting self-determination is critically important for students with disabilities,…

  7. 49 CFR 1151.4 - Board determination.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false Board determination. 1151.4 Section 1151.4 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION RULES OF PRACTICE FEEDER RAILROAD DEVELOPMENT PROGRAM § 1151.4 Board determination...

  8. 40 CFR 35.2103 - Priority determination.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Priority determination. 35.2103 Section 35.2103 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2103 Priority determination...

  9. 36 CFR 297.5 - Determination.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Determination. 297.5 Section 297.5 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE WILD AND SCENIC RIVERS Water Resources Projects § 297.5 Determination. (a) The Secretary of Agriculture will consent to...

  10. 36 CFR 223.220 - Quantity determination.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Quantity determination. 223.220 Section 223.220 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Special Forest Products § 223.220 Quantity determination...

  11. 5 CFR 2502.7 - Initial determination.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Initial determination. 2502.7 Section 2502.7 Administrative Personnel OFFICE OF ADMINISTRATION, EXECUTIVE OFFICE OF THE PRESIDENT... § 2502.7 Initial determination. The General Counsel or his or her designee shall have the authority to...

  12. 44 CFR 206.38 - Presidential determination.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Presidential determination. 206.38 Section 206.38 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY....38 Presidential determination. (a) The Governor's request for a major disaster declaration may result...

  13. 18 CFR 286.108 - Determination.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Determination. 286.108 Section 286.108 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... Contested Audit Findings and Proposed Remedies § 286.108 Determination. If no formal hearing is had the...

  14. 75 FR 39277 - Sorbitol From France; Determination

    Science.gov (United States)

    2010-07-08

    ... The Commission instituted this review on July 1, 2009 (74 FR 31762, July 2, 2009) and determined on... publishing the notice in the Federal Register on December 17, 2009 (74 FR 66992). The hearing was held in... COMMISSION Sorbitol From France; Determination On the basis of the record \\1\\ developed in the subject...

  15. 22 CFR 181.3 - Determinations.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Determinations. 181.3 Section 181.3 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL AGREEMENTS COORDINATION, REPORTING AND PUBLICATION OF INTERNATIONAL AGREEMENTS § 181.3 Determinations. (a) Whether any undertaking, document, or set of documents...

  16. 78 FR 52956 - Proposed Flood Hazard Determinations

    Science.gov (United States)

    2013-08-27

    ... 77662. City of Pinehurst Pinehurst City Hall, 2497 Martin Luther King Jr. Drive, Orange, TX 77630. City... SECURITY Federal Emergency Management Agency Proposed Flood Hazard Determinations AGENCY: Federal Emergency... Register (78 FR 36220-36222) a proposed flood hazard determination notice that contained an erroneous...

  17. 75 FR 59989 - Final Flood Elevation Determinations

    Science.gov (United States)

    2010-09-29

    ... Lufkin. downstream of Bonita Street. Approximately 230 feet +304 upstream of Martin Luther King Drive... SECURITY Federal Emergency Management Agency 44 CFR Part 67 Final Flood Elevation Determinations AGENCY... (FEMA) makes the final determinations listed below for the modified BFEs for each community...

  18. 76 FR 39063 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2011-07-05

    ... City Hall, 100 North Martin Luther King Jr. Avenue, Waukegan, IL 60085. City of Zion Maps are available... SECURITY Federal Emergency Management Agency 44 CFR Part 67 Proposed Flood Elevation Determinations AGENCY... make determinations of BFEs and modified BFEs for each community listed below, in accordance...

  19. Determination of grain boundary geometry using TEM

    NARCIS (Netherlands)

    Jang, H.; Farkas, D.; Hosson, J.T.M. De

    1992-01-01

    An experimental method to obtain the grain boundary geometry using the transmission electron microscope is presented. The method allows Σ determination including grain boundary plane orientation. In order to determine the specialness of the grain boundary, three different criteria for maximum allowa

  20. Determining Enzyme Activity by Radial Diffusion

    Science.gov (United States)

    Davis, Bill D.

    1977-01-01

    Discusses advantages of radial diffusion assay in determining presence of enzyme and/or rough approximation of amount of enzyme activities. Procedures are included for the preparation of starch-agar plates, and the application and determination of enzyme. Techniques using plant materials (homogenates, tissues, ungerminated embryos, and seedlings)…

  1. Using Mobile Learning: Determinates Impacting Behavioral Intention

    Science.gov (United States)

    Lowenthal, Jeffrey N.

    2010-01-01

    This study examined the factors or determinates that impact the behavioral intention of students to use mobile learning (m-learning) technology. These determinates include performance expectancy, effort expectancy, and self-management of learning, all mediated by age, gender, or both. Regression coefficients showed strong and significant…

  2. On the applicability of requirements determination methods

    NARCIS (Netherlands)

    Bollen, Petrus Wilhelmus Laurentius

    2004-01-01

    In this thesis we have studied the field of requirements determination for enterprise information systems. We discovered that in the ERP era that characterizes the information systems in many (large) enterprises at the beginning of the 21st century, the issue of requirements determination is still r

  3. Determination of generator losses and efficiency

    Directory of Open Access Journals (Sweden)

    Klasnić Ilija

    2015-01-01

    Full Text Available The paper presents the results of deriving by calculation the local and total losses of the generator as well as efficiency determination of the revitalised hydro-generator unit A4 in HPP 'Djerdap 1'. In order to determine the generator losses and generator efficiency, measurements are performed during the acceptance tests of revitalised aggregate A4 in HPP 'Djerdap 1'.

  4. Determination of grain boundary geometry using TEM

    NARCIS (Netherlands)

    Jang, H.; Farkas, D.; Hosson, J.T.M. De

    An experimental method to obtain the grain boundary geometry using the transmission electron microscope is presented. The method allows Σ determination including grain boundary plane orientation. In order to determine the specialness of the grain boundary, three different criteria for maximum

  5. 48 CFR 30.202-7 - Determinations.

    Science.gov (United States)

    2010-10-01

    ... Section 30.202-7 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING...) Adequacy determination. (1) As prescribed by 48 CFR 9903.202-6 (FAR Appendix), the auditor shall— (i...; and (ii) Report the results to the CFAO. (2) The CFAO shall determine if the Disclosure Statement...

  6. Determining Enzyme Activity by Radial Diffusion

    Science.gov (United States)

    Davis, Bill D.

    1977-01-01

    Discusses advantages of radial diffusion assay in determining presence of enzyme and/or rough approximation of amount of enzyme activities. Procedures are included for the preparation of starch-agar plates, and the application and determination of enzyme. Techniques using plant materials (homogenates, tissues, ungerminated embryos, and seedlings)…

  7. 5 CFR 295.206 - Final determination.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Final determination. 295.206 Section 295.206 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS TESTIMONY BY OPM... for Testimony and Production of Documents § 295.206 Final determination. The General Counsel makes...

  8. ZWY Sex Determination in Xenopus tropicalis

    Science.gov (United States)

    Most vertebrate species with described genetic sex determination are either male (XY) or female (ZW) heterogametic. To date, studies with Xenopus species indicate that members of this genus operate under a ZW sex determination system. We used two different approaches and demonst...

  9. Framing the Future: Self-Determination

    Science.gov (United States)

    Wehmeyer, Michael L.

    2015-01-01

    There is an established and still-growing evidence base that promoting self-determination has positive school and post-school benefits for students with disabilities, and yet efforts to do so remain sporadic, at best. This article examines the evidence that promoting self-determination is critically important for students with disabilities,…

  10. 40 CFR 230.11 - Factual determinations.

    Science.gov (United States)

    2010-07-01

    ... sanitary landfill located in waters of the U.S. Activities to be conducted on fast land created by the... the physical, chemical, and biological components of the aquatic environment in light of subparts C...) Physical substrate determinations. Determine the nature and degree of effect that the proposed discharge...

  11. EFFICIENCY INCREASE OF CONGESTION FLOWS DETERMINATION

    Directory of Open Access Journals (Sweden)

    O. Denysenko

    2009-01-01

    Full Text Available A short review of congestion flows determination methods (CF is presented. The models for time intervals determination of vehicles flow at the stop-line and the magnitude of the ideal CF are presented. The estimation of modeling results according to experimental data is carried out.

  12. Information Measures for Statistical Orbit Determination

    Science.gov (United States)

    Mashiku, Alinda K.

    2013-01-01

    The current Situational Space Awareness (SSA) is faced with a huge task of tracking the increasing number of space objects. The tracking of space objects requires frequent and accurate monitoring for orbit maintenance and collision avoidance using methods for statistical orbit determination. Statistical orbit determination enables us to obtain…

  13. Institutional Determinants of International Production in Russia

    Directory of Open Access Journals (Sweden)

    N A Volgina

    2009-06-01

    Full Text Available The article analyses institutional determinants of foreign direct investment that substantially influences international production in Russia. Author pays special attention on the following determinants as legal infrastructure, protection property rights, including intellectual property, effectiveness of enforcement mechanisms, and corruption. Author comes to a conclusion that without development of proper institutions Russia would hardly expect dynamic development of international production.

  14. Using Mobile Learning: Determinates Impacting Behavioral Intention

    Science.gov (United States)

    Lowenthal, Jeffrey N.

    2010-01-01

    This study examined the factors or determinates that impact the behavioral intention of students to use mobile learning (m-learning) technology. These determinates include performance expectancy, effort expectancy, and self-management of learning, all mediated by age, gender, or both. Regression coefficients showed strong and significant…

  15. Determination of spectrophotometric absorptivity by analytical ultracentrifugation

    Directory of Open Access Journals (Sweden)

    M Senthilraja

    2011-01-01

    Full Text Available Rapid determination of the absorptivity for a recombinant IgG monoclonal antibody using the Beckman equipped with both Raleigh interference and UV absorbance optical systems. The analytical ultracentrifuge data for determining spectrophotometric absorptivities is compared to experimental data from quantitative amino acid analysis and an enzymatic digestion method.

  16. Determining the specific electric resistance of rock

    Energy Technology Data Exchange (ETDEWEB)

    Persad' ko, V.Ia.

    1982-01-01

    Data are presented on perfecting the method of laboratory determination of the specific electric resistance of a rock formation. The average error in determining the specific electric resistance of the core at various locations is no more than two percent with low resistance values (2-5 ohms).

  17. Choosing a Self-Determination Curriculum.

    Science.gov (United States)

    Test, David W.; Karvonen, Meagan; Wood, Wendy M.; Browder, Diane; Algozzine, Bob

    2000-01-01

    This article describes a project to help educators improve the self-determination of students with disabilities. The project identified critical curricular components and developed a checklist to evaluate the different curricula designed to promote self-determination skills. Five curricula that have published research documenting their…

  18. Determining Extinction Ratio Of A Laser Diode

    Science.gov (United States)

    Unger, Glenn L.

    1992-01-01

    Improved technique to determine extinction ratio of pulsed laser diode based partly on definition of extinction ratio applicable to nonideal laser pulses. Heretofore, determinations involved assumption of ideal laser pulses, and neglected optical power from background light. Because power fluctuates during real pulse, more realistic to define extinction ratio in terms of energy obtained.

  19. Shadowing Lemma and Chaotic Orbit Determination

    CERN Document Server

    Spoto, Federica

    2015-01-01

    Orbit determination is possible for a chaotic orbit of a dynamical system, given a finite set of observations, provided the initial conditions are at the central time. In a simple discrete model, the standard map, we tackle the problem of chaotic orbit determination when observations extend beyond the predictability horizon. If the orbit is hyperbolic, a shadowing orbit is computed by the least squares orbit determination. We test both the convergence of the orbit determination iterative procedure and the behaviour of the uncertainties as a function of the maximum number $n$ of map iterations observed. When the initial conditions belong to a chaotic orbit, the orbit determination is made impossible by numerical instability beyond a computability horizon, which can be approximately predicted by a simple formula. Moreover, the uncertainty of the results is sharply increased if a dynamical parameter is added to the initial conditions as parameter to be estimated. The uncertainty of the dynamical parameter decrea...

  20. How Darwinian reductionism refutes genetic determinism.

    Science.gov (United States)

    Rosoff, Philip M; Rosenberg, Alex

    2006-03-01

    Genetic determinism labels the morally problematical claim that some socially significant traits, traits we care about, such as sexual orientation, gender roles, violence, alcoholism, mental illness, intelligence, are largely the results of the operation of genes and not much alterable by environment, learning or other human intervention. Genetic determinism does not require that genes literally fix these socially significant traits, but rather that they constrain them within narrow channels beyond human intervention. In this essay we analyze genetic determinism in light of what is now known about the inborn error of metabolism phenylketonuria (PKU), which has for so long been the poster child 'simple' argument in favor of some form of genetic determinism. We demonstrate that this case proves the exact opposite of what it has been proposed to support and provides a strong refutation of genetic determinism in all its guises.

  1. Determinants of adjacency matrices of graphs

    Directory of Open Access Journals (Sweden)

    Alireza Abdollahi

    2012-12-01

    Full Text Available We study the set of all determinants of adjacency matrices of graphs with a given number of vertices. Using Brendan McKay's data base of small graphs, determinants of graphs with at most $9$ vertices are computed so that the number of non-isomorphic graphs with given vertices whose determinants are all equal to a number is exhibited in a table. Using an idea of M. Newman, it is proved that if $G$ is a graph with $n$ vertices and ${d_1,dots,d_n}$ is the set of vertex degrees of $G$, then $gcd(2m,d^2$ divides the determinant of the adjacency matrix of $G$, where $d=gcd(d_1,dots,d_n$. Possible determinants of adjacency matrices of graphs with exactly two cycles are obtained.

  2. The GEOS-3 orbit determination investigation

    Science.gov (United States)

    Pisacane, V. L.; Eisner, A.; Yionoulis, S. M.; Mcconahy, R. J.; Black, H. D.; Pryor, L. L.

    1978-01-01

    The nature and improvement in satellite orbit determination when precise altimetric height data are used in combination with conventional tracking data was determined. A digital orbit determination program was developed that could singly or jointly use laser ranging, C-band ranging, Doppler range difference, and altimetric height data. Two intervals were selected and used in a preliminary evaluation of the altimeter data. With the data available, it was possible to determine the semimajor axis and eccentricity to within several kilometers, in addition to determining an altimeter height bias. When used jointly with a limited amount of either C-band or laser range data, it was shown that altimeter data can improve the orbit solution.

  3. Mechanisms of Ionizing Radiation-Induced Cell Death in Primary Lung Cells

    Science.gov (United States)

    2013-03-05

    Zhai M, et al. 2007. Protein oxidation implicated as the primary determinant of bacterial radioresistance. PLoS Biol 5:e92 43. Demidenko ZN...oxidative stress induces senescence in retinal pigment epithelial cells via TGF-beta release. Investigative ophthalmology & visual science 50:926- 35

  4. Resistance of hypoxic cells to ionizing radiation is influenced by homologous recombination status.

    NARCIS (Netherlands)

    Sprong, D.; Janssen, H.L.K.; Vens, C.; Begg, A.C.

    2006-01-01

    PURPOSE: To determine the role of DNA repair in hypoxic radioresistance. METHODS AND MATERIALS: Chinese hamster cell lines with mutations in homologous recombination (XRCC2, XRCC3, BRAC2, RAD51C) or nonhomologous end-joining (DNA-PKcs) genes were irradiated under normoxic (20% oxygen) and hypoxic (&

  5. Chromatin structure and cellular radiosensitivity : A comparison of two human tumour cell lines

    NARCIS (Netherlands)

    Woudstra, EC; Roesink, JM; Rosemann, M; Brunsting, JF; Driessen, C; Orta, T; Konings, AWT; Peacock, JH; Kampinga, HH

    1996-01-01

    The role of variation in susceptibility to DNA damage induction was studied as a determinant for cellular radiosensitivity. Comparison of the radiosensitive HX142 and radioresistant RT112 cell lines previously revealed higher susceptibility to X-ray-induced DNA damage in the sensitive cell line usin

  6. Chromatin structure and cellular radiosensitivity : A comparison of two human tumour cell lines

    NARCIS (Netherlands)

    Woudstra, EC; Roesink, JM; Rosemann, M; Brunsting, JF; Driessen, C; Orta, T; Konings, AWT; Peacock, JH; Kampinga, HH

    1996-01-01

    The role of variation in susceptibility to DNA damage induction was studied as a determinant for cellular radiosensitivity. Comparison of the radiosensitive HX142 and radioresistant RT112 cell lines previously revealed higher susceptibility to X-ray-induced DNA damage in the sensitive cell line

  7. Critical flux determination by flux-stepping

    DEFF Research Database (Denmark)

    Beier, Søren; Jonsson, Gunnar Eigil

    2010-01-01

    In membrane filtration related scientific literature, often step-by-step determined critical fluxes are reported. Using a dynamic microfiltration device, it is shown that critical fluxes determined from two different flux-stepping methods are dependent upon operational parameters such as step......, such values are more or less useless in itself as critical flux predictors, and constant flux verification experiments have to be conducted to check if the determined critical fluxes call predict sustainable flux regimes. However, it is shown that using the step-by-step predicted critical fluxes as start...

  8. Determinants of Corporate Philanthropy in Pakistan

    Directory of Open Access Journals (Sweden)

    Muhammad Abdul Majid Makki

    2008-09-01

    Full Text Available The importance of corporate philanthropy and its related philosophy of corporate social responsibility have captured the attention of researchers and humanitarian groups in WTO era. Corporate donations have been considered as a critical tool to improve corporate image in a highly competitive environment. This paper explores the determinants of corporate donations based on LSE-25 index companies over the five year period 2002-06. Multiple regression techniques have been used for gauging the determinants of corporate philanthropy after collecting data from audited financial reports of companies. The study is a pioneering attempt in measuring the determinants of philanthropy in corporate sector of Pakistan.

  9. Development of Methods for Determination of Aflatoxins.

    Science.gov (United States)

    Xie, Lijuan; Chen, Min; Ying, Yibin

    2016-12-09

    Aflatoxins can cause damage to the health of humans and animals. Several institutions around the world have established regulations to limit the levels of aflatoxins in food, and numerous analytical methods have been extensively developed for aflatoxin determination. This review covers the currently used analytical methods for the determination of aflatoxins in different food matrices, which includes sampling and sample preparation, sample pretreatment methods including extraction methods and purification methods of aflatoxin extracts, separation and determination methods. Validation for analysis of aflatoxins and safety considerations and precautions when doing the experiments are also discussed.

  10. Determination of proteolytic activity in cereals

    Directory of Open Access Journals (Sweden)

    D. Wojciechowska

    2015-01-01

    Full Text Available Results have been presented indicating that native proteolytic enzymes and bromelain acted variously ion wheat proteins differentiated in quality, they also act nonspecifically ton haemoglobin. It was thought useful to elaborate a new method of proteolytic activity determination based on the application of a standard natural substrate. The latter consists of gluten extract in acetic acid from a definite flour sample. The method of substrate selection and the determination procedure are described and some examples of wheat proteolytic activity determination are given.

  11. A Multichannel Bioluminescence Determination Platform for Bioassays.

    Science.gov (United States)

    Kim, Sung-Bae; Naganawa, Ryuichi

    2016-01-01

    The present protocol introduces a multichannel bioluminescence determination platform allowing a high sample throughput determination of weak bioluminescence with reduced standard deviations. The platform is designed to carry a multichannel conveyer, an optical filter, and a mirror cap. The platform enables us to near-simultaneously determine ligands in multiple samples without the replacement of the sample tubes. Furthermore, the optical filters beneath the multichannel conveyer are designed to easily discriminate colors during assays. This optical system provides excellent time- and labor-efficiency to users during bioassays.

  12. Woodcock age and sex determination from wings

    Science.gov (United States)

    Martin, F.W.

    1964-01-01

    Age of woodcock (Philohela minor) can be accurately determined throughout the year by differences in pattern, color, and wear of secondary feathers. Immature woodcock retain most secondaries during the postjuvenal molt that begins in July or August and ends in October. In contrast, subadults (first-year adults) and older woodcock molt all secondaries during the postnuptial molt beginning in June or July and ending in October. Retention of juvenal secondaries by immatures and molt of these feathers by adults form the basis for age determination. Sex of woodcock can be accurately determined by width of the outer three primaries, which are conspicuously narrower on males.

  13. Astrometric Determination of VSOP-2 Orbital Parameters

    Science.gov (United States)

    Fomalont, E.; Moellenbrock, G.; Claussen, M.

    2009-08-01

    VSOP-2 phase referencing, needed to image faint sources and to determine accurate positions, will require an orbit accuracy of about 2 cm at 23 GHz. This accuracy, however, may not be obtainable by direct orbital measurements. We propose an observation scheme, similar to that used at the VLBA, to be included during a phase referencing observation of about one orbit in order to determine a more accurate orbit determination. We show the effects of orbit errors, explain the suggested observations and reduction methods, and discuss the potential problems that might impede the use of this technique.

  14. Determining Price Reasonableness in Federal ESPCs

    Energy Technology Data Exchange (ETDEWEB)

    Shonder, J.A.

    2005-03-08

    This document reports the findings and implementation recommendations of the Price Reasonableness Working Group to the Federal ESPC Steering Committee. The working group was formed to address concerns of agencies and oversight organizations related to pricing and fair and reasonable price determination in federal energy savings performance contracts (ESPCs). This report comprises the working group's recommendations and is the proposed draft of a training curriculum on fair and reasonable price determination for users of federal ESPCs. The report includes: (1) A review of federal regulations applicable to determining price reasonableness of federal ESPCs (section 2), (2) Brief descriptions of the techniques described in Federal Acquisition Regulations (FAR) 15.404-1 and their applicability to ESPCs (section 3), and (3) Recommended strategies and procedures for cost-effectively completing price reasonableness determinations (sections 4). Agencies have struggled with fair and reasonable price determinations in their ESPCs primarily because this alternative financing vehicle is relatively new and relatively rare in the federal sector. The methods of determining price reasonableness most familiar to federal contracting officers (price competition based on the government's design and specifications, in particular) are generally not applicable to ESPCs. The regulatory requirements for determining price reasonableness in federal ESPCs have also been misunderstood, as federal procurement professionals who are inexperienced with ESPCs are further confused by multiple directives, including Executive Order 13123, which stresses life-cycle cost-effectiveness. Uncertainty about applicable regulations and inconsistent practice and documentation among agencies have fueled claims that price reasonableness determinations have not been sufficiently rigorous in federal ESPCs or that the prices paid in ESPCs are generally higher than the prices paid for similar goods and

  15. Does turbulence determine the initial mass function?

    Science.gov (United States)

    Liptai, David; Price, Daniel J.; Wurster, James; Bate, Matthew R.

    2017-02-01

    We test the hypothesis that the initial mass function (IMF) is determined by the density probability distribution function (PDF) produced by supersonic turbulence. We compare 14 simulations of star cluster formation in 50 M⊙ molecular cloud cores where the initial turbulence contains either purely solenoidal or purely compressive modes, in each case resolving fragmentation to the opacity limit to determine the resultant IMF. We find statistically indistinguishable IMFs between the two sets of calculations, despite a factor of 2 difference in the star formation rate and in the standard deviation of log (ρ). This suggests that the density PDF, while determining the star formation rate, is not the primary driver of the IMF.

  16. [Compatibility determinations Squaw Creek National Wildlife Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This document provides two compatibility determinations; one stated that the proposed agricultural practices (row crop farming) are compatible with Refuge...

  17. Species and prevalence determination of Human Intestinal ...

    African Journals Online (AJOL)

    ADOWIE PERE

    Species and prevalence determination of Human Intestinal Parasites among Patients attending two ... the maintenance of proper personal hygiene, creating awareness to the ..... (2007), who reported a value of 21.1% in Owerri,. Imo State and ...

  18. Determinants of Global Competitiveness of Chinese Economy

    National Research Council Canada - National Science Library

    Elmas Demircioğlu Karabıyık

    2015-01-01

    .... Main aim of this study is to investigate the determinants of the global competitiveness of Chinese economy by considering economic development process of the Chinese economy and World Economic Forum...

  19. Determinants of Global Competitiveness of Chinese Economy

    National Research Council Canada - National Science Library

    Elmas Demircioglu Karabiyik

    2016-01-01

    .... Main aim of this study is to investigate the determinants of the global competitiveness of Chinese economy by considering economic development process of the Chinese economy and World Economic Forum...

  20. Determinants of farm diversification in the Netherlands

    NARCIS (Netherlands)

    Meraner, M.; Heijman, W.J.M.; Kuhlman, J.W.; Finger, R.

    2015-01-01

    Farm diversification has been prominently supported by agricultural policy makers aiming to support rural development. To increase the understanding of determinants influencing diversification and hence to increase the efficiency of policies aiming to support farm diversification this paper presents

  1. Demagnetization using a determined estimated magnetic state

    Science.gov (United States)

    Denis, Ronald J; Makowski, Nathanael J

    2015-01-13

    A method for demagnetizing comprising positioning a core within the electromagnetic field generated by a first winding until the generated first electrical current is not substantially increasing, thereby determining a saturation current. A second voltage, having the opposite polarity, is then applied across the first winding until the generated second electrical current is approximately equal to the magnitude of the determined saturation current. The maximum magnetic flux within the core is then determined using the voltage across said first winding and the second current. A third voltage, having the opposite polarity, is then applied across the first winding until the core has a magnetic flux equal to approximately half of the determined maximum magnetic flux within the core.

  2. short communication quantitative determination of formaldehyde by ...

    African Journals Online (AJOL)

    Preferred Customer

    2Chemistry Department, Faculty of Science, Zanjan University, Zanjan, Iran ... in textiles was determined by discoloring kinetic spectrophotometry [5]; food ... be an idea to cover the lack of a model by which the reaction trend is also possible to.

  3. Immigration as a social determinant of health.

    Science.gov (United States)

    Castañeda, Heide; Holmes, Seth M; Madrigal, Daniel S; Young, Maria-Elena DeTrinidad; Beyeler, Naomi; Quesada, James

    2015-03-18

    Although immigration and immigrant populations have become increasingly important foci in public health research and practice, a social determinants of health approach has seldom been applied in this area. Global patterns of morbidity and mortality follow inequities rooted in societal, political, and economic conditions produced and reproduced by social structures, policies, and institutions. The lack of dialogue between these two profoundly related phenomena-social determinants of health and immigration-has resulted in missed opportunities for public health research, practice, and policy work. In this article, we discuss primary frameworks used in recent public health literature on the health of immigrant populations, note gaps in this literature, and argue for a broader examination of immigration as both socially determined and a social determinant of health. We discuss priorities for future research and policy to understand more fully and respond appropriately to the health of the populations affected by this global phenomenon.

  4. 7 CFR 47.49 - Determinations.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE MARKETING OF PERISHABLE AGRICULTURAL COMMODITIES RULES OF PRACTICE UNDER THE PERISHABLE AGRICULTURAL COMMODITIES ACT Rules Applicable to the Determination As to Whether...

  5. Independent Payment Advisory Board (IPAB) Determination

    Data.gov (United States)

    U.S. Department of Health & Human Services — Section 1899A of the Social Security Act requires the Chief Actuary of the Centers for Medicare and Medicaid Services (CMS) to determine by April 30, 2013, and...

  6. SPECIATION AND DETERMINATION OF PRIORITY METALS IN ...

    African Journals Online (AJOL)

    locations and the samples were analyzed for some certain priority metals to determine the .... the use of a pestle, sieved with a laboratory test sieve of size 500 µm, ..... Hanoi. City,. Vietnam,. Seminar. Paper,. Institutional for markvetenskap,.

  7. 40 CFR 1042.315 - Determining compliance.

    Science.gov (United States)

    2010-07-01

    ... value for the final test results on that engine. Include the Green Engine Factor to determine low-hour... place. (b) For Category 1 and Category 2 engines, if a production-line engine fails to meet...

  8. Field determination of bacterial disappearance in seawater

    DEFF Research Database (Denmark)

    Harremoës, Poul

    1970-01-01

    The article presents two approaches to field determination of disappearance of viable, fecal bacteria after discharge with sewage into a marine environment. The first approach is based on simultaneous sampling for bacterial counting and monitoring of dilution using a conservative tracer, which...... is released continuously with the sewage. The second approach uses an abrupt release of tracer for determination of both dilution and residence time in the sewage field. In both cases, the disappearance rate is best determined by comparison of fluxes of two bacteria and of tracer through cross......-sections of the field. The approaches are exemplified with two case reports, which show that the disappearance rate can be determined to less than 10 per cent inaccuracy....

  9. Simultaneous determination of protein structure and dynamics

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Best, Robert B.; DePristo, M. A.

    2005-01-01

    We present a protocol for the experimental determination of ensembles of protein conformations that represent simultaneously the native structure and its associated dynamics. The procedure combines the strengths of nuclear magnetic resonance spectroscopy-for obtaining experimental information at ...

  10. Psychological and Sociological Determinants of Academic ...

    African Journals Online (AJOL)

    Six self-report measures were administered randomly to 280 senior secondary ... and locus of control, self-esteem, parent's education, parental discipline, culture, and governance) could jointly determine academic achievement of adolescents.

  11. Farm-Level Determinants of output Commercialization:

    African Journals Online (AJOL)

    MARC-AB

    The key determinants of commercialization among haricot bean ... The objective of the study is improved understanding of the practices, challenges and opportunities ... The market distance is used as a proxy for fixed transaction costs and the.

  12. Simulation training in brain death determination.

    Science.gov (United States)

    Hocker, Sara; Wijdicks, Eelco F M

    2015-04-01

    Skill in the determination of brain death is traditionally acquired during training in an apprenticeship model. Brain death is not frequently determined, and thus exposure to the techniques used is marginal. Brain death is therefore ideally suited for competency-based education models such as simulation. Simulation can ensure that all trainees have direct experience in brain death determination irrespective of their specialty, program design, or institutional protocol. In this review, the authors discuss the advantages and barriers to simulation and how to develop simulation scenarios for instruction in the determination of brain death. Future research should focus on validation of brain death simulation methods and assessment tools as well as the impact of simulation on performance in clinical practice.

  13. Laboratory Building for Accurate Determination of Plutonium

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>The accurate determination of plutonium is one of the most important assay techniques of nuclear fuel, also the key of the chemical measurement transfer and the base of the nuclear material balance. An

  14. Uranium Determination by Delayed Neutron Counting

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>Uranium is a very important resource in nuclear industry, especially in the exploiture of nuclear energy. Determination of uranium using delayed neutron counting (DNC) is simple, non-destructive, and

  15. Preliminary Determination of Epicenters (PDE) Bulletin

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The NEIC global earthquake bulletin is called the Preliminary Determination of Epicenters or PDE, and is one of many discrete products in the ANSS Comprehensive...

  16. Determinants of woody cover in African savannas

    CSIR Research Space (South Africa)

    Sankaran, M

    2005-12-08

    Full Text Available Savannas are globally important ecosystems of great significance to human economies. In these biomes, which are characterized by the co-dominance of trees and grasses, woody cover is a chief determinant of ecosystem properties (1...

  17. Determining cerebral death with radiologic diagnostic procedures

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, R.M.

    1980-05-01

    Cerebral death determination has become a very important medicolegal question. The imaging modalities of computed tomographic scanning, nuclear medicine, and cerebral angiography are enabling the physician to better evaluate those conditions that may mimic cerebral death.

  18. Determinants of intercultural adjustment among expatriate spouses

    NARCIS (Netherlands)

    Ali, Anees; Van der Zee, K.I.; Sanders, G

    2003-01-01

    The adaptation of expatriate families to a host country seems crucial to successful fulfilment of international business assignments. The present study focused on personality, family characteristics and characteristics of expatriates' work life as determinants of the intercultural adjustment of expa

  19. Determinant factors of Yemeni maxillary arch dimensions

    Directory of Open Access Journals (Sweden)

    Nabil Muhsen Al-Zubair

    2015-01-01

    Conclusion: Measurements of palatal depth and relationships of the canines to one another and to other teeth thus had the widest ranges, implying that these dimensions are the strongest determinants of maxillary arch size.

  20. Determinant of securitization asset pricing in Malaysia

    Science.gov (United States)

    Bakri, M. H.; Ali, R.; Ismail, S.; Sufian, F.; Baharom, A. H.

    2014-12-01

    Malaysian firms have been reported involve in Asset Back Securities since 1986s where Cagamas is a pioneer. This research aims to examine the factor influencing primary market spread. Least square method and regression analysis are applied for the study period 2004-2012. The result shows one determinants in internal regression model and three determinants in external regression influence or contribute to the primary market spread and are statistically significant in developing the securitization in Malaysia. It can be concluded that transaction size significantly contribute to the determinant primary market spread in internal regression model while liquidity, transaction size and crisis is significant in both regression model. From five hypotheses, three hypotheses support that the determinants have a relationship with primary market spread.

  1. Determination of steroids in manure and soil

    DEFF Research Database (Denmark)

    Hansen, Martin; Björklund, Bengt Erland; Halling-Sørensen, Bent

    A genuine analytical method to determine native steroids (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, estrone, 17b-estradiol, and 17a-estradiol) and one anthropogenic steroid (ethynylestradiol) in environmental solid samples is presented...

  2. Adult Learning Open University Determinants study: psychological determinants of study success

    NARCIS (Netherlands)

    Neroni, Joyce; De Groot, Renate; Kirschner, Paul A.

    2013-01-01

    Neroni, J., De Groot, R. H. M., & Kirschner, P. A. (2013, 30 August). Adult Learning Open University Determinants study: psychological determinants of study success. Poster presentation at the 15th Biennial EARLI conference 2013, Munich, Germany.

  3. DETERMINATION OF IMPURITY ELEMENTS IN ALUMINIUM

    Institute of Scientific and Technical Information of China (English)

    侯小琳; 张永保

    1994-01-01

    Twenty five impurity elements in aluminium applied as reactor material are determined.Titanium and nickel are determined with epithermal neutron activation analysis(NAA),magnesium and silicon by inductance coupling plasma emission spectra(ICP),other elements by thermal NAA.The fission coefficient of uranium is given by an experiment,the interferences of uranium to Ce,Nd,Mo,Zr,La,Sm are subtracted.The detection limits of these methods to all of impurity elements in aluminium are calculated.

  4. Yield stress determination of a physical gel

    DEFF Research Database (Denmark)

    Hvidt, Søren

    2013-01-01

    Pluronic F127 solutions form gels in water with high elastic moduli. Pluronic gels can, however, only withstand small deformations and stresses. Different steady shear and oscillatory methods traditionally used to determine yield stress values are compared. The results show that the yield stresses...... values of these gels depend on test type and measurement time, and no absolute yield stress value can be determined for these physical gels....

  5. Determining the stress of rock massif

    OpenAIRE

    2014-01-01

    Defining the stress rock massif is essential for design of underground facilities and methods of mining in the mines. Assessment the value of stress state of rock massif and rock strength in the various loads allows rational design. This is of particular importance when sizing columns, determining the extent of excavation, the cross-sections of underground rooms in problems with rock bursts and others. This paper briefly gives the basic methods of determining the rock massif stress as part of...

  6. Studies on Determining Method of Trehalose

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Trehalose can be determined by thin layer chromatography and high performance liquid chromatography. But it's difficult to distinguish trehalose from the similar bisaccharides. If the reaction of the reduced bisaccharides with phenyl hydrazine to form osazone is used, then the disturbance of the similar reduced bisaccharides can be rapidly and conveniently excluded, or via the ammoniated-reduced reaction, aliline can be specially bounded to the reduced hydroxyl of the bisaccharides. In that way trehalose can be accurately determined.

  7. Substrates and method for determining enzymes

    Science.gov (United States)

    Smith, Robert E.; Bissell, Eugene R.

    1981-01-01

    A method is disclosed for determining the presence of an enzyme in a biological fluid, which includes the steps of contacting the fluid with a synthetic chromogenic substrate, which is an amino acid derivative of 7-amino-4-trifluoromethylcoumarin; incubating the substrate-containing fluid to effect enzymatic hydrolysis; and fluorometrically determining the presence of the free 7-amino-4-trifluoromethylcoumarin chromophore in the hydrolyzate.

  8. Determination of Even Degree of Animal Population

    Institute of Scientific and Technical Information of China (English)

    SongRen-xue; YangYun-qing

    1999-01-01

    The even degree of animal population is generlay measured by the coefficient of variation of major economic characters.Facing the coefficient of variation,a statistic with complex properties,we achieved indirectly the determination of confidence interval for even degree of an animal population by analysing the reciprocal of the statistic.The sample size which is suitable to the determination of the even degree of an animal population was probed into within the extent of permissive estimation error.

  9. Determination of Even Degree of Animal Population

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The even degree of animal population is generlay measured by the coefficient of variation of major eco- nomic characters. Facing the coefficient of variation,a statistic with complex properties,we achieved indirectly the determination of confidence interval for even degree of an animal population by analysing the reciprocal of the statistic. The sample size which is suitable to the determination of the even degree of an animal population was probed into within the extent of permissive estimation error.

  10. Spectrophotometric determination of fluorine in silicate rocks

    Science.gov (United States)

    Peck, L.C.; Smith, V.C.

    1964-01-01

    The rock powder is sintered with a sodium carbonate flux containing zinc oxide and magnesium carbonate, the sinter-cake leached with water and the resulting solution filtered. Fluorine is separated from the acidified filtrate by steam distillation and determined spectrophotometrically by means of a zirconium-SPADNS reagent. If a multiple-unit distillation apparatus is used, 12 determinations can be completed per man-day. ?? 1964.

  11. The determinants of physical activity and exercise.

    OpenAIRE

    Dishman, R. K.; Sallis, J F; Orenstein, D R

    1985-01-01

    Evaluation and delivery of physical activity and exercise programs appear impeded by the substantial numbers of Americans who are unwilling or unable to participate regularly in physical activity. As a step toward identifying effective interventions, we reviewed available research on determinants relating to the adoption and maintenance of physical activity. We categorized determinants as personal, environmental, or characteristic of the exercise. We have considered supervised participation s...

  12. Determination of fat in vegetable foods.

    Science.gov (United States)

    Rosenthal, I; Merin, U; Popel, G; Bernstein, S

    1985-01-01

    The fat in vegetable foods--tree nuts, peanuts, sunflower seeds, avocado, and olives--can be determined volumetrically by acid digestion of the material and separation of the fat. The assay can be performed conveniently by using the equipment developed for fat determination of milk (Gerber method). The results agree well with those obtained by Soxhlet extraction. The advantages of using the Gerber method for vegetable foods are simplicity, speed, low operation cost, and elimination of the use of inflammable solvents.

  13. Quantitative determination of atmospheric hydroperoxyl radical

    Science.gov (United States)

    Springston, Stephen R.; Lloyd, Judith; Zheng, Jun

    2007-10-23

    A method for the quantitative determination of atmospheric hydroperoxyl radical comprising: (a) contacting a liquid phase atmospheric sample with a chemiluminescent compound which luminesces on contact with hydroperoxyl radical; (b) determining luminescence intensity from the liquid phase atmospheric sample; and (c) comparing said luminescence intensity from the liquid phase atmospheric sample to a standard luminescence intensity for hydroperoxyl radical. An apparatus for automating the method is also included.

  14. Intercomparison of Rn-222 determination from groundwater

    DEFF Research Database (Denmark)

    Vesterbacka, P.; Pettersson, H.; Hanste, U.-M.;

    2010-01-01

    An intercomparison exercise on Rn-222 determination in groundwater was organized between eight Nordic laboratories. The individual laboratory results were in most cases within 20% of the median value and within reported uncertainties. Considering the particular difficulties in preparing, transpor......An intercomparison exercise on Rn-222 determination in groundwater was organized between eight Nordic laboratories. The individual laboratory results were in most cases within 20% of the median value and within reported uncertainties. Considering the particular difficulties in preparing...

  15. Evans Functions, Jost Functions, and Fredholm Determinants

    Science.gov (United States)

    Gesztesy, Fritz; Latushkin, Yuri; Makarov, Konstantin A.

    2007-12-01

    The principal results of this paper consist of an intrinsic definition of the Evans function in terms of newly introduced generalized matrix-valued Jost solutions for general first-order matrix-valued differential equations on the real line, and a proof of the fact that the Evans function, a finite-dimensional determinant by construction, coincides with a modified Fredholm determinant associated with a Birman-Schwinger-type integral operator up to an explicitly computable nonvanishing factor.

  16. Determination of Vessel Attitudes Using GPS

    Institute of Scientific and Technical Information of China (English)

    王书寅; 周丰年; 金建霞; 吴敬文

    2002-01-01

    With the development of GPS carrier wave phase technology, it becomes possible that the height accuracy of centimeter level is got by GPS RTK technology. Vessel attitudes are very important parameters in marine survey. In this paper, they were determined by 4 GPS receivers. At the same time, the arithmetic and procedure of vessel attitude determining were given. Based on an experiment, some useful conclusions were obtained and the corresponding methods were put forward to improve the accuracy.

  17. The Determinants of FDI in BRIC countries

    OpenAIRE

    Lu, Wenbo

    2012-01-01

    The combined economies of Brazil, Russia, India, and China (BRIC) have attracted more and more Foreign Direct Investment (FDI) and developed rapidly. This Study examines the determinant factors of FDI inflows into BRIC countries using a set of Panel data from 2001 to 2011. The study conducts panel data analysis and finds the variables as Market Size, Inflation Rate, Labor Cost, Trade Openness, Currency Value and Political Risk are potential determining factors of FDI inflows to BRIC countries...

  18. Asteroseismic age determination for dwarfs and giants

    CERN Document Server

    Aguirre, V Silva

    2015-01-01

    Asteroseismology can make a substantial contribution to our understanding of the formation history and evolution of our Galaxy by providing precisely determined stellar properties for thousands of stars in different regions of the Milky Way. We present here the different sets of observables used in determining asteroseismic stellar properties, the typical level of precision obtained, the current status of results for ages of dwarfs and giants and the improvements than can be expected in the near future in the context of Galactic archaeology.

  19. DETERMINING PUBLIC STRUCTURE CROWD EVACUATION CAPACITY

    Directory of Open Access Journals (Sweden)

    Pejman Kamkarian

    2013-11-01

    Full Text Available This paper explores a strategy for determining public space safety. Due to varied purposes and locations, each public space has architecture as well as facilities. A generalized analysis of capacities for public spaces is essential. The method we propose is to examine a public space with a given architecture. We used Bayesian Belief Network to determine the level of safety and identify points of weakness in public spaces.

  20. DETERMINING PUBLIC STRUCTURE CROWD EVACUATION CAPACITY

    OpenAIRE

    Pejman Kamkarian; Henry Hexmoor

    2013-01-01

    This paper explores a strategy for determining public space safety. Due to varied purposes and locations, each public space has architecture as well as facilities. A generalized analysis of capacities for public spaces is essential. The method we propose is to examine a public space with a given architecture. We used Bayesian Belief Network to determine the level of safety and identify points of weakness in public spaces.